ASHP Best Practices 2015-2016 PDF


best
practices
POSITION &
GUIDANCE
DOCUMENTS
OF ASHP
2015-2016
Edition
T he ASHP policies in this book, positions and guidance documents, are intended
to foster improvements in pharmacy practice and patient care. The content of
individual positions and guidance documents should be assessed in the context of
your own health system, its policies and procedures, as well as applicable federal and
state laws and regulations.
G uidance documents, in particular, evolve because of advances in technology, new

knowledge from research, and lessons from experience. Additionally, medication
information is constantly evolving because of ongoing research and clinical experience,
and it is often subject to interpretation and unique clinical situations. The American
Society of Health-System Pharmacists (ASHP) endeavors to ensure the completeness
and timeliness of the information presented. However, the reader is advised that the
publisher, contributors, editors, and reviewers make no representations concerning the
suitability of the information for any purpose, and are not responsible for the immediate
currency of the information, for any errors or omissions, or for any consequences arising
from the use of these materials. All decisions made within the context of pharmacy
practice should be based on the independent judgment of the practitioner.
A SHP is the national professional organization whose more than 40,000 members
include pharmacists, student pharmacists, and pharmacy technicians who serve as
patient care providers on healthcare teams in acute and ambulatory settings. For over
70 years, ASHP has been on the forefront of efforts to improve medication use and
advance healthcare. For more information about the wide array of ASHP activities and
the many ways in which pharmacists help people make the best use of medicines, visit
ASHP’s website, www.ashp.org, or its consumer website, www.safemedication.com.
Editor: Bruce Hawkins
Published by the American Society of Health-System Pharmacists, 7272 Wisconsin Avenue,

Bethesda, MD 20814.
ASHP® is a service mark of the American Society of Health-System Pharmacists®, Inc.; registered
in the U.S. Patent and Trademark Office.
© Copyright 2015, American Society of Health-System Pharmacists®, Inc. All rights reserved.
No part of this publication may be reproduced or transmitted in any form or by any means,
electronic or mechanical, including photocopying, microfilming, and recording, or by any
information storage and retrieval systems, without written permission from the American Society
of Health-System Pharmacists®.
ISBN: 978-1-58528-533-4
10 9 8 7 6 5 4 3 2 1
Contents iii
Contents
Page Locator for Guidance Documents by Type and Title.................................... xiii

Acknowledgments..................................................................................................... xvi
Introduction................................................................................................................. xix
Mission Statement..................................................................................................... xxii
Vision Statement........................................................................................................ xxii
Automation and Information Technology
Positions: *1529 - Online Pharmacy and Internet Prescribing..................................................................4
1418 - Risk Assessment of Health Information Technology...................................................4
1302 - Interoperability of Patient-Care Technologies.............................................................4
1211 - Pharmacist’s Role in Health Care Information Systems..............................................4
1212 - Clinical Decision Support Systems..............................................................................4
1006 - Definition of Meaningful Use of Health Information Technology..............................4
1020 - Role of Pharmacists in Safe Technology Implementation...........................................5
0712 - Electronic Health and Business Technology and Services..........................................5
0507 - Electronic Information Systems...................................................................................5
0105 - Computerized Prescriber Order Entry.........................................................................5
9920 - Telepharmacy...............................................................................................................5
9813 - Regulation of Automated Drug Distribution Systems.................................................5
Statements: Bar-Code-Enabled Medication Administration Technology...................................................6
Bar-Code Verification During Inventory, Preparation, and Dispensing of Medications.........9
*Pharmacist’s Role in Clinical Informatics.............................................................................12
Pharmacist’s Role with Respect to Drug Delivery Systems and Administration Devices..........16
Pharmacy Technician’s Role in Pharmacy Informatics.........................................................18
Use of Social Media by Pharmacy Professionals..................................................................21
Guidelines: *Design of Database-Driven Clinical Decision Support: Strategic Directions for
Drug Database and Electronic Health Records Vendors.....................................24
Pharmacy Planning for Implementation of CPOE Systems in Hospitals
and Health Systems.............................................................................................30
Remote Medication Order Processing...................................................................................50
Safe Use of Automated Compounding Devices for the Preparation of Parenteral
Nutrition Admixtures...........................................................................................56
Safe Use of Automated Dispensing Devices ........................................................................61
Drug Distribution and Control

Positions: 0611 - Redistribution of Unused Medications.......................................................................70
0401 - Pharmaceutical Counterfeiting...................................................................................70
0303 - Pharmacy Drug Theft.................................................................................................70
*Indicates content that has been added or revised since the 2014–2015 edition.
iv Contents
0232 - Pharmacist’s Role in Drug Procurement, Distribution, Surveillance,

and Control..........................................................................................................70
9903 - Optimizing the Medication-Use Process...................................................................70
PROCUREMENT
Guidelines: Managing Drug Product Shortages in Hospitals and Health Systems..................................71
Selecting Pharmaceutical Manufacturers and Suppliers.......................................................78
PREPARATION AND HANDLING

Positions: 0903 - Pharmaceutical Waste................................................................................................80
0614 - Safe Disposal of Patients’ Home Medications...........................................................80
0616 - Safe and Effective Extemporaneous Compounding..................................................80
0617 - Accreditation of Compounding Facilities..................................................................80
Guidelines: Compounding Sterile Preparations........................................................................................81
Handling Hazardous Drugs.................................................................................................101
Pharmacy-Prepared Ophthalmic Products..........................................................................121
TAB: Compounding Nonsterile Products in Pharmacies..............................................................123
DISTRIBUTION
Positions: 0310 - Technician-Checking-Technician Programs............................................................130
0010 - Dispensing by Nonpharmacists and Nonprescribers...............................................130
Statements: Pharmacist’s Responsibility for Distribution and Control of Drug Products......................131
Unit Dose Drug Distribution...............................................................................................132
TABs: Hospital Drug Distribution and Control..............................................................................133
Repackaging Oral Solids and Liquids in Single Unit and Unit Dose Packages.................142
Single Unit and Unit Dose Packages of Drugs...................................................................144
Education and Training

Positions: *1518 - Developing Leadership Competencies....................................................................148
*1519 - Pharmacy Technician Training and Certification.....................................................148
1414 - Cultural Competency and Cultural Diversity..........................................................148
1316 - Pharmacy Resident and Student Roles in New Practice Models.............................148
1317 - Education and Training in Health Care Informatics................................................148
1201 - Preceptor Skills and Abilities...................................................................................148
1203 - Qualifications of Pharmacy Technicians in Advanced Roles..................................148
1108 - Quality of Pharmacy Education and Expansion of Colleges of Pharmacy..............148
1109 - Residency Equivalency............................................................................................149
1110 - Pharmacy Internships...............................................................................................149
1111 - State-Specific Requirements for Pharmacist Continuing Education........................149
1112 - Innovative Residency Models..................................................................................149
1008 - Employment Classification and Duty Hours of Pharmacy Residents.....................149
1014 - Interprofessional Education and Training................................................................149
Contents v
0913 - Pharmacy Student Experiences in Medically Underserved Areas...........................149

0915 - Pharmacy Expertise in the Preparation and Handling of Injectable Medications...149
0916 - Continuing Professional Development....................................................................149
0917 - Pharmacy Residency Training.................................................................................150
0804 - Collaboration Regarding Experiential Education....................................................150
0701 - Requirement for Residency......................................................................................150
0704 - Residency Programs.................................................................................................150
0705 - ASHP Guidelines, Statements, and Professional Policies as an Integral Part
of the Educational Process................................................................................150
0510 - Communication Among Health-System Pharmacy Practitioners, Patients,
and Other Health Care Providers......................................................................150
0315 - Practice Sites for Colleges of Pharmacy..................................................................150
0323 - Licensure for Pharmacy Graduates of Foreign Schools..........................................150
0325 - Public Funding for Pharmacy Residency Training..................................................151
0005 - Residency Training for Pharmacists Who Provide Direct Patient Care...................151
8507 - Career Counseling....................................................................................................151
Endorsed: Definitions of Pharmacy Residencies and Fellowships......................................................152
Ethics
Positions: *1531 - Pharmacist Role in Capital Punishment...................................................................156
1403 - Pharmacist’s Role on Ethics Committees................................................................156
1116 - Ethical Use of Placebos in Clinical Practice............................................................156
0610 - Pharmacist’s Right of Conscience and Patient’s Right of Access to Therapy.........156
0013 - Patient’s Right to Choose.........................................................................................156
9915 - ASHP Position on Assisted Suicide.........................................................................156
9006 - Nondiscriminatory Pharmaceutical Care.................................................................156
Statements: Leadership as a Professional Obligation.............................................................................157
Pharmacist’s Decision-making on Assisted Suicide............................................................159
Professionalism...................................................................................................................162
Guideline: Pharmacists’ Relationships with Industry...........................................................................165
Endorsed: Code of Ethics for Pharmacists...........................................................................................166
Formulary Management (Medication-Use Policy Development)

Positions: 1104 - Pharmacogenomics..................................................................................................168
0809 - Medications Derived from Biologic Sources...........................................................168
0817 - Generic Substitution of Narrow Therapeutic Index Drugs......................................168
0305 - Expression of Therapeutic Purpose of Prescribing..................................................168
0228 - Appropriate Dosing of Medications in Patient Populations with
Unique Needs....................................................................................................168
0102 - Medication Formulary System Management...........................................................168
0103 - Gene Therapy...........................................................................................................168
9819 - Role of Pharmacists and Business Leaders in Health
Care Services and Policies................................................................................169
vi Contents
9601 - Standardization of Drug Medication Formulary Systems.......................................169

9106 - Medical Devices.......................................................................................................169
8708 - Therapeutic Interchange...........................................................................................169
Statements: Pharmacy and Therapeutics Committee and the Formulary System..................................170
Use of Medications for Unlabeled Uses..............................................................................173
Guidelines: Medication-Use Evaluation.................................................................................................175
Pharmacy and Therapeutics Committee and the Formulary System..................................178
Endorsed: Principles of a Sound Drug Formulary System...................................................................188
Government, Law, and Regulation

Positions: *1501 - Pharmacist Participation in Health Policy Development.........................................194
*1502 - Pharmacist Recognition as a Healthcare Provider...................................................194
*1503 - Pharmaceutical Product and Supply Chain Integrity...............................................194
*1506 - Premarketing Comparative Clinical Studies............................................................194
*1507 - Funding, Expertise, and Oversight of State Boards of Pharmacy............................194
*1508 - Support for FDA Expanded Access (Compassionate Use) Program.......................194
*1509 - Approval of Biosimilar Medications........................................................................195
*1512 - Development of Abuse-Resistant Narcotics............................................................195
*1513 - Quality Patient Medication Information..................................................................195
1405 - Automatic Stop Orders.............................................................................................195
1406 - Federal and State Regulation of Compounding.......................................................195
1407 - 340B Drug Pricing Program Sustainability.............................................................195
1408 - State Prescription Drug Monitoring Programs........................................................196
1410 - Access to Oral Contraceptives Through an Intermediate Category
of Drug Products...............................................................................................196
1411 - Expedited Pathways for FDA Drug Approval..........................................................196
1412 - FDA Oversight of Laboratory-Developed Tests......................................................196
1310 - Regulation of Telepharmacy Services .....................................................................196
1311 - Regulation of Centralized Order Fulfillment...........................................................197
1314 - DEA Scheduling of Hydrocodone Combination Products.......................................197
1315 - DEA Scheduling of Controlled Substances.............................................................197
1216 - Pharmacy Technicians..............................................................................................197
1219 - Stable Funding for HRSA Office of Pharmacy Affairs............................................197
1223 - Globalization of Clinical Trials................................................................................197
1101 - Medical Marijuana ..................................................................................................197
1102 - Agricultural Use of Hormone and Prohormone Therapies .....................................198
1103 - Direct-to-Consumer Clinical Genetic Tests ............................................................198
1118 - Drug Product Shortages...........................................................................................198
1121 - Poison Control Center Funding................................................................................198
1001 - Health Insurance Coverage for U.S. Residents........................................................198
1002 - Risk Evaluation and Mitigation Strategies..............................................................199
Contents vii
1003 - FDA Authority on Recalls........................................................................................199

1004 - Postmarketing Comparative Clinical and Pharmacoeconomic Studies...................199
1007 - Regulation of Home Medical Equipment Medication Products and Devices.........199
1009 - Preservation of Antimicrobials for Medical Treatment...........................................199
1011 - Use of Surrogate Endpoints for FDA Approval of Drug Uses.................................199
0909 - Regulation of Interstate Pharmacy Practice.............................................................200
0811 - Regulation of Dietary Supplements.........................................................................200
0813 - Medicare Prescription Drug Benefit........................................................................200
0814 - Federal Review of Anticompetitive Practices by Drug Product Manufacturers......200
0719 - FDA Authority to Prohibit Reuse of Brand Names.................................................200
0602 - Minimum Effective Doses.......................................................................................200
0612 - Streamlined Licensure Reciprocity..........................................................................200
0515 - Postmarketing Safety Studies..................................................................................201
0516 - Mandatory Registry of Clinical Trials.....................................................................201
0413 - Importation of Pharmaceuticals...............................................................................201
0220 - Intermediate Category of Drugs...............................................................................201
0222 - Greater Access to Less Expensive Generic Drugs...................................................201
0012 - FDA’s Public Health Mission...................................................................................202
9010 - Generic Pharmaceutical Testing...............................................................................202
Statements: Criteria for an Intermediate Category of Drug Products.....................................................203
Over-the-Counter Availability of Statins.............................................................................206
Principles for Including Medications and Pharmaceutical Care in
Health Care Systems.........................................................................................209
Medication Misadventures
Positions: *1505 - Statutory Protection for Medication-Error Reporting..............................................212
*1524 - Support for Second Victims.....................................................................................212
*1530 - Standardization of Small-Bore Connectors to Avoid Wrong-Route Errors.............212
1115 - Just Culture...............................................................................................................212
1021 - Just Culture and Reporting Medication Errors........................................................212
0604 - Minimizing the Use of Abbreviations......................................................................212
0020 - Drug Names, Labeling, and Packaging Associated with Medication Errors...........212
0021 - Medication Errors and Risk Management...............................................................212
9805 - Medication Misadventures.......................................................................................213
9609 - Human Factors Concepts.........................................................................................213
Statements: Reporting Medical Errors....................................................................................................214
Role of the Medication Safety Leader.................................................................................215
Guidelines: Adverse Drug Reaction Monitoring and Reporting............................................................219
Preventing Medication Errors in Hospitals.........................................................................222
Preventing Medication Errors with Chemotherapy and Biotherapy...................................231
viii Contents
Medication Therapy and Patient Care
ORGANIZATION AND DELIVERY OF SERVICES

Positions: *1504 - Patient Adherence Programs as Part of Health Insurance Coverage.......................258
*1511 - Complementary and Alternative Medicine in Patient Care......................................258
*1520 - Impact of Insurance Coverage Design on Patient Care Decision............................258
*1523 - Pharmacist’s Role in Population Health Management.............................................258
*1525 - Standardization of Doses.........................................................................................258
1401 - Standardization of Oral Liquid Medication Concentrations....................................258
1419 - Documentation of Patient-Care Services in the Permanent Health Record.............258
1306 - Standardization of Intravenous Drug Concentrations..............................................258
1312 - Medication Overuse.................................................................................................259
1313 - Drug-Containing Devices........................................................................................259
1202 - Qualifications and Competencies Required to Prescribe Medications....................259
1208 - Transitions of Care...................................................................................................259
1213 - Pharmacist Prescribing in Interprofessional Patient Care........................................259
1215 - Pharmacist’s Role in Team-Based Care...................................................................259
1217 - Collaborative Drug Therapy Management..............................................................259
1222 - Medication Adherence.............................................................................................260
1107 - Patient-Reported Outcomes Tools............................................................................260
1114 - Pharmacist Accountability for Patient Outcomes ....................................................260
1117 - Pharmacists’ Role in Medication Reconciliation.....................................................260
1005 - Medication Therapy Management...........................................................................260
1022 - Patient Access to Pharmacy Services in Small and Rural Hospitals.......................260
1023 - Scope and Hours of Pharmacy Services..................................................................260
0806 - Health-System Use of Medications and Administration Devices
Supplied Directly to Patients.............................................................................261
0816 - Pharmacist’s Leadership Role in Anticoagulation Therapy Management...............261
0707 - Standard Drug Administration Schedules................................................................261
0601 - Universal Influenza Vaccination..............................................................................261
0619 - Integrated Team-Based Approach for the Pharmacy Enterprise..............................261
0502 - Health Care Quality Standards and Pharmacy Services..........................................261
0505 - Health-System Facility Design................................................................................261
0525 - Mandatory Tablet Splitting for Cost Containment...................................................262
0202 - Performance Improvement.......................................................................................262
0101 - Pharmacy Benefits for the Uninsured......................................................................262
0104 - Patient Satisfaction...................................................................................................262
9921 - Pharmacist Validation of Information Related to Medications................................262
9801 - Collaborative Drug Therapy Management Activities..............................................262
9820 - Medication Administration by Pharmacists.............................................................262
Contents ix
Statements: Confidentiality of Patient Health Care Information............................................................263

Health-System Pharmacist’s Role in National Health Care Quality Initiatives..................264
Hospitalist–Pharmacist Collaboration.................................................................................266
Pharmaceutical Care............................................................................................................270
Guidelines: Documenting Pharmaceutical Care in Patient Medical Records........................................273
Pharmacist-Conducted Patient Education and Counseling.................................................276
Pharmacist’s Role in the Development, Implementation, and Assessment of
Critical Pathways...............................................................................................279
Standardized Method for Pharmaceutical Care...................................................................285
SPECIFIC PRACTICE AREAS

Positions: *1510 - Naloxone Availability..............................................................................................288
*1514 - Safety and Effectiveness of Ethanol Treatment for Alcohol
Withdrawal Syndrome.......................................................................................288
*1516 - Chemotherapy Parity...............................................................................................288
*1517 - Documentation of Penicillin Allergy as a Component
of Antimicrobial Stewardship............................................................................288
*1526 - Prescription Drug Abuse..........................................................................................288
*1527 - Pharmacist’s Role in Urgent and Emergency Situations..........................................288
1402 - Safe Use of Radiopharmaceuticals..........................................................................288
1404 - Safe Use of Fentanyl Transdermal System Patches.................................................288
1305 - Education About Performance-Enhancing Substances............................................288
1309 - Pharmacists’ Role in Immunization.........................................................................288
1214 - Pharmacist’s Role in Accountable Care Organizations............................................289
1221 - Criteria for Medication Use in Geriatric Patients....................................................289
1224 - Tobacco and Tobacco Products................................................................................289
1105 - Safe and Effective Use of IV Promethazine.............................................................289
1106 - Pain Management.....................................................................................................289
0902 - Pharmacist’s Role in Providing Care for an Aging Population................................290
0908 - Pharmacist Role in the Health Care (Medical) Home.............................................290
0912 - Safe and Effective Use of Heparin in Neonatal Patients.........................................290
0307 - Pharmacist Support for Dying Patients....................................................................290
9711 - Interventions to Reduce High-Risk Behavior in Intravenous Drug Users...............290
9407 - Primary and Preventive Care...................................................................................290
Statements: Pharmacist’s Role in Antimicrobial Stewardship and Infection Prevention
and Control........................................................................................................291
Pharmacist’s Role in Clinical Pharmacogenomics..............................................................294
Pharmacist’s Role in Clinical Pharmacokinetic Monitoring...............................................297
Pharmacist’s Role in Hospice and Palliative Care..............................................................299
Pharmacist’s Role in Medication Reconciliation................................................................303
Pharmacist’s Role in Primary Care.....................................................................................306
x Contents
*Pharmacist’s Role in Substance Abuse Prevention, Education, and Assistance.................309

Pharmacy Services to the Emergency Department.............................................................313
Racial and Ethnic Disparities in Health Care......................................................................316
Role of Health-System Pharmacists in Emergency Preparedness.......................................321
Role of Health-System Pharmacists in Public Health.........................................................323
Use of Dietary Supplements................................................................................................328
Guidelines: Emergency Medicine Pharmacist Services.........................................................................333
*Pharmacist Involvement in HIV Care.................................................................................348
Pharmacist’s Role in Immunization....................................................................................372
Pharmacist’s Role in Providing Drug Information..............................................................378
Providing Pediatric Pharmaceutical Services in Organized Health Care Systems.............383
Surgery and Anesthesiology Pharmaceutical Services........................................................386
Pharmaceutical Industry
DRUG PRODUCTS, LABELING, AND PACKAGING

Positions: *1528 - Excipients in Drug Products....................................................................................396
1413 - Ensuring Effectiveness, Safety, and Access to Orphan Drug Products...................396
0920 - Standardized Clinical Drug Nomenclature..............................................................396
0720 - Standardizing Prefixes and Suffixes in Drug Product Names.................................396
0618 - Elimination of Surface Contamination on Vials of Hazardous Drugs.....................396
0501 - Mandatory Labeling of the Presence of Latex.........................................................396
0402 - Ready-to-Use Packaging for All Settings................................................................396
0309 - Unit Dose Packaging Availability............................................................................396
0002 - Drug Shortages.........................................................................................................397
9707 - Pediatric Dosage Forms...........................................................................................397
9608 - Use of Color to Identify Drug Products...................................................................397
9309 - Expiration Dating of Pharmaceutical Products........................................................397
9211 - Tamper-Evident Packaging on Topical Products.....................................................397
9011 - Drug Nomenclature..................................................................................................397
8709 - Codes on Solid Dosage Forms of Prescription Drug Products................................397
8613 - Elimination of Apothecary System..........................................................................397
8310 - Size, Color, and Shape of Drug Products.................................................................397
MARKETING
Positions: *1521 - Identification of Prescription Drug Coverage and Eligibility for
Patient Assistance Programs..............................................................................398
1420 - Manufacturer-Sponsored Patient Assistance Programs...........................................398
1119 - Direct-to-Consumer Advertising of Prescription
and Nonprescription Medications.....................................................................398
1120 - Regulation of Off-label Promotion and Marketing..................................................398
1016 - Pharmaceutical Distribution Systems......................................................................398
Contents xi
0714 - Restricted Drug Distribution....................................................................................398

9702 - Drug Samples...........................................................................................................399
Guideline: Activities of Vendors’ Representatives in Organized Health Care Systems.......................400
Pharmacy Management
Positions: *1522 - Disposition of Illicit Substances..............................................................................404
1416 - Pharmacy Department Business Partnerships..........................................................404
1417 - Integration of Pharmacy Services in Multifacility Health Systems.........................404
1303 - Proliferation of Accreditation Organizations...........................................................404
0901 - Workload Monitoring and Reporting.......................................................................404
0918 - Pharmacist Leadership of the Pharmacy Department..............................................404
0504 - Pharmacy Staff Fatigue and Medication Errors.......................................................405
Statements: *Roles and Responsibilities of the Pharmacy Executive......................................................406
Standards-Based Pharmacy Practice in Hospitals and Health Systems..............................410
Guidelines: Medication Cost Management Strategies for Hospitals and Health Systems.....................412
Outsourcing Pharmaceutical Services.................................................................................427
*Outsourcing Sterile Compounding Services.......................................................................434
COMPENSATION AND REIMBURSEMENT

Positions: 1301 - Payer Processes for Payment Authorization and Coverage Verification.................446
1304 - Drug Product Reimbursement..................................................................................446
1205 - Revenue Cycle Compliance and Management........................................................446
1209 - Value-Based Purchasing...........................................................................................446
0206 - Reimbursement for Unlabeled Uses of FDA-Approved Drug Products.................446
HUMAN RESOURCES
Positions: 1415 - Credentialing, Privileging, and Competency Assessment.......................................447
1207 - Financial Management Skills...................................................................................447
1225 - Board Certification for Pharmacists.........................................................................447
1113 - Professional Socialization........................................................................................447
0905 - Credentialing and Privileging by Regulators, Payers, and Providers for
Collaborative Drug Therapy Management........................................................447
0919 - Intimidating or Disruptive Behaviors......................................................................447
0810 - Education, Prevention, and Enforcement Concerning Workplace Violence............448
0812 - Appropriate Staffing Levels.....................................................................................448
0703 - Image of and Career Opportunities for Hospital and
Health-System Pharmacists...............................................................................448
0615 - Influenza Vaccination Requirements to Advance Patient Safety and
Public Health.....................................................................................................448
0201 - Staffing for Safe and Effective Patient Care............................................................448
0211 - Image of and Career Opportunities for Pharmacy Technicians...............................449
0218 - Pharmacist Recruitment and Retention....................................................................449
xii Contents
0112 - Professional Development as a Retention Tool........................................................449

9103 - Drug Testing.............................................................................................................449
9108 - Employee Testing.....................................................................................................449
Guideline: Recruitment, Selection, and Retention of Pharmacy Personnel..........................................450
Report: Long-Range Vision for the Pharmacy Work Force in Hospitals and Health Systems........456
Practice Settings
Positions: 1024 - Use of Two Patient Identifiers in the Outpatient Setting.........................................468
0414 - Home Intravenous Therapy Benefit.........................................................................468
Guidelines: Home Infusion Pharmacy Services.....................................................................................469
*Minimum Standard for Ambulatory Care Pharmacy Practice............................................484
Minimum Standard for Pharmacies in Hospitals................................................................498
Pharmaceutical Services in Correctional Facilities.............................................................509
Research
Positions: *1515 - Research on Drug Use in Obese Patients.................................................................514
0711 - Institutional Review Boards and Investigational Use of Drugs...............................514
0229 - Clinical Investigations of Drugs Used in Elderly and Pediatric Patients.................514
Statement: Pharmaceutical Research in Organized Health-Care Settings............................................515
Guidelines: Clinical Drug Research.......................................................................................................516
Pharmaceutical Research in Organized Health-Care Settings............................................523
ASHP Therapeutic Position Statements

Cessation of Tobacco Use............................................................................................................................526
Institutional Use of 0.9% Sodium Chloride Injection to Maintain Patency of Peripheral Indwelling
Intermittent Infusion Devices............................................................................................................... 542
Role of Pharmacotherapy in Preventing Venous Thromboembolism in Hospitalized Patients...................545
Strategies for Identifying and Preventing Pneumococcal Resistance......................................................... 562
Therapeutic Monitoring of Vancomycin in Adult Patients: A Consensus Review.......................................569
Use of Second-Generation Antipsychotic Medications in the Treatment of Adults with
Psychotic Disorders.............................................................................................................................. 585
ASHP Therapeutic Guidelines

Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery......................................................600
Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the
Adult Critically Ill Patient.................................................................................................................... 686
Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium
in Adult Patients in the ICU...................................................................................................................702
Index..................................................................................................................................................................751
Page Locator xiii
Page Locator for Guidance Documents

by Type and Title
ASHP Statements
Bar-Code-Enabled Medication Administration Technology............................................................................6
Bar-Code Verification During Inventory, Preparation, and Dispensing of Medications..................................9
Confidentiality of Patient Health Care Information.....................................................................................263
Criteria for an Intermediate Category of Drug Products..............................................................................203
Drug Delivery Systems and Administration Devices ....................................................................................16
Health-System Pharmacist’s Role in National Health Care Quality Initiatives...........................................264
Hospitalist–Pharmacist Collaboration..........................................................................................................266
Leadership as a Professional Obligation......................................................................................................157
Over-the-Counter Availability of Statins .....................................................................................................206
Pharmaceutical Care ....................................................................................................................................270
Pharmaceutical Research in Organized Health-Care Settings .....................................................................515
Pharmacist’s Decision-making on Assisted Suicide ....................................................................................159
Pharmacist’s Responsibility for Distribution and Control of Drug Products ..............................................131
Pharmacist’s Role in Antimicrobial Stewardship and Infection Prevention and Control............................291
Pharmacist’s Role in Clinical Informatics......................................................................................................12
Pharmacist’s Role in Clinical Pharmacogenomics.......................................................................................294
Pharmacist’s Role in Clinical Pharmacokinetic Monitoring .......................................................................297
Pharmacist’s Role in Hospice and Palliative Care ......................................................................................299
Pharmacist’s Role in Medication Reconciliation.........................................................................................303
Pharmacist’s Role in Primary Care ..............................................................................................................306
Pharmacist’s Role in Substance Abuse Prevention, Education, and Assistance ..........................................309
Pharmacy and Therapeutics Committee and the Formulary System............................................................170
Pharmacy Services to the Emergency Department.......................................................................................313
Pharmacy Technician’s Role in Pharmacy Informatics..................................................................................18
Principles for Including Medications and Pharmaceutical Care in Health Care Systems ...........................209
Professionalism ............................................................................................................................................162
Racial and Ethnic Disparities in Health Care ..............................................................................................316
Reporting Medical Errors ............................................................................................................................214
Role of Health-System Pharmacists in Emergency Preparedness ...............................................................321
Role of Health-System Pharmacists in Public Health .................................................................................323
Role of the Medication Safety Leader..........................................................................................................215
Roles and Responsibilities of the Pharmacy Executive...............................................................................406
Standards-Based Pharmacy Practice in Hospitals and Health Systems.......................................................410
Unit Dose Drug Distribution .......................................................................................................................132
xiv Page Locator
Use of Dietary Supplements ........................................................................................................................328

Use of Medications for Unlabeled Uses ......................................................................................................173
Use of Social Media by Pharmacy Professionals...........................................................................................21
ASHP Guidelines
Activities of Vendors’ Representatives in Organized Health Care Systems ................................................400
Adverse Drug Reaction Monitoring and Reporting ....................................................................................219
Clinical Drug Research ................................................................................................................................516
Compounding Sterile Preparations.................................................................................................................81
Design of Database-Driven Clinical Decision Support: Strategic Directions for Drug Database
and Electronic Health Records Vendors.................................................................................................24
Documenting Pharmaceutical Care in Patient Medical Records .................................................................273
Emergency Medicine Pharmacist Services...................................................................................................333
Handling Hazardous Drugs .........................................................................................................................101
Home Infusion Pharmacy Services..............................................................................................................469
Managing Drug Product Shortages in Hospitals and Health Systems...........................................................71
Medication Cost Management Strategies for Hospitals and Health Systems .............................................412
Medication-Use Evaluation .........................................................................................................................175
Minimum Standard for Ambulatory Care Pharmacy Practice .....................................................................484
Minimum Standard for Pharmacies in Hospitals .........................................................................................498
Outsourcing Pharmaceutical Services .........................................................................................................427
Outsourcing Sterile Compounding Services................................................................................................434
Pharmaceutical Research in Organized Health-Care Settings .....................................................................523
Pharmaceutical Services in Correctional Facilities .....................................................................................509
Pharmacist-Conducted Patient Education and Counseling .........................................................................276
Pharmacist Involvement in HIV Care..........................................................................................................348
Pharmacists’ Relationships with Industry ....................................................................................................165
Pharmacist’s Role in the Development, Implementation, and Assessment of Critical Pathways................279
Pharmacist’s Role in Immunization .............................................................................................................372
Pharmacist’s Role in Providing Drug Information.......................................................................................378
Pharmacy and Therapeutics Committee and the Formulary System............................................................178
Pharmacy Planning for Implementation of CPOE Systems in Hospitals and Health Systems......................30
Pharmacy-Prepared Ophthalmic Products ...................................................................................................121
Preventing Medication Errors in Hospitals .................................................................................................222
Preventing Medication Errors with Chemotherapy and Biotherapy............................................................231
Providing Pediatric Pharmaceutical Services in Organized Health Care Systems ......................................383
Recruitment, Selection, and Retention of Pharmacy Personnel ..................................................................450
Remote Medication Order Processing............................................................................................................50
Safe Use of Automated Compounding Devices for the Preparation of Parenteral Nutrition Admixtures.....56
Page Locator xv
Safe Use of Automated Dispensing Devices .................................................................................................61

Selecting Pharmaceutical Manufacturers and Suppliers ...............................................................................78
Standardized Method for Pharmaceutical Care ...........................................................................................285
Surgery and Anesthesiology Pharmaceutical Services ................................................................................386
ASHP Report
Long-Range Vision for the Pharmacy Work Force in Hospitals and Health Systems.................................456
ASHP Technical Assistance Bulletins

Compounding Nonsterile Products in Pharmacies.......................................................................................123
Hospital Drug Distribution and Control.......................................................................................................133
Repackaging Oral Solids and Liquids in Single Unit and Unit Dose Packages...........................................142
Single Unit and Unit Dose Packages of Drugs.............................................................................................144
xvi Acknowledgments
Acknowledgments
A
SHP gratefully acknowledges the following organizations and individuals for drafting and reviewing the new and revised
guidance documents in this edition.
ASHP Statement on the Roles and Responsibilities Barbara Giacomelli, Pharm.D., M.B.A.,
of the Pharmacy Executive FASHP
Nancy Hope Goodbar, Pharm.D., BCPS
Council on Pharmacy Management James Hoffman, Pharm.D., M.S.
Joan Kapusnik-Uner, Pharm.D. FASHP
Contributing Janet M Kozakiewiz, M.S., Pharm.D.,
Reviewers: Karl Kappeler, M.S., FASHP FASHP
Michael Nnadi, Pharm.D, MHS Emily Kirkwold, Pharm.D.
Sam Calabrese, M.B.A., FASHP Kabeer Mago, Pharm.D.
Debra Cowan, Pharm.D., FASHP Ben McDaniel, Pharm.D.
Bonnie Kirshenbaum, M.S., FASHP, FCSHP Karen Michaud, Pharm.D., BCPS
John Lewin, Pharm.D., M.B.A. Richard Pacitti, Pharm.D., M.B.A.
Christine Marchese, Pharm.D. Lois F. Parker, B.S.Pharm.
Tricia Meyer, Pharm.D., M.S., FASHP Shea Polk, Pharm.D.
Brandon Ordway, Pharm.D., M.S. James A. Ponto, M.S., RPh, BCNP, FASHP
Roger Woolf, Pharm.D., Jason J. Schafer, Pharm.D., M.P.H., BCPS
Rusol Karralli, Pharm.D., M.S. Philip J. Schneider, M.S.
Kelly Sennett, B.S. Terry L. Seaton, Pharm.D., FCCP, BCPS
(AMIA-PWGL)
Nancy R. Smestad, M.S., CMI
ASHP Statement on the Pharmacist’s Role in Substance
Shelly Spiro, B.S.Pharm., FASCP (PHITC)
Abuse Prevention, Education and Assistance
Mark St. Cyr, D.Ph., M.P.H.
Craig Stern, RPh, Pharm.D., M.B.A.
Contributors: Jeffrey N. Baldwin, Pharm.D.
Tate N. Trujillo, Pharm.D., BCPS, FCCM,
Chelsea Leeper, Pharm.D.
FASHP
Elizabeth Wade, Pharm.D., BCPS (NHSHP)
ASHP Statement on the Jody Jacobson Wedret, FASHP
Pharmacist’s Role in Clinical Informatics Marc Willner, Pharm.D.
Author: Mark Siska, M.B.A./TM, B.S.Pharm.

ASHP Guidelines on Pharmacist Involvement in HIV Care
Reviewers: American Association of Colleges of
Authors: Jason J. Schafer, Pharm.D., M.P.H, BCPS,
Pharmacy (AACP)
AAHIVP
American Medical Informatics Association,
Taylor K. Gill, Pharm.D., BCPS, AAHIVP
Pharmacoinformatics Working Group
Elizabeth M. Sherman, Pharm.D., AAHIVP
Leadership (AMIA-PWGL)
Ian R. McNicholl, Pharm.D., FCCP, BCPS
Kansas Council of Health-System
(AQ-ID), AAHIVP
Pharmacists (KCHP)
New Hampshire Society of Health-System
Reviewers: American Pharmacists Association (APhA)
Pharmacists (NHSHP)
Canadian HIV/AIDS Pharmacists Network
Pharmacy HIT Collaborative (PHITC)
(CHAP)
Ernest R. Anderson, Jr., M.S., FASHP
HIV Medicine Association (HIVMA)
Paul J. Barrett, Pharm.D., MPA, BCPS,
Society of Infectious Disease Pharmacists
FASHP
South Carolina Society of Health-System
Janinah Barreto, Pharm.D., M.S.
Pharmacists (SCSHP)
Carol J. Bickford, Ph.D., RN-BC, CPHIMS
Sarah Bledsoe, Pharm.D. Melissa Badowski, Pharm.D., BCPS,
Lynette R. Bradley-Baker, Ph.D. (AACP) AAHIVP
Max E. Burchett, Jr., Pharm.D. Carol J. Bickford, Ph.D., RN-BC, CPHIMS
Gregory Burger, Pharm.D., CPPS (KCHP) Shanna Chan, B.Sc.Pharm., ACPR,
Michelle DeLuca Fraley, Pharm.D., RPD AAHIVP (CHAP)
Patrick Clay, Pharm.D. FCCP, CCTI (APhA)
*Review does not imply endorsement.

Acknowledgments xvii
Natalie Dayneka, B.Sc.Pharm., ACPR, Cyndy A. Clegg, M.H.A.

Pharm.D., FCSHP (CHAP) Sandra F. Durley, Pharm.D.
Heather Easterling, Pharm.D., M.B.A. Kelly T. Epplen, Pharm.D.
(SCSHP) Laurel M. Marsden, B.S.Pharm., M.S.H.A.
Devon Flynn, Pharm.D., BCPS, AAHIVP Bridgette A. Thomas, Pharm.D.
Michelle Foisy, B.Sc.Pharm., Pharm.D., Nathan S. Thompson, B.S.Pharm., M.B.A.
FCSHP, AAHIVP (CHAP)
Patricia Pecora Fulco, Pharm.D., BCPS, Contributions by:
FASHP, AAHIVP Section of Ambulatory Care Practitioners
Barbara Giacomelli, Pharm.D., M.B.A., Executive Committee
FASHP Seena L. Haines, Pharm.D., FASHP, FAPhA,
Pierre Giguère, B.Sc.Pharm., M.Sc. (CHAP) BCACP, BC-ADM, CDE
Christine Hughes, B.Sc.Pharm., Pharm.D, Gloria P. Sachdev, Pharm.D.
AAHIVP (CHAP) Jennifer Askew Buxton, Pharm.D., CPP
Tara K. Jellison, Pharm.D., M.B.A., FASHP Melanie A. Dodd, Pharm.D., Ph.C., BCPS
Deborah V. Kelly, B.Sc.Pharm., ACPR, Sandra Leal, Pharm.D., FAPhA, CDE
Pharm.D, FCSHP, AAHIVP (CHAP) Steven M. Riddle, Pharm.D., BCPS, FASHP
William Kuykendall, Pharm.D. Justine Coffey, J.D., LL.M.
Kristina Lantis, Pharmacy Student, Class of
2016 Association and Organization Reviewers:
J. Craig Phillips, Ph.D., LLM, RN, ARNP, Academy of Managed Care Pharmacy
PMHCNS-BC, ACRN (AMCP)*
Carlo Quaia, B.Sc.Pharm., ACPR (CHAP) American Association of Critical-Care
James R. Rinehart, R.Ph., M.S., FASHP Nurses (AACN)*
Linda Robinson, B.Sc.Pharm., AAHIVE American College of Clinical Pharmacy
(CHAP) (ACCP)*
Nancy Sheehan, B.Sc.Pharm., M.Sc. American Geriatric Society*
(CHAP) The Joint Commission (TJC)*
Shannon Stone, B.Sc.Pharm., ACPR Cindi Brennan, Pharm.D., M.H.A.*
(CHAP) Mark N. Brueckl, M.B.A. (AMCP)*
Alice Tseng, B.Sc.Pharm., Pharm.D., Anne Burns, Pharm.D.*
FCSHP, AAHIVP (CHAP) Frank P. Castronovo, Jr., Ph.D*
Andrea Weddle, M.S.W. (HIVMA) Sharon Connor, Pharm.D.*
Jody Jacobson Wedret, FASHP, FCSHP Paul F. Davis, B.S.Pharm.*
Deborah Yoong, B.Sc.Pharm., ACPR, Ernest Dole, Pharm.D., FASHP*
Pharm.D. (CHAP) Melanie A. Dodd, Pharm.D., Ph.C., BCPS*
Scott R. Drab, Pharm.D., CDE, BC-ADM*
Sarah K. Ford, Pharm.D., BCPS, CPP*
ASHP Guidelines on Outsourcing
Seena L. Haines, Pharm.D., FASHP, FAPhA,
Sterile Compounding Services
BCACP, BC-ADM, CDE*
Deanne L. Hall, Pharm.D., CDE*
Revised by: Patricia C. Kienle, M.P.A., FASHP
Philip E. Johnson, M.S., FASHP*
Tom Kaye, M.B.A., FASHP*
Contributor: Bona E. Benjamin, B.S.Pharm.
Sandra Leal, Pharm.D., FAPhA, CDE*
Jeff Little, Pharm.D., MPH, BCPS*
Reviewers: Darrell Chan, Pharm.D.
Jimmy R. Mitchell, M.S., M.P.H.*
Michael Cunningham, Pharm.D.
Bruce A. Nelson, M.S.*
Kate Douglass, M.S., RN, APN,C, CRNI
Colleen O’Malley, M.S., B.S.Pharm.*
Bernadette Henrichs, Ph.D., CRNA, CCRN
James A. Ponto, M.S., BCNP*
Eric Kastango, M.B.A., FASHP
Matt Ransom, Pharm.D., BCACP*
Michael Koch, M.B.A.
Steven M. Riddle, Pharm.D., BCPS,
Rich Kruzynski, B.S.Pharm., M.B.A.
FASHP*
Kathy Parrinello, Ph.D., RN
Christine Ruby, Pharm.D., BCPS*
James R. Rinehardt, M.S., FASHP
Gloria P. Sachdev, Pharm.D.*
Douglas Smith, Pharm.D.
Paul M. Schyve, M.D. (TJC)
Ross W. Thompson, M.S., B.S.Pharm.
Pamela Shellner, R.N., M.A. (AACN)*
Tom Woller, M.S., FASHP
Melissa Somma-McGivney, Pharm.D.,
CDE*
ASHP Guidelines: Minimum Standard Richard L. Stambaugh, M.S., Pharm.D.,
for Ambulatory Care Pharmacy Practice BCPS*
Marc H. Stranz, Pharm.D.*
Authors: Jennifer Askew Buxton, Pharm.D., CPP Megan Wagner, Pharm.D.*
RoseMarie Babbitt, B.S.Pharm., M.A. C. Edwin Webb, Pharm.D., M.P.H. (ACCP)*
xviii Acknowledgments
Jody Jacobson Wedret, FASHP, FCSHP* Christopher J. Scott, Pharm.D.

Steven J. Kelsey, Pharm.D.
Thomas Payne, M.D., FACMI
ASHP Guidelines on the Design of Database-Driven
Greg Burger, Pharm.D.
Clinical Decision Support: Strategic Directions for Drug
Toby Clark, M.Sc., FASHP, FFIP
Database and Electronic Health Records Vendors
Laura Fochtmann, M.D., MBI
Jody Jacobson Wedret, FASHP, FCSHP
Authors: Bruce W. Chaffee, Pharm.D.
James J. Cimino, M.D., FACP, FACMI
Raymond C. Chan, Pharm.D.
Michelle DeLuca Fraley, Pharm.D.
Allen Flynn, Pharm.D.
John Poikonen
Michael A. Jones, Pharm.D
Brittany L. Melton, Ph.D., Pharm.D.
Andrew P. Laegeler, M.S., Pharm.D.
Kerry Goldrosen, Pharm.D.
Trinh Le, B.S.Pharm., M.S., FASHP
Tejal Gandhi, M.D., M.P.H (NPSF)
Andrew H. Smith, B.S.Pharm., M.H.A.
Philip Emberley, Pharm.D., M.B.A. (CPA)
David Troiano, B.S.Pharm., MSIA, CPPS
Elizabeth Wade, Pharm.D., BCPS (NHSHP)
Howard Strasberg (WKH)
Reviewers: Marc Willner, Pharm.D.
Gary J. Kerr, M.B.A., Pharm.D.
Organization Reviewers:
Lois F. Parker, B.S.
National Patient Safety Foundation (NPSF)*
Adrienne Au, Pharm.D., M.S., FASHP
Canadian Pharmacists Association (CPA)*
James Ponto, M.S., BCNP, FASHP
New Hampshire Society of Health-System
Karen Michaud, Pharm.D., BCPS
Pharmacists (NHSHP)*
John Hamiel, Pharm.D.
Wolters Kluwer Health (WKH)*
Philip J. Schneider, M.S.
Introduction xix
Introduction
ASHP is the national professional organization whose more The guidance documents of ASHP represent a con-
than 40,000 members include pharmacists, student pharma- sensus of professional judgment, expert opinion, and docu-
cists, and pharmacy technicians who serve as patient care mented evidence. They provide guidance and direction to
providers on healthcare teams in acute and ambulatory set- ASHP members and pharmacy practitioners and to other
tings. For over 70 years, ASHP has been on the forefront of audiences who affect pharmacy practice. Their use may help
efforts to improve medication use and advance healthcare. to comply with federal and state laws and regulations, to
ASHP is also a national accrediting organization for phar- meet accreditation requirements, and to improve pharmacy
macy residency and pharmacy technician training programs. practice and patient care. They are written to establish rea-
sonable goals, to be progressive and challenging, yet attain-
The Compendium able as “best practices” in applicable health-system settings.
They generally do not represent minimum levels of practice,
ASHP, since its founding, has developed official professional unless titled as such, and should not be viewed as ASHP
policies in the form of policy positions and guidance docu- requirements.
ments about pharmacy practice, first for hospitals, and then The use of ASHP’s guidance documents by members
for the continuum of practice settings in integrated health and other practitioners is strictly voluntary. Their content
systems. Since 1984, these policies have been compiled an- should be assessed and adapted based on independent
nually in this compendium, a compilation of ASHP policy judgment to meet the needs of local health-system settings.
positions, statements, guidelines, technical assistance bulle- The need for authoritative guidance in pharmacy
tins, therapeutic position statements, therapeutic guidelines, practice has grown with changes in health care and with
and selected ASHP-endorsed documents. Best Practices the shifting influences from regulatory, accrediting, risk-
reflects the intent of ASHP’s professional policies to foster management, financing, and other bodies. Because of the
improvements in pharmacy practice and patient care. complex nature of ASHP guidance documents, ASHP does
The compendium is organized by topic to help readers not typically undertake immediate development of new
quickly locate related documents. The table of contents documents or expedited revisions to existing documents in
is structured by topic, and under each topic the relevant response to environmental changes. Other ASHP activities
ASHP policy positions, statements, guidelines, technical and services, such as educational sessions at national
assistance bulletins, and endorsed documents are listed. The meetings and American Journal of Health-System Pharmacy
therapeutic documents are listed by type. Following the table (AJHP) articles, provide more timely information that may
of contents is a page locator for documents by type and title, be helpful, until sufficient experience is gained to serve as
and the index lists each document, to assist readers who are the basis for a document.
accustomed to searching for a specific document by its title.
Definitions
Origins and Purposes of ASHP’s Policy
Positions and Guidance Documents The types of guidance documents included in this compen-
dium are defined as follows:
Policy positions generally originate with an ASHP coun-
cil and are approved by the ASHP Board of Directors and ASHP Policy Position: A pronouncement on an issue related
ASHP House of Delegates. Some policy positions originate to pharmacy professional practice, as approved by the Board
as House of Delegate resolutions. Statements, guidelines, of Directors and House of Delegates.
and technical assistance bulletins originate with an ASHP
council or commission. Statements are approved by the ASHP Statement: A declaration and explanation of ba-
Board of Directors and the House of Delegates, because of sic philosophy or principle, as approved by the Board of
their broad philosophical nature. Other types of documents Directors and the House of Delegates.
are approved by the Board of Directors only. Therapeutic
position statements and therapeutic guidelines originate with ASHP Guideline: Advice on the implementation or op-
the ASHP Council on Therapeutics and are approved by the eration of pharmacy practice programs, as approved by the
Board of Directors. Board of Directors.
There is a gradation in detail among the guidance
documents. Policy positions are short pronouncements, ASHP Technical Assistance Bulletin: Specific, detailed ad-
intended to address professional practice. Often, principles vice on pharmacy programs or functions as developed by
established in policy positions are elaborated on in state- an ASHP staff division in consultation with experts, as ap-
ments and guidelines. Statements express basic philosophy, proved by the Board of Directors.*
guidelines offer programmatic advice, and technical assis-
tance bulletins offer more detailed programmatic advice. ASHP Therapeutic Guideline: Thorough, systematically
Of the two types of therapeutic documents, therapeutic developed advice for health-care professionals on appropri-
guidelines are thorough discussions of drug use and thera- ate use of medications for specific clinical circumstances, as
peutic position statements are concise responses to specific approved by the Board of Directors.
therapeutic issues.
xx Introduction
ASHP Therapeutic Position Statement: Concise statements of particular interest to ASHP’s membership may be
that respond to specific therapeutic issues of concern to published in AJHP, posted on ASHP’s Web site, or
health care consumers and pharmacists, as approved by the discussed at an open hearing or in a network forum
Board of Directors. during an ASHP Summer or Midyear Clinical meeting
to solicit comments.
ASHP-Endorsed Document: Professional policy developed 3. Based on the comments, a revised draft is submitted to
by another organization that offers guidance on some aspect the appropriate ASHP policy-recommending body for
of pharmacy practice or medication use, as approved by the action. When the draft meets the established criteria
Board of Directors. for content and quality, that body recommends that the
Board of Directors approve the document.
*The ASHP Board of Directors voted in November 1997 to discon-

ASHP Therapeutic Guidelines and
tinue the title “Technical Assistance Bulletin” in ASHP guidance Therapeutic Position Statements
documents, assigning the title “Guidelines” in its place. Over time,
the title “Guidelines” will replace the title “Technical Assistance The Council on Therapeutics (COT) has responsibility for
Bulletin” on existing documents when they are revised. the development of ASHP therapeutic guidelines and ASHP
therapeutic position statements.
Development of Guidance Documents Therapeutic Guidelines—The development of these docu-

ments generally includes the following steps:
The responsible ASHP council or commission recommends
the development of a guidance document after considering 1. When the COT identifies a topic for therapeutic
whether the topic: a) has generated a need among practitio- guidelines development, ASHP formally solicits pro-
ners for authoritative advice; b) has achieved some stability posals for a contractual arrangement with an indi-
and there is sufficient experience upon which to base a state- vidual, group, or organization to draft the guidelines
ment or guideline; c) is relevant to the practice of a signifi- document and coordinate its review. The contractor
cant portion of ASHP’s members; d) is within the purview of will work with a panel of 6–10 experts appointed by
pharmacy practice in health systems; e) is without other suf- ASHP who have diverse backgrounds relevant to the
ficient guidance; and f) does not pose significant legal risks topic.
to ASHP. Another consideration is whether ASHP leadership 2. A systematic analysis of the literature is performed,
believes that there is room for improvements in practice and and scientific evidence is evaluated based on prede-
that an ASHP document would foster that improvement. The termined criteria. Recommendations in the document
Board of Directors must support the recommendations be- are based on scientific evidence or expert consensus.
fore developmental processes begin. When expert judgment must be used, the document
The processes used to draft and review new or revised indicates the scientific reasoning that influenced the
documents vary depending on the body responsible for their decision. Scientific evidence takes precedence over
development and on the type of document. These processes expert judgement. Each recommendation is accom-
are described below. Once approved, the document draft panied by projections of the relevant health and cost
becomes an official ASHP policy and is published in AJHP, outcomes that could result.
added to ASHP’s Web site, and incorporated into the next 3. The expert panel and COT review each draft of the
edition of this compendium. Therapeutic documents are re- guidelines document and provide comments. This pro-
viewed and revised as needed every three years, and policy cess is repeated until the expert panel and COT are
positions and practice documents every five years. satisfied with the content.
4. ASHP solicits multidisciplinary expert input on the
ASHP Statements and Guidelines draft. Reviewers consist of members and selected in-
dividuals knowledgeable in the content area, represen-
Any of the ASHP policy-recommending bodies (councils tatives of various ASHP bodies, and other professional
and commissions) may initiate and oversee the develop- organizations.
ment of ASHP statements and guidelines; however, most of 5. Once the above processes are completed, COT recom-
them are initiated by the Council on Pharmacy Practice. The mends that the ASHP Board of Directors approve it.
development of these documents generally includes the fol-
lowing steps: ASHP Therapeutic Position Statements (TPS)—The devel-
opment of these documents generally includes the following
1. A group of experts on a given topic volunteers to steps:
develop a preliminary draft. Drafters are selected
based on demonstrated knowledge of the topic and 1. One or more experts on a given topic are assigned to
their practice settings. Most often, the drafters are draft the TPS. Drafters are selected based on demon-
ASHP members. strated knowledge of the topic and their practice set-
2. The draft is sent by ASHP to reviewers who have inter- ting. Most often, the drafters are ASHP members.
est and expertise in the given topic. Reviewers consist 2. The proposed draft document is reviewed by COT,
of members and selected individuals knowledgeable which may suggest modifications. This process is re-
in the content area, representatives of various ASHP peated until COT is satisfied with the content.
bodies, and other professional organizations. A draft
Introduction xxi
3. ASHP solicits multidisciplinary expert input on the Opportunities to Be a Part of Guidance

draft. Reviewers consist of members and selected in-
Document Development
dividuals knowledgeable in the content area, represen-
tatives of various ASHP bodies, and other professional
ASHP members determine the needs for policy guidance
organizations.
documents. They write and review the drafts. And, as mem-
4. Once the above processes are completed, COT final-
bers of policy-recommending bodies, the Board of Directors,
izes the draft and recommends that the ASHP Board of
and House of Delegates, they approve the documents.
Directors approve it.
ASHP members are encouraged to take an active
role in the development of documents by suggesting topic
Access to ASHP Positions ideas for new documents or modifications to current ones,
and Guidance Documents volunteering to be drafters or reviewers, and completing
survey and evaluation forms. Members may comment on or
Besides publishing in AJHP and this compendium, policy express their interests in participating in the development of
positions and guidance documents are available through documents by contacting the editor at (301) 657-3000 or by
ASHP’s Web site at www.ashp.org. They are located at the e-mail at standards@ashp.org.
“Policy Positions & Guidelines” heading under “Policy and
Practice” on the ASHP Web site (www.ashp.org/bestpractices),
where a chronological compendium of policy positions (ASHP
Policy Positions 1982–2015) is also available.
xxii ASHP Mission Statement and Vision Statement
Mission Statement of the American Society

of Health-System Pharmacists (ASHP)
The mission of pharmacists is to help people achieve op-
timal health outcomes. ASHP helps its members achieve Approved by the ASHP Board of Directors, December 6, 2012.
this mission by advocating and supporting the professional
practice of pharmacists in hospitals, health systems, ambula- Copyright © 2012, American Society of Health-System
tory clinics, and other settings spanning the full spectrum of Pharmacists. All rights reserved.
medication use. ASHP serves its members as their collective
voice on issues related to medication use and public health.
Vision Statement of the American Society

of Health-System Pharmacists (ASHP)
ASHP’s vision is that medication use will be optimal, Approved by the ASHP Board of Directors, December 6, 2012.
safe, and effective for all people all of the time.
Copyright © 2012, American Society of Health-System
Pharmacists. All rights reserved.
ASHP Policy Positions,
Statements, Guidelines, and
Technical Assistance Bulletins
Automation and Information
Technology
4 Automation and Information Technology–Positions
Automation and Information Technology

Online Pharmacy and Internet Prescribing (1529) Pharmacist’s Role in Health Care Information Systems
Source: Council on Pharmacy Practice (1211)
To support efforts to regulate prescribing and dispensing of Source: Council on Pharmacy Management
medications via the Internet; further, To strongly advocate key decision-making roles for phar-
To support legislation or regulation that requires on- macists in the planning, selection, design, implementation,
line pharmacies to list the states in which the pharmacy and and maintenance of medication-use information systems,
pharmacists are licensed, and, if prescribing services are electronic health records, computerized provider order en-
offered, requires that the sites (1) ensure that a legitimate try systems, and e-prescribing systems to facilitate clinical
patient-prescriber relationship exists (consistent with profes- decision support, data analysis, and education of users for
sional practice standards) and (2) list the states in which the the purpose of ensuring the safe and effective use of medica-
prescribers are licensed; further, tions; further,
To support mandatory accreditation of online phar- To advocate for incentives to hospitals and health sys-
macies by the National Association of Boards of Pharmacy tems for the adoption of patient-care technologies; further,
Verified Internet Pharmacy Practice Sites or Veterinary- To recognize that design and maintenance of medica-
Verified Internet Pharmacy Practice Sites; further, tion-use information systems is an interdisciplinary process
To support appropriate consumer education about the that requires ongoing collaboration among many disciplines;
risks and benefits of using online pharmacies; further, further,
To support the principle that any medication distri- To advocate that pharmacists must have accountability
bution or drug therapy management system must provide for strategic planning and direct operational aspects of the
timely access to, and interaction with, appropriate profes- medication-use process, including the successful deploy-
sional pharmacist patient-care services. ment of medication-use information systems.
This policy supersedes ASHP policy 0523. This policy supersedes ASHP policy 0921.
Risk Assessment of Health Information Technology Clinical Decision Support Systems (1212)
(1418) Source: Council on Pharmacy Management
Source: Council on Pharmacy Management To advocate for the development of clinical decision support
To urge hospitals and health systems to directly involve de- (CDS) systems that are proven to improve medication-use
partments of pharmacy in performing appropriate risk as- outcomes and that include the following capabilities: (1)
sessment before new health information technology (HIT) is alerts, notifications, and summary data views provided to
implemented or existing HIT is upgraded, and as part of the the appropriate people at the appropriate times in clinical
continuous evaluation of current HIT performance; further, workflows, based on (a) a rich set of patient-specific data,
To advocate that HIT vendors provide estimates of the (b) standardized, evidence-based medication-use best prac-
resources required to implement and support new HIT; fur- tices, and (c) identifiable patterns in medication-use data in
ther, the electronic health record; (2) audit trails of all CDS alerts,
To collaborate with HIT vendors to encourage the notifications, and follow-up activity; (3) structured clinical
development of HIT that improves patient-care outcomes; documentation functionality linked to individual CDS alerts
further, and notifications; and (4) highly accessible and detailed
To advocate for changes in federal law that would rec- management reporting capabilities that facilitate assessment
ognize HIT vendors’ safety accountability. of the quality and completeness of CDS responses and the
effects of CDS on patient outcomes.
Interoperability of Patient-Care Technologies (1302)
Source: Council on Pharmacy Management Definition of Meaningful Use of Health Information
To encourage interdisciplinary development and imple- Technology (1006)
mentation of technical and semantic standards for health Source: Council on Public Policy
information technology (HIT) that would promote the in- To advocate to policymakers (public and private) that defini-
teroperability of patient-care technologies that utilize med- tions of “meaningful use of health information technology”
ication-related databases (e.g., medication order processing address interoperability of medication orders and prescrip-
systems, automated dispensing cabinets, intelligent infusion tions, medication decision support and continuous improve-
pumps, electronic health records); further, ment, and quality reporting; further,
To encourage the integration, consolidation, and har- To advocate with respect to interoperability of medica-
monization of medication-related databases used in patient- tion orders and prescriptions that (1) a common medication
care technologies to reduce the risk that outdated, inaccu- vocabulary be mandated to promote the semantic interop-
rate, or conflicting data might be used and to minimize the erability of medication use across the continuum of care,
resources required to maintain such databases. because a common vocabulary is essential for comparative
effectiveness research and for communicating medication
information; and (2) communication of orders and elec-
tronic prescriptions must be demonstrated to be functional
and semantically interoperable with pharmacy information
systems; further,
Automation and Information Technology–Positions 5
To advocate with respect to medication decision sup- To urge computer software vendors and pharmaceuti-
port and continuous improvement that (1) medication deci- cal suppliers to provide standards for definition, collection,
sion support should include but not be limited to allergy, coding, and exchange of clinical data used in the medication-
drug interaction (e.g., drug-lab or drug-disease interactions), use process; further,
duplicate therapy, and dose-range checking; and (2) that To pursue formal and informal liaisons with appro-
such a decision-support service must include an ongoing, priate health care associations to ensure that the interests
continuous improvement process to attune the decision-sup- of patient care and safety in the medication-use process are
port service to the needs of the providers who use it; further, fully represented in the standardization, integration, and
To advocate with respect to quality reporting that implementation of electronic information systems; further,
the ability to quantify improved patient safety, quality out- To strongly encourage health-system administrators,
comes, and cost reductions in the medication-use process regulatory bodies, and other appropriate groups to provide
is essential, particularly in antimicrobial and adverse event health-system pharmacists with full access to patient-specific
surveillance. clinical data.
This policy was reviewed in 2014 by the Council on This policy was reviewed in 2014 by the Council on
Public Policy and by the Board of Directors and was found Pharmacy Practice and by the Board of Directors and was
to still be appropriate. found to still be appropriate.
Role of Pharmacists in Safe Technology Implementation Computerized Prescriber Order Entry (0105)
(1020) Source: Council on Administrative Affairs
Source: Council on Pharmacy Practice To advocate the use of computerized entry of medication or-
To affirm the essential role of the pharmacist in the evalua- ders or prescriptions by the prescriber when (1) it is planned,
tion, implementation, and ongoing assessment of all technol- implemented, and managed with pharmacists’ involvement,
ogy intended to ensure safety, effectiveness, and efficiency (2) such orders are part of a single, shared database that is
of the medication-use process. fully integrated with the pharmacy information system and
This policy was reviewed in 2014 by the Council on other key information system components, especially the
Pharmacy Practice and by the Board of Directors and was patient’s medication administration record, (3) such com-
found to still be appropriate. puterized order entry improves the safety, efficiency, and
accuracy of the medication-use process, and (4) it includes
Electronic Health and Business Technology and Services provisions for the pharmacist to review and verify the or-
(0712) der’s appropriateness before medication administration, ex-
Source: Council on Pharmacy Practice cept in those instances when review would cause a medically
To encourage pharmacists to assume a leadership role in unacceptable delay.
their hospitals and health systems with respect to strategic This policy was reviewed in 2010 by the Council on
planning for and implementation of electronic health and Pharmacy Management and by the Board of Directors and
business technology and services; further, was found to still be appropriate.
To encourage hospital and health-system administra-
tors to provide dedicated resources for pharmacy depart- Telepharmacy (9920)
ments to design, implement, and maintain electronic health Source: Council on Professional Affairs
and business technology and services; further, To foster among health-system pharmacists and leaders of
To advocate the inclusion of electronic health tech- the telecommunications industry a common vision for the
nology and telepharmacy issues and applications in college integration of telecommunication technology into the deliv-
of pharmacy curricula. ery of pharmaceutical care.
Pharmacy Practice and by the Board of Directors and was Pharmacy Practice and by the Board of Directors and was
found to still be appropriate. found to still be appropriate.
Electronic Information Systems (0507) Regulation of Automated Drug Distribution Systems (9813)
Source: Council on Administrative Affairs Source: Council on Legal and Public Affairs
To advocate the use of electronic information systems, with To work with the Drug Enforcement Administration and
appropriate security controls, that enable the integration of other agencies to seek regulatory and policy changes to
patient-specific data that is accessible in all components of a accommodate automated drug distribution in health systems.
health system; further, This policy was reviewed in 2012 by the Council on
To support the use of technology that allows the trans- Public Policy and by the Board of Directors and was found
fer of patient information needed for appropriate medication to still be appropriate.
management across the continuum of care; further,
6 Automation and Information Technology–Statements
ASHP Statement on Bar-Code-Enabled Medication

Administration Technology
Position implemented BCMA systems have tremendous potential to
improve patient safety. In addition, the reengineering of the
The American Society of Health-System Pharmacists (ASHP) medication-use process required to implement a BCMA sys-
encourages health systems to adopt bar-code-enabled medica- tem can provide opportunities for performance improvement
tion administration (BCMA) technology to improve patient in patient care and clinical documentation.
safety and the accuracy of medication administration and A 2005 ASHP survey estimated that only 13.2% of
documentation. To support the goal of having all medications hospitals used a BCMA system.6 Although this percentage is
electronically verified before they are administered, BCMA small, it represents an almost 10-fold increase since 2002.7
systems should be used in all areas of health systems in which The rapid adoption of BCMA systems presents challenges to
medications are used. Pharmacists must be involved in the health systems, and ASHP believes that pharmacists have a
interdisciplinary planning, development, implementation, and crucial role in responding to those challenges.
management of BCMA systems and must ultimately be re-
sponsible for developing and maintaining the infrastructure Role of the Pharmacist
required to ensure BCMA success. Health systems deploying
BCMA programs must provide the funding and staffing nec- Pharmacists should take the lead in ensuring that the imple-
essary to permit pharmacists to fulfill this role. mentation of BCMA systems and the reengineering of the
ASHP urges the Food and Drug Administration (FDA) medication-use system address the complexities of the proc-
and other regulatory agencies, standard-setting bodies, con- ess and that the goal of improving patient safety is achieved.
tracting entities, health systems, and others to mandate that Poor design and inadequate planning can compromise the
pharmaceutical manufacturers use symbologies that are effectiveness of a BCMA system and may even introduce
readily deciphered by commonly used scanning equipment new sources of error into the medication-use process.8
to code for the National Drug Code (NDC), lot number, and Growing experience with BCMA systems has produced a
expiration date on all unit dose, unit-of-use, and injectable body of knowledge that will aid hospitals and health systems
drug packaging. Pharmaceutical manufacturers should also in the adoption of BCMA systems.9–12
provide all medications used in health systems in unit dose Pharmacy leadership needs to engage the chief infor-
packages. FDA, pharmaceutical manufacturers and packag- mation officer, chief nursing officer, and other key stake-
ers, and the manufacturers of BCMA systems should collab- holders in planning for BCMA systems as early as possible.
orate to minimize or eliminate the causes of false rejection Pharmacists and nurses should be involved with the prein-
of valid medication doses. Certain characteristics of the cur- stallation evaluation and selection of the BCMA system.
rent NDC identification system contribute to the burden of Allowing end users to provide crucial advice about system
implementing BCMA systems, and ASHP urges stakehold- design will increase acceptance and utility of the system.
ers to participate in efforts to develop a system that more Implementation of a BCMA system must be accompa-
reliably identifies the unique drug (or combination of drugs), nied by the development of policies and procedures that en-
strength, dosage form, and route of administration. sure the system’s safety. These policies and procedures should
Although bar-coding systems are currently a widely be developed by an interdisciplinary team that includes phar-
used point-of-care technology, ASHP recognizes that other macists.10 Pharmacists and nurses should be involved with
types of machine-readable coding (e.g., radio-frequency postinstallation evaluation and system improvement.
identification) may evolve. ASHP supports the use of new The role of nurses as end users of this technology
technologies that are as effective as or improve upon exist- should not be underestimated; nursing involvement is essen-
ing systems and believes the principles outlined in this state- tial to successful system implementation and use. Processes
ment apply to such systems. ASHP urges further research on for delivery and storage of medications (e.g., in medicine
such systems as well as research that will definitively deter- rooms or bedside storage spaces) should be examined by
mine the extent to which BCMA systems reduce preventable pharmacists and nurses to avoid workarounds or diversion.
medication errors and provide a financial return on invest-
ment for health systems. Elements of a BCMA System
Background Although every hospital and health system will need to de-
velop a BCMA system that meets its own needs, the follow-
Since the 1980s, health care practitioners and policymakers ing general principles should guide the implementation and
have recognized the potential benefits of using bar-coding use of such systems.
technology in the medication dispensing and administration Use of the BCMA system should be universal within
process.1–5 Although there is a consensus of professional the health system. To the fullest extent feasible, every pa-
judgment and expert opinion on the advancement of BCMA tient, care provider, and medication should receive a unique
technology, more studies are needed to definitively deter- identifier, and that identifier should be used not only to ver-
mine the impact of BCMA systems on medication errors and ify care prescribed for a patient but also to document every
the finances of health systems. ASHP believes that optimally significant step in the medication-use process.
Automation and Information Technology–Statements 7
A process should be in place to ensure simple, secure, ASHP believes that pharmaceutical manufacturers
and controllable placement and replacement of a patient should be required to place machine-readable coding that
identification tag. To ensure that there is only one active includes the NDC, lot number, and expiration date on all
wristband per patient, this process should discourage the unit dose, unit-of-use, and injectable drug packaging, us-
printing of multiple labels.12 In addition to appropriate hu- ing symbologies that are readily deciphered by commonly
man-readable information, machine-readable patient wrist- used scanning equipment. ASHP also urges further research
bands should contain information (e.g., a photograph or the that will definitively determine the extent to which BCMA
patient’s medical record number) in order to uniquely iden- systems reduce preventable medication errors or provide a
tify the patient. financial return on investment for health systems.
The BCMA system should have a secure user-identification
system. Every care provider should be assigned and use a References
unique identifier. The care provider administering a medi-
cation should be able to use the BCMA system to verify 1. Hokanson JA, Keith MR, Guernsey BG et al. Potential
that the medication to be administered is appropriate for the use of barcodes to implement automated dispens-
patient (i.e., confirming that the five rights of medication ing quality assurance programs. Hosp Pharm. 1985;
administration13 are met). The BCMA system should docu- 20:327–37.
ment the information in the electronic medication adminis- 2. Nold EG, Williams TC. Barcodes and their potential
tration record. applications in hospital pharmacy. Am J Hosp Pharm.
The pharmacy must be able to ensure that doses re- 1985; 42:2722–32.
ceived in patient care areas can be scanned without inappro- 3. Barry GA, Bass GE, Eddlemon JK et al. Bar-code
priate rejection and that those scans reliably indicate whether technology for documenting administration of large-
the medication is appropriate for a particular patient. For the volume intravenous solutions. Am J Hosp Pharm.
implementation of a BCMA system to succeed, the health 1989; 46:282–7.
system must commit the pharmacy resources necessary to 4. Lefkowitz S, Cheiken H, Barhart MR. A trial of the
verify that each incoming medication is scannable and that use of bar code technology to restructure a drug distri-
the data encoded within its bar code accurately represent the bution and administration system. Hosp Pharm. 1991;
product. 26:239–42.
Every medication possible should be packaged in unit 5. Meyer GE, Brandell R, Smith JE et al. Use of bar
doses, and each unit dose package should be labeled with codes in inpatient drug distribution. Am J Hosp Pharm.
both human-readable medication identification information 1991; 48:953–66.
and a machine-readable code that includes the medication’s 6. Pedersen CA, Schneider PJ, Scheckelhoff DJ. ASHP
unique identifier and, when feasible, its lot number and ex- national survey of pharmacy practice in hospital set-
piration date. Pharmacy information systems must be able to tings: dispensing and administration—2005. Am J
generate bar codes for multiple-component items. Pharmacy Health-Syst Pharm. 2006; 63:327–45.
departments must develop a validation process for ensuring 7. Pedersen CA, Schneider PJ, Scheckelhoff DJ. ASHP
that every item has a bar code that can be scanned by all national survey of pharmacy practice in hospital set-
equipment supporting the BCMA system, including phar- tings: dispensing and administration—2002. Am J
macy automation systems, automated medication storage Health-Syst Pharm. 2003; 60:52–68.
and distribution devices, and nursing BCMA scanning units. 8. Patterson ES, Cook RI, Render ML. Improving patient
An adequate number of scanners should be provided safety by identifying side effects of introducing bar
for each patient care area to facilitate scanning at peak times. coding in medication administration. J Am Med Inform
Scanners should have the capacity to autodiscriminate the Assoc. 2002; 9:540–53.
variety of symbologies encountered on pharmaceutical and 9. Patterson E, Rogers M, Render M. Fifteen best prac-
pharmacy-prepared containers. tice recommendations for bar-code medication admin-
Finally, contingency plans should exist to ensure pa- istration in the Veterans Health Administration. Joint
tient safety during system downtime. These policies should Comm J Qual Saf. 2004; 30:355–65.
require that medications administered during downtime are 10. Neuenschwander M, Cohen MR, Vaida AJ et al.
retrospectively documented electronically in the medical Practical guide to bar coding for patient medication
record so that decision-support systems accurately reflect safety. Am J Health-Syst Pharm. 2003; 60:768–79.
clinical trends associated with the patient, medication ad- 11. ASHP Research and Education Foundation
ministration, and medication effects. Implementing a bar-coded medication safety program:
a pharmacist’s toolkit. www.ashpfoundation.org/
Conclusion MainMenuCategories/Education/SpecialPrograms/
ImplementingaBarCodedMedSafetyProgram.aspx
ASHP encourages health systems to adopt BCMA technol- (accessed 2008 Dec 3).
ogy, with the goal of having all medications electronically 12. Cummings J, Bush P, Smith D et al. Bar-coding medi-
verified before they are administered. Pharmacists must cation administration overview and consensus recom-
ultimately be responsible for developing and maintaining mendations. Am J Health-Syst Pharm. 2005; 62:2626–
the infrastructure necessary to ensure BCMA success, and 9.
health systems deploying BCMA systems must provide the 13. 10 Golden rules for administering drugs safely.
funding and staffing necessary to permit pharmacists to In: McGovern K. Preventing medication errors.
fulfill this role. Springhouse, PA: Springhouse; 1994:2–3.
Suggested Readings or Other Resources

Developed through the ASHP Section of Pharmacy Informatics
ASHP guidelines on preventing medication errors in hospi- and Technology and approved by the ASHP Board of Directors on
tals. Am J Hosp Pharm. 1993; 50:305–14. March 7, 2008, and by the ASHP House of Delegates on June 10,
Aspden P, Wolcott J, Bootman JL et al., eds. Preventing 2008. Supersedes ASHP policy position 0308.
medication errors: quality chasm series. Washington,
DC: National Academies Press; 2007. Copyright © 2009, American Society of Health-System Pharmacists,
Cohen MR, ed. Medication errors. Washington, DC: Inc. All rights reserved.
American Pharmaceutical Association; 1999.
Johnson CL, Carlson RA, Tucker CL et al. Using BCMA Arash T. Dabestani, Pharm.D., M.H.A. and Alicia B. Perry,
software to improve patient safety in Veterans Pharm.D., are gratefully acknowledged for drafting versions of this
Administration medical centers. J Healthc Inf Manage. statement.
2002; 16:46–51.
Leape LL. Error in medicine. JAMA. 1994; 272:1851–7. The bibliographic citation for this document is as follows: American
Poon EG, Cina JL, Churchill W et al. Medication dispens- Society of Health-System Pharmacists. ASHP statement on bar-
ing errors and potential adverse drug events before and code-enabled medication administration technology. Am J Health-
after implementing bar code technology in the phar- Syst Pharm. 2009; 66:588–90.
macy. Ann Intern Med. 2006; 145:426–34.
Puckett F. Medication management component of a point
of care information system. Am J Health-Syst Pharm.
1995; 52:1305–9.
ASHP Statement on Bar-Code Verification

During Inventory, Preparation, and Dispensing
of Medications
Position In addition, for BCMA to function, a vast majority of doses

must be accurately bar coded, meaning there must be a
The American Society of Health-System Pharmacists en- highly reliable relationship between the information in the
courages hospital and health-system pharmacies to incor- bar code and the contents of the dose. Additionally, the bar
porate bar-code scanning into inventory management, dose code must be readable by commercially-available scan-
preparation and packaging, and dispensing of medications. ners. Although doses delivered directly from manufacturer-
The purpose of such scanning is to ensure that drug products labeled packages generally meet these conditions, there are
distributed, deployed to intermediate storage areas, or used numerous drug products that may not:
in the preparation of patient doses are the correct products,
are in-date, and have not been recalled. Such bar-code scan- • Commercial products may lack a readily readable bar
ning should be employed in: code, may have an irregular package shape that con-
founds the ability of scanning equipment to read the
• Stocking of inventory both in the pharmacy and in bar code, or may have a bar code in a symbology for-
other locations from which patient medications may mat that cannot be interpreted by the institution’s bar-
be dispensed (e.g., an automated dispensing device), code scanning software.
• Manual packaging of oral solid and liquid medica- • Nurse-prepared medications (e.g., insulin doses, hepa-
tions, rin boluses, or syringes pre-drawn in the operating
• Compounding, repackaging, and labeling processes room) may be prepared at a location other than the pa-
(e.g., scanning of source ingredients), tient’s bedside, with the result that there is no labeling
• Retrieving medications from automated dispensing of any kind on the dose when it is administered.
devices, and • Compounded medications (e.g., sterile preparations)
• Dispensing from the pharmacy to any location. are often labeled by the pharmacy with a bar code
that references a prescription or order number that
Prudent use of bar-coding technology in these processes will describes the intended contents of the prescribed dose
enhance patient safety and the quality of care by improv- but provides no assurance that the prescribed contents
ing the accuracy of core pharmacy functions, closing poten- were actually used in the product’s preparation.
tial gaps in the bar-code-assisted medication administration
(BCMA) process, and allowing better allocation of pharma- Benefits of Bar-Code Verification During
cists’ knowledge and skills. Inventory, Preparation, and Dispensing
Background Initial estimates of the contribution of pharmacy dispens-

ing errors to the overall medication errors were quite low.3
Discussion of the role of technology in improving medica- However, recent reports have suggested that adding bar cod-
tion safety almost universally focuses on BCMA or coming to the pharmacy dispensing process can significantly re-
puterized provider order entry (CPOE), despite evidence of duce opportunities for medication errors at the bedside and
medication errors that neither CPOE nor BCMA could pre- reduce the occurrence of potential adverse drug reactions.4-6
vent.1,2 A number of activities in the medication-use process Incorporating bar-code scanning in inventory management,
create opportunities for error outside of medication ordering dose preparation and packaging, and dispensing can im-
and administration systems, such as: prove patient safety in the following ways:
• Receiving of inventory from suppliers and stocking of • Scanning during stocking in the pharmacy or patient-
inventory locations from which patient medications care locations (e.g., loading of an automated dispens-
may be dispensed (e.g., stocking unit-based automated ing device) can help ensure that the product is placed
dispensing devices with medications that may not be in the correct location.
delivered to the bedside in their original packaging). • Scanning during the retrieval of medications mitigates
• Packaging of medications, which has become more the hazards of erroneous medication stocking, which is
prevalent as BCMA systems are more widely adopted especially important in the case of automated dispens-
by health systems and manufacturers have discontin- ing devices, where there is a potential risk that caregiv-
ued unit dose packaging of medications. ers will override controls and remove medications for
• Manual packaging of liquid medications in ready-to- immediate use.
administer form. • Scanning of source ingredients during compound-
• The compounding of medications. ing, repackaging, or labeling processes can ensure
• The dispensing of patient-specific medications (e.g., that labeled doses contain the appropriate ingredients.
24-hour medication carts, nurse servers). Additionally, such scanning creates a reliable link be-
tween the information in the final package’s bar code, the entire system, as the system cannot properly recognize
its contents, and the National Drug Code (NDC) of and evaluate the drug products being scanned. Procedures
the source container, which may be required to sat- should address such issues as the expected behavior while
isfy billing requirements (e.g., those of the Centers for scanning occurs, specific prohibited acts, and the penalties
Medicare & Medicaid Services). associated with known at-risk behavior.11
• Scanning on dispensing can help prevent look-alike, In addition, this statement should not be interpreted to
sound-alike medication substitution errors that are dif- express a preference for bar-code scanning over other forms
ficult to visually detect, can identify and remove from of automated identification of medications. Currently, bar
distribution drug products whose bar codes are miss- coding is the least-expensive mechanism to introduce and
ing or unreadable, and prevent the distribution of ex- deploy throughout the medication management cycle.12
pired or recalled products or facilitate retrieval in case Should other technologies (e.g., radio-frequency identifica-
of a recall. tion) demonstrate similar or better capabilities, the princi-
• Scanning during any of these activities permits accu- ples articulated in this statement will continue to apply.
mulation of an audit trail for each transaction in the
inventory, preparation, and dispensing process. This Validation
information provides indications of the frequency of
error encounter and detection, a record of the amount As with all such systems, bar coding on dispensing presumes
of time needed to perform selected functions, and evi- that the scanning software, the scanning hardware, and the
dence of success or failure of manual processes to de- associated underlying database are accurate and complete.
liver the correct medication. To ensure accuracy and completeness, organizations using
a bar coding process will need to validate both that the soft-
Bar-code verification is optimized, and its potential nega- ware operates as expected and that the underlying database
tive impacts on productivity minimized, when the scanning information is correct and reliable. A process will also need
system is configured to use bar codes on bulk packages (e.g., to be in place to immediately remediate problems if it is
the bar code on an unopened case of unit-dose-packaged tab- discovered that the hardware, software, or database are not
lets) to confirm the contents of each item in the case, es- operating properly.
pecially during batch processes. For patient-specific doses,
each individual container used for the dose must be scanned.
The equipment and training costs for a pharmacy-based Conclusion
bar-code scanning implementation is quite small, especially
when compared to those of BCMA systems.7 Pharmacy-based Prudent use of bar-code scanning in inventory management,
bar-code scanning implementation may be considered a pre- dose preparation and packaging, and dispensing of medica-
requisite for BCMA success, because unreadable bar codes tions can enhance patient safety and the quality of care. Such
are a significant cause of BCMA implementation failures.8,9 scanning also provides the opportunity to accumulate and
use statistics on the pharmacy distributive operation that can
direct more appropriate staffing, identify sources of routine
Limitations error, and generally permit better management of the drug
distribution process.
As with BCMA, adoption of bar code scanning within dis-
tribution processes creates the necessity to ensure that the
scanning system will recognize and appropriately respond References
to every bar code it scans. This verification activity is likely
to create significant additional work for the pharmacy. 1. Wolf R. Preventable medication error responsible
Pharmacies planning on implementing such systems must for infant deaths. Injury Board.com. Available at:
plan for the resources needed to ensure that properly bar- http://dallas.injuryboard.com/medical-malpractice/
coded products are presented to, and readable by, the scan- preventable-medication-error-responsible-for-infant-
ning system. deaths.aspx?googleid=206592 (accessed 2010 Jan 11).
In addition, as with other bar-code technology imple- 2. Institute for Safe Medication Practices. Failed check
mentations, pharmacy-based bar-code scanning systems will system for chemotherapy leads to pharmacist’s no
only be beneficial if appropriately deployed. For example, contest plea for involuntary manslaughter. www.ismp.
given the need to scan three vials of medication to prepare org/Newsletters/acutecare/articles/20090423.asp (ac-
an IV admixture, such a system cannot distinguish between cessed 2010 Mar 4).
scanning each vial and scanning the same vial three times, 3. Bates DW, Cullen DJ, Laird N et al. Incidence of ad-
although the latter defeats the purpose of the scanning. Any verse drug events and potential adverse drug events.
program of pharmacy-based bar-code scanning should be ac- Implications for prevention. ADE Prevention Study
companied by appropriate training, policies, and procedures Group. JAMA. 1995; 274:29–34.
to promote and optimize safe use of the system, as well as a 4. Cina J, Fanikos J, Mitton P et al. Medication errors in
regular program of auditing to ensure that the program is be- a pharmacy-based bar-code-repackaging center. Am J
ing properly deployed by staff. Additionally, such programs Health-Syst Pharm. 2006; 63:165–8.
require hospitals and health systems to compile and maintain 5. Poon EG, Cina JL, Churchill W et al. Medication dis-
a complete database of bar codes in use throughout the insti- pensing errors and potential adverse drug events be-
tution. The availability of such information in a timely fash- fore and after implementing bar code technology in the
ion is a well-recognized problem.10 An incomplete database pharmacy. Ann Intern Med. 2006;145:426–34.
or the absence of bar codes on drug products can undermine
6. Ragan R, Bond J, Major K et al. Improved control of

medication use with an integrated bar-code-packaging Developed through the ASHP Section of Pharmacy Informatics and
and distribution system. Am J Health-Syst Pharm. Technology and approved by the ASHP Board of Directors on April
2005; 62:1075–9. 15, 2010, and by the ASHP House of Delegates on June 6, 2010.
7. Maviglia SM, Yoo JY, Franz C et al. Cost-benefit anal-
ysis of a hospital pharmacy bar code solution. Arch This statement was drafted by the ASHP Section of Pharmacy
Intern Med. 2007; 167:788–94. Informatics and Technology 2009–2010 Section Advisory Group
8. Koppel R, Wetterneck T, Telles JL et al. Workarounds on Pharmacy Operations Automation (Dennis A. Tribble, Pharm.D.;
to barcode medication administration systems: their Ron Burnette, B.S.Pharm., M.B.A.; Dawn M. Biller; Leslie Brookins,
occurrences, causes and threats to patient safety. J Am M.S.; Richard Capps III, Pharm.D.; Marvin H. Choi; Kavish J.
Med Inform Assoc. 2008;15:408–23. Choudhary, Pharm.D., M.S.; Seth Aaron Cohen, Pharm.D.; Thomas
9. Young D. VA pursues bar code quality. Am J Health- W. Cooley M.B.A.; Arash T. Dabestani, Pharm.D., M.H.A., FABC;
Syst Pharm. 2004; 61:1312–4. Charles De la Torre, M.S., MIS; Doina Dumitru, Pharm.D., M.B.A.;
10. ASHP statement on bar-code-enabled medication ad- Christopher Fortier, B.S.Pharm.; Barbara Giacomelli, Pharm.D.,
ministration technology. Am J Health-Syst Pharm. 2009; MBA, FASHP; Staci Hermann, M.S., Pharm.D.; Gary L. Johnson,
66:588–90. www.ashp.org/DocLibrary/BestPractices/ Jr., Pharm.D., M.H.A.; Seth A. Kuiper, Pharm.D.; Denise Mckenzie,
AutoITStBCMA.aspx. (accessed 2010 Mar 4). B.S.Pharm.; Rhonda B. McManus, Pharm.D.; Eric C. Nemec, II,
11. ASHP policy position 0910: reporting medication er- Pharm.D.; Beth Prier, Pharm.D., M.S.; Brad Rognrud, M.S., R.Ph.;
rors. In: Hawkins B, ed. Best practices for hospital Kevin A. Scheckelhoff, M.B.A.; Paul M. Seelinger, B.S.Pharm.;
and health-system pharmacy: positions and guidance Suzanne B. Shea, M.B.A.; David A. Tjhio, M.S., Pharm.D.;
documents of ASHP. 2009-2010 ed. Bethesda, MD: Christopher J. Urbanski, M.S.; Gwen Volpe, B.S.Pharm.; Rayburn
American Society of Health-System Pharmacists; Brian Vrabel, Pharm.D.; and Robynn P. Wolfschlag, M.B.A.).
2006:160. www.ashp.org/DocLibrary/BestPractices/
MedMisPositions09.aspx (accessed 2010 Mar 08). ASHP gratefully acknowledges the following organizations and
12. Cummings J, Bush P, Smith D et al. Bar-coding medi- individuals for reviewing drafts of this statement (review does not
cation administration: overview and consensus recom- imply endorsement): American Association of Critical Care Nurses
mendations. Am J Health-Syst Pharm. 2005; 62:2626–9. (AACCN); American Nurses Association (ANA); Institute for
Safe Medication Practices (ISMP); Rhode Island Society of Health
Suggested Reading System Pharmacists (RISHP); South Carolina Society of Health-
System Pharmacists (SCSHP); Wyoming Society of Health-System
Bates DW, Cullen JC, Laird N et al. Incidence of adverse Pharmacy (WSHP); Linda Annecchini, M.S.; James L. Besier,
drug events and potential adverse drug events. JAMA. Ph.D., FASHP; Carol J. Bickford, Ph.D., RN-BC (ANA); Denny C.
1995; 274:29–34. Briley, Pharm.D.; Mary E. Burkhardt, M.S., FASHP; Richard Capps,
Nold EG, Williams TC. Bar codes and their potential appli- Pharm.D.; William W. Churchill, M.S.; Debra Cowan, Pharm.D.;
cations in hospital pharmacy. Am J Hosp Pharm. 1985; Michele Danish, Pharm.D, FASHP; Brent I. Fox, Pharm.D., Ph.D.;
42:2722–32. Karl F. Gumpper, BCNSP, BCPS, FASHP; Kathleen M. Gura,
Meyer GE, Brandell R, Smith JE et al. Use of bar codes in Pharm.D., BCNSP, FASHP; J. Chad Hardy, Pharm.D., M.S.; Robi
inpatient drug distribution. Am J Hosp Pharm. 1991;
Hellman, RN, MSN, CNS (AACCN); Matthew R. Keith, B.S.Pharm.,
48:953–66.
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ASHP Statement on the Pharmacist’s Role

in Clinical Informatics
Position Roles and Responsibilities
ASHP believes that pharmacists have the training, knowl- Pharmacists who practice clinical informatics must col-
edge, background, and responsibility to assume a significant laborate with other healthcare and information technol-
role in clinical informatics. ogy professionals to promote the safe, efficient, effective,
timely, and optimal use of medications. They contribute to
Background the transformation of healthcare by analyzing, designing,
implementing, maintaining, and evaluating information and
Healthcare organizations continue to invest a significant communication systems that improve medication-related
amount of financial and human resource in health informa- outcomes and strengthen the pharmacist-patient relation-
tion technology (HIT) initiatives, including advanced clini- ship. The role of a pharmacy informaticist revolves around
cal systems, electronic health records, business intelligence their knowledge of pharmacy practice, safe medication use,
clinical decision-making, and improving medication therapy
and analytics tools, and applications that deliver the highest
outcomes, combined with their understanding of the disci-
levels of patient safety and value. This growth has led to a
pline of informatics and HIT systems.10 Their primary roles
considerable demand for HIT workers but more importantly
and responsibilities must encompass five broadly defined
has identified the need for a workforce with training and
categories:
skills to create a successful and safe interface between HIT
and the healthcare delivery system. This workforce must un- Data, information, and knowledge management—

derstand healthcare; information and communication tech- Managing medication-related information while pro-
nology; and the people, processes, and culture of an organi- moting integration, interoperability, and information
zation. The intersection of these skills has commonly been exchange.
described as the discipline of biomedical and health infor-
Information and knowledge delivery—Delivering
matics, more recently termed clinical informatics.1 Evidence
medication-related information and knowledge
continues to emerge regarding the value a well-trained in-
throughout the clinical knowledge lifecycle, from the
dividual in clinical informatics can bring to an organization
point of knowledge generation through cataloging,
faced with implementing highly complex and transformative
embedding knowledge into the workflow, and measur-
HIT systems.2,3
ing the usage and effectiveness of that knowledge.
Pharmacy informatics has grown to be an integral
discipline within the clinical informatics domain, centered Practice analytics—Developing point-of-business
on the effective management and delivery of medication- analytic solutions for improving decision-making.
related data, information, and knowledge across systems Applied clinical informatics—Applying user experi-
that support the medication-use process. Pharmacists’ pro- ences, research, and theoretical informatics principles
fessional identity, education, training, and experience with to improve clinical practice and usability.
medication management make them ideal candidates to Leadership and management of change—Leading and
play a significant role and fill a critical need in pharmacy participating in the procurement, development, imple-
informatics. Their firm understanding of core pharmacy mentation, customization, management, evaluation,
operations, clinical practice, the medication-use process, and continuous improvement of clinical information
standards, and regulations and their long history of utiliz- systems.
ing technology to support medication management provide
the essential components for effectively transitioning into Data, Information, and Knowledge Management. Pharmacy
this role. Despite the growing number of formally trained informaticists play a key role in maintaining the data, infor-
pharmacy informaticists, the path and skills required for a mation, and knowledge assets across all systems that support
career in informatics has varied considerably, emphasizing medication management. They are instrumental in ensuring
the need to build core competencies and grow the number data quality and safety, minimizing data quality risks, and af-
of available programs.4-6 The American Board of Medical firming medication-related data, information, and knowledge
Specialties (ABMS) recognition of clinical informatics as a management best practices.10,11 Data quality and information
physician subspecialty will likely play an important role in management best practices encompass:
evolving pharmacy informatics beyond its current state to
one with a clinical edge, centered on analytics and delivering • Providing the appropriate level of data governance and
information and knowledge at the point of care. The ABMS stewardship.
decision may also impact the development of a standardized, • Adopting standard human and machine interpretable
interprofessional educational roadmap for individuals seek- formats.
ing a career in pharmacy informatics.7-9 • Utilizing controlled terminology for integration and
interoperability.
• Ensuring that data are accurate, accessible, complete,
consistent, current, timely, precise, at appropriate level
of granularity, reliable, relevant, conforming, and
understandable across all data quality management formatics plays a key role in analyzing these data for the
domains. purpose of understanding performance; evaluating process;
• Ensuring consistent use of maps to internal and exter- and reporting, predicting, and harvesting new information to
nal standards and reference data. create new knowledge for improving outcomes.
• Ensuring that system architecture supports data inter- Knowledge application and delivery. Pharmacy infor-
change. matics is responsible for leveraging knowledge at the right
• Ensuring that data, information, and knowledge are time and place within a provider’s workflow to improve
audited, measured, and evaluated for effectiveness. caregiver effectiveness, work satisfaction, patient satisfac-
• Ensuring that data, information, and knowledge assets tion, and the quality of care. Pharmacy informatics must
are validated, integrated, normalized, consolidated, continue to evolve to optimize clinical decision support use
and routinely optimized. and develop tools that reduce information overload and pro-
• Developing infrastructure for knowledge, metadata, vider burden. Pharmacy informatics is responsible for look-
and terminology management. ing beyond the traditional means of delivering knowledge by
• Ensuring that information is readily and rapidly under- analyzing process and outcomes data from existing applica-
stood and accessed within the workflow. tions to develop and implement new solutions for embed-
• Ensuring that information and knowledge are centrally ding knowledge into the workflow.13
managed, collaboratively developed, and easily dis- Knowledge asset management. Pharmacy informat-
seminated and maintained. ics must play a significant role in managing and support-
• Ensuring that information and knowledge are plat- ing a healthcare system’s technology-enabled medication
form-independent. information and knowledge assets. This role would include
• Developing tools to effectively maintain and manage assisting with authoring, encoding, cataloging, versioning,
data, information, and knowledge. updating, disseminating, and maintaining an inventory of
medication-related information and knowledge. Despite the
Maintenance roles and responsibilities include: emergence of commercial content management systems and
groupware, pharmacy informatics must provide the appro-
• Corrective maintenance—Taking corrective and edu-
priate level of oversight and governance for these activities
cative steps required to correct problems with the uti-
and play a role in the development of future knowledge as-
lization of a clinical information system or technology.
set management systems that support end-to-end knowledge
• Customized maintenance—Modifying features al-
engineering.
ready in production systems that require updating or
modification for user needs. Customized maintenance
Practice Analytics. The healthcare industry has historically
is essential in clinical information systems, as health-
generated large amounts of data driven by financial, regula-
care is constantly changing (e.g., with new drugs, new
tory, compliance, and patient-care-related activities. These
treatment guidance, new procedures).
data have primarily been stored in hard copy form, making it
• Enhancement maintenance—Improving the perfor-
difficult to process through traditional database management
mance of applications and people associated with the
tools. Paper records have also limited opportunities for effec-
use of tools.
tive exchange of information with other healthcare systems
• Preventive maintenance—Taking steps in advance to
or providing actionable insight on reducing costs, improving
reduce the risk of a problem that includes testing prior
to a new release or system upgrade.12 performance, and making decisions. The recent infusion of
financial incentives and regulation involving HIT from the
Information and Knowledge Delivery. Healthcare delivery American Recovery and Reinvestment Act (ARRA)14 has
is inherently complex and knowledge-dependent, and it is fueled the implementation of technologies across the United
becoming ever more challenging for providers to absorb and States, contributing to an exponential growth of available
assimilate the growing volume and granularity of knowl- and useable healthcare data. Healthcare organizations are
edge needed for safe and effective patient care. The clinical looking for every opportunity to transform and leverage data
knowledge available is often conflicted, misaligned, and not into information that provides concise, timely, descriptive,
readily identified or available at the point of care. To serve predictive, and prescriptive insight into their business and
the needs of any clinical encounter, relevant patient-centered clinical data. Business intelligence (BI) and analytics (BA)
knowledge must be accessible to the person supplying care processes and technologies are enabling health systems to
at the right time in the workflow. Such knowledge can be de- improve their performance and maintain their competitive
livered proactively (before decisions are made), interactively advantage while creating an additional demand for clinical
(as decisions are made), or asynchronously or passively as informatics professionals. Pharmacy informatics plays a sig-
reference information that can be searched online. Pharmacy nificant role in all efforts surrounding medication manage-
informatics plays a key role in supporting and overseeing ment-related BI and BA activities. Pharmacy informaticists’
the core processes involving information and knowledge understanding of basic software and database design, ability
delivery throughout the clinical knowledge lifecycle. This to grasp the big picture, and functional knowledge of detail,
role includes knowledge discovery and creation, knowledge coupled with their analytical skills, create opportunities to
application and delivery, and knowledge asset management. develop evidence-driven answers for practice improvement
Knowledge discovery and creation. As technology- and performance questions, such as
driven transactions for results, ordering, documentation,
task completion, communication, and patient monitoring • How are pharmacists performing in relation to cost,
continue to grow, so will the amount of data. Pharmacy in- quality, and service?
• How can pharmacists improve performance and safety • Educating, disseminating, and discussing—Commu-
within and outside their service lines? nicating effectively to students and to other audiences
• How can pharmacy practice identify patients who are in multiple disciplines in persuasive written and oral
at risk for readmission? form.
• How can pharmacy practice identify patients requiring
medication therapy management services?15,16 Leading and Managing Change. To ensure that HIT sys-
tems support safe and effective medication use, pharmacy
Pharmacy informatics roles and responsibilities in BI and informaticists are expected to lead as well as manage the
BA must include: risks and changes associated with the development, imple-
mentation, safety, and use of systems that support medica-
• Ensuring data are standardized, structured, and mod- tion management. Their knowledge and skills in compre-
eled to support a data-driven BI and BA culture. hending and evaluating organizational culture, managing
• Creating effective analytics tools that allow for mul- change, working effectively in interdisciplinary teams, com-
tiple formats and layers of analysis, from summary munication, synthesizing user requirements, and articulating
reports for a population of patients to a practice and at HIT needs within the context of broader strategic goals al-
the individual patient-encounter level. low them to play a significant role in
• Development, maintenance, and quality assurance
of clinical, operational, and financial dashboards, • Leading health-system, professional, industry, regu-
scorecards, screening, and surveillance tools to guide latory, standards-setting, and governmental organiza-
achievement of treatment and strategic goals. tions to sound conclusions regarding the use of tech-
• Driving analytics to the front line by creating greater nology in medication management.
end-user accessibility to BI and BA tools. • Leading and managing the evaluation and communi-
• Monitoring effectiveness of tools and information to cation of the potential risks of a newly implemented
deploy or further develop point of care or analytical technology and developing plans to mitigate potential
systems. hazards.
• Translating user requirements into safe and effective
Applied Clinical Informatics. Pharmacy informatics plays system designs.
a key role in delivering informatics research principles and • Implementing project management best practices.
best practices to the bedside. Through informal and for- • Attaining key leadership roles within the healthcare
mal partnerships with the research community, pharmacy technology industry, professional practice associa-
informaticists must work collaboratively with members of tions, and healthcare technology organizations.4,10,11
various disciplines to improve the effectiveness, efficiency,
and safety of systems that support medication management.
They must actively participate in relevant associations and
Conclusion
workgroups in the clinical informatics field to maintain their
As the scope for development and complexity of systems
current skills and play a significant role in the following
that support medication management continues to grow, so
activities:
does the need for individuals to lead, manage, and evalu-
ate them. A pharmacy informaticist is uniquely qualified
• Acquiring professional perspective—Understanding
and possesses the necessary skills to fulfill this need. Their
and analyzing the history and values of the discipline
knowledge of pharmacy practice and safe medication use,
and its relationship to other fields while demonstrat-
combined with their understanding of informatics concepts,
ing an ability to read, interpret, and critique the core
methods, and tools, provide the framework for effectively
literature.
leading and participating in the procurement, customization,
• Analyzing problems—Analyzing, understanding, ab-
development, implementation, management, evaluation, and
stracting, and modeling a specific biomedical problem
continuous improvement of clinical information systems.
in terms of data, information, and knowledge compo-
nents.
• Producing solutions—Troubleshooting and effectively References
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2015–2016 went to press. Some minor editorial differences may ex-
Approved by the ASHP Board of Directors on April 10, 2015 and by ist between this document and the official one that will eventually
the ASHP House of Delegates on June 7, 2015. Developed through appear in AJHP and subsequent editions of this publication.
ASHP Statement on the Pharmacist’s Role with

Respect to Drug Delivery Systems and
Administration Devices
Technological advances in drug delivery systems and ad- 7. Monitoring of the ongoing clinical effectiveness and
ministration devices frequently enable improved control of suitability of specific drug delivery systems or admin-
drug administration. Such advances may offer numerous istration devices with respect to specific patients and
potential benefits to patients, including improved thera- the communication of clinically relevant observations
peutic outcomes in disease management, improved patient and recommendations to prescribers and other health
compliance with drug regimens, and greater efficiency and professionals involved in the patients’ care.
economy in disease therapy. These advances constitute an
important aspect of pharmaceutical knowledge and are rou- Failures or malfunctions of drug administration de-
tinely incorporated into pharmacy practice as they occur. vices may lead to patient harm. Reports of such problems
A drug delivery system is defined as one in which a should be made in accordance with the provisions of the
drug (one component of the system) is integrated with another Safe Medical Devices Act of 1990 (PL 101–629).
chemical, a drug administration device, or a drug adminis
tration process to control the rate of drug release, the tissue site
of drug release, or both. A drug administration device is an ap- Recommendations for
paratus that is used for introducing a drug to the body or con- Additional Reading
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drug delivery. Considering product features and costs and the ASHP House of Delegates, June 9, 1993. Revised by the
in selecting a system for intermittent i.v. drug delivery. ASHP Council on Professional Affairs. Supersedes a previous ver-
Am J Hosp Pharm. 1987; 44:2533–8. sion approved by the ASHP House of Delegates on June 5, 1989,
Reilly KM. Current problems and innovations in intravenous and the ASHP Board of Directors on November 16, 1988.
drug delivery. Problems in administration techniques
and dose measurement that influence accuracy of i.v. Copyright © 1993, American Society of Hospital Pharmacists, Inc.
drug delivery. Am J Hosp Pharm. 1987; 44:2545–50. All rights reserved.
Reiss RE. Volumetric IV pumps. Pharm Tech. 1983(Suppl);
7:46–9. The bibliographic citation for this document is as follows: American
Self TH, Brooks JB, Lieberman P, et al. The value of Society of Hospital Pharmacists. ASHP statement on the pharma-
demonstration and role of the pharmacist in teaching cist’s role with respect to drug delivery systems and administration
the correct use of pressurized bronchodilators. Can devices. Am J Hosp Pharm. 1993; 50:1724–5.
Med Assoc J. 1983; 128:129–31.
ASHP Statement on the Pharmacy Technician’s Role

in Pharmacy Informatics
Position cialized PTIs will help fill these important roles. The purpose
of this statement is to provide a preliminary description of the
The American Society of Health-System Pharmacists potential roles and responsibilities of the PTI in the evolving
(ASHP) believes that specially trained pharmacy technicians HIT landscape as well as the knowledge, skills, and abilities
can assume important supportive roles in pharmacy informat- required to assume those roles and responsibilities.
ics. These roles include automation and technology systems
management, management of projects, training and educa- Roles and Responsibilities
tion, policy and governance, customer service, charge integ-
rity, and reporting. Such roles require pharmacy technicians In general, the PTI will be a health care professional, work-
to gain expertise in information technology (IT) systems, ing under the supervision of a registered pharmacist, who
including knowledge of interfaces, computer management uses his or her knowledge to influence and adapt IT systems
techniques, problem resolution, and database maintenance. to improve the effectiveness and efficiency of the health sys-
This knowledge could be acquired through specialized train- tem. The roles of PTIs will vary, depending on the needs of
ing or experience in a health science or allied scientific field the health care institution and the knowledge, skills, and abil-
(e.g., health informatics). With appropriate safeguards and ities of the individual. A PTI specializing in the management
supervision, pharmacy technician informaticists (PTIs) will of health-system pharmacy IT services may, for example,
manage IT processes in health-system pharmacy services, perform workflow assessment and optimization in clinical,
ensuring a safe and efficient medication-use process. administrative, educational, or research domains; adapt soft-
ware controls to existing workflow; provide subject-matter
Background expertise for new technology assessment and usability; or
serve as a resource for pharmacist informaticists when mis-
The National Library of Medicine defines health informatics sion-critical updates are needed or problems are identified.
as the “the interdisciplinary study of the design, develop- The areas of responsibility of the PTI will also vary consid-
ment, adoption and application of IT-based innovations in erably but may include automation and technology systems
healthcare services delivery, management and planning.”1 management, management of projects, end-user training and
Health informatics is a discipline at the intersection of in- education, policy and governance, customer service, charge
formation science, health care, and computer science that integrity, and reporting.
designs and delivers information to improve clinical care,
individual and public health care, and biomedical research. Automation and Technology Systems Management. With
Health informatics optimizes the usability, acquisition, and training and experience in health informatics, the PTI can
processing of health-related information, using resources serve as a knowledgeable expert for placement, configura-
and tools that span the IT spectrum, from people to pro- tion, monitoring, maintaining, and troubleshooting automa-
cesses, from information to knowledge, and from algorithms tion and technology systems and provides users and staff
to data. The broad definition of health informatics and the with consultative support. The PTI participates in assessing
number of disciplines involved present an opportunity for the functions, benefits, and constraints of technology and au-
the growth of subspecialties within the field. One of these tomation systems for drug procurement, pharmacy inventory
subspecialties is pharmacy informatics, which has been management, prescribing medications, order processing,
defined as “the use and integration of data, information, distribution and dispensing of medications, administering
knowledge, technology, and automation in the medication- and documenting administration of medications, and effects
use process for the purpose of improving health outcomes.”2 monitoring. The PTI consults, advises, and educates staff
ASHP believes that pharmacists have the unique knowledge, on methods and means to make automation and technology
expertise, and responsibility to assume a significant role in systems more effective and efficient. The PTI’s functions
health informatics.2 A properly trained and qualified phar- include integration of information and workflow processes
macy technician may assume a supporting role in the field to achieve successful adoption and application of new tech-
of informatics as well.3 nologies to support health care operations and systems.
The potential for health informatics to improve health The PTI provides relevant technological or adminis-
outcomes has prompted the health care industry, large health trative data to identify, quantify, and resolve organizational
care purchasers, and state and federal governments to under- or operational problems. PTIs integrate software applica-
take sweeping health information technology (HIT) initia- tions for technological services by: (1) evaluating the unique
tives. These initiatives have greatly increased the demand needs of the specific services in conjunction with the capa-
for a highly skilled HIT workforce. The Bureau of Labor bilities of the software and coordinating required modifica-
Statistics estimates that 37,700 new medical records and HIT tions; (2) reviewing the effectiveness of the systems and pro-
technician jobs will be created between 2010 and 2020.4 This cedures to assure optimum benefit to patient-care activities;
tremendous increase will affect organizations’ ability to re- and (3) determining the cause of and the solution to prob-
cruit and retain the qualified personnel necessary for health lems when functionality is compromised.
care operations. Although not all pharmacy technicians are Using the applicable software manager menu systems
qualified to fill this pressing need, an emerging cadre of spe- and tools, the PTI develops, modifies, and tests components
specific to fields and data that individualize or customize ap- Customer Service. The PTI maintains an ongoing personal
plications to user roles or needs while maintaining integrity relationship with onsite peers, pharmacist informaticists,
among multiple software packages. The PTI also provides technical support staff, administrative staff, and health care
for the maintenance and updating of site parameters and professionals within the facility. The PTI will frequently
site-specific files to ensure proper functioning of complex, need to contact offsite technical support personnel and clini-
interrelated, and interdependent software applications, ef- cal and subject-matter experts as needed. External contacts
fectively and efficiently managing multiple competing pri- may include contract developers, for whom the PTI can
orities. serve as a primary contact and knowledge resource.
Management of Projects. The PTI collaborates with the Charge Integrity. The PTI maintains appropriate charging
pharmacist informaticist in managing technology and infor- controls to ensure accurate patient and third-party billing.
mation systems based on a shared understanding of system The PTI will be engaged with pharmaceutical wholesalers
requirements, capabilities, and limitations. The PTI serves and distributors to validate price files in clinical and auto-
as an interdisciplinary team member to complete HIT sys- mation systems, as well as Healthcare Common Procedure
tem initiatives using analytical and evaluative techniques Coding System (HCPCS) coding, units, and quantities. The
to assess the effectiveness of results and other related pro- PTI will also monitor charging and transaction interfaces for
grams. For example, the PTI may contribute to planning for errors in charge application, quantities, or amounts.
acquisition and implementation of a technology or automa-
tion system by assisting the pharmacist informaticist in de- Reporting. The PTI extracts, compiles, and analyzes stan-
veloping a plan for the evaluation of the system; writing a re- dard reports from clinical and automation systems to fa-
quest for proposal (RFP) for the system; assessing responses cilitate organizational and individual decision-making. An
to the RFP; or developing a plan for implementation, testing, advanced PTI customizes reports and provides advanced da-
or maintenance of the system. The PTI may participate in tabase management (e.g., via SQL or Microsoft Access) to
the implementation of a technology or automation system by address organizational needs not addressed through standard
contributing to system installation (including supplemental reporting tools.
build-outs), testing, and training of staff for use of the sys-
tem, as well as maintaining the system according to an estab- Knowledge, Skills, and Abilities
lished plan. The PTI may also participate in development of
a contingency plan for failure or compromise of technology The PTI is uniquely qualified to serve in these roles because
or automation systems. of the combination of technological knowledge, skills, abili-
ties, experience, and training. The PTI will be required to
End-user Training and Education. The PTI identifies end- understand IT systems, including interfaces, computer man-
user educational requirements and training needs and devel- agement techniques, problem resolution, and database main-
ops educational programs, instructional materials, and ap- tenance. The PTI will need to be familiar with pharmacy,
propriate tools to educate users and support staff at all levels medication, and medical terminologies as well as medica-
of the organization. In collaboration with the pharmacist tion-use workflow processes, including drug procurement,
informaticist, the PTI monitors end-user satisfaction to drive pharmacy inventory, medication ordering, order manage-
enhancements and increase performance. The PTI functions ment, dispensing, drug preparation, distribution, and billing
in a supportive role with the pharmacist informaticist to systems.
ensure the technological changes are aligned with the orga- The PTI will require a thorough knowledge of the
nizational needs and participates on process improvement, clinical environment, including practices, procedures, poli-
root cause analysis, and system redesign teams. cies, strengths, and weaknesses in order to effectively use
data to track and manage patient care. Thorough and current
Policy and Governance. The PTI maintains state-of-the-art knowledge of emerging and state-of-the-art technology, reg-
knowledge of changes in technology and the clinical envi- ulations, programs, and processes related to health informat-
ronment to identify, propose, formulate, and support new ics will be necessary for the PTI to propose and formulate
or revised major technological policies and directives for administrative and clinical policies and directives, instruct
automation and systems technology. PTIs collaborate with practitioners on the changes and application of new policies
pharmacist informaticists on the structure of programmatic and directives, and provide leadership on informatics com-
and security requirements for data access in IT to ensure that mittees or teams.
best practices are applied to operational requirements. The PTI must have practical, in-depth knowledge of
The PTI applies statistical analyses and interprets their automation and software systems that affect clinical prac-
significance, including evaluation of the validity of measures tice, as well as knowledge of technologies that may benefit
used to generate outcomes related to patient management health care delivery processes. The PTI should be able to
systems. PTIs will work cooperatively with the pharmacist troubleshoot functionality issues and develop solutions, and
informaticist to develop recommendations for improving to ensure quality management of clinical operations.
clinical data management methods, follow-up procedures, The PTI should have comprehensive knowledge of the
and timely compliance with regulatory guidelines. Finally, data life cycle, including data design, collection, and man-
the PTI instructs staff members in the proper use of informa- agement, in order to input, retrieve, analyze, summarize, and
tion management tools in compliance with policy, regula- present information effectively. The required knowledge
tions, and best practices. base is extensive and includes usability, data standards, data
validation, understanding content relationships, and interop-
erability among systems.
The PTI should understand common network stan- 4. Bureau of Labor Statistics. Occupational Outlook
dards and network architectures and the functions and pur- Handbook: Medical Records and Health Information
poses of common hardware components and configurations. Technicians. www.bls.gov/ooh/healthcare/medical-
The PTI should also understand the design of safe technol- records-and-health-information-technicians.htm#tab-6.
ogy and automation systems. Finally, the PTI should possess
the database skills to successfully create patient and medica-
tion information data sets and successfully construct reports.
The PTI should be skilled in communicating both
orally and in a variety of written media for a variety of au- Approved by the ASHP Board of Directors on April 12, 2013, and by
diences, from information technology and clinical experts the ASHP House of Delegates on June 2, 2013. Developed through
to end-users. As a specialist with training and experience the ASHP Section of Pharmacy Informatics and Technology.
in health informatics, the PTI guides the evolution of auto-
mation technology and processes using creative and well- Nancy R. Smestad, M.S.; Trinh Le, M.S.; Adelaide Quansah-Arku,
developed interpersonal skills to achieve effective commu- B.S.B.A.; Karl F. Gumpper, BCNSP, BCPS, FASHP; and Andy
nication with end users and management. Laegeler, Pharm.D., M.S. are gratefully acknowledged for drafting
this statement.
Conclusion The following individuals and organizations are gratefully ac-

knowledged for reviewing this statement (review does not imply
The ASHP Pharmacy Practice Model Initiative provides endorsement): John A. Armitstead, M.S., FASHP; Mark Banzon,
several recommendations regarding use of technology to CPhT, PMP; Frank Barnett (Wiregrass Georgia Technical College);
ensure medication safety. Meeting these recommendations Louis D. Barone, Pharm.D., FASHP; Bob Begliomini, Pharm.D.,
will require an expansion of pharmacy resources devoted to M.B.A., FASHP; Jeff Brittain, Pharm.D., BCPS; Mark P. Chabot,
the implementation and maintenance of HIT. A trained and M.H.A., M.B.A.; Bruce Chaffee, Pharm.D.; Sister Mary Louise
educated PTI has unique skill sets that combine technical Degenhart, M.B.A.; Robert Fink, Pharm.D., M.B.A., FASHP,
knowledge with an understanding of medication vocabu- FACHE, BCNSP, BCPS; Patricia C. Kienle, M.P.A., FASHP;
lary and pharmacy operational workflow. Through these Nicole Grimmer; Kathleen M. Gura, Pharm.D., BCNSP, FASHP,
specialized skills, the PTI is able to support and coordinate FPPAG; Nik Johnson (Academy of Managed Care Pharmacy);
pharmacy technologies under the direction of the pharmacy Kevin Marvin, M.S., FASHP, FHIMSS; Firouzan (Fred) Massoomi,
department or an accountable pharmacist. The PTI possesses Pharm.D., FASHP; Lisa McCartney, BAAS, CPhT, PhTR; Michael
a working knowledge of the technology and automation sys- McGregory, Pharm.D., M.B.A.; Rhonda McManus, Pharm D; Jutia
tems and processes that support the medication-use system DeVae Merriweather, A.S, B.S., CPhT; Kelly Meyer, B.S, M.Ed,
and can contribute to ensuring their safety and efficiency. CPhT, PhTR; Timothy O’Connor-Crowe, CPhT, M.P.H., M.S.H.I.;
Brandon Ordway, Pharm.D., M.S.; Ashley Overy, Pharm.D.;
References William Pennington, LVN, CPhT; Curt W. Quap, M.S., FASHP;
Catherine Sharafanowich; Steven Silverstein, Pharm.D., BCPS;
1. National Library of Medicine. Health Services Lori Stepp, BSE, CPhT; Dennis A. Tribble, Pharm. D., FASHP;
Research Information Central: Health Informatics. David Troiano, M.S.I.A.; James A. Trovato, Pharm.D., M.B.A.,
www.nlm.nih.gov/hsrinfo/informatics.html (accessed BCOP, FASHP; Alan Vogenberg, FASCP; and Deb Wagner,
2012 Dec 13). Pharm.D., FASHP.
2. American Society of Health-System Pharmacists.
ASHP statement on the pharmacist’s role in informat- Copyright © 2013. American Society of Health-System Pharmacists,
ics. Am J Health-Syst Pharm. 2007; 64:200–3. Inc. All rights reserved.
3. American Society of Health-System Pharmacists. The
consensus of the Pharmacy Practice Model Summit. The bibliographic citation for this document is as follows: American
Am J Health-Syst Pharm. 2011; 68:1148-52. Available Society of Health-System Pharmacists. ASHP Statement on the
at: www.ajhp.org/content/68/12/1148.full.pdf (ac- Pharmacy Technician’s Role in Pharmacy Informatics. Am J Health-
cessed 8 March 2013). Syst Pharm. 2014; 71:247–50.
ASHP Statement on Use of Social Media

by Pharmacy Professionals
Position Participation in Social Media
The American Society of Health-System Pharmacists Hospitals or health systems that choose to use social media
(ASHP) encourages pharmacy professionals working in or permit practice-related social media use by staff should
hospitals and health systems who use social media to do so have in place policies and procedures that
in a professional, responsible, and respectful manner. Such
use may complement and enhance their relationships with • Balance the benefits social media provide with the ob-
patients, caregivers, other members of the health care team, ligations and liabilities they may create, and
and the public. To achieve that goal, pharmacy professionals • Encourage the development and application of best
should practices by users of social media.
• Thoroughly consider the purposes and potential out- The details of such policies, procedures, and best practices
comes of participation in social media and develop the are beyond the scope of this statement, which has as its pur-
strategies and skills required to effectively utilize so- pose to briefly outline some of the considerations that should
cial media to meet their goals, and guide pharmacy professionals’ participation in social media.
• Exercise professional judgment and adhere to pro- Pharmacy professionals should carefully consider the
fessional standards and legal requirements in both purposes and potential outcomes of their participation in so-
private and public social media communications, es- cial media and develop the strategies and skills required to
pecially legal and ethical obligations to protect the pri- achieve their goals. They need to be aware of and employ
vacy of personal health information. best practices when using social media, because health care
practitioners, including pharmacy professionals, are held to
a higher standard of professionalism within and outside the
Background workplace than members of the public.6 Pharmacy profes-
sionals who participate in social media should strive for a high
The term “social media” may be defined as online tools that degree of professionalism in their communications and ensure
allow interaction among individuals. Examples include pro- that patient privacy is not compromised.
fessional networks such as ASHP Connect, career-building
networks such as LinkedIn, and sites such as Facebook Professionalism
and Twitter that are primarily social but which may serve
multiple purposes.1-3 Informational sites regarding medical ASHP has long advocated for the adoption of high profes-
information that allow for commentary from users and medi- sional aspirations for pharmacy practice. Pharmacists’ re-
cal professionals (e.g., PharmQD, The Pharmacist Society, sponsibilities as professionals include “advancing the well-
Sermo) should also be considered collaborative social me- being and dignity of their patients, acting with integrity and
dia. conscience, [and] collaborating respectfully with health care
Social media have transformed the way people com- colleagues.” 7 The following recommendations for the use
municate by reducing barriers to the exchange of informa- of social media represent high professional aspirations, and
tion, increasing both the amount of communication and the pharmacy professionals are encouraged to exercise their pro-
number of people who can participate. Health care organiza- fessional judgment in incorporating them into their practices.
tions (e.g., hospitals, health systems, professional societies,
pharmaceutical companies, patient advocacy groups, phar- Advancing the Well-Being and Dignity of Patients. The fol-
macy benefit companies) have chosen to use social media lowing recommendations can help pharmacy professionals
for both communication and marketing. who choose to participate in social media advance the well-
Like other health care professionals, pharmacy profes- being and dignity of patients.
sionals have adapted to advancing technology and are using
social media to communicate with patients, caregivers, other 1. Medical advice offered through social media should
health care professionals, and the public. Pharmacy profes- be provided in accordance with the professional stan-
sionals (including pharmacy students as professionals in dards of pharmacy practice. For example, pharmacy
training) should continue to incorporate these new tools into professionals should provide medical advice only
the armamentarium of pharmacy practice and apply them with a complete understanding of the patient’s medi-
with professional judgment to pursue the goal of helping cal conditions and only if they accept the associated
people make the best use of medications. Social media pro- liabilities, especially those regarding privacy and the
vide pharmacy professionals with opportunities to educate requirements of pharmacy practice. Pharmacy profes-
patients and practitioners, seek advice from and provide ad- sionals should be aware that providing medical advice
vice to colleagues, optimize the medication use of individual may create a pharmacist–patient relationship, with all
patients and populations, promote the role of pharmacists its attendant obligations and liabilities. All online rela-
in caring for patients, and engage in debate about issues in tionships should conform to the ethical boundaries of
health care practice and policy, among other things.1-5 an appropriate pharmacist–patient relationship.8
2. Pharmacy professionals should be cognizant of both healthy debate about health care and pharmacy practice,
the benefits and limitations of online communication. such debate should be conducted in a respectful manner.
Social media may serve especially well as a point of Reasoned debate sometimes requires constructive criticism,
initial contact or as a convenient way to maintain con- but pharmacy professionals should not use social media to
tact between patients and care providers, but profes- make ad hominem comments or needlessly denigrate spe-
sionals must recognize when a patient’s health care cific care providers, institutions, or professions.
needs would be better met through other means (e.g.,
phone consultation, office visit). Patient Privacy
3. Pharmacy professionals should view social media as
a means to not only provide timely and accurate drug Health care professionals have long confronted the chal-
information but also to rebut inaccurate, misleading, lenge of “communicat[ing] freely with each other while
or outdated information. While the purpose of specific maintaining patient confidentiality and privacy.”12 Social
social media content may not always be apparent, phar- media, by their very nature, present new issues of privacy
macy professionals need to be aware of and alert to the and confidentiality by extending the reach of communica-
use of social media for marketing and sales purposes. tions. The following recommendations may help pharmacy
4. Complaining about or disparaging patients, even in professionals protect patient privacy and confidentiality as
general terms, does not advance the dignity of patients they navigate this new terrain.
or the profession. Communications that contain pa-
tients’ identifying information would violate privacy 1. Pharmacy professionals should continue to adhere to
requirements, which are discussed in more detail be- all laws, regulations, standards, and other mandates
low. Pharmacy professionals should keep in mind that intended to protect patient privacy and confidentiality
simply avoiding the name of a patient may not be suf- in all environments, including social media.8
ficient to avoid patient identification. 2. Pharmacy professionals should exercise professional
judgment and employ established best practices to
Acting with Integrity and Conscience. The following rec- ensure compliance with privacy requirements when
ommendations are intended to assist pharmacy professionals communicating with patients or about specific patient
to act with integrity and conscience in their use of social cases on social media.9,13,14
media. 3. Pharmacy professionals should select privacy set-
tings in social media accounts that provide the greatest
1. Pharmacy professionals should carefully distinguish degree of protection for personal information, keep-
between personal and professional information within ing in mind that privacy settings are not perfect and
social media and make conscientious decisions regard- that information posted online is likely permanent.
ing who will have access to personal or professional Continuous self-monitoring of privacy settings is nec-
information. Although some organizations recommend essary, as social media sites change privacy policies.10
use of a strictly personal page and a separate, strictly
practice-related page,9 professionals will quickly rec-
ognize the difficulty of making such distinctions. The
higher standards of conduct expected of professionals, Conclusion
even in personal behavior, apply as well to their par-
ticipation in social media.6,10 Social media are emerging as important modes of communi-
2. Pharmacy professionals must be conscious that con- cation and are increasingly being used for personal, profes-
tent posted to social media may have consequences on sional, and business communication, as well as for patient
reputations or careers for years to come, reflect poorly care. As medical professionals held to high standards of per-
upon the pharmacy profession, or undermine patient sonal, professional, ethical, and moral conduct, pharmacy
confidence in the care provided. Postings on social professionals have a responsibility to use social media ap-
media should be subject to the same professional stan- propriately.
dards and ethical considerations as other personal or
public interactions. References
3. The apparent anonymity provided by social media
does not release pharmacy professionals from their 1. Fox BI, Varadarajan R. Use of Twitter to encourage
ethical obligation to disclose potential conflicts of interaction in a multi-campus pharmacy management
interest, especially when representing themselves as course. Am J Pharm Educ. 2011; 75(5):88.
professionals. Some circumstances may require per- 2. Estus E. Using Facebook within a geriatric pharmaco-
sonal identification or disclosure of potential compet- therapy course. Am J Pharm Educ. 2010; 74(8):145.
ing interests.9 3. Cain J, Fox BI. Web 2.0 and pharmacy education. Am
4. Although all pharmacists should use social media in J Pharm Educ. 2009; 73(7):120.
ways that set positive examples for pharmacy students 4. Clauson KA, Seamon MJ, Fox BI. Pharmacists’ duty
and residents, preceptors and mentors have a special to warn in the age of social media. Am J Health-Syst
responsibility to model appropriate practices.7,11 Pharm. 2010; 67:1290–3.
5. Mattingly TJ, Cain J, Fink JL. Pharmacists on
Collaborating Respectfully with Health Care Colleagues. Facebook: online social networking and the profes-
Although social media can and should be used to promote sion. J Am Pharm Assoc. 2010; 50:424–7.
6. Williams J, Field C, James K. The effects of a social
media policy on pharmacy students’ Facebook secu- Developed through the ASHP Pharmacy Student Forum and the
rity settings. Am J Pharm Educ. 2011; 75(9):177. ASHP Section of Pharmacy Informatics and Technology and ap-
7. American Society of Health-System Pharmacists. proved by the ASHP Board of Directors on April 13, 2012, and by
ASHP statement on professionalism. Am J Health-Syst the ASHP House of Delegates on June 10, 2012.
Pharm. 2008; 65:172–4.
8. University of California, San Diego. Guidelines and This statement was drafted by Ashley M. Overy, Pharm.D. The
best practices for online social media use by student following individuals are also acknowledged for their contribu-
pharmacists. http://pharmacy.ucsd.edu/current/pdf/ tions to this statement: Kevin A. Clauson, Pharm.D.; Brent I. Fox,
Social_Media_Guidelines.pdf (accessed 2012 Feb 1). Pharm.D., Ph.D.; Karl F. Gumpper, BCNSP, BCPS, FASHP; Arpit
9. Ohio State Medical Association. Social networking Mehta, Pharm.D.; and David R. Witmer, Pharm.D. The drafters and
and the medical practice: guidelines for physicians, contributors have declared no potential conflicts of interest.
office staff, and patients. www.osma.org/files/
documents/tools-and-resources/running-a-practice/ ASHP gratefully acknowledges the following individuals and organi-
social-media-policy.pdf (accessed 2012 Feb 1). zations for reviewing drafts of this statement (review does not imply
10. American Medical Association. AMA policy: profes- endorsement): Academy of Managed Care Pharmacy (AMCP); Paul
sionalism in the use of social media. www.ama-assn. Barrett, Pharm.D., M.P.A., BCPS, FASHP; Mark Brueckl, M.B.A.
org/ama/pub/meeting/professionalism-social-media. (AMCP); Jeff Cain, Ed.D., M.S.; Michael S. Edwards, Pharm.D.,
shtml (accessed 2012 Feb 1). M.B.A., BCOP, FASHP; Erin R. Fox, Pharm.D.; Becky Harvey,
11. Kukreja P, Sheehan AH, Riggins J. Use of social me- Pharm.D.; John Hertig, Pharm.D., M.S.; Justin Julius, Pharm.D.;
dia by pharmacy preceptors. Am J Pharm Educ. 2011; Nishaminy Kasbekar, Pharm.D., FASHP; Linda McElhiney,
75(9):176. Pharm.D., FASHP, FIACP; Sean Mirk, Pharm.D.; John F. Mitchell,
12. American Society of Health-System Pharmacists. Pharm.D., FASHP; David B. Moore, M.P.A., CPh.; Linda A. Nelson,
ASHP statement on confidentiality of patient health Pharm.D.; Agatha Nolen, Ph.D.; James Ponto, M.S., FASHP; Curt
care information. Am J Health-Syst Pharm. 2009; W. Quap, M.S., FASHP; Marcus Ravnan, Pharm.D.; Jamie S.
66:411–2. Sinclair, M.S., FASHP; Kelly M. Smith, Pharm.D., BCPS, FASHP,
13. Dimov V. Case reports and HIPAA rules. http://cas- FCCP; and Jody Jacobson Wedret, B.S.Pharm., FASHP, FCSHP.
esblog.blogspot.com/2005/07/case-reports-and-hipaa-
rules.html (accessed 2012 Feb 1). Copyright © 2012, American Society of Health-System Pharmacists,
14. Dimov V. How to write a medical blog and not get Inc. All rights reserved.
fired. http://casesblog.blogspot.com/2008/02/how-to-
write-medical-blog-and-not-get.html (accessed 2012 The bibliographic citation for this document is as follows: American
Feb 1). Society of Health-System Pharmacists. ASHP statement on use of
social media by pharmacy professionals. Am J Health-Syst Pharm.
2012; 69:2095–7.
24 Automation and Information Technology–Guidelines
ASHP Guidelines on the Design of Database-Driven

Clinical Decision Support: Strategic Directions for Drug
Database and Electronic Health Records Vendors
ASHP believes that use of clinical decision support (CDS) Purpose
tools can make patient care more efficient and effective.1
Currently available pharmacotherapy CDS systems are not The purposes of these guidelines are to describe essential
as effective as they need to be at helping all practice set- functions and capabilities that should be available to reduce
tings achieve the goal of safe and effective pharmacother- alert fatigue, increase user satisfaction, and increase the ef-
apy. The focus of these guidelines is commercially available fectiveness of these CDS systems; and to advocate for col-
pharmacotherapy warning systems such as drug interaction, laboration between health information system vendors, drug
allergy, and dose monitoring CDS. Pharmacotherapy warn- database vendors, and the end-user community on design
ing CDS systems are collectively referred to as “database- and testing of the CDS systems as well as new algorithmic
driven CDS” in these guidelines. Database-driven alert as- models for pharmacotherapy warnings.
sociations are compiled by drug database vendors and are
incorporated as alerts into clinical information systems by
electronic health record (EHR) vendors. All practice settings Background
are usually limited in their ability to customize the content
of messages or severity levels of alerts created by the drug There are two different types of CDS, passive and active, as
database or EHR vendors. In contrast, free-form, rule-based well as several types of active CDS (Figure 1).
alerts are created by users based on coded logic rules us-
ing information contained in the EHR database. Although 1. Passive CDS. This type of CDS directs the user to-
free-form, rule-based alerts are an important tool, these ward the most appropriate practices unobtrusively;
guidelines limit their focus to active, interruptive database examples include order sets and limited selections in
warnings. These guidelines outline an approach that would drop-down lists or check boxes. Passive CDS is de-
provide all practice settings with the power and flexibility rived from population data, or more commonly clini-
to implement database-driven CDS so that it is a useful cal guidelines, and is therefore not patient-specific by
tool for improving the quality, cost efficiency, and safety of nature. It is left to the patient’s healthcare provider to
medication use. Adoption of this functionality by all practice make these patient-specific.
settings is of course critical to meeting the goal of deliver- 2. Active CDS. There are two types of active CDS,
ing improved, patient-centered care. These database-driven interruptive and noninterruptive. Active CDS is
CDS rules should be shareable between all practice settings patient-specific in that it uses at least two pieces of
so that each institution can make the customizations needed patient data to trigger an alert (e.g., two interacting
for its particular circumstances. drugs, or the patient’s age and an ordered dose).
Figure 1. Types of clinical decision support (CDS).
Passive CDS
Active CDS
This type of CDS directs
the user toward the most
appropriate practices
Noninterruptive CDS Interruptive CDS
unobtrusively; examples
are order sets and limited
With noninterruptive CDS, With interruptive CDS, just-in-time alerts are presented directly
selections in drop-down
new patient information (e.g., to the user, and the user is required to take some action to
lists or check boxes.
lab values, allergy information) respond to the alert (e.g., drug interaction and dose checking at
is posted to work queue/lists order entry). Two kinds of active interruptive message systems
or forms for resolution at a are in frequent use.
time convenient to the
clinician.
Free-form, Rule-based Database-driven
Alerts Alerts
The alerts give all practice These alerts utilize a large

settings more flexibility to database containing drug
develop the characteristics of interaction, dose range
messages without the benefit and condition, and allergy
of predefined data. interaction content.
Automation and Information Technology–Guidelines 25
a. Noninterruptive CDS. With noninterruptive which states “that we can achieve CDS-supported improve-
CDS, new patient information (e.g., lab values, ments in desired healthcare outcomes if we communicate:
allergy information) is posted to work queue/
lists or forms for resolution at a time convenient 1. The right information: evidence-based, suitable to
to the clinician. guide action, pertinent to the circumstance
b. Interruptive CDS. With interruptive CDS, just- 2. To the right person: considering all members of the
in-time alerts are presented directly to the user, care team, including clinicians, patients, and their
and the user is required to take some action to caretakers
respond to the alert (e.g., drug interaction and 3. In the right CDS intervention format: such as an alert,
dose checking at order entry). Two kinds of ac- order set, or reference information to answer a clinical
tive interruptive message systems are in frequent question
use: 4. Through the right channel: for example, a clinical
i. Database-driven alerts. These alerts uti- information system (CIS) such as an electronic medi-
lize a large database containing drug in- cal record (EMR), personal health record (PHR), or a
teraction, dose range and condition, and more general channel such as the Internet or a mobile
allergy interaction content.
device
ii. Free-form, rule-based alerts. The alerts 5. At the right time in workflow: for example, at time of
give all practice settings more flexibility
decision/action/need.”10
to develop other decision models and the
characteristics of patient-specific mes-
The Healthcare Standards Organization Health Level Seven
sages. Ideally, in the future it will be com-
(HL7) and the American National Standards Institute have
mon for free-form CDS rules to be able to
developed and maintain a standard programming language
access the content of commercially devel-
design for clinical informaticists to build medical logic mod-
oped pharmacotherapy CDS databases.
ules capable of sophisticated clinical logic. There are also
many HL7 standards (e.g., Arden Syntax, GELLO, HQMF,
Although database-driven CDS systems have been
Infobutton, DSS) that can assist in this endeavor and offer a
commercially available for over 30 years, most of these
mechanism across all practice settings around the world to
systems have not progressed beyond the use of simple rules
collaborate on the development of effective database-driven
for drug–drug, drug–food, and drug–allergy checking. Most
CDS.11 Use of these standards could improve the ability for
provide limited logic to determine a patient’s true suscepti-
users to share logic developed to capitalize on the function-
bility to these drug interactions, and some provide limited
ality presented below.
drug–disease state screening and age-based dose checking.2
ASHP encourages pharmacists, hospital and health-
Most currently available database-driven CDS systems have
system administrators, drug database vendors, and EHR sys-
excellent content and can generally inform the right person;
tem vendors to use the recommendations in these guidelines
however, they have limited options for format, channel, and
to increase the usefulness and flexibility of database-driven
right time in workflow. These limitations cause a high in-
CDS tools. In essence, the goal of their collaborative efforts
cidence of false-positive alerts in computerized prescriber-
should be to provide the flexibility and customization ca-
order-entry and pharmacy information systems, which can
pabilities as are currently available in the free-form rules
in turn decrease users’ sensitivity to alerts, also known as
engines provided by most EHR vendors today. This would
“alert fatigue.” Alert fatigue is more than just an annoyance;
allow users to build alerts that have greater specificity and
it increases the risk of harm to both patients and providers.2-4
higher positive predictive performance.
The lack of clinical usefulness of the majority of drug in-
teraction, drug allergy, and dose monitoring tools has been
demonstrated by physician alert override rates that exceeded Essential CDS Capabilities
90% in some studies.3-8 The relevance and specificity of CDS
tools will be improved, and the value of CDS tools enhanced, The following are essential database-driven CDS capabili-
when the rate of meaningful warnings is increased and the ties that should be available in all EHR systems for any com-
incidence of clinically irrelevant alerts is reduced. Achieving bination of drug database vendor and EHR vendor used by
these goals will require more than the currently available a hospital or health system. These recommendations are not
simple logic, especially for dose monitoring and mathemati- listed in order of feasibility or priority; all are considered
cal algorithms. These systems also need broader access to the vitally important for the development of more patient ap-
rich patient data that are now available in the EHR. propriate care.
The meaningful use requirements of the American
Recovery and Reinvestment Act9 contain explicitly stated 1. The institution should be able to configure and/or cus-
objectives for CDS, spurring healthcare facilities to invest tomize “drug groups” that can be used in alert triggers
in new EHR systems with an increased focus on CDS. or criteria. Drug groups should be defined as lists of
Although these systems are the most current ones available, individual medication products or generic or therapeu-
many of them continue to use the same simple logic for tic groupings. Individual medication products should
database-driven CDS. What is needed is more sophisticated be capable of being included in multiple drug groups,
logic, such as statistical methods and branching algorithms and drug groups should be able to subsume other drug
to reduce the false-positive and false-negative alerts. The groups. The drug group construct should be an option
Agency for Healthcare Research and Quality recommends for using the configuration functionality described be-
that CDS developers consider the CDS Five Rights model, low. The drug group must have a free-text comment
field of at least 1000 characters to allow the institution over a defined period of time (e.g., decrease in
to identify the drug group’s owner and purpose and to hemoglobin of 2 grams in 2 days, or increase of
construct a history of changes. hemoglobin A1c > 2.0% in 3 months).
2. Warnings should be available in real time and be ca- e. Conditional statements. If-then-else state-
pable of being tailored to the specific patient situation ments that direct action based on the result of
using available patient information (e.g., age, gender, a Boolean logic statement (AND, OR, NOT).
weight, laboratory values, radiology procedures, di- Duration conveniences must allow construction
etary needs, diagnosis, current problem list, location of temporal logic such as:
of care delivery) together with information contained 1. If age < 6 days then …
in the drug database to construct inclusion and exclu- 2. Else if age < 2 years then …
sion criteria that make alerts more useful and reduce In this case, age (a duration) is automatically
alert fatigue. The patient information should conform converted to days and then years.
to standard terminology, such as Logical Observation 6. All practice settings should have the ability to con-
Identifiers Names and Codes (LOINC) for laboratory figure whether a warning acknowledgment cannot be
tests. The drug database vendor should consider de- bypassed (i.e., a “hard stop”), can only be bypassed
veloping an external database that translates standard by documenting a valid reason for bypassing the alert
terminologies (e.g., RxNorm, LOINC, Systematized (i.e., a “soft stop”), or can be bypassed without doc-
Nomenclature of Medicine, and International umenting a reason, and whether an additional com-
Classification of Diseases codes) to an internal dic- ment is required by user type and venue (e.g., critical
tionary of medical terms used in their knowledge base. care, ambulatory). If a drop-down menu is utilized, it
3. Medication-order-specific information (e.g., dosage should specifically relate to the context and content
forms, routes, frequencies, dose, order status, ordering of an alert.
provider) should also be available to be utilized in alert 7. Users should be able to take action from the synchro-
inclusion and exclusion criteria. nous alert presentation window. Such actions should
4. All practice settings should have the ability to (a) custom- be specific to the type of alert presented and include
ize how an alert looks (e.g., color, shape, audio, size) to at least the following seven choices, by type of user or
emphasize the criticality or type of warning, and (b) offer user category:
response options based on characteristics of the potential a. Discontinue the conflicting order.
harm (e.g., prevalence of problem, extent of risk or sever- b. Cancel the order being entered.
ity) (see “Notification System” in Figure 2). c. Modify the order being entered (e.g., change
5. All practice settings should have the ability to con- dose, dosage form, route, frequency, start date,
figure the information displayed in the warnings. The or end date).
CDS rule development language must enable the rule d. Modify the preexisting order (e.g., change dose,
to build patient-specific alert messages during rule ex- dosage form, route, frequency, start date, or end
ecution. The following five basic types of logic must date).
be supported by the rule development tool kit. e. Add monitoring orders (e.g., laboratory tests or
a. String handling. This type of logic allows the other parameters).
rule developer to incorporate useful patient- f. Continue with current order as requested.
specific suggestions based on patient informa- g. Suspend the current order (i.e., put it in a held/
tion. It also allows displaying of useful data such suspended state).
as allergies, relevant medications, and other pa- 8. The EHR system should be able to handle logic rules
tient characteristics or data, in the form of text that determine how an alert can be transmitted to the
or structured data values, directly into the warn- clinician as well as specifying the individuals and/or
ing message, so the information contained in the groups that are to receive the alert. The importance of
alert can help the clinician determine the best the alert should also be included in the logic rules for
response to the alert. determining who is notified about the alert and how
b. Loop functions. This type of logic allows alert they are notified. The alert notification should be able
designers to gather or group all related informa- to be transmitted in any electronic form, depending
tion into a single warning (e.g., sort through lists on the technology available at the institution, includ-
of patient data to find relevant drug, lab result, or ing but not limited to the electronic message inbox
diagnosis). In addition, the loop functions should within the EHR, e-mail (where the alert information
allow the use of mathematical algorithms (e.g., is available within the e-mail message), pagers, text
statistical methods to test trends of data, calcu- message, fax, and printers. Encryption or secured
late glomerular filtration rate, or perform patient messaging must be utilized to protect patient health
scoring). information. The alert notification system should
c. Math functions. This type of logic allows an include a means of stratifying the alert importance
alert to perform calculations and must include and associating the type of alert notification with the
logarithmic and other standard mathematical level of the alert (e.g., an alert of moderate impor-
functions. This will be necessary to perform spe- tance would be e-mailed to the clinician, whereas
cialized calculations that are available in but not a more urgent alert such as a direct allergy match
retrievable from the EHR. would be sent via text message). This type of stratifi-
d. Trends over time. This type of logic provides the cation would be included in the logic using “if-then”
ability to configure alerts based on trends in data types of statements.
Figure 2. Conceptual schematic of a potential new architecture with a clinical rules engine (CRE). Not shown here is the integrated development
environment, where the rules are built by a clinician analyst. CPOE = computerized provider order entry, eMAR = electronic medication
administration record, MedIA = medication interaction alert (e.g., drug–drug, drug–allergy, dose check, drug–disease).
:
Notification System sends alerts by several methods:
1) pop-up (several formats based on priority)
CPOE System 2) internal e-mail, pager/phone text message
3) printer or other device
4) Database to trigger other alert or report
HL7 message
or integrated
CRE Format
Alert Notification HL7 message Alert
System message
Pharmacy
Information
System
If alert needed CRE builds Alert message
HL7 message assigns notification method based on priority
Block original Alert Message
or integrated if CRE has a rule for this
Med Interaction alert
Clinical
eMAR Event Monitor detects Rules Engine
HL7 message for (CRE)
Med alerts that have Determines need
existing rule in CRE for Med Interaction
Alert
HL7 message
CRE queries
patient data
Medication
HL7 Interaction
message Alert Event Monitor also
checks for lab results
and other events that
affect drug therapy EMR Database
Patient Records
MedIA System & HL7 message

MedlA Database
9. The EHR system should provide the capability to al- 10. The alerts system should allow sub-second response
low all practice settings to determine whether end us- times (i.e., the absence of user waiting for system
ers can customize the conditions under which they must response) for warning notification and filing user re-
respond to specific alerts within the larger list of alerts sponse. Although response time is contingent upon a
assigned to them. Appropriate warnings and audit trails practice setting’s hardware configuration, a short re-
must be in place to support this functionality. Database sponse time is essential to winning user acceptance.
managers should be able to customize the conditions Reporting or database updates should not impact real-
and options for the user to respond to specific alerts to time system performance.
a. “Snooze” the alert: delaying a response to the 11. All practice settings should have the capability to con-
alert, whether globally or for user-identified in- figure and record (or track) when an alert notification
dividual patients for a predetermined amount of displays, which implies when the checking occurs
time with the ability to limit how many times an (e.g., when the medication is first selected, when a
alert may be ignored before an action is required. portion of the order information is changed, when the
b. Forward the alert: send the alert to an EHR mes- order or group of orders is filed). If an alert is overrid-
sage box with a time constraint based on the den but then the triggering order is discontinued within
follow-up action needed. a certain time period of the alert firing, the data should
indicate that the alert had a user response that resulted order or alert via inquiry and as part of subsequent
in discontinuing an order. alerts at order verification or other transactions related
12. Clinicians and EHR system managers should have to the order. The inquiry should provide the ability for
easy access to the supporting data available for each a user to check a patient’s record for any alerts dis-
alert viewed in the EHR. Supporting evidence, includ- played in the system, including a historical account of
ing citations, should be available as specified in the all alerts that have displayed for a patient (pertaining
American Recovery and Reinvestment Act of 2009 to the current or prior inpatient or outpatient visits),
Stage 2 meaningful-use requirements.9 Supporting ev- including all information mentioned in item 15 above.
idence formats that should be available would include 17. Data related to user actions in response to alerts and
a. References that are included with the data im- messages must be available within the context of CDS,
ports from the various knowledge databases. and standard queries should be available. Data on
b. Internal system policies and protocols. alerts and responses to those alerts should be export-
c. External reference databases or guidelines. able to an external database or spreadsheet to support
EHR systems should be able to display these refer- retrospective auditing. Studies are needed to determine
ences, the quality of the references, and any other sup- if documenting override reasons improves or dimin-
porting evidence provided by the knowledge vendor. ishes alert effectiveness and patient outcomes. Rates
EHRs should allow links to external databases or doc- of overrides and other simple measures of alert effec-
umentation when deemed appropriate by the institu- tiveness can be useful for identifying potential oppor-
tion. These links should allow viewing of more details tunities to improve system performance, but additional
than what is presented in the initial alert. Supporting studies are needed to document the effect of changes
information should be easily retrieved by the user as made to CDS alerting rules. The reporting mechanism
part of the typical workflow. Supporting evidence should facilitate the capture of the chronological his-
should be formatted so that it could be presented in tory of alerts associated with an order across the mul-
either a soft- or hard-alert format. tiple users who receive them.
13. If there is additional information located within the 18. Outcome documentation should be consistent across
EHR that is relevant to the alert, the EHR should pro- vendor systems so that healthcare organizations can
vide a link or other means of easily accessing that con- accurately compare and benchmark database-driven
tent as part of the clinician workflow. Examples would CDS outcomes among organizations. To achieve this
include goal, vendors and CDS researchers may need to estab-
a. Allergy information. lish a consensus database schema for CDS outcomes.
b. All orders flagged by the alert. 19. The alerts system must facilitate easy identification of
c. Links to orders needed for entry as determined any facility-specific custom data that will be affected
by the alert (e.g., laboratory test, medication). by modifications that a vendor has made to data or
Setting up links for internal or custom external docu- functionality.
ments via the EHR alert should be a simple process. 20. CDS rules must be easily exportable to a text file. The
14. The EHR system should provide the ability to in- exported rule must contain rule logic and all documen-
voke the database for synchronous and asynchronous tation contained in the rule. The exported rule does not
checking based on different system transactions (i.e., have to contain external data queries or external desti-
not only order entry). Examples include laboratory test nation logic referenced within the rule’s logic, as this
values filing to the patient chart, entering of patient information is unique to the hospital or health system.
information (e.g., diagnosis, problem, allergy), medi- 21. The CDS system must allow batch import of CDS
cation administration (see “Event Monitor” in Figure rules from standalone files of prespecified types and
2), or to delay alert notification to allow completion formats. There must be options to overwrite existing
of orders (e.g., for an aminoglycoside order, allowing rules and add new rules.
time for the practitioner to determine whether serum 22. The CDS system must allow users to flag alerts for
creatinine, drug levels, or a consult has also been or- usefulness or intrusiveness so as to give the user a
dered). mechanism to provide immediate feedback to the CDS
15. The CDS system must log all alert warnings and user team. This functionality would be an extremely helpful
actions taken in response to the alert (i.e., record alert tool to allow for a real-time evaluation tool for CDS,
outcomes). Those alert outcomes should include, at a especially when changes are made to a system before
minimum, the following: the CDS team has a chance to collect and collate data.
a. User who has received the alert.
b. Users who have viewed the alert. Conclusion
c. Overridden alerts.
d. Alerts that have occurred and had an action Database-driven CDS could have a major impact on the qual-
taken on them. ity, safety, and cost of healthcare. Unfortunately, its potential
e. Subsequent actions taken from the synchronous is largely unfulfilled due to the high number of false-positive
alert or view window. warnings produced by most CDS systems. Alert fatigue from
f. Current patient data related to the alert. these warnings is common among physician and pharma-
g. Communications associated with the alert (e.g., cist users of EHR systems. To realize the promise of CDS,
reasons, required responses, comments). drug database and EHR vendors must work collaboratively
16. All responses entered during the alert session should to develop CDS systems that offer flexible patient-specific
be available to subsequent users who view either the checking, reduce false-positive and false-negative warnings,
and provide useful warning information to clinicians. It is of management. Section 2: overview of CDS five rights.
equal importance that all practice settings embrace this new Improving medication use and outcomes with clinical
functionality and aggressively use it to improve the specific- decision support: a step-by-step guide. http://heal-
ity and appropriateness of patient care. By giving all practice thit.ahrq.gov/ahrq-funded-projects/clinical-decision-
settings the power to tailor drug database warning systems support-initiative/chapter-1-approaching-clinical-
as they do with their EHR rules engines, the needed specific- decision/section-2-overview-cds-five-rights (accessed
ity to patient factors can be obtained. 2014 Sep 26).
11. Health Level Seven International. HL7 standards—
References master grid. www.hl7.org/implement/standards/prod-
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1. Bates DW, Cohen M, Leape LL, et al. Reducing the
frequency of errors in medicine using information
technology. J Am Med Inform Assoc. 2001; 8:299–308. Developed through the ASHP Section of Pharmacy Informatics
2. Kuperman GJ, Reichley RM, Bailey TC. Using com- and Technology Section Advisory Group on Clinical Information
mercial knowledge bases for clinical decision support: Systems. Approved by the ASHP Section of Pharmacy Informatics
opportunities, hurdles, and recommendations. J Am and Technology Executive Committee on December 6, 2014, and by
Med Inform Assoc. 2006; 13:369–71. the ASHP Board of Directors on April 10, 2015.
3. Kesselheim A, Cresswell K, Phansalkar S, et al.
Clinical decision support systems could be modified David Troiano, B.S.Pharm., M.S.I.A., CPPS, is Director of
to reduce “alert fatigue” while still minimizing the risk Consulting, Dearborn Advisors, Chicago, IL. Michael A. Jones,
of litigation. Health Aff. 2011; 30:2310–7. Pharm.D., is Informatics Pharmacist for Clinical Decision Support,
4. Phansalkar S, van der Sijs H, Tucker AD, et al. Drug– University of Colorado Hospital, Aurora. Andrew H. Smith,
drug interactions that should be noninterruptive in or- B.S.Pharm., M.H.A., is Pharmacy Clinical Applications Analyst,
der to reduce alert fatigue in electronic health records. Novant Health, Winston-Salem, NC. Raymond C. Chan, Pharm.D.,
J Am Med Inform Assoc. 2013; 20:489–93. is Informatics Residency Coordinator—Information Technology,
5. Lin CP, Payne TH, Nichol WP, et al. Evaluating clini- Sentara HealthCare, Norfolk, VA. Andrew P. Laegeler, M.S.,
cal decision support systems: monitoring CPOE order Pharm.D., is Pharmacy Informatics Operations Manager, Harris
check override rates in the Department of Veterans County Hospital District, Houston, TX. Trinh Le, B.S.Pharm, M.S.,
Affairs’ computerized patient record system. J Am FASHP, is Clinical Pharmacy Manager—Informatics, Department
Med Inform Assoc. 2008; 15:620–6. of Pharmacy, University of North Carolina Health Care, Chapel
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and override rates of order checks in a practitioner or- Innovators, Ann Arbor, MI. Bruce W. Chaffee, Pharm.D., is
der entry system. Proc AMIA Symp. 2002:602–6. Coordinator for Strategic Projects and Adjunct Clinical Associate
7. Weingart SN, Toth M, Sands DZ, et al. Physicians’ Professor of Pharmacy, Department of Pharmacy Services, College
decisions to override computerized drug alerts in pri- of Pharmacy, University of Michigan, Ann Arbor.
mary care. Arch Intern Med. 2003; 163:2625–31.
8. Karsh BT. Clinical practice improvement and rede- Copyright © 2015, American Society of Health-System Pharmacists,
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10. Agency for Healthcare Research and Quality. Chapter
1: approaching clinical decision support in medication
ASHP Guidelines on Pharmacy Planning for

Implementation of Computerized Provider-Order-
Entry Systems in Hospitals and Health Systems
Purpose and Scope CPOE and the Electronic Health Record
The purpose of these guidelines is to provide guidance to In its 1999 report To Err is Human,1 the Institute of Medicine
pharmacists in hospitals and health systems on planning for, (IOM) shocked the nation with its estimate of deaths due
implementing, and enhancing safe computerized provider- to medical errors. Two large studies, one conducted in New
order-entry (CPOE) systems. To date, most CPOE guide- York2,3 and the other in Utah and Colorado,4 revealed ad-
lines have concentrated on the functionality required of a verse events occurring in 2.9% and 3.7% of hospitalizations,
CPOE system, despite the fact that most CPOE system respectively. Over half of these adverse events were judged
implementations occur using commercial systems whose to be preventable. Based on these studies, IOM estimated
functionality is largely pre-determined. These guidelines are that 44,000–98,000 Americans die each year due to medical
intended to help pharmacy directors, managers, informati- errors in hospitals.1 Many of these deaths are caused by med-
cists, and project managers successfully engage in this type ication errors or preventable adverse drug events (ADEs).5,6
of CPOE system implementation. CPOE is commonly part When it was recognized that errors resulting in pre-
of a larger health information technology (IT) plan or system ventable ADEs involved a wide range of drug classes and
implementation. Though many health care technologies im- most commonly occurred at the prescribing stage,7 interest
pact patient care and pharmacy practice, this guideline will in CPOE systems grew. In a second report, Crossing the
focus on CPOE only. This document is the first of a planned Quality Chasm: A New Health System for the 21st Century,8
series of ASHP guidelines on CPOE and related technolo- the IOM called for IT, including CPOE, to take a central role
gies and addresses the planning phase of a health-system in the redesign of the health care system to improve quality,
CPOE implementation, primarily focusing on acute care and increase efficiency, and reduce errors. In addition to IOM,
associated ambulatory care clinics. The guideline will focus organizations such as the Leapfrog Group and the National
on using CPOE in the medication-use process, though it is Quality Forum have pushed for hospitals to adopt CPOE.9,10
important to realize that CPOE includes all orders for patient The American Recovery and Reinvestment Act of 2009
care (laboratory, nursing, respiratory, and others). Topics (Recovery Act) authorizes the Centers for Medicare and
covered in these guidelines include Medicaid Services (CMS) to provide reimbursement incen-
tives for eligible professionals and hospitals who are success-
• Developing an interdisciplinary planning and imple- ful in becoming “meaningful users” of certified electronic
mentation team, health record (EHR) technology. This law will likely increase
• Defining the vision, goals, and objectives of the CPOE the adoption of CPOE in hospitals and health systems.11
system, CPOE has the potential to affect the ordering of all
• Establishing essential metrics to measure the success medications, laboratory tests, medical imaging, nursing or-
of CPOE system implementation, ders, and more. Even a basic CPOE system can eliminate
• Understanding current and future workflow in order illegible and incomplete orders and facilitate efficient order
to reengineer the medication-use process as part of processing through instantaneous transmission of orders
CPOE system implementation, to hospital departments such as pharmacy and laboratory.
• Planning for scope and depth of clinical decision sup- Additionally, CPOE integrated with a pharmacy information
port (CDS), system and the electronic medication administration record
• Determining the functionality that ensures the safety (eMAR) can nearly eliminate transcription errors, resulting
of the CPOE system, and in another potential 6% decrease in ADEs.7 A homegrown
• Educating and training health care providers to use the CPOE system has been shown to decrease medication errors
CPOE system. by 55–80%.12,13 There are many reports of improvements
in physician practices and patient outcomes with health IT
Terms used in these guidelines are defined in the appended related to ordering,14-21 but in some reports it is difficult to
glossary. The recommendations presented in these guidelines distinguish whether the benefits were due to CPOE, CDS,
can be used for strategic planning with the organization’s the EHR, or a combination of all three. The synergy of the
decision-makers, drafting contract provisions, prospectively three of these will likely lead to the most significant im-
comparing CPOE systems, and creating an implementation provements.15,16 Although there are many reported benefits
plan. These guidelines should be used in conjunction with to CPOE, there is a growing body of research pointing to
other literature on the topic and information from prospec- new problems introduced by CPOE. These new problems
tive or selected CPOE vendors. Pharmacists should exercise are collectively known as e-iatrogenesis, which is defined
professional judgment in assessing their health system’s as patient harm caused at least in part by the application of
needs regarding CPOE systems and in adapting these guide- health IT.22 Though the systems themselves may contribute
lines to meet those needs. to these problems, design and implementation decisions play
a role in the avoidance of these new errors.
More recently, attention has focused on the develop- use process; and planning for CDS. Project management
ment of an integrated information system to support the co- and change management skills are vital for the conversion
ordination and integration of clinical and business processes. to CPOE. Because the enormous change in workflow will
The terminology for such information systems is evolving, affect every clinician, standard project management and
with enterprise information system sometimes used to de- change management tools, such as a formal project charter,
scribe the broader system that integrates clinical and busi- will help keep the implementation on track and manage ex-
ness systems, and EHR used to describe the clinical infor- pectations. Establishing a plan for communication is impor-
mation system, which may include a patient portal or the tant from day 1.
ability to link to a personal health record (PHR).23 CPOE
must be viewed in the context of the EHR, which would in- Assembling an Interdisciplinary Planning
tegrate CPOE, CDS, and departmental information systems and Implementation Team
and make patient-specific clinical information available to
providers. The transition to CPOE is an immense cultural change
The EHR is a longitudinal electronic record of patient that will affect every member of the health care team. No
health information generated by one or more encounters in individual or department will be exempt from the impact
any care delivery setting.24 It contains medical histories, of CPOE. Support for the project at the executive level
medication histories, laboratory test results, diagnostic im- is a prerequisite. Medical and administrative leadership/
ages, clinical documentation, progress notes, narrative sum- sponsorship are instrumental in the development of a clear
maries (such as operative reports or consultations), and other vision for CPOE. An interdisciplinary team approach to
information related to patient encounters. EHRs provide the planning and implementation is essential for a safe, well-
ability to manipulate, organize, and present data in ways designed, user-friendly, and successful CPOE system.
that are clinically meaningful during the care planning, or- Physicians must be central players in the decision-
dering, and care processes and allow broad clinician access making process, as prescriber buy-in and acceptance is
to patient-specific clinical information, which is important crucial to CPOE success. Key departments (such as phar-
to clinical quality and patient safety. When fully deployed macy, nursing, laboratory, radiology, admissions, di-
within a facility through protected networks, the EHR serves etary, and respiratory therapy) must dedicate resources
as an information source and platform to coordinate patient and be involved in the initial effort, including workflow/
care and communicate with the health care team. In addition, process analysis and redesign, system analysis, integration
codified data can be used to trigger effective CDS as well as between ancillary systems, review of organizational culture,
to provide data for continuous quality improvement. and compliance with regulatory, legal, and reimbursement
For CPOE to be most useful it must be deployed as requirements.
part of an EHR and not as a stand-alone module. CPOE is The involvement of pharmacists in the development
the process of health care providers entering orders and re- and implementation of CPOE is essential for several rea-
lated information directly into the EHR. It places the pro- sons. Pharmacists have the benefit of years of experience
vider at the center of patient care, allowing direct access and with electronic order entry systems. Pharmacists’ experience
secure sharing of health information. with human factors issues related to the interaction between
The EHR, including electronic clinician (e.g., physi- human and computer is invaluable, even though pharmacy
cian, pharmacist, nurse) documentation with CPOE and systems may differ from CPOE systems in significant ways.
CDS, is important to support the complex effort needed to In addition, the medication-order-entry aspect of CPOE sys-
improve hospital care.15,16 The integration of CPOE and tems leads to the most significant increase in patient safety
CDS within an EHR can create a platform upon which to and is likely the most complex part of the system.21,29–32 The
build and improve the delivery of health care today and in initial decision to purchase a completely integrated CPOE
the future. Many organizations implement these in a step- system or develop one that can interface with existing elec-
wise fashion because of the enormous work effort and the tronic systems (e.g., the pharmacy department’s informa-
significant workflow changes required. Although there is tion system) is an important one that would benefit from
no single solution that fits every circumstance, the litera- the pharmacist’s perspective. Although the number of suc-
ture offers many examples for others to follow or avoid.25–28 cessful implementations is increasing on a yearly basis,33 the
Regardless of the vendor, organization size, or other factors complexity of the systems should not be underestimated.
that could potentially affect success, there are quite a num- Collaboration among health care staff and the IT de-
ber of implementation decisions that can increase the likeli- partment is critical to the selection, implementation, and
hood of a clinician-accepted CPOE installation that leads to maintenance of CPOE systems. Although a CPOE system
quality and safety improvements. cannot be developed and implemented without IT expertise,
the CPOE system is intended to serve the best interests of
Planning for the Transition to CPOE patients and clinicians. Clinicians and IT staff do not always
talk the same language, and differences of opinion are not
A successful CPOE implementation starts with a well-orga- uncommon. Though difficult at times, these groups must
nized, realistic plan. In planning for the transition to CPOE, work together for success. IT understands the technical as-
initial tasks include assembling an interdisciplinary plan- pects, but physicians, nurses, and pharmacists are best suited
ning and implementation team; developing a vision, goals, to determine how the CPOE system can be implemented to
and objectives for the CPOE system; establishing essential best serve the interests of patients and clinicians.
baseline and post-go-live metrics; mapping current physi-
cian, pharmacist, and nurse workflows as they relate to the Recommendations for Team Structure. The organization
medication-use process; defining the desired medication- should carefully consider the structure of the interdisciplin-
ary implementation team, which should include physicians, important as early as possible. The hospital should consider
nurses, pharmacists, IT staff, the chief medical information the merits of compensation for time spent away from clini-
officer, and staff from all ancillary departments (e.g., labora- cal duties. The health system’s existing committee structure
tory services, respiratory therapy). In addition to front-line may be utilized as oversight authority for CPOE initiatives
practitioners, patient safety and quality improvement staff before, during, and after the system goes live. However, it is
can help immensely with some of the workflow and design highly recommended to create small work groups consist-
decisions. CPOE systems by definition require ownership by ing of physicians, administrators, pharmacists, nurses, and
the medical staff. Therefore, prescribers (mainly physicians) IT personnel to make and approve design decisions and form
must be actively solicited for system requirements and be specific task groups as needed when policy or process is-
involved in key decisions. CPOE system design, including sues arise. Quick and timely action will be required during
the content, the user interface, and the flow of CDS, will the implementation phase to keep the project moving for-
be influenced by the vendor’s product, but acceptance will ward on schedule and in an organized and cohesive manner.
ultimately reside with the medical staff. This interdisciplinary group should refer matters of policy to
The team structure for implementing CPOE must take existing policy-making committees (e.g., P&T committee,
into account the interests and expertise of the following medication safety committee, executive committee, practice
types of individuals: guidelines committee, leadership council). The interdisci-
plinary CPOE committee is not a policymaking committee,
• Clinical content experts. Physicians, pharmacists, but rather a tool to provide structure to existing policies.
mid-level providers, nurses, and practitioners of other Some organizations may find it necessary to keep this new
disciplines who have clinical knowledge and work- formal committee for ongoing oversight of clinical informa-
flow experience that can help shape the CPOE system tion systems and CDS decision-making.
to be most useful in the local environment. Pharmacists are needed to provide oversight of
• Medical record content experts. Health care informa- medication-use process development. Pharmacist involve-
tion management representatives who oversee the le- ment should begin in the initial CPOE planning stages and
gal medical record. continue throughout all phases of CPOE development and
• Technical experts. Typically, IT professionals who un- optimization. The pharmacists that serve on the interdisci-
derstand the capabilities of the system, write or config- plinary team would ideally be relieved of clinical duties to
ure the software, and test and troubleshoot problems. the extent possible in order to commit much of their time to
• Front-line users. Physicians, nurses, pharmacists, and the complex project. Those pharmacists could remain in the
others who care for patients on a regular basis and who pharmacy or be physically relocated to whatever space the
will understand the positive and negative implications interdisciplinary team is allocated. Any pharmacist chosen
of each proposal regarding CPOE. CPOE’s effects on to serve on the team should be
nurses cannot be overstated. The workflow of incom-
ing information completely changes with the imple- • A team player,
mentation of CPOE. The unit secretary will no longer • Well-respected within and outside the pharmacy de-
be the gatekeeper and notifier of new orders. The department,
velopment of an electronic means to notify nurses of • A good communicator,
new orders must be considered and incorporated into • Knowledgeable about all facets of the medication-use
the nursing workflow to enhance patient care. system, especially the thought process prescribers use
• Project managers. Individuals responsible for over- to determine a treatment or treatment plan,
seeing the completion of project tasks and managing • Well-versed in the regulatory and legal requirements
timelines and resources. There may be both a facility of medication management,
project manager and a project manager for the vendor • Current on patient safety initiatives and issues, both
or outside contractor. external and internal to the health system,
• Workflow analysts. Team members responsible for • Detail-oriented, with sharp analytical skills,
analyzing the workflow and processes of patient care, • Open to new ideas,
from admission through the entire hospitalization (in- • Very interested in informatics,
cluding transfers, surgeries, and procedures) to dis- • Capable of handling stressful situations and limited
charge. time lines, and
• Project sponsors. Clinician champions and organiza- • Able to differentiate the requirements of an ordering
tion leaders who can, with frequent reports from the system from those of a dispensing system and translate
CPOE team, help overcome the many real and imag- those requirements for others.
ined barriers to the CPOE transition and keep the im-
plementation on track. Outside Consultants. External consultants may be used
• Others. Ancillary staff whose roles or responsibilities in a variety of roles, including evaluation and ven-
may change with the implementation of CPOE. dor selection as well as project management and post-
implementation assessments. Use of outside consultants
Representatives from each of these areas of expertise should may be warranted if there are insufficient resources, lack of
work together regularly, in a variety of committees and work on-site knowledge of the vendor’s application, or a desire
group formats. The team should report to a key organizational for a quicker implementation timeline. Consultants add a
committee (e.g., the pharmacy and therapeutics [P&T] com- unique dimension to the team structure in that they have ex-
mittee) as well as medical staff or other governance-related perienced how other hospitals have solved similar problems,
bodies. Communication with many formal committees is can offer a variety of solutions based on their experience
from other facilities, and have a network of colleagues they tion and not an IT implementation. The implementation team
can contact for advice. Having a consultant engaged early in should determine whether there are other issues that may
the process can provide continuity to the development and influence CPOE implementation, such as new buildings or
implementation processes. other system changes (e.g., pharmacy, bar-coding, or eMAR
External consultants should work in conjunction with systems). The team should review and attempt to antici-
permanent members of the implementation team. It is im- pate trends in regulation or best practices (e.g., from CMS,
portant that the permanent members of the team know and the Joint Commission, the Institute for Safe Medication
understand how the system was designed, how its compo- Practices, or ASHP) and adopt practices from similar sites
nents fit together, and how each item was built by the con- that have implemented CPOE. Finally, it should be remem-
sultants. Changes in one part of the system may have in- bered that CPOE is only one element of the hospital’s IT in-
tended and unintended downstream effects. Modifications to frastructure. Care should be taken to integrate these disparate
the system are inevitable, and the on-site team must have the systems, with the end result of a complete EHR.
knowledge to understand and execute the necessary future Pharmacy involvement in CPOE development and im-
changes. It is detrimental to have this knowledge leave with plementation will be related mainly to medication use within
the consultant when the contract expires. Formal documen- the health system. Pharmacists often have experience with
tation and knowledge transfer meetings should be part of the entry of medication orders into a computer system. This ex-
consultant deliverables. perience can be used to help providers adapt to the changes
that come with CPOE, but pharmacists should be aware of
Allocating Resources. The resources required to manage the the differences between ordering medications and verifying
transition to a CPOE system will vary, based on a number of and dispensing them. Financial goals, hospital infrastruc-
factors: the size and complexity of the institution, whether ture, integration, and regulatory compliance also play an im-
it is an academic or a community setting, types of patients portant role in the development of a vision for CPOE.
served, current IT infrastructure, the scope of the CPOE Developing a vision for medication orders in a CPOE
project, commitment of implementation project team mem- system can be divided into three main tasks: defining the
bers, degree of system integration, and other circumstances. goals and objectives for the CPOE system, mapping the cur-
There are no general rules about the time, money, or number rent and desired medication-use processes, and determining
of employees required for such a transition. Vendors may CPOE system performance requirements to reach those goals.
perform an assessment to help determine the resources that An organization’s physicians, nurses, pharmacists, other pro-
will be required based on the institution’s circumstances. viders, and administrators can team up to prepare this vision.
The resources needed should be identified and ap- The vision might include describing how products should be
proved before the project begins, and monitoring of ongoing named for easy identification or the configuration of special
resource needs and allocation will be necessary. Planning populations of orders. Consideration should also be given to
often focuses on capital expenses, underestimating the per- how medication orders relate to other orders, laboratory test
sonnel required to build, test, maintain, improve, and train results, allergies, and other clinical information.
staff on the use of the system.29 Having these resources in
place is critical to the success of an implementation. During Defining Goals and Objectives for the
planning and implementation, resource needs may vary, CPOE System
based on project activities. Following implementation, or-
der sets and CDS are integral components of managing care, Implementing CPOE is an immense cultural change that
and the ongoing maintenance to keep the care components involves every part of an organization. After an overarch-
current and in line with practice requires ongoing resources. ing vision for the components of the CPOE system has been
In addition, as the complexity of the system increases with established, the implementation team should reach out to all
enhancements and user requests, resources needed for ongo- areas of the institution to develop and explain the goals and
ing management may increase. Understanding these needs objectives of the CPOE system. Widespread understanding
before implementation can help in resource planning. and acceptance of these goals and objectives will facilitate
development and implementation of the CPOE system. The
Developing a Vision for the CPOE System central goals of a CPOE system typically include improving
medication safety and the quality of health care processes.
A vision statement helps describe where the organization
wants to be after CPOE implementation and helps define Medication Safety. Improving the safety of the medication-
decision-making criteria and the framework for metrics. It is ordering process should always be in the forefront of any de-
imperative that the CPOE vision align tightly with the vision sign decision, programming modification, or enhancement to
of the organization as a whole. Large-scale projects should in- CPOE. The analysis of the existing medication-use process
clude a clear organizational vision, which might be as simple (see “Mapping the Current Medication-use Process” below)
as increasing patient safety or improving provider access to should identify any safety deficiencies that can be corrected
information. Taking the time to develop these criteria will with CPOE, as well as the strengths of the current processes.
focus the team throughout the design and implementation The addition of safety features to CPOE will be an ongoing
processes, help the team communicate the rationale for endeavor, as acceptance of the system grows and clinicians
the necessary change that front-line clinicians will have to realize how the system can improve their practices.
make, and lay the groundwork for ongoing measurement. CPOE systems need to be monitored for unexpected
CPOE is a vital component of the institution’s overall safety failures. CPOE can introduce previously unknown
patient safety and IT development plans. It is important to safety failures through user interaction with the system,
establish from the beginning that CPOE is a clinical interven- programming changes, or poor system design.26 To prevent
the introduction of new medication errors, careful analysis, to drug–drug interactions, prescribing errors related to drug
review, and testing needs to be conducted with initial im- dose, and drugs withheld due to contraindications identified
plementation and subsequent additions, modifications, and via CDS.
enhancements. Constant surveillance for errors and unan-
ticipated outcomes is an ongoing necessity.29 This evalua- Establishing Post-Go-Live Metrics
tion can also be used to develop the goals and objectives for
implementation. Implementation metrics can be used to help measure
A major impetus behind CPOE is that the deployment achievement of organizational goals. Comparing baseline
of a well-designed CPOE system with effective CDS can and post-go-live measures can identify which areas have im-
reduce medication errors and ADEs. A systematic review proved and which need further review. Metrics are quantita-
of the effects of CPOE with CDS on medication errors and tive, measurable parameters, and may include
ADEs supports the successful use of CPOE in health care fa-
cilities.18 Many hospitals will implement CPOE to improve
patient care, while focusing less on research that explores its
• Order entry time (e.g., average time it takes a provider
to enter an order36),
impact. Nevertheless, internal systems for tracking medica-
tion errors and ADEs should be continually used to assess
• Compliance with established evidence-based order
sets,
the impact of CPOE. CPOE could potentially
• Number of entered orders,
• Missing doses,
• Reduce some forms of ADEs or medication errors,
• Pharmacist interventions related to order entry prob-
• Qualitatively change some forms of ADEs or medica- lems,
tion errors (e.g., an error of omission may become a
wrong-time error), and
• Changes to scheduled administration times in the sys-
tem,
• Introduce new types of ADEs or medication errors
• First dose medication administration turnaround time,
(e.g., a physician may select the wrong drug or wrong
patient from a list appearing on the computer screen or
• Assess possible financial indicators of success,
inappropriately select a default dose).
• Frequency of provider contact (e.g., pages for ques-
tions or errors on order entry), and
Quality of Health Care Processes. In addition to improv-
• Documented medication errors.
ing medication safety, the goals of CPOE implementation When reporting these data, the hospital should be careful not
may include such things as decreasing drug or laboratory to overstate the impact of the CPOE system on patient out-
costs, reducing the time required for pharmacist medication comes. The measures listed above are process measures, not
order review, improving data collection, or increasing com- outcome measures. For example, although the CPOE system
munication among health care team members. If efficiencies may have flagged a patient allergy and prevented adminis-
from the direct entry of medication orders by the physician tration of the medication, it is possible that even without the
result in time savings in the pharmacy, the pharmacy depart- CPOE system the pharmacist or nurse would have identified
ment could potentially direct more pharmacist resources to the allergy and intervened before the drug was administered.
patient interaction or areas such as pharmacotherapy consul- It is important to identify and report new errors or
tation, pharmacokinetics, anticoagulation monitoring, drug ADEs introduced by the CPOE system.22,25,26,31,37–40 The
regimen review, antibiotic streamlining, or intravenous-to- hospital should actively engage clinicians at all levels in
oral (i.v.-to-p.o.) conversions. Such goals will be different open dialogue and reporting of such issues. These reports
for every organization, but it is important to establish them should be used to make rapid changes in the design of the
during the planning phase of the project. The transition to system in the spirit of continuous quality improvement.
CPOE represents a major paradigm shift for most organiza-
tions. The organized, goal-oriented institution will benefit
from creating concise, measurable goals and objectives.19 Describing the Current Medication-Use
Process And System Design
Establishing Baseline Data
To ensure that the integrity, safety, and efficiency of the
entire current medication process are maintained, if not en-
In conjunction with the analysis of the current medication-
hanced, it is important to perform a complete analysis of the
use process, the interdisciplinary team should develop a
current medication-use process. This analysis should include
clear and complete understanding of the institution’s current
the interdisciplinary workflows associated with medication
medication safety data (e.g., medication errors, ADEs) as
use for multiple types of medications. The output can be rep-
well as the resources devoted to the manual medication or-
resented in a variety of ways, including flow charts, narra-
der system.34,35 It is important to track data for at least three
tive scenarios, analyzed issue/problem reports, and compari-
months in advance of implementation to assemble adequate
sons of current practices to known best practices.
baseline data. These data can then be compared with data
The analysis of the current medication-use process
from the CPOE system at designated intervals. Data should
should consider a variety of medication order types, based
be tracked over time to assess the impact of the CPOE on the
on frequency of use or potential impact on patient safety, in
medication-use process. This information can help identify
all different process settings (e.g., acute care, critical care,
workflow bottlenecks or discrepancies in the CPOE system,
emergency department), procedural areas (e.g., diagnostic
providing opportunities for improvement. Examples of data
imaging), and patient populations (e.g., pediatric, geriat-
that may change with the implementation of CPOE and CDS
ric, adult). The project team should consider a representa-
include errors related to known drug allergies, ADEs related
tive group of orders that includes the basic types of orders Developing the Future Medication-Use
prescribers typically write. How orders are currently entered
Process and System Design
into the system may not necessarily be intuitive to a phy-
sician. Most importantly, the project team should consider
Once the current state of the medication-use process is well
how the prescriber currently orders medications and what
understood, one or more instances of the future state (de-
would make the most sense to the prescriber when order-
pending on the plan for phasing in the CPOE system) can
ing electronically. CPOE systems should be designed from
be designed. This future state should be designed to meet
the prescribers’ perspective, with an eye on how orders flow
or exceed the current levels of service and other important
over the course of their existence, to encompass all facets
designated metrics and priorities (e.g. patient safety, first-
of medication use, ensuring the process is complete from
dose delivery time) and address any desired improvements.
medication reconciliation through ordering, renewing, and
The CPOE system should be designed to support the
discontinuing. Complex medication orders and/or protocols
hospital’s ideal medication-use process as much as is pos-
may need special attention because of current technology
sible. The system should be configured to support clini-
limitations or workflow differences. The types of medication
cians and promote improved patient care processes, rather
orders that should be reviewed and included in the design,
than compromising these processes to accommodate system
as well as the processes across which they should be consid-
functionality. It will likely be necessary (and desirable) to
ered, are listed in Figure 1.
change many of the key work processes to ensure that ben-
The description of the current medication-use process
efits (such as improved medication safety) are achieved. A
should be developed from a number of sources: observation,
description of the ideal medication-use process is beyond the
paper order sets, discussion with clinicians, and the knowl-
scope of these guidelines, but key steps in a typical medica-
edge of those who have worked on the organization’s pre-
tion-use process are outlined in Figure 2.
vious process-improvement efforts. This process is an op-
A successful CPOE design is a combination of pro-
portunity to engage staff pharmacists who service various
cess, information systems, and supporting technologies that
areas of the organization. Pharmacists often have a broad
work together to allow the desired improvements to occur.
view of the medication-use process, seeing it from end to
Figures 3-6 list some of the process and technology en-
end, both receiving orders from physicians and helping ad-
hancements that should be considered for incorporation into
dress complex administration scheduling issues. The proj-
the new process/technology/system design.
ect team should strive to understand the current state of the
The desired benefits of the CPOE implementation
medication-use process in terms of the components listed in
should be clearly identified, and the process and system
Table 1, which also lists the form best used to represent the
design should make those benefits possible. The design
component.
should include the practices, work processes, and techno-
Figure 1. Types of medication orders and processes that should be reviewed and included in CPOE design.
Medication Order Types
Oral solids Medical staff protocols that include medications

Oral liquids Automated dispensing device overrides
Topicals Irrigations
High-risk medications (e.g., anticoagulants, heparin, insulin, Immunizations
or potassium chloride) Patient-controlled analgesia, including epidural analgesia
Compounded medications, such as triple mix or Sliding scale insulin and heparin
acetazolamide suspension (e.g., oral swish-and swallow Chemotherapy standard and non-standard protocols
or dermatological preparations made in the pharmacy) Conditional orders
Combination products (e.g., hydrocodone-acetaminophen, Hemodialysis, peritoneal dialysis, and continuous renal
multi-drug inhalers) replacement solutions
Combination doses Investigational medications
Respiratory therapy Herbal medications
Total parenteral nutrition Ophthalmic or otic medications
I.V. medications Injectable medications (e.g., i.v. push, i.m.)
Piggy-back i.v.’s Medications used in operative and procedural areas
Continuous infusion medications and titrations Linked or interdependent orders
Flushes Medications used for diagnostic imaging
Medication Order Processes
Ordering (physician or other clinician) Medication schedule changes

Electronic signature, signing of verbal orders Holding orders
Medication reconciliation Code medications
Preparation and labeling On-call to operating room or procedures
Medication order review Future orders
Dispensing and distribution (including interface to Negative orders (e.g., do not give aspirin)
automated dispensing devices) Charging
Administration and documentation Transfer orders
Table 1.
Components of the Medication-use Process and Formats Best Suited to Representing Them
Component Representation
Activities performed Process flow chart
Strengths and weaknesses of the current process Text/table
The person(s) performing the activities Text
The information needed in order to perform the activitiy Text
The tools and systems used to perform the activity Flow chart
The outputs of the activity and where they are sent/recorded Text
The time/effort used to perform the activities’ Text
The barriers, constraints, reductions in efficiency, and limitations on the activity Text
logical components in an integrated fashion. General pro- These process redesign sessions should be as practically
cess design principles are listed in Figure 7. focused as possible and should demonstrate prototypes of
The future state design should be an interdisciplin- orders and output from the system. They should provide a
ary effort that considers the entire medication-use process, forum to discuss what to do and how it will be done. The
even though parts of the process may not change or may not redesign will likely take at least three or four sessions to
change much with CPOE implementation. It is important to cover the necessary detail of all the affected processes. The
maintain the continuity and integrity of the process by mak- information gathered from these sessions can then be used to
ing sure that the design of the component activities is com- complete the process and system design and build the policy
patible and completely accounts for manual or previously and procedure and training documents.
automated processes.
The draft future state design is typically done with a Failure Mode and Effects Analysis. A safety analysis of
small interdisciplinary group of clinicians (the “core team”) the future state design should be done prior to implementa-
who understand the current process and the capabilities and tion to identify unintended or unidentified consequences.41
limitations of the CPOE system. This group should consist Failure mode and effects analysis (FMEA) is a useful tool to
of clinicians who order (physicians, nurse practitioners, and prospectively evaluate the potential risks associated with the
pharmacists), dispense (pharmacists and pharmacy techni- new process and identify inconsistencies or omissions that
cians), and administer (nurses and physicians) medications. may have the unwanted effect of increasing risk to patient
This core team should have dedicated time for the project, safety rather than reducing it.41–44
or at least be relieved of their regular staff schedules for the
time spent working on the project. The charge of this group Other Design Considerations. It should be determined
is to weave into the system design the following factors: whether there are required elements at provider order entry
in order for the pharmacy to verify orders (e.g., patient aller-
• Existing work processes and systems, gies, weight). Integrated systems start to break down the si-
• Best practices, los in which physicians, nurses, and pharmacists sometimes
• New systems, with consideration for their capabilities practice. There should be one shared field for allergy and
and limitations, weight documentation, so any expected workflow changes
• Physical limitations (e.g., space, facility issues, staff- need to be discussed prior to implementation. Though it is
ing limitations), the right thing to do, this standardization often uncovers
• Political issues (e.g., organizational priorities, limited workflow issues that were previously hidden in the paper
physician cooperation or interest in CPOE), process. The current process for handling allergy conflicts
• Desired benefits and performance improvements, and or drug interactions should be examined and it should be
• Compliance with regulatory, legal, and reimbursement determined how users will handle an alert in a critical or
requirements. time-dependent area, such as the emergency room. It should
also be determined whether there is a need for an additional
This redesign typically starts with a high-level process flow set of elements for order processing (e.g., laboratory or other
diagram that describes the activities performed by each results).
member in the medication-use process, coupled with dem-
onstrations of the system capabilities and flow. Through Medication Use within the Context of CPOE and the
successive iterations, the workflow and system design is EHR. Whether your organization implements CPOE alone
brought into increasing levels of detail and expanded to ad- or along with other parts of the EHR (such as the eMAR),
dress the factors listed above.34 Once the core team is satis- other parts of the medication-use process will be affected. To
fied with the design, practicing clinicians can be brought in meet the long-term goal of a complete EHR, all medication
to validate and improve the design. The clinicians involved orders should be included in CPOE. Having disparate or-
in these process redesign sessions should be experienced and dering systems (i.e., manual and electronic systems) causes
practicing clinicians who understand the current process and confusion, creates additional work for health care profes-
will likely find the potential issues with the new processes. sionals, and presents risks to patient safety. The hospital
Figure 2. Medication-use process model. Reprinted, with permission, from reference 32. Copyright, VHA, Inc. 2001.
History-Taking
Document
Obtain medication
medication history
related history Reconcile Meds Procurement
Formulary, Inventory
purchasing management
Order-Transcribing
decisions
Diagnostic/
Therapeutic Medication Order verified
Decisions ordering and submitted
in the beginning.45,46 Therefore, there must be considerable

the medical staff spends on prescribing medications, at least
must recognize that CPOE may increase the amount of time
dialogue with the medical staff about their role in the overall
Meds
Quality Assurance Pharmacy Management
Access and document

patient response to
medication Evaluate/ Select Prepare Dispense/ Drug Use
Approve order medication medication distribute Evaluations
according to
medication
defined parameters
Administration Management
Monitor/Evaluate Response Document Administer Medication Education
Access and document Administer

Intervene as Document according Select the
patient response to correct drug Educate patient Educate staff
indicated for administration to order
medication for the correct regarding regarding
adverse and associated and standards
according to patient medication medications
reaction/error information for drug
defined parameters
orders and improve the timeliness, accuracy, and safety of

patient care and that efficiency should improve over time.

that CPOE is an effective way for them to communicate their
medication-use process. It is important that they understand
Figure 3. Potential process and technology interventions in order writing and submission to improve medication safety. Reprinted, with permission,
from reference 32. Copyright VHA, Inc. 2001.
Ordering: Order Writing and Submission

Process Interventions Technology Interventions
Establish standards for abbreviations Implement tools to guide the user:
Establish policies that do not accept incomplete or vague Order entry (CPOE) with standard order sets and
orders such as “continue previous medications” protocols
Establish standard protocols for drug dosing and Mandatory fields to complete an order
administration Rules-based ordering to include dose adjustment,
Develop standard order sets to include drug order, time interaction checking, and accompanying orders
associated tests, and associated medicines Provide formulary selections
Provide routine staff education on common causes of error Provide mobile charting devices to allow for ordering at the
Educate staff on back-up procedures for system down time point of care
Establish policies for routine review and updating of current Adequate back-up procedures for system down
orders Updated Mar generated by CPOE or pharmacy sytem on
Monitor the bypass of rules and alerts to complete order routine basis (minimum every 24 hours)
Do not dispense drug prior to written order or verbal order Automated reminders or alerts for changes in patient status
verification unless critical Automated dispensing units do not dispense drug prior to
Minimize verbal order use order verification unless a critical medication
Figure 4. Potential process and technology interventions in medication history-taking and medication reconciliation to improve medication safety.
Reprinted, with permission, from reference 32. Copyright VHA, Inc. 2001.
Medication History-Taking and Medication Reconciliation

Establish procedures for obtaining admission history Implement tools to guide the user
Establish minimum data set to include medications, Clinical documentation with templates and checklists
diagnoses, height, weight, and allergies Prompts for required fields to include minimum data set
Establish accountability for obtaining minimum data set Flags to highlight changes in minimum data set from
Use standardized templates previous data
Multi-disciplinary clinical documentation Improve access to patient record through implementation of
Instruct patient/family on need to bring all current computer-based patient record/clinical data repository
medications with them, including over-the-counter Establish communication links with primary and extended
medications care providers to support transitions in level of care
Select and identify “record of truth” Provide mobile charting devices to allow for documentation
Establish communication links with primary and extended at the point of care
care providers to support transitions in level of care Structured for computer-based clinical documentation
Replace free text with checklists when appropriate Technology adherence to standards
Establish standard abbreviations for medication recording
Provide wallet cards or other forms to prompt patients to
bring complete home medication information
Figure 5. Potential process and technology interventions in pharmacy evaluation of orders to improve medication safety. Reprinted, with permission,
from reference 32. Copyright VHA, Inc. 2001.
Pharmacy Evaluation of Orders

Establish standards for abbreviations Adequate back-up procedures for system downtime
Establish policies that do not accept incomplete or Minimize system downtime
vague orders such as “continue previous medications” Automated reminders or alerts for patient changes in
Develop standard order sets to include drug order, status
associated tests and associated medications Pharmacy alerts and reminders based on change in lab
Provide routine staff education on common causes of value, drug-to-drug interaction, dose-checking, drug-to-
error diagnosis, drug-to-allergy checking
Do not dispense drug prior to order evaluation unless Targeted alerts that vary by individual receiving them to
critical reduce alert fatigue
Establish procedures for evaluation of orders and when Ability to view online clinical information to include: lab
to clarify values, clinical documentation and orders
Establish procedures for pharmacy dosing Interfaces to auto-populate pharmacy system with ADT,
Develop procedures for escalating an order that is on laboratory, clinical documentation
hold for clarification Access to drug knowledge base
Figure 6. Potential process and technology interventions in administering medications to improve medication safety. Reprinted, with permission,
from reference 32. Copyright VHA, Inc. 2001. RFID = radio frequency identification.
Administering Medications

Standardize medication administration times MAR with time based schedule
Standardize equipment for IV infusion; minimize number Electronic MAR
of different kinds of devices Automated drug distribution carts at the point of care
Provide tools that assist staff in calculating correct rate Smart infusion pumps
of infusion Alerts to caregiver to obtain and document clinical
Stock pre-mixed IV drugs information prior to administering a drug
Establish standard dose packaging and labeling Bar code/RFID administration systems
Patients with multiple IV access lines have line clearly Comprehensive wireless network coverage
marked at distal end Needleless administration system
Distal ports of non-IV tubing incompatible with Other medication delivery technologies
medication oral syringe
Standard protocols for the physical assessment prior to
administering a specific drug throughout the hospital
Computers (both wired and wireless) should be avail-
able in sufficient quantities so that no clinician has to wait
to use one. It is critical that the technologies used for sta-
Figure 7. General CPOE process design principles. tionary and mobile computing be matched to the anticipated
workflow. It is likely that stationary computers, handheld
CPOE Process Design Principles devices (e.g., personal digital assistants), and tablet and
Standardization of order entry and management information cart-mounted computers will all be needed for some part of
and workflows across the organization to the degree medication ordering for various users. If they are not part
possible. of an integrated system, the CPOE, eMAR, and pharmacy
Simplifying processes. information systems should be available on the same com-
Creating an effective interdisciplinary, team-based approach puter to facilitate switching between systems. Any other
(i.e., improving communication).
technologies that are used by providers (e.g., voice recogni-
Designing mechanisms for reporting and learning from
errors.
tion) should not only be on the same computer but ideally
Seeking redundancy through use of technology to support available from these devices as well. Users should be able to
clinical decision making. easily switch between different applications if needed, and
Avoiding reliance on memory. clinical data should freely flow between applications so that
Using constraints and forcing functions where appropriate. the pharmacist and other providers have real-time access to
Simulating planned and unplanned events for how people the same information.
interact with each other and technology.
Planning for failure and designing for recovery.
Providing access to a core set of integrated clinical Planning for CDS
information at the time and point of decision-making.
CPOE is an important part of an organization’s plan for im-
proved safety and quality. The addition of CDS to the EHR
and CPOE is essential for the prevention of adverse events
The hospital should provide incentives for prescribers to uti- and improvement in patient outcomes.17,20,21 A full discus-
lize the system and disincentives for giving verbal orders sion of CDS is beyond the scope of this document. ASHP
or continuing to handwrite orders. To facilitate use of the plans to cover the topic in future guidelines. The purpose of
system, prescribers should have access to the CPOE system this section is to provide an overview of CDS that will allow
from multiple venues, including their offices and homes and incorporation of CDS to be addressed in planning.
via wireless computers. If clinicians have the ability to en- CDS can be defined as providing the appropriate cli-
ter orders from multiple locations such as home or office, a nicians with clinical knowledge and/or patient information
defined process should exist to easily reach the prescriber if intelligently filtered and presented at appropriate times to
there is a problem with the order (e.g., non-formulary, lack enhance patient care.48 CDS has many intervention types,
of availability). including but not limited to the following49:
All new orders should be verified by a pharmacist
and reviewed by a nurse, and these actions should be docu- • Documentation forms/templates (structured guidance,
mented in the EHR prior to medication administration. The required or restricted fields, checklists),
nurse should work directly in the EHR for all clinical docu- • Relevant data presentation (optimize decision making
mentation, including medication administration. To com- by ensuring all pertinent data are considered),
ply with the “five rights” of medication administration,47 a • Order/prescription creation facilitators (pick-lists, pre-
workstation must be available close to the patient’s bedside completed order sentences and order sets),
with ready access to that patient’s relevant information to • Protocol/pathway support (multistep care plans, link
facilitate resolution of any questions on the medications that to evidence or protocol, pertinent reference informa-
arise. Figure 8 lists some design considerations for the work- tion or institution-specific best practice guidance),
group as new workflows are designed for different clinical
scenarios.
Figure 8. CPOE design considerations.
Design Considerations
How do orders post to the MAR, and what is the relationship between the MAR and intake/output flowsheets?
Are there other documentation flowsheets that are also used or needed (e.g., patient-controlled anesthesia, continuous renal
replacement therapy)?
When do orders need to be approved by pharmacy before a nurse can chart or administer the first dose of the medication?
Can nursing staff easily tell when the order has been verified by pharmacy?
Is there a mechanism to have critically needed orders available on the eMAR before pharmacist review?
What medication information is displayed to the nurse for administration (i.e., both brand and generic names)?
How are orders sorted on the MAR (e.g., are as-needed orders separated from scheduled orders)?
Are administration instructions and notes required (e.g., do not administer oral ciprofloxacin with Maalox)? Will they be supplied
from the CPOE system or from the pharmacy system?
Are nondrug items needed on the MAR (e.g., wet to dry dressings)? If so, how will these items be entered (i.e., are these orders
that pharmacy must review and approve)? Can some type of treatment administration record be created for these items?
Is there a chart on removal from an automated dispensing cabinet or are auto-charting functions in use?
How will the health system develop a bar-coding system for medication administration?
Override rates of alerts by both pharmacists and providers to better set sensitivities for the warning.
Order verification times by pharmacists to determine turn-around times for different priorities of medication ordering.
Compliance to clinical practice guidelines and order sets.
If integration of the CPOE system is available with automated dispensing devices, then monitoring for overrides would be
warranted.
Monitoring free-text orderables in the system, to better address the provider’s needs and provide guidance for appropriate
formulary build.
Does the software provide the ability to designate a medication and document “First Dose Effectiveness”?
How are enteral nutritional supplements and tube feeding supplements documented, ordered, etc?
Does the software provide “Query Tools”?
Will provider, pharmacist, nursing software “Hand Off” IT tools be needed?
Does the software handle “Look-A-Like, Sound-A-Like” medications and due to this aspect should generate medication
nomenclature be utilized exclusively?
Does the software provide the functionality for “after hours” entry and how will the review be completed if pharmacy service is
closed?
How will MAR/eMAR handle multi-component medication orders?
How will MAR/eMAR process fractional doses of medication package forms?
How will reporting needs be developed and integrated into the system for users? When?
How are co-signatures or verbal order sign-offs obtained?
• Alerts and reminders (drug–drug interactions, thera- gether and may even threaten clinician acceptance of CPOE.
peutic duplication, drug–disease, allergy alerts, and The way alerts are prioritized and presented to the user may
others), and be as important as which alerts are presented. Alerts for very
• Automated ADE detection based on patient symptoms, serious clinical situations may be ignored when lost in a sea
labs, diagnostic results, and patient notes. of less important ones.54 Some vendor systems allow clients
to change severity levels or even disable some alerts in an
Because CDS has such a broad definition, the line between effort to bring alert interruptions to a better signal-to-noise
CDS and CPOE is not always clear. Basic forms of CDS, ratio and thus decrease the potential for alert fatigue, par-
such as fully defined order sentences and order sets, are an ticularly for physician recipients.50–52 Ideally, there needs to
important aspect of CPOE and can decrease errors while be an alternative mechanism to provide CDS feedback to
enhancing clinician acceptance of the system.27,28 This type prescribers that is not intrusive but still allows the prescriber
of basic CDS encourages clinicians to make proper choices to know that there may be issues with an order. If ignored,
initially rather than alerting them to potentially problematic these alerts can be acted upon by the pharmacist.
choices after the fact and is an essential part of any CPOE The strategy for prioritization of CDS should be de-
implementation. fined as early as possible, and pharmacists should take a
An organization must recognize that to realize the ben- leading role in all medication-related CDS. It is likely that
efits of CDS, the CPOE system must be accepted by clini- organizations will be eager to implement CDS along with
cians and used effectively. Poor design or too many alerts CPOE. Pharmacists should ensure that the CPOE system is
could lead to system rejection or, even worse, unanticipated implemented with basic CDS, such as order sets and sen-
outcomes such as increased errors or adverse events.25,26,50–53 tences, while using appropriate caution when implement-
Some CDS, including checks for allergies, drug–drug ing alerts.27 Although vendor systems are continuously im-
interactions, drug duplications, and dose ranges, are typi- proving and may allow tiering of alerts, there is typically
cally delivered via an interruptive alert to the user or dis- a significant amount of work necessary to vet any changes
played as a passive warning on an order entry screen. Such and carry out the technical work involved in the customiza-
CDS should be considered before CPOE implementation, tion. The combination of pharmacists’ clinical knowledge
but designers should keep in mind that a high number of of drugs and their experience with the interruptive alerts
interruptive alerts may cause clinicians to ignore alerts alto- that have been present in pharmacy information systems for
years provide pharmacists with a unique understanding of the patient record while an order session is ongoing, without
the many implications of implementing medication-related losing the session. All displays should contain the patient
CDS. Pharmacists should work with medical leadership, ei- name, patient location, user name, and function in consis-
ther through the P&T, informatics, or another interdisciplin- tent screen locations. The system should support third-party
ary committee, to decide how and when medication-related data entry for prescribers by simultaneous display of the
CDS will be added to CPOE. Pharmacists are well posi- same session in multiple locations and default fields where
tioned to formulate local evidence criteria, collect informa- possible or helpful. The CPOE system should permit user
tion on medication therapy outcomes, and to bring together definition of data elements and fields that can be attached
institutional health providers for the purpose of setting pri- to any portion of the database. The system should permit
orities and targeted outcomes where select IT interventions user-friendly, error-free medication order processing by pro-
are made. The design, implementation, and optimization of viding the functionalities for the CPOE interface and order
CDS is an exciting area of opportunity for pharmacists now processing listed in Figure 9.
and in the years to come.
Levels of Access. The team will need to determine the levels
Elements of a Safe CPOE System of access or security permitted to staff throughout the hos-
pital. The team may find it easier to begin with the current
Minimum Features and Functions. The implementation level of privileges for existing systems.
group and key stakeholders should consider what features In general, pharmacists require a high level of access
and functions of the CPOE system are desired both now and (full access to medication orders, and in some cases the
in the future. Starting with a pilot group of users allows ex- ability place lab orders) because they cover multiple areas;
perience with the system to build and permits users to work place, alter, or discontinue orders; and may practice under
through some process issues before system usage is wide- protocols that require monitoring of laboratory test results.
spread. Any pilot should be brief, with plans for a roll-out There may be different levels of access within the pharmacy
shortly after addressing the major discoveries. A highly so- department (e.g., actions by a pharmacy student, intern, or
phisticated system may take so long to develop that interest resident may need to be reviewed by a senior pharmacist;
is lost, or it may be too sophisticated or rigid in its initial pharmacy technicians may require different levels of access,
application to be well accepted. depending on duties). Staff may also need off-site or alterna-
An important consideration during CPOE implemen- tive site access.
tation is the determination of which functionalities are re- In addition to pharmacy personnel access, the design
quired for go-live. CPOE will always be a work in progress, team will need to determine levels of access for other staff
and there will be opportunities for modifications and en- members. This should include all categories of physicians
hancements. At a minimum, the project team should evaluate that practice at the site (e.g., attendings, specialists, con-
all existing manual medication ordering processes, including sultants, community clinicians with privileges, residents or
such complex orders as epidurals, patient-controlled anal- other trainees, fellows, and medical students). The medical
gesia, weight-based dosing, lab-result-dependent dosing, staff office, medical staff executive committees, or P&T
tapering medication doses, total parenteral nutrition, and committees may be able to make recommendations for ap-
chemotherapy, along with critical patient safety functional- propriate access based on existing policies. Nursing will
ity driven from known internal or external sentinel events. need to consider similar access issues and ensure compli-
An agreed-upon list of basic functionality should be estab- ance with provider practice acts. Ideally, these issues are
lished in order to ensure a timely yet successful go-live. If addressed by existing policies that will only need to be re-
some complex or high-risk medication orders will be left on viewed and implemented. Other ancillary staff will need to
paper at the initial go-live (e.g., chemotherapy), be sure this be granted access, depending on their need for information
is well communicated during training. As well, this principle and orders that will be built within CPOE and routed to the
applies to other identified yet unresolved design topics. The appropriate department for action.
project team will to need re-visit these topics for completion
in the post-go-live period. User Levels and Co-Signatures. The CPOE system should
permit restriction of medication orders by user type, indi-
General Features and Functions. The user interface is of- vidual order, or class of order. Each medication order should
ten a problematic aspect of CPOE. Users have been reported indicate the name and user level of the ordering party. The
to enter orders for the wrong patient or to select the wrong CPOE system should support the entry of unverified orders
item (or wrong feature of an order) unintentionally because and the editing and verification of unverified orders, and this
they did not use selection lists properly or because it is very function should be role-based and restricted. The system
easy to select the wrong item from a drop-down list.38 The should also support the creation of reminders or inbox mes-
CPOE user interface should incorporate appropriate human- sages for orders that require a co-signature. The pending pre-
factors engineering to avoid risk-prone workflows and con- scriber co-signature name should default into the field from
trols (e.g., memorized mnemonic codes or function keys, service, team, or coverage schedules, and there should be
long selection lists) that may produce order-entry errors. The an option to override the name. The system should provide
order entry functionality should be independent of patient the ability to require that all orders be countersigned prior
setting (e.g., inpatient, outpatient), and users should be able to placing a discharge order if the organization wishes to
to combine data (e.g., order history) from all settings without implement this.
a need for independent searches or screen selections. The
system should include an online help function for system Medication Order Status. Considerations regarding medica-
navigation and provide notification if another user modifies tion order status include the following:
Figure 9. Functionalities for CPOE interface and order processing.
CPOE Interface
• Multiple active sessions on one display (i.e., ability to put a current order session on hold and review other information, then
return to the original work session without losing the work in progress).
• Side-by-side viewing of active order lists and any system-maintained order list (e.g., a standard order set, personal favorites list,
or critical path order set).
• Alignment of orders by department while in side-by-side view.
• Switching between applications on the same display without exiting order functions.
• Utilization of all functions via either keyboard or mouse.
• Forward and backward navigation anywhere in the application.
• Access to the Internet from anywhere in the orders application.
• Access from multiple locations (e.g., sign-on, viewing, data entry, and verification at clinical or remote location).
• Order entry with minimal (<3) screen flips and user definition of defaulted fields.
CPOE Medication Order Processing

• Ability to return user to previous screen.
• Online access to error message documentation.
• Hospital-defined error messages.
• Ability to audit and track all errors and alerts.
• Robust search functionality available from all screens.
• Support for coding all diagnoses, tests, and procedures with institutional, departmental, and user-definable subsets of preferred
terms (e.g., the appropriate edition of the International Classification of Diseases,55 SnoMed CT,56 or others).
• Ability to establish cross-references for tests or procedures, including:
o Information regarding the name of a procedure or test (i.e., the ability to use alternate names for a procedure).
o Information regarding indications for, execution of, cost of, and medical literature pertinent to a procedure.
o Diagnosis codes that can be restricted based on type of exam or test.
o Diagnosis code restrictions that staff can override by direct entry of the code or access to full table for lookup.
o Ability to enter a diagnosis code along with reason for exam.
o Ability to maintain orders online for the duration of the patient stay and to display the status of the orders (e.g., open, in
process, completed, scheduled to expire, expired) during order inquiry.
o Ability to store, display, and print patient test instructions as well as preparation instructions for the order.
• Ability to perform global set-up changes (i.e., changes to a master file table element can be optionally set to automatically
populate all relevant items throughout the table).
• Ability to update patient service and physician(s).
• Ability to clearly note, flag and color-code order status.
• Option to have active orders remain visible on the same screen while writing new orders.
• Ability to view all orders, including stopped and interrupted (partially entered) orders.
• Automatic assignment of unique order identification numbers used in mapping to other systems, with the order identification
number large enough, or based on an algorithm, so that such numbers are not repeated within 5 years.
• Ability to retain multiple order numbers or other unique identifiers from other systems.
• Option to manually update order status, with the ability to restrict such updates to specific order items or specific users or user
classes.
• Ability to create user-defined order status.
• One-step cancel/reorder process.
• Discontinue, discontinue/renew, cancel occurrence, and hold order functions.
• Automatic calculations.
• Option to input order information using free text.
• Ability to search for, track, and audit free text orders.
• Ability to drill down for detail from every screen.
• Ability to drill down to the following during the order entry process:
o Medication and doses, since initial orders include suspended and discontinued orders.
o Termination date and time of current orders.
o Allergies (coded).
o Patient diagnoses (coded).
o Demographic information.
o Visit information (medical).
o Physicians responsible for the patient (resident, attending, and consultant physicians, at a minimum).
o Active and completed orders with dates and times.
o Patient location and service.
• Modules with data specific to clinical specialties, including sets for reporting results, CDS, and order sets.
• Whether all orders must be reviewed by a pharmacist change administration times, and place medication orders on
before they are active or posted to the MAR. or remove them from hold or conditional status. Changes
• If the answer to the above question is yes, the process made to administration times in the eMAR should back-
in which the organization will handle urgent medica- populate the CPOE and pharmacy information systems.
tions that are administered before pharmacist review.
• Should the CPOE system have some medications on Medication Orderable Design
override for urgent use? Are these medications always
on override or are there alternative methods for order-
and Build Considerations
ing them?
The design and build of the medication orderables are key
• Does the pharmacy have sufficient staff to deal with
tasks in implementing the CPOE system. Care should be
the volume of orders? Pharmacy will potentially see
taken in designing and building the formulary or formular-
all changes, i.v. fluid orders, discontinuation orders,
ies, as well as the standard orders and order sets that are built
and titration orders. Design considerations will need
from the formulary. The pharmacy department must have di-
to address the disposition of the orders prior to imple-
rect involvement in this task.
mentation.
The CPOE formulary cannot be simply a copy of the
• If a prescriber enters and then changes an order, how
pharmacy inventory. Prescribers need to have the orderables
are those two orders reconciled into one order?
constructed to match how they order medications (therapeu-
• How does the system handle an order by a physician
tic entity), rather than how the pharmacy maintains medica-
assistant or student that requires a co-signature before
tion inventory (dosage form/product). In addition, care must
becoming active?
be exercised when deciding on the default dose, frequency,
• Do hold orders need a defined duration to be accepted?
and route values for items that will be displayed to the pre-
Do these orders automatically discontinue if on hold
scriber and in developing the construction of standard or-
for a certain amount of time?
ders. Medication errors can result from a hurried prescriber
accepting the default that he or she assumes must be cor-
Except in urgent situations as described by the Joint
rect.25 The CPOE system should be able to generate formu-
Commission,57 a pharmacist should verify every medica-
lary lists by generic name, trade name, and dosage form.
tion order prior to drug dispensing and administration. Once
The CPOE system should allow routine online up-
verified by a pharmacist, the order should populate the
dating of the formulary and clinical checks of information
pharmacy computer system, generate labels and other items
without system functionality downtime. The system should
necessary for dispensing, release the drug in the automated
provide authorized personnel the ability to maintain and
dispensing device (if applicable), and populate the eMAR as
display the formulary with pertinent data (e.g., formulary
an active order. The order should be available to the eMAR
code, generic name, trade name, national drug code [NDC],
as soon as it is placed, but it should be clear to the nurse
or American Hospital Formulary Service [AHFS] number),
whether the pharmacist has verified the order or not.
while limiting access to certain formulary data by role. The
CPOE system should include the ability to identify whether
Order History. The CPOE system should permit viewing
an i.v. with a medication additive is to be handled as a large-
of orders from all previous patient encounters regardless
volume i.v. or as a small-volume i.v. for appropriate han-
of enterprise location, setting, or patient status. The system
dling within the pharmacy department for compounding and
should be capable of storing and retrieving previous patient
dispensing. The system should allow the ability to make
order lists and sorting, reporting, and printing patient order
changes to the medication identifier (NDC or RxNorm iden-
lists by date and date range, setting, patient status (e.g., dis-
tifier), communicate those changes to other systems, and re-
charge), service, department, and provider.
ceive changes from other systems.
The system should allow pharmacists to maintain
eMARs and permit online updates, provide online capabil-
ity to automatically generate a hard copy of eMARs for Build Considerations
downtime back-up, provide the ability to display and/or
print patient medication profiles or eMARs on demand or IT analysts design and build the system from documents or
at a specified time, and include the ability to have multiple order sets reviewed and approved by the multidisciplinary
formats that are definable by systems-level staff. group. Standard IT processes should be followed, beginning
with the design phase. Once the design has been approved,
Documentation in the eMAR. The CPOE system should IT staff should build the system in a test environment. A test
seamlessly build the eMAR from orders in real time. Some environment protects from mishaps in the live (or “produc-
institutions may want medication administration time tion”) environment. It is important for the test environment
changes to be modifiable from the eMAR, and the eMAR to match the production environment so that testers get a true
may have a bi-directional interface to the pharmacy infor- feel for how the build will work and interact. IT staff should
mation system (if it is not an integrated system). The system meet with nursing and pharmacy throughout building and
should provide the ability to enable bar-code medication testing phases to resolve any issues that may arise.
documentation. Pharmacist order validation should auto- After the builder is satisfied that the requested build
matically update the eMAR. The pharmacy and nursing de- or order set is complete, the builder should then develop a
partments should work together to ensure that the eMAR is testing plan. The builder should work through the test plan
designed to be readable and user-friendly from the nurse’s initially and sign off when the build works as designed.
perspective. Pharmacists and nurses should have the ability Next, pharmacy and nursing should perform testing.
to add or delete patient allergies, enter special instructions, This testing should involve patient scenarios throughout
the patient’s visit. Pharmacy is integral to this process and sets only.28 Discontinuation of an order set should trigger the
should ensure proper medication management and work- automatic ability to review, edit, or discontinue all linked
flow. When the build passes pharmacy and nursing testing, orders.
physicians should review, test, and sign off. Because the CPOE system may permit initiation of
When all aspects have been tested and fixed, and any standard order sets with a single action (mouse click, key-
necessary education is completed, the build may be moved board stroke, etc.), order sets’ ease of use may lead to in-
to production. Follow-up is critical to ensure the build meets appropriate or excess medications being ordered. Order
the needs of providers and is not adversely affecting ancillary sets should be allowed to include linked orders, but orders
staff. A mechanism to report issues quickly must be estab- grouped in a standard order set need not be linked. The insti-
lished, so that the implementation team can investigate and tution should decide whether all orders in the set are going to
resolve them. The CPOE group should maintain reports of be active once they are signed or if prescribers are required to
problems and review those lists for recurrent issues. Providing actively check and click on each medication before signing.
feedback and updates to the persons reporting problems is vi- The CPOE system should require designation of an
tal to progression of the project. Clinicians need to know they owner (i.e., department, service, person, or role) for each
have been heard and resolution is being sought. order set. CPOE order sets should be reviewed on a peri-
odic basis for therapy updates. Item and service maintenance
Dependent or Joined Orders. Support for dependent or should be performed at the departmental level, with updates
joined orders is important in the case of i.v. medications and in item or service definition flagged for review by the owner
the diluent used for administration, two drugs to be taken of the standard order set containing that item or service (i.e.,
together, or a drug and a measurement requirement (e.g., the change triggers a report that the order set requires re-
digoxin and pulse rate). The CPOE system needs to make view). The CPOE system should support restriction of de-
it easy for the prescriber to order these types of formulary partmental or service standard order set creation or editing
items. The system should be flexible enough for the pre- by role or individual.
scriber to select the drug form and size or indicate the dilu- The CPOE system should support standard order set
ent for an i.v. piggy-back when ordering if so desired or to maintenance and review by
allow these choices to be made once the order reaches the
pharmacy system. • Grouping order sets by department/service,
• Dating the creation and review of order sets,
Order Sets. Requiring providers to use a CPOE system re- • Providing periodic (user-defined intervals or dates,
quires a change in workflow, and many fear it may increase or as-needed) reporting of standard order sets that re-
the time clinicians spend processing orders.46 Configuring quire review by owner (department, service, person,
pre-constructed order sentences and order sets prior to im- or role), and
plementing CPOE may increase speed, accuracy, and ac- • Permitting global changes.
ceptability of CPOE.27,28,58 Careful deliberation is needed
prior to the creation of CPOE order sets, including consider- Critical Pathways and Protocol Order Sets. Critical path-
ation of how order sets are currently developed and revised ways and paper-based order sets, a very basic form of CDS
(e.g., by department or by individual practitioners), what the already widely used in hospitals, provide a starting point in
process to propose and review order sets is, and what level efforts to standardize care and improve quality and safety
of medical oversight is in place for order set development through the CPOE system. With the implementation of ev-
and use. It is also important to understand ordering patterns idence-based order sets, organizations can provide the pre-
when developing order sets for use by clinicians. Many or- scriber with a direct link to the electronic literature support-
ganizations use this opportunity to improve and standard- ing the recommended practice. The work of synthesizing
ize across important aspects of care, such as post-operative and classifying the available evidence is done by organiza-
nausea and vomiting or pain management, as well as move tions such as the National Guideline Clearinghouse59 and the
to evidence-based order sets from their legacy order sets.28 Cochrane Database of Systematic Reviews.60 Organizations
The system should permit development of specific ad- may incorporate these guidelines into electronic order sets
mission pathways (e.g., order sets capable of including any and critical pathways, in addition to providing the link to
type of order and intervention) and integrate with data docu- give prescribers point-of-care access to the evidence-based
mented elsewhere in the EHR (e.g., medical histories, medi- literature at the time of order entry.
cation lists, laboratory results, diagnostic images, clinical The CPOE system should support all functions listed
documentation, progress notes, narrative summaries [such under general order sets for critical pathways and protocol
as operative reports or consultations]). Order set availabil- order sets. The system should provide a default set of proto-
ity should be limitable by user, user role, location, service, cols that are available by service and physician and a default
or patient status or diagnosis. The system should permit an set of protocols that are restricted by location. The CPOE
unlimited number of orders within an order set and an un- system should include an alert system for orders not com-
limited number of order sets within departments, across depleted within user-defined time parameters or time param-
partments, and with user-definable time parameters. Order eters required by critical paths or research protocol.
sets can include nursing orders, tests, and medications, and
should include appropriate laboratory tests at appropriate Medication Order Linking. The CPOE system should in-
intervals to assist in monitoring therapy. Though many sys- clude the ability to identify orders as linked and sequential
tems allow users to create and save their own order sets in a or mutually exclusive or time off-set, and to specify inter-
favorites list, this flexibility needs to be weighed against the vals, as well as cascade changes in future orders to maintain
desire to standardize care by allowing hospital-based order sequence and timing. It should permit an order stop to auto-
matically bring up any linked orders for re-verification, with
the default being to cancel unless re-verified. The system text in which each individual drug order was prescribed.
should provide automatic re-sequencing of future orders if Additionally, any functionality to help the pharmacist pri-
any item identified as sequential is moved on the timeline, oritize the review and approval of orders will improve the
and it should permit linked orders (i.e., reflexive occur- care of patients.
rences that trigger other procedures) that cascade through Pharmacists should receive and work with orders elec-
multiple levels. tronically in a queue. Patients with stat orders should appear
at the top of the list and be clearly differentiated from less
Favorites Lists. The CPOE system should permit use of fa- urgent orders. Pharmacists should have the ability to screen
vorites lists by individual user that may include orders for their view of orders based on the nursing units they are re-
multiple departments (e.g., laboratory, pharmacy, radiology). sponsible for on a given shift. At no time should a pharma-
The system should provide default components of medica- cist be able to view orders for more than one patient at the
tion prescribing (“Sigs”), such as dose route frequency, and same time.
length of order, that are user-definable at the nursing unit When working with paper orders, pharmacists often
level and that have discharge orders or discharge worksheet gain insight into the medication orders from the context of
functionality. The system should provide default Sigs and the surrounding patient care orders. CPOE systems should
permit users to save favorite Sigs in user favorites. Users preserve that context so that pharmacists can view an order
should be able to create favorites lists that include orders in terms of the other therapies, tests, nutrition, and nursing
from multiple departments on one list. Favorites lists should care surrounding it.
be fully editable on an ad hoc basis for an active order ses-
sion, and user-specific favorites lists should be editable by Communication Among Departments
the user. Users should be able to designate any order list as
a favorite and may name or rename the list ad hoc (i.e., the The CPOE system should allow for notification of clinicians
save function automatically prompts for name, defaulting to for pending orders needing signature via e-mail, pager, text
the existing name if available). There should be an option to message, or inbox message. Pharmacist order notification
save an order list as a favorite, either as a new favorite or as should be allowed via printout, work queue, e-mail message,
a replacement for an existing favorite; that option should be system message, or pager. The default method for receiving
available during any ordering session. Favorites lists should notification of orders should be definable by the department
be allowed to contain ordering details that default into the or service, and the system should support special notifica-
order, and default details should be editable and replaceable tion methods for specific services or items different from
during order entry. The CPOE system should support con- the departmental or service default, without affecting sum-
text-specific favorites lists by user, nursing unit, service, and mary reporting by department. Users should be able to print
diagnosis, and by combinations of user and diagnosis or by orders to alternate locations and to send messages, orders,
combinations of user, diagnosis, and setting (e.g., outpatient, and alerts to additional departments (including information
inpatient). User favorites lists should be copied and shared about scheduling and priority of orders) as a single order
easily, and the system should allow favorites lists to be built is being entered or completed. The CPOE system should
by opening and then editing standard order sets and saving have an option that order placement generates user-defined
as a favorite. Favorites lists may also include reminders. The worklists. The system should also provide the ability to e-
system should permit review of favorites lists. mail patient and preparation instructions and to reference
on-call lists.
Pharmacy Department Considerations
Education and Training of
The ideal CPOE system will have to be integrated with or
have a fully functional bi-directional interface with the hos-
Health Care Providers
pital’s pharmacy computer system so that orders entered or
The rate of adoption of the new CPOE system may be di-
modified in one system will populate fields in the other sys-
rectly linked to the extent of training provided to users prior
tem, avoiding the need for dual order entry. The bi-directional
to and during the implementation. One cannot spend too
feature of an interface is important because it prevents poten-
much time training users, as the change the new system en-
tially dangerous discrepancies between data in the pharmacy
tails will be overwhelming. This training can be in the form
and EHR systems and removes the transcription step of the
of formal classroom training, local expert training, or “at-
medication-use process. In addition, if the distribution and
the-elbow” support and training (the type of training typi-
administration components of medication management are
cally most welcomed by physicians) during implementation.
not linked, then documentation and billing will not be either,
Organizations may find the most success in using a combi-
causing more opportunities for error and audit problems.
nation of all three. The more familiar the users are with the
In their day-to-day interaction with the CPOE system,
system at the time of implementation, the easier the transi-
pharmacists should be working primarily in the pharmacy
tion will be.
system, which has all relevant patient information fully
The facility should train and employ a group of pre-
integrated with the EHR and CPOE module. The pharma-
scriber “super users.” These users will support the go-live,
cist’s roles include verifying all orders, reviewing and re-
help the institution refine the CPOE system to be as effi-
sponding to alerts, and clinical monitoring of the patient.
cient as possible, and serve as liaisons and CPOE champions
The pharmacist should have security privileges to enter and
to the other members of the medical staff. There should be
modify orders under protocol (such as formulary or formu-
ongoing, open dialogue with leadership and medical staff
lation changes).The pharmacist should see all orders within
members to continually improve the system.
a particular group of orders so that they can see the con-
Each training session should be geared toward the type likely not be realized until implementation processes have
of user, since utilization will differ by clinician type (e.g., been completed and stabilized. A time analysis should also
physician, respiratory therapist, nurse, pharmacist, labora- be performed comparing how long it takes CPOE-trained
tory technician). The initial training of users is important, nursing staff to administer and document medications in
but ongoing training for new users, changes in program- the CPOE system versus the manual system. This analy-
ming, and functionality require that training be given a high sis should determine whether time is saved by eliminating
priority after transition to the new system. manual transcription of orders and manual development and
maintenance of MARs. If the time analysis demonstrates a
Overview of System. The initial introduction to the system negative impact on workload, the facility should make ap-
should familiarize the user with the layout of the system. It propriate staffing adjustments. These adjustments will vary,
should review toolbars and menus of each application. The based on the percentage of orders directly entered by the pre-
first glimpse should include any definitions that are new or scriber, and should be continually assessed.
to which meanings may be different from the current pro-
cess. Conclusion
Accessing Data. This section of training should familiar- These guidelines provide guidance to pharmacists in hospi-
ize the user with the various methods for accessing data. tals and health systems on planning for and implementing
It should provide information on sorting and filtering data. safe CPOE systems. Pharmacists should utilize their unique
Because access to data will vary based upon the type of user, knowledge and skills as part of the interdisciplinary CPOE
separating different user types for training purposes at this planning and implementation team. Participation by phar-
stage may be beneficial, and this is a good time to discuss macists is critical in defining the vision, goals, and objec-
security and privileges. tives of the CPOE system; establishing essential metrics
to measure the success of CPOE system implementation;
Documenting Information. This section should teach users re-engineering the medication-use process as part of CPOE
how to document information pertinent to their practices. system implementation; determining the functionality that
These tasks would include adding basic patient information ensures the safety of the CPOE system; planning for CDS;
and documentation onto flow sheets, as well as clinical prog- and educating and training health care providers to use the
ress notes. CPOE system. Finally, for optimal benefits to patients, or-
ganizations should realize that the implementation is merely
Orders. The training sessions on medication orders will the beginning and that pharmacists should continue to take
be the most comprehensive. Some users will be limited a central role in ongoing system optimization and continued
to ordering tests or procedures specific to their practices. CDS implementation.
Physicians, nurses, and pharmacists, however, will spend a
large percentage of their time in the CPOE system work-
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44. Beuscart-Zéphir MC, Pelayo S, Bernonville S.
Adverse drug event (ADE): ASHP defines a significant
Example of a human factors engineering approach ADE as any unexpected, unintended, undesired, or exces-
to a medication administration work system: poten- sive response to a drug that
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death.
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Management Systems Society; 2005. document the medication in the eMAR.
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Electronic medical record (EMR): An electronic record
55. International classification of diseases, ninth revision, of health-related information on an individual that can be
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57. Medication Management Standard MM.4.10—pre- dress three leadership groups: The governing body, the
paring and dispensing. In: Comprehensive accredi- chief executive and other senior managers, and the leaders
tation manual for hospitals. Oakbrook Terrace, IL: of the licensed independent practitioners.
Joint Commission on the Accreditation of Healthcare Legal medical record (LMR): The legal health record is
Organizations: 2006:MM-10. the documentation of health care services provided to an
individual during any aspect of health care delivery in any FASHP; Kate Farthing, Pharm.D., BCPS; Burt W. Finkelstein,
type of health care organization. It is consumer or patient- Pharm.D.; William L. Fritz, M.S., FASHP; Kimberly A. Galt,
centric. The legal health record contains individually Pharm.D., FASHP; Barry R. Goldspiel, Pharm.D., FASHP; Frances
identifiable data, stored on any medium, and collected and M. Jordan, M.B.A., FASHP; Renee B. Marino, Pharm.D.; Kevin C.
directly used in documenting health care or health status.
Marvin, M.S., FASHP; Steven Meisel, Pharm.D.; Alicia S. Miller,
National drug code (NDC): A universal 11-digit product
identifier used in the United States for drugs intended M.S.; Sandi Mitchell, M.S.I.S., FASHP; Kuldip R. Patel, Pharm.D.;
for human use. The Drug Listing Act of 1972 requires Alicia B. Perry, Pharm.D.; John Poikonen, Pharm.D.; Mark H.
registered drug establishments to provide the Food and Siska, B.S.Pharm.; and Mary Windle, Pharm.D.
Drug Administration (FDA) with a current list of all drugs
manufactured, prepared, propagated, compounded, or ASHP also acknowledges the following organizations and indi-
processed by it for commercial distribution.
viduals for reviewing drafts of these guidelines (review does not
Orderable: An authoritative direction or instruction from
a prescriber to perform a task (e.g., a radiology test or imply endorsement): American Academy of Family Physicians
administer a medication or treatment). (AAFP); American Association of Critical Care Nurses (AACCN);
Medication administration record (MAR): Medication American Health Information Management Association (AHIMA);
administration record usually handwritten or printed from American Hospital Association (AHA); California Society of
an electronic pharmacy information system. Health-System Pharmacists (CSHP); Healthcare Information and
Personal health record (PHR): An electronic record of Management Systems Society (HIMSS); Jeanine (Porter) Abrons,
health-related information on an individual that conforms
to nationally recognized interoperability standards and Pharm.D., M.S.; Christel Anderson (HIMSS); Dan Buffington;
that can be drawn from multiple sources while being man- Peggy Brashear, B.S.Pharm.; Tim R. Brown, Pharm.D., FASHP;
aged, shared, and controlled by the individual. Dominick A. Caselnova III, M.H.A.; Thomas W. Cooley, M.B.A.;
RxNorm: RxNorm is a standardized nomenclature for clini- Debby Cowan, Pharm.D.; Michele Danish, Pharm.D., FASHP;
cal drugs and drug delivery devices and is produced by the Neil Davis; Charlie De la Torre; Robert DeChristoforo, M.S.,
National Library of Medicine. FASHP; Jean Douglas, Pharm.D.; Brent R. Ekins, Pharm.D.,
Sponsorship: An identified executive or clinical leader who
DABA; Elizabeth Fang, Pharm.D.; Tim Lanese, M.B.A., FASHP,
assumes responsibility for another person or a group dur-
ing a period of project planning implementation follow- CPHIMS; Lisa Gunther Lum, Pharm.D., FASHP, FCSHP; Robi
up. Hellman, RN, MSN, CNS (AACCN); James M. Hoffman, Pharm.D.,
Systematized nomenclature of medicine (SNOMed): A M.S., BCPS; Carol J. Hope, Pharm.D., M.S.; Amey Hugg; Joan
multiaxial, hierarchical classification system. As in any E. Kapusnik-Uner, Pharm.D., FCSHP; Linda L. Kloss, RHIA,
such system, a disease may be located in a body organ, FAHIMA (AHIMA); Ronald E. Lay, M.S.; Jeff Little, Pharm.D.;
which results in a code in a topography axis and may lead
Bob Lobo, Pharm.D.; LTC Eric M. Maroyka, Pharm.D., BCPS;
to morphological alterations represented by a morphology
code. Greg Matsuura, Pharm.D., BCPS; Patrick J. McDonnell, Pharm.D.;
Workflow: The flow or progress of work done by a com- Michael McGregory, Pharm.D., M.B.A., BCPS; Robert Moore,
pany, industry, department, or person. B.S.Pharm., BCPS; Susan J. Morikawa, Pharm.D., BCPS; Kevin
Olsen, RN, BSN; Peg Panella-Spangler M.S.; Christine Pavlak,
M.H.A., FASHP; Stephanie C. Peshek, Pharm.D., FASHP; Tommie
Peterson; Minh James Pham, Pharm.D.; James A. Ponto, M.S.,
Developed through the ASHP Section of Pharmacy Informatics BCNP, FASHP; Donald W. Rucker, M.D.; Richard Sakai; Kevin
and Technology and approved by the ASHP Board of Directors on Scheckelhoff; Thomas R. Schafer, Pharm.D., BCPS; Terry Seaton,
September 24, 2010. Pharm.D.; Suzanne Shea; Pamela Shellner, M.A., RN (AACCN);
Clyde Spence, Pharm.D., M.B.A.; Richard L. Stambaugh, Pharm.D.,
A work group of the ASHP Section of Pharmacy Informatics and M.S., BCPS; Craig S. Stern, Pharm.D., M.B.A.; Scott H. Takahashi,
Technology Section Advisory Group on Clinical Information Pharm.D., FCSHP (CSHP); Dennis A. Tribble, Pharm.D.; Jody
Systems is gratefully acknowledged for developing these guide- Jacobson Wedret, FASHP, FCSHP; Rich Umbdenstock (AHA); Ray
lines: Anne M. Bobb, B.S.Pharm.; Jennifer Boehne, Pharm.D.; W. Vrabel, Pharm.D.; Steven E. Waldren, M.D., M.S. (AAFP); Eric
Lynn Ethridge, Pharm.D.; J. Chad Hardy, Pharm.D., M.S.; Randy Weber; Barbara White, M.S., PMP, FASHP.
Herring, B.S.Pharm.; Richard S. Jacobs, Pharm.D.; Michael A.
Jones, Pharm.D.; Timothy W. Lynch, Pharm.D., M.S.; Leslie R. Copyright © 2011, American Society of Health-System Pharmacists,
Mackowiak, M.S.; Tommy J. Mannino, B.S.; Jayson J. Przybyla, Inc. All rights reserved.
Pharm.D.; Brendan J. Reichert, M.S.; Ranee M. Runnebaum,
Pharm.D.; Nancy R. Smestad, M.S.; David L. Troiano, M.B.A., The bibliographic citation for this document is as follows: American
MSIA; Laura L. Tyndall, Pharm.D.; and Lori Wright, Pharm.D. Society of Health-System Pharmacists. ASHP guidelines on phar-
macy planning for implementation of computerized provider- order-
ASHP also gratefully acknowledges the contributions of the fol- entry systems in hospitals and health systems. Am J Health-Syst
lowing people: Bruce W. Chaffee, Pharm.D.; Toby Clark, M.Sc., Pharm. 2011; 68:e9–31.
ASHP Guidelines on Remote

Medication Order Processing
Purpose services and supplemental workload balancing, which in-
cludes network workload balancing and on-call assistance.
Because of the complexity of the care that pharmacists Each of these models has unique characteristics that must be
provide patients, the American Society of Health-System considered in planning for its use.
Pharmacists (ASHP) advocates that patients have 24-hour
access to the pharmacist responsible for their care and that Contracted Services. In this model, a hospital pharmacy that
the pharmacist be physically accessible to the patient when is not continuously open contracts with a larger hospital or
feasible. ASHP recognizes that such access is not always a service to provide RMOP when its pharmacy is closed.
possible and encourages the development of remotely deliv- This model is typically applied when a hospital without 24-
ered pharmacist care as a supplement to onsite care. hour pharmacy services has sufficient automated dispensing
Medication order review is one aspect of pharmacist cabinet capacity that RMOP allows nursing staff to keep
patient care. All health-system pharmacies have an obliga- functioning without having a pharmacist present,2 although
tion to provide a review of medication orders that ensures some institutions have developed models for remote verifi-
safe medication use.1 When onsite pharmacist review is not cation by pharmacists of dispensing performed by pharmacy
available, health systems may determine that remote phar- technicians at the client site.3
macist review of medication orders is a suitable alternative.
The purpose of these guidelines is to describe the policies Supplemental Workload Balancing. Similar to the model
and procedures that must be in place to safely employ re- described above, in this case a health system with a number
mote medication order processing (RMOP). Health-system of hospitals relies on the ones that have a 24-hour pharmacy
policies and procedures regarding RMOP should address department or on a service to provide RMOP for hospitals
quality assurance and safety; access to drug information and whose pharmacies are closed or that experience unantici-
hospital policy resources; training and orientation; minimum pated peaks in order processing workload. For example, in
technical standards and specifications; confidentiality, pri- an on-call model, a staff pharmacist from the client site or a
vacy, and security; regulatory and accreditation standards; contracted service is placed on call to help with managing
and communication and problem resolution. These guide- workload. This pharmacist works remotely (sometimes from
lines also describe some general considerations for RMOP a home office, where allowed by state regulation) to help the
implementation, and Appendix A provides a checklist for as- client’s pharmacy department manage unanticipated peaks
sessing implementation readiness. Appendix B contains an in order processing workload (often on the second or third
outline of a model agreement for RMOP. A glossary of terms shift). In this model, the remote pharmacist is responsible for
used in these guidelines appears in Appendix C. medication order entry and/or review, and medication order
Because of the rapid pace of change, differences in fulfillment occurs through the client-site pharmacy.
practice settings and RMOP models, and the complexi-
ties of health care organizational arrangements, aspects of
these guidelines may not be applicable to all settings. These Quality Assurance and Safety
guidelines are not intended to describe best practices for
the operational relationships between satellite and central Medication-use management and safety in the RMOP envi-
pharmacies in acute care settings. Readers should also note ronment require special efforts in the coordination of quality-
that these guidelines do not attempt to address all aspects assurance, quality-improvement, and patient safety practices
of remotely delivered pharmacist care and should interpret between the client site and the remote site. Differences in local
them as limited to the subject of RMOP. These guidelines practice standards and organizational cultures, combined with
address remote order verification only when medication or- unique human factors issues, have the potential to magnify
der fulfillment occurs through automated medication storage the risk of errors. Quality, safety, and risk management strat-
and distribution devices. Remote end verification of the dis- egies should be jointly examined and agreed on and should
pensed drug product (e.g., visual approval of the drug prod- address the procedures and communication pathways unique
uct by video camera or other means) is beyond the scope to RMOP systems. These include critical workflow steps and
of these guidelines. Health-system administrators and phar- handoffs involved in medication ordering, review, and verifica-
macy managers should therefore exercise their professional tion; communication among prescriber, pharmacist, and nurse;
judgment in assessing and adapting these guidelines to meet and assessing the patient’s response to drug therapy and achiev-
the needs of their particular settings and to comply with the ing desired therapeutic outcomes.
health care organization’s policies and procedures.
Review of the Patient’s Profile. The remote pharmacist must
Models of RMOP Services be able to review the patient’s profile for
The technologies used in RMOP are relatively new and • Medication history and medication reconciliation re-
rapidly changing, so different methods for RMOP have ports,
evolved, and further evolution should be encouraged. At • Diagnosis,
least two models of RMOP are currently in use: contracted • Allergies and prior adverse drug reactions,
• Height, weight, age (measured versus estimated), and Access to Drug Information
sex,
and Hospital Policy Resources
• Pregnancy status for women of childbearing potential,
• Duplications of drug therapies,
• Potential drug interactions,
Drug Information Resources. Drug information resources
• Pertinent laboratory data, and
are essential tools for health care organizations. Drug infor-
• Other information as needed.
mation resources, specific to the needs and scope of patients
served, are essential for practicing evidence-based medicine
in a safe and efficient manner. In health care systems that
Clarification of Medication Orders. The remote pharmacist
use RMOP procedures, each institution needs point-of-care
must have a process by which he or she can clarify the medi-
access to internal and external drug information systems.
cation order with the prescriber. The remote pharmacist must
Internal drug information resources include the client’s
alert other health care providers caring for the patient (e.g.,
formulary, laboratory reference values, newsletters, and
the client nursing and pharmacy staff) of the need for addi-
drug-use guidelines based on local standards. External
tional review and clarification. There must be a mechanism
drug information resources include commercially avail-
for the remote pharmacist to readily communicate by phone
able electronic and print media that organize information
or leave a note in the patient profile for other health care
into full-text and bibliographic retrieval systems.
providers, including the client site pharmacy staff, to clarify
Drug information resources available in the remote
the order or otherwise respond within an appropriate period
pharmacy should at a minimum meet the state board of phar-
of time. The remote pharmacy must have a mechanism for
macy requirements for both the client and remote pharmacy
timely follow-up on medication orders that are pending clar-
sites and include the current edition of a drug information
ification.
reference (hard copy or electronic). Other reference mate-
rial (hard copy or electronic media) should be available, de-
Quality-Assurance and Medication Error Reporting
pending on the scope of care being provided. Recommended
Systems. The remote pharmacy must participate in the cli-
clinical and drug information reference materials available
ent site’s quality-assurance and medication error reporting
in the remote pharmacy include
systems. These systems should include the collection and
reporting of medication errors and process variances as de-
scribed below:
• Two sources of pediatric dosing information (ideally,
one of which is the same resource used by clinicians in
the remote pharmacy),
• The medication error reporting system should include
• Internet access to online drug information resources,
potential adverse events that reach the patient (with or
including the Food and Drug Administration,
without harm) and potential adverse events that are in-
tercepted before reaching the patient.
• Drug compatibility and drug interaction resources,
• Poison information and poison control resources (at a
• Medication error reports related to RMOP procedures
minimum, the telephone number for a certified poison
and communications should be tracked by outcome,
control center), and
type, cause, severity, preventability, and source.
• Drug information center contact number.
• Corrective action plans should be directed toward the
system failures that contributed to or caused the error,
Drug information requirements, resources, and staff com-
variance, or adverse event.
petencies in the use of drug information systems should be
• Policies and procedures should ensure that quality-
reviewed at least annually to ensure that patient care needs
assurance data and medication error reports are jointly
are met.
reviewed in a timely manner by pharmacy leadership
and safety officers (if applicable) at both the client and
Hospital Policy and Procedures. The minimum information
remote sites and that relevant information is shared
on client site hospital policies and procedures that the re-
with relevant frontline practitioners at both sites, in-
mote pharmacist should have available is
cluding remote pharmacists and client-site nursing and
pharmacy staff.
• Client site’s pharmacy department’s policies and pro-
cedures,
The quality-assurance program should include indica-
tors that measure important aspects of RMOP, including • Client site’s formulary,
measures of (1) timeliness (e.g., elapsed time to receive and • Client site’s relevant nursing department policies and
procedures,
verify an order), (2) system performance (e.g., percentage
of time information technology systems are not available • Standard medication administration times,
for RMOP), (3) compliance with contractual requirements, • Standard drip concentrations or drug protocols,
(4) employee satisfaction at the client and remote sites, and • High-risk policies including the “Do Not Use” abbre-
viations list,
(5) unanticipated problems (e.g., breaks in privacy stan-
dards, communication and handoff problems). • Drug-specific clinical guidelines,
• Restrictions by indication or prescriber,
Handoff Communication. The remote site should have a • Chemotherapy protocols, pain protocols, and antico-
agulation protocols,
documented process for handoff communication that meets
the requirements of Joint Commission National Patient • Standing or protocol orders,
Safety Goals.4
• Pre- and postoperative antibiotic selection and admin- • The remote site must have the ability to access the cli-
istration protocols, and other protocols as determined, ent facility via the client’s Internet solution or via the
• Therapeutic interchange list, client’s computer network.
• Client’s policies and procedures for processing non- • The remote site must, to the extent possible, have
formulary medication orders, redundant systems in place to ensure RMOP service
• Client’s policies and procedures for handling a clini- availability (e.g., computer network and Internet con-
cal message order to alert nursing staff and pharmacy nectivity, other information systems used to facilitate
department of the need to address an issue at a future RMOP).
time, and • The remote site must have the ability to operate re-
• Client’s pharmacokinetic and renal dosing policies motely the client’s order transmittal system.
along with written medical staff approval to write or- • The systems used by the remote pharmacist to view
ders in the patient’s chart if required to comply with the patient orders and other medical information must
these policies. comply with the technical standards set by the Health
Insurance Portability and Accountability Act of 1996
The remote site must have a procedure that ensures the and ensure technical and physical safeguarding of pa-
timely and complete communication of changes in client tient health care information.
site hospital policies and procedures, including changes to
formularies and medication protocols.
Confidentiality, Privacy, and Security
Training and Orientation To ensure the confidentiality, privacy, and security of patient
health care information, the following conditions must be
Pharmacists, through training and orientation, are competent met:
to review and enter medication orders written by prescrib-
ers into a computerized database to maintain a complete • Remote pharmacists must adhere to the client’s confi-
patient profile. This patient profile can be used by nurses dentiality policy.
and other providers to access medications appropriate for • The remote site, if a business entity, must have a signed
their patients. This training and orientation are critical for business associate agreement with the client.
pharmacists to accurately document and transcribe the ap- • The client must provide individual pharmacist-specific
propriate information to maintain an accurate and up-to-date access to the client’s hospital computer system.
profile. Requirements for training and orientation include
the following:
Regulatory Considerations
• All education and orientation are documented in a per-
State regulation of RMOP varies considerably. The client
manent record maintained in the pharmacy department
of the remote site (if applicable) and shared with client and the remote site should jointly analyze state regulations
sites or in the pharmacy department of the client site, governing pharmacy practice at both sites to determine and
as appropriate. meet applicable requirements. This analysis should be re-
• All pharmacy personnel accessing the pharmacy infor- peated on a routine basis, as regulations may change. To
mation system are tested for competency prior to use ensure regulatory compliance, at a minimum the following
of the system and annually thereafter. should be verified and approved by the client and the remote
• When upgrades or significant changes are made to site before implementing RMOP:
the client site’s computer system, the client site will
communicate to the remote site the need for follow-up • Remote site’s approval to operate by the client’s state
training. board of pharmacy, if required,
• When significant changes are made to the client site’s • The policy and procedure manual for the RMOP op-
clinical policies or procedures, the client site will com- eration, including but not limited to procedures for
municate to the remote site the need for follow-up handling computer system or connectivity downtime,
training. issue escalation, annual competency renewal verifica-
• The client and the remote site must have a process for tion, and communication between the client site and
documenting the remote pharmacist’s competencies. If remote site personnel,
the remote site is responsible for the documentation • Copies of all licensure required by the states in which
of those competencies, the client and the remote site the client and the remote site are located (some states
must have a system for reporting those competencies require remote pharmacists to have a consultant li-
to the client. cense in addition to a state pharmacist license for each
hospital for which the pharmacist performs RMOP
Minimum Technical Standards services), and
and Specifications • Copies of any hospital job-specific competency re-
quirements for pharmacy personnel.
The client and the remote site must ensure that the follow-
ing minimum technical standards and specifications are met: Communication and Problem Resolution
• The remote site must have access to the client’s network To ensure the safety of the RMOP service, the client and the
or Internet, phone, and scan or fax access to the client. remote site must establish effective communication chan-
nels between personnel at the two sites. Communication when feasible. Because 24-hour pharmacy services are not
among prescriber, pharmacist, and nurse will be critical to achievable in all circumstances, health systems may em-
assessing the patient’s response to drug therapy and achiev- ploy remote pharmacist review and processing of medica-
ing desired therapeutic outcomes. The remote pharmacist tion orders. The purpose of these guidelines is to describe
must have the ability to immediately contact the prescriber the policies and procedures that must be in place to safely
or client site’s nursing staff to discuss any concerns identi- employ RMOP. Health-system policies and procedures re-
fied during review of the patient’s information. The client garding RMOP should address quality assurance and safety;
must provide its nursing supervisor with a 24-hour telephone access to drug information and hospital policy resources;
number to contact the remote site or remote pharmacist and training and orientation; minimum technical standards and
encourage nurses to communicate with the remote pharma- specifications; confidentiality, privacy, and security; regula-
cist. In the event the nursing supervisor is unable to resolve a tory and accreditation standards; and communication and
problem or concern, the client pharmacist on call is available problem resolution. Given the rapid pace of change in tech-
for consultation and problem resolution if the problem can- nology, differences in practice settings and RMOP models,
not wait until the client pharmacist is on duty again. Patient and the complexities of health care organizational arrange-
profile information, including laboratory results, should be ments, health-system administrators and pharmacy manag-
communicated to the remote site electronically; oral com- ers should exercise their professional judgment in assessing
munication of laboratory results should be limited to excep- and adapting these guidelines to their particular settings.
tional circumstances, and such oral communications should
be documented in the patient medical record as soon as pos-
sible. Downtime procedures should provide mechanisms for References
direct communication among the remote pharmacist, nurses,
and the prescriber. 1. The Joint Commission. Elements of performance
for medication management standard 4.10 (prepar-
ing and dispensing). Comprehensive accreditation
Considerations for Implementation manual for hospitals. Oakbrook Terrace, IL: The Joint
Commission; 2007:MM-10.
The success of RMOP implementation will depend on a host 2. Stratton TP, Worley MW, Schmidt M, et al. Imple-
of specific factors. Below are some considerations that are menting after-hours pharmacy coverage for critical
generally applicable. Appendix A provides a brief checklist access hospitals in northeast Minnesota. Am J Health-
for implementation readiness. Syst Pharm. 2008; 65:1727–34.
3. Clifton GD, Byer H, Heaton K, et al. Provision of
• Terms of the contract or agreement should allow flex-
pharmacy services to underserved populations via re-
ibility for the number of orders processed, since esti-
mote dispensing and two-way videoconferencing. Am
mates prior to “go-live” may be inaccurate.
J Health-Syst Pharm. 2003; 60:2577–82.
• Early and frequent communication between the cli-
4. The Joint Commission. 2009 National Patient Safety
ent site and the remote site, especially in the first few
Goals: hospital program. www.jointcommission.org/
weeks after go-live, is critical to the success of the
PatientSafety/NationalPatientSafetyGoals/09_hap_
implementation and ongoing operation.
npsgs.htm. (accessed 2009 Dec 28).
• After-hours technical support at both the remote site
and the client site will be essential to the success of
the implementation and ongoing operation. Plan for Appendix A—Checklist/Assessment for
information technology support in advance of go-live. Implementation Readiness
• Education will be required for all nurses at the client
site, not just those whose shifts coincide with RMOP 1. All automation has been tested and is functional, in-
coverage. In particular, changes to the client site’s cluding
override processes will need to be planned in collabo- a. Communication of medication orders (fax ma-
ration with nurses. chines or scanners)
• The client should implement a mechanism for commu- b. Computer systems maintaining patient profiles
nication between the remote site and nursing via the c. Connectivity to automated medication dispens-
electronic medication administration record (eMAR) ing cabinets
system. For example, if the remote pharmacist re- d. Electronic reference resources
views the patient’s home medication reconciliation list e. Remote connectivity
and identifies items not stocked by the pharmacy, it 2. All personnel training for remote site and client site is
would be helpful to have a drug dictionary item (e.g., completed and documented:
“Pharmacy Note to Nurse”) whereby the remote phar- a. Computer systems
macist can make an entry in the eMAR that informs b. Clinical guidelines
nurses that the remote pharmacist has reviewed the c. Client site pharmacy policies and procedures re-
order but that some action at the client site is required. lated to review, authorization, and entry of medi-
cation orders
Conclusion d. Communication procedures
3. Pre-go-live test of mock patients and scenarios has
ASHP believes that patients should have 24-hour access been performed for
to the pharmacist responsible for their care and that the a. Fax/scan orders
pharmacist should be physically accessible to the patient b. Admission, transfer, and discharge of patient
c. Medication order entry f. Compliance with laws, regulations, guidelines,
d. Communication procedures and accrediting body standards (e.g., Joint
4. System downtime protocols have been well commu- Commission)
nicated to all applicable personnel at both the remote
site and client site (e.g., pharmacy, nursing, informa- Appendix C—Glossary
tion technology, and administrative personnel)
5. Go-live date and service level expectations have been Terms used to describe remote medication order process-
well communicated to all applicable personnel at both ing (RMOP) practices are evolving and vary considerably.
the remote site and client site Readers should be alert to these inconsistencies and exercise
6. Communication process that includes quality report- caution in interpreting the literature. The following terms are
ing, system changes/availability, and policy and pro- used in these guidelines:
cedure updates as well as shift change communication
has been agreed on, established, and well communi- Client: The health care organization receiving the RMOP
cated to all applicable personnel at both the remote site service.
and client site Client Site: The site receiving the RMOP service (the site
where the patient is receiving care).
RMOP: Medication order processing provided by a remote
Appendix B—Outline for Model pharmacist; this term includes remote order entry and
Agreement Between remote order review.
Remote Pharmacist: A licensed pharmacist processing the
Remote Site and Client medication order from the remote site.
Remote Site: The site that is electronically linked to the cli-
The agreements between a remote site and the client must ent site via a computer system and/or a video or auditory
be approved by both contract office and risk management in communication system approved by the appropriate state
both facilities (if applicable). The agreement should include board(s) of pharmacy. The remote site may be a licensed
pharmacy or other location permitted by the appropriate
1. Services to be provided, including the roles of both state board(s) of pharmacy.
parties:
a. Hours of service
Developed through the ASHP Council on Pharmacy Management
b. Technology requirements
and approved by the ASHP Board of Directors on September 25,
c. Order processing services
2009.
d. All clinical services provided
e. Management services
ASHP gratefully acknowledges the expert panel that authored
f. Quality measures
these guidelines. At the time of writing, members of the ex-
g. Other services (e.g., vacation, emergency, or
pert panel held the following positions. Bruce Thompson, M.S.,
other hours of coverage)
was Director of Pharmacy Services, Hennepin County Medical
h. Qualification of pharmacy and pharmacists
Center, Minneapolis, MN; Greg Conrad was Director, Pharmacy,
i. Security of information
Willamette Falls Hospital, Oregon City, OR; Michael O. Gum was
j. Limitations
Pharmacy Director, Presbyterian Hospital, Charlotte, NC; John M.
k. Access to records, including information re-
Kessler, Pharm.D., BCPS, was Founder and Chief Clinical Officer,
quired to review patient profiles
SecondStory Health LLC, Carrboro, NC; Tim Larson was Pharmacy
2. Terms and renewal of the agreement
Director, Cardinal Rxe-source Center–Chicago region, Westmont,
3. Mutual indemnification and insurance
IL; Dallas Moore, M.S., was Pharmacy Director, American Fork
4. Termination of the agreement, including changes in
Hospital–Intermountain Healthcare, American Fork, UT; Kelly
laws or regulations
Morrison was Director of Sales & Marketing, Rxe-source, Cardinal
5. Confidentiality, including requirements set by the
Health, Houston, TX; and Mickey Price was Vice President, Rxe-
Health Insurance Portability and Accountability Act of
source, Cardinal Health, Dublin, OH.
1996
6. Limitations of liability
The contributions of Stephen R. Novak, M.P.A., FASHP, to these
7. No exclusion from federal health care programs
guidelines are gratefully acknowledged. At the time of his con-
8. Dispute resolution
tribution, Mr. Novak was Director, Pharmacy Services, Pardee
9. Fees and payment terms:
Hospital, Hendersonville, NC. ASHP also acknowledges the fol-
a. Hourly rates
lowing organizations and individuals for reviewing drafts of these
b. Per-order rates
guidelines (review does not imply endorsement): Accreditation
c. Order volume
Council for Pharmacy Education (ACPE); Healthcare Information
d. Overpayment and underpayment exposure
and Management Systems Society (HIMSS) Pharmacy Informatics
e. Penalty charges
Task Force; Emily Alexander, Pharm.D., BCPS; David B. Archer,
f. Addition of new services
D.Ph.; David Aresco, B.S.Pharm., FASCP; John A. Armitstead,
10. Miscellaneous issues, including
M.S., FASHP; Darrel W. Box, M.H.A.; Michael Brown, Pharm.D.;
a. Independent contractors
Kimberly K. Daugherty, Pharm.D., BCPS; Doug DeJong, M.B.A.,
b. Notices
FASHP; Mike Dudzik, M.H.A.; Francis J. Dunn, Jr., B.S.Pharm.;
c. Compliance with the terms
Jeanne Ezell, M.S., FASHP; Kelly Guhr, Pharm.D., BCPS; George
d. Rights of the parties
Hill, M.B.A.; Linda Horton, Pharm.D.; Jody Jacobson Wedret,
e. Conflict of laws
FASHP, FCSHP; Ken Kester, Pharm.D., J.D.; Patricia Kienle,
M.P.A., FASHP; Nancy Konieczny, M.B.A.; Donald H. Lynx, Copyright © 2010, American Society of Health-System Pharmacists,
M.B.A., FASHP; Lynnae M. Mahaney, M.B.A.; Peter G. Mayberry; Inc. All rights reserved.
Roland Patry, Dr.P.H., FASHP; James A. Ponto, M.S., BCNP,
FASHP; Cliff Richards, Pharm.D.; Mike Rouse, B.Pharm.(Hons), The bibliographic citation for this document is as follows: American
M.P.S. (ACPE); Terry Seaton, Pharm.D., FCCP, BCPS; Timothy P. Society of Health-System Pharmacists. ASHP guidelines on re-
Stratton, Ph.D., BCPS, FAPHA; Basil J. Thoppil, M.Sc., Pharm.D.; mote medication order processing. Am J Health-Syst Pharm. 2010;
and Dennis A. Tribble, Pharm.D. 67:672–7.
ASHP Guidelines on the Safe Use

of Automated Compounding Devices
for the Preparation of Parenteral
Nutrition Admixtures
Purpose pharmacist and in the appropriate environment.2 The historical

method of compounding these multicomponent admixtures has
Automated compounding devices are frequently used by been to manually use gravity-driven transfers for large-volume
pharmacists for the extemporaneous preparation of parenteral additives, such as amino acids, dextrose, lipids, and sterile water.
nutrition admixtures. This continuing shift from manual Small-volume additives, such as electrolytes, trace minerals,
compounding procedures comes as a result of significant multivitamins, and drugs, have often been added manually and
advances in automated technology, as well as in response separately with a syringe. Thus, this compounding method is
to changing health care demands to provide admixture com- limited by the visual inspection of volumes transferred between
pounding in a safer, more efficient, and more accurate man- stock containers, as well as by the precision of the calibrations
ner. Approximately 65% of the hospitals in the United States marked on the stock containers or transfer devices.
currently use automated compounding devices for parenteral The manual method of parenteral nutrition admixture
nutrition admixtures on a daily basis.a Compounders are also compounding is labor-intensive and requires multiple ma-
used for other types of intravenous admixtures and in other nipulations of infusion containers, sets, syringes, needles,
settings, including home care and long-term-care facilities; and so forth, which can lead to the extrinsic contamination
therefore, the overall magnitude of their use may be sub of the final admixture with sterile and nonsterile contami-
stantial. As with other automated systems or devices, the nants. A sterile contaminant can be particulate matter from
benefits can be realized only when the technology is used elastomeric vial enclosures (needle cores), and nonsterile
appropriately. Significant patient harm may occur when contaminants can be bacteria and other infectious materials.
safety and quality assurance measures are overlooked or Minimizing the number of extemporaneous manipulations
circumvented.1 of the parenteral infusion containers and supplies improves
The purpose of these guidelines is to outline the key compounding efficiency and reduces the risk of extrinsic
issues that should be considered to safely and cost-effectively contamination and associated sequelae.3
incorporate this technology into the pharmacy operations of The emergence of automated technology as an alterna-
health care organizations. The guidelines focus on parenteral tive approach to parenteral nutrition admixture compounding
nutrition admixtures, but the safety issues are also applicable has led to potentially improved compounding accuracy with
to the use of compounders for other types of i.v. admixtures. the use of fluid pump technology and software that controls
The term “health care organization” is used throughout the the compounder pump. Fluid can be delivered from the source
guidelines as a general descriptor and is intended to be inclu- container to the final container by using either a volumetric
sive of any of the practice settings and types of facilities in or a gravimetric fluid pumping system. Volumetric systems
which compounders are used, including, for example, home transfer a specified volume of fluid from a source container
infusion companies. These guidelines should be used in con- to a final container via a rotary peristaltic pump. The tubing
junction with the ASHP Guidelines on Quality Assurance for is stretched around a rotor and, as the rotor turns, solution is
Pharmacy-Prepared Sterile Products and device manufactur- pulled from the source container and pushed toward the final
ers’ instruction manuals and training materials. Pharmacists container. Measurements are based on the theory that each
should use professional judgment in assessing their health care rotor movement advances a constant amount of fluid through
organization’s needs for automated compounding devices and the system. The total volume delivered is calculated by the
in adapting these guidelines to meet those needs. volume pulled into the tubing by each rotor movement mul-
tiplied by the number of movements. These systems usually
Background incorporate a final check of the actual total bag weight by
comparing it with a calculated expected weight.
The act of extemporaneously compounding any parenteral In gravimetric systems, measurement of fluid volume
formulation is complex and not without inherent risks; delivered from the source container to the final container
therefore, compounding tasks are best performed by person- is determined by weighing the fluid transferred and divid-
nel most qualified to do so. An incompatible, unstable, or ing the weight by the solution’s known specific gravity,
contaminated i.v. infusion may induce significant patient thereby converting weight to volume. Two types of gravi-
morbidity and even mortality.1 Pharmacists are specifically metric pumps are available: additive and subtractive. With
educated and legally responsible for performing these tasks an additive pump, a single load cell is positioned to measure
safely. Pharmacists are also responsible for training other each fluid as it is delivered to the final container. With a sub-
personnel to perform relatively simple tasks with the least tractive pump, load cells are positioned beneath the source
risk possible. containers to measure each fluid as it is being pumped from
The extemporaneous preparation of multiadditive its source container. Weight is determined by subtracting
products, such as parenteral nutrition admixture compound- the posttransfer weight from the pretransfer weight of the
ing, should be performed under the direct supervision of a container for each source solution. When all transfers are
completed, the system compares the actual total bag weight reduced by consolidating source solutions to a few
with a calculated expected weight. high-concentration, large-volume additives.
In addition to the compounder, dedicated software
may be used to electronically transfer information to the In some cases in which the cost of implementing au-
compounding device. Automated compounding software tomated compounding technology in one facility is prohibi-
has additional features that can enhance the management of tive, health care organizations have opted to explore regional
the parenteral nutrition program. Software issues and their compounding centers or outsourcing to contractors.
integrity are additional critical components unique to com-
pounder methods and require continuous monitoring to en-
Performance Requirements
sure that the operations are correct.4
and Responsibilities
Justification for the Use of The use of automated devices for compounding parenteral
Automated Compounding Devices nutrition admixtures should be clearly defined by the health
care organization and the manufacturer. This includes the
When is it appropriate to use compounders, and how will ongoing responsibilities of the pharmacy department and
decisions affect others within and outside the pharmacy de- those of the manufacturer during and after implementation
partment? It is incumbent upon the pharmacist to ensure that of the compounder in the pharmacy practice setting.
the department is fully knowledgeable about the operation of Three areas need to be clearly defined before choosing
the compounder and that a minimum acceptable standard of an automated compounding system: (1) the system’s perfor-
pharmacy practice is met. First, internal decisions need to be mance requirements, (2) the manufacturer’s responsibilities,
made to justify the expenses associated with this technology. and (3) the pharmacy department’s responsibilities. The perfor
Second, policies and procedures should be in place to assess mance requirements of the automated compounding system
workflow, establish training programs, and standardize com- should ensure that
pounder use in the specific pharmacy practice setting. Third,
changing current compounder contracts may result in more 1. The compounder exceeds the level of accuracy
cost than the savings that might appear in the new contracts. achieved with manual compounding. The automated
Specifically, the initial incorporation of an automated com- compounding device should be accurate to within 5%
pounder into daily pharmacy practice is a labor-intensive of the amount programmed, with verification of the
effort, and such transitions can be disruptive and can even amount pumped versus the programmed amount for
increase the risk of errors. This may be particularly true dur- each ingredient.
ing staff orientation to new devices. Such changes must be 2. The automated compounding device has inherent
carefully reviewed; if they are determined to be worthwhile, safeguards, including the ability to detect inadvertent
a well-coordinated transition plan should be devised before- source-solution mixups; the ability to detect situations
hand. Whether transition costs (including the potential for that could result in inaccurate deliveries, such as occluded
unused sets and supplies) can be deferred to the new contract transfer-set tubing and empty source containers; and the
is another factor for consideration. ability to keep incompatible source solutions separate.
The principal emphasis associated with using auto- 3. The automated compounding software alerts the user
mated compounding devices in health care organizations when formulation issues arise.
should be improving patient care and enhancing efficiency 4. The automated compounding software meets the
while remaining cost-effective. “Cost-effectiveness” is, standards of the American Society for Parenteral and
therefore, a relative term with respect to personnel, as the Enteral Nutrition for parenteral nutrition label formats.5
labor saved is often redirected to other aspects of pharma- 5. The automated compounding software assists the
ceutical care that could also improve patient safety. Time pharmacist in producing physicochemically compat-
that was previously spent on operations associated with par- ible parenteral nutrition formulations.
enteral nutrition admixture compounding can now be aimed 6. The automated compounding software provides useful
at other issues, such as optimization of drug and nutritional clinical information.
therapies, reorganization of product utilization, quality assur- 7. The automated compounding software integrates with
ance programs, and augmentation of other core pharmaceuti- existing pharmacy programs wherever possible to op-
cal services. Specific objectives related to cost justification of timize patient care and avoid therapeutic duplications.
automated compounding devices may include the following:
The contractual agreement with the manufacturer
1. Enhanced efficiency and worker safety during the should provide continuous support of the compounder and
parenteral nutrition compounding process and patient software, including information updates, problem solving,
safety with parenteral use. and emergency coverage. FDA considers all automated
2. Reduction in labor associated with manually com- compounding devices class II devices,6 and as such they
pounded parenteral nutrition admixtures. Assessment must comply with federal regulations. The manufacturer’s
of the overall labor and material costs associated with responsibilities are as follows:
the current manual compounding methods should in-
clude hidden costs such as pharmacists’ time to perform 1. The manufacturer should supply, and the pharmacist
calculations, quality assurance checks, and compounder should verify, that the device is 510K cleared as evi-
set-up, as well as staff training (initial and on-going). dence of compliance with regulatory requirements;
3. Reduction in waste through more efficient use of that the device meets the fire and safety standards
base solutions and additives. Inventory can often be established by Underwriters Laboratories (i.e., is
UL-approved); that the operator’s manual and other Safety and Efficacy Features
documentation support recommendations for use; and
that accuracy statements and manufacturer claims are valid. The complexity of automated compounding device functions
2. The manufacturer should provide 24-hour support for makes it imperative that the pharmacy department develop
the compounder and its software throughout the life of a specific plan for ensuring safe and efficacious use at
the contract. all times. The safety and efficacy features should outline
3. The manufacturer should routinely provide the latest the core principles necessary for carrying out the complex
version of the compounder software in a timely manner. tasks of parenteral nutrition compounding. The plan should
4. The manufacturer should ensure adequate availability identify the minimum standards that are routinely assessed
of compounding supplies. through an established monitoring and surveillance pro-
5. The manufacturer should provide detailed informa- gram. Automated compounding devices on the market dif-
tion and instructions on the appropriate use of the com- fer in hardware design, mechanisms of fluid transfer, and
pounder and its software. References should be pro-
software applications. Consequently, sterility and quality
vided when appropriate.
assurance testing procedures and measures are also differ-
6. The manufacturer should comply with FDA require-
ent, including routine assessments of accuracy in the delivery
ments for reporting adverse events.
of correct amounts of nutrients. Consideration should be
given to the following in accordance with the device manu-
Within the pharmacy department, specific policies and
facturer’s specific instructions:
procedures should be developed that address responsibili-
ties for compounder operations and maintenance, staff train-
1. Establishing minimum competency standards for all
ing, and monitoring compounder performance at all times.
personnel who have access to and operate the com-
Before selecting and implementing an automated com-
pounder. Competency standards should ensure that the
pounder, the pharmacy department should
compounder user has sufficient expertise to identify
1. Define and agree on automated compounding system errors that may inadvertently bypass quality assur-
needs and performance requirements. ance systems. The competency standards should be
2. Develop an implementation team with a lead person. reviewed and validated on a routine basis for all per-
3. Develop a set of policies and procedures. sonnel operating the compounder.
2. Establishing specific procedures for the operation of
the compounder that standardize its use, irrespective of
Control of the Automated the individual operator. Changes in compounder opera-
Compounding Device in Daily tions should occur only when authorized and should be
Operations communicated to all staff involved in compounding.
3. Including sterility and quality assurance measures to
The pharmacy department is responsible for the use, main- avoid extrinsic contamination and to ensure accurate
tenance, and performance of the automated compound- delivery of parenteral nutrition additives.
ing device, including decisions about who has access to 4. Ensuring that compounder tubing changes occur at
the compounder and its operations. Specific consideration appropriate specified time intervals in accordance
should be given to the following: with the manufacturer’s recommendations.
5. Devising methods for assessing and calibrating the
1. Only designated pharmacy department personnel accuracy of the compounder in delivering precise
should have access to the compounder and its soft- levels of substrates and additives.
ware. The level of access should correspond to the 6. Developing a contingency plan and a readily available
level of authority and expertise of the personnel. backup system or method for providing uninterrupted
2. Before being granted access to a compounder, phar- parenteral nutrition therapy to patients in the event of
compounder failure.
macy personnel should pass established competency-
7. Ensuring that adequate amounts of solutions and
standard testing.
supplies for automated compounding are on hand.
3. Access to and use of the compounder by pharmacy
support personnel (i.e., pharmacy technicians, stu-
dents, and other designated support staff) should be Quality Assurance Monitoring and
directly supervised by an authorized pharmacist. Documentation
4. The additive configuration or sequence of the com-
pounder for compounding parenteral nutrition admix- Automated compounding devices are intended to provide
tures should not be altered from the established format a higher margin of accuracy and to streamline the labor
without the authorization of a designated pharmacist. intensive tasks associated with the manual extemporaneous
5. The compounder should not be used for any purpose preparation of large-volume, multiadditive parenteral nutri-
other than parenteral nutrition admixture compounding tion admixtures and other admixtures. The compounders are
without authorization from a designated pharmacist. not designed to replace oversight functions, which require
If the compounder is used for other extemporaneous the expertise of a pharmacist.
drug preparation, this should be done separately from In theory, automated compounding devices provide
the schedule for parenteral nutrition admixtures.The compounding accuracy superior to that of traditional meth-
use of the compounder in this manner will likely re- ods of manual compounding. However, the performance
quire the use of new compounding sets and admix- of compounders must be critically challenged by the phar-
ture configurations. macist to ensure that their manufacturing specifications are
equal to the task. In the pharmaceutical industry, that process and admixture ingredients. Other departments, such as
is called validation. Ongoing quality assurance measures materials management, may order and store additional
specified by the device manufacturer for assessing the per- supplies for the compounder yet defer to the pharmacy for the
formance of the compounder, as well as corrective actions, selection of the components necessary for proper compounder
should be clearly delineated in policies separate from those operation. Specific consideration should be given to
dedicated to operational tasks. “Ongoing” means daily, and
whatever measures are determined to be essential should be 1. Maintaining an adequate inventory of supplies neces-
performed each day because random checks may not detect sary for compounder operation and patient needs.
a more insidious, intermittent flaw that could assume major 2. Procuring all large-volume parenteral nutrition com-
clinical significance.7,8 ponents (amino acids, dextrose, and lipids) from one
The pharmacy department may work with other depart- manufacturer unless such combinations have adequate
ments to assess the compounder’s performance if such expertise physicochemical data that ensure the stability, compat-
is not available within the pharmacy department. For exam ibility, and safety of the final formulations commen-
ple, portions of parenteral nutrition admixtures may be sent surate with the data for single-source products.5 Any
to the health care organization’s laboratory to determine proposed substitute products should be assessed for
dextrose content. However, laboratory methods are usually compatibility and approved by designated pharmacy
designed for biological rather than pharmaceutical systems and personnel qualified to do so and possibly by the phar-
should be validated to meet USP requirements for the com- macy and therapeutics committee if clinical issues are
ponents being tested. If outside departments participate in identified.
the quality assurance program, their methods should be 3. If a health care organization’s contract requires a
appropriately validated in accordance with USP specifica- change in the brand of parenteral products, designated
tions and the results documented within the pharmacy de- pharmacy personnel should verify that the new prod-
partment records on the compounder’s performance. ucts are compatible. If a new product is approved,
The pharmacy department should develop a monitor- designated pharmacy personnel should verify that the
ing and surveillance plan with output reports that encom- new product is compatible, add it to the compounder
passes the principles outlined under the section on safety and formulary, and revise the admixture requirements and
efficacy features. The plan should detail specific policies and instructions relevant to the compounder’s operations.
procedures that will ensure the continuing operation of the
automated compounding device at optimum performance
levels at all times. The data generated by the monitoring Education and Training
procedures should be reported to the pharmacy director and
other appropriate oversight personnel and kept as a perma- Pharmacists, by education and training, are competent to
nent record of the compounder’s operations. These reports safely compound pharmaceuticals, including parenteral
should be regularly reviewed in the assessment of trends and nutrition admixtures. Nevertheless, the introduction of au-
other long-term measures of performance. Specific consider- tomated compounding devices requires specific training of
ation should be given to pharmacists as well as other pharmacy personnel in the op-
eration, maintenance, and quality assurance of compound-
1. Establishing performance standards and continuous ers. Specific consideration should be given to ensuring that
quality assurance measures for assessing the com-
pounder’s performance and product quality during 1. Pharmacy administration determines the individuals
setup and in-process (during compounding) and end- who will be responsible for education and training in
process testing. the use of the compounders.
2. Establishing quality assurance testing of user-defined 2. All education and training are documented in a per-
software variables validating that the correct responses manent record maintained in the pharmacy department
to user commands occur. and in personnel files.
3. Validating all quality assurance testing before imple- 3. All pharmacy personnel using or supervising com-
mentation. pounder operations are tested at regular intervals
4. Establishing a minimum performance standard for to ensure that individuals meet the department’s
each quality assurance test. For example, deviations minimum competency standards.
in the accuracy of delivering a single additive cannot 4. Retraining, competency assessment, and appropriate
exceed a predetermined percent error without immediate documentation accompany upgrades and new versions
corrective actions. of the compounder to ensure the continued proficiency
5. Documenting all quality assurance data on a daily basis. of personnel, safety of compounder operations, and
A comprehensive review of the data and documenta- adequacy of oversight.
tion of performance trends should be performed at
scheduled intervals as necessitated by aseptic condi- Device Variability
tions. The compounder should have scheduled, routine
cleaning and maintenance according to the manufac- Automated compounding devices are marketed by several
turer’s recommendations to ensure proper operation. manufacturers. Even though there are similarities among
compounders, there may be significant differences in the
Storage and Inventory design, accuracy, operation, maintenance, software, and
manufacturing support, among other things. The safe opera-
The pharmacy department is responsible for housing the tion and supervision of any given compounder depend on
automated compounding device, related disposable supplies, adherence to the manufacturer’s specific instructions and
continuous quality assurance monitoring of compounder 6. Trautman KA. The FDA and worldwide quality
performance. The safe and efficient operation of an automated system requirements guidebook for medical devices.
compounding system depends on defined responsibilities for Milwaukee, WI: ASQ Quality Press; 1997.
the pharmacy and manufacturer, as well as on strict adher- 7. Driscoll DF. Delivery of nutritional therapy: quality
ence to policies, procedures, and quality assurance programs. assurance of automated compounding devices.
Nutrition. 1996; 12:651–2. Editorial.
References 8. Fields HS. Establishing core performance require-
ments for automated TPN compounders. Am J Health-
1. Food and Drug Administration. Safety alert: hazards Syst Pharm. 1996; 53:1607. Letter.
of precipitation associated with parenteral nutrition.
Am J Hosp Pharm. 1994; 51:1427–8. a
Mihalski T, Clintec Nutrition Division, Baxter Healthcare. Personal
2. American Society of Hospital Pharmacists. ASHP
communication. 1999 Mar 15.
technical assistance bulletin on quality assurance
for pharmacy-prepared sterile products. Am J Hosp
Approved by the ASHP Board of Directors on April 27,
Pharm. 1993; 50:2386–98.
2000. Developed through the ASHP Council on Professional
3. McClendon RR. A comparative evaluation of methods
Affairs.
used to compound parenteral nutrition solutions. Nutr
Support Serv. 1983; 3:46–9.
Copyright © 2000, American Society of Health-System Pharmacists,
4. Driscoll DF. Clinical delivery of nutritional therapy:
Inc. All rights reserved.
automated compounders and patient-specific feeding.
Nutrition. 1996; 12:461–2. Editorial.
The bibliographic citation for this document is as follows: American
5. American Society for Parenteral and Enteral Nutrition
Society of Health-System Pharmacists. ASHP guidelines on the
National Advisory Group on Standards and Practice
safe use of automated compounding devices for the preparation of
Guidelines for Parenteral Nutrition. Safe practices for
parenteral nutrition admixtures. Am J Health-Syst Pharm. 2000;
parenteral nutrition formulations. JPEN J Parenter
57:1343–8.
Enteral Nutr. 1998; 22:49–66.
ASHP Guidelines on the Safe Use

of Automated Dispensing Devices
Purpose and nurses, improves accountability and storage of medica-
tions, and improves the accuracy and timeliness of medica-
The purposes of these guidelines are to (1) propose goals tion product availability. Experience with automated dis-
and objectives for the safe use of automated dispensing de- pensing devices suggests that, when used appropriately, these
vices in the medication-use process, (2) provide guidance benefits can be realized.3–11 When automated dispensing de-
on the safe use of automated dispensing devices to phar- vices are not used appropriately, their complexity, design and
macists and others involved in the medication-use proc- function variations, maintenance and education require-
ess, (3) advise vendors of automated dispensing devices ments, and other factors can have undesirable effects and
about the safety needs of health care professionals who use compromise patient safety.12,13 The National Association of
their systems, and (4) recommend standardization for Health Boards of Pharmacy (NABP) includes language on automa-
Level 7 (HL7) interfaces between pharmacy information tion in the NABP Model State Pharmacy Act and Model
systems and automated dispensing devices. The recommen- Rules.14,15 The NABP Model Act uses the term “automated
dations presented in these guidelines should be used in con- pharmacy systems” and defines them to include, but not be
junction with other literature on the topic and information limited to, “mechanical systems that perform operations or
from prospective or selected automated dispensing device or activities, other than Compounding or Administration, rela-
system vendors, established guidelines, and state and federal tive to the storage, packaging, Dispensing, or Distribution
regulations. Pharmacists should exercise professional judg- of medications, and which collect, control, and maintain all
ment in assessing their health system’s needs regarding auto- transaction information.”14 Data processing and bar code
mated dispensing devices and systems and in adapting these technologies, although incorporated as integral components
guidelines to meet those needs. of some of these systems, are not considered in the NABP
Automated pharmacy systems are designed for central- Model Act definition as automated drug distribution tech-
ized filling of individual patient prescriptions and unit-dose nology. The NABP Model Rules suggest specific require-
medication orders, decentralized dispensing, and other pur- ments and options for helping individual states determine
poses. These guidelines address primarily computer-controlled which automated pharmacy systems are appropriate for
decentralized medication-dispensing cabinets, which will be use.15 These ASHP guidelines reflect and expand on the re-
referred to as “automated dispensing devices.” Since many quirements of the NABP Model Rules.
of the concepts discussed here may be applicable to related The use of automated dispensing devices continues to
technologies, the term “automated pharmacy system” will be evolve. Some health care organizations deploy one or several
used generally and the term “automated dispensing device” devices in selected areas, such as emergency departments,
will be used specifically. Automated dispensing devices are that are floor-stock intensive and where lost charges can be
located in hospital patient care units, surgical suites, emer- substantial. Some devices are used for selected categories of
gency rooms, long-term care facilities, physicians’ offices, medications, such as controlled substances, that have time-
and other settings. Several manufacturers produce automated consuming tracking and documentation requirements. Some
dispensing devices with a variety of configurations and soft- organizations deploy devices throughout patient care areas
ware capabilities that may interface with the pharmacy or to cover nearly all medications used.
health care organization’s information systems.1,2 The rapid development of technology applications in
health care, including automated dispensing devices, and
Background pressures to expand their use have raised concerns about
patient safety, access to medications, and possible legisla-
The appropriate, accurate, and timely distribution of medica- tive and regulatory barriers. While technologies can be
tions to patients is a well-established responsibility of phar- designed to minimize opportunities for medication errors,
macists. In acute care settings in particular, distribution sys- that same design can create other, often unanticipated, op-
tems have been developed that enable pharmacists to review portunities for medication errors. Consideration of the use
patient-specific medication orders and oversee the prepara- of automated dispensing devices, like consideration of any
tion and packaging or selection of these medication doses, as other technology, must include serious evaluation of existing
well as the delivery of these medication doses to patient care and potential opportunities for error and the implementation
units. Automation has evolved to ease fulfillment of pharma- of mitigating strategies to minimize or prevent such errors.
cists’ distributive responsibilities, expand distribution system Pharmacists have a professional responsibility to ensure that
capabilities, and improve efficiency in distribution. appropriate policies, procedures, and quality-assurance pro-
Automated dispensing devices are an increasingly grams are in place to address the safety, accuracy, security,
prevalent component of the medication-use process in health and patient confidentiality of automated pharmacy systems,
care organizations today. The pharmacy profession’s transi- including automated dispensing devices.
tion to an emphasis on direct patient care, changes in health
care systems, and pressures to reduce costs have all created
interest in the availability and use of automated dispensing Goals and Objectives
devices. ASHP supports the use of automated dispensing de-
vices when it frees pharmacists from labor-intensive distribu- Goals for the use of automated dispensing devices in the
tive functions, helps improve patient care by both pharmacists medication-use process should focus on improving patient
care and resource use. Specific objectives related to these • Determining the responsibilities of the automated dis-
goals may include the following: pensing device vendor and the organization for instal-
lation, validation, maintenance, education, operations,
• Information necessary for appropriate medication and troubleshooting.
management and patient care is accurate, accessible, • Assessing the impact of automation on organizational
and timely. culture. Automation has a significant impact on em-
• Appropriate medications are readily available and ac- ployees, particularly pharmacy technicians and nurses.
cessible to meet patient needs within safety and secu- Optimal preparation and support should be considered.
rity controls. • Ensuring effective education for the organization’s em-
• Vulnerabilities to medication errors are minimized, ployees who use the automated dispensing device or
and those that remain are identified, documented, and whose responsibilities are affected by its use.
mediated. • Developing an ongoing support plan.
• Staff members involved in the medication-use process
are safety conscious, accurate, and productive. Since the medication-use process involves multiple health
• Patients are satisfied with the quality and delivery of care disciplines, selection of automated dispensing devices
care. and establishment of policies and procedures for their use
• Medication distribution services are facilitated across will require decisions that meet the needs of all disciplines
the continuum of practice settings in the health care involved. However, since pharmacists have a professional
system. and legal responsibility for the safety and integrity of the en-
• Resource management is improved by linking supply tire medication-use process, they should provide leadership
ordering channels to the medication distribution sys- in the development and maintenance of policies and proce-
tem. dures for the safe use of automated pharmacy systems. Any
• Billing accuracy is improved by allowing charges and system or device adopted for drug distribution and control,
credits to post when medications are dispensed from or including automated dispensing devices, should meet the
returned to the automated dispensing device. intent of established professional standards and guidelines
regarding patient safety. The automated system or device
Requirements should provide the following inherent safety features of unit-
dose drug distribution systems:
Automated dispensing devices should be regarded by users
as tools for improving the medication-use process rather than • Medications are contained in, and administered from,
inherent solutions to problems in that process. Consideration single-unit or unit-dose packages.
should be given to how the technology can be adapted to • Medications are dispensed in ready-to-administer
meet the goals and objectives of the user rather than how the form to the extent possible.17
user’s systems should be redesigned to fit the automated dis- • Medications are available for administration to the pa-
pensing device. It is important to consider the recommended tient only at the time at which they are to be adminis-
workflow for the automated dispensing device while si- tered, according to the institution’s policy.
multaneously reviewing the facility’s current workflow and • An electronic patient medication profile is concur-
practices to ultimately determine the best practices that will rently maintained in the pharmacy for each patient and
provide safe and efficient patient care while maximizing the made easily accessible to the pharmacist.
safety and efficiency advantages offered by the automated • Medications are accessible to different categories of
dispensing device. health care professionals with the ability to limit ac-
Before deciding to deploy automated dispensing de- cess based on policy or law.
vices in the medication-use process, an organization should
assess its logistical, financial, and cultural circumstances; the In addition, the automated systems or devices should ensure
safety, patient care, and resource benefits it hopes to gain; and safe medication storage, distribution, access, and use wher-
how these benefits would be observed and measured. The or- ever they are deployed, including meeting required environ-
ganization should also determine if the automated dispensing mental conditions for the storage and handling of medica-
devices in consideration are capable of producing the desired tions. Plans for use of automated dispensing devices should
benefits. Specific consideration should be given to include
• Incorporating the use of automated dispensing de- • Sufficient quantity and appropriate location of devices
vices into the organization’s strategic planning (i.e., to support intended use and efficient work processes,
ensuring that automation is compatible with the vi- • Selection of a location that minimizes distractions and
sion and mission of the organization). interruptions during use,
• Assessing the use of automation from a complete • Consideration of surrounding work-space to allow ef-
systems perspective. Automated dispensing devices ficient device operation and movement of staff,
should integrate smoothly with other systems and pro- • Ensuring appropriate ventilation and temperature
cesses, both manual and automated. Interfaces with control, including refrigeration for applicable medica-
overall patient care computer systems especially must tions,
be considered. • Ensuring adequate infection control policies and pro-
cedures are maintained when appropriate for the in-
• Establishing performance standards for safety, accu-
tended use and placement of the device,
racy, timeliness, and costs.16
• Ensuring appropriate and sufficient lighting to support various purposes in support of the medication-use process,
the safe and accurate verification of medication orders, including the following:
reading of medication labels, and administration docu-
mentation, • Commanding distribution of medications from a phar-
• Establishing proximity of the device to medication in- macy location,
formation and documentation systems, • Maintaining current data on patient population, includ-
• Selection of location or placement of the device that ing demographics and patient location, for the auto-
permits only the patient’s caregivers access to pro- mated pharmacy system,
tected health information, and • Maintaining a current and accurate patient medication
• Ensuring power and data connections essential to the profile for each patient served by the automated phar-
operation of the device are included in the facility’s macy system,
emergency backup power and data management sys- • Maintaining current formulary information,
tems, so that support and information are provided in • Recording the addition, removal, or dispensing of
a reliable manner during power or data interruptions. medications from automated dispensing devices,
• Issuing charges for medications removed or dispensed
Finally, the automated system or device should comply with from automated dispensing devices (if this is the
applicable federal and state consumer protection laws and charge method of choice), and
regulations. State boards of pharmacy may have different • Integrating with bedside point-of-care systems to as-
requirements for the use of automated dispensing devices sure accurate medication dispensing and patient ad-
in various practice settings and for obtaining approval for ministration.
their use.
Interfaces are effectively used to communicate patient de-
Override Access to Medications Through mographic information, medication order information, for-
mulary additions and updates, dispensing/charting informa-
Automated Dispensing Devices
tion, and inventory management transactions between the
automated dispensing device and the pharmacy information
All medication distribution systems have medication with-
system (or pharmacy functionality in a hospital information
drawal functions that allow nurses and other caregivers
system). Such interfaces may also pose challenges related to
limited access to certain medications before order review
the complexity of their own deployment and maintenance.
and approval by a pharmacist, especially in cases of patient
Their completeness and level of application may also impact
emergencies. This function is typically referred to as an
the workflow associated with the use of automated dispens-
“override.” Clearly stated organizational policies and crite-
ing devices. For these reasons, it is important to consider the
ria for system overrides should be developed that limit ac-
impact that specific interfaces will have on the hospital and
cess to medications before orders have been reviewed and
system users.
approved by a pharmacist.16,18,19 Override access to medica-
tions should be limited to cases in which the drug product Interfaces between automated dispensing devices and
has been approved by a multidisciplinary committee of phy- pharmacy systems can be costly to create and maintain. Most
sicians, pharmacists, and nurses as having a clinically urgent vendors base these interfaces on HL7 standards21 but do not
need for the medication that outweighs the potential risk of necessarily interpret and apply the HL7 specifications in the
medication error. same way. The result is that automated dispensing device
Subsequent order-based retrieval of the same medica- interfaces should be easily customizable and thoroughly
tion should cause the user to be reminded that an override tested prior to implementation. Pharmacists should consult
supply of medication was recently dispensed for the patient. with other users of the same pharmacy system, automated
Provision should be made for the retrospective review and dispensing device, and interface for advice on functionality
reconciliation by a pharmacist of orders that were initiated and customization.
without a pharmacist’s review and approval. Override data ASHP believes that the vendor community should
(e.g., name of medication, quantity, location of the auto- work with the HL7 organization to identify one standard
mated device, any associated adverse drug events) should be message set for communicating key transactions to and from
routinely reviewed to help evaluate and manage those medi- automated dispensing devices to permit interfaces to be
cations approved for override access. Override data evalua- more easily implemented and supported. In addition, ven-
tion can aid an organization in improving the outcomes of dors should be prepared to support XML-based interfaces
automated dispensing device use by decreasing medication with the newer Web-based pharmacy applications.
errors and potential adverse drug events20 and should be
considered part of the routine management process for auto- Safety Checks
mated dispensing devices.
The pharmacy is responsible for ensuring that the automated
Interfaces with Automated pharmacy system operates as designed and is well main-
Pharmacy Systems tained to prevent errors and system interruptions. All ele-
ments of the automated pharmacy system require periodic
Proper planning should include the development of an in- monitoring, including, as applicable, patient information and
terface strategy. Automated pharmacy systems interface medication profiles, computer controls for access, opera-
with systems for pharmacy information, electronic medical tions of drawers and bins, and transaction records.
records, admission/discharge/transfer, bar-coded medica- Any organization that uses an automated pharmacy
tion administration (BCMA), and materials management for system should have a written plan for the safe and effective
use of the system. The plan should be developed by the phar- products do not reach the active inventory before confirma-
macy and nursing staff, with input from respiratory therapy, tion that the product’s bar code is accurately loaded into the
medicine, and other disciplines that may be affected by the appropriate cross-reference file. If possible, the machine-
system.22,23 The plan should address readable identification should also be used to ensure that
medication supplies are not expired or in immediate danger
• Conformance with industry and government standards of expiring.28 If a hospital utilizes BCMA, all medications
as well as accepted practice standards, present in an automated dispensing device must be encoded
• Potential sources of medication errors and the proce- with a bar code that will appropriately identify them in the
dures to follow to avoid such errors, BCMA system.
• Limits on access to medications,24 The organization should have a written contingency
• How medications will be packaged and labeled, in- plan for maintaining timely medication distribution, secu-
cluding standardizing and limiting available concen- rity, and documentation when system interruptions occur.
trations, A profile interface in which all medication order infor-
• How medications will be safely and securely trans- mation is sent from the pharmacy information system to the
ported from the pharmacy to the automated dispensing automated dispensing device should be present whenever
device, 24/7 pharmacy order entry is available. (For facilities that
• The use of clinical alerts for high-risk medications, do not have 24/7 pharmacy order entry, a profile interface
• How medications will be transported from the auto- should be employed whenever feasible.) A profile interface
mated dispensing device to the patient to reduce risk is important for patient safety because it requires that a phar-
of administration to the wrong patient or at the wrong macist review medication orders before the caregiver can ac-
time,16 cess the medication from the automated dispensing device.
• How patient and medication information will be Profiling functionality should include
available and displayed while maintaining patient pri-
vacy,16 • Transmission of all components of medication and
• How user privacy, security, and safety will be en- i.v. orders, including drug, dose and/or infusion rate,
sured, route, frequency, dosing schedule, and order start/stop
• Procedures for ensuring the security of all stored medi- times,
cations, especially controlled substances, with a proc- • Ensuring that all patient care areas use the profiling
ess in place to prevent and detect diversion,25,26 functionality, including ambulatory and outpatient ar-
• Procedures for auditing all system transactions, eas such as the emergency department, whenever pos-
• Procedures for avoiding drug product cross-contamination sible,
(evident or trace amounts of a liquid or solid drug that • Limiting the variety and quantity of medications that
may contaminate another drug or package), are accessible without pharmacist review (override),
• Procedures for identifying and removing medications and
prior to expiration, and • The option to require a double-check (witness) at the
• Procedures for reporting malfunction or breakdown of time of dispensing of an identified high-alert medica-
the automated dispensing device. tion from automated devices, especially when pharma-
cist review and order entry have not occurred.16
The organization should have a written plan for ensuring the
accuracy of (1) medications stored and accessed through an The organization should include a process for comparing pa-
automated pharmacy system and (2) machine-readable iden- tient allergies with the current medication profile. Automated
tification on medication labels. This plan should provide devices should receive coded allergy information from the
pharmacy or hospital information system, which would al-
• A thorough review of the automated pharmacy system low an alert to be displayed when a medication to which a
to identify potential sources of error that may be intro- patient is allergic is dispensed.
duced by the system,
• Policies and procedures designed to preclude errors, Monitoring and Surveillance
and
• A quality-assurance program for reviewing override Pharmacists are legally and organizationally responsible for
data and medication error data associated with the au- ensuring that drug supplies are adequately controlled and
tomated dispensing device and identifying opportuni- that medication use is documented within the health care
ties for improvement, including a process for validat- organization. Automated pharmacy systems usually pro-
ing any medications that have been designated as high vide options for tracking and accounting for medication use,
risk via machine-readable coding on removal. which can be used to help monitor important data, such as
the number of adverse drug events.29,30 These options often
Any organization that allows external suppliers to replenish include freestanding computer-controlled access and record
medications in the automated pharmacy system should have keeping for each device, computer-controlled access and
a written plan for ensuring medication accuracy.27 When pos- record keeping linked to the pharmacy information system,
sible, this plan should include the use of machine-readable and computer linking among the pharmacy, patient record,
identification to ensure placement of medications in the ap- and billing information systems. Appropriate interfaces with
propriate containers within automated dispensing devices, pharmacy and overall patient care computer systems are
as well as recording that the proper filling was performed. critical. Each of these options may require a different level
To support this, processes must be in place to ensure that of oversight.
The organization should have a written plan for the or special preparation or storage requirements, present
monitoring and surveillance of medications accessed through cross-contamination risks, or are hazardous),
automated pharmacy systems. The plan should be developed • The need for ongoing monitoring and optimization of
by the pharmacy, with input from nursing staff and other cli- the contents of the automated dispensing device by
nicians, and communicated to staff members responsible for a pharmacist, taking into consideration such matters
its implementation. The plan should include18,25,26,31 as evolving therapeutic trends, the differing needs of
individual patient care areas, and the capabilities and
• Identification of the data to be captured and the reports safety features of the automated pharmacy system,17
to be generated for monitoring medication use, waste • Oversight of the positioning of look-alike and sound-
reconciliation, and discrepancies (data and reports alike drugs, high-alert drugs, and drugs with multiple
may vary by drug categories and requirements for con- strengths throughout the automated dispensing de-
trol and accountability), vice as well as procedures to minimize the incorrect
• Assignment of responsibility for reviewing reports, restocking of these medications (e.g., keeping these
scheduling the frequency of report reviews, and re- items as far apart as possible),
porting discrepancies, • Procedures to prevent and/or minimize the return of
drugs directly to the automated dispensing device by
• Assignment of responsibility for resolving discrepan-
cies, scheduling the resolution of discrepancies, fol- nursing staff to decrease the potential for error,
lowing up on unresolved discrepancies, and taking • Specification of the individual(s) responsible for add-
action if the discrepancy is not resolved on schedule, ing, modifying, or reviewing formulary items on a
regular and ongoing basis to ensure they correctly dis-
• A description of the process for investigating trends
play and interface map. Tall-man lettering, standard-
in discrepancies and assigning responsibility for con-
ducting the investigation, ized concentration displays, and form designations are
just a few of the many items that need to be maintained
• Appropriate access by personnel, including timely re-
for safety,
moval of access when no longer employed or creden-
tialed by the facility, • Procedures for keeping policies, procedures, and edu-
cation current,
• Determination of frequency of narcotic counts, who
• Policies addressing drug product integrity, including
will perform them, and who is responsible for verify-
ing that the narcotic counts were completed, • The importance of accuracy and integrity of
product labels,
• Examination of charge and credit flow to ensure bill-
• How to handle medications that are removed
ing accuracy, and
from an automated dispensing device but not
• Assignment of reviewing overrides to ensure the
used,
function is being used appropriately.
• How medication waste is accounted for,
Compliance with the plan should be monitored through the
• Checking products for expiration and beyond-
use dates,
organization’s quality-assurance program.
• Identifying and following up on tampered prod-
ucts,
Storage and Inventory • Storing products, and
• Procedures for delivering medications to patient
The drawer, bin, and pocket configurations of automated care units and individual patients.
dispensing devices vary depending on device design and • Controls that ensure accurate restocking of automated
hospital preferences. Open matrix drawers, pockets that dispensing devices, such as
open or light up for a specific drug, and multiple open bins • Access controls on drawers, bins, and pockets,
within a cabinet door are just a few of many different con- including software restrictions and use of loca-
figurations available from various vendors. The pharmacy tion lights and/or locking bin or pocket systems
should develop criteria for determining the drug products that support safe access,
and quantities that will be stored under different levels of • Process redundancies to ensure correct restock-
access control in specific configurations of drawers, pock- ing,16
ets, or bins. Patient safety should be the primary concern in • Standardization of16restocking procedures to limit
establishing these criteria. The criteria should address process variation, and
• When the system permits, use of bar coding to
restock the correct medication in the correct
• The frequency and appropriateness of individual med-
ication use, drawer, bin, or pocket, and
• The effective use of reports related to the safe, accu- • Controlling access to medications to limit the potential
rate, and timely withdrawal of medications available for inadvertent selection of the wrong medication, and
through the automated pharmacy system, assuring that each drug has a unique and segregated lo-
cation within the automated dispensing device so only
• The party responsible for medication safety oversight
the specific drug needed is accessible.16
and administrative control of drug availability in the
automated pharmacy system (e.g., the pharmacy and
therapeutics committee),16
• The identification of drug products that are considered Security and Responsibility
inappropriate for inclusion in automated dispensing
devices (e.g., products that have short expiration dates Among pharmacy’s responsibilities for the medication-use
process is preventing threats to patient and employee safety
and economic loss through medication misuse, pilferage, The organization should define the level of support that will
and diversion. be provided internally and ensure that staff are sufficiently
Any organization that uses an automated pharmacy educated to deliver the defined level of internal support. The
system should have a written plan that assigns responsibility organization will need to negotiate with the vendor the pur-
for and addresses issues of security. The plan should be de- chase of spare parts needed to optimally recover from me-
veloped by the pharmacy, with input from nursing, medicine, chanical failures.
and other disciplines that may be affected by the system. The
plan should clearly identify that the pharmacist in charge has Conclusion
general responsibility for the automated pharmacy system.
The plan should specify who in the pharmacy and elsewhere Automated dispensing devices are increasingly being used
in the organization has responsibility for computer interface in health systems for centralized filling of individual patient
issues; operational problems; the accuracy of medications prescriptions and unit-dose medication orders, decentralized
contained in the system; maintenance of access codes, mag- dispensing, and other purposes. When such devices and the
netic cards, and other positive identification methods; and systems that support them are not used appropriately, their
education of users and the determination of skill levels those complexity, design and function variations, maintenance and
individuals must achieve. education requirements, and other factors can compromise
The specific responsibilities and privileges of all per- patient safety and have other harmful effects. ASHP sup-
sonnel involved in operating or using the automated phar- ports the appropriate use of automated dispensing devices
macy system should be set forth in written policies and pro- and has developed these guidelines to provide recommenda-
cedures. The policies and procedures should minimize the use tions to pharmacists and others involved in their use.
of temporary user and patient identifications and should de-
scribe the circumstances in which these features may be used. References
Downtime procedures in case of software or hard-
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affecting normal operations should be developed to ensure medication-management systems. Am J Hosp Pharm.
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systems. Health Devices. 1996; 25:436–73.
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tomated point-of-use drug distribution system. Hosp
Automated pharmacy systems bring together information Pharm. 1995; 30: 18, 20–3, 27–30.
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the risks associated with the use and foreseeable misuse of activities before and after implementation of an auto-
automated pharmacy systems.16 The organization should mated dispensing system. Am J Health-Syst Pharm.
1996; 53:548–54.
• Have procedures in place for ensuring that all staff 6. Schwarz HO, Brodowy BA. Implementation and
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receive adequate education, both initially and on an Health-Syst Pharm. 1995; 52:823–8.
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• Ensure that adequate resources are provided for effec- of a closed-loop electronic prescribing and administra-
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• Ensure that the content of the education programs is rors and staff time: a before-and-after study. Qual Saf
continually updated, Health Care. 2007; 16:279–84.
• Evaluate staff members to ensure competency in the 8. Gaunt MJ, Johnston J, Davis MM. Automated dispens-
use of the automated pharmacy system and document ing cabinets. Don’t assume they’re safe; correct design
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• Share with staff members the lessons learned from 9. Crane J, Crane FG. Preventing medication errors in
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ing technologies on medication errors and adverse drug
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service level agreement with the vendor that meets the or- Pharm. 1995; 52:2445–7.
ganization’s minimal acceptable downtime requirements.
13. Tribble DA. How automated systems can (and do) fail. on an analysis of atypical drug transactions. Anesth
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14. National Association of Boards of Pharmacy. Model 27. Louie C, Brethauer B, Dong D et al. Use of a drug
State Pharmacy Act. Article 1, section 105(h), p. 3. wholesaler to process refills for automated medication
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doc (accessed 2009 Mar 18). 28. ASHP 2015 Initiative, Objective 5.1. www.ashp.
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FINAL.doc (accessed 2009 Mar 18). event reports collected using an automated dispensing
16. Institute for Safe Medication Practices (ISMP). ISMP system. Am J Health-Syst Pharm. 2005; 62:1375–80.
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18. Kowiatek JG, Weber RJ, Skledar SJ et al. Assessing
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Developed through the ASHP Section of Pharmacy Informatics
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and Technology and approved by the ASHP Board of Directors on
32:309–17.
July 21, 2009. These guidelines supersede the ASHP Guidelines on
19. Kester K, Baxter J, Freudenthal K. Errors associated
the Safe Use of Automated Medication Storage and Distribution
with medications removed from automated dispensing
Devices dated April 22, 1998.
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41:535–7.
A work group of the ASHP Section of Pharmacy Informatics and
20. Oren E, Griffiths L, Guglielmo J. Characteristics of
Technology 2008–2009 Section Advisory Group on Automation
antimicrobial overrides associated with automated
and Documentation (Leslie Brookins, M.S.; Ron Burnette,
dispensing machines. Am J Health-Syst Pharm. 2002; M.B.A.; Thomas W. Cooley, M.B.A.; Paul M. Seelinger,
59:1445–8. B.S.Pharm.; and Gwen Volpe, B.S.Pharm.) is gratefully acknowl-
21. Health Level 7 (HL7). HL7 standards. www.hl7.org/ edged for revising these guidelines. Other members of the sec-
Library/standards.cfm (accessed 2009 Mar 19). tion advisory group included Christopher J. Urbanski, M.S.,
22. Novek J, Bettess S, Burke K et al. Nurses’ perceptions Chair; Arash T. Dabestani, Pharm.D., M.H.A., FABC, Vice
of the reliability of an automated medication dispens- Chair; Jim Besier, Ph.D., FASHP; Kimberly Dove, Pharm.D.;
ing system. J Nurs Care Qual. 2000; 14:1–13. Craig P. Frost, M.B.A.; Rick K. Glabach, B.S.Pharm.; Gary
23. Rebidas D, Smith ST, Denomme P. Redesigning medi- L. Johnson, Jr., Pharm.D., M.H.A.; Denise Mckenzie; Brad
cation distribution systems in the OR. AORN J. 1999; Rognrud, M.S.; Charles De la Torre, M.S., M.I.S.; Rayburn Brian
69:184–6,188,190. Vrabel, Pharm.D.; Matt Marshall, Pharm.D.; Marvin H. Choi
24. Botwin KJ, Chan J, Jacobs R et al. Restricted access (Student Member); Dennis A. Tribble, Pharm.D. (Executive
to automated dispensing machines for surgical antimi- Committee Liaison); and Karl Gumpper, Pharm.D., BCNSP, BCPS.
crobial prophylaxis. Am J Health-Syst Pharm. 2001;
58:797–9. Copyright © 2010, American Society of Health-System Pharmacists,
25. Vigoda MM, Gencorelli FJ, Lubarsky DA. Discrep- Inc. All rights reserved.
ancies in medication entries between anesthetic and
pharmacy records using electronic databases. Anesth The bibliographic citation for this document is as follows: American
Analg. 2007; 105:1061–5. Society of Health-System Pharmacists. ASHP guidelines on the safe
26. Epstein RH, Gratch DM, Grunwald Z. Development of use of automated dispensing devices. Am J Health-Syst Pharm.
a scheduled drug diversion surveillance system based 2010; 67:483–90.
70 Drug Distribution and Control–Positions

Redistribution of Unused Medications (0611) Pharmacy Drug Theft (0303)
Source: Council on Legal and Public Affairs Source: House of Delegates Resolution
To advocate that any program for the return and reuse of To support the development of policies and guidelines
medications comply with all federal and state laws (includ- for health-system pharmacists designed to deter drug
ing laws regarding controlled substances); further, product theft and thereby enhance both the integrity of
To advocate that in order to ensure patient safety and the drug distribution chain and the safety of the work-
provide an equal standard of care for all patients, such a pro- place; further,
gram should include the following elements: (1) compliance To encourage the development of systems that limit
with practice standards, accreditation standards, and laws the diversion and abuse potential of medications, includ-
related to prescription dispensing; (2) a requirement that ing high-cost drugs and controlled substances, and thereby
these medications must not have been out of the possession reduce the likelihood that these products will be targets of
of a licensed health care professional or his or her desig- theft.
nee; (3) protection of the privacy of the patient for whom the This policy was reviewed in 2013 by the Council on
prescription was originally dispensed; (4) inclusion of only Pharmacy Management and by the Board of Directors and
those drug products that are in their original sealed packag- was found to still be appropriate.
ing or in pharmacy-prepared unit-of-use packaging that is
not expired and has been properly stored; (5) the presence Pharmacist’s Role in Drug Procurement, Distribution,
of a system for identifying medications for the purpose of a Surveillance, and Control (0232)
drug recall or market withdrawal; (6) a definition of patient Source: Council on Professional Affairs
eligibility for participation in the program; and (7) adequate To affirm the pharmacist’s expertise and responsibility in the
compensation of participating pharmacists for any associ- procurement, distribution, surveillance, and control of all
ated costs. drugs used within health systems; further,
This policy was reviewed in 2010 by the Council on To encourage the Joint Commission on Accreditation
Public Policy and by the Board of Directors and was found of Healthcare Organizations, other accreditation bodies, and
to still be appropriate. governmental entities to enhance patient safety by support-
ing the pharmacist’s role in drug procurement, distribution,
Pharmaceutical Counterfeiting (0401) surveillance, and control.
Source: Council on Professional Affairs (Note: For purposes of this policy, drugs include those
To foster increased pharmacist and public awareness of drug used by inpatients and outpatients, large- and small-volume
product counterfeiting; further, injectables, radiopharmaceuticals, diagnostic agents includ-
To encourage pharmacists to purchase and handle ing radiopaque contrast media, anesthetic gases, blood-fraction
medications in ways that enhance the transparency and in- drugs, dialysis fluids, respiratory therapy drugs, biotechno-
tegrity of the drug product supply chain; further, logically produced drugs, investigational drugs, drug samples,
To encourage pharmacists to identify instances of drugs brought to the setting by patients or family, and other
drug product counterfeiting and to respond by assisting the chemicals and biological substances administered to patients
patient in receiving appropriate treatment and monitoring, to evoke or enhance pharmacologic responses.)
documenting patient outcomes, and notifying the patient, This policy was reviewed in 2011 by the Council on
prescriber, and appropriate state and federal regulatory bod- Pharmacy Practice and by the Board of Directors and was
ies (e.g., the Food and Drug Administration’s MedWatch found to still be appropriate.
system); further,
To provide consumers and health professionals with Optimizing the Medication-Use Process (9903)
information on how to avoid counterfeit drug products and Source: Council on Administrative Affairs
how to recognize, respond to, and report encounters with To urge health-system pharmacists to assume leadership, re-
suspicious drug products; further, sponsibility, and accountability for the quality, effectiveness,
To foster research and education on the extent, meth- and efficiency of the entire medication-use process (includ-
ods, and impact of drug product counterfeiting and on ing prescribing, dispensing, administration, monitoring, and
strategies for preventing and responding to drug product education) across the continuum of care; further,
counterfeiting. To urge health-system pharmacists to work in collab-
This policy was reviewed in 2013 by the Council on oration with patients, prescribers, nurses, and other health
Pharmacy Practice and by the Board of Directors and was care providers in improving the medication-use process.
found to still be appropriate. This policy was reviewed in 2013 by the Council on
Pharmacy Management and by the Board of Directors and
was found to still be appropriate.
Drug Distribution and Control: Procurement–Guidelines 71
ASHP Guidelines on Managing Drug Product

Shortages in Hospitals and Health Systems
Purpose follow contribute to disruptions in the availability of drug
products.
Drug product shortages can adversely affect drug therapy,
compromise or delay medical procedures, and result in med- Raw and Bulk Material Unavailability. Disruptions in the
ication errors.1,2 Health care professionals are increasingly supply of raw or bulk materials are especially problematic
concerned about the clinical effect that shortages have on when the primary or sole source experiences production
patients and the tremendous resources required to address difficulties or discontinues production, affecting multiple
shortages.3–5 Adverse patient outcomes related to drug prod- manufacturers. An estimated 80% of the raw materials used
uct shortages1,2,6–9 have prompted aggressive management in pharmaceuticals comes from outside the United States.4
strategies by health care providers and gained the attention Availability problems can arise when armed conflict or po-
of the Joint Commission,10 the government,11,12 and the litical upheaval disrupts trade, animal diseases contaminate
media.13,14 Drug product shortages adversely affect health- tissue from which raw materials are extracted, climatic and
system finances by increasing the cost of delivering patient other environmental conditions depress the growth of plants
care, largely through higher drug acquisition and personnel used to produce raw materials, or raw materials are degraded
costs.6 In addition, shortages create a high level of frustra- or contaminated during harvesting, storage, or transport.
tion for everyone involved, including purchasing agents,
pharmacists, nurses, physicians, and patients.7 Manufacturing Difficulties and Regulatory Issues. Drug
Managing drug product shortages is particularly com- product shortages can also occur when the primary or sole
plex for practitioners in hospitals and health systems (here- manufacturer of a drug product halts or delays production
inafter, “health systems”), because these facilities routinely in response to a Food and Drug Administration (FDA) en-
treat patients with acute or emergent conditions, use a signif- forcement action concerning noncompliance with current
icant number of medically necessary or single-source prod- good manufacturing practices (cGMPs). Contributing fac-
ucts, and use high-cost new drug technologies. These health tors may include antiquated manufacturing equipment, a
care providers are challenged during drug product shortages shift of resources from maintenance of equipment and fa-
to ensure the provision of seamless, safe, and therapeutically cilities to research and development, loss of manufacturer
equivalent drug therapy, preferably at comparable costs. personnel experienced in production and compliance issues
The pharmacy department must take a leadership role in ef- as a result of company mergers or retirements, cGMP-re-
forts to develop and implement appropriate strategies and lated problems with subcontractors who supply products to
processes for informing practitioners of shortages and en- multiple pharmaceutical manufacturers, and limited FDA
suring the safe and effective use of therapeutic alternatives. resources for timely inspections of manufacturing sites.4
Strategic planning is required for managing drug product Resolution of these issues is often a lengthy process and
shortages, just as it is for disasters such as major weather may include inspections to ascertain cGMP compliance, is-
events and mass-casualty incidents. suance of an injunction against the manufacturer, or seizure
Because a thorough understanding of why drug prod- of products. In some instances, a manufacturer’s decision
uct shortages occur is essential for their successful manage- to close a specific manufacturing facility results in unin-
ment, these guidelines begin with a description of factors tended drug product shortages. Such was the case when the
that contribute to or exacerbate shortages. The guidelines sole source for hyaluronidase production closed, leaving no
then describe a three-phase approach to contingency plan- supplier.5
ning for management of drug product shortages and include FDA enforcement actions are intended to protect the
strategies for prevention. Given the differences and com- public from potentially unsafe drug products. These actions
plexities in health-system organizational arrangements and are evaluated by FDA’s Center for Drug Evaluation and
practice settings, some aspects of these guidelines may not Research (CDER) drug shortage coordinator to determine if
be applicable in all settings. Pharmacy managers should use the action might create a shortage of a medically necessary
their professional judgment in assessing and adapting these drug product.12 (FDA’s definition of a medically necessary
guidelines to meet their needs. product is discussed in the “Government intervention” sec-
tion below.) In the event that a significant corrective action
involves a medically necessary product, FDA will help the
Contributing Factors manufacturer return to compliance, consider qualifying ad-
ditional manufacturing sites, or, in extreme circumstances,
For the purpose of these guidelines, a drug product short- permit importation of the product from a foreign manufac-
age is defined as a supply issue that affects how the phar- turing source once the required quality controls are met.
macy prepares or dispenses a drug product or influences
patient care when prescribers must use an alternative agent.
Shortages can be the result of one or a combination of fac- Voluntary Recalls. Voluntary recalls, generally related to
tors throughout the supply chain. The supply chain includes manufacturing problems, can cause shortages, especially
sources of raw materials, manufacturers, regulators, whole- when a sole manufacturer’s drug product dominates the mar-
salers or distributors, prime vendors, group purchasing orga- ket supply. Voluntary recalls are generally temporary and oc-
nizations, and end-user health care systems. The factors that cur as a result of a minor lapse in manufacturing procedures
72 Drug Distribution and Control: Procurement–Guidelines
that would not be subject to FDA legal action. Recalls usu- limit the availability of specific drug products. Only selected
ally affect specific lots and are conducted either because of suppliers and end users who comply with manufacturer
a lack of assurance that the recalled product is safe or for agreements can obtain the product. A manufacturer can also
reasons not related to safety, such as technical deficiencies in place restrictions on available limited supplies, requiring
the drug’s labeling. An ethical dilemma could arise when it health systems to order directly from the manufacturer or
is predictable that complying with the voluntary recall may through a specialty distributor to receive an allocation.
cause a drug product shortage in a given health system.
Inventory Practices. Communication and transportation ef-
Change in Product Formulation or Manufacturer. Changes ficiencies throughout the supply chain have allowed inven-
in a product’s formulation or manufacturer may also delay tory reductions at all levels. Most manufacturers, distribu-
product availability. One example is the transition from al- tion centers, and health systems use “just-in-time” inventory
buterol metered-dose inhalers (MDIs) containing chlorofluo- management to reduce the cost of inventory on hand and op-
rocarbons to MDIs containing hydro-fluoroalkanes in 2006. timize cash flow. This strategy is recognized as sound busi-
ness management for all stakeholders, but an unexpected
Manufacturers’ Production Decisions and Economics. shortage at any point in the supply chain can significantly
Manufacturers’ business decisions are based on a variety affect the end user and patient. Some manufacturers and dis-
of factors, including availability of generic products, mar- tributors use inventory management strategies that minimize
ket size, patent expiration, drug-approval status, regulatory end-of-quarter or end-of-year product inventories or limit
compliance requirements, and anticipated clinical demand. shipments based on yearly quotas.
Occasionally, manufacturers temporarily or permanently Poor ordering practices, stockpiling before price in-
reduce production quantities of certain drug products as creases, hoarding caused by rumors of an impending short-
they shift production efforts or reallocate resources to other age, and unexpected delivery delays may affect inventory
products. A manufacturer’s reasoned, sound business deci- levels in individual health systems. Hospitals in rural areas
sion to discontinue production of a drug product because of face additional inventory challenges caused by distant dis-
insufficient financial return or a high cost to correct manu- tribution centers and the inability to easily borrow an item
facturing issues can cause an unanticipated, serious shortage, from a nearby hospital. Drug product shortages may also oc-
especially in the instance of a sole-source or medically nec- cur when all hospitals in an area disproportionately use the
essary product.15 For example, a shortage of diphtheria and same wholesaler. Some shortages are wholesaler dependent,
tetanus toxoids and acellular pertussis vaccine adsorbed was as shortages of drugs can occur when contracts with suppli-
precipitated when one of the manufacturers, claiming low ers are delayed.
revenues, discontinued its product in 2000.5 Manufacturers
are not required to notify FDA of a drug discontinuation un- Unexpected Increases in Demand and Shifts in Clinical
less the product is a sole-source or medically necessary prod- Practice. Occasionally, the demand for a drug product un-
uct.16 For medically necessary drugs, FDA can encourage expectedly increases or exceeds production capacity. This
other manufacturers to produce the product or request that may occur when a new indication is approved for an exist-
the manufacturer not suspend production until an alternative ing drug product, when usage patterns change in response to
source is available. However, FDA does not have the author- new therapeutic guidelines, when a substantial disease out-
ity to require a company to make any product, even if it is break occurs, or when unpredictable factors influence de-
medically necessary. Even with advance notice, some agents, mand. Shortages may be prolonged when the raw materials
such as vaccines or antibiotics, are complex to manufacture, are limited or manufacturing processes are complex or de-
and shortages may result even if other manufacturers are pendent on a long lead time. For example, when the Centers
willing and able to produce the product. Similarly, business for Disease Control and Prevention (CDC) recommended
decisions on the part of wholesale distributors and end-user annual influenza vaccination for children age 6–59 months
health systems may contribute to drug product shortages. in 2006, only one product had FDA-approved labeling for
use in children 6–23 months old.17,18
Industry Consolidations. Manufacturer mergers often result
in decisions to narrow the focus of product lines or move Nontraditional Distributors. The increased frequency of
a production line to a new facility, resulting in the discon- drug product shortages has precipitated the development of
tinuation or delayed availability of drug products. Mergers nontraditional distributors, also known as open-market, gray-
between two companies that manufacture similar product market, or alternative distributors. These specialty, licensed
lines typically result in single-source products. As the num- distributors or brokers obtain products in short supply for
ber of manufacturers of a product decreases, resiliency in the purpose of reselling them to end users who are unable to
the supply chain also decreases, making product supplies obtain them through their normal suppliers. These distribu-
more vulnerable. Many vaccines in the United States are tors aggressively market the availability of these products to
single-source products, in part because of discontinuations hospitals, specialty health systems, home care agencies, and
and consolidations. physician practices, generally at substantially higher prices.
Typically, these distributors have a limited quantity of prod-
Restricted Drug Product Distribution And Allocation. Most uct, often only enough for one or two patients. Many do not
hospitals and health systems obtain the majority of their offer a return or refund on a product if it expires or is not
drug products through wholesale distributors. Restricted dis- used. Especially worrisome is the inability to ascertain the
tribution methods that bypass the normal supply chain can product’s pedigree or ensure the reliability of the product’s
also create shortages. As the result of either market approval source, which could be outside the United States, and proper
requirements or postmarketing surveillance, manufacturers handling and storage throughout the chain of custody. The
extent to which the activities of such nontraditional distribu- In an ideal world, there would be a system for warning
tors contribute to drug product shortages is unknown. providers in advance of impending drug product shortages;
Compounding pharmacies have also pursued the pro- this would give them ample opportunity to proactively ad-
duction of drugs that are in short supply. Caution is war- dress and manage all aspects and implications of the short-
ranted because preparations from these pharmacies may not age. In lieu of this ideal, pharmacists, when confronted with
meet applicable state or federal standards (e.g., United States the unavailability of a drug product, want information on
Pharmacopeia chapter 797 or FDA labeling requirements). which to base decisions about meeting patient needs for the
The sources of raw materials used by compounding pharma- product. Segments of the supply chain, especially manufac-
cies have been questioned, and apparent lapses in quality con- turers and distributors, have been inconsistent in providing
trol have resulted in serious patient injury, including death.13 information and assistance to health systems. The difficulty
in obtaining information is exacerbated by the many players,
Natural Disasters. Natural disasters can have a profound ef- complexities, and uncertainties in the supply chain.
fect on the availability of drug products. Damage to manu- The pharmacy department must take a leadership role
facturing facilities, particularly those that are the sole source in managing shortages by developing and implementing
of a drug product or category of products, is likely to cause appropriate strategies and processes for optimizing the safe
long-term shortages. Damage
to manufacturing facilities in
Puerto Rico in 1998 from hur-
ricane George caused shortages Figure 1. Process for decision-making in the management of drug product shortages.
of several drug products. Fires,
hurricanes, tornadoes, and floods
are examples of natural disasters Drug shortage identified
that may temporarily compromise
drug product supplies. In some
instances, these shortages may be
exacerbated by an escalated need
for certain classes of drug prod-
Operational assessment Therapeutic assessment
ucts to care for victims of the di-
1. Validate details of shortage 1. Identify primary patient
saster. In 2005, areas affected by 2. Determine stock on hand population affected
hurricanes Katrina and Rita were 3. Determine supply from 2. Identify therapeutic
affected by both an increased need predetermined alternative alternatives
for medications and the inability sources
4. Determine purchase history (May be done by pharmacists
to obtain them. and/or true use history or a multidisciplinary team)
5. Estimate time to impact on the
health system
Phased Approach 6. Determine supply of alternative
to Planning for Drug drug products
Product Shortages (Typically done by the pharmacy
department)
The discovery of a shortage initi-
ates a cascade of events surround-
ing drug procurement and thera-
peutic decision-making (Figure 1). Shortage impact analysis
Drug procurement considerations Estimate impact on patient care
include validating the shortage 1. Therapeutic differences
2. Prescribing processes
and its anticipated duration, deter-
3. Distribution processes
mining the availability of supplies 4. Administration processes
from alternative sources, locating 5. Financial ramifications
and procuring alternative supplies
(if available), investigating the (May be done by pharmacists or a
implications of compounding the multidisciplinary team)
product, and researching and pro-
viding education about alternative
agents and the cost implications of Establish final plan
all scenarios. The outcome of this
process may prompt an evaluation
of the shortage’s potential effect on
Communicate Implement
patient care and development of a 1. Shortage 1. Information system
strategy for effectively communi- 2. Effective date changes
cating the needed information to 3. Identified therapeutic 2. Technological changes
all professionals involved and to alternative (e.g., bar coding)
4. Temporary guidelines 3. Inventory system changes
affected patients when warranted. 5. Temporary procedures 4. New procedures
and effective use of therapeutic alternatives. Health sys- determine the health system’s ability to endure the shortage and
tems should develop a contingency planning strategy to guide its short- and long-term management strategies.
prepare for the possibility of a prolonged drug product Although the end result is the same, the time to impact
shortage.19 Although it often is not possible to predict when and the duration of effect vary according to the reason for
shortages will occur, the process for dealing with them can the shortage and where in the supply chain problems oc-
be defined in advance. The health system should identify cur—from raw materials to manufacturer, manufacturer to
a point person to implement and monitor this process and wholesaler, or wholesaler to health system. A lack of raw
establish an organizational approach to decision-making materials may affect several manufacturers of the finished
and communication. The institution should determine com- drug product. A manufacturer’s problems may affect only
mittee structures and responsibilities for decision-making its product. Effects on distributors are dependent on their
during each phase of the process (e.g., pharmacy and thera- inventory levels.
peutics committee, medical executive committee). Inventory on hand. Once a shortage is confirmed, the
Planning can be divided into three phases: identi- pharmacy should count the inventory on hand and estimate
fication and assessment, preparation, and contingency. the time period it will cover. Available inventory includes
Assessment requires a critical evaluation of the current situ- all supplies of the drug product within the health system,
ation and the potential effect of the shortage on the health including the pharmacies, inpatient units, ambulatory care
system. An effective evaluation examines the reason for the clinics, automated medication storage and distribution de-
shortage and estimates an end date; both internal and exter- vices, floor stock, resuscitation carts, and prepared trays.
nal supply availabilities are assessed. Based on available quantities and historical usage, the
The preparation phase consists of all activities that pharmacy should estimate how long the health system can
can be performed before the actual effects of the short- endure a shortage. Usage history can be obtained from pro-
age are felt. Depending on the health system’s inventory, curement and issue records held by distributors, the purchas-
when a back order or other notice is received, there is often ing department, and the pharmacy department. Billing and
lead-time before actual stock depletion. All patients whose automated medication storage and dispensing device records
treatment depends on the unavailable drug product and al- can assist in determining actual usage within the system.
ternative therapies should be identified. Since many drug Inventory counts of all alternative drug products should
products have limited therapeutic alternatives, outages can be converted into common measurement units to augment es-
have significant patient care and cost consequences. Health timates of use. Both current use rates and reduced rates after
systems need to gauge the effect of those consequences on conservation measures are implemented should be included
their institutions. Preparation should also include the devel- when assessing how long the available inventory of the short-
opment of methods for implementation and communication. age drug product and possible alternative products will last.
The contingency phase involves operations and cir- Threat to patient care and costs. A threat analysis eval-
cumstances for which preparation is limited because of uates all factors relevant to the shortage (e.g., duration, cur-
incomplete information, financial constraints, or circum- rent inventory, medical necessity, alternative sources or ther-
stances beyond the health system’s control. For example, apies) to determine the shortage’s potential effect on patient
biological products are available only in increments and at care and costs. Shortages affect safe medication practices
a very high cost when no therapeutic alternatives are read- throughout the medication distribution and administration
ily available or when shortages are longer than anticipated. process within a health system. When considering alterna-
Since direct control over availability is not possible, health tive dosage forms or therapies, pharmacists must consider
systems must prepare for a product’s unavailability. changes in their procedures for look-alike and sound-alike
medications, bar coding, distribution paths, and the effect on
Identification and Assessment Phase. The purchasing agent automation, contract compliance, and final product prepara-
is often the person who identifies a shortage and may be the tion.20 The extent to which a health system will be affected
person responsible for managing drug product shortages. by a given shortage depends on the health system’s scope
This person must be cognizant of aberrant fluctuations in the and level of services and its service population.
health system’s supply chain that may indicate a potential
shortage (e.g., partial orders filled, one strength difficult to Preparation Phase. Once an imminent shortage is con-
obtain, most manufacturers have no more stock). If the pur- firmed, the health system should take steps to prepare for
chasing agent is not a pharmacist, he or she must work with known and potential problems in maintaining patient care
a designated pharmacist. and controlling costs.
When a shortage is identified, the point person or his Therapeutic alternatives. The first step in the prepa-
or her designee should conduct an assessment to evaluate ration phase is to identify therapeutic alternatives to the
its potential effect. A threat analysis using the shortage’s ex- unavailable drug product. A formal process for identifying
pected duration and an assessment of the current inventory and approving therapeutic alternatives for the health system
and usage patterns can be used to determine the potential should be established. The health system should make deci-
consequences of the shortage. sions about alternative agents in collaboration with medical,
Details and duration of shortage. Pharmacists can con- nursing, and pharmacy representatives and obtain approval
tact product manufacturers, distributors, FDA, CDC, and other of the appropriate medical committees. Therapeutic alterna-
sources to determine the reason for the shortage and its ex- tives should be inventoried to ensure adequate supplies to
pected duration. This information may already be available on meet new demand. In many cases, supplies of the best alter-
the ASHP Drug Shortage Resource Center Web site (www.ashp. native agent may be affected by the current shortage.
org/shortages). If not, visitors to the site can report a shortage Communication and patient safety. Information about
online. Predictions of when the product will be available help the drug product shortage, alternative therapies, temporary
therapeutic guidelines, and implementation plans should be may arise that pose threats to, but do not reach, end users.
communicated to clinical staff by the most effective means This happens when the supply chain, from raw material to
available within the health system. Communication of this finished product, contains several months’ supply; the long
information is essential for ensuring patient safety and pre- lead-time allows corrections that avert a shortage.
venting medication errors caused by confusion over differ- During shortages, manufacturers and distributors of-
ences between drug products’ dosages, onsets, durations, ten allocate a product on the basis of past usage. An initial
and other factors. Automated systems and order-entry sys- stockpile order generally has no effect on increasing an al-
tems must be updated with changes. Pharmacy department location.
staff responsible for assisting prescribers with medication
orders and aiding nursing staff with administration should Contingency Phase. Health systems must establish clear
be thoroughly informed about the alternative therapy deci- guidelines for dealing with situations in which a product is
sions and implementation plans. Sustained communication available only from a compounding source or nontraditional
is necessary to reach medical, nursing, and pharmacy staffs source or when a critical drug is not available at all.
working varied shifts or services. Risk management and liability. One potential compli-
External relationships with other health systems. The cation of a shortage is litigation by patients who feel that
preparation phase includes, when applicable, the establish- they have received improper care or suffered unanticipated
ment of collaborative arrangements with other institutions adverse drug events as a result of delays, prioritization, al-
within a regional network or system. Available supplies of a ternative therapy, or nontraditional drug product sources.
potentially unavailable product and information about alter- This situation is most likely with agents for which no al-
native therapies should be shared among the facilities. This ternatives are available. Even though risk management and
option is limited for rural hospitals and for area hospitals legal representatives may have participated in earlier phases
served by a single wholesaler. of the process, they should be notified immediately when all
Patient prioritization. When a limited supply of a drug options for obtaining either the drug product or acceptable
remains available and alternatives for specific patient groups alternatives have been exhausted.
are undesirable, a health system may prioritize the drug for Each health system must determine its philosophy
specific patient groups. National organizations (e.g., CDC, on purchasing drugs from the gray-market or compound-
medical organizations) may provide guidance on setting ing pharmacies and on compounding agents inhouse. These
patient priorities. Medication-use evaluation data on pre- decisions should be made before the pressure and emotion
scribing and utilization trends, if available for the drug in of a specific shortage occur. Each option and its potential
question, may be useful in developing prioritization criteria effect on patient risk should be evaluated. Nontraditional
to guide appropriate drug use. Such criteria are particularly drug product sources (e.g., secondary wholesalers) have ex-
helpful in dealing with long-term shortages such as with in- tremely limited supplies, and the quality of these products
travenous immunoglobulin. To limit product use for select may be questionable, as the provenance of the medication
patients or services in the health system, criteria should be may be unknown. Compounding pharmacies may also pres-
developed by a multidisciplinary team. Communication is ent patient risks; several deaths have been associated with
essential to ensure that adequate supplies are available to improperly sterilized compounded products.9 Health sys-
complete courses of therapy. Clear guidelines for prioritiza- tems may choose to compound products if they can meet the
tion must be provided to assist pharmacists in evaluating the necessary guidelines; however, obtaining raw materials may
appropriateness of medication orders. be difficult in some cases.
Consultation with risk management and ethics staff Budget considerations. In the event that the drug prod-
members or committees may be useful when supplies are uct is available only from noncontracted manufacturers or
severely limited. For example, during the influenza vaccine through nontraditional distributors, the increased costs of
shortage of 2004–05, many health systems did not have suf- using these sources should be estimated. Using alternative
ficient product to follow recommended CDC guidelines and therapies may also increase costs. The financial implications
further restricted use of the product to specific patient groups. should be presented through budget channels, with a request
Stockpiling restraint. Inventory management is a chal- and justification for contingency funds. Additional expendi-
lenge during a shortage. Despite pressure to do otherwise, tures caused by drug product shortages (e.g., overtime spent
stockpiling (hoarding) in advance of a feared shortage can in locating product, extra or priority deliveries, inhouse
occur; this can exacerbate the shortage and divert unneeded compounding or packaging) must be documented to explain
supplies away from other health systems with patients in budget variances and to support future budget proposals.
need.21 Health systems should refrain from stockpiling, Information coordination and communication. Clear
which causes two distinct problems: communication with all affected clinicians about the status
of a shortage is vital. Some health systems may designate a
1. Stockpiling can cause artificial shortages when health specific department to manage communications; others may
systems drain the supply chain and exceed manufac- find that a collaborative strategy involving various organiza-
turing capacities, and tional departments and committees works best. Patients or
2. Increased inventory is costly and may not be absorbed family members should be counseled when a drug product
by normal usage if shortages do not occur as antici- shortage will delay or compromise care, especially when pa-
pated. tients have been stabilized on the drug product and when
alternatives may not be as effective (e.g., pain or blood
Speculative purchasing in response to a potential short- pressure medications). The Joint Commission requires that
age has drawbacks, depending on the likely cause of the short- prescribers potentially affected by drug product shortages be
age and where it might occur in the supply chain. Problems actively alerted.10
Strategies for Prevention is impractical to prepare for every potential shortage, proper
planning can minimize adverse effects on patient care and
Communication with the media, national professional or health-system costs and prevent problems from escalating
patient organizations, and government agencies can raise into crises. The key to success will undoubtedly be found
awareness of the shortage and its potential consequences. in the effectiveness of information gathering, teamwork to
Notifying ASHP or FDA about a drug product shortage can assess options, and communication with providers, patients,
initiate these efforts. Drawing attention to the shortage may and administrators.
encourage production by other manufacturers, collaborative
efforts to develop alternative therapies, and ad hoc training References
opportunities on the safe and effective use of alternatives.
1. U.S. Pharmacopeia Center for the Advancement of
Patient Safety. Section I: USP medication error analy-
Government Intervention
sis; drug shortages affect patient safety. www.usp.org/
pdf/EN/patientSafety/capsLink2004-10-01.pdf (ac-
FDA is responsible for assisting with drug product short-
cessed 2008 Sep 17).
ages to the extent of its authority.11 Its responsibilities are
2. Institute for Safe Medication Practices. Safety
dispersed among several components of CDER. The extent
briefs: drug shortage causes error. www.bfr06.com/
of FDA’s activities depends on whether a shortage meets
ISMP_12_3.pdf (accessed 2009 Mar 23).
“medical necessity” criteria. FDA will attempt to prevent
3. Schwartz MA. Prescription drugs in short supply: case
or alleviate shortages of medically necessary products. A
histories. New York: Marcel Dekker; 1980.
product is considered to be medically necessary or a medical
4. Provisional observations on drug product shortages:
necessity if it “is used to treat or prevent a serious disease
effects, causes, and potential solutions. Am J Health-
or medical condition, and there is no other available source
Syst Pharm. 2002; 59:2173–82.
of that product or alternative drug that is judged by medical
5. Fox ER, Tyler LS. Managing drug shortages: seven
staff to be an adequate substitute.”12 Inconvenience to the
years’ experience at one health system. Am J Health-
patient and cost to the patient, institution, and manufacturer
Syst Pharm. 2003; 60:245–53.
are insufficient reasons for classifying a product as a medi-
6. Baumer AM, Clark AM, Witmer DR et al. National
cal necessity.
survey of the impact of drug shortages in acute care
A determination of medical necessity involves a risk–
hospitals. Am J Health-Syst Pharm. 2004; 61:2015–
benefit evaluation of the compromising issue with the prod-
22.
uct versus the medical need. When FDA has determined
7. Institute for Safe Medication Practices. National sur-
that a shortage of a medically necessary product exists, the
vey on drug shortages reveals high level of frustration,
agency will act within its authority; actions may include dis-
low regard for safety. www.ismp.org/Newsletters/
cussions with pharmaceutical manufacturers to encourage
acutecare/articles/20010321_2.asp (accessed 2009
additional sources, technical assistance to manufacturers ex-
Mar 23).
periencing cGMP difficulties, or expedited reviews of drug
8. Institute for Safe Medication Practices. Recent na-
product marketing applications or cGMP-related improve-
tional shortage of fentanyl products presents potential
ments. FDA may take these actions whether the cause of the
problems when substituting sufentanil. ISMP Med Saf
shortage involves business decisions to stop manufacturing
Alert. 2001; 6(Feb 7):1.
the product, voluntary recalls, FDA enforcement actions,
9. Traynor K. Meningitis deaths linked to drug shortages.
or other factors. Information on the availability of medi-
www.ashp.org/import/news/HealthSystemPharmacy
cally necessary drug products is posted on CDER’s web-
News/newsarticle.aspx?id=648 (accessed 2008 Sep
site, and information regarding the availability of blood and
17).
vaccine products regulated by FDA’s Center for Biologics
10. Element of performance 7, medication manage-
Evaluation and Research (CBER) is posted on CBER’s web-
ment standard 2.10 (selection and procurement). In:
site. FDA encourages consumers and health care profession-
Comprehensive acccreditation manual for hospitals.
als and organizations to report product shortages. Reports of
Oakbrook Terrace, IL: Joint Commission; 2007:MM-
drug product shortages can be made by e-mail via CDER’s
7.
Drug Shortages website (www.fda.gov/cder/drug/short-
11. Jensen V, Kimzey LM,Goldberger MJ. FDA’s role
ages/default.htm), and reports on vaccine and blood product
in responding to drug shortages. Am J Health-Syst
shortages via CBER’s Biological Products Shortage website
Pharm. 2002; 59:1423–5.
(www.fda.gov/cber/shortage/shortage.htm). FDA’s shortage
12. CDER manual of policies and procedures (MAPP)
team will obtain information about availability and will work
6003.1: drug shortage management. Rockville, MD:
cooperatively with ASHP’s drug product shortage team.
Food and Drug Administration; 2006.
13. Rubin AJ, Gosselin PG. Shortages of drugs threaten
Conclusion patients. http://articles.latimes.com/2001/may/06/
news/mn-60196 (accessed 2009 Mar 23).
Drug product supply issues are becoming more frequent, 14. Szabo L. Shortages of pediatric cancer drugs are com-
whether they result from manufacturing difficulties or natu- mon. www.usatoday.com/news/health/2005-07-19-
ral disasters that affect production, reductions in the supply cancer-drugs_x.htm (accessed 2009 Mar 23).
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decisions, FDA enforcement actions to ensure public safety, try profits elsewhere, U.S. lacks vaccines, antibiotics.
or stockpiling that leads to artificial shortages. Although it Wall St J. 2005; Nov 8:A1.
16. Food and Drug Administration. Federal Food, Drug, ASHP gratefully acknowledges the expert panel that developed
and Cosmetic Act, Sec. 506C (21 U.S.C. 356c). these guidelines: Erin R. Fox, Pharm.D.; Annette Birt, M.B.A.,
Discontinuance of a life-saving product. www.fda.gov/ M.P.H.; Ken B. James, Pharm.D.; Heather Kokko, Pharm.D.; Sandra
opacom/laws/fdcact/fdcact5a3.htm#sec506c (accessed Salverson, Pharm.D., BCPS; and Donna L. Soflin, B.S.Pharm.
2009 Mar 23).
17. Smith NM, Bresee JS, Shay DK et al. Prevention Erin R. Fox, Pharm.D., is Director, Drug Information Service,
and control of influenza: recommendations of the University of Utah Hospitals & Clinics, Salt Lake City. Annette
Advisory Committee on Immunization Practices Birt, M.B.A., M.P.H., is Pharmacy Communications Manager
(ACIP). MMWR Recomm Rep. 2006; 55(RR-10):1–42. at Novation, Irving, TX. Ken B. James, Pharm.D., is Supervisor,
[Erratum, MMWR. 2006; 55:800.] Drug Information Services, Kaiser-Permanente Medical Center,
18. FluZone (influenza vaccine) package insert. Santa Clara, CA. Heather Kokko, Pharm.D., is Manager, Pharmacy
Swiftwater, PA: Sanofi Pasteur; 2006. Support Services, Department of Pharmacy Services, and Clinical
19. Schrand LM, Troester TS, Ballas ZKet al. Preparing Assistant Professor, Medical University of South Carolina. Sandra
for drug shortages: one teaching hospital’s approach to Salverson, Pharm.D., BCPS, is Drug Information/Infectious
the IVIG shortage. Formulary. 2001; 36:52,56–9. Disease Pharmacist, OSF Saint Francis Medical Center, Peoria, IL.
20. Pick AM, Massoomi F, Neff WJet al. A safety assess- Donna L. Soflin is Pharmacy Director, Tri-County Area Hospital,
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21. Myers CE. Artificial shortages of drug supplies. Am J Copyright © 2009, American Society of Health-System Pharmacists.
Health-Syst Pharm. 1999; 56:727. Editorial. All rights reserved.

Society of Health-System Pharmacists. ASHP guidelines on manag-
Developed through the ASHP Council on Pharmacy Management ing drug product shortages in hospitals and health systems. Am J
and approved by the ASHP Board of Directors on January 15, 2009. Health-Syst Pharm. 2009; 66:1399–406.
These guidelines supersede the ASHP Guidelines on Managing
Drug Product Shortages dated March 28, 2001.
ASHP Guidelines for Selecting Pharmaceutical

Manufacturers and Suppliers
Pharmacists are responsible for selecting, from hundreds of 10. On request, the supplier should furnish proof of any
manufacturers and suppliers of drugs, those that will enable claims made with respect to the efficacy, safety, and
them to fulfill an important obligation: ensuring that patients superiority of its products.
receive pharmaceuticals and related supplies of the highest 11. On request, the supplier should furnish, at no charge, a
quality and at the lowest cost. These guidelines are offered reasonable quantity of its products to enable the phar-
as an aid to the pharmacist in achieving this goal. macist to evaluate the products’ physical traits, includ-
ing pharmaceutical elegance (appearance and absence
Obligations of the Supplier of physical deterioration or flaws), packaging, and
labeling.
Pharmacists may purchase with confidence the products of
those suppliers meeting the criteria presented here. Other Distribution Policies
factors such as credit policies, delivery times, and the
breadth of a supplier’s product line also must be considered 1. Whenever possible, delivery of a drug product should
when selecting a supplier. be confined to a single lot number.
2. Unless otherwise specified or required by stability
Technical Considerations considerations, not less than a 12-month interval be-
tween a product’s time of delivery and its expiration
1. On request of the pharmacist, the supplier should date should be present.
furnish 3. The supplier should accept for full credit (based
a. Analytical control data. on purchase price), without prior authorization,
b. Sterility testing data. any unopened packages of goods returned within
c. Bioavailability data. 12 months of the expiration date. Credits should be in
d. Bioequivalency data. cash or applied to the institution’s account.
e. Descriptions of testing procedures for raw mate- 4. The supplier should ship all goods in a timely manner,
rials and finished products. freight prepaid, and enclose a packing list with each
f. Any other information that may be indicative of shipment. All items “out of stock” should be noted,
the quality of a given finished drug product. and the anticipated availability of the item should be
Testing data developed by independent laboratories clearly indicated. There should be no extensive recur-
should be identified by the supplier. All information rence of back orders.
should be supplied at no charge. 5. The supplier should warrant title to commodities sup-
2. There should be no history of recurring product recalls plied, warrant them to be free from defects and imper-
indicative of deficient quality control procedures. fections and fit for any rational use of the product, and
3. The supplier should permit visits (during normal busi- indemnify and hold the purchaser harmless against
ness hours) by the pharmacist to inspect its manufac- any and all suits, claims, and expenses, includ-ing attor-
turing and control procedures. neys’ fees, damages, and injuries or any claims by third
4. All drug products should conform to the requirements parties relating to the products.
of The United States Pharmacopeia—The National
Formulary (USP—NF) (the most recent edition) un- Marketing and Sales Policies
less otherwise specified by the pharmacist. Items not
recognized by USP—NF should meet the specifica- 1. The supplier should not, without written consent, use
tions set forth by the pharmacist. the pharmacist’s or his or her organization’s name in any
5. To the extent possible, all products should be available in advertising or other promotional materials or activities.
single unit or unit dose packages. These packages should 2. The supplier should honor formulary decisions made by
conform to the “ASHP Technical Assistance Bulletin on the organization’s pharmacy and therapeutics committee,
Single Unit and Unit Dose Packages of Drugs.”1 and the supplier’s sales representatives should comply with
6. The name and address of the manufacturer of the final the organization’s regulations governing their activities.
dosage form and the packager or distributor should be 3. The supplier should not offer cash, equipment, or mer-
present on the product labeling. chandise to the organization or its staff as an induce-
7. Expiration dates should be clearly indicated on the ment to purchase its products.
package label and, unless stability properties warrant 4. Discounts should be in cash or cash credit, not mer-
otherwise, should occur in January or July. chandise, and should be clearly indicated on invoices
8. Therapeutic, biopharmaceutic, and toxicologic informa- and bills rather than consisting of end-of-year rebates
tion should be available to the pharmacist on request. or similar discount practices.
Toxicity information should be available around the clock. 5. In entering into a contract to supply goods, the supplier
9. Patient/staff educational materials that are important for should guarantee to furnish, at the price specified, any
proper use of the product should be routinely available. minimum amount of products so stated. If the supplier
is unable to meet the supply commitment, the supplier 7. The quantities specified in the invitation to bid should
should reimburse the organization for any excess costs be a reasonable estimate of requirements.
incurred in obtaining the product from other sources. 8. If the invitation to bid is offered on behalf of a group
If, during the life of the contract, a price reduction oc- of purchasers, the individual members of the group
curs, the lower price should prevail. should not engage in bidding procedures of their own
6. All parties to the bidding process should respect the in- and should purchase the goods in question from the
tegrity of the process and the contracts awarded thereby. winning bidder.
Responsibilities of the Purchaser Reference

It may be desirable to purchase drugs or other commodities on a 1. American Society of Hospital Pharmacists. ASHP
competitive bid basis. The pharmacist should ensure that com- technical assistance bulletin on single unit and unit
petitive bidding procedures conform to the guidelines below: dose packages of drugs. Am J Hosp Pharm. 1985;
42:378–9.
1. Invitations to bid should be mailed to the suppliers’
home offices with copies to their local representatives
(if any), unless suppliers specify otherwise. Approved by the ASHP Board of Directors, November 14, 1990.
2. Potential bidders should be given no less than 3 weeks Revised by the ASHP Council on Professional Affairs. Supersedes
to submit a bid. previous versions approved November 17–18, 1983, and September
3. The opening date for bids should be specified and hon- 22, 1989.
ored by the purchaser.
4. The language of the invitation to bid should be clear Copyright © 1991, American Society of Hospital Pharmacists, Inc.
and should indicate the person (and organization ad- All rights reserved.
dress and telephone number) the bidder should contact
in the event of questions or problems. Specifications The bibliographic citation for this document is as follows: American
should be complete with respect to products, packag- Society of Hospital Pharmacists. ASHP guidelines for selecting
ings, and quantities desired. pharmaceutical manufacturers and suppliers. Am J Hosp Pharm.
5. If bidding forms are used, they should contain adequate 1991; 48:523–4.
space for the bidder to enter the information requested.
6. The winning bidder should be notified in writing.
Unsuccessful bidders may be informed of who won
the award at what price, if they so request.
80 Drug Distribution and Control: Preparation and Handling–Positions
Preparation and Handling

Pharmaceutical Waste (0903) Safe and Effective Extemporaneous Compounding
Source: Council on Pharmacy Practice (0616)
To collaborate with regulatory bodies and appropriate or- Source: Council on Professional Affairs
ganizations to develop standards for the disposal of phar- To affirm that extemporaneous compounding of medica-
maceutical hazardous waste as defined in the Resource tions, when done to meet immediate or anticipatory patient
Conservation and Recovery Act (RCRA), for the purpose of needs, is part of the practice of pharmacy and is not manu-
simplifying the disposal of these substances by health sys- facturing; further,
tems; further, To support the principle that medications should not
To encourage pharmaceutical manufacturers and the be extemporaneously compounded when they are commer-
Environmental Protection Agency (EPA) to provide guidance cially and readily available in the form necessary to meet
and assistance to hospitals and health systems in proper phar- patient needs; further,
maceutical waste disposal and destruction efforts; further, To encourage pharmacists who compound medications
To advocate that EPA update the list of hazardous sub- to use only drug substances that have been manufactured in
stances under RCRA and establish a process for maintaining Food and Drug Administration-approved facilities and that
a current list; further, meet official United States Pharmacopeia (USP) compendial
To urge federal, state, and local governments to har- requirements where those exist; further,
monize regulations regarding disposal of hazardous pharma- To support the principle that pharmacists be ade-
ceutical waste; further, quately trained and have sufficient facilities and equipment
To advocate that the Food and Drug Administration that meet technical and professional standards to ensure the
standardize labeling of drug products with information relat- quality of compounded medications; further,
ing to appropriate disposal; further, To encourage USP to develop drug monographs for
To promote awareness within hospitals and health sys- commonly compounded preparations; further,
tems of pharmaceutical waste regulations; further, To educate prescribers and other health care profes-
To encourage research on the environmental and pub- sionals about the potential risks associated with the use of
lic health impacts of drug products and metabolites excreted extemporaneously compounded preparations.
in human waste; further, This policy was reviewed in 2010 by the Council on
To encourage pharmaceutical manufacturers to stream- Pharmacy Practice and by the Board of Directors and was
line packaging of drug products to reduce waste materials. found to still be appropriate..
This policy was reviewed in 2013 by the Council on
Pharmacy Practice and by the Board of Directors and was Accreditation of Compounding Facilities (0617)
found to still be appropriate. Source: Council on Professional Affairs
To encourage facilities where extemporaneous compound-
Safe Disposal of Patients’ Home Medications (0614) ing of medications occurs to seek accreditation by a nation-
Source: Council on Professional Affairs ally credible accreditation body.
To minimize the patient safety consequences and public This policy was reviewed in 2010 by the Council on
health impact of inappropriate disposal of patients’ home Pharmacy Practice and by the Board of Directors and was
medications by working collaboratively with other interested found to still be appropriate.
organizations to (1) develop models for patient-oriented
medication disposal programs that will minimize acciden-
tal poisoning, drug diversion, and potential environmental
impact, (2) advocate that the pharmaceutical industry and
regulatory bodies support the development and implementa-
tion of such models, and (3) educate health professionals,
regulatory bodies, and the public regarding safe disposal of
unused home medications.
Pharmacy Practice and by the Board of Directors and was
found to still be appropriate.
Drug Distribution and Control: Preparation and Handling–Guidelines 81
ASHP Guidelines on
Compounding Sterile Preparations
Purpose Legal and Regulatory Considerations
The compounding of medications is a fundamental part of Significant legal and regulatory changes have taken place
pharmacy practice. All compounding personnel, mainly since publication of the previous ASHP guidelines (Figure 1).
pharmacists and pharmacy technicians, are responsible for At the time of its publication, section 503A of the
compounding and dispensing sterile products and prepara- U.S. Food and Drug Administration Modernization Act
tions of correct ingredient identity, purity (freedom from (FDAMA) served to define the limits of legitimate com-
physical contaminants, such as precipitates,1 and chemical pounding.18 When section 503A of FDAMA was ruled un-
contaminants), strength (including stability2 and compat- constitutional in 2001, the delineation between compound-
ibility), and sterility and for dispensing them in appropriate ing and manufacturing reverted to earlier regulations based
containers that are labeled accurately and appropriately for on the Federal Food, Drug, and Cosmetics Act.19 Under
the end user. In contemporary health care organizations, pa- those regulations, compounding is considered part of the
tients receive compounded sterile preparations (CSPs) that practice of pharmacy and in most states, is governed by state
are stored for extended periods before use. It has long been law and regulation. Manufacturing is regulated by the fed-
recognized that extended storage of CSPs may allow for the eral government through the auspices of the Food and Drug
growth of a pathological bioburden of microorganisms3 and Administration (FDA). In most cases, extemporaneously
that patient morbidity and mortality can result from con- compounded preparations must be prepared pursuant to a
taminated or incorrectly compounded sterile preparations.4–9 prescriber’s prescription for a specific patient. Some states
When quality monitoring is inadequate, personnel respon- have specific regulations dealing with CSPs for office use.
sible for sterile compounding may not know that inaccurate Some pharmacies whose primary purpose is preparing CSPs
or contaminated products are dispensed.10–13 for hospitals and other facilities may be registered with the
These guidelines are intended to help compounding FDA as manufacturers and must adhere to federal good
personnel prepare CSPs of high quality and reduce the po- manufacturing practices. Some state boards of pharmacy
tential for harm to patients and consequences for compound- permit one pharmacy to compound for another pharmacy
ing personnel. The recommendations in these guidelines are under central fill regulations. Most pharmacies compound
based on published data, when available; on expert opinion only pursuant to a prescriber’s prescription and follow state
and procedures used in similar industries; and on applica- regulations regarding compounding.
ble regulations and standards. These guidelines are a revi- On January 1, 2004, USP chapter 797, Pharmaceutical
sion of the 2000 ASHP Guidelines on Quality Assurance of Compounding—Sterile Preparations,15 became official, re-
Pharmacy-Prepared Sterile Products,14 with the goals of placing USP chapter 1206, Sterile Drug Products for Home
providing more current recommendations and harmoniz- Use.20 The change from a chapter numbered above 1000 to a
ing the ASHP guidelines with United States Pharmacopeia chapter below 1000 marked a change from an advisory stan-
(USP) chapter 797, Pharmaceutical Compounding—Sterile dard to an enforceable one. USP chapter 797 has since been
Preparations.15 To help achieve that harmonization, these revised.15 Some state regulations require full compliance
guidelines employ the definitions and terminology of USP with USP chapter 797, some have indirect references to the
chapter 797 rather than those of the previous guidelines. chapter, some do not mention the chapter, and some have ad-
Many health care settings also use CSPs prepared ditional regulations.21 The National Association of Boards of
by compounding pharmacies. Although these guidelines Pharmacy supports the incorporation of compounding regu-
may be useful in assessing the quality of CSPs prepared by lations into state pharmacy practice legislation by including
compounding pharmacies, more information on the topic such wording in the association’s Model Rules and Model
of outsourcing sterile compounding services is available in State Pharmacy Act.22 State boards of pharmacy should be
the ASHP Guidelines on Outsourcing Sterile Compounding consulted to determine the current status of sterile com-
Services.16 pounding regulations, as there are significant differences in
Finally, while these guidelines are generally appli- regulation among states.
cable to all personnel who prepare CSPs and all facilities
in which CSPs are prepared, pharmacists and other health Accreditation Considerations
care professionals responsible for the preparation, selection,
and use of CSPs are urged to use professional judgment in The Centers for Medicare and Medicaid Services (CMS)
interpreting and applying these guidelines to their specific Hospital Conditions of Participation and Interpretive
circumstances. Users of these guidelines are cautioned that Guidelines, the Joint Commission, the American Osteopathic
the information provided is current as of publication and are Association’s Healthcare Facilities Accreditation Program,
urged to consult current editions of original sources (e.g., and DNV Healthcare’s National Integrated Accreditation
laws, regulations, and applicable standards, including USP for Healthcare Organizations all include statements con-
compendial standards) to ensure patient safety as well as le- cerning safe practices for storage and preparation of sterile
gal and regulatory compliance. compounds.23–26 Clinics, long-term care facilities, home care
organizations, rehabilitation facilities, and physician offices
(all of which come under the purview of USP chapter 79715)
82 Drug Distribution and Control: Preparation and Handling–Guidelines
2008—USP
2002— 2004—USP Chapter 797
1990—4 deaths, FDAMA Chapter 797 revisions become
1971—Deadly 2 cases of 1991 and 1995— 1997— section 503A becomes official
nationwide blindness from ASHP national FDAMA ruled official
nosocomial 2006—PCAB
contaminated compounding signed unconsti-
infection established
CSPs surveys into law tutional
outbreak
1970 1980 1990 1995 2000 2005 2010
1975−80: NCCLVP 2002—ASHP national

publishes compounding survey 2012—
recommendations 1992—FDA 1993—ASHP USP Sterile contaminated
Compliance TABs on Quality Compounding CSPs injure
Guide, USP Assurance for Expert 271 and cause
2000—ASHP 2010—ASHP
Dispensing Pharmacy- Committee 21 deaths in 16
Guidelines on Guidelines on
Practices for Prepared Sterile formed states
Quality Outsourcing
Sterile Drug Products and on Assurance for Sterile
Products Pharmacy- Pharmacy- Compounding
Intended for Prepared Prepared Sterile Services
Home Use Ophthalmic Products published
published Products published
published
Figure 1. Evolution of Sterile Compounding Standards, 1970—2010. Adapted from The ASHP Discussion Guide on USP Chapter <797> for
Compounding Sterile Preparations.17 NCCLVP, National Coordinating Committee on Large Volume Parenterals; CSPs, compounded sterile
preparations; USP, United State Pharmacopeia; TAB, technical assistance bulleting; FDAMA, Food and Drug Administration Modernization Act;
PCAB, Pharmacy Compounding Accreditation Board.
may all be subject to specific additional governance of ster- tion prevention practices in the United States. Safe infusion,
ile compounding practices, depending on the agencies regu- injection, and medication vial practices have been addressed
lating or accrediting the facility. In addition, organizations by CMS50 and the Association for Professionals in Infection
preparing hazardous drugs27,28 should comply with National Control and Epidemiology,51 and the Association of peri-
Institute for Occupational Safety and Health (NIOSH) rec- Operative Registered Nurses has recommended practices for
ommendations to ensure that compounding personnel are medication safety in perioperative settings.52
operating in a safe environment.29,30
Physical Facilities and Equipment
Other Compounding-Related Guidelines
Design and Functionality Requirements
ASHP provides several guidelines for safe compounding Facility requirements are intended to establish a safe en-
practices28,31,32 and a discussion guide on USP chapter 79717 vironment for compounding CSPs. The International
and has recognized USP chapter 797 as a relevant practice Organization for Standardization (ISO) air cleanliness clas-
standard in the ASHP Guidelines: Minimum Standard for sification of the compounding environment is a critical mea-
Pharmacies in Hospitals.33 Other professional organizations sure that is affected by facility design.
also provide guidance on specific aspects of compounding.
Standards for prescribing, preparation, administration, and Primary Engineering Controls (PECs). A PEC is a device
monitoring of parenteral nutrition are available through the or room that provides an ISO Class 5 environment for com-
American Society for Parenteral and Enteral Nutrition.34,35 pounding CSPs. PECs all rely on a special type of high-
The Institute for Safe Medication Practices provides rec- efficiency particle air (HEPA) filter that is >99.99% efficient
ommendations for preventing medication errors, including in removing particles as small as 0.3 microns in size (the
those involving CSPs.36,37 The Infusion Nurses Society of- most penetrating particle size [MPPS], which refers to the
fers standards, professional development, and resources for largest-sized particle that may escape the filter, although
all aspects of infusion care.38 The Controlled Environment particles of all sizes may be captured). The unidirectional
Testing Association (CETA) provides numerous CETA (horizontal or vertical) HEPA-filtered air must provide
Application Guides (CAGs) for the proper use, cleaning, sufficient velocity to sweep particles away from the direct
and certification of primary engineering controls (PECs) compounding area and maintain unidirectional flow during
and buffer areas (generally referred to as “cleanrooms”).39–45 preparation of CSPs. (More information about HEPA filtra-
Guidelines for Hand Hygiene in Healthcare Settings,46 tion and first-air concepts can be found in the ASHP publica-
Guidelines for Prevention of Intravascular Catheter-Related tions Compounding Sterile Preparations,53 Basics of Aseptic
Infections,47 Guidelines for Environmental Infection Control Compounding Technique,54 Getting Started in Aseptic
in Healthcare Facilities,48 and Protect Patients Against Compounding,55 and Compounding Sterile Preparations:
Preventable Harm from Improper Use of Single-dose/ ASHP Video Guide to USP <797>.56)
Single-use Vials,49 all from the Centers for Disease Control PEC devices include laminar airflow workbenches
and Prevention (CDC), serve as the backbone for most infec- (LAFWs), biological safety cabinets (BSCs), compounding
aseptic isolators (CAIs), and compounding aseptic contain- Facilities for preparation of radiopharmaceuticals have
ment isolators (CACIs) (Table 1). Properly designed, uni- some different requirements. Refer to USP chapter 79715 and
directional airflow CAIs function in a similar manner as other relevant standards for specifics.
LAFWs, but the direct compounding area does not interact Facilities without USP chapter 797-compliant ante ar-
with room air because it is within a closed system, with the eas and buffer areas may prepare low-risk, non-hazardous
air sweeping particles away from the compounding site. CSPs in a PEC within a segregated compounding area. A
Smoke tests of PECs assist a facility in verifying unidirec- segregated compounding area is an unclassified space (i.e.,
tional airflow and lack of turbulence and reverse flows. an area with no specific ISO classification) and does not in-
CAIs or CACIs located outside of an ISO Class 7 en- clude ante or buffer areas. It is required to be separated from
vironment must be coupled with documentation from the activities that are not essential to the preparation of CSPs;
manufacturer that the device will meet or exceed USP chap- not be located adjacent to food preparation sites, ware-
ter 797 standards under these conditions and be dynamically houses, or construction sites; and not have unsealed win-
tested on site to USP 797 and CETA requirements. If the dows or doors that connect to the outdoors or high-traffic
CACI used for hazardous drug preparation is located outside areas.15 This architecture type is most often seen in satellite
the buffer area (see Architecture, below), it must be located pharmacies, small hospitals, procedural areas, or clinics. The
in a segregated and dedicated area that maintains at least beyond-use dating for sterile preparations compounded in a
0.01-inch water column negative pressure and maintains, at segregated compounding area cannot exceed 12 hours (see
a minimum, 12 air changes per hour (ACPH). Expiration and Beyond-Use Dating).
Architecture. The sterile compounding area includes a well- Buffer Areas

lit buffer area and ante area (both are secondary engineering Air Supply. A buffer area differs from an ordinary ventilated
controls) and an area for storage of sterile products and sup- room by having the following:
plies. A buffer area (or “cleanroom”) is defined as an area
where a PEC is located and where activities such as prepa- • Increased air supply.
ration, compounding, and staging of CSPs occur. This area • HEPA filtration (the filtered air should be introduced
should provide adequate space for the PEC and may include at the ceiling, with returns mounted low on the walls;
a limited amount of shelving and/or carts for staging of com- ceiling-mounted returns should not be used) including
pounding (not for storing stock). An ante area provides space a terminal air filter (a filter at the end of the heating,
for hand washing, garbing, and product decontamination; ventilation, and air conditioning [HVAC] ducting).
it also serves as a way to further segregate the buffer area • Room pressurization.
from other, less-clean areas of the facility. Water sources, • A perforated plate or swirl supply air diffuser (if an air
such as sinks or floor drains, are not permitted in the buffer diffuser is necessary); high-induction supply air dif-
area and should not be immediately adjacent to segregated fusers should not be used in buffer areas.
compounding areas outside of a buffer area. A storage area
outside the buffer and ante areas should provide adequate Structural components must be coupled with HEPA
space for placement of sterile products and supplies. filtration and air exchanges in order to provide a complete
The sterile compounding area (ante and buffer areas) buffer area environment and proper ISO classifications.
may be constructed of either hard- or soft-walled enclosures, Buffer areas must meet or exceed ISO Class 7 air cleanli-
with the zones being delineated by open or closed architec- ness standards. Ante areas must at least meet ISO Class 8
ture. Closed architecture is formed by walls and doors be- standards; ante areas opening into a negative pressure prepa-
tween the buffer and ante areas and is required for high-risk ration area must meet ISO Class 7 standards. The number of
compounding (Table 2). ACPH is based upon air/room pressure, velocity or air han-
Open architecture has openings between the buffer and dler capacity, HEPA flow restriction, duct size, the amount
ante areas and relies on a defined airflow velocity to divide of processing completed on a daily basis, and temperature.
the two areas, which are marked by a line of demarcation; ACPH must occur at a minimum of 30 times per hour in
this type of facility may only be utilized for low- and me- buffer and ante areas, but may need to be increased in high-
dium-risk compounding. Demarcation lines should be indi- traffic/high-volume areas in order to maintain the room’s
cated by colored tiles or other elements integrated into the specified ISO classification (Table 2) under dynamic condi-
flooring pattern but may be as simple as marking on the floor. tions. Facilities may incorporate the contribution of up to 15
air changes per hour from a LAFW in the total air changes
Table 1. per hours in a nonhazardous buffer area. By design, these
Primary Engineering Controls (PECs) devices filter room air as it passes through the HEPA filter.
Airflow within the room should be as steady as pos-
Used to Prepare sible, having as few interruptions as possible. Within the
Non-Hazardous Used to Prepare PEC, it must be unidirectional,39 with as few interruptions in
PEC Device CSPs Hazardous CSPs steady airflow as possible. PEC placement within the room
Conventional Laminar airflow Class II Biological should be well designed, with PECs placed where they are
workbench safety cabinet least affected by opened doors, HVAC systems, or personnel
(LAFW) (BSC) traffic. For non-hazardous preparations, positive pressure
Isolators Compounding Compounding is required between rooms physically divided by walls or
aseptic isolator aseptic doors (closed architecture style) and should be maintained
(CAI) containment at a minimum of positive 0.02 inch water column. If a room
isolator (CACI) does not have physical barriers (i.e., has an open architecture
Table 2.
Facilities Features Required for Specific Types of Compounding (Data from USP Chapter 79715 Except as Noted)
Low-Risk with
≤12-hour BUD Low-Risk Medium-Risk High-Risk
(Non-Hazardous) (Non-Hazardous) (Non-Hazardous) (Non-Hazardous) Hazardous Drugs
Architectural Stylea Segregated Open or closed Open or closed Closed Closed
Buffer zone ISO N/A ISO Class 7 or ISO Class 7 or ISO Class 7 or ISO Class 7 or
classification better better better better
Ante area ISO N/A ISO Class 8 (ISO ISO Class 8 (ISO ISO Class 8 (ISO ISO Class 7 or
classification Class 7 if opens Class 7 if opens Class 7 if opens better
into negative into negative into a negative
pressure area) pressure area) pressure area)
or better or better or better
Minimum air N/A 30 30 30 30
exchanges for
buffer areab
Minimum air N/A 20 if ISO 8; 30 if 20 if ISO 8; 30 if 20 if ISO 8; 30 if 30
exchanges for ISO 7 ISO 7 ISO 7
ante areac
Pressure N/A Positive Positive Positive Negative
a
Architectural style (“open” and “closed”) is not defined in USP chapter 797, but the concept of physical separation of ante areas and buffer
rooms is described in the chapter. For the purposes of these guidelines, “closed architecture” indicates that the buffer and ante areas are separated
by a door (i.e., are physically separate rooms) and maintain a pressure differential of no less than 0.02-inch water column positive pressure. “Open
architecture” indicates that the buffer and ante areas are in one room, not separated by a door (i.e., not physically separated). Displacement airflow
is used to separate open architecture spaces, with at least 40 feet per minute of airflow across the entire plane of the opening. A segregated
compounding area contains a PEC within a restricted space.
b
If an ISO Class 5 recirculating device is in place, a minimum of 15 air changes per hour (ACPH) is sufficient if the ACPH is 30 between the device
and the area supply HEPA filters.
c
USP chapter 797 does not address the air changes in ISO Class 8 ante areas. The FDA Aseptic Processing Guide57 recommends a minimum
of 20 ACPH to maintain ISO 8. However, this is a minimum value intended for industry. Since ante areas for CSPs include ungowned personnel and
other activities, a minimum of 30 ACPH is best practice for ISO Class 8 ante areas and required for ISO 7 ante areas.
style) and relies on a line of demarcation, the displacement Work surfaces should preferably be stainless steel,
airflow concept requiring air velocity of 40 feet per minute but at a minimum are required to be non-porous and eas-
(0.2 meter per second) from the buffer area across the entire ily sanitized. Carts and shelves, ideally made of stainless
plane of line of demarcation into the ante area is required. steel wire, nonporous plastic, or rustproof metal, should be
Open architecture is not permitted in areas used for high-risk easy to move and clean, if necessary. Office equipment (e.g.,
preparations. computers and components [including washable keyboard
When designing buffer areas, facilities must con- and mouse], telephones, printers) placed in the buffer area
sider workflow patterns, such as how personnel performing must be easily cleanable and placed in such a manner that
double-checks will affect air quality. If supervisory person- they have no material impact on the ISO air cleanliness clas-
nel are not located in the buffer area, movement in and out sification of the area.
of the buffer area is likely to increase airflow interruption.
Communication devices should be used to minimize traffic Renovations
between areas, and cameras may be installed to supplement To meet requirements for sterile compounding, many facili-
supervision of staff or check compounding accuracy, if per- ties choose to renovate existing space rather than construct
mitted by state regulations. new facilities. Whether designing a new area or retrofitting
one, the specific types (e.g., hazardous or nonhazardous) and
Surfaces. Surfaces of any kind in the buffer area and ante risk levels of CSPs that will be prepared in the area should
area must be smooth, impervious, and easy to clean, with guide the facility design and construction. A plan for how
no cracks or crevices that could trap dust or contaminants. operations will continue without interruption should be de-
All materials used in the facilities must be non-shedding. vised prior to construction.
Walls and ceilings must be made of either hard plastic or
epoxy-painted gypsum board. If ceiling tiles are used, they Power and Other Utility Interruptions
must be coated with hard polymer and caulked both around The facility’s emergency management plan should include
the perimeter and around each tile. Ceiling lights must be steps to meet patient-care needs during time of utility in-
smooth, mounted flush, and sealed. Floors should be made terruptions, including the need for CSPs. In some cases,
of wide, heavy-duty sheet vinyl, rubber, or epoxy that is immediate-use procedures may be safely implemented to
coved around the corners and rolled up onto the walls. Paint meet some needs. Methods to identify and safely meet in-
must be an epoxy, acrylic, or other non-porous sealant type. terim compounding needs or address patient-care needs with
noncompounded alternatives should be developed, put into Table 3.

standard operating procedures (SOPs), inserviced to staff, Minimum Frequency for Cleaning of Specific Sites
and tested as part of the organization’s emergency planning (Reprinted with Permission from USP Chapter
process. 79715)
Site Minimum Frequency
Pharmacy Compounding Devices
Pharmacy compounding devices are utilized to increase ISO Class 5 PEC Beginning of each shift
efficiency while decreasing the potential for human error. Before each batch
Devices that do not create their own ISO Class 5 environ- Every 30 minutes when
compounding
ment must be located within an ISO Class 5 PEC and adhere
After spills
to applicable standards for accuracy and precision. All com-
When surface contamination
pounding devices must be monitored and validated for ac- is known or suspected
curacy consistent with device manufacturer specifications.
Counters and easily Daily
Automated Compounding Devices (ACDs) are uti-
cleanable work
lized to accurately combine multiple drugs and solutions
surfaces
into a single delivery container. These devices are most com-
monly used for parenteral nutrition preparation, but may be Floors Daily
used for cardioplegia solutions, continuous renal replace- Walls Monthly
ment therapy, or other complex processes. ASHP Guidelines Ceilings Monthly
on the Safe Use of Automated Compounding Devices for the
Storage shelving Monthly
Preparation of Parenteral Nutrition Admixtures32 should be
consulted for further details on utilizing ACDs. Accuracy
and precision testing for ACDs is required by USP chapter
79715 and incorporate gravimetric, volumetric, and chemical Environmental Monitoring
analyses. These analyses, as determined by facility protocol, Environmental monitoring and related documentation must
must be monitored and recorded on a daily basis, with evalu- be completed on a routine basis to ensure adequate environ-
ation for outliers occurring at least weekly. mental and personnel controls are in place to prevent con-
Repeater pumps are devices used to pump a preset vol- tamination of CSPs. Ensuring a safe compounding environ-
ume of fluid in a consistent and reproducible manner. They ment requires viable and nonviable airborne particle testing,
must be calibrated according to manufacturer specifications, pressure differential or displacement airflow measurement,
which may depend on the volume and frequency of use. temperature monitoring, and surface disinfection sampling
Robotic systems automate the compounding and label- and assessment. Nonviable particles are particles that do not
ing of parenteral doses in syringes and bags using an en- contain a living organism, such as particles shed from pa-
closed chamber that must create an ISO Class 5 air cleanli- per or dust. Viable particles are living organisms, such as
ness environment or better. bacteria or fungal spores, that require nonviable particles to
The proper use of ACDs, repeater pumps, robotic sys- travel. Monitoring of humidity,39,44 sound,39 and lighting39
tems, and other compounding equipment used in the prepa- may also be considered by facilities to enhance the environ-
ration of CSPs remains the responsibility of the pharmacist. mental monitoring program.
Each element of the monitoring program must be
Cleaning and Disinfecting included in a sampling plan with sample locations, meth-
Cleaning with a germicidal detergent and water will remove ods of collection, sampling frequency, and other specifics
visible solids or soiling before disinfecting. Disinfecting depending on the type of monitoring being performed. The
environmental monitoring sampling frequency must occur
removes microbial contamination. It is critical that an ap-
at a minimum as listed below, with possible additional times
propriate germicidal detergent and water be used to clean
based on the type of testing:
all surfaces of the buffer and ante areas in addition to all of
the PECs. Great care must be exercised to avoid getting the
HEPA filters wet during cleaning. Cleaning with a germi- • At the commissioning and certification of new facili-
ties and equipment.
cidal detergent will leave a residue that needs to be removed
from work surfaces (e.g., counter and PEC surfaces). This • Every six months during routine re-certification of
equipment and facilities.
residue is best removed by using sterile 70% isopropyl al-
cohol (IPA).
• After any facility or equipment maintenance, includ-
ing construction or remodeling of adjacent depart-
Appendix II of USP chapter 79715 provides infor- ments or work on shared air handlers.
mation on types of products that can be used for cleaning
and disinfecting the ante and buffer areas, including floors,
• At any point when problems are identified with prod-
ucts, preparations, or employee technique or if a CSP
walls, and ceilings. Choice of cleaning and disinfection is suspected to be the source of a patient infection.
products should be approved by the organization’s appropri-
ate authority (e.g., the Infection Control Committee). Records of data collected through the monitoring pro-
Policies and procedures must be developed to ensure gram must be maintained as part of the overall quality assur-
consistent practices, including dilution of cleaning products. ance program of the facility. The data should be reviewed by
Table 3 describes the minimum frequency for cleaning sur- management personnel or their designees and by the facil-
faces used to compound low- and medium-risk CSPs in the ity’s Infection Control Committee to ensure that the findings
sterile compounding area. of the reports are addressed. Table 4 provides an overview of
environmental monitoring requirements.
Table 4.
Environmental Monitoring Requirements (Adapted from USP Chapter 79715)
Parameter Monitored By Frequency
Temperature Compounding personnel or facilities Documented daily (at a minimum)
management staff (if electronic monitoring is
centralized)
Pressure differential or Compounding personnel Documented each shift (preferably), daily (at a
velocity across line of minimum)
demarcation
Qualified certifier At least every 6 months
Nonviable particles Qualified certifier At least every 6 months
Surface sampling Compounding or laboratory personnel Periodically, as defined by compounding and
infection control personnel, at least every
6 months or after significant changes in
procedures or cleaning practices
Electronic device sample of Compounding personnel or qualified certifier At least every 6 months
viable particles
Table 5. Results of pressure differential and/or velocity of air

Controlled Temperatures (Data from USP General displacement must be reviewed and documented each shift
Notices and Requirements58) (at least daily) or by a continuous device with alarms.
Storage Condition Centigrade Fahrenheit
Nonviable Airborne Particle Testing Program. Determination
Room temperature 20 to 25 °C 68 to 77 °F of the ISO classification of an area or device is dependent
Cold temperature 2 to 8 °C 36 to 46 °F on nonviable particle testing (“certification”), which must
(refrigerated) be completed by qualified personnel complying with the
Freezer (frozen) −25 to −10 °C –13 to 14 °F Certification Guide for Sterile Compounding Facilities
(CAG-003-2006).39 PECs such as LAFWs, BSCs, CAIs,
and CACIs must be certified every 6 months and whenever
the device is relocated or serviced. Both primary (LAFWs,
BSCs, CAIs, and CACIs) and secondary engineering con-
trols (buffer areas and ante areas) must be checked for total
Temperature Monitoring. Any controlled temperature area particle counts every 6 months according to the manufac-
used for compounding sterile preparations or for storage of turer’s specifications or CETA recommendation and when a
sterile products or CSPs must be monitored at least once device or room is relocated or altered. Thresholds for each
daily and results documented in a log. The facilities should ISO class are presented in Table 6.
maintain a comfortable room temperature (20 °C [68 ºF] or
cooler) for properly garbed compounding personnel. If fa- Viable Airborne Particle Testing Program. Classified space
cilities use continuous temperature recording devices, they (PECs and buffer and ante areas) must undergo routine vi-
must be monitored and documented once daily to ensure able particle testing. The testing plan should include the re-
they are functioning properly. Controlled temperature ranges quired sample locations, method of collection, frequency,
are listed in Table 5. the volume of air to be tested, and the time of day testing
will occur. Testing must occur every 6 months in all com-
Pressure Differential or Air Displacement. Since positive- pounding areas (PECs, buffer areas, ante areas, and areas
and/or negative-pressure rooms are required for sterile adjacent to segregated compounding areas) as part of the
compounding, the appropriate differential pressure or air overall compounding recertification process. The method
displacement velocities must be maintained. If closed archi- of testing must be impaction via an electronic air sampling
tecture is used, a pressure differential between general, ante, device, as settling plates alone are not considered an accept-
and buffer areas must be monitored. A facility with open able method.
architecture design must monitor the differential airflow Sampling plans should be detailed and include all
across the opening between ante and buffer areas. high-traffic locations within the compounding area and any
A pressure gauge or velocity meter must be in place to sites prone to contamination. Turbulence caused by airflow
monitor airflow between relevant areas. Pressure between disruption, such as within an ISO Class 5 LAFW or door-
ISO Class 7 positive-pressure areas and the general area ways, should be included in the testing plan, along with ar-
must be at least 5 Pa (0.02-inch water column). Negative eas where garbing, cleaning, labeling, and staging occur. In
pressure areas should have no less than 2.5 Pa (0.01-inch segregated compounding areas, sampling should include lo-
water column) negative pressure to adjacent positive pres- cations within the ISO Class 5 PEC and other areas in close
sure. A monitored pressure indicator must be installed to en- proximity to the PEC.
sure proper pressurization. If differential airflow is used as a Viable particle testing must be performed using a gen-
measure, the velocity must be at least 0.2 meter per second eral microbiological growth medium, such as sterile nutrient
(40 feet per minute).
Table 6.
Particle Limits for Sterile Compounding Areas (Adapted from USP Chapter 79715)
Buffer Area and Ante-Area
Primary Engineering Controls Opening into a Negative Ante-Area Opening Only into
(LAFW, BSC, CAI, CACI) Pressure Room a Positive Pressure Room
ISO Class 5 7 8
Limit on number of ≥ 0.5 3,520 352,000 3,520,000
micron particles/m3 of air
contact surfaces that must be cleaned with sterile water and

Table 7.
disinfected with sterile 70% IPA.
Viable Environmental Monitoring Recommended
Results must be reported in colony-forming units
Action Levels for Microbial Contamination
(CFUs) per plate. Reevaluation of work practices and clean-
(Adapted from USP Chapter 79715)
ing procedures should occur if the CFU count exceeds the
Recommended Action suggested action levels (Table 8). Investigation into the
ISO Levels for Microbial source of contamination should be undertaken, the sources
Classification Contamination (CFUs/m3)a eliminated, and the area cleaned and re-sampled.
5 1b Environmental monitoring and quality assurance pro-
7 10 grams and documentation may be completed by a limited
number of personnel in any given facility, but the actions
8 or above 100
of all compounding personnel may affect these two critical
a
CFUs/m3, colony-forming units per cubic meter.
b
elements of compliance. All compounding personnel should
Samples from ISO Class 5 environments should normally yield no be familiar with all facility policies and procedures specific
microbiological contaminants.
to CSPs, even if the procedures are not typically their re-
sponsibility.
agar. In facilities that compound high-risk preparations, test-

ing must also be done with a medium that supports fungal Expiration and Beyond-Use Dating
growth, such as malt extract. The growth medium should be
incubated (outside of the sterile preparation area) according A manufacturer’s expiration date is the date assigned pursu-
to the manufacturer’s recommendations. ant to manufacturer testing. The drug product is guaranteed
Sample data must be reviewed as a means of evaluat- by the manufacturer to be safe and effective up to the listed
ing control of the compounding environment. Results above date when products are stored as described in the product
recommended action levels (see Table 7) should prompt labeling.
reevaluation of work practices, cleaning procedures, and A beyond-use date (BUD) is the date or time after
HEPA filtration. Any microbial growth that results from vi- which administration of a CSP shall not be initiated. As
able environment sampling must be identified to the genus described in previous ASHP guidelines14 and in USP chap-
level by microbiology personnel. If any highly pathogenic ter 797,15 the BUD is determined from the date or time the
organisms (e.g., gram-negative rods or yeasts) are identi- preparation is compounded, its chemical stability, and the
fied, infection control specialists should immediately be sterility limits described later in these guidelines. Both the
consulted to assist in formulating a response to the situation. stability of the components and the sterility limits described
above must be taken into consideration when determining
Surface Disinfection Sampling and Assessment. Touch BUDs, and the BUD must be the shorter of the sterility dat-
contamination originating from contaminated work surfaces ing or chemical stability dating. Information regarding sta-
must be minimized and prevented if possible. Surface sam- bility dating procedures and defaults can be found in USP
pling provides facilities with a snapshot of the effectiveness chapter 795, Pharmaceutical Compounding—Non-Sterile
of their disinfection procedures (including technique and Preparations,59 and other published literature sources.60,61
cleaning products) and must be part of the overall quality Processes such as thin-layer chromatography (TLC)
assurance plan. Using a sterile nutrient agar contact plate and high-performance liquid chromatographic (HPLC) as-
for flat surfaces or swabs for equipment and other non-flat says are the most reliable means of determining the stability
surfaces, sampling must be performed in all ISO classified of a product and should be used in place of theoretical pre-
areas on a periodic basis, at a minimum, every 6 months or dictions of stability when published literature is not avail-
when significant procedural or cleaning changes are imple- able. The use of commercial reference laboratories that of-
mented. A specific plan detailing the location of each sam- fer qualitative and quantitative testing may serve as a key
ple must be devised so that the same locations are repeated resource for end-product testing.
with each testing session. Contact plates require pressing a
plate directly to the surface being tested, while swabbing re- Risk Level Classification
quires swabbing an area, submersing the swab in the correct
amount of diluent, and then swabbing onto or into a ster- In these guidelines, as in previous ASHP guidelines14 and
ile nutrient agar surface. Agar plates will leave a residue on USP chapter 797,15 CSPs are stratified by potential risk of
Table 8.
Recommended Action Levels for Personnel Testing (Adapted from USP Chapter 79715)
PEC Buffer Area Ante Area
Viable airborne particle testing action levels for >1 >10 >100
contamination (CFUs per cubic meter [1000
L] of air per plate)
Surface sample contamination (CFUs per plate) >3 >5 >100
Glove fingertip sampling >3 N/A N/A
a
CFUs = colony-forming units.
microbial contamination into three primary categories: low-, not required to be located within an ISO Class 7 buffer area.
medium-, and high-risk CSPs, with an additional category The PEC must be separate from other operations, including
for CSPs intended for immediate use15 and a sub-category sinks and other water sources or drains, and away from un-
for low-risk CSPs intended for use within 12 hours.15 The sealed windows or doors that connect to high traffic areas,
potential risk is based on the danger of exposing multiple pa- construction, warehouses, or food preparation areas. Distinct
tients to microbial bioburden and based on microbial growth labeling for conveying short BUDs should be considered.
factors influenced by product storage time, temperature and
product ability to support microbial growth, surface and Medium-Risk CSPs
time exposure of critical sites, and microbial bioburden in This category encompasses preparations requiring more
the environment. Compounding personnel must determine complex compounding processes, including:
the appropriate risk level and the appropriate BUD for use
based upon chemical stability and the potential for micro- • Multiple doses of sterile products combined or pooled
bial, physical, or chemical contamination during compound- to prepare a product that will be administered either
ing. In making a risk-level determination, compounding per- to multiple patients (i.e., batching of syringes or large
sonnel must evaluate where the preparation is being made, volumes), or one patient on multiple occasions (e.g.,
the number of components or the number of aseptic breaches preparation for use over several days).49
needed to compound the preparation, and the complexity of • More than three commercially available sterile prod-
the compounding process. When circumstances make risk- ucts are used to produce the compound.
level assignment unclear, guidelines for the more stringent • More complex compounding processes (e.g., total par-
risk level should prevail. For examples and a comparison of enteral nutrition).
the risk levels, requirements, and BUDs to be used in risk-
level determination, see Table 9. All requirements for low-risk compounding regarding
location and aseptic technique must be followed.
Low-Risk CSPs
This category encompasses simple admixtures involving High-Risk CSPs
closed-system transfer, measuring, and mixing of three or High-risk CSPs are those
fewer commercially manufactured sterile products (includ-
ing the infusion solution). Low-risk compounding condi- • Prepared from nonsterile ingredients, including manu-
tions must include all of the following: factured products not intended for sterile routes of ad-
ministration;
• CSPs are compounded using aseptic technique within • Compounded using a nonsterile device prior to termi-
an ISO Class 5 PEC (e.g., LAFW, BSC, CAI, or CACI) nal sterilization;
that is located within an ISO Class 7 buffer area with • Containing nonsterile water that are stored for more
an ISO Class 8 ante area. than 6 hours before sterilization;
• Each container, including the final container, may not • Exposed to conditions worse than ISO Class 5 air
be entered more than twice to prepare the CSP. quality for longer than 1 hour, if they contain or are
• Compounding is limited to aseptic manipulations of compounded from sterile contents of commercially
disinfected containers using sterile needles and sy- manufactured products or CSPs without antimicrobial
ringes. preservatives;
• Containing bulk ingredients whose chemical purity and
Low-Risk CSPs for Use Within 12 Hours. Under limited content strength are not verified by labeling and docu-
circumstances, sterile compounding may occur in a seg- mentation from suppliers or by direct determination; or
regated compounding area (such as a satellite pharmacy • Prepared by compounding personnel who are improp-
or dedicated sterile compounding space) in which the ISO erly garbed or gloved.
Class 5 PEC is not located within an ISO Class 7 buffer area.
A segregated compounding area is a designated space, ei- Presterilization procedures for high-risk level CSPs,
ther a demarcated area or room, in which compounding is such as weighing and mixing, shall be completed in no
restricted to preparing low-risk, nonhazardous CSPs with a worse than an ISO Class 8 environment.
beyond-use time of no more than 12 hours from the time of CSPs in this category must be terminally sterilized
preparation. All other requirements for low-risk CSPs must before administration to patients. Terminal sterilization is
be followed, with the exception that the ISO Class 5 PEC is defined by the FDA as the application of a lethal process
Table 9.
CSP Risk Levels and Beyond-Use Dates (BUDs) (Adapted from USP Chapter 79715)a
BUDs of CSP Stored at
Aseptic
Risk Compounding Garbing Technique Room Frozen
Category Location Required Required Examples Temperature Refrigerated (≤ 10 °C)
Low-risk ISO Class 5 Yes Yes Reconstitution of a 48 hours 14 days 45 days
PEC, ISO single-dose vial, single
Class 7 preparation of a small
buffer area, volume parenteral,
ISO Class 8b single large volume
ante area IV replacement fluids
with no more than 3
components
Low-risk ISO Class Yes Yes Same as low- 12 hours 12 hours N/A
with 5 PEC risk examples,
< 12-hour segregated non-hazardous
BUD from other preparations only
operations
Medium-risk ISO Class 5 Yes Yes Batched syringes, 30 hours 9 days 45 days
PEC, ISO total parenteral
Class 7 nutrition, ophthalmic
buffer area, preparations made
ISO Class 8b from sterile products,
ante area pooled admixtures,
batch-compounded
preparations without
bateriostatic additives,
preparations made
using automated
compounders or other
automated devices,
elastomeric pumps
High-risk ISO Class 5 Yes Yes CSPs prepared from 24 hours 3 days 45 days
PEC, ISO bulk, nonsterile
Class 7 components or in
buffer area, final containers
ISO Class 7 which are not sterile;
ante area preparations that must
be terminally sterilized
before administration
Immediate- Medication No Yes Emergent use 1 hour N/A N/A
use preparation preparations such as
areas should epidurals prepared
be clean, by anesthesia for
uncluttered, immediate injection or
and infusion, diagnostics,
functionally any non-hazardous
separatec preparations that
might cause harm
due to delays in
administration
a
ISO = International Organization for Standardization, PEC = primary engineering control, IV = intravenous.
b
Ante area must be ISO 7 if it opens into a negative pressure buffer area.
c
Source: The Joint Commission. MM.05.01.07, EP2.24
(e.g., steam under pressure or autoclaving) to sealed contain- filtrated units. All filters used to sterilize CSPs must undergo
ers for the purpose of achieving a sterility assurance level filter integrity (bubble-point) testing.
of less than 10-6 or a probability of 1 nonsterile unit per 1
million sterilized units.57 For CSPs that are heat-labile and Immediate-Use CSPs
cannot be processed as above, sterilization using an alterna- The immediate-use category should be reserved for emergent
tive method, such as a sterilizing grade 0.22 micron filter, use or situations in which adhering to low-risk compounding
must be done. Filtration only achieves a sterility assurance procedures would add additional risk due to delays in patient
level of 10-3, which is only 1 nonsterile unit per one thousand care. Examples of such situations may include cardiopulmo-
nary resuscitation, diagnostic procedures, or short-stability stored for longer than 1 hour prior to activation should be
medications that must be prepared immediately before ad- assembled (but not activated) by pharmacy staff within an
ministration outside health care facilities (e.g., in home infu- ISO Class 5 environment. Activation of the devices should
sion or emergency care at the accident site or in an ambu- be completed at the point of care just prior to administration.
lance). Immediate-use CSPs do not need to be compounded
in an ISO Class 5 environment and garbing and gowning are
Ampuls, Single-Dose, and
not required, as long as all of the following criteria are met:
Multiple-Dose Containers
• Hand hygiene per CDC recommendations46;
Ampuls may not be reused or saved at any time during the
• Aseptic technique is followed;
compounding process. To minimize particulate contamina-
• No hazardous drugs are used;
tion, 5 micron filter straws or filter needles must be used
• Only simple transfer of no more than three sterile,
when withdrawing contents of ampuls. Refer to the drug
non-hazardous drugs in the manufacturer’s original
labeling for manufacturer’s recommendations concerning
containers are involved in the compounding, and no
filtration.
more than two entries into any one container occur;
The environmental conditions in which drug vials are
• No more than 1 hour elapses from the time compound-
entered determine the BUD for the CSP. Single-dose vials
ing commences to the time administration to the pa-
are intended to be used to prepare single doses; however, in
tient begins (although best practice dictates that there
times of critical need, contents from unopened single-dose/
are no intervening steps between compounding and
single-use vials may be repackaged for multiple patients.49
administration);
This repackaging should only be performed by qualified
• No batching or storage of CSPs occurs; and
health care personnel in accordance with the procedures de-
• The preparation is labeled with patient identification,
scribed in these guidelines and in USP chapter 797.15
names and amounts of all ingredients, name or initials
Pharmacy bulk packages (PBPs), a type of vial con-
of preparer, and exact 1-hour BUD and time.
taining many single doses,65 must be considered a single-
dose vial for purposes of determining BUDs. Manufacturer’s
If CSPs prepared for immediate use are not admin-
information for each PBP contains recommended BUDs,
istered within 1 hour, they must be properly discarded. All which are usually between 4 and 8 hours.
medications must be labeled to meet regulatory and accredi- Multiple-dose vials may be reused or saved up to the
tation standards and in accordance with facility policy. manufacturer’s recommended BUD, if they are not opened
in a direct patient-care area and if facility policy does not
Point-of-Care Activation Systems require a shorter period.66 If there is no manufacturer recom-
mendation, multiple-dose vials may be reused or saved up
Point-of-care (POC) activation systems (i.e., vial/bag sys- to a maximum of 28 days or for a shorter period dictated by
tems) create a physical barrier between components (fluid facility policy. Table 11 illustrates the dating for these prod-
and medication) that can be activated to allow the compo- ucts based on environmental conditions.
nents to mix. These devices are designed to create a closed The person who first punctures a multiple-dose con-
system by which the end user activates the components just tainer intended for re-use must note the BUD and other in-
prior to the administration of the medication. BUDs for formation required by facility policy (e.g., his or her initials)
these products are based on the individual manufacturer’s on the vial or attached label. A label indicating “use by”
recommendations for labeling and dating. Table 10 provides clarifies that the date is the BUD rather than the opening
a summary of manufacturer-recommended BUDs for POC date. If a vial lacks a BUD, it should not be used and should
systems at time of publication. To decrease potential for con- be properly discarded.
tamination and errors, POC systems that will be attached and
Table 10.
Beyond-Use Date (BUD) at Room Temperature for Point-of-Care Activated Devices Assembled in ISO Class 5
Environmenta
Device Company BUDb Applicable Products
ADD-Vantage62 Hospira 30 days from date diluent
removed from overwrap
Mini-Bag Plus63 Baxter 15 days from date diluent 50 and 100 mL bags
removed from overwrap
Mini-Bag Plus63 Baxter 30 days from date diluent 100 mL containers docked with the following drugs: cefazolin
removed from overwrap 1 g, cefuroxime (Zinacef) 750 mg, ceftriaxone (Rocephin)
1 g, aztreonam (Azactam) 1 g, piperacillin and tazobactam
(Zosyn) 3.375 g
addEASE64 B. Braun 70 days When connected to 50 mL and 100 mL bags
56 days When connected to Excel 250 mL bags
a
Information is current as of January 2011. The manufacturer’s package insert should always be checked for the most current recommendation for
dating.
b
BUD for assembled but not activated system.
Batch Compounding and Sterility Testing dotoxin units/hour/kg or units/hour/m2), if established, are
included in the official monograph for the product or may
Use of CSPs stored for extended periods of time is guided by be found in other formula sources. If specific endotoxin lim-
the chemical stability of components and the sterility limits its are not available, default guidance can be found in USP
of the CSP defined above. If medium-risk batches are pre- chapter 85.68
pared and assigned a BUD within those limits, no sterility For high-risk preparations, batches of 25 or fewer
testing is required. However, if those limits are exceeded, CSPs do not require sterility testing.15 However, facilities
each batch must be tested for sterility according to the re- should consider sterility testing of such CSPs as part of their
quirements of USP chapter 71.67 quality assurance plans to ensure that proper procedures are
Facilities that wish to store CSPs for periods longer being followed.
than those described above must complete sterility testing
for each batch to determine the extended BUD. Each batch Outsourced CSPs
of any risk-level CSP intended for storage outside the limits
described above must be tested for sterility, according to the Outsourcing the preparation of CSPs to pharmacies that
requirements of USP chapter 71, Sterility Tests.67 The results specialize in sterile compounding provides an option for
must be evaluated along with stability data to establish the facilities that cannot or do not wish to prepare all or some
extended BUD. The policies and procedures of the indi- types of CSPs (e.g., radiopharmaceuticals, high-risk CSPs,
vidual facility must outline the processes used to determine parenteral nutrition) in their own facility. Facilities consid-
extended BUDs. ering outsourcing compounding should consult the ASHP
Batches of high-risk CSPs prepared as multiple- Guidelines on Outsourcing Sterile Compounding Services.16
dose vials intended for administration to multiple patients, The decision to use CSPs prepared by outside compounding
batches of high-risk CSPs exposed for more than 12 hours pharmacies should be reviewed and approved by hospital
to temperatures of 2 to 8 °C (36 to 46 ºF) or for more than 6 leadership,23,70 and such use should only occur in accordance
hours to temperatures above 8 °C (46 ºF) before sterilization, with written policies and procedures.
or batches of more than 25 identical, single-dose, high-risk
CSPs must undergo sterilization and microbial and bacterial
Administration of CSPs
endotoxin (pyrogen) testing prior to dispensing or adminis-
tration. Sterility testing, as outlined in USP chapter 71, must
USP chapter 797 does not include any specifications for ad-
be completed prior to dispensing or administration.67 USP
ministration or timing during this crucial period of the drug
Membrane Filtration, USP Direct Inoculation of the Culture
delivery cycle. CDC provides the most comprehensive guid-
Medium, or another testing method that produces verifica-
ance regarding administration of intravenous medications,
tion results statistically comparable with those methods may
including administration times, frequency of infusion set
be utilized.67
changes, use of filters, and prevention of catheter-related
If sterility testing results are not received prior to dis-
infections.38,47
pensing, procedures must be in place for daily observation
of the sterility test specimens, immediate recall of dispensed
CSPs, and notification of patients and their physicians if mi- Personnel
crobial or fungal growth is observed. An investigation into
the root cause of contamination must occur if sterility testing Personnel Responsibilities
is positive. The term compounding personnel refers to any individual
All high-risk CSPs prepared in batches of more than involved in compounding sterile preparations, regardless
25 units, with the exception of inhalation or ophthalmic of profession. Compounding personnel are responsible for
preparations, must be tested to ensure that they do not con- ensuring that CSPs are accurately identified, measured, di-
tain excessive bacterial endotoxins, as described in USP luted, and mixed and are correctly purified, sterilized, pack-
chapter 85, Bacterial Endotoxins Test,68 and USP chapter aged, sealed, labeled, stored, dispensed, distributed, and
151, Pyrogen Test.69 Endotoxin limits (reported in USP en- disposed of if not used. Emphasis should be on the need to
Table 11.
Beyond-Use Dates for Ampuls, Single-Dose, and Multiple-Dose Containers (Adapted from USP Chapter 79715)
Opened and Maintained within an ISO Opened Outside an ISO Class 5 Environment or
Container Class 5 Environment Taken from ISO Class 5 Conditions to Less Clean Air
Ampuls One time use; cannot be stored One time use; cannot be stored
Single-dose vials One time use, cannot be stored; contents One time use; cannot be stored
of unopened vial may be repackaged in
times of critical need49
Pharmacy bulk packages 6 hoursa Not intended for use outside ISO 5 environment
a
Multiple-dose vials 28 days 28 daysa
a
Unless otherwise specified by manufacturer.
maintain quality standards for the control of processes, com- • Drying hands and arms with nonshedding disposable
ponents, and environments and for the skill and knowledge towels or an electronic hand dryer.
of personnel who prepare CSPs. • Sanitizing hands with application of a waterless,
Accurate identification and inspection of quality and alcohol-based hand rub (ABHR) with persistent activ-
purity of non-sterile chemicals or non-sterile ingredients ity prior to donning sterile gloves.
are necessary for the integrity of the finished preparations.
Upon arrival from the manufacturer and subsequently after Garbing occurs in the ante area and should be sequenced as
opening, bulk packages should be inspected for breaks in follows (from “dirtiest” to “cleanest”):
the package or closure integrity and for proper appearance,
color, odor, and texture. • Don shoe covers, hair and beard covers, and a mask.
If nonsterile ingredients are not official USP or • Perform hand hygiene.
National Formulary products, compounding personnel must • Don gown, fastened securely at the neck and wrists.
require a Certificate of Analysis from the manufacturer to • Sanitize hands using an ABHR and allow hands to dry.
accompany the products.59 Once a product is received from • Enter the buffer area (if facility layout dictates, this
the manufacturer, the date of receipt must be clearly marked step may occur after the following two steps).
on each package. If a manufacturer’s expiration date is not • Don sterile powder-free gloves.
provided, chemicals should be given a three-year BUD from • Sanitize the gloves with application of 70% sterile IPA
the time of opening unless inspection or testing deems the and allow gloves to dry.
product within drug monograph specification (if available)
to be used for a longer time.59 Studies support the use of sterile rather than nonsterile
Compounding personnel must have an understanding gloves in the reduction of initial bioburden.71 Furthermore,
of how combining different agents in a preparation may af- nonsterile gloves run the risk of cross-contamination from
fect bioavailability, compatibility (visual and chemical), pH, hands touching multiple gloves as they are removed from a
and concentration effects. Factors that influence stability stock box or container. Gloves must be inspected by person-
(e.g., temperature, pH, sorption, photolysis, and chemical nel on a routine basis during the compounding process to
degradation) must be carefully evaluated and supported by check for tears or holes. The gloves should be disinfected
references or appropriate testing. with sterile 70% IPA throughout the compounding process
Compounding personnel must understand and dem- and each time contaminated items are touched.
onstrate competency in aseptic technique and for the prod- When high-risk compounding operations prior to ter-
ucts and systems used in CSP preparation, such as needles, minal sterilization occur, personnel must glove and garb as
syringes, administration sets, fluid containers, and com- stated above.
pounding devices. Aseptic principles and techniques are When exiting the compounding area during a work shift,
explained in depth in Compounding Sterile Preparations53 gowns that are not soiled may be removed and retained in the
and demonstrated in Basics of Aseptic Compounding ante area and re-worn during the same work shift. All other
Technique,54 Getting Started in Aseptic Compounding,55 and garb, including gloves, must be removed and replaced, and
Compounding Sterile Preparations: ASHP’s Video Guide to proper hand hygiene must be completed before re-entering
Chapter <797>.56 Personnel must understand the types of the compounding area. When CAIs are utilized, compounding
PECs, HEPA filtration, and airflow concepts that are critical personnel must glove and garb as above, unless the manufac-
to sterile compounding. turer of the isolator provides written documentation based on
Policies should be developed in conjunction with em- environmental testing that any or all of the components of
ployee health or infection control personnel to set thresh- personnel hygiene and garbing are not required based on the
olds for health status fitness for compounding personnel. PECs of the facility where the device is located.
Compounding personnel with weeping sores, rashes, con- Proper garb should always be used with CACIs, be-
junctivitis, or respiratory infections must not participate in cause personnel will be handling hazardous materials. Vials
compounding processes until these conditions resolve. may be contaminated, even upon delivery,72–74 and the garb
is needed to protect compounding personnel from unex-
Hygiene and Garbing. Proper preparation for sterile, non- pected drug residue and from inadvertent spills.
hazardous drug compounding must include effective hand
hygiene and garbing procedures. To minimize the number of Compounding Areas. Compounding personnel must under-
particles introduced into the sterile compounding area and stand the purposes of and relationships between ante, buffer,
to minimize the risk of bacteria, all outer jackets and sweat- segregated, and storage areas. A systematic process of enter-
ers, visible jewelry, and cosmetics must be removed prior to ing and exiting the various areas is necessary to minimize
initiating the handwashing and garbing processes. Personal contamination. Food, drinks, and gum are prohibited in all of
electronic devices (e.g., cell phones, MP3 players) and any these areas. Since shedding from paper and labels provides a
associated attachments must be removed prior to hand hy- source of nonviable particles, only paper products essential
giene and garbing and should not be used within the sterile to the compounding process should be allowed in the buffer
compounding area. area. Corrugated cardboard packaging must be eliminated
Hand hygiene must be performed prior to and after from buffer areas and should be eliminated from ante areas,
gowning and includes: with all products and components such as needles, syringes,
and tubing removed from their outer cardboard packaging
• Washing hands, under the fingernails, wrists, and up and decontaminated by wiping the individual packages (if
to the elbow for 30 seconds with a facility-approved not in an overwrap) with a suitable disinfectant (e.g.,70%
agent. IPA) prior to entering the buffer area.
When used for sterile compounding, items in plastic Storage of CSPs

or foil overwrap should remain in the overwrap until intro-
duced into the ISO Class 5 PEC, at which point they should Temperatures of areas used for storage on patient-care and
be opened immediately before placing in the PEC and the procedural units, including room temperature and in refrig-
overwrap immediately discarded.75 Items stored in the buf- erators, freezers, and warmers, must be monitored and re-
fer area but not in an overwrap must be decontaminated corded daily. On at least a monthly basis, compounding per-
again prior to entering the PEC, as items may be stored in a sonnel or designated pharmacy personnel should evaluate
buffer area for an extended period of time and may become storage areas for appropriate secure conditions, separation
contaminated by dust or other particles. of drugs and food, and proper use and disposal of single- and
multiple-dose vials.
Packaging and Labeling
Control and Oversight of IV Solutions
Packaging and subsequent labeling are critical to patient
safety. Packaging must be appropriate to preserve both ste- Some facilities delegate storage and distribution of paren-
rility and stability until the BUD. Proper labeling requires an teral solutions to materials management. Since the products
understanding of compounding risk levels and how to deter- are prescription drugs, the pharmacy must maintain over-
mine BUDs based on both stability and sterility. sight, including selection of appropriate products, package
Labels for single compounded preparations must, at a sizes, and forms; safe and secure storage; and temperature
minimum, include the following: control. IV solutions that contain medications (e.g., potas-
sium chloride, heparin, dopamine, dextran, mannitol) or
• Names of active ingredients, high-risk agents (e.g., sterile water, sodium chloride greater
• Amounts or concentrations of active ingredients, than 0.9%, and parenteral nutrition components) should be
• BUD and time, stored in and distributed by the pharmacy.
• Storage requirements, and
• Identification of responsible compounding personnel.
Transporting CSPs
Labels for batch-prepared CSPs must also include:
All personnel involved in the handling, transport, or stor-
age of CSPs, whether they are compounding personnel or
• Control or lot number,
not, must be properly trained to complete these tasks, and
• Appropriate auxiliary labeling (including precau-
the performance of all personnel, including contractors,
tions), and
must be monitored for compliance with facility policies.
• Device-specific instructions (when appropriate).
Transportation methods for CSPs should be evaluated, as
Federal and state regulations and accreditation re- some forms of transportation, such as pneumatic tube sys-
quirements may necessitate additional label information be- tems, may adversely affect stability or integrity. Pneumatic
fore the CSP is dispensed to a specific patient. tube delivery may require additional padding around con-
Verification of compounding accuracy and sterility tainers to ensure that heat and light exposure and impact are
incorporates physical inspection, ensuring compounding ac- minimized. Some preparations may degrade if shaken, and
curacy processes are in place, and (when applicable) steril- therefore personnel, including pharmacy and nursing per-
ity and endotoxin testing. Finished preparation evaluation is sonnel, should be aware of which preparations may not be
the responsibility of compounding personnel and should be delivered via a pneumatic tube device.
performed during the compounding process and when the Hazardous drug transport must incorporate measures
preparation leaves the storage area. Visual inspection should to maintain CSP integrity while minimizing the risk of drug
assess particulate matter, coring, cloudiness, leaks, and con- residue exposure to patients, personnel, and the environ-
tainer and closure integrity. ment. These preparations should always be delivered in a
Compounding accuracy checks must comply with fed- bag to prevent leakage or accidental exposure during trans-
eral and state dispensing regulations and include accuracy port, and they should not be delivered using a pneumatic
of the product or preparation and the labeling. Prescription tube device due to the risk of contamination to the environ-
orders, compounding procedures, records, and materi- ment if breakage occurs. Cleaning protocols for pneumatic
als used to prepare the compounds should be evaluated. A tube systems are inadequate for hazardous drug contamina-
process should be implemented to confirm that the com- tion throughout the system.
pounding process and end-preparation testing are properly Transport may occur outside of the compounding facil-
done. Checking procedures should follow facility policy ity to other facilities or directly to patients. In these situations,
and procedures and may be accomplished via cameras or compounding personnel must ensure physical integrity, steril-
other devices, by video recordings, or by keeping the used ity, and stability are maintained during transit. Proper packag-
additive containers and syringes with the final product until ing must be chosen to prevent contamination, leaks, damage,
checked. The check ideally should be performed by some- and temperature variations and to protect the end recipients
one other than the compounder to decrease confirmation and transporting personnel from harm. Handling and expo-
bias. Accuracy can be further verified by weighing when ap- sure instructions should be legibly displayed on the outside of
plicable and practical. When using an ACD, specific gravity shipping containers. BUDs, storage instructions, and disposal
values must be independently confirmed after being entered instructions for out-of-date preparations must be available to
to ensure proper volumes are delivered during the com- recipients, and recipients must be able to properly store CSPs
pounding process. (e.g., in a refrigerator or freezer, if necessary).
Redispensing CSPs Personnel Responsibilities

for Specialty Preparations
If facility policy allows redispensing of CSPs, the process
must only be done by compounding personnel to ensure Specialty preparations (e.g., allergen extracts, radiopharma-
continued sterility, purity, and stability. Facilities must de- ceuticals, and evolving technology and therapeutics such as
termine how to track original preparation and thaw dates (if biologics and nanotechnology) provide specific treatments
applicable) and be able to detect product tampering. There for patients and require specialized procedures to be fol-
must be policies and procedures in place to provide assur- lowed. Although compounding of intradermal or subcuta-
ance of proper storage conditions for each product or prepa- neous injections of allergen extracts would ideally occur
ration (e.g., refrigeration, protection from light, package in- under conditions for similar risk-level CSPs, they may not
tegrity) before redispensing. CSPs must not be redispensed necessarily be subject to the same personnel, environmen-
if package integrity has been compromised, including tem- tal, and storage requirements as for other CSPs of a similar
perature variations. risk level, as long as the following criteria outlined by USP
chapter 797,15 in conjunction with the American Academy
Personnel Responsibilities for Handling, of Otolaryngic Allergy and the Joint Council of Allergy,
Preparation, and Disposal of Cytotoxic Asthma and Immunology,78 are met:
and Other Hazardous Agents
• Compounding process involves simple transfer using
The Occupational Safety and Health Administration (OSHA) sterile components and allergen products.
requires that employers and employees be made aware of the • All allergen extracts contain effective preservatives to
hazards of all chemicals used in the workplace, including prevent microbial growth.
drugs.76 Compounding personnel of reproductive capabil- • All hand hygiene, garbing, and gloving procedures for
ity shall confirm in writing that they understand the risks of low-risk compounding, with the exception of donning
handling hazardous drugs.15 Personnel at high risk of expo- shoe covers, must be followed.
sure to hazardous drugs should be enrolled in a medical sur- • Ampul necks and vial stoppers are disinfected by wip-
veillance program. In many larger facilities, the employee’s ing with sufficient amounts of sterile 70% IPA to en-
health department will determine who should be enrolled. sure that the critical sites remain wet for 10 seconds
Specific guidance about surveillance for health care workers and are allowed to dry.
exposed to hazardous drugs is available from NIOSH,77 as • Direct contact contamination of critical sites is mini-
is a list of drugs NIOSH considers hazardous.27 The risks of mized by utilizing aseptic compounding.
occupational exposure to hazardous drugs and their poten- • Multiple-dose vials are labeled with the name of one
tial effects on compounding personnel should be conveyed patient and a BUD and storage temperature range
to employees during employee orientation and in an ongo- based on manufacturer recommendations or published
ing manner through continuing education and monitoring at literature. Single-dose extracts are not to be stored for
least annually. Training and competency programs should be subsequent use after entry.
provided in addition to competencies for compounding of
non-hazardous sterile drugs, with details of differentiating Nuclear pharmacies are regulated by the Nuclear Regu-
the garbing, storage, preparation, and disposal procedures latory Commission as well as other applicable pharmacy laws
for hazardous drugs. USP chapter 797 requires that training, and regulations. USP chapter 823, Radiopharmaceuticals for
at a minimum, include: Positron Emission Tomography,79 provides the standards for
production facilities. Once the components for use in posi-
• Safe aseptic manipulation practices. tron emission tomography are released as finished prepa-
• Negative pressure techniques when compounding. rations, handling, manipulation, and use are considered
• Proper utilization of a BSC or CACI. compounding by USP chapter 79715 and for the purposes
• Correct use of closed-system transfer devices of these guidelines. Low-risk-level radiopharmaceuticals are
(CSTDs), if used. those compounded from sterile components with a volume
• Containment, cleanup, and disposal procedures for of less than 100 mL for a single-dose injection or no more
breakages and spills. than 30 mL taken from a multiple-dose container.15 These
• Treatment of personnel contact and inhalation expo- radiopharmaceutical preparations must be compounded in
sure.15 an ISO Class 5 PEC within an ISO Class 8 environment.
Non-radiopharmaceuticals compounded in nuclear
OSHA requires more general training on chemical pharmacies must be compounded under full USP 797 compli-
label elements and safety data sheet (SDS) format.76 When ant conditions. The radiopharmaceutical exemption in USP
training or evaluating competency, facilities may choose chapter 79715 does not apply to non-radiopharmaceuticals.
products to objectively evaluate hazardous drug compound- The concept of limiting radiation exposure to a level
ing technique. These products utilize dyes or fluorescence to that is as low as reasonably achievable (ALARA) must be
determine personnel technique and assess for spills or haz- adhered to for handling, compounding, and visual inspec-
ardous drug exposures. tion of products. Technetium-99m/molybdenum-99 gen-
Definitions of hazardous drugs and proper handling erator system operations and storage must occur within an
of hazardous drugs, including receiving, distribution, stock- ISO Class 8 environment and must further comply with
ing, inventorying, preparation, transport, and disposal, are all manufacturer’s recommendations and federal and state
all concepts discussed in detail in the ASHP Guidelines on regulations. Manufacturer’s guidelines for BUDs should be
Handling Hazardous Drugs.28 followed for radiopharmaceutical multiple-dose vials that
are compounded with technetium-99m and exposed to ISO aseptic technique.15 Media-fill tests should be customized to
Class 5 conditions with no direct contact contamination. mimic the most challenging preparations compounded by
personnel on a regular basis in a specific facility. Testing
Personnel Compounding Competency should occur at least every 12 months for personnel who
compound low- and medium-risk preparations, while testing
Touch contamination remains the primary cause of micro- at least every 6 months is required for personnel involved
bial contamination in sterile compounding.71,80 For this rea- in compounding high-risk preparations. The actual test-
son, personnel training and assessment of competency are ing should take place under conditions that reflect realistic
of utmost importance to ensure the lowest possible risk for workflow, such as the end of a shift, to simulate a worst-
contamination due to human error. For low- and medium- case scenario environment for compounding sterile prepa-
risk operations, training and competency assessment are re- rations. Once started, the test should be completed without
quired initially upon hire or upon transfer to compounding interruption. Fluid culture media are available commercially
responsibilities, and again at least every 12 months for all for low- and medium-risk evaluations. High-risk assess-
staff involved in the compounding of sterile products. High- ments may utilize nonsterile nutrient medium in a powder
risk operations require more frequent assessments, and staff form, which may be diluted and sterilized by filter methods.
must be evaluated upon hire or transfer and again at least Finished tests should be incubated per manufacturer’s rec-
every six months. ommendations. If incubators are in the pharmacy, they must
As part of the training competency assessment, a writ- be placed outside the sterile compounding area. Ideally, the
ten test that evaluates knowledge about proper compound- facility’s microbiology services should incubate and read
ing SOPs, aseptic technique, cleaning and garbing, environ- the tests, providing an independent evaluation by qualified
mental monitoring, calculations, risk levels and BUDs, and individuals. Turbidity in the culture media signifies failure
quality assurance principles must be successfully completed. of the media-fill testing and requires retesting of compound-
Thresholds for passing the written examination should be set ing personnel. Personnel who fail these tests will require
by the facility. While written tests assess knowledge, hands- re-training and may not compound sterile preparations until
on observation of daily duties assesses for proper technique. tests have been repeated with successful results.
Personnel should be able to demonstrate at least the follow-
ing in a hands-on, witnessed assessment, as applicable to Glove Fingertip Testing
their compounding responsibilities: Three sets of glove fingertip evaluations must be completed
with no growth prior to personnel being allowed to com-
pound sterile preparations. This initial testing involves com-
• Proper hand hygiene technique (see Appendix III of
pounding personnel completing all necessary hand hygiene
USP chapter 79715 for a sample assessment form).
and garbing procedures (with the exception of applying
• Proper gloving and garbing technique, including suc-
sterile 70% IPA to gloves). Immediately upon completion
cessful glove fingertip test (see Appendix III of USP
chapter 79715 for a sample assessment form). of these procedures, the glove fingertip and thumb samples
from each hand are placed on sterile nutrient agar plates. The
• Proper aseptic technique, including successful media-
samples should be incubated (such as by the facility’s mi-
fill test (see Appendix IV of USP chapter 79715 for a
sample assessment form). crobiology personnel) according to manufacturer standards.
This test must be successfully completed three times ini-
• Proper cleaning and disinfecting procedures, including
tially, then at least every 12 months. Personnel compound-
successful surface sampling test (see Appendix V of
USP chapter 79715 for a sample assessment form and ing high-risk products must successfully complete the test
Appendix II for information about cleaning products). at least every 6 months. Suggested thresholds for contami-
nation limits can be found in Table 6. Patterns of failures
• Competency in the compounding of hazardous drugs.
(personnel, media, or facility) must be evaluated as part of
• Competency in the compounding of allergen extracts.
the facility’s quality assurance plan. Qualified microbiology
• Competency in the compounding of radiopharmaceu-
personnel and the facility’s infection control practitioner
ticals.
should be consulted.
• Competency in the use of sterile devices, such as filter
needles, injection port adapters, sterile fluid transfer
devices, and CSTDs. Growth Media Requirements
Sterile nutrient agar for media-fill testing, plates for fin-
• Competency in the use of pharmacy compounding de-
gertip testing, and surface testing materials are available
vices.
from multiple vendors. USP chapters 797 and 1116 provide
• Ability to fill pump reservoirs.
specifications and requirements.15,81 The media-fill testing
• Competency to perform end-product testing and steril-
growth media and viable airborne particle plates should uti-
ization.
lize a Soybean-Casein Digest medium, which may also be
USP chapter 79715 requires specific assessments to be sold as Tryptic Soy Agar/Broth. The agar plates for glove
completed using sterile nutrient agar growth media to test fingertip testing and surface testing should utilize general
for potential contamination. Personnel-specific examples of nutrient agar with neutralizing agents such as lecithin and
this type of testing include media-fill testing of aseptic tech- polysorbate 80.
nique and glove fingertip testing of compounding personnel.
SOP Development
Media-Fill Testing
As described in USP chapter 797, the media-fill component SOPs are documents containing detailed, step-by-step in-
of personnel assessment provides an objective evaluation of structions on how to perform a task or procedure so that all
personnel consistently perform the task or procedure in the • Safety—injuries, hazardous spills, and accidental ex-
same manner. SOPs are part of a good quality assurance pro- posures.
gram within the pharmacy. They provide assurance that: • Quality assurance—inspection of CSPs, testing of
CSPs, BUDs, delivery, and storage of final CSPs, pa-
• Equipment and facilities are properly maintained in tient monitoring, adverse event reporting, and person-
good working order. nel and environmental monitoring.
• Personnel are properly educated, trained, and evaluated. • Administration—record keeping and management.
• Supplies are received, stored, and disposed of properly
and meet compendial standards. All significant procedures performed in a pharmacy
• All tasks and procedures are performed uniformly and should be covered by SOPs and documentation. These pro-
documented. cedures should be routinely reviewed and modified for im-
provements at least annually.
There are several components that should be included
in an SOP:
Quality Assurance Program
• Title—should clearly identify the task.
The purpose of a quality assurance program is to provide
• SOP number—an internal department number as-
a mechanism for monitoring, evaluating, correcting, and
signed by the organization to identify it.
improving activities and processes. A quality assurance pro-
• Author(s)—the name of the person or persons who
gram should review and analyze objective data and use these
write the SOP so that problems and revisions can be
addressed. data to develop action plans. Facilities should actively work
to correct problems detected and improve activities and pro-
• Date effective—date when the SOP is implemented
into the compounding routine. cesses as needed. Any plan designed to correct problems
should include follow-up parameters to make certain actions
• Authorization signature—person or committee that
approves the SOP. were taken and were effective.
Activities and processes that are identified based on
• Responsibility—person- or persons-in-charge who are
responsible for making sure that the SOP is performed their high frequency, high risk, or problem-prone nature
properly. should have specific monitoring and evaluation criteria as-
• Purpose of the procedure—brief explanation of why signed for objective and measurable assessment. The quality
the SOP is necessary or being implemented. assurance program should encompass any and all activities
• Equipment and supplies required—list of equipment that are included in previous sections of this document as
and supplies needed to perform the SOP. elements which should be assessed and documented. This
• Procedure—detailed step-by-step explanation that can includes, but is not limited to:
be easily followed by different individuals with the
same results. The instructions should be concise to • Personnel training and assessment,
minimize any required interpretation. • Environmental monitoring, and
• References—references should be listed to support the • Equipment calibration and maintenance.
implementation and use of the SOP.
• Documentation form—easily accessible written re- Specific quality assurance measures, pursuant to each
cord or log that demonstrates that the SOP is being risk level compounded in a facility, include routine cleaning
performed routinely and properly. and disinfection and air quality testing, visual confirmation
• Revision—documentation of the date that an SOP has of proper garbing procedures, review of all orders and prep-
been reviewed and the name of the reviewer. arations to ensure accuracy of compounded products, and
visual inspection of final CSPs to confirm the absence of
USP chapter 79715 lists and recommends SOPs and particulate matter or leakage.
should be reviewed to guide the pharmacy department in de- A critical part of any quality assurance program is
veloping, writing, and implementing SOPs. There should be proper documentation, corrective action, and follow-up.
SOPs written to address tasks or procedures in the following Institutions must determine how results will be reported
general categories: and evaluated, including development of action limits and
thresholds. Thresholds and follow-up mechanisms must
• Personnel—training, education, skills, competency be in place prior to initiating a quality assurance program
evaluations, and responsibilities. or immediately after collecting initial benchmark data.
• Facilities—access, cleaning, maintenance, use, moni- Responsible persons for completing these tasks should be
toring, and testing. identified and trained, if necessary, in the proper execution
• Equipment—calibration, maintenance, cleaning, certi- of the quality assurance plan. Results of monitoring and
fication, verification, and use. measurements should be reported within and outside of the
• Supplies—ordering, storing, certification, inspection, department responsible for compounding practices to com-
and disposal. mittees such as Infection Control and Quality Improvement.
• Compounding procedures—preparation of various If corrective action is needed, the problem should be
sterile compounded medications (e.g., batches, total resolved as soon as possible. Assessment of problems with
parenteral nutrition, hazardous drugs, epidural, pa- compounding errors, evident contamination during prepara-
tient-controlled analgesia, or ophthalmics), formulas, tion, quarantine, or patterns of personnel or environmental
assigning BUDs, handling, and packaging. monitoring outside the established parameters require for-
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68. Bacterial endotoxins test (general information chapter The United States Pharmacopeial Convention; 2011:
85). In: The United States pharmacopeia, 34th rev., 633–41.
and The national formulary, 29th ed. Rockville, MD: 82. Agency for Healthcare Research and Quality Patient
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78–82. root cause analysis. www.psnet.ahrq.gov/primer.
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United States pharmacopeia, 34th rev., and The na- 83. DeRosier J, Stalhandske E, Bagian JP, et al. Using
tional formulary, 29th ed. Rockville, MD: The United health care failure mode and effects analysis: the VA
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70. Oversight of Care, Treatment, and Services analysis system. Jt Comm J Qual Improv. 2002; 28:
Provided through Contractual Agreement (Standard 248–67.
LD.04.03.09). Comprehensive accreditation manual
for hospitals: the official handbook. Oakbrook Terrace, Approved by the ASHP Board of Directors on June 2, 2013.
IL: The Joint Commission; 2012. Developed through the ASHP Council on Pharmacy Practice. These
guidelines supersede the ASHP Guidelines on Quality Assurance for D. Bing, M.S., FASHP; E. Clyde Buchanan, M.S., FASHP; Ryan
Pharmacy-Prepared Sterile Products dated April 27, 2000. A. Forrey, Pharm.D., M.S.; Eric S. Kastango, M.B.A., FASHP; Lee
B. Murdaugh, Ph.D.; Daryl McCollum, Pharm.D.; Luci A. Power,
Patricia C. Kienle, M.P.A., FASHP, is gratefully acknowledged M.S.; Philip J. Schneider, M.S., FASHP; and James T. Wagner.
for leading the development of and drafting substantial portions of
these guidelines. Linda F. McElhiney, Pharm.D.; Richard B. Osteen, Copyright © 2014, American Society of Health-System Pharmacists,
D.Ph.; Ed Troell, M.B.A.; Fred Massoomi, Pharm.D., FASHP; Inc. All rights reserved.
Kathleen Sheehy, M.B.A.; and Angela T. Cassano, Pharm.D.,
BCPS, are also gratefully acknowledged for their contributions to The bibliographic citation for this document is as follows: American
these guidelines. Society of Health-System Pharmacists. ASHP Guidelines on
Compounding Sterile Preparations. Am J Health-Syst Pharm. 2014;
ASHP gratefully acknowledges the following individuals for review- 71:145–66.
ing these guidelines (review does not imply endorsement): Caryn
ASHP Guidelines on Handling Hazardous Drugs

In 1990, the American Society of Health-System Pharmacists as well as long-term effects. Anecdotal and case reports
(ASHP) published its revised technical assistance bulletin in the literature range from skin-related and ocular effects
(TAB) on handling cytotoxic and hazardous drugs.1 The in- to flu-like symptoms and headache.4,5,10–17 Two controlled
formation and recommendations contained in that document surveys have reported significant increases in a number of
were current to June 1988. Continuing reports of workplace symptoms, including sore throat, chronic cough, infections,
contamination and concerns for health care worker safety dizziness, eye irritation, and headaches, among nurses, phar-
prompted the Occupational Safety and Health Administration macists, and pharmacy technicians routinely exposed to
(OSHA) to issue new guidelines on controlling occupational hazardous drugs in the workplace.18,19 Reproductive stud-
exposure to hazardous drugs in 1995.2,3 In 2004, the National ies on health care workers have shown an increase in fetal
Institute for Occupational Safety and Health (NIOSH) issued abnormalities, fetal loss, and fertility impairment result-
the “NIOSH Alert: Preventing Occupational Exposure to ing from occupational exposure to these potent drugs.20–23
Antineoplastic and Other Hazardous Drugs in Health Care Antineoplastic drugs and immunosuppressants are some of
Settings.”4 The following ASHP Guidelines on Handling the types of drugs included on lists of known or suspected
Hazardous Drugs include information from these recom- human carcinogens by the National Toxicology Program24
mendations and are current to 2004. and the International Agency for Research on Cancer.25
Although the increased incidence of cancers for occupa-
Purpose tionally exposed groups has been investigated with varying
results,26,27 a formal risk assessment of occupationally ex-
The purpose of these guidelines is to (1) update the reader posed pharmacy workers by Sessink et al.28 estimated that
on new and continuing concerns for health care workers cyclophosphamide causes an additional 1.4–10 cases of
handling hazardous drugs and (2) provide information on cancer per million workers each year. This estimate, which
recommendations, including those regarding equipment, considered workplace contamination and worker contamina-
that have been developed since the publication of the previ- tion and excretion in combination with animal and patient
ous TAB. Because studies have shown that contamination studies, was based on a conservative exposure level. Connor
occurs in many settings, these guidelines should be imple- et al.29 found greater surface contamination in a study of
mented wherever hazardous drugs are received, stored, pre- U.S. and Canadian clinical settings than had been reported
pared, administered, or disposed.2–7 in European studies conducted by Sessink and colleagues.30–32
Comprehensive reviews of the literature covering an- Ensslin et al.33 reported an almost fivefold greater daily
ecdotal and case reports of surface contamination, worker average excretion of cyclophosphamide in their study than
contamination, and risk assessment are available from that reported by Sessink. These later findings could add
OSHA,2,3 NIOSH,4 and individual authors.5–7 The primary 7–50 additional cancer cases per year per million workers to
goal of this document is to provide recommendations for the Sessink’s estimate. From these and other studies that show
safe handling of hazardous drugs. variations in work practices and engineering controls,34,35
These guidelines represent the recommendations of it may be assumed that such variations contribute to differ-
many groups and individuals who have worked tirelessly ences in surface and worker contamination.
over decades to reduce the potential harmful effects of haz-
ardous drugs on health care workers. The research available Routes of Exposure. Numerous studies showed the pres-
to date, as well as the opinions of thought leaders in this ence of hazardous drugs in the urine of health care work-
area, is reflected in the guidelines. Where possible, recom- ers.30–34,36–41 Hazardous drugs enter the body through in-
mendations are evidence based. In the absence of published halation, accidental injection, ingestion of contaminated
data, professional judgment, experience, and common sense foodstuffs or mouth contact with contaminated hands, and
have been used. dermal absorption. While inhalation might be suspected
as the primary route of exposure, air sampling studies of
pharmacy and clinic environments have often demonstrated
Background
low levels of or no airborne contaminants.30–32,40 Recent
concerns about the efficacy of the sampling methods42 and
Workers may be exposed to a hazardous drug at many points
the possibility that at least one of the marker drugs may be
during its manufacture, transport, distribution, receipt, stor-
volatile42–45 and thus not captured on the standard sampling
age, preparation, and administration, as well as during waste
filter leave the matter of inhalational exposure unresolved.
handling and equipment maintenance and repair. All work-
Surface contamination studies do, however, suggest that
ers involved in these activities have the potential for contact
dermal contact and absorption may be a primary route of
with uncontained drug.
exposure.31,46 While some hazardous drugs are dermally
Early concerns regarding the safety of workers han-
absorbed, a 1992 report showed no detectable skin absorp-
dling potentially hazardous drugs focused on antineoplastic
tion of doxorubicin, daunorubicin, vincristine, vinblastine,
drugs when reports of second cancers in patients treated with
or melphalan.47 An alternative to dermal absorption is that
these agents were coupled with the discovery of mutagenic
surface contamination transferred to hands may be ingested
substances in nurses who handled these drugs and cared for
via the hand-to-mouth route.48,49 One or more of these routes
treated patients.8,9 Exposure to these drugs in the workplace
might be responsible for workers’ exposure.
has been associated with acute and short-term reactions,
Hazard Assessment. The risk to health care personnel from Definition of Hazardous Drugs
handling hazardous drugs is the result of a combination of
the inherent toxicity of the drugs and the extent to which The federal hazard communication standard (HCS) defines
workers are exposed to the drugs in the course of their daily a hazardous chemical as any chemical that is a physical or
job activities. Both hazard identification (the qualitative health hazard.52,53 A health hazard is defined as a chemical
evaluation of the toxicity of a given drug) and an exposure for which there is statistically significant evidence, based on
assessment (the amount of worker contact with the drug) are at least one study conducted in accordance with established
required to complete a hazard assessment. As the hazard as- scientific principles, that acute or chronic health effects may
sessment is specific to the safety program and safety equip- occur in exposed employees. The HCS further notes that the
ment in place at a work site, a formal hazard assessment may term health hazard includes chemicals that are carcinogens,
not be available for most practitioners. An alternative is a toxic or highly toxic agents, reproductive toxins, irritants,
performance-based, observational approach. Observation of corrosives, sensitizers, and agents that produce target organ
current work practices, equipment, and the physical layout effects.
of work areas where hazardous drugs are handled at any A 1990 ASHP TAB proposed criteria to determine
given site will serve as an initial assessment of appropriate which drugs should be considered hazardous and handled
and inappropriate practices.4 within an established safety program.1 OSHA adopted these
criteria in its 1995 guidelines, which were posted on its Web
Hazardous Drugs as Sterile Preparations site in 1999.2,3 The TAB’s definition of hazardous drugs was
revised by the NIOSH Working Group on Hazardous Drugs
Many hazardous drugs are designed for parenteral adminis- for the 2004 alert.4 These definitions are compared in Table
tration, requiring aseptic reconstitution or dilution to yield a 1.
final sterile preparation. As such, the compounding of these Each facility should create its own list of hazardous
products is regulated as pharmaceutical compounding by drugs based on specific criteria. Appendix A of the NIOSH
the United States Pharmacopeia (USP), chapter 797.50 The alert contains related guidance and a sample list.4 When
intent of chapter 797 is to protect patients from improperly drugs are purchased for the first time, they must be evalu-
compounded sterile preparations by regulating facilities, ated to determine whether they should be included in the
equipment, and work practices to ensure the sterility of ex- facility’s list of hazardous drugs. As the use and number of
temporaneously compounded sterile preparations. Chapter hazardous drugs increase, so too do the opportunities for
797 addresses not only the sterility of a preparation but also health care worker exposure. Investigational drugs must be
the accuracy of its composition. Because many hazardous evaluated according to the information provided to the prin-
drugs are very potent, there is little margin for error in com- cipal investigator. If the information provided is deemed in-
pounding. sufficient to make an informed decision, the investigational
The initial version of chapter 797, released in early drug should be considered hazardous until more information
2004, provided only minimal guidance for the handling of is available.
hazardous drugs, limiting this issue to a short discussion
of chemotoxic agents in the document’s section on aseptic Recommendations
technique. The chapter referred to standards established by
the International Organization for Standardization (ISO)51 Safety Program. Policies and procedures for the safe handling
that address the acceptable air quality (as measured by par- of hazardous drugs must be in place for all situations in which
ticulate counts) in the critical environment but failed to dis- these drugs are used throughout a facility. A comprehensive
cuss airflow, air exchanges per hour, or pressure gradients safety program must be developed that deals with all aspects of
of the ISO standards for cleanrooms and associated envi- the safe handling of hazardous drugs. This program must be a
ronments for compounding sterile products. The chapter collaborative effort, with input from all affected depart-
did not describe the containment procedures necessary for ments, such as pharmacy, nursing, medical staff, housekeep-
compounding sterile hazardous agents, leaving it to the prac- ing, transportation, maintenance, employee health, risk man-
titioner to simultaneously comply with the need to maintain agement, industrial hygiene, clinical laboratories, and safety.
a critical environment for compounded sterile products for A key element of this safety program is the Material Safety
patient safety while ensuring a contained environment for Data Sheet (MSDS) mandated by the HCS.52,53 Employers
worker safety. The use of positive-pressure isolators for are required to have an MSDS available for all hazardous
compounding hazardous drugs or placement of a Class II bi- agents in the workplace. A comprehensive safety program
ological-safety cabinet (BSC) for use with hazardous drugs must include a process for monitoring and updating the
in a positive-pressure environment may result in airborne MSDS database. When a hazardous drug is purchased for
contamination of adjacent areas. Engineering assessment the first time, an MSDS must be received from the manufac-
of designs of areas where this may occur should be done turer or distributor. The MSDS should define the appropriate
to address concerns of contaminant dissemination. Because handling precautions, including protective equipment, con-
hazardous drugs are also compounded in areas adjacent to trols, and spill management associated with the drug. Many
patients and their family members (e.g., in chemotherapy MSDSs are available online through the specific manufac-
infusion centers), inappropriate environmental containment turer or through safety-information services.
puts them, as well as health care workers, at risk. Because Drugs that have been identified as requiring safe han-
USP review is a dynamic and ongoing process, future revi- dling precautions should be clearly labeled at all times dur-
sions are likely to address these concerns. Practitioners are ing their transport and use. The HCS applies to all workers,
encouraged to monitor the process and participate when ap- including those handling hazardous drugs at the manufac-
propriate.
Table 1. unpack cartons. Visual examina-

Comparison of 2004 NIOSH and 1990 ASHP Definitions of Hazardous Drugsa tion of such cartons for outward
signs of damage or breakage
NIOSH4 ASHP1 is an important first step in the
Carcinogenicity Carcinogenicity in animal models, in the receiving process. Policies and
patient population, or both as reported procedures must be in place for
by the International Agency for handling damaged cartons or con-
Research on Cancer tainers of hazardous drugs (e.g.,
Teratogenicity or developmental toxicityb Teratogenicity in animal studies or in returning the damaged goods to
treated patients the distributor using appropriate
Reproductive toxicityb Fertility impairment in animal studies or containment techniques). These
in treated patients procedures should include the use
Organ toxicity at low dosesb Evidence of serious organ or other
of PPE, which must be supplied by
toxicity at low doses in animal models
or treated patients
the employer. As there may be no
Genotoxicityc Genotoxicity (i.e., mutagenicity and ventilation protection in the area
clastogenicity in short-term test where damaged containers are
systems) handled, the use of complete PPE,
Structure and toxicity profile of new drugs including an NIOSH-certified
that mimic existing drugs determined respirator, is recommended.56,57
hazardous by the above criteria As required by OSHA, a com-
a
plete res piratory program, in-
NIOSH = National Institute for Occupational Safety and Health, ASHP = American Society of Health-
System Pharmacists. cluding proper training and fit
b
NIOSH’s definition contains the following explanation: “All drugs have toxic side effects, but some testing, must be completed by all
exhibit toxicity at low doses. The level of toxicity reflects a continuum from relatively nontoxic to production staff required to use respirators.56
of toxic effects in patients at low doses (for example, a few milligrams or less). For example, a daily
therapeutic dose of 10 mg/day or a dose of 1 mg/kg/day in laboratory animals that produces serious Surgical masks do not provide ad-
organ toxicity, developmental toxicity, or reproductive toxicity has been used by the pharmaceutical equate protection from the harm-
industry to develop occupational exposure limits (OELs) of less than 10 micrograms/meter3 after
applying appropriate uncertainty factors. OELs in this range are typically established for potent or toxic
ful effects of these drugs.
drugs in the pharmaceutical industry. Under all circumstances, an evaluation of all available data should
be conducted to protect health care workers.”
c
NIOSH’s definition contains the following explanation: “In evaluating mutagenicity for potentially Labeling and Packaging from
hazardous drugs, responses from multiple test systems are needed before precautions can be required Point of Receipt. Drug packages,
for handling such agents. The EPA evaluations include the type of cells affected and in vitro versus in bins, shelves, and storage areas
vivo testing.”
for hazardous drugs must bear
distinctive labels identifying those
drugs as requiring special han-
turer and distributor levels. Employers are required to es- dling precautions. Segregation of hazardous drug inventory
tablish controls to ensure worker safety in all aspects of the from other drug inventory improves control and reduces the
distribution of these drugs. number of staff members potentially exposed to the danger.
The outside of the vials of many commercial drugs Hazardous drugs should be stored in an area with sufficient
are contaminated by the time they are received in the phar general exhaust ventilation to dilute and remove any air-
macy.30,54,55 Although the possibility has not been studied, borne contaminants.4 Hazardous drugs placed in inventory
the contamination may extend to the inside of the packing must be protected from potential breakage by storage in bins
cartons and onto the package inserts placed around the vial that have high fronts and on shelves that have guards to pre-
within the carton. Such contamination would present an ex- vent accidental falling. The bins must also be appropriately
posure risk to anyone opening drug cartons or handling the sized to properly contain all stock. Care should be taken to
vials, including workers receiving open or broken shipping separate hazardous drug inventory to reduce potential drug
cartons or selecting vials to be repackaged at a distribution errors (e.g., pulling a look-alike vial from an adjacent drug
point (e.g., a worker at the drug wholesaler selecting haz- bin). Because studies have shown that contamination on the
ardous drugs for shipping containers or a pharmacy worker drug vial itself is a consideration,30,54,55 all staff members
dividing a hazardous drug in a multidose container for re- must wear double gloves when stocking and inventorying
packaging into single-dose containers). These activities may these drugs and selecting hazardous drug packages for fur-
present risks, especially for workers who too often receive ther handling. All transport of hazardous drug packages must
inadequate safety training. Housekeepers and patient care be done in a manner to reduce environmental contamination
assistants who handle drug waste and patient waste are also in the event of accidental dropping. Hazardous drug pack-
at risk and are not always included in the safe handling train- ages must be placed in sealed containers and labeled with
ing required by safety programs. Safety programs must iden- a unique identifier. Carts or other transport devices must be
tify and include all workers who may be at risk of exposure. designed with guards to protect against falling and break-
The packaging (cartons, vials, ampuls) of hazard- age. All individuals transporting hazardous drugs must have
ous drugs should be properly labeled by the manufacturer safety training that includes spill control and have spill kits
or distributor with a distinctive identifier that notifies per- immediately accessible. Staff handling hazardous drugs or
sonnel receiving them to wear appropriate personal protec- cleaning areas where hazardous drugs are stored or handled
tive equipment (PPE) during their handling. Sealing these must be trained to recognize the unique identifying labels
drugs in plastic bags at the distributor level provides an used to distinguish these drugs and areas. Warning labels
additional level of safety for workers who are required to and signs must be clear to non-English readers. All personnel
who work with or around hazardous drugs must be trained tection.4 These devices minimize worker exposure by con-
to appropriately perform their jobs using the established pre- trolling the emission of airborne contaminants. Depending
cautions and required PPE.52 on the design, ventilated cabinets may also be used to pro-
vide the critical environment necessary to compound sterile
Environment. Hazardous drugs should be compounded in a preparations. When asepsis is not required, a Class I BSC
controlled area where access is limited to authorized person- or a containment isolator may be used to handle hazardous
nel trained in handling requirements. Due to the hazardous drugs. When sterile hazardous drugs are being compounded,
nature of these preparations, a contained environment where a Class II or III BSC or an isolator intended for aseptic prep-
air pressure is negative to the surrounding areas or that is aration and containment is required.4 Recommendations for
protected by an airlock or anteroom is preferred. Positive- work practices specific to BSCs and isolators are discussed
pressure environments for hazardous drug compounding later in these guidelines.
should be avoided or augmented with an appropriately de- Class II BSCs. In the early 1980s, the Class II BSC
signed antechamber because of the potential spread of air- was determined to reduce the exposure of pharmacy com-
borne contamination from contaminated packaging, poor pounding staff to hazardous preparations, as measured by
handling technique, and spills. the mutational response to the Ames test by urine of exposed
Only individuals trained in the administration of haz- subjects.58,59 Studies in the 1990s, using analytical methods
ardous drugs should do so. During administration, access significantly more specific and sensitive than the Ames test,
to the administration area should be limited to patients re- indicated that environmental and worker contamination oc-
ceiving therapy and essential personnel. Eating, drinking, curs in workplace settings despite the use of controls recom-
applying makeup, and the presence of foodstuffs should mended in published guidelines, including the use of Class
be avoided in patient care areas while hazardous drugs are II BSCs.29–35,37–41,60,61 The exact cause of contamination has
administered. For inpatient therapy, where lengthy admin- yet to be determined. Studies have shown that (1) there is
istration techniques may be required, hanging or removing contamination on the outside of vials received from manu-
hazardous drugs should be scheduled to reduce exposure of facturers and distributors,30,54,55 (2) work practices required
family members and ancillary staff and to avoid the potential to maximize the effectiveness of the Class II BSC are ne-
contamination of dietary trays and personnel. glected or not taught,32,46 and (3) the potential vaporization of
Because much of the compounding and administration hazardous drug solutions may reduce the effectiveness of
of hazardous drugs throughout the United States is done in the high-efficiency particulate air (HEPA) filter in provid-
outpatient or clinic settings with patients and their family ing containment.42–45 Studies of surface contamination have
members near the compounding area, care must be taken to discovered deposits of hazardous drugs on the floor in front
minimize environmental contamination and to maximize the of the Class II BSC, indicating that drug may have escaped
effectiveness of cleaning (decontamination) activities. The through the open front of the BSC onto contaminated gloves
design of such areas must include surfaces that are read- or the final product or into the air.29–32
ily cleaned and decontaminated. Upholstered and carpeted Workers must understand that the Class II BSC does
surfaces should be avoided, as they are not readily cleaned. not prevent the generation of contamination within the cabi-
Several studies have shown floor contamination and the in net and that the effectiveness of such cabinets in containing
effectiveness of cleaning practices on both floors and sur hazardous drug contamination depends on operators’ use of
faces.29,30,46 Break rooms and refreshment areas for staff, proper technique.
patients, and others should be located away from areas of Some Class II BSCs recirculate airflow within the cab-
potential contamination to reduce unnecessary exposure to inet or exhaust contaminated air back into the work environ-
staff, visitors, and others. ment through HEPA filters.62 The Class II BSC is designed
Hazardous drugs may also be administered in nontra- with air plenums that are unreachable for surface decontami-
ditional locations, such as the operating room, which present nation; the plenum under the work tray collects room dirt and
challenges to training and containment. Intracavitary admin- debris that mix with hazardous drug residue when the BSC
istration of hazardous drugs (e.g., into the bladder, perito- is operational.1 Drafts, supply-air louvers, and other laminar
neal cavity, or chest cavity) frequently requires equipment flow equipment placed near the BSC can interfere with the
for which locking connections may not be readily available containment properties of the inflow air barrier, resulting in
or even possible. All staff members who handle hazardous contamination of the work environment.63 More information
drugs should receive safety training that includes recogni- on the design and use of Class II BSCs is available from
tion of hazardous drugs and appropriate spill response. the NSF International (NSF)/American National Standards
Hazardous drug spill kits, containment bags, and disposal Institute (ANSI) standard 49-04.62 Recommendations for use
containers must be available in all areas where hazardous of Class II BSCs are listed in Appendix A.
drugs are handled. Techniques and ancillary devices that Alternatives to Class II BSCs. Alternatives to the open-
minimize the risk of open systems should be used when front Class II BSC include the Class III BSC, glove boxes, and
administering hazardous drugs through unusual routes or in isolators. By definition, a Class III BSC is a totally enclosed,
nontraditional locations. ventilated cabinet of leak-tight construction.64 Operations in
the cabinet are conducted through fixed-glove access. The
cabinet is maintained under negative air pressure. Supply air
Ventilation Controls. Ventilation or engineering controls are is drawn into the cabinet through HEPA filters. The exhaust
devices designed to eliminate or reduce worker exposure to air is treated by double HEPA filtration or by HEPA filtration
chemical, biological, radiological, ergonomic, and physical and incineration. The Class III BSC is designed for use with
hazards. Ventilated cabinets are a type of ventilation or en- highly toxic or infectious material. Because of the costs of
gineering control designed for the purpose of worker pro-
purchasing and operating a Class III BSC, it is seldom used present exposure concerns similar to those of unvented Class
for extemporaneous compounding of sterile products. II BSCs if there is a possibility that the hazardous drugs han-
Less rigorous equipment with similar fixed-glove ac- dled in them may vaporize. Isolators used for compounding
cess include glove boxes and isolators. Although standard- hazardous drugs should be at negative pressure or use a pres-
ized definitions and criteria exist for glove boxes, these surized air lock to the surrounding areas to improve contain-
guidelines currently focus on applications in the nuclear ment. Some isolators rely on a low-particulate environment
industry and not on compounding hazardous drugs.65 There rather than laminar-airflow technology to protect the sterility
are no standardized definitions or criteria for pharmaceutical of the preparations. Recommendations for use of Class III
compounding applications for this equipment and no perfor- BSCs and isolators are summarized in Appendix B.
mance standards determined by an independent organization Closed-system drug-transfer devices. Closed-system
to aid the purchaser in the selection process. NIOSH recom- drug-transfer devices mechanically prevent the transfer of
mends that only ventilated engineering controls be used to environmental contaminants into the system and the es-
compound hazardous drugs and that these controls be de- cape of drug or vapor out of the system.4 ADD-Vantage and
signed for containment.4 NIOSH defines these controls and Duplex devices are closed-system drug-transfer devices cur-
details their use and selection criteria as well as recommen- rently available for injectable antibiotics. A similar system
dations for airflow, exhaust, and maintenance. NIOSH fur- that may offer increased environmental protection for haz-
ther differentiates between ventilated engineering controls ardous drugs is a proprietary, closed-system drug-transfer
used for hazard containment that are intended for use with device known as PhaSeal. This multicomponent system uses
sterile products (aseptic containment) and those for use with a double membrane to enclose a specially cut injection can-
nonsterile handling of hazardous drugs.4 nula as it moves into a drug vial, Luer-Lok, or infusion-set
An isolator may be considered a ventilated controlled connector.
environment that has fixed walls, floor, and ceiling. For asep- Several studies have shown a reduction in environmen-
tic use, supply air must be drawn through a high-efficiency tal contamination with marker hazardous drugs during both
(minimum HEPA) filter. Exhaust air must also be high- compounding and administration when comparing standard
efficiency filtered and should be exhausted to the outside of techniques for handling hazardous drugs with the use of
the facility, not to the workroom. Workers access the isola- PhaSeal.73–78 It should be noted, however, that PhaSeal com-
tor’s work area, or main chamber, through gloves, sleeves, ponents cannot be used to compound all hazardous drugs.
and air locks or pass-throughs. Currently available isolators In 1984, Hoy and Stump79 concluded that a commer-
have either unidirectional or turbulent airflow within the cial air-venting device reduced the release of drug aerosols
main chamber. For compounding sterile preparations, the during reconstitution of drugs packaged in vials. The testing
filtered air and airflow must achieve an ISO class 5 (former was limited to visual analysis. The venting device does not
FS-209E class 100) environment within the isolator.50,51,66,67 lock onto the vial, which allows it to be transferred from
Isolators for sterile compounding have become increasingly one vial to another. This practice creates an opportunity for
popular as a way to minimize the challenges of a traditional both environmental and product contamination. Many de-
cleanroom and some of the disadvantages of the Class II vices labeled as “chemo adjuncts” are currently available.
BSC.50,68–70 The totally enclosed design may reduce the es- Many feature a filtered, vented spike to facilitate reconstitut-
cape of contamination during the compounding process. The ing and removing hazardous drugs during the compounding
isolator may be less sensitive to drafts and other laminar- process. However, none of these devices may be considered
airflow equipment, including positive-pressure environ- a closed-system drug-transfer device, and none has been
ments. Issues unique to isolators include pressure changes formally studied with the results published in peer-reviewed
when accessing the fixed-glove assembly, pressure changes journals. As other products become available, they should
in the main chamber when accessing the antechamber or meet the definition of closed-system drug-transfer devices
pass-through, positive- versus negative-pressure isolators established by NIOSH4 and should be required to demon-
used to compound hazardous drugs, and ergonomic consid- strate their effectiveness in independent studies. Closed-
erations associated with a fixed-glove assembly. Many isola- system drug-transfer devices (or any other ancillary devices)
tors produce less heat and noise than Class II BSCs.68 The are not a substitute for using a ventilated cabinet.
Controlled Environment Testing Association has developed
an applications guide for isolators in health care facilities.71 Personal Protective Equipment. Gloves. Gloves are essen-
Isolators, like Class II BSCs, do not prevent the gen- tial for handling hazardous drugs. Gloves must be worn at
eration of contamination within the cabinet workspace, and all times when handling drug packaging, cartons, and vials,
their effectiveness in containing contamination depends on including while performing inventory control procedures and
proper technique.72 The potential for the spread of hazardous when gathering hazardous drugs and supplies for compound-
drug contamination from the pass-through and main chamber ing a batch or single dose. During compounding in a Class II
of the isolator to the workroom may be reduced by surface de BSC, gloves and gowns are required to prevent skin surfaces
contamination, but no wipe-down procedures have been stud- from coming into contact with these agents. Studies of gloves
ied. Surface decontamination may be more readily conducted indicate that many latex and nonlatex materials are effec-
in isolators than in Class II BSCs. (See Decontamination, de tive protection against penetration and permeation by most
activation, and cleaning for more information.) hazardous drugs.80–84 Recent concerns about latex sensitiv-
Recirculating isolators depend on high-efficiency ity have prompted testing of newer glove materials. Gloves
(HEPA or ultra-low penetrating air [ULPA]) filters. These made of nitrile or neoprene rubber and polyurethane have
filters may not sufficiently remove volatile hazardous drug been successfully tested using a battery of antineoplastic
contamination from the airflow. Isolators that discharge air drugs.82–84 The American Society for Testing and Materials
into the workroom, even through high-efficiency filters, (ASTM) has developed testing standards for assessing the
resistance of medical gloves to permeation by chemotherapy the BSC. For aseptic protection of sterile preparations, the
drugs.85 Gloves that meet this standard earn the designation outer gloves must be sanitized with an appropriate disinfec-
of “chemotherapy gloves.” Gloves selected for use with haz- tant when reentering the BSC. Gloves must also be changed
ardous drugs should meet this ASTM standard. immediately if torn, punctured, or knowingly contaminated.
Connor and Xiang86 studied the effect of isopropyl al- When wearing two pairs of gloves in the BSC, one pair is
cohol on the permeability of latex and nitrile gloves exposed worn under the gown cuff and the second pair placed over
to antineoplastic agents. During the limited study period of the cuff. When removing the gloves, the contaminated glove
30 minutes, they found that the use of isopropyl alcohol dur- fingers must only touch the outer surface of the glove, never
ing cleaning and decontaminating did not appear to affect the inner surface. If the inner glove becomes contaminated,
the integrity of either material when challenged with six an- then both pairs of gloves must be changed. When removing
tineoplastic agents. any PPE, care must be taken to avoid introducing hazardous
In most glove-testing systems, the glove material re- drug contamination into the environment. Both the inner and
mains static, in contrast to the stressing and flexing that oc outer gloves should be considered contaminated, and glove
cur during actual use. In one study designed to examine surfaces must never touch the skin or any surface that may
glove permeability under static and flexed conditions, no be touched by the unprotected skin of others. Gloves used
significant difference in permeation was reported, except in to handle hazardous drugs should be placed in a sealable
thin latex examination gloves.87 Another study, however, de- plastic bag for containment within the BSC or isolator pass-
tected permeation of antineoplastic drugs through latex through before disposal as contaminated waste.
gloves during actual working conditions by using a cotton If an i.v. set is attached to the final preparation in the
glove under the latex glove.88 The breakthrough time for cy- BSC or isolator, care must be taken to avoid contaminat-
clophosphamide was only 10 minutes. The authors specu- ing the tubing with hazardous drug from the surface of the
lated that the cotton glove may have acted as a wick, draw- gloves, BSC, or isolator.
ing the hazardous drug through the outer glove. Nonetheless, Class III BSCs and isolators are equipped with at-
under actual working conditions, double gloving and wear- tached gloves or gauntlets. They should be considered
ing gloves no longer than 30 minutes are prudent practices. contaminated once the BSC or isolator has been used for
Permeability of gloves to hazardous drugs has been compounding hazardous drugs. For compounding sterile
shown to be dependent on the drug, glove material and preparations, attached gloves or gauntlets must be routinely
thickness, and exposure time. Powder-free gloves are pre- sanitized per the manufacturer’s instructions to prevent mi-
ferred because powder particulates can contaminate the ster- crobial contamination. Hazardous drug contamination from
ile processing area and absorb hazardous drug contaminants, the gloves or gauntlets may be transferred to the surfaces
which may increase the potential for dermal contact. Hands of all items within the cabinet. Glove and gauntlet surfaces
should be thoroughly washed before donning gloves and must be cleaned after compounding is complete. All fi-
after removing them. Care must be taken when removing nal preparations must be surface decontaminated by staff,
gloves in order to prevent the spreading of hazardous drug wearing clean gloves to avoid spreading contamination.68
contaminants. Recommendations for use of gloves are summarized in
Several studies have indicated that contamination of Appendix C.
the outside of gloves with hazardous drug is common af- Gowns. Gowns or coveralls are worn during the com-
ter compounding and that this contamination may be spread pounding of sterile preparations to protect the preparation
to other surfaces during the compounding process.30–33,39 from the worker, to protect the worker from the preparation,
Studies have also shown that hazardous drug contamination or both. The selection of gowning materials depends on the
may lead to dermal absorption by workers not actively in- goal of the process. Personal protective gowns are recom-
volved in the compounding and administration of hazardous mended during the handling of hazardous drug preparations
drugs.30,88 The use of two pairs of gloves is recommended to protect the worker from inadvertent exposure to extrane-
when compounding these drugs. In an isolator, one addi- ous drug particles on surfaces or generated during the com-
tional pair of gloves must be worn within the fixed-glove pounding process.
assembly.68 Guidelines for the safe handling of hazardous drugs
Once compounding has been completed and the final recommend the use of gowns for compounding in the
preparation surface decontaminated, the outer glove should BSC, administration, spill control, and waste management
be removed and contained inside the BSC. The inner glove is to protect the worker from contamination by fugitive drug
worn to affix labels and place the preparation into a sealable generated during the handling process.1–4,89,90 Early recom-
containment bag for transport. This must be done within the mendations for barrier protective gowns required that they
BSC. In the isolator, the fixed gloves must be surface cleaned be disposable and made of a lint-free, low-permeability fab-
before wiping down the final preparation, placing the label ric with a closed front, long sleeves, and tight-fitting elas-
onto the preparation, and placing it into the pass-through. tic or knit cuffs.1 Washable garments (e.g., laboratory coats,
The inner gloves should be worn to complete labeling and scrubs, and cloth gowns) absorb fluids and provide no barrier
to place the final preparation into a transport bag in the pass- against hazardous drug absorption and permeation. Studies
through. The inner gloves may then be removed and con- into the effectiveness of disposable gowns in resisting per-
tained in a sealable bag within the pass-through. If the final meation by hazardous drugs found variation in the protec-
check is conducted by a second staff member, fresh gloves tion provided by commercially available materials. In an
must be donned before handling the completed preparation. evaluation of polypropylene-based gowns, Connor91 found
During batch compounding, gloves should be changed that polypropylene spun-bond nonwoven material alone and
at least every 30 minutes. Gloves (at least the outer gloves) polypropylene–polyethylene copolymer spun-bond provided
must be changed whenever it is necessary to exit and re-enter little protection against permeation by a battery of aqueous-
and nonaqueous- based hazardous drugs. Various construc- ate gowning practices are established. Recommendations for
tions of polypropylene (e.g., spun-bond/melt-blown/spun- use of gowns are summarized in Appendix D.
bond) result in materials that are completely impermeable Additional PPE. Eye and face protection should
or only slightly permeable to hazardous drugs. Connor91 be used whenever there is a possibility of exposure from
noted that these coated materials are similar in appearance splashing or uncontrolled aerosolization of hazardous drugs
to several other nonwoven materials but perform differently (e.g., when containing a spill or handling a damaged ship-
and that workers could expect to be protected from expo- ping carton). In these instances, a face shield, rather than
sure for up to four hours when using the coated gowning safety glasses or goggles, is recommended because of the
materials. Harrison and Kloos92 reported similar findings in improved skin protection afforded by the shield.
a study of six disposable gowning materials and 15 hazard- Similar circumstances also warrant the use of a respira-
ous drugs. Only gowns with polyethylene or vinyl coatings tor. All workers who may use a respirator must be fit-tested
provided adequate splash protection and prevented drug per- and trained to use the appropriate respirator according to
meation. In a subjective assessment of worker comfort, the the OSHA Respiratory Protection Standard.56,57 A respira-
more protective gowns were found to be warmer and thus tor of correct size and appropriate to the aerosol size, physi-
less comfortable. These findings agree with an earlier study cal state (i.e., particulate or vapor), and concentration of the
that found that the most protective gowning materials were airborne drug must be available at all times. Surgical masks
the most uncomfortable to wear.93 Resistance to the use of do not provide respiratory protection. Shoe and hair cover-
gowns, especially by nurses during administration of haz- ings should be worn during the sterile compounding process
ardous drugs, has been reported.94 The lack of comfort could to minimize particulate contamination of the critical work
cause resistance to behavioral change. zone and the preparation.50 With the potential for hazard-
Researchers have looked at gown contamination with ous drug contamination on the floor in the compounding and
fluorescent scans, high-performance liquid chromatography, administration areas, shoe coverings are recommended as
and tandem mass spectrometry.39,95 In one study, researchers contamination-control mechanisms. Shoe coverings must be
scanned nurses and pharmacists wearing gowns during the removed with gloved hands when leaving the compounding
compounding and administration of hazardous drugs.95 Of area. Gloves should be worn and care must be taken when re-
a total of 18 contamination spots detected, 5 were present moving hair or shoe coverings to prevent contamination from
on the gowns of nurses after drug administration. No spots spreading to clean areas. Hair and shoe coverings used in the
were discovered on the gowns of pharmacists after com- hazardous drug handling areas must be contained, along with
pounding. In contrast, researchers using a more sensitive used gloves, and discarded as contaminated waste.
assay placed pads in various body locations, both over and
under the gowns used by the subjects during compounding Work Practices. Compounding sterile hazardous drugs. Work
and administration of cyclophosphamide and ifosfamide.39 practices for the compounding of sterile hazardous drugs differ
Workers wore short-sleeved nursing uniforms, disposable somewhat with the use of a Class II BSC, a Class III BSC, or an
or cotton gowns, and vinyl or latex gloves. More contami- isolator. Good organizational skills are essential to minimize
nation was found during compounding than administra- contamination and maximize productivity. All activities not
tion. Contamination found on the pads placed on the arms requiring a critical environment (e.g., checking labels, doing
of preparers is consistent with the design and typical work calculations) should be completed before accessing the BSC
practices used in a Class II BSC, where the hands and arms or isolator. All items needed for compounding must be gath-
are extended into the contaminated work area of the cabi- ered before beginning work. This practice should eliminate
net. Remarkably, one preparer had contamination on the the need to exit the BSC or isolator once compounding has
back of the gown, possibly indicating touch contamination begun. Two pairs of gloves should be worn to gather hazard-
with the Class II BSC during removal of the final product. ous drug vials and supplies. These gloves should be care-
While early guidelines do not contain a maximum length of fully removed and discarded. Fresh gloves must be donned
time that a gown should be worn, Connor’s91 work would and appropriately sanitized before aseptic manipulation.
support a two- to three-hour window for a coated gown. Only supplies and drugs essential to compounding the
Contamination of gowns during glove changes must be a dose or batch should be placed in the work area of the BSC
consideration. If the inner pair of gloves requires chang- or main chamber of the isolator. BSCs and isolators should
ing, a gown change should be considered. Gowns worn as not be overcrowded to avoid unnecessary hazardous drug
barrier protection in the compounding of hazardous drugs contamination. Luer-Lok syringes and connections must be
must never be worn outside the immediate preparation area. used whenever possible for manipulating hazardous drugs,
Gowns worn during administration should be changed when as they are less likely to separate during compounding.
leaving the patient care area and immediately if contami- Spiking an i.v. set into a solution containing hazardous
nated. Gowns should be removed carefully and properly dis- drugs or priming an i.v. set with hazardous drug solution in
posed of as contaminated waste to avoid becoming a source an uncontrolled environment must be avoided. One recom-
of contamination to other staff and the environment. mendation is to attach and prime the appropriate i.v. set to
Hazardous drug compounding in an enclosed environ- the final container in the BSC or isolator before adding the
ment, such as a Class III BSC or an isolator, may not require hazardous drug. Closed-system drug-transfer devices should
the operator to wear a gown. However, because the process achieve a dry connection between the administration set and
of handling drug vials and final preparations, as well as ac- the hazardous drug’s final container. This connection allows
cessing the isolator’s pass-throughs, may present an oppor- the container to be spiked with a secondary i.v. set and the
tunity for contamination, the donning of a gown is prudent. set to be primed by backflow from a primary nonhazardous
Coated gowns may not be necessary for this use if appropri- solution. This process may be done outside the BSC or isola-
tor, reducing the potential for surface contamination of the
i.v. set during the compounding process. A new i.v. set must work zone, so manipulations should be performed at least
be used with each dose of hazardous drug. Once attached, six inches away from each sidewall in the horizontal plane.
the i.v. set must never be removed from a hazardous drug A small waste–sharps container may be placed along the
dose, thereby preventing the residual fluid in the bag, bottle, sidewall toward the back of the BSC. One study has sug-
or tubing from leaking and contaminating personnel and the gested that a plastic-backed absorbent preparation pad in a
environment. Class II BSC may interfere with airflow,39 but another study
Transport bags must never be placed in the BSC or determined that use of a flat firm pad that did not block the
in the isolator work chamber during compounding to avoid grilles of the cabinet had no effect on airflow.96 The use of
inadvertent contamination of the outer surface of the bag. a large pad that might block the front or rear grilles must be
Final preparations must be surface decontaminated after avoided. In addition, because a pad may absorb small spills,
compounding is complete. In either the BSC or isolator, it may become a source of hazardous drug contamination
clean inner gloves must be worn when labeling and plac- for anything placed upon it. Preparation pads are not read-
ing the final preparation into the transport bag. Handling ily decontaminated and must be replaced and discarded after
final preparations and transport bags with gloves contami- preparation of each batch and frequently during extended
nated with hazardous drugs will result in the transfer of the batch compounding. More information on the design and
contamination to other workers. Don fresh gloves whenever use of Class II BSCs is available from the NSF/ANSI stan-
there is a doubt as to the cleanliness of the inner or outer dard 49-04.62
gloves. Isolators. For work in an isolator, all drugs and sup-
Working in BSCs or isolators. With or without ancil- plies needed to aseptically compound a dose or batch should
lary devices, none of the available ventilation or engineer- be gathered and sanitized with 70% alcohol or appropriate
ing controls can provide 100% protection for the worker. disinfectant and readied for placement in the pass-through.
Workers must recognize the limitations of the equipment A technique described in the literature involves the use of
and address them through appropriate work practices.1 The a tray that will fit into the pass-through.97 A large primary
effectiveness of Class II BSCs and isolators in containing sealable bag is placed over the tray. Labels and a second
contamination depends on proper technique.72 Hazardous sealable (transport) bag, which is used to contain the final
drug contamination from the work area of the isolator may preparation, are placed into the primary sealable bag on the
be brought into the workroom environment through the pass- tray surface. Vials, syringes, needles, and other disposables
throughs or air locks and on the surfaces of items removed are placed on top of the sealed bag. The enclosed tray is
from the isolators (e.g., the final preparation). Surface de- then taken into the main chamber of the isolator, where the
contamination of the preparation before removal from the drug and supplies are used to compound the dose. The con-
isolator’s main chamber should reduce the hazardous drug taminated materials, including the primary sealable bag, are
contamination that could be transferred to the workroom, removed using the closed trash system of the isolator, if so
but no wipe-down procedures have been studied. Surface equipped, or sealed into a second bag and removed via the
decontamination may be accomplished using alcohol, sterile pass-through for disposal as contaminated waste. The dose
water, peroxide, or sodium hypochlorite solutions, provided is then labeled and placed into the second sealable bag for
the packaging is not permeable to the solution and the labels transport.
remain legible and intact. Recommendations for working in This technique does not address contamination on
BSCs and isolators are summarized in Appendix E. the isolator gloves or gauntlets. Additional work practices
BSCs. Class II BSCs use vertical-flow, HEPA-filtered may include cleaning off the gloves or gauntlets and final
air (ISO class 5) as their controlled aseptic environment. preparation after initial compounding and before handling
Before beginning an operation in a Class II BSC, personnel the label and second sealable bag. Care must be taken when
should wash their hands, don an inner pair of appropriate transferring products out of the pass-through and disposing
gloves, and then don a coated gown followed by a second of waste through the pass-through or trash chute to avoid
pair of gloves. The work surface should be cleaned of sur- accidental contamination.
face contamination with detergent, sodium hypochlorite, and Aseptic technique. Stringent aseptic technique, de-
neutralizer or disinfected with alcohol, depending on when it scribed by Wilson and Solimando98 in 1981, remains the
was last cleaned. For the Class II BSC, the front shield must foundation of any procedure involving the use of needles and
be lowered to the proper level to protect the face and eyes. syringes in manipulating sterile dosage forms. This tech-
The operator should be seated so that his or her shoulders nique, when performed in conjunction with negative pres-
are at the level of the bottom of the front shield. All drugs sure technique, minimizes the escape of drug from vials and
and supplies needed to aseptically compound a dose or batch ampuls. Needleless devices have been developed to reduce
should be gathered and sanitized with 70% alcohol or ap- the risk of blood-borne pathogen exposure through needle
propriate disinfectant. Avoid exiting and reentering the work sticks. None of these devices has been tested for reduction of
area. Being careful not to place any sterile objects below hazardous drug contamination. The appropriateness of these
them, i.v. bags and bottles may be hung from the bar. All devices in the safe handling of hazardous drugs has not been
items must be placed well within the Class II BSC, away determined.
from the unfiltered air at the front barrier. By design, the In reconstituting hazardous drugs in vials, it is critical
intended work zone within the Class II BSC is the area be- to avoid pressurizing the contents of the vial. Pressurization
tween the front and rear air grilles. The containment char- may cause the drug to spray out around the needle or through
acteristics of the Class II BSC are dependent on the airflow a needle hole or a loose seal, aerosolizing the drug into the
through both the front and back grilles; these grilles should work zone. Pressurization can be avoided by creating a slight
never be obstructed. Due to the design of the Class II BSC, negative pressure in the vial. Too much negative pressure,
the quality of HEPA-filtered air is lowest at the sides of the however, can cause leakage from the needle when it is with-
drawn from the vial. The safe handling of hazardous drug ously compounded oral liquids may start with the parenteral
solutions in vials or ampuls requires the use of a syringe form, or they may require that tablets be crushed or cap-
that is no more than three-fourths full when filled with the sules opened. Tablet trituration has been shown to cause fine
solution, which minimizes the risk of the plunger separat- dust formation and local environmental contamination.100
ing from the syringe barrel. Once the diluent is drawn up, Procedures for the preparation and the use of equipment
the needle is inserted into the vial and the plunger is pulled (e.g., Class I BSCs or bench-top hoods with HEPA filters)
back (to create a slight negative pressure inside the vial), must be developed to avoid the release of aerosolized pow-
so that air is drawn into the syringe. Small amounts of di- der or liquid into the environment during manipulation of
luent should be transferred slowly as equal volumes of air hazardous drugs. Recommendations for preparation and
are removed. The needle should be kept in the vial, and the handling of noninjectable hazardous drug dosage forms are
contents should be swirled carefully until dissolved. With summarized in Appendix F.
the vial inverted, the proper amount of drug solution should Decontamination, deactivation, and cleaning. Decon
be gradually withdrawn while equal volumes of air are ex- tamination may be defined as cleaning or deactivating.
changed for solution. The exact volume needed must be Deactivating a hazardous substance is preferred, but no sin-
measured while the needle is in the vial, and any excess drug gle process has been found to deactivate all currently avail-
should remain in the vial. With the vial in the upright posi- able hazardous drugs. The use of alcohol for disinfecting the
tion, the plunger should be withdrawn past the original start- BSC or isolator will not deactivate any hazardous drugs and
ing point to again induce a slight negative pressure before may result in the spread of contamination rather than any
removing the needle. The needle hub should be clear before actual cleaning.30,47
the needle is removed. Decontamination of BSCs and isolators should be
If a hazardous drug is transferred to an i.v. bag, care conducted per manufacturer recommendations. The MSDSs
must be taken to puncture only the septum of the injection for many hazardous drugs recommend sodium hypochlorite
port and avoid puncturing the sides of the port or bag. After solution as an appropriate deactivating agent.101 Researchers
the drug solution is injected into the i.v. bag, the i.v. port, have shown that strong oxidizing agents, such as sodium
container, and set (if attached by pharmacy in the BSC or hypochlorite, are effective deactivators of many hazardous
isolator) should be surface decontaminated. The final prepa- drugs.102,103 There is currently one commercially available
ration should be labeled, including an auxiliary warning, and product, SurfaceSafe (SuperGen, Dublin, CA), that provides
the injection port covered with a protective shield. The final a system for decontamination and deactivation using so-
container should be placed, using clean gloves, into a seal- dium hypochlorite, detergent, and thiosulfate neutralizer. A
able bag to contain any leakage.1 ventilated cabinet that runs continuously should be cleaned
To withdraw hazardous drugs from an ampul, the neck before the day’s operations begin and at regular intervals or
or top portion should be gently tapped.98 After the neck is when the day’s work is completed. For a 24-hour service, the
wiped with alcohol, a 5-µm filter needle or straw should cabinet should be cleaned two or three times daily. Cabinets
be attached to a syringe that is large enough that it will be used for aseptic compounding must be disinfected at the be-
not more than three-fourths full when holding the drug. The ginning of the workday, at the beginning of each subsequent
fluid should then be drawn through the filter needle or straw shift (if compounding takes place over an extended period of
and cleared from the needle and hub. After this, the needle or time), and routinely during compounding.
straw is exchanged for a needle of similar gauge and length; Appropriate preparation of materials used in com-
any air and excess drug should be ejected into a sterile vial pounding before introduction into the Class II BSC or the
(leaving the desired volume in the syringe); aerosolization pass-through of a Class III BSC or isolator, including spray-
should be avoided. The drug may then be transferred to an ing or wiping with 70% alcohol or appropriate disinfectant,
i.v. bag or bottle. If the dose is to be dispensed in the syringe, is also necessary for aseptic compounding.
the plunger should be drawn back to clear fluid from the The Class II BSC has air plenums that handle contami-
needle and hub. The needle should be replaced with a lock- nated air. These plenums are not designed to allow surface
ing cap, and the syringe should be surface decontaminated decontamination, and many of the contaminated surfaces
and labeled. (plenums) cannot be reached for surface cleaning. The area
Training and demonstration of competence. All staff under the work tray should be cleaned at least monthly to
who will be compounding hazardous drugs must be trained reduce the contamination level in the Class II BSC (and in
in the stringent aseptic and negative-pressure techniques isolators, where appropriate).
necessary for working with sterile hazardous drugs. Once Surface decontamination may be accomplished by the
trained, staff must demonstrate competence by an objective transfer of hazardous drug contamination from the surface of
method, and competency must be reassessed on a regular a nondisposable item to disposable ones (e.g., wipes, gauze,
basis.99 towels). Although the outer surface of vials containing haz-
Preparation and handling of noninjectable hazardous ardous drugs has been shown to be contaminated with haz-
drug dosage forms. Although noninjectable dosage forms ardous drugs,30,54,55 and hazardous drug contamination has
of hazardous drugs contain varying proportions of drug to been found on the outside of final preparations,30 no wipe-
nondrug (nonhazardous) components, there is the potential down procedures have been studied. The amount of hazard-
for personnel exposure to and environmental contamina- ous drug contamination placed into the BSC or isolator may
tion with the hazardous components if hazardous drugs are be reduced by surface decontamination (i.e., wiping down)
handled (e.g., packaged) by pharmacy staff. Although most of hazardous drug vials. While no wipe-down procedures
hazardous drugs are not available in liquid formulations, have been studied, the use of gauze moistened with alco-
such formulations are often prescribed for small children hol, sterile water, peroxide, or sodium hypochlorite solutions
and adults with feeding tubes. Recipes for extemporane-
may be effective. The disposable item, once contaminated, cial entities. The RCRA outlines four “characteristics” of
must be contained and discarded as contaminated waste. hazardous waste107 and contains lists of agents that are to be
Administration of hazardous drugs. Policies and pro- considered hazardous waste when they are discarded.108 Any
cedures governing the administration of hazardous drugs discarded drug that is on one of the lists (a “listed” waste) or
must be jointly developed by nursing and pharmacy for the meets one of the criteria (a “characteristic” waste) is consid-
mutual safety of health care workers. These policies should ered hazardous waste. The listed drugs include epinephrine,
supplement policies designed to protect patient safety during nicotine, and physostigmine, as well as nine chemotherapy
administration of all drugs. All policies affecting multiple drugs: arsenic trioxide, chlorambucil, cyclophosphamide,
departments must be developed with input from manag- daunomycin, diethylstilbestrol, melphalan, mitomycin C,
ers and workers from the affected areas. Extensive nurs- streptozocin, and uracil mustard. They require handling,
ing guidelines for the safe and appropriate administration containment, and disposal as RCRA hazardous waste.
of hazardous drugs have been developed by the Oncology The RCRA allows for the exemption of “empty con-
Nursing Society90,104 and OSHA.2,3 Recommendations for tainers” from hazardous waste regulations. Empty containers
reducing exposure to hazardous drugs during administration are defined as those that have held U-listed or characteristic
in all practice settings are listed in Appendix G. wastes and from which all wastes have been removed that
Spill management. Policies and procedures must be can be removed using the practices commonly employed to
developed to attempt to prevent spills and to govern cleanup remove materials from that type of container and no more
of hazardous drug spills. Written procedures must specify than 3% by weight of the total capacity of the container
who is responsible for spill management and must address remains in the container.109 Disposal guidelines developed
the size and scope of the spill. Spills must be contained and by the National Institutes of Health (NIH) and published
cleaned up immediately by trained workers. in 1984 coined the term “trace-contaminated” waste using
Spill kits containing all of the materials needed to clean the 3% rule.110 Note that a container that has held an acute
up spills of hazardous drugs should be assembled or pur- hazardous waste listed in §§261.31, 261.32, or 261.33(e),
chased (Appendix H). These kits should be readily available such as arsenic trioxide, is not considered empty by the 3%
in all areas where hazardous drugs are routinely handled. A rule,111 and that spill residues from cleanup of hazardous
spill kit should accompany delivery of injectable hazardous agents are considered hazardous waste.105
drugs to patient care areas even though they are transported In addition, many states are authorized to implement
in a sealable plastic bag or container. If hazardous drugs are their own hazardous waste programs, and requirements un-
being prepared or administered in a nonroutine area (e.g., der these programs may be more stringent than those of the
home setting, unusual patient care area), a spill kit and respi- EPA. State and local regulations must be considered when
rator must be obtained by the drug handler. Signs should be establishing a hazardous waste policy for a specific facility.
available to warn of restricted access to the spill area. General categories of hazardous waste found in health
Only trained workers with appropriate PPE and respi- care settings would include trace-contaminated hazardous
rators should attempt to manage a hazardous drug spill. All waste, bulk hazardous waste, hazardous drugs not listed
workers who may be required to clean up a spill of hazardous as hazardous waste, and hazardous waste and mixed infec-
drugs must receive proper training in spill management and in tious–hazardous waste.
the use of PPE and NIOSH-certified respirators. Trace-contaminated hazardous drug waste. By the
The circumstances and handling of spills should be NIH definition of trace chemotherapy waste,110 “RCRA-
documented. Staff and nonemployees exposed to a hazardous empty” containers, needles, syringes, trace-contaminated
drug spill should also complete an incident report or exposure gowns, gloves, pads, and empty i.v. sets may be collected
form and report to the designated emergency service for initial and incinerated at a regulated medical waste incinerator.
evaluation. Sharps used in the preparation of hazardous drugs should
All spill materials must be disposed of as hazardous not be placed in red sharps containers or needle boxes, since
waste.105 Recommendations for spill cleanup procedure are these are most frequently disinfected by autoclaving or mi
summarized in Appendix I. crowaving, not by incineration, and pose a risk of aerosoliza-
Worker contamination. Procedures must be in place to tion to waste-handling employees.
address worker contamination, and protocols for medical at- Bulk hazardous drug waste. While not official, the
tention must be developed before the occurrence of any such term bulk hazardous drug waste has been used to differenti-
incident. Emergency kits containing isotonic eyewash sup- ate containers that have held either (1) RCRA-listed or char-
plies (or emergency eyewashes, if available) and soap must acteristic hazardous waste or (2) any hazardous drugs that
be immediately available in areas where hazardous drugs are are not RCRA empty or any materials from hazardous drug
handled. Workers who are contaminated during the spill or spill cleanups. These wastes should be managed as hazard-
spill cleanup or who have direct skin or eye contact with ous waste.
hazardous drugs require immediate treatment. OSHA-rec Hazardous drugs not listed as hazardous waste. The
ommended steps for treatment are outlined in Appendix J. federal RCRA regulations have not kept up with drug de-
velopment, as there are over 100 hazardous drugs that are
Hazardous Waste Containment and Disposal. In 1976, the not listed as hazardous waste, including hormonal agents. In
Resource Conservation and Recovery Act (RCRA) was en- some states, such as Minnesota, these must be managed as
acted to provide a mechanism for tracking hazardous waste hazardous waste. In other states, organizations should man-
from its generation to disposal.106 Regulations promulgated age these drugs as hazardous waste as a best- management
under RCRA are enforced by the Environmental Protection practice until federal regulations can be updated.
Agency and apply to pharmaceuticals and chemicals dis- Hazardous waste and mixed infectious–hazardous
carded by pharmacies, hospitals, clinics, and other commer- waste. Most hazardous waste vendors are not permitted to
manage regulated medical waste or infectious waste; there- care providers of their occupation and possible hazardous
fore, they cannot accept used needles and items contaminated drug exposure when obtaining routine medical care.4
with squeezable, flakable, or drippable blood. Organizations
should check carefully with their hazardous waste vendors Conclusion
to ensure acceptance of all possible hazardous waste, includ-
ing mixed infectious waste, if needed. Once hazardous waste These guidelines represent the recommendations of many
has been identified, it must be collected and stored according groups and individuals who have worked tirelessly over de-
to specific EPA and Department of Transportation require- cades to reduce the potential of harmful effects on health care
ments.112 Properly labeled, leakproof, and spill-proof con- workers exposed to hazardous drugs. No set of guidelines
tainers of nonreactive plastic are required for areas where on this topic, however comprehensive, can address all the
hazardous waste is generated. Hazardous drug waste may needs of every health care facility. Health care professionals
be initially contained in thick, sealable plastic bags before are encouraged to rely on their professional judgment, expe-
being placed in approved satellite accumulation containers. rience, and common sense in applying these recommenda-
Glass fragments should be contained in small, puncture- tions to their unique circumstances and to take into account
resistant containers to be placed into larger containers ap- evolving federal, state, and local regulations, as well as the
proved for temporary storage. requirements of appropriate accrediting institutions.
Waste contaminated with blood or other body flu-
ids must not be mixed with hazardous waste. Transport of
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85. American Society for Testing and Materials D 6978-05 toxic agents. Am J Health-Syst Pharm. 1996; 53:402–
standard practice for assessment of resistance of medi- 7.
cal gloves to permeation by chemotherapy drugs. West 100. Shahsavarani S, Godefroid RJ, Harrison BR. Evalua
Conshohocken, PA: American Society for Testing and tion of occupational exposure to tablet trituration dust.
Materials; 2005. Paper presented at ASHP Midyear Clinical Meeting.
86. Connor TH, Xiang Q. The effect of isopropyl alcohol Atlanta, GA; 1993 Dec 6.
on the permeation of gloves exposed to antineoplastic 101. Johnson EG, Janosik JE. Manufacturers’ recommen-
agents. J Oncol Pharm Pract. 2000; 6:109–14. dations for handling spilled antineoplastic agents. Am
87. Colligan SA, Horstman SW. Permeation of cancer J Hosp Pharm. 1989; 46:318–9.
chemotherapeutic drugs through glove materials under 102. Benvenuto JA, Connor TH, Monteith DK et al.

static and flexed conditions. Appl Occup Environ Hyg. Degradation and inactivation of antitumor drugs. J
1990; 5:848–52. Pharm Sci. 1993; 82:988–91.
88. Sessink PJ, Cerna M, Rossner P et al. Urinary cyclo- 103. Hansel S, Castegnaro M, Sportouch MH et al.

phosphamide excretion and chromosomal aberrations Chemical degradation of wastes of antineoplastic
in peripheral blood lymphocytes after occupational agents: cyclophosphamide, ifosfamide, and melpha-
exposure to antineoplastic agents. Mutat Res. 1994; lan. Int Arch Occup Environ Health. 1997; 69:109–14.
309:193–9. 104. Polovich M, Belcher C, Glynn-Tucker EM et al. Safe
89. National Institutes of Health. Recommendations for handling of hazardous drugs. Pittsburgh: Oncology
the safe handling of cytotoxic drugs. www.nih.gov/od/ Nursing Society; 2003.
ors/ds/pubs/cyto/index.htm (accessed 2004 Nov 1). 105. 40 C.F.R. 261.33.
90. Polovich M, White JM, Kelleher LO, eds. Chemother 106. Resource Conservation and Recovery Act of 1976. 42
apy and biotherapy guidelines and recommendations U.S.C. 82 §6901-92.
for practice. 2nd ed. Pittsburgh: Oncology Nursing 107. 40 C.F.R. 261.20-24C.
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91. Connor TH. An evaluation of the permeability of dis- 109. 40 C.F.R. 261.7.
posable polypropylene-based protective gowns to a 110. Vaccari PL, Tonat K, DeChristoforo R et al. Disposal
battery of cancer chemotherapy drugs. Appl Occup of antineoplastic wastes at the National Institutes of
Environ Hyg. 1993; 8:785–9. Health. Am J Hosp Pharm. 1984; 41:87–93.
92. Harrison BR, Kloos MD. Penetration and splash pro- 111. 40 C.F.R. 261.7(b)(1)-(3).
tection of six disposable gown materials against fif- 112. 49 C.F.R. 172.0-.123,173,178,179.
teen antineoplastic drugs. J Oncol Pharm Pract. 1999; 113. 29 C.F.R. 1910.120(e)(3)(i).
5:61–6. 114. 29 C.F.R. 1910.120(q)(1-6).
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seven antineoplastic drugs. Am J Hosp Pharm. 1985;
42:2449–54.
Appendix A—Recommendations drugs, handling of hazardous drug waste or waste from

for Use of Class II BSCs patients recently treated with hazardous drugs, and
cleanup of hazardous drug spills.
1. The use of a Class II BSC must be accompanied by a 2. Select powder-free, high-quality gloves made of latex,
stringent program of work practices, including train- nitrile, polyurethane, neoprene, or other materials that
ing, demonstrated competence, contamination reduc- meet the ASTM standard for chemotherapy gloves.
tion, and decontamination. 3. Inspect gloves for visible defects.
2. Only a Class II BSC with outside exhaust should be 4. Sanitize gloves with 70% alcohol or other appropriate
used for compounding hazardous drugs; type B2 total disinfectant before performing any aseptic compound-
exhaust is preferred. Total exhaust is required if the ing activity.
hazardous drug is known to be volatile.4 5. Change gloves every 30 minutes during compounding
3. Without special design considerations, Class II BSCs or immediately when damaged or contaminated.
are not recommended in traditional, positive-pressure 6. Remove outer gloves after wiping down final prepara-
cleanrooms, where contamination from hazardous tion but before labeling or removing the preparation
drugs may result in airborne contamination that may from the BSC.
spread from the open front to surrounding areas. 7. Outer gloves must be placed in a containment bag
4. Consider using closed-system drug-transfer devices while in the BSC.
while compounding hazardous drugs in a Class II 8. In an isolator, a second glove must be worn inside the
BSC; evidence documents a decrease in drug contam- fixed-glove assembly.
inants inside a Class II BSC when such devices are 9. In an isolator, fixed gloves or appendix must be sur-
used.4 face cleaned after compounding is completed to avoid
5. Reduce the hazardous drug contamination burden in spreading hazardous drug contamination to other sur-
the Class II BSC by wiping down hazardous drug vials faces.
before placing them in the BSC. 10. Clean gloves (e.g., the clean inner gloves) should be
used to surface decontaminate the final preparation,
place the label onto the final preparation, and place it
Appendix B—Recommendations for into the pass-through.
Use of Class III BSCs and Isolators 11. Don fresh gloves to complete the final check, place
preparation into a clean transport bag, and remove the
1. Only a ventilated cabinet appendix to protect workers bag from the pass-through.
and adjacent personnel from exposure and to provide 12. Wash hands before donning and after removing gloves.
an aseptic environment may be used to compound ster- 13. Remove gloves with care to avoid contamination.
ile hazardous drugs. Specific procedures for removal must be established
2. Only ventilated cabinets that are designed to contain and followed.
aerosolized drug product within the cabinet should be 14. Gloves should be removed and contained inside the
used to compound hazardous drugs. Class II BSC or isolator.
3. The use of a Class III BSC or isolator must be accom- 15. Change gloves after administering a dose of hazardous
panied by a stringent program of work practices, in- drugs or when leaving the immediate administration
cluding operator training and demonstrated compe- area.
tence, contamination reduction, and decontamination. 16. Dispose of contaminated gloves as contaminated
4. Decontamination of the Class III BSC or isolator must waste.
be done in a way that contains any hazardous drug sur-
face contamination during the cleaning process.
Appendix D—Recommendations
5. Appropriate decontamination within the cabinet must
be completed before the cabinet is accessed via pass- for Use of Gowns
throughs or removable front panels.
6. Gloves or gauntlets must not be replaced before com- 1. Gowns should be worn during compounding, during
pletion of appropriate decontamination within the administration, when handling waste from patients re-
cabinet. cently treated with hazardous drugs, and when clean-
7. Surface decontamination of final preparations must be ing up spills of hazardous drugs.
done before labeling and placing into the pass-through. 2. Select disposable gowns of material tested to be pro-
8. Final preparations must be placed into a transport bag tective against the hazardous drugs to be used.
while in the pass-through for removal from the cabi- 3. Coated gowns must be worn no longer than three
net. hours during compounding and changed immediately
when damaged or contaminated.
4. Remove gowns with care to avoid spreading contami-
Appendix C—Recommendations nation. Specific procedures for removal must be estab-
for Use of Gloves lished and followed.
5. Dispose of gowns immediately upon removal.
1. Wear double gloves for all activities involving hazard- 6. Contain and dispose of contaminated gowns as con-
ous drugs. Double gloves must be worn during any taminated waste.
handling of hazardous drug shipping cartons or drug 7. Wash hands after removing and disposing of gowns.
vials, compounding and administration of hazardous
Appendix E—Recommendations for 18. Surface decontamination of final preparations must be

Working in BSCs and Isolators done before labeling and placing into the pass-through.
19. Final preparations must be placed into a transport bag
1. The use of a Class II or III BSC or isolator must be ac- while in the pass-through for removal from the cabi-
companied by a stringent program of work practices, net.
including operator training and demonstrated compe-
tence, contamination reduction, and decontamination. Appendix F—Recommendations
2. Do not place unnecessary items in the work area of the for Compounding and Handling
cabinet or isolator where hazardous drug contamina- Noninjectable Hazardous Drug
tion from compounding may settle on them.
3. Do not overcrowd the BSC or isolator.
Dosage Forms
4. Gather all needed supplies before beginning com-
1. Hazardous drugs should be labeled or otherwise iden-
pounding. Avoid exiting and reentering the work area
tified as such to prevent improper handling.
of the BSC or isolator.
2. Tablet and capsule forms of hazardous drugs should
5. Appropriate handling of the preparation in the BSC
not be placed in automated counting machines, which
or pass-through of the isolator, including spraying or
subject them to stress and may introduce powdered
wiping with 70% alcohol or another appropriate disin-
contaminants into the work area.
fectant, is necessary for aseptic compounding.
3. During routine handling of noninjectable hazardous
6. Reduce the hazardous drug contamination burden in
drugs and contaminated equipment, workers should
the BSC or isolator by wiping down hazardous drug
wear two pairs of gloves that meet the ASTM standard
vials before placing them in the BSC or isolator.
for chemotherapy gloves.85
7. Transport bags must never be placed in the BSC or the
4. Counting and pouring of hazardous drugs should be
isolator work chamber during compounding to avoid
done carefully, and clean equipment should be dedi-
inadvertent contamination of the outside surface of the
cated for use with these drugs.
bag.
5. Contaminated equipment should be cleaned initially
8. Final preparations should be surface decontaminated
with gauze saturated with sterile water; further cleaned
within the BSC or isolator and placed into the trans-
with detergent, sodium hypochlorite solution, and neu-
port bags in the BSC or in the isolator pass-through,
tralizer; and then rinsed. The gauze and rinse should be
taking care not to contaminate the outside of the trans-
contained and disposed of as contaminated waste.
port bag.
6. Crushing tablets or opening capsules should be
9. Decontaminate the work surface of the BSC or isolator
avoided; liquid formulations should be used whenever
before and after compounding per the manufacturer’s
possible.
recommendations or with detergent, sodium hypo-
7. During the compounding of hazardous drugs (e.g.,
chlorite solution, and neutralizer.
crushing, dissolving, or preparing a solution or an oint-
10. Decontaminate all surfaces of the BSC or isolator at
ment), workers should wear nonpermeable gowns and
the end of the batch, day, or shift, as appropriate to the
double gloves. Compounding should take place in a
workflow. Typically, a BSC or isolator in use 24 hours
ventilated cabinet.
a day would require decontamination two or three
8. Compounding nonsterile forms of hazardous drugs
times daily. Disinfect the BSC or isolator before com-
in equipment designated for sterile products must be
pounding a dose or batch of sterile hazardous drugs.
undertaken with care. Appropriate containment, deac-
11. Wipe down the outside of the Class II BSC front open-
tivation, and disinfection techniques must be utilized.
ing and the floor in front of the BSC with detergent,
9. Hazardous drugs should be dispensed in the final dose
sodium hypochlorite solution, and neutralizer at least
and form whenever possible. Unit-of-use containers
daily.
for oral liquids have not been tested for containment
12. Seal and then decontaminate surfaces of waste and
properties. Most exhibit some spillage during prepa-
sharps containers before removing from the BSC or
ration or use. Caution must be exercised when using
isolator.
these devices.
13. Decontamination is required after any spill in the BSC
10. Bulk containers of liquid hazardous drugs, as well as
or isolator during compounding.
specially packaged commercial hazardous drugs (e.g.,
14. Seal all contaminated materials (e.g., gauze, wipes,
Neoral [manufactured by Novartis]), must be handled
towels, wash or rinse water) in bags or plastic contain-
carefully to avoid spills. These containers should be
ers and discard as contaminated waste.
dispensed and maintained in sealable plastic bags to
15. Decontamination of the Class III BSC or isolator must
contain any inadvertent contamination.
be done in a way that contains any hazardous drug sur-
11. Disposal of unused or unusable noninjectable dosage
face contamination during the cleaning process.
forms of hazardous drugs should be performed in the
16. Appropriate decontamination within the cabinet must
same manner as for hazardous injectable dosage forms
be completed before the cabinet is accessed via the
and waste.
pass-throughs or removable front panels.
17. Gloves or gauntlets must not be replaced before com-
pletion of appropriate decontamination within the
cabinet.
Appendix G—Recommendations 4. Syringes should have Luer-Lok connections and be

for Reducing Exposure to Hazardous less than three-fourths full.
5. Designate a workplace for handling hazardous drugs.
Drugs During Administration 6. Have a spill kit and hazardous drug waste container
in All Practice Settings104 readily available.
7. Procedure for gloving: Wash hands; don double
Intravenous administration gloves.
1. The use of gloves, gown, and face shield (as needed 8. Always work below eye level.
for splashing) is required. 9. Visually examine hazardous drug dose while still con-
2. Gather all necessary equipment and supplies, includ- tained in transport bag.
ing PPE. 10. If hazardous drug dose appears intact, remove it from
3. Use needleless systems whenever possible. the transport bag.
4. Use Luer-Lok fittings for all needleless systems, sy- 11. Remove the syringe cap and connect appropriate
ringes, needles, infusion tubing, and pumps. safety needle.
5. Needleless systems may result in droplets leaking at 12. Do not expel air from syringe or prime the safety nee-
connection points; use gauze pads to catch leaks. dle.
6. Designate a workplace for handling hazardous drugs. 13. After administration, discard hazardous drug syringes
7. Have a spill kit and hazardous drug waste container (with the safety needle attached) directly into a hazard-
readily available. ous drug waste container.
8. Procedure for gowning and gloving: Wash hands, don 14. Wearing gloves, contain and dispose of materials con-
first pair of gloves, don gown and face shield, and then taminated with hazardous drugs.
don second pair of gloves. Gloves should extend be 15. Do not push or force materials contaminated with haz-
yond the elastic or knit cuff of the gown. Double-glov ardous drugs into the hazardous drug waste container.
ing requires one glove to be worn under the cuff of the 16. Carefully remove, contain, and discard gloves.
gown and the second glove over the cuff. 17. Wash hands thoroughly after removing gloves.
9. Always work below eye level.
10. Visually examine hazardous drug dose while it is still
Oral administration
contained in transport bag.
1. Double gloves are required, as is a face shield if there
11. If hazardous drug dose appears intact, remove it from
is a potential for spraying, aerosolization, or splashing.
the transport bag.
2. Workers should be aware that tablets or capsules may
12. Place a plastic-backed absorbent pad under the admin-
be coated with a dust of residual hazardous drug that
istration area to absorb leaks and prevent drug contact
could be inhaled, absorbed through the skin, ingested,
with the patient’s skin.
or spread to other locations and that liquid formula-
13. If priming occurs at the administration site, prime i.v.
tions may be aerosolized or spilled.
tubing with an i.v. solution that does not contain haz-
3. No crushing or compounding of oral hazardous drugs
ardous drugs or by the backflow method.
may be done in an unprotected environment.
14. Place a gauze pad under the connection at injection
4. Gather all necessary equipment and supplies, includ-
ports during administration to catch leaks.
ing PPE.
15. Use the transport bag as a containment bag for materi-
5. Designate a workplace for handling hazardous drugs.
als contaminated with hazardous drugs, drug contain-
6. Have a spill kit and hazardous drug waste container
ers, and sets.
readily available.
16. Discard hazardous drug containers with the adminis-
7. Procedure for gloving: Wash hands and don double
tration sets attached; do not remove the set.
gloves.
17. Wash surfaces that come into contact with hazardous
8. Always work below eye level.
drugs with detergent, sodium hypochlorite solution,
9. Visually examine hazardous drug dose while it is still
and neutralizer, if appropriate.
contained in transport bag.
18. Wearing gloves, contain and dispose of materials con-
10. If hazardous drug dose appears intact, remove it from
taminated with hazardous drugs and remaining PPE as
the transport bag.
contaminated waste.
11. Place a plastic-backed absorbent pad on the work area,
19. Hazardous drug waste container must be sufficiently
if necessary, to contain any spills.
large to hold all discarded material, including PPE.
12. After administration, wearing double gloves, contain
20. Do not push or force materials contaminated with haz-
and dispose of materials contaminated with hazardous
ardous drugs into the hazardous drug waste container.
drugs into the hazardous drug waste container.
21. Carefully remove, contain, and discard gloves. Wash
13. Do not push or force materials contaminated with haz-
hands thoroughly after removing gloves.
ardous drugs into the hazardous drug waste container.
14. Carefully remove, contain, and discard gloves.
Intramuscular or subcutaneous administration
15. Wash hands thoroughly after removing gloves.
1. The use of double gloves is required.
2. Gather all necessary equipment and supplies, includ-
ing PPE.
3. Use Luer-Lok safety needles or retracting needles or
shields.
Appendix H—Recommended 3. Utility gloves (from spill kit) should be worn to re-
Contents of Hazardous Drug Spill Kit move broken glass in a BSC or an isolator. Care must
be taken not to damage the fixed-glove assembly in
1. Sufficient supplies to absorb a spill of about 1000 mL the isolator.
(volume of one i.v. bag or bottle). 4. Place glass fragments in the puncture-resistant hazard-
2. Appropriate PPE to protect the worker during cleanup, ous drug waste container located in the BSC or discard
including two pairs of disposable gloves (one outer pair into the appropriate waste receptacle of the isolator.
of heavy utility gloves and one pair of inner gloves); 5. Thoroughly clean and decontaminate the BSC or iso-
nonpermeable, disposable protective garments (cover- lator.
alls or gown and shoe covers); and face shield. 6. Clean and decontaminate the drain spillage trough
3. Absorbent, plastic-backed sheets or spill pads. located under the Class II BSC or similarly equipped
4. Disposable toweling. Class III BSC or isolator.
5. At least two sealable, thick plastic hazardous waste 7. If the spill results in liquid being introduced onto the
disposal bags (prelabeled with an appropriate warning HEPA filter or if powdered aerosol contaminates the
label). “clean side” of the HEPA filter, use of the BSC or
6. One disposable scoop for collecting glass fragments. isolator should be suspended until the equipment has
7. One puncture-resistant container for glass fragments. been decontaminated and the HEPA filter replaced.
Appendix I—Recommendations for Spill Appendix J—OSHA-Recommended

Cleanup Procedure Steps for Immediate Treatment
of Workers with Direct Skin or Eye
General Contact with Hazardous Drugs3
1. Assess the size and scope of the spill. Call for trained
help, if necessary. 1. Call for help, if needed.
2. Spills that cannot be contained by two spill kits may 2. Immediately remove contaminated clothing.
require outside assistance. 3. Flood affected eye with water or isotonic eyewash for
3. Post signs to limit access to spill area. at least 15 minutes.
4. Obtain spill kit and respirator. 4. Clean affected skin with soap and water; rinse thor-
5. Don PPE, including inner and outer gloves and respi- oughly.
rator. 5. Obtain medical attention.
6. Once fully garbed, contain spill using spill kit. 6. Document exposure in employee’s medical record and
7. Carefully remove any broken glass fragments and medical surveillance log.
place them in a puncture-resistant container. 7. Supplies for emergency treatment (e.g., soap, eye-
8. Absorb liquids with spill pads. wash, sterile saline for irrigation) should be immedi-
9. Absorb powder with damp disposable pads or soft ately located in any area where hazardous drugs are
toweling. compounded or administered.
10. Spill cleanup should proceed progressively from areas
of lesser to greater contamination. Glossary
11. Completely remove and place all contaminated mate-
rial in the disposal bags. Antineoplastic drug: A chemotherapeutic agent that con-
12. Rinse the area with water and then clean with deter- trols or kills cancer cells. Drugs used in the treatment
gent, sodium hypochlorite solution, and neutralizer. of cancer are cytotoxic but are generally more damag-
13. Rinse the area several times and place all materials ing to dividing cells than to resting cells.4
used for containment and cleanup in disposal bags. Aseptic: Free of living pathogenic organisms or infected
Seal bags and place them in the appropriate final con- materials.4
tainer for disposal as hazardous waste. Biological-safety cabinet (BSC): A BSC may be one of
14. Carefully remove all PPE using the inner gloves. Place several types.4
all disposable PPE into disposal bags. Seal bags and Class I BSC: A BSC that protects personnel and the work
place them into the appropriate final container. environment but does not protect the product. It is a
15. Remove inner gloves; contain in a small, sealable bag; negative-pressure, ventilated cabinet usually operated
and then place into the appropriate final container for with an open front and a minimum face velocity at the
disposal as hazardous waste. work opening of at least 75 ft/min. A class I BSC is
16. Wash hands thoroughly with soap and water. similar in design to a chemical fume hood except that
17. Once a spill has been initially cleaned, have the area all of the air from the cabinet is exhausted through a
recleaned by housekeeping, janitorial staff, or environ- high-efficiency particulate air (HEPA) filter (either
mental services. into the laboratory or to the outside).
Class II BSC: A ventilated BSC that protects personnel, the
Spills in a BSC or isolator product, and the work environment. A Class II BSC
1. Spills occurring in a BSC or isolator should be cleaned has an open front with inward airflow for personnel
up immediately. protection, downward HEPA-filtered laminar airflow
2. Obtain a spill kit if the volume of the spill exceeds 30
mL or the contents of one drug vial or ampul.
for product protection, and HEPA-filtered exhausted pass-through box (such as an autoclave) that can be
air for environmental protection. decontaminated between uses.
Type A1 (formerly type A): These Class II BSCs main- Chemotherapy drug: A chemical agent used to treat dis-
tain a minimum inflow velocity of 75 ft/min, have eases. The term usually refers to a drug used to treat
HEPA-filtered down-flow air that is a portion of the cancer.4
mixed down-flow and inflow air from a common ple- Chemotherapy glove: A medical glove that has been ap-
num, may exhaust HEPA-filtered air back into the proved by FDA for use when handling antineoplastic
laboratory or to the environment through an exhaust drugs.4
canopy, and may have positive-pressure contami- Chemotherapy waste: Discarded items such as gowns,
nated ducts and plenums that are not surrounded by gloves, masks, i.v. tubing, empty bags, empty drug
negative-pressure plenums. They are not suitable for vials, needles, and syringes used while preparing and
use with volatile toxic chemicals and volatile radio- administering antineoplastic agents.4
nucleotides. Closed system: A device that does not exchange unfiltered
Type A2 (formerly type B3): These Class II BSCs maintain a air or contaminants with the adjacent environment.4
minimum inflow velocity of 100 ft/min, have HEPA- Closed-system drug-transfer device: A drug-transfer de-
filtered down-flow air that is a portion of the mixed vice that mechanically prohibits the transfer of envi-
down-flow and inflow air from a common exhaust ronmental contaminants into the system and the escape
plenum, may exhaust HEPA-filtered air back into the of hazardous drug or vapor concentrations outside the
laboratory or to the environment through an exhaust system.4
canopy, and have all contaminated ducts and plenums Cytotoxic: A pharmacologic compound that is detrimental
under negative pressure or surrounded by negative- or destructive to cells within the body.4
pressure ducts and plenums. If these cabinets are used Deactivation: Treating a chemical agent (such as a hazard-
for minute quantities of volatile toxic chemicals and ous drug) with another chemical, heat, ultraviolet light,
trace amounts of radionucleotides, they must be ex- or another agent to create a less hazardous agent.4
hausted through properly functioning exhaust cano- Decontamination: Inactivation, neutralization, or removal
pies. of toxic agents, usually by chemical means.4 Surface
Type B1: These Class II BSCs maintain a minimum inflow decontamination may be accomplished by the transfer
velocity of 100 ft/min, have HEPA-filtered down-flow of hazardous drug contamination from the surface of
air composed largely of uncontaminated, recirculated a nondisposable item to disposable ones (e.g., wipes,
inflow air, exhaust most of the contaminated down- gauze, towels).
flow air through a dedicated duct exhausted to the Disinfecting: Removal of viable organism from surfaces us-
at-mosphere after passing it through a HEPA filter, ing 70% alcohol or other appropriate disinfectant prior
and have all contaminated ducts and plenums under to compounding of sterile hazardous drugs.
negative pressure or surrounded by negative-pressure Engineering controls: Devices designed to eliminate or
ducts and plenums. If these cabinets are used for work reduce worker exposures to chemical, biological, ra-
involving minute quantities of volatile toxic chemicals diological, ergonomic, or physical hazards. Examples
and trace amounts of radionucleotides, the work must include laboratory fume hoods, glove bags, retracting
be done in the directly exhausted portion of the cabi- syringe needles, sound-dampening materials to reduce
net. noise levels, safety interlocks, and radiation shield-
Type B2 (total exhaust): These Class II BSCs maintain a ing.4
minimum inflow velocity of 100 ft/min, have HEPA- Genotoxic: Capable of damaging DNA and leading to muta
filtered down-flow air drawn from the laboratory or tions.4
the outside, exhaust all inflow and down-flow air to Glove box: A controlled environment work enclosure
the atmosphere after filtration through a HEPA filter providing a primary barrier from the work area.
without recirculation inside the cabinet or return to Operations are performed through sealed gloved open-
the laboratory, and have all contaminated ducts and ings to protect the worker, the ambient environment,
plenums under negative pressure or surrounded by di- and/or the product.4
rectly exhausted negative-pressure ducts and plenums. Hazardous drug: Any drug identified by at least one of the
These cabinets may be used with volatile toxic chemi- following six criteria: carcinogenicity, teratogenicity
cals and radionucleotides. or developmental toxicity, reproductive toxicity in
Class III BSC: A BSC with a totally enclosed, ventilated humans, organ toxicity at low doses in humans or ani-
cabinet of gastight construction in which operations mals, genotoxicity, and new drugs that mimic existing
are conducted through attached rubber gloves and ob- hazardous drugs in structure or toxicity.4
served through a nonopening view window. This BSC Hazardous waste: Any waste that is an RCRA-listed haz-
is maintained under negative pressure of at least 0.50 ardous waste [40 C.F.R. 261.30-.33] or that meets an
in of water gauge, and air is drawn into the cabinet RCRA characteristic of ignitability, corrosivity, reac-
through HEPA filters. The exhaust air is treated by tivity, or toxicity as defined in 40 C.F.R. 261.21-.24.4
double HEPA filtration or single HEPA filtration–in Health care settings: All hospitals, medical clinics, outpa-
cineration. Passage of materials in and out of the cabi- tient facilities, physicians’ offices, retail pharmacies,
net is generally performed through a dunk tank (ac- and similar facilities dedicated to the care of patients.4
cessible through the cabinet floor) or a double-door Health care workers: All workers who are involved in the
care of patients. These include pharmacists, pharmacy
technicians, nurses (registered nurses, licensed practi-
cal nurses, nurses’ aides, etc.), physicians, home health Risk assessment: Characterization of potentially adverse
care workers, and environmental services workers health effects from human exposure to environmen-
(housekeeping, laundry, and waste disposal).4 tal or occupational hazards. Risk assessment can be
HEPA filter: Filter rated 99.97% efficient in capturing par- divided into five major steps: hazard identification,
ticles 0.3-µm in diameter.4 dose–response assessment, exposure assessment, risk
Horizontal-laminar-airflow hood (horizontal-laminar- characterization, and risk communication.4
airflow clean bench): A device that protects the work Surface decontamination: Transfer of hazardous drug con-
product and the work area by supplying HEPA-filtered tamination from the surface of nondisposable items to
air to the rear of the cabinet and producing a horizontal disposable ones (e.g., wipes, gauze, towels). No proce-
flow across the work area and out toward the worker.4 dures have been studied for surface decontamination
Isolator: A device that is sealed or is supplied with air of hazardous drug contaminated surfaces. The use of
through a microbially retentive filtration system gauze moistened with alcohol, sterile water, peroxide,
(HEPA minimum) and may be reproducibly decon- or sodium hypochlorite solutions may be effective.
taminated. When closed, an isolator uses only decon- The disposable item, once contaminated, must be con-
taminated interfaces (when necessary) or rapid trans- tained and discarded as hazardous waste.
fer ports for materials transfer. When open, it allows Ventilated cabinet: A type of engineering control designed
for the ingress and egress of materials through defined for purposes of worker protection (as used in these
openings that have been designed and validated to guidelines). These devices are designed to minimize
preclude the transfer of contaminants or unfiltered air worker exposures by controlling emissions of airborne
to adjacent environments. An isolator can be used for contaminants through (1) the full or partial enclosure
aseptic processing, for containment of potent com- of a potential contaminant source, (2) the use of air-
pounds, or for simultaneous asepsis and containment. flow capture velocities to capture and remove airborne
Some isolator designs allow operations within the iso- contaminants near their point of generation, and (3)
lator to be conducted through a fixed-glove assembly the use of air pressure relationships that define the di-
without compromising asepsis or containment.4 rection of airflow into the cabinet. Examples of ven-
Aseptic isolator: A ventilated isolator designed to exclude tilated cabinets include BSCs, containment isolators,
external contamination from entering the critical zone and laboratory fume hoods.4
inside the isolator.4
Aseptic containment isolator: A ventilated isolator designed
to meet the requirements of both an aseptic isolator Developed through the ASHP Council on Professional Affairs and
and a containment isolator.4 approved by the ASHP Board of Directors on January 12, 2006.
Containment isolator: A ventilated isolator designed to pre-
vent the toxic materials processed inside it from escap- These guidelines supersede the ASHP technical assistance bulletin
ing to the surrounding environment.4 on handling cytotoxic and hazardous drugs (Am J Hosp Pharm.
Laboratory coat: A disposable or reusable open-front coat, 1990; 47:1033–49).
usually made of cloth or other permeable material.4
Material safety data sheet: Contains summaries provided Luci A. Power, M.S., is gratefully acknowledged for leading the
by the manufacturer to describe the chemical proper- revision of these guidelines. ASHP acknowledges the following
ties and hazards of specific chemicals and ways in individuals for their contributions to these guidelines: Thomas H.
which workers can protect themselves from exposure Connor, Ph.D., CAPT (ret.) Joseph H. Deffenbaugh Jr., M.P.H.,
to these chemicals.4 CDR Bruce R. Harrison, M.S., BCOP, Dayna McCauley, Pharm.D.,
Mutagenic: Capable of increasing the spontaneous muta- BCOP, Melissa A. McDiarmid, M.D., M.P.H., Kenneth R. Mead,
tion rate by causing changes in DNA.4 M.S., PE, and Martha Polovich, M.N., RN, AOCN.
Personal protective equipment (PPE): Items such as
gloves, gowns, respirators, goggles, and face shields Copyright © 2006, American Society of Health-System Pharmacists,
that protect individual workers from hazardous physi- Inc. All rights reserved.
cal or chemical exposures.4
Respirator: A type of PPE that prevents harmful materials The bibliographic citation for this document is as follows: American
from entering the respiratory system, usually by filter- Society of Health-System Pharmacists. ASHP guidelines on han
ing hazardous agents from workplace air. A surgical dling hazardous drugs. Am J Health-Syst Pharm. 2006; 63:1172–
mask does not offer respiratory protection.4 93.
ASHP Guidelines on
Pharmacy-Prepared Ophthalmic Products
Pharmacists are frequently called on to prepare sterile prod- dered, necessitating multiple dilutions. Decimal errors
ucts intended for ophthalmic administration when a suitable in the preparation of these products may have serious
sterile ophthalmic product is not available from a licensed consequences.
manufacturer. These products may be administered topically 5. Accuracy in compounding ophthalmic products is
or by subconjunctival or intraocular (e.g., intravitreal and further enhanced by the use of larger volumes, which
intracameral) injection and may be in the form of solutions, tends to diminish the effect of errors in measurement
suspensions, or ointments. caused by the inherent inaccuracy of measuring de-
The sterility of these products, as well as accuracy in vices. Larger volumes, however, also necessitate
the calculation and preparation of doses, is of great importance. special attention to adequate mixing procedures,
Ocular infections and loss of vision caused by contamination especially for ointments.
of extemporaneously prepared ophthalmic products have 6. Strict adherence to aseptic technique and proper ster-
been reported.1,2 Drugs administered by subconjunctival or ilization procedures are crucial in the preparation of
intraocular injection often have narrow therapeutic indices. ophthalmic products. All extemporaneous compound-
In practice, serious errors in technique have occurred in the ing of ophthalmic products should be performed in a
preparation of intravitreal solutions, which resulted in con- certified laminar airflow hood (or, for preparing cy-
centrations up to double the intended amounts.3 To ensure totoxic or hazardous agents, a biological safety cabi-
adequate stability, uniformity, and sterility, ophthalmic products net).5 Only personnel trained and proficient in the
from licensed manufacturers should be used whenever possible. techniques and procedures should prepare ophthalmic
The following guidelines are intended to assist phar- products. Quality-assurance principles for compound-
macists when extemporaneous preparation of ophthalmic ing sterile products should be followed, and methods
products is necessary. These guidelines do not apply to the should be established to validate all procedures and
manufacturing of sterile pharmaceuticals as defined in state processes related to sterile product preparation. In ad-
and federal laws and regulations. Other guidelines on extem- dition, the following should be considered:
poraneous compounding of ophthalmic products also have a. Ingredients should be mixed in sterile empty
been published.4,5 containers. Individual ingredients often can first
be drawn into separate syringes and then injected
1. Before compounding any product for ophthalmic use, into a larger syringe by insertion of the needles
the pharmacist should review documentation that sub- into the needle-free tip of the larger syringe. The
stantiates the safety and benefit of the product when larger syringe should be of sufficient size to al-
administered into the eye. If no such documentation low for proper mixing of ingredients.
is available, the pharmacist must employ professional b. To maximize measurement accuracy, the smallest
judgment in determining suitability of the product for syringe appropriate for measuring the required
ophthalmic administration. volume should be used. When the use of a single
2. Important factors to be considered in preparing an syringe would require estimation of the volume
ophthalmic medication include the following:6 (e.g., measuring 4.5 mL in a 5-mL syringe with
a. Sterility. no mark at the 4.5-mL level), the use of two sy-
b. Tonicity. ringes of appropriate capacities (or two separate
c. pH, buffering. syringe “loads”) should be considered in order to
d. Inherent toxicity of the drug. provide a more accurate measurement.
e. Need for a preservative. c. A fresh disposable needle and syringe should be
f. Solubility. used at each step to avoid contamination and
g. Stability in an appropriate vehicle. prevent error due to residual contents.
h. Viscosity. d. When multiple dilutions are required, the con-
i. Packaging and storage of the finished product. tainers of interim concentrations should be la-
3. A written procedure for each ophthalmic product com- beled to avoid confusion.
pounded should be established and kept on file and e. In the preparation of an ophthalmic product from
should be easily retrievable. The procedure should either (1) a sterile powder that has been recon-
specify appropriate steps in compounding, including stituted or (2) a liquid from a glass ampul, the
aseptic methods, and whether microbiologic filtration ingredients should be filtered through a 5-μm
or terminal sterilization (e.g., autoclaving) of the fin- filter to remove any particulate matter.
ished product is appropriate. 7. For ophthalmic preparations that must be sterilized,
4. Before preparation of the product is begun, math- an appropriate and validated method of sterilization
ematical calculations should be reviewed by another should be determined on the basis of the characteris-
person or by an alternative method of calculation in tics of the particular product and container. Filtration
order to minimize error. This approach is especially of thepreparation through a 0.22-μm filter into a sterile
important for products, such as intraocular injections, final container is a commonly used method; however,
for which extremely small doses are frequently or- this method is not suitable for sterilizing ophthalmic
suspensions and ointments.7 When an ophthalmic 2. Associated Press. Eye drop injuries prompt an FDA
preparation is compounded from a nonsterile ingre- warning. N Y Times. 1990; 140(Dec 9):39I.
dient, the final product must be sterilized before it 3. Jeglum EL, Rosenberg SB, Benson WE. Preparation
is dispensed. Sterilization by autoclaving in the final of intravitreal drug doses. Ophthalmic Surg.
container may be possible, provided that product sta- 1981; 12:355–9.
bility is not adversely affected and appropriate quality 4. Reynolds LA. Guidelines for preparation of sterile
control procedures are followed.6 ophthalmic products. Am J Hosp Pharm. 1991;
8. Preservative-free ingredients should be used in the 48:2438–9.
preparation of intraocular injections, since some pre- 5. Reynolds LA, Closson R. Ophthalmic drug formu-
servatives are known to be toxic to many of the internal lations. A handbook of extemporaneous products.
structures of the eye.6 Vancouver, WA: Applied Therapeutics; (in press).
9. In the preparation of ophthalmic products from cyto- 6. The United States Pharmacopeia, 22nd rev., and
toxic or other hazardous agents, the pharmacist should The National Formulary, 17th ed. Rockville, MD:
adhere to established safety guidelines for handling such The  United States Pharmacopeial Convention;
agents.8,9 1989:1692–3.
1 0. The final container should be appropriate for the 7. Allen LV. Indomethacin 1% ophthalmic suspension.
ophthalmic product and its intended use and should US Pharm. 1991; 16(May):82–3.
not interfere with the stability and efficacy of the prep- 8. American Society of Hospital Pharmacists. ASHP
aration.10 Many ophthalmic liquids can be packaged in technical assistance bulletin on handling cytotoxic and
sterile plastic bottles with self-contained dropper tips hazardous drugs. Am J Hosp Pharm. 1990; 47:1033–49.
or in glass bottles with separate droppers. Ophthalmic 9. OSHA work-practice guidelines for personnel deal-
ointments should be packaged in sterilized ophthalmic ing with cytotoxic (antineoplastic) drugs. Am J Hosp
tubes. Injectables that are not for immediate use should Pharm. 1986; 43:1193–204.
be packaged in sterile vials rather than in syringes, and 10. Ansel HC, Popovich NG. Pharmaceutical dosage
appropriate overfill should be included. All containers forms and drug delivery systems. 5th ed. Philadelphia:
should be adequately sealed to prevent contamination. Lea & Febiger; 1990:354–7.
11. The pharmacist should assign appropriate expira- 11. Stolar MH. Expiration dates of repackaged drug prod-
tion dates to extemporaneously prepared ophthalmic ucts. Am J Hosp Pharm. 1979; 36:170. Editorial.
products; these dates should be based on documented 12. Remington’s pharmaceutical sciences. 19th ed. Gennaro
stability data as well as the potential for microbial con- AR, ed. Easton, PA: Mack Publishing; 1990:1581–
tamination of the product.11 The chemical stability of 959.
the active ingredient, the preservative, and packaging
material should be considered in determining the over-
all stability of the final ophthalmic product.12 These guidelines were reviewed in 2008 by the Council on Pharmacy
1 2. Ophthalmic products should be clearly and accurately Practice and by the Board of Directors and were found to still be ap-
labeled. In some cases, it may be appropriate to label propriate.
the products with both the weight and concentration
of active ingredients and preservatives. Labels should Approved by the ASHP Board of Directors, April 21, 1993.
also specify storage and handling requirements and Developed by the ASHP Council on Professional Affairs.
expiration dates. Extemporaneously prepared ophthal-
mic products dispensed for outpatient use should be Copyright © 1993, American Society of Hospital Pharmacists, Inc.
labeled in accordance with applicable state regulations All rights reserved.
for prescription labeling.
Society of Hospital Pharmacists. ASHP technical assistance bulle-
References
tin on pharmacy-prepared ophthalmic products. Am J Hosp Pharm.
1993; 50:1462–3.
1. Associated Press. Pittsburgh woman loses eye to
tainted drugs; 12 hurt. Baltimore Sun. 1990; Nov 9:3A.
Drug Distribution and Control: Preparation and Handling–Technical Assistance Bulletin 123
ASHP Technical Assistance Bulletin on

Compounding Nonsterile Products in Pharmacies
Introduction sensitivity of ±1 mg (or 0.1 mg), and 1-mg, 100-mg, 1-g, and
100-g weights for checking. Balances should be maintained
Pharmacists are the only health care providers formally in areas of low humidity and should be stored on flat, non-
trained in the art and science of compounding medications.1,2 vibrating surfaces away from drafts. At least annually, the
Therefore pharmacists are expected, by the medical commu- performance of balances should be checked according to the
nity and the public, to possess the knowledge and skills neces- guidelines found in Remington’s Pharmaceutical Sciences,3
sary to compound extemporaneous preparations. Pharmacists USP XXII NF XVII: The United States Pharmacopeia–The
have a responsibility to provide compounding services for pa- National Formulary (USP–NF),4 or USP DI Volume III:
tients with unique drug product needs. Approved Drug Products and Legal Requirements5 or the in-
This Technical Assistance Bulletin is intended to assist structions of the balance manufacturer. Performance should
pharmacists in the extemporaneous compounding of non- be documented.
sterile drug products for individual patients. Included in this Weights should be stored in rigid, compartmental-
document is information on facilities and equipment, ingre- ized boxes and handled with metal, plastic, or plastic-
dient selection, training, documentation and record keeping, tipped forceps—not fingers—to avoid scratching or soil-
stability and beyond-use dating, packaging and labeling, and ing. Since most Class III prescription balances are only
limited batch compounding. This document is not intended accurate to ±5 or 10 mg, Class P weights may be used for
for manufacturers or licensed repackagers. compounding purposes.4 The USP–NF recommends that the
class of weights used be chosen to limit the error to 0.1%. In
Facilities and Equipment practical terms this means that Class P weights can be used
for weighing quantities greater than 100 mg.
Facilities. It is not necessary that compounding activities be The minimum weighable quantity must be determined
located in a separate facility; however, the compounding area for any balance being used for compounding. To avoid errors
should be located sufficiently away from routine dispensing and of 5% or more on a Class III balance with a sensitivity require-
counseling functions and high traffic areas. The area should be ment of 6 mg, quantities of less than 120 mg of any substance
isolated from potential interruptions, chemical contaminants, should not be weighed. Smaller quantities may be weighed on
and sources of dust and particulate matter. To minimize chemical more sensitive balances. If an amount is needed that is less
contaminants, the immediate area and work counter should be than the minimum weighable quantity determined for a bal-
free of previously used drugs and chemicals. To minimize dust ance, an aliquot method of measurement should be used.
and particulate matter, cartons and boxes should not be stored
or opened in the compounding area. The compounding area Measuring Equipment. The pharmacist should use judgment
should not contain dust-collecting overhangs (e.g., ceiling in selecting measuring equipment. The recommendations given
utility pipes, hanging light fixtures) and ledges (e.g., window- in the USP–NF General Information section on volumetric ap-
sills). Additionally, at least one sink should be located in or near paratus should be followed. For maximum accuracy in measur-
the compounding area for hand washing before compounding ing liquids, a pharmacist should select a graduate with a capacity
operations. Proper temperature and humidity control within equal to or slightly larger than the volume to be measured. The
the compounding area or facility is desirable. general rule is to measure no less than 20% of the capacity of
Work areas should be well lighted, and work sur- a graduate. Calibrated syringes of the appropriate size may be
faces should be level and clean. The work surface should be preferred over graduated cylinders for measuring viscous liquids
smooth, impervious, free of cracks and crevices (preferably such as glycerin or mineral oil, since these liquids drain slowly
seamless), and nonshedding. Surfaces should be cleaned at and incompletely from graduated cylinders. Viscous liquids may
both the beginning and the end of each distinct compounding also be weighed if this is more convenient, provided that the ap-
operation with an appropriate cleaner or solvent. The entire propriate conversions from volume to weight are made by using
compounding facility should be cleaned daily or weekly (as the specific gravity of the liquid. Thick, opaque liquids should be
needed) but not during the actual process of compounding. weighed. For example, if a formulation specifies 1.5 mL of a liq-
uid, it is better to use a 3-mL syringe with appropriate graduations
Equipment. The equipment needed to compound a drug to measure 1.5 mL than to use a 10-mL graduated cylinder, since
product depends upon the particular dosage form requested. quantities of less than 2.0 mL cannot be accurately measured in
Although boards of pharmacy publish lists of required a 10-mL graduate. Also, if an opaque, viscous chemical, such as
equipment and accessories, these lists are not intended to Coal Tar, USP, must be measured, it is more accurate to weigh the
limit the equipment available to pharmacists for compound- substance than to try to read a meniscus on a graduated cylinder
ing.2 Equipment should be maintained in good working or- or a fill line on a syringe.
der. Pharmacists are responsible for obtaining the required For volumes smaller than 1 mL, micropipettes are rec-
equipment and accessories and ensuring that equipment is ommended, in sizes to cover the range of volumes measured.
properly maintained and maintenance is documented. Two or three variable pipettes can usually cover the range
from about 50 μL to 1 mL.
Weighing Equipment. In addition to a torsion balance, pharma- Although conical graduates are convenient for mixing
cists who routinely compound may need to use a top-loading solutions, the error in reading the bottom of the meniscus
electronic balance that has a capacity of at least 300 g, a increases as the sides flare toward the top of the graduate.
124 Drug Distribution and Control: Preparation and Handling–Technical Assistance Bulletin
Therefore, for accurate measurements, cylindrical gradu- freezer—in some cases, an ultrafreezer capable of maintain-
ates are preferred. Conical graduates having a capacity of ing temperatures as low as –80 °C.
less than 25 mL should not be used in prescription com-
pounding.4 Ingredients
Compounding Equipment. Pharmacists need at least two Ideally, only USP or NF chemicals manufactured by FDA-
types of mortars and pestles—one glass and one Wedgwood inspected manufacturers should be used for compounding.
or porcelain. The sizes of each will depend on the drug prod- Although chemicals labeled USP or NF meet USP–NF stan-
ucts being compounded. Glass mortars should be used for dards for strength, quality, and purity for human drug prod-
liquid preparations (solutions and suspensions) and for mix- ucts, the facilities in which the chemicals were manufactured
ing chemicals that stain or are oily. Generally, glass mortars may not meet FDA Good Manufacturing Practice (GMP)
should be used for antineoplastic agents. Because of their standards. In the event that a needed chemical is not avail-
rough surface, Wedgwood mortars are preferred for reduc- able from an FDA-inspected facility, the pharmacist should,
ing the size of dry crystals and hard powder particles and by next best preference, obtain a USP or NF product. If that
for preparing emulsions. Porcelain mortars have a smoother is not available, the pharmacist should use professional judg-
surface than Wedgwood mortars and are ideal for blending ment and may have to obtain the highest-grade chemical pos-
powders and pulverizing soft aggregates or crystals. When sible. Chemical grades that may be considered in this situation
Wedgwood mortars are used for small amounts of crystals or are ACS grade (meeting or exceeding specifications listed for
powders, the inside surface may first be lightly dusted with reagent chemicals by the American Chemical Society) and
lactose to fill any crevices in which the crystals or powders FCC grade (meeting or exceeding requirements defined by the
might lodge. If the contact surfaces of the mortar and pestle Food Chemicals Codex). Additional professional judgment is
become smooth with use, rubbing them with a small amount especially necessary in cases of chemical substances that have
of sand or emery powder may adequately roughen them. not been approved for any medical use. Particularly in these
Over extended use, a pestle and a mortar become shaped to cases, but also in others as needed, the pharmacist, prescriber,
each other’s curvature. Thus, to ensure maximum contact and patient should be well informed of the risks involved.
between the surface of the head of each pestle and the inte- Selection of ingredients may also depend on the dos-
rior of its corresponding mortar, pestles and mortars should age form to be compounded. In most cases, the prescriber
not be interchanged.3 specifies a particular dosage form, such as a topical oint-
The compounding area should be stocked with appro- ment, oral solution or rectal suppository. Sometimes, how-
priate supplies. Although supply selection depends on the ever, the prescriber relies on the pharmacist to decide on
types of products compounded, all areas should have weigh- an appropriate form. Irrespective of how the drug order is
ing papers, weighing cups, or both to protect balance pans written, the pharmacist should evaluate the appropriateness
and spatulas. Glassine weighing papers (as opposed to bond of ingredients and the drug delivery system recommended.
weighing paper) should be used for products such as oint- Factors to consider in selecting the dosage form include (1)
ments, creams, and some dry chemicals. Disposable weigh- physical and chemical characteristics of the active ingredi-
ing dishes should also be stocked for substances like Coal ent, (2) possible routes of administration that will produce
Tar, USP. the desired therapeutic effect (e.g., oral or topical), (3) pa-
Each compounding area should have stainless steel tient characteristics (e.g., age, level of consciousness, ability
and plastic spatulas for mixing ointments and creams and to swallow a solid dosage form), (4) specific characteristics
handling dry chemicals. The pharmacist should exercise of the disease being treated, (5) comfort for the patient, and
judgment in selecting the size and type of spatula. Small (6) ease or convenience of administration.
spatula blades (6 inches long or less) are preferred for han- In checking the physical form of each ingredient, the
dling dry chemicals, but larger spatula blades (>6 inches) are pharmacist should not confuse drug substances that are avail-
preferred for large amounts of ointments or creams and for able in more than one form. For example, coal tar is available
preparing compactible powder blends for capsules. Plastic as Coal Tar, USP, or Coal Tar Topical Solution, USP; phenol
spatulas should be used for chemicals that may react with is available as Liquified Phenol, USP, or Phenol, USP; sulfur
stainless steel blades. A variety of spatulas should be stocked is available as Precipitated Sulfur, USP, or Sublimed Sulfur,
in the compounding area, including 4-, 6-, and 8-inch stain- USP. If ingredients are liquids, the pharmacist should consider
less steel spatulas (one each) and 4- and 6-inch plastic spat- compounding liquid dosage forms such as solutions, syrups, or
ulas (one each). Imprinted spatulas should not be used in elixirs for the final product. If ingredients are crystals or pow-
compounding, since the imprinted ink on the spatula blade ders and the final dosage form is intended to be a dry dosage
may contaminate the product. form, options such as divided powders (powder papers) or cap-
The compounding area should contain an ointment sules should be considered. If ingredients are both liquids and
slab, pill tile, or parchment ointment pad. Although parch- dry forms, liquid formulations such as solutions, suspensions,
ment ointment pads are convenient and reduce cleanup elixirs, syrups, and emulsions should be considered.
time, parchment paper cannot be used for the preparation Care must be exercised when using commercial drug
of creams because it will absorb water. Therefore, an oint- products as a source of active ingredients. For example,
ment slab or pill tile is necessary. If suppositories are com- extended-release or delayed-release products should not be
pounded, appropriate suppository molds, either reusable or crushed. Also, since chemicals such as preservatives and
disposable, should be available. excipients in commercial products may affect the overall
Other useful equipment and supplies may include stability and bioavailability of the compounded product, their
funnels, filter paper, beakers, glass stirring rods, a source presence should not be ignored. Information on preservatives
of heat (hot plate or microwave oven), a refrigerator, and a and excipients in specific commercial products can be found in
package inserts and also in the dosage form section of selected and maintain competence in compounding. Training programs
product monographs in USP DI Volume I.6 should include instruction in the following areas:
If an injectable drug product is a possible source of active
ingredient, the pharmacist should check the salt form of the in- • Proper use of compounding equipment such as bal-
jectable product to make sure it is the same salt form ordered. ances and measuring devices—including guidelines
If it is necessary to use a different salt because of physical or for selecting proper measuring devices, limitations of
chemical compatibility considerations or product availability, weighing equipment and measuring apparatus, and the
the pharmacist should consult with the prescriber. Some inject- importance of accuracy in measuring.
able products contain active constituents in the form of prodrugs • Pharmaceutical techniques needed for preparing com-
that may not be active when administered by other routes. For pounded dosage forms (e.g., levigation, trituration,
example, if an injectable solution is a possible source of active methods to increase dissolution, geometric dilution).
ingredient for an oral product, the pharmacist must consider the • Properties of dosage forms (see Pharmaceutical
stability of the drug in gastric fluids, the first-pass effect, and Dosage Forms in USP–NF) to be compounded and re-
palatability. Also, if injectable powders for reconstitution are lated factors such as stability, storage considerations,
used, expiration dating may have to be quite short. and handling procedures.
• Literature in which information on stability, solubility,
Storage and related material can be found (see suggested refer-
ences at the end of this document).
All chemicals and drug products must be stored according to • Handling of nonhazardous and hazardous materials
USP–NF and manufacturer specifications. Most chemicals in the work area, including protective measures for
and drug products marketed for compounding use are pack- avoiding exposure, emergency procedures to follow
aged by the manufacturer in tight, light-resistant containers. in the event of exposure, and the location of Material
Chemicals intended for compounding should be purchased Safety Data Sheets (MSDSs) in the facility.7–10
in small quantities and stored in the manufacturer’s original • Use and interpretation of chemical and pharmaceutical
container, which is labeled with product and storage infor- symbols and abbreviations in medication orders and in
mation. This practice fosters the use of fresh chemicals and product formulation directions.
ensures that the manufacturer’s label remains with the lot of • Pharmaceutical calculations.
chemical on hand. Certificates of purity for chemical ingre-
dients should be filed for a period of time no less than the Procedures should be established to verify the ability of staff
state’s time requirement for retention of dispensing records. to meet established competencies. These procedures may
The manufacturer’s label instructions for storage include observation, written tests, or quality control testing
should be followed explicitly to ensure the integrity of of finished products.
chemicals and drug products and to protect employees. Most
chemicals and commercial drug products may be stored at Attire. Personnel engaged in compounding should wear
controlled room temperature, between 15 and 30 °C (59 and clean clothing appropriate for the duties they perform.
86 °F); however, the pharmacist should always check the Protective apparel, such as head, face hand, and arm cover-
manufacturer’s label for any special storage requirements. ings, should be worn as necessary to preclude contamination
Storage information provided for specific commercial drug of products and to protect workers.
products in USP DI Volume I and on product labels follows Generally, a clean laboratory jacket is considered ap-
the definitions for storage temperatures found in the General propriate attire for most personnel performing nonsterile com-
Notices and Requirements section of USP–NF. An accept- pounding activities. Personnel involved in compounding haz-
able refrigerator maintains temperatures between 2 and 8 °C ardous materials should wear safety goggles, gloves, a mask or
(36 and 46 °F); an acceptable freezer maintains temperatures respirator, double gowns, and foot covers as required, depending
between −20 and −10°C (− 4 to +14 °F) on the substance being handled. To avoid microbial contamina-
To protect pharmacy employees and property, hazard- tion of compounded drug products, written policies should be
ous products such as acetone and flexible collodion must be established that address appropriate precautions to be observed
stored appropriately. Safety storage cabinets in various sizes if an employee has an open lesion or an illness. Depending on
are available from laboratory suppliers. the situation, an affected employee may be required to wear
special protective apparel, such as a mask or gloves, or may be
Personnel directed to avoid all contact with compounding procedures.
Compounding personnel include pharmacists and supportive Reference Materials

personnel engaged in any aspect of the compounding pro-
cedures. Pharmacists and supportive personnel must have ready access
to reference materials on all aspects of compounding (see sug-
Training. The pharmacist—who is responsible for ensuring that gested references at the end of this document). Earlier editions
the best technical knowledge and skill, most careful and accu- of some references, such as Remington’s Pharmaceutical
rate procedures, and prudent professional judgment are consis- Sciences, provide more comprehensive compounding infor-
tently applied in the compounding of pharmaceuticals—must mation than do the later editions. Information on compound-
supervise all compounding activities and ensure that supportive ing extemporaneous dosage forms from commercially available
personnel are adequately trained to perform assigned func- products can sometimes be obtained from the product’s FDA-
tions. Both pharmacists and the compounding personnel they approved labeling (package insert), the manufacturer, a local
supervise should participate in programs designed to enhance pharmacy college, or a drug information center. It is essential
that the stability and proper storage conditions for extempo- substances resulting from contamination or from the inten-
raneous products be thoroughly researched. Therefore, the tional mixing of products can influence stability.4
availability of adequate references and appropriate training in Since compounded drug products are intended for
the use of the references is important. consumption immediately or storage for a very limited
time, stability evaluation and expiration dating are differ-
Documentation and Record Keeping ent for these products than for manufactured drug products.
According to criteria for assigning dating in the USP–NF4
Each step of the compounding process should be docu- General Notices and Requirements section and the Code of
mented. Pharmacists should maintain at least four sets of re- Federal Regulations,11 the pharmacist labeling extemporane-
cords in the compounding area: (1) compounding formulas ously compounded drug products should be concerned with the
and procedures, (2) a log of all compounded items, including beyond-use date as used by USP–NF or the expiration date as
batch records and sample batch labels (see section on pack- used by the Code of Federal Regulations. For uniformity, the
aging and labeling), (3) equipment-maintenance records, term beyond-use date will be used in the remainder of this bul-
including documentation of checks of balances, refrigera- letin. The beyond-use date is defined as that date after which a
tors, and freezers, and (4) a record of ingredients purchased, dispensed product should no longer be used by a patient.
including certificates of purity for chemicals (see section on Determination of the period during which a com-
ingredient selection) and MSDSs. pounded product may be usable after dispensing should be
Compounding procedures should be documented in based on available stability information and reasonable pa-
enough detail that preparations can be replicated and the his- tient needs with respect to the intended drug therapy. When
tory of each ingredient can be traced. Documentation should a commercial drug product is used as a source of active in-
include a record of who prepared the product (if the com- gredient, its expiration date can often be used as a factor in
pounder is not a pharmacist, the supervising pharmacist should determining a beyond-use date. For stability or expiration
also sign the compounding record); all names, lot numbers, information on commercial drug products, the pharmacist
and quantities of ingredients used; the order of mixing, includ- can refer to USP DI Volume I.6 If no information is available,
ing any interim procedures used (such as preparing a solution the manufacturer should be contacted. When the active in-
and using an aliquot); the assigned beyond-use date; and any gredient is a USP or NF product, the pharmacist may be able
special storage requirements (see section on stability and expi- to use the expiration dating of similar commercial products
ration dating). Compounding formulas and procedures should for guidance in assigning a beyond-use date. In addition, the
be written in a typeface that can be read easily. If formulas pharmacist can often refer to published literature to obtain
originate from published articles, copies of the articles should stability data on the same active ingredient under varying
be attached to or filed with the written procedures. conditions and in different formulations.12
Equipment maintenance and calibrations should be docu- The pharmacist must assess the potential for instabil-
mented and the record maintained in an equipment-mainte- ity that may result from the new environment for the active
nance record file. Refrigerator and freezer thermometers should ingredients—from the combination of ingredients and the
be checked and documented routinely, as should alarm systems packaging materials. According to USP–NF,4 hydrolysis,
indicating that temperatures are outside of acceptable limits. oxidation-reduction, and photolysis are the most common
Follow-up contact with patients who have received ex- chemical reactions that cause instability. When the possibil-
temporaneously compounded products is recommended to as- ity of such reactions exists, the pharmacist should seek ad-
certain that the product is physically stable and that no adverse ditional stability data or consider other approaches. These
effects have occurred from use of the product. Documentation could, in extreme cases, include the preparation and dispens-
of the contact and the findings is recommended. ing of more than one compounded drug product or the use
of alternative methods of dosing. For some drugs, the lat-
ter methods might include, for example, crushing a tablet
Stability, Expiration, and or emptying the contents of a hard gelatin capsule into an
Beyond-Use Dating appropriate food substance at each dosing time.
In assigning a beyond-use date for compounded drug
The USP–NF4 defines stability as the extent to which a products, the pharmacist should use all available stability
dosage form retains, within specified limits and throughout information, plus education and experience in deciding how
its period of storage and use, the same properties and char- factors affecting product stability should be weighted. In the
acteristics that it possessed at the time of its preparation. The absence of stability data to the contrary or any indication of
USP–NF lists the following five types of stability: a stability problem, the following general criteria for assign-
ing maximum beyond-use dates are recommended. It must be
• Chemical
emphasized that these are general criteria. Professional judg-
• Physical
ment as discussed elsewhere in this section must be used in
• Microbiological
deciding when these general criteria may not be appropriate.
• Therapeutic
• Toxicological
• When a manufactured final-dosage-form product is
Factors affecting stability include the properties of used as a source of active ingredient, use no more than
each ingredient, whether therapeutically active or inactive. 25% of the manufacturer’s remaining expiration dat-
Environmental factors such as temperature, radiation, light, hu- ing or six months, whichever is less;
midity, and air can also affect stability. Similarly, such factors • When a USP or NF chemical not from a manufactured
as particle size, pH, the properties of water and other solvents final-dosage-form product is used, use no more than
employed, the nature of the container, and the presence of other six months;
• In other cases, use the intended period of therapy or no cases where the dosage strength is less than a whole number,
more than 30 days, whichever is less. a zero should precede the decimal point (e.g., 0.25 μg).3
In expressing salt forms of chemicals on a label, it is
All compounded products should be observed for signs of permissible to use atomic abbreviations. For example, HCl
instability. Observations should be performed during prepa- may be used for hydrochloride, HBr for hydrobromide, Na
ration of the drug product and any storage period that may for sodium, and K for potassium.
occur before the compounded drug product is dispensed. A Vehicles should also be stated on labels, especially if
list of observable indications of instability for solid, liquid, similar products are prepared with different vehicles. For ex-
and semisolid dosage forms appears in USP–NF. ample, if a pharmacist prepares two potassium syrups, one
using Syrup, USP, as the vehicle and one using a sugar-free
Packaging and Labeling syrup as the vehicle, the name of the vehicle should be in-
cluded on the labels.
The packaging of extemporaneously compounded products Liquids and semisolid concentrations may be expressed
for ambulatory patients should comply with regulations in terms of percentages. When the term “percent” or the
pertaining to the Poison Prevention Packaging Act of 1970. symbol “%” is used without qualification for solids and semi-
These regulations can be found in USP–NF.4 solids, percent refers to weight in weight; for solutions or sus-
Containers for compounded products should be pensions, percent refers to weight in volume; for solutions of
appropriate for the dosage form compounded. For example, liquids in liquids, percent refers to volume in volume.4
to minimize administration errors, oral liquids should never Labels for compounded products that are prepared
be packaged in syringes intended to be used for injection. in batches should include a pharmacy-assigned lot number.
The drug product container should not interact physi- Assignment of a pharmacy lot number must enable the history
cally or chemically with the product so as to alter the strength, of the compounded product to be traced, including the person
quality, or purity of the compounded product. Glass and compounding the product and the product’s formula, ingredi-
plastic are commonly used in containers for compounded ents, and procedures. Being able to trace the history of a batch is
products. To ensure container inertness, visibility, strength, essential in cases of a drug product recall or withdrawal.
rigidity, moisture protection, ease of reclosure, and economy In the preparation of labels for batches of compounded
of packaging, glass containers have been the most widely products, all extra labels should be destroyed, since phar-
used for compounded products.3 Amber glass and some plas- macy lot numbers change with each batch. If computers,
tic containers may be used to protect light-sensitive products memory typewriters, or label machines are used to print
from degradation; however, glass that transmits ultraviolet or batch labels, care must be taken to ensure that the memory
violet light rays (this includes green, blue, and clear [“flint”] and printing mechanism have been cleared and the correct
glass) should not be used to protect light-sensitive products. information is programmed before any additional labels are
The use of plastic containers for compounded products made. It is a good practice to run a blank label between each
has increased because plastic is less expensive and lighter in batch of labels to ensure that the memory has been erased
weight than glass. Since compounded products are intended or cleared. To document the information printed on each
for immediate use, most capsules, ointments, and creams set of labels, a sample label printed for the batch should be
should be stable in high-density plastic vials or ointment attached to the compounded-product log. If labels are se-
jars. Only plastic containers meeting USP–NF standards quentially prepared for different drug products, procedures
should be used.4 Reclosable plastic bags may be acceptable should exist to minimize the risk of mislabeling the com-
for selected divided powders that are intended to be used pounded products. These procedures should ensure, for ex-
within a short period of time. ample, that labels for one drug product are physically well
Each compounded product should be appropriately la- separated from labels for any other drug product.
beled according to state and federal regulations. Labels should Auxiliary labels are convenient for conveying special
include the generic or chemical name of active ingredients, storage or use information. Auxiliary labels should be at-
strength or quantity, pharmacy lot number, beyond-use date, tached conspicuously to containers, if possible. If the con-
and any special storage requirements. If a commercial prod- tainer is too small for both a general label and an auxiliary
uct has been used as a source of drug, the generic name of the label, special storage and use instructions should appear on
product should be used on the label. The trade name should not the label in a format that will emphasize the instructions.
be used because, once the commercial drug product has been
altered, it no longer exists as the approved commercial prod- Limited Batch Compounding
uct. Listing the names and quantities of inactive ingredients on
labels is also encouraged. The coining of short names for con- The purpose of extemporaneously compounding products
venience (e.g., “Johnson’s solution”) is strongly discouraged; is to provide individualized drug therapy for a particular
these names provide no assistance to others who may need to patient. When a pharmacist is repeatedly asked to prepare
identify ingredients (e.g., in emergency circumstances). identical compounded products, it may be reasonable and
Capsules should be labeled with the quantity (micro- more efficient for the pharmacist to prepare small batches of
grams or milligrams) of active ingredient(s) per capsule. Oral the compounded product.
liquids should be labeled with the strength or concentration Batch sizes should be consistent with the volume of drug
per dose (e.g., 125 mg/5 mL or 10 meq/15 mL). If the quantity orders or prescriptions the pharmacist receives for the com-
of an active ingredient is a whole number, the number should pounded product and the stability of the compounded product.
not be typed with a decimal point followed by a zero. For The pharmacist should use judgment in deciding reasonable
example, the strength of a capsule containing 25 mg of active batch sizes. Product assays should be performed by a chemi-
ingredient should be labeled as 25 mg and not 25.0 mg. In cal analysis laboratory on a regular basis to ensure product
consistency among various lots, product uniformity, and sta- for any signs of instability. Such observations should be per-
bility. Analyses should be repeated every time an ingredient formed during preparation of the drug product and during
(active or inert) or procedure is changed. Documentation of as- any storage period that may occur before the compounded
say findings should be filed for a period no less than the state’s drug product is dispensed.
time requirement for the retention of dispensing records. If specific packaging information is not available,
a light-resistant, tight container, such as an amber vial or
General Compounding Considerations bottle, should be used to maximize stability (see section on
packaging and labeling).
To provide the patient with the most stable drug product, the The pharmacist should label the compounded drug
pharmacist should take the following steps upon receiving a product, including an appropriate beyond-use date and stor-
prescription order that requires compounding. age instructions for the patient.
First, the pharmacist should determine if a similar com-
mercial product is available. A pharmacist can refer to vari- Specific Compounding Considerations
ous reference texts to check the availability of identical or
similar products. Package inserts from commercially avail- Accepted, proven compounding procedures for products
able products also contain information on inactive ingredi- including solutions, suspensions, creams, ointments, cap-
ents that can be compared with the requested formulation. If sules, suppositories, troches, emulsions, and powders may
there is a commercially manufactured identical product, the be found in reference sources or the pharmacy literature. For
local availability of the product should be determined. additional information, pharmacists should check references
When a similar product is commercially available, the cited in this document or consult colleagues or colleges of
pharmacist should determine which ingredients are different pharmacy with known expertise in compounding.
from the requested formulation to decide whether or not the
commercial product can be used. At this stage, the pharma-
cist should seek answers to the following questions: Glossary
• Are all of the ingredients appropriate for the condition For the purposes of this document, the following terms are
being treated? used with the meanings shown.
• Are the concentrations of the ingredients in the drug
order reasonable? Active Ingredient: Any chemical that is intended to furnish
• Are the physical, chemical, and therapeutic proper- pharmacologic activity in the diagnosis, cure, mitigation,
ties of the individual ingredients consistent with the treatment, or prevention of disease or to affect the struc-
expected properties of the ordered drug product? ture or function of the body of man or other animals.4
Batch: Multiple containers of a drug product or other
If the answers to these questions are positive, the pharma- material with uniform character and quality, within
cist should consult the prescriber about the possibility of specified limits, that are prepared in anticipation of
dispensing the commercial product. (In some states, phar- prescription drug orders based on routine, regularly
macists may not be required to obtain permission from the observed prescribing patterns.
prescriber to dispense a commercial product if the formula- Cold: Any temperature not exceeding 8 °C (46 °F).4
tion is identical to the drug order.) Dispensing a commercial Commercially Available Product: Any drug product manu-
product is preferable to extemporaneously compounding a factured by a producer registered with the Department
drug product because commercial products carry the manu- of Health and Human Services as a pharmaceutical
facturer’s guarantee of labeled potency and stability. manufacturer.
If there is not a commercial product available with the Compounding: The mixing of substances to prepare a drug
same or similar formulation, the pharmacist should consider product.
asking the prescriber the following questions: Container: A device that holds a drug product and is or may
be in direct contact with the product.3
• What is the purpose of the order? There may be another Cool: Any temperature between 8 and 15 °C (46 and 59 °F).4
way to achieve the purpose without compounding a Drug Product: A finished dosage form that contains an active
product. drug ingredient usually, but not necessarily (in the case
• Where did the formula originate (article, meeting, col- of a placebo), in combination with inactive ingredients.4
league)? Extemporaneous: Impromptu; prepared without a standard
• How will the drug product be used? formula from an official compendium; prepared as re-
• Does the patient have other conditions that must be quired for a specific patient.
considered? Inactive Ingredient: Any chemical other than the active in-
• For how long will the drug product be used? gredients in a drug product.4
Manufacturer: Anyone registered with the Department
If possible, the pharmacist should obtain a copy of the origi- of Health and Human Services as a producer of drug
nal formula to determine the extent to which the formula- products.14
tion has been tested for stability. When documentation is not Sensitivity Requirements: The maximal load that will
available, the pharmacist should review the ingredients for cause one subdivision of change on the index plate in
appropriateness and reasonable concentrations. the position of rest of the indicator of the balance.4
For drug products that must be compounded, the phar- Stability: The chemical and physical integrity of a drug
macist should closely observe the compounded drug product product over time.4
Trituration: The reducing of substances to fine particles by 2. Allen LV Jr. Establishing and marketing your extem-
rubbing them in a mortar with a pestle.3 poraneous compounding service. US Pharm. 1990;
Warm: Any temperature between 30 and 40 °C (86 and 104 °F).4 15(Dec):74–7.
3. Remington’s pharmaceutical sciences. 18th ed.
Suggested References Gennaro AR, ed. Easton, PA: Mack Publishing; 1990;
1630–1, 1658, 1660.
Product Availability 4. The United States Pharmacopeia, 22nd rev., and The
American Drug Index National Formulary, 17th ed. Rockville, MD: The
Drug Facts & Comparisons United States Pharmacopeial Convention; 1989.
Physicians’ Desk Reference 5. USP DI Volume III: Approved drug products and
The Extra Pharmacopoeia (Martindale) legal requirements. 14th ed. Rockville, MD: The
CHEMSOURCES United States Pharmacopeial Convention; 1994.
AHFS Drug Information 6. USP DI Volume I: Drug information for the health
care professional. 14th ed. Rockville, MD: The United
Compounding Techniques States Pharmacopeial Convention; 1994.
Compounding Companion PC-Based Software 7. 29 §C.F.R. 1910. 1200(1990).
King’s Dispensing of Medications 8. ASHP technical assistance bulletin on handling cyto-
Remington’s Pharmaceutical Sciences toxic and hazardous drugs. Am J Hosp Pharm. 1990;
Contemporary Compounding column in U.S. Pharmacist 47:1033–49.
9. Feinberg JL. Complying with OSHA’s Hazard
Pharmaceutical Calculations Communication Standard. Consult Pharm. 1991;
Stoklosa and Ansel’s Pharmaceutical Calculations 6:444, 446, 448.
Math—Use It or Lose It column in Hospital Pharmacy 10. Myers CE. Applicability of OSHA Hazard Communi
Calculations in Pharmacy column in U.S. Pharmacist cation Standard to drug products. Am J Hosp Pharm.
1990; 47:1960–1.
Drug Stability and Compatibility 11. 21 C.F.R. §211.137.
American Journal of Hospital Pharmacy 12. Connors KA, Amidon GL, Stella VJ. Chemical stabil-
ASHP’s Handbook on Extemporaneous Formulations ity of pharmaceuticals: a handbook for pharmacists.
ASHP’s Handbook on Injectable Drugs 2nd ed. New York: Wiley; 1986.
International Pharmaceutical Abstracts 13. American Society of Hospital Pharmacists. ASHP
Journal of the Parenteral Drug Association (now guidelines on preventing medication errors in hospi-
Journal of Pharmaceutical Science and Technology) tals. Am J Hosp Pharm. 1993; 50:305–14.
Canadian Society of Hospital Pharmacists Extempora- 14. Fitzgerald WL Jr. The legal authority to compound in
neous Oral Liquid Dosage Preparations pharmacy practice. Tenn Pharm. 1990; 26(Mar):21–2.
Pediatric Drug Formulations
Physicians’ Desk Reference
Contemporary Compounding column in U.S. Phar Approved by the ASHP Board of Directors, April 27, 1994.
macist Developed by the Council on Professional Affairs.
AHFS Drug Information
The Merck Index Copyright © 1994, American Society of Hospital Pharmacists, Inc.
All rights reserved.
References
1. Pancorbo SA, Campagna KD, Devenport JK, et al. Society of Hospital Pharmacists. ASHP technical assistance bulle-
Task force report of competency statements for phar- tin on compounding nonsterile products in pharmacies. Am J Hosp
macy practice. Am J Pharm Educ. 1987; 51:196–206. Pharm. 1994; 51:1441–8.
130 Drug Distribution and Control: Distribution–Positions
Distribution
Technician-Checking-Technician Programs (0310) Dispensing by Nonpharmacists and Nonprescribers (0010)
Source: Council on Administrative Affairs Source: Council on Legal and Public Affairs
To advocate technician-checking-technician programs (with To reaffirm the position that all medication dispensing func-
appropriate quality control measures) in order to permit redirec- tions must be performed by, or under the supervision of, a
tion of pharmacist resources to patient care activities; further, pharmacist; further,
To advocate state board of pharmacy approval of these To reaffirm the position that any relationships that are
programs. established between a pharmacist and other individuals in
This policy was reviewed in 2012 by the Council on order to carry out the dispensing function should preserve
Pharmacy Management and by the Board of Directors and the role of the pharmacist in (a) maintaining appropriate
was found to still be appropriate. patient protection and safety, (b) complying with regulatory
and legal requirements, and (c) providing individualized
patient care.
Public Policy and by the Board of Directors and was found
to still be appropriate.
Drug Distribution and Control: Distribution–Statements 131
ASHP Statement on Pharmacist’s Responsibility

for Distribution and Control of Drug Products
A fundamental purpose of pharmaceutical services in any research areas, and all other areas in which drugs are handled
setting is to ensure the safe and appropriate use of drug prod- and used. The pharmacist should be responsible for drug-use
ucts and drug-related devices. Fulfillment of this responsi- policies and routine inspection of all drug stocks, even if direct
bility is enhanced through the pharmacist’s involvement in custody and distribution are not possible.
all aspects of the use of drugs.1 The pharmacist also has an advocacy responsibility
This involvement should include decisions and actions with respect to decisions and policies about the use of drug-
with respect to the evaluation, procurement, storage, distri- related devices as they affect drug therapy. As appropriate,
bution, and administration of all drug products. The phar- the pharmacist may also be assigned direct responsibility
macist is responsible for development, in consultation with for control and distribution of drug-related devices.3 Drug-
appropriate other professionals, departments, and interdis- related devices include electromechanical pumps, devices
ciplinary committees in the setting, of all drug-use control for administration of injectable drugs, devices for monitor-
policies. The pharmacist should be directly responsible for ing plasma drug concentration, and devices for monitoring
the control and distribution of all stocks of drugs. drug administration rate.
The Federal Food, Drug, and Cosmetic Act defines the
term drug as “(A) articles recognized in the official United References
States Pharmacopeia, official Homeopathic Pharmacopeia
of the United States, or official National Formulary, or any 1. American Society of Hospital Pharmacists. ASHP
supplement to any of them; and (B) articles intended for use guidelines: minimum standard for pharmacies in insti-
in the diagnosis, cure, mitigation, treatment, or prevention of tutions. Am J Hosp Pharm. 1985; 42:372–5.
disease in man or other animals; and (C) articles (other than 2. 21 U.S.C. §321 (g) (1).
food) intended to affect the structure or any function of the 3. American Society of Hospital Pharmacists. ASHP
body of man or other animals; and (D) articles intended for statement on the pharmacist’s role with respect to drug
use as a component of any article specified in clauses (A), delivery systems and administration devices. Am J
(B), or (C) of this paragraph; but does not include devices or Hosp Pharm. 1989; 46:802–4.
their components, parts, or accessories.”2
For purposes of this document, drugs include those
used by inpatients and outpatients, large- and small-volume This statement was reviewed in 2005 by the Council on Professional
injections, radiopharmaceuticals, diagnostic agents including Affairs and by the Board of Directors and was found to still be
radiopaque contrast media, anesthetic gases, blood-fraction appropriate.
drugs, dialysis fluids, respiratory therapy drugs, biotechno-
logically produced drugs, investigational drugs, drug samples, Approved by the ASHP Board of Directors, November 16, 1994,
drugs brought to the setting by patients or family, and other and by the ASHP House of Delegates, June 5, 1995. Revised by the
chemicals and biological substances administered to patients ASHP Council on Professional Affairs. Supersedes a previous ver-
to evoke or enhance pharmacologic responses. sion dated June 3, 1992.
The pharmacist’s responsibility for drug-use control ex-
tends throughout the setting served. This purview extends to all Copyright © 1996, American Society of Health-System Pharmacists,
pharmacy satellite locations (inpatient and outpatient, including Inc. All rights reserved.
those serving the general public), emergency rooms, surgical
and labor and delivery suites (and related areas such as recovery The bibliographic citation for this document is as follows: ASHP
rooms), anesthesiology, nuclear medicine, radiology, dialysis statement on the pharmacist’s responsibility for distribution and
areas, ambulatory care clinics and treatment (including surgery) control of drug products. In: Practice Standards of ASHP 1996–97.
areas, respiratory therapy areas, central sterile supply centers, Deffenbaugh JH, ed. Bethesda, MD: American Society of Health-
blood banks, intensive care areas, cardiac catheterization suites, System Pharmacists; 1996.
132 Drug Distribution and Control: Distribution–Statements
ASHP Statement on Unit Dose Drug Distribution

The unit dose system of medication distribution is a phar- In view of these demonstrated benefits, the American
macy-coordinated method of dispensing and controlling Society of Hospital Pharmacists considers the unit dose sys-
medications in organized health-care settings. tem to be an essential part of drug distribution and control
The unit dose system may differ in form, depending on in organized health-care settings in which drug therapy is an
the specific needs of the organization. However, the following integral component of health-care delivery.
distinctive elements are basic to all unit dose systems: medica-
tions are contained in single unit packages; they are dispensed References
in as ready-to-administer form as possible; and for most medi-
cations, not more than a 24-hour supplya of doses is delivered 1. Summerfield MR. Unit dose primer. Bethesda, MD:
to or available at the patient-care area at any time.1,2 American Society of Hospital Pharmacists; 1983.
Numerous studies concerning unit dose drug distri- 2. American Society of Hospital Pharmacists. ASHP
bution systems have been published over the past several technical assistance bulletin on hospital drug distribu-
decades. These studies indicate categorically that unit dose tion and control. Am J Hosp Pharm. 1980; 37:1097–
systems, with respect to other drug distribution methods, are 1103.
(1) safer for the patient, (2) more efficient and economical
for the organization, and (3) a more effective method of uti-
lizing professional resources. a
In long-term care facilities, a larger supply of medication (e.g., 48
More specifically, the inherent advantages of unit dose or 72 hours) may be acceptable.
systems over alternative distribution procedures are
Approved by the ASHP Board of Directors, November 16, 1988,
1. A reduction in the incidence of medication errors. and by the ASHP House of Delegates, June 5, 1989. Supersedes pre-
2. A decrease in the total cost of medication-related vious versions approved by the House of Delegates on June 8, 1981,
activities. and by the Board of Directors on April 19, 1975, and November
3. A more efficient usage of pharmacy and nursing per- 13–14, 1980.
sonnel, allowing for more direct patient-care involve-
ment by pharmacists and nurses. Copyright © 1989, American Society of Hospital Pharmacists, Inc.
4. Improved overall drug control and drug use monitoring. All rights reserved.
5. More accurate patient billings for drugs.
6. The elimination or minimization of drug credits. The bibliographic citation for this document is as follows: American
7. Greater control by the pharmacist over pharmacy Society of Hospital Pharmacists. ASHP statement on unit dose drug
workload patterns and staff scheduling. distribution. Am J Hosp Pharm. 1989; 46:2346.
8. A reduction in the size of drug inventories located in
patient-care areas.
9. Greater adaptability to computerized and automated
procedures.
Drug Distribution and Control: Distribution–Technical Assistance Bulletins 133

Hospital Drug Distribution and Control
Drug control (of which drug distribution is an important control. Among the agencies and organizations affecting in-
part) is among the pharmacist’s most important responsi- stitutional pharmacy practice are those described below.
bilities. Therefore, adequate methods to assure that these re-
sponsibilities are met must be developed and implemented. Regulatory Agencies and Organizations. The U.S. govern-
These guidelines will assist the pharmacist in preparing drug ment, through its Food and Drug Administration (FDA),
control procedures for all medication-related activities. The is responsible for implementing and enforcing the federal
guidelines are based on the premise that the pharmacy is re- Food, Drug, and Cosmetic Act. The FDA is responsible for
sponsible for the procurement, distribution, and control of the control and prevention of misbranding and of adultera-
all drugs used within the institution. In a sense, the entire tion of food, drugs, and cosmetics moving in interstate com-
hospital is the pharmacy, and the pharmacy service is simply merce. The FDA also sets label requirements for food, drugs,
a functional service extending throughout the institution’s and cosmetics; sets standards for investigational drug stud-
physical and organizational structures. ies and for marketing of new drug products; and compiles
It should be noted that, although this document is di- data on adverse drug reactions.
rected toward hospitals, much of it is relevant to other types The U.S. Department of the Treasury influences
of health-care facilities. pharmacy operation by regulating the use of tax-free alco-
hol through the Bureau of Alcohol, Tobacco and Firearms.
Pharmacy Policies, Procedures, and The U.S. Department of Justice affects pharmacy practice
Communications through its Drug Enforcement Agency (DEA) by enforcing
the Controlled Substances Act of 1970 and other federal
Policy and Procedure Manuals.1 The effectiveness of the laws and regulations for controlled drugs.
drug control system depends on adherence to policies (broad, Another federal agency, the Health Care Financing
general statements of philosophy) and procedures (detailed Administration, has established Conditions of Participation
guidelines for implementing policy). The importance of an for hospitals and skilled nursing facilities to assist these in-
up-to-date policy and procedure manual for drug control can- stitutions to qualify for reimbursement under the health in-
not be overestimated. All pharmacy staff must be familiar with surance program for the aged (Medicare) and for Medicaid.
the manual; it is an important part of orientation for new staff The state board of pharmacy is the agency of state gov-
and crucial to the pharmacy’s internal communication mecha- ernment responsible for regulating pharmacy practice within
nism. In addition, preparing written policies and procedures the state. Practitioners, institutions, and community pharma-
requires a thorough analysis of control operations; this review cies must obtain licenses from the board to practice pharmacy
might go undone otherwise. or provide pharmacy services in the state. State boards of
Drug control begins with the setting of policy. The au- pharmacy promulgate numerous regulations pertaining to
thority to enforce drug control policy and procedures must drug dispensing and control. (In some states, the state board
come from the administration of the institution, with the en- of health licenses the hospital pharmacy separately or through
dorsement of the medical staff, via the pharmacy and therapeu- a license that includes all departments of the hospital.)
tics (P&T) committee and/or other appropriate committee(s). Standards and guidelines for pharmaceutical ser-
Because the drug control system interfaces with numerous devices have been established by the Joint Commission on
partments and professions, the P&T committee should be the Accreditation of Hospitals (JCAH)2 and the American
focal point for communications relating to drug control in the Society of Hospital Pharmacists (ASHP)3. The United States
institution. The pharmacist, with the cooperation of the P&T Pharmacopeial Convention also promulgates certain phar-
committee, should develop media such as newsletters, bul- macy practice procedures as well as official standards for
letins, and seminars to communicate with persons functioning drugs and drug testing. Professional practice guidelines and
within the framework of the control system. standards generally do not have the force of law but rather
are intended to assist pharmacists in achieving the highest
Inservice Training and Education. Intra- and interdepartmental level of practice. They may, however, be employed in legal
education and training programs are important to the effective proceedings as evidence of what constitutes acceptable prac-
implementation of policies and procedures and the institution’s tice as determined by the profession itself.
drug control system in general. They are part of effective com- In some instances, both federal and state laws may
munication and help establish and maintain professional relation- deal with a specific activity; in such cases, the more strin-
ships among the pharmacy staff and between it and other hospital gent law will apply.
departments. Drug control policies and procedures should be in-
cluded in the pharmacy’s educational programs. The Medication System
Standards, Laws, and Regulations Procurement: Drug Selection, Purchasing Authority, Res
ponsibility, and Control.4–6 The selection of pharmaceuticals
The pharmacist must be aware of and comply with the laws, is a basic and extremely important professional function of
regulations, and standards governing the profession. Many the hospital pharmacist who is charged with making decisions
of these standards and regulations deal with aspects of drug regarding products, quantities, product specifications, and
134 Drug Distribution and Control: Distribution–Technical Assistance Bulletins
sources of supply. It is the pharmacist’s obligation to establish Personnel involved in the purchase, receipt, and con-
and maintain standards assuring the quality, proper storage, trol of drugs should be well trained in their responsibilities
control, and safe use of all pharmaceuticals and related sup- and duties and must understand the serious nature of drugs.
plies (e.g., fluid administration sets); this responsibility must All nonprofessional personnel employed by the pharmacy
not be delegated to another individual. Although the actual should be selected and supervised by the pharmacist.
purchasing of drugs and supplies may be performed by a non- Delivery of drugs directly to the pharmacy or other
pharmacist, the setting of quality standards and specifications pharmacy receiving area is highly desirable; it should be
requires professional knowledge and judgment and must be considered mandatory for controlled drugs. Orders for con-
performed only by the pharmacist. trolled substances must be checked against the official order
Economic and therapeutic considerations make it neces- blank (when applicable) and against hospital purchase order
sary for hospitals to have a well-controlled, continuously updated forms. All drugs should be placed into stock promptly upon
formulary. It is the pharmacist’s responsibility to develop and receipt, and controlled substances must be directly trans-
maintain adequate product specifications to aid in the purchase ferred to safes or other secure areas.
of drugs and related supplies under the formulary system. The
USP–NF is a good base for drug product specifications; there Drug Storage and Inventory Control. Storage is an important
also should be criteria to evaluate the acceptability of manufac- aspect of the total drug control system. Proper environmental
turers and distributors. In establishing the formulary, the P&T control (i.e., proper temperature, light, humidity, conditions of
committee recommends guidelines for drug selection. However, sanitation, ventilation, and segregation) must be maintained
when his knowledge indicates, the pharmacist must have the au- wherever drugs and supplies are stored in the institution.
thority to reject a particular drug product or supplier. Storage areas must be secure; fixtures and equipment used to
Although the pharmacist has the authority to select a brand store drugs should be constructed so that drugs are accessible
or source of supply, he must make economic considerations only to designated and authorized personnel. Such personnel
subordinate to those of quality. Competitive bid purchasing is must be carefully selected and supervised. Safety also is an im-
an important method for achieving a proper balance between portant factor, and proper consideration should be given to the
quality and cost when two or more acceptable suppliers market safe storage of poisons and flammable compounds. Externals
a particular product meeting the pharmacist’s specifications. In should be stored separately from internal medications.
selecting a vendor, the pharmacist must consider price, terms, Medications stored in a refrigerator containing items other than
shipping times, dependability, quality of service, returned goods drugs should be kept in a secured, separate compartment.
policy, and packaging; however, prime importance always must Proper control is important wherever medications
be placed on drug quality and the manufacturer’s reputation. It are kept, whether in general storage in the institution or the
should be noted that the pharmacist is responsible for the quality pharmacy or patient-care areas (including satellite pharma-
of all drugs dispensed by the pharmacy. cies, nursing units, clinics, emergency rooms, operating
rooms, recovery rooms, and treatment rooms). Expiration
Records. The pharmacist must establish and maintain ad- dates of perishable drugs must be considered in all of these
equate recordkeeping systems. Various records must be locations, and stock must be rotated as required. A method
retained (and be retrievable) by the pharmacy because of to detect and properly dispose of outdated, deteriorated, re-
governmental regulations; some are advisable for legal pro- called, or obsolete drugs and supplies should be established.
tection, others are needed for JCAH accreditation, and still This should include monthly audits of all medication storage
others are necessary for sound management (evaluation of areas in the institution. (The results of these audits should be
productivity, workloads, and expenses and assessment of documented in writing.)
departmental growth and progress) of the pharmacy depart- Since the pharmacist must justify and account for the
ment. Records must be retained for at least the length of time expenditure of pharmacy funds, he must maintain an ade-
prescribed by law (where such requirements apply). quate inventory management system. Such a system should
It is important that the pharmacist study federal, state, enable the pharmacist to analyze and interpret prescribing
and local laws to become familiar with their requirements trends and their economic impacts and appropriately mini-
for permits, tax stamps, storage of alcohol and controlled mize inventory levels. It is essential that a system to indicate
substances, records, and reports. subminimum inventory levels be developed to avoid “out-
Among the records needed in the drug distribution and ages,” along with procedures to procure emergency supplies
control system are of drugs when necessary.
• Controlled substances inventory and dispensing records. In-House Manufacturing, Bulk Compounding, Packaging,
• Records of medication orders and their processing. and Labeling.7,8 As with commercially marketed drug
• Manufacturing and packaging production records. products, those produced by the pharmacy must be ac-
• Pharmacy workload records. curate in identity, strength, purity, and quality. Therefore,
• Purchase and inventory records. there must be adequate process and finished product
• Records of equipment maintenance. controls for all manufacturing/bulk compounding and
• Records of results and actions taken in quality-assurance packaging operations. Written master formulas and batch
and drug audit programs. records (including product test results) must be main-
tained. All technical personnel must be adequately trained
Receiving Drugs. Receiving control should be under the aus- and supervised.
pices of a responsible individual, and the pharmacist must Packaging and labeling operations must have controls
ensure that records and forms provide proper control upon sufficient to prevent product/package/label mixups. A lot
receipt of drugs. Complete accountability from purchase or- number to identify each finished product with its production
der initiation to drug administration must be provided. and control history must be assigned to each batch.
The Good Manufacturing Practices of the FDA is a use- in the patient’s medical chart pertinent to the patient’s drug
ful model for developing a comprehensive control system. therapy. (Proper authorization for this must be obtained.12)
The pharmacist is encouraged to prepare those drug Also, a duplicate record of the entry can be maintained in
dosage forms, strengths, and packagings that are needed for the pharmacy profile.
optimal drug therapy but that are commercially unavailable. In computerized patient data systems, each prescriber
Adequate attention must be given to the stability, palatabil- should be assigned a unique identifier; this number should
ity, packaging, and labeling requirements of these products. be included in all medication orders. Unauthorized person-
nel should not be able to gain access to the system.
Medication Distribution (Unit Dose System).9–11 Medication (2) Physician’s drug order: medication order sheets. The
distribution is the responsibility of the pharmacy. The phar- pharmacist (except in emergency situations) must receive the
macist, with the assistance of the P&T committee and the physician’s original order or a direct copy of the order before
department of nursing, must develop comprehensive policies the drug is dispensed. This permits the pharmacist to resolve
and procedures that provide for the safe distribution of all questions or problems with drug orders before the drug is dis-
medications and related supplies to inpatients and outpatients. pensed and administered. It also eliminates errors which may
For reasons of safety and economy, the preferred arise when drug orders are transcribed onto another form for
method to distribute drugs in institutions is the unit dose use by the pharmacy. Several methods by which the pharmacy
system. Although the unit dose system may differ in form may receive physicians’ original orders or direct copies are
depending on the specific needs, resources, and characteris-
tics of each institution, four elements are common to all: (1) 1. Self-copying order forms. The physician’s order form is
medications are contained in, and administered from, single designed to make a direct copy (carbon or NCR) which
unit or unit dose packages; (2) medications are dispensed in is sent to the pharmacy. This method provides the phar-
ready-to-administer form to the extent possible; (3) for most macist with a duplicate copy of the order and does not
medications, not more than a 24-hour supply of doses is pro- require special equipment. There are two basic formats:
vided to or available at the patient-care area at any time; and a. Orders for medications included among treat-
(4) a patient medication profile is concurrently maintained ment orders. Use of this form allows the physi-
in the pharmacy for each patient. Floor stocks of drugs are cian to continue writing his orders on the chart as
minimized and limited to drugs for emergency use and rou- he has been accustomed in the past, leaving all
tinely used “safe” items such as mouthwash and antiseptic other details to hospital personnel.
solutions. b. Medication orders separated from other treat-
(1) Physician’s drug order: writing the order. ment orders on the order form. The separation of
Medications should be given (with certain specified excep- drug orders makes it easier for the pharmacist to
tions) only on the written order of a qualified physician or review the order sheet.
other authorized prescriber. Allowable exceptions to this rule 2. Electromechanical. Copying machines or similar de-
(i.e., telephone or verbal orders) should be put in written form vices may be used to produce an exact copy of the
immediately and the prescriber should countersign the nurse’s physician’s order. Provision should be made to trans-
or pharmacist’s signed record of these orders within 48 (prefer- mit physicians’ orders to the pharmacy in the event of
ably 24) hours. Only a pharmacist or registered nurse should mechanical failure.
accept such orders. Provision should be made to place physi- 3. Computerized. Computer systems, in which the physi-
cian’s orders in the patient’s chart, and a method for sending cian enters orders into a computer which then stores
this information to the pharmacy should be developed. and prints out the orders in the pharmacy or elsewhere,
Prescribers should specify the date and time medica- are used in some institutions. Any such system should
tion orders are written. provide for the pharmacist’s verification of any drug
Medication orders should be written legibly in ink and orders entered into the system by anyone other than an
should include authorized prescriber.
• Patient’s name and location (unless clearly indicated (3) Physician’s drug order: time limits and changes.
on the order sheet). Medication orders should be reviewed automatically when
• Name (generic) of medication. the patient goes to the delivery room, operating room, or a
• Dosage expressed in the metric system, except in in- different service. In addition, a method to protect patients
stances where dosage must be expressed otherwise from indefinite, open-ended drug orders must be provided.
(i.e., units, etc.). This may be accomplished through one or more of the fol-
• Frequency of administration. lowing: (1) routine monitoring of patients’ drug therapy
• Route of administration. by a pharmacist; (2) drug class-specific, automatic stop-
• Signature of the physician. order policies covering those drug orders not specifying a
• Date and hour the order was written. number of doses or duration of therapy; and (3) automatic
cancellation of all drug orders after a predetermined (by the
Any abbreviations used in medication orders should P&T committee) time interval unless rewritten by the pre-
be agreed to and jointly adopted by the medical, nursing, scriber. Whatever the method used, it must protect the patient,
pharmacy, and medical records staff of the institution. as well as provide for a timely notification to the prescriber
Any questions arising from a medication order, in- that the order will be stopped before such action takes place.
cluding the interpretation of an illegible order, should be (4) Physician’s drug order: receipt of order and drug
referred to the ordering physician by the pharmacist. It is profiles. A pharmacist must review and interpret every medi-
desirable for the pharmacist to make (appropriate) entries cation order and resolve any problems or uncertainties with
it before the drug is entered into the dispensing system. This should be noted. A way should be provided to determine, for
means that he must be satisfied that each questionable medi- all doses dispensed, who prepared the dose, its date of dis-
cation order is, in fact, acceptable. This may occur through pensing, the source of the drug, and the person who checked
study of the patient’s medical record, research of the profes- it. Other information, such as the time of receipt of the order
sional literature, or discussion with the prescriber or other and management data (number of orders per patient day and
medical, nursing, or pharmacy staff. Procedures to handle a the like) should be kept as desired. Medication profiles also
drug order the pharmacist still believes is unacceptable (e.g., may be useful for retrospective drug use review studies.
very high dose or a use beyond that contained in the package (6) Physician’s drug order: special orders.5,6,13,14
insert) should be prepared (and reviewed by the hospital’s Special orders (i.e., “stat” and emergency orders and those
legal counsel). In general, the physician must be able to sup- for nonformulary drugs, investigational drugs, restricted use
port the use of the drug in these situations. It is generally ad- drugs, or controlled substances) should be processed ac-
visable for the pharmacist to document actions (e.g., verbal cording to specific written procedures meeting all applicable
notice to the physician that a less toxic drug was available regulations and requirements.
and should be used) relative to a questionable medication (7) Physician’s drug order: other considerations. The
order on the pharmacy’s patient medication profile form or pharmacy, nursing, and medical staffs, through the P&T
other pharmacy document (not in the medical record). committee, should develop a schedule of standard drug ad-
Once the order has been approved, it is entered into the ministration times. The nurse should notify the pharmacist
patient’s medication profile. A medication profile must be main- whenever it is necessary to deviate from the standard medi-
tained in the pharmacy for all inpatients and those outpatients cation schedule.
routinely receiving care at the institution. (Note: Equivalent A mechanism to continually inform the pharmacy of
records also should be available at the patient-care unit.) This patient admissions, discharges, and transfers should be es-
essential item, which is continuously updated, may be a written tablished.
copy or computer maintained. It serves two purposes. First, it (8) Intravenous admixture services.15 The preparation of
enables the pharmacist to become familiar with the patient’s sterile products (e.g., intravenous admixtures, “piggybacks,”
total drug regimen, enabling him to detect quickly potential in- and irrigations) is an important part of the drug control system.
teractions, unintended dosage changes, drug duplications and The pharmacy is responsible for assuring that all such products
overlapping therapies, and drugs contraindicated because of used in the institution are (1) therapeutically and pharmaceuti-
patient allergies or other reasons. Second, it is required in unit cally appropriate (i.e., are rational and free of incompatibilities
dose systems in order for the individual medication doses to be or similar problems) to the patient; (2) free from microbial and
scheduled, prepared, distributed, and administered on a timely pyrogenic contaminants; (3) free from unacceptable levels of
basis. The profile information must be reviewed by the phar- particulate and other toxic contaminants; (4) correctly pre-
macist before dispensing the patient’s drug(s). (It also may be pared (i.e., contain the correct amounts of the correct drugs);
useful in retrospective review of drug use.) and (5) properly labeled, stored, and distributed. Centralizing
Patient profile information should include all sterile compounding procedures within the pharmacy de-
partment is the best way to achieve these goals.
• Patient’s full name, date hospitalized, age, sex, weight, Parenteral admixtures and related solutions are sub-
hospital I.D. number, and provisional diagnosis or rea- ject to the same considerations presented in the preceding
son for admission (the format for this information will sections on “physician’s drug order.” However, their special
vary from one hospital to another). characteristics (e.g., complex preparation or need for steril-
• Laboratory test results. ity assurance) also mandate certain additional requirements
• Other medical data relevant to the patient’s drug ther- concerning their preparation, labeling, handling, and quality
apy (e.g., information from drug history interviews). control. These are described in Reference 15.
• Sensitivities, allergies, and other significant contra- It is important that the pharmacy is notified of any
indications. problems that arise within the institution pertaining to the
• Drug products dispensed, dates of original orders, use of intravenous drugs and fluids (infections, phlebitis,
strengths, dosage forms, quantities, dosage frequency and product defects).
or directions, and automatic stop dates. (9) Medication containers, labeling, and dispensing:
• Intravenous therapy data (this information may be kept stock containers. The pharmacist is responsible for labeling
on a separate profile form, but there should be a method medication containers. Medication labels should be typed or
for the pharmacist to review both concomitantly). machine printed. Labeling with pen or pencil and the use of
• Blood products administered. adhesive tape or china marking pencils should be prohibited.
• Pharmacist’s or technician’s initials. A label should not be superimposed on another label. The
• Number of doses or amounts dispensed. label should be legible and free from erasures and strike-
• Items relevant or related to the patient’s drug therapy overs. It should be firmly affixed to the container. The labels
(e.g., blood products) not provided by the pharmacy. for stock containers should be protected from chemical ac-
tion or abrasion and bear the name, address, and telephone
(5) Physician’s drug order: records. Appropriate re- number of the hospital. Medication containers and labels
cords of each medication order and its processing in the phar- should not be altered by anyone other than pharmacy per-
macy must be maintained. Such records must be retained in sonnel. Prescription labels should not be distributed outside
accordance with applicable state laws and regulations. Any the pharmacy. Accessory labels and statements (shake well,
changes or clarifications in the order should be written in the may not be refilled, and the like) should be used as required.
chart. The signature(s) or initials of the person(s) verifying the Any container to be used outside the institution should bear
transcription of medication orders into the medication profile its name, address, and phone number.
Important labeling considerations are Any special instructions to or procedures required of

the patient relative to the drug’s preparation, storage, and
1. The metric system should be given prominence on all administration should be either a part of the label or ac-
labels when both metric and apothecary measurement company the medication container received by the patient.
units are given. Counseling of the patient sufficient to ensure understanding
2. The names of all therapeutically active ingredients and compliance (to the extent possible) with his medication
should be indicated in compound mixtures. regimen must be conducted. Nonprescription drugs, if used
3. Labels for medications should indicate the amount of in the institution, should be labeled as any other medication.
drug or drugs in each dosage unit (e.g., per 5 mL and (12) Delivery of medications. Couriers used to deliver
per capsule). medications should be reliable and carefully chosen.
4. rugs and chemicals in forms intended for dilution or Pneumatic tubes, dumbwaiters, medication carts, and
reconstitution should carry appropriate directions. the like should protect drug products from breakage and theft.
5. he expiration date of the contents, as well as proper In those institutions having automatic delivery equipment,
storage conditions, should be clearly indicated. such as a pneumatic tube system, provision must be made for
6. The acceptable route(s) of administration should be an alternative delivery method in case of breakdown.
indicated for parenteral medications. All parts of the transportation system must protect medi-
7. Labels for large volume sterile solutions should permit cations from pilferage. Locks and other security devices should
visual inspection of the container contents. be used where necessary. Procedures for the orderly transfer of
8. Numbers, letters, coined names, unofficial synonyms, medications to the nurse should be instituted; i.e., drug carts or
and abbreviations should not be used to identify pneumatic tube carriers should not arrive at the patient-care area
medications, with the exception of approved letter or without the nurse or her designee acknowledging their arrival.
number codes for investigational drugs (or drugs being Medications must always be properly secured. Storage
used in blinded clinical studies). areas and equipment should meet the requirements presented
9. Containers presenting difficulty in labeling, such as small in other sections of these guidelines.
tubes, should be labeled with no less than the prescription (13) Administration of medications. The institution
serial number, name of drug, strength, and name of the should develop detailed written procedures governing medi-
patient. The container should then be placed in a larger cation administration. In doing so, the following guidelines
carton bearing a label with all necessary information. should be considered:
10. The label should conform to all applicable federal,
state, and local laws and regulations. 1. All medications should be administered by appropriately
11. Medication labels of stock containers and repackaged trained and authorized personnel in accordance with the
or prepackaged drugs should carry codes to identify laws, regulations, and institutional policies governing
the source and lot number of medication. drug administration. It is particularly important that there
12. Nonproprietary name(s) should be given prominence are written policies and procedures defining responsibil-
over proprietary names. ity for starting parenteral infusions, administering all in-
13. Amount dispensed (e.g., number of tablets) should be travenous medications, and adding medications to flow-
indicated. ing parenteral fluids. Procedures for drug administration
14. Drug strengths, volumes, and amounts should be given by respiratory therapists and during emergency situations
as recommended in References 11 and 16. also should be established. Exceptions to any of these
policies should be provided in writing.
(10) Medication containers, labeling, and dispensing: 2. All medications should be administered directly from
inpatient medications.11,16 Drug products should be as ready the medication cart (or equivalent) at the patient’s
for administration to the patient as the current status of room. The use of unit dose packaged drugs eliminates
pharmaceutical technology permits. Inpatient medication the need for medication cups and cards (and their as-
containers and packages should conform to applicable USP sociated trays), and they should not be used. A medica-
requirements and the guidelines in References 11 and 16. tion should not be removed from the unit dose package
Inpatient self-care and “discharge” medications should until it is to be administered.
be labeled as outpatient prescriptions (see below). 3. Medications prepared for administration but not used
(11) Medication containers, labeling, and dispensing: must be returned to the pharmacy.
outpatient medications.17 Outpatient medications must be 4. Medications should be given as near the specified time
labeled in accordance with state board of pharmacy and as possible.
federal regulations. As noted, medications given to patients 5. The patient for whom the medication is intended
as “discharge medication” must be labeled in the pharmacy should be positively identified by checking the pa-
(not by nursing personnel) as outpatient prescriptions. tient’s identification band or hospital number or by
The source of the medication and initials of the dis- other means as specified by hospital policy.
penser should be noted on the prescription form at the time of 6. The person administering the medication should
dispensing. If feasible, the lot number also should be recorded. stay with the patient until the dose has been taken.
An identifying check system to ensure proper identifi- Exceptions to this rule are specific medications which
cation of outpatients should be established. may be left at the patient’s bedside upon the physi-
Outpatient prescriptions should be packaged in ac- cian’s written order for self-administration.
cordance with the provisions of the Poison Prevention 7. Parenteral medications that are not to be mixed to-
Packaging Act of 1970 and any regulations thereunder. They gether in a syringe should be given in different injec-
must also meet any applicable requirements of the USP. tion sites on the patient or separately injected into the
administration site of the administration set of a com- Emergency Medication Supplies. A policy to supply emer-
patible intravenous fluid. gency drugs when the pharmacist is off the premises or when
8. The pharmacy should receive copies of all medication there is insufficient time to get to the pharmacy should ex-
error reports or other medication-related incidents. ist. Emergency drugs should be limited in number to include
9. A system to assure that patients permitted to self-med- only those whose prompt use and immediate availability are
icate do so correctly should be established. generally regarded by physicians as essential in the proper
treatment of sudden and unforeseen patient emergencies.
(14) Return of unused medication. All medications that The emergency drug supply should not be a source for nor-
have not been administered to the patient must remain in the mal “stat” or “p.r.n.” drug orders. The medications included
medication cart and be returned to the pharmacy. Only those should be primarily for the treatment of cardiac arrest, cir-
medications returned in unopened sealed packages may be culatory collapse, allergic reactions, convulsions, and bron-
reissued. Medications returned by outpatients should not be chospasm. The P&T committee should specify the drugs and
reused. Procedures for crediting and returning drugs to stock supplies to be included in emergency stocks.
should be instituted. A mechanism to reconcile doses not Emergency drug supplies should be inspected by phar-
given with nursing and pharmacy records should be provided. macy personnel on a routine basis to determine if contents
(15) Recording of medication administration. All ad- have become outdated and are maintained at adequate lev-
ministered, refused, or omitted medication doses should be els. Emergency kits should have a seal which visually indi-
recorded in the patient’s medical record according to an es- cates when they have been opened. The expiration date of
tablished procedure. Disposition of doses should occur im- the kit should be clearly indicated.
mediately after administering medications to each patient
and before proceeding to the next patient. Information to be Pharmacy Service When the Pharmacy Is Closed. Hospitals
recorded should include the drug name, dose and route of provide services to patients 24 hours a day. Pharmaceutical
administration, date and time of administration, and initials services are an integral part of the total care provided by the
of the person administering the dose. hospital, and the services of a pharmacist should be avail-
able at all times. Where around the clock operation of the
Drug Samples and Medical Sales Representatives.18 The use pharmacy is not feasible, a pharmacist should be available
of drug samples within the institution is strongly discouraged on an “on call” basis. The use of “night cabinets” and drug
and should be eliminated to the extent possible. They should dispensing by nonpharmacists should be minimized and
never be used for inpatients (unless, for some reason, no other eliminated wherever possible.
source of supply is available to the pharmacy). Any samples Drugs must not be dispensed to outpatients or hospital
used must be controlled and dispensed through the pharmacy. staff by anyone other than a pharmacist while the pharmacy
Written regulations governing the activities of medical is open. If it is necessary for nurses to obtain drugs when the
sales representatives within the institution should be estab- pharmacy is closed and the pharmacist is unavailable, writ-
lished. Sales representatives should receive a copy of these ten procedures covering this practice should be developed.
rules and their activities should be monitored. They generally should provide for a limited supply of the
drugs most commonly needed in these situations; the drugs
Investigational Drugs.13 Policies and procedures govern- should be in proper single dose packages and a log should be
ing the use and control of investigational drugs within the kept of all doses removed. This log must contain the date and
institution are necessary. Detailed procedural guidelines are time the drugs were removed, a complete description of the
given in Reference 13. drug product(s), name of the (authorized) nurse involved,
and the patient’s name.
Radiopharmaceuticals. The basic principles of compound- Drugs should not be dispensed to emergency room pa-
ing, packaging, sterilizing, testing, and controlling drugs in tients by nonpharmacist personnel if the pharmacy is open.
institutions apply to radiopharmaceuticals. Therefore, even When no pharmacist is available, emergency room patients
if the pharmacy department is not directly involved with the should receive drugs packaged, to the extent possible, in
preparation and dispensing of these agents, the pharmacist single unit packages; no more than a day’s supply of doses
must ensure that their use conforms to the drug control prin- should be dispensed. The use of an emergency room “formu-
ciples set forth in this document. lary” is recommended.20
“Bring-In” Medications. The use of a patient’s own medica- Adverse Drug Reactions. The medical, nursing, and pharmacy
tions within the hospital should be avoided to the extent pos- staffs must always be alert to the potential for, or presence of,
sible. They should be used only if the drugs are not obtainable adverse drug reactions. A written procedure to record clinically
by the pharmacy. If they are used, the physician must write significant adverse drug reactions should be established. They
an appropriate order in the patient’s medical chart. The drugs should be reported to the FDA, the involved drug manufac-
should be sent to the pharmacy for verification of their iden- turer, and the institution’s P&T committee (or its equivalent).
tity; if not identifiable, they must not be used. They should be Adverse drug reaction reports should contain
dispensed as part of the unit dose system, not separate from it.
• Patient’s age, sex, and race.
Drug Control in Operating and Recovery Rooms.19 The • Description of the drug reaction and the suspected cause.
institution’s drug control system must extend to its operating • Name of drug(s) suspected of causing the reaction.
room complex. The pharmacist should ensure that all drugs • Administration route and dose.
used within this area are properly ordered, stored, prepared, • Name(s) of other drugs received by patient.
and accounted for. • Treatment of the reaction, if any.
These reports, along with other significant reports substituting liquid for a tablet) of an oral dosage form
from the literature, should be reviewed and evaluated by the to facilitate administration is generally not an error.
P&T committee. Steps necessary to minimize the incidence 7. Wrong time error: administration of a dose of drug
of adverse drug reactions in the facility should be taken. greater than ± X hours from its scheduled administra-
tion time, X being as set by hospital policy.
Medication Errors. If a medication error is detected, the 8. Wrong preparation of a dose: incorrect preparation of
patient’s physician must be informed immediately. A written the medication dose. Examples are incorrect dilution
report should be prepared describing any medication errors of or reconstitution, not shaking a suspension, using an
clinical import observed in the prescribing, dispensing, or ad- expired drug, not keeping a light-sensitive drug pro-
ministration of a medication. This report, in accordance with tected from light, and mixing drugs that are physically/
hospital policy, should be prepared and sent to the appropriate chemically incompatible.
hospital officials (including the pharmacy) within 24 hours. 9. Incorrect administration technique: situations when
These reports should be analyzed, and any necessary the drug is given via the correct route, site, and so
action taken, to minimize the possibility of recurrence of forth, but improper technique is used. Examples are
such errors. Properly utilized, these incident reports will not using Z-track injection technique when indicated
help to assure optimum drug use control. Medication error for a drug, incorrect instillation of an ophthalmic oint-
reports should be reviewed periodically by the P&T commitment, and incorrect use of an administration device.
tee. (It should be kept in mind that, in the absence of an orga-
nized, independent error detection system, most medication
errors will go unnoticed.)
The following definitions of medication errors are sug- Special Considerations
gested. A medication error is broadly defined as a dose of Contributing to Drug Control
medication that deviates from the physician’s order as writ-
ten in the patient’s chart or from standard hospital policy and Pharmacy Personnel and Management.21–24 Adequate num
procedures. Except for errors of omission, the medication dose bers of competent personnel and a well-managed pharmacy
must actually reach the patient; i.e., a wrong dose that is de- are the keys to an effective drug control system. References
tected and corrected before administration to the patient is not 21–24 provide guidance on the competencies required of the
a medication error. Prescribing errors (e.g., therapeutically in- pharmacy staff and on administrative requirements of a
appropriate drugs or doses) are excluded from this definition. well-run pharmacy department.
Following are the nine categories of medication errors:
Assuring Rational Drug Therapy: Clinical Services.21,25
1. Omission error: the failure to administer an ordered Maximizing rational drug use is an important part of the
dose. However, if the patient refuses to take the medi- drug control system. Although all pharmacy services con-
cation, no error has occurred. Likewise, if the dose is tribute to this goal in a sense, the provision of drug informa-
not administered because of recognized contraindication to the institution’s patients and staff and the pharmacy’s
tions, no error has occurred. clinical services are those that most directly contribute to
2. Unauthorized drug error: administration to the patient rational drug therapy. They are, in fact, institutional pharma-
of a medication dose not authorized for the patient. This cists’ most important contributions to patient care.
category includes a dose given to the wrong patient, du-
plicate doses, administration of an unordered drug, and Facilities. Space and equipment requirements relative to
a dose given outside a stated set of clinical parameters drug storage have been discussed previously. In addition
(e.g., medication order to administer only if the patient’s to these considerations, space and equipment must be suf-
blood pressure falls below a predetermined level). ficient to provide for safe and efficient drug preparation and
3. Wrong dose error: any dose that is the wrong number distribution, patient education and consultation, drug infor-
of preformed units (e.g., tablets) or any dose above or mation services, and proper management of the department.
below the ordered dose by a predetermined amount
(e.g., 20%). In the case of ointments, topical solutions, Hospital Committees Important to Drug Control.26,27 Several
and sprays, an error occurs only if the medication or- hospital committees deal with matters of drug control, and the
der expresses the dosage quantitatively, e.g., 1 inch of pharmacist must actively participate in their activities. Among
ointment or two 1-second sprays. these committees (whose names may vary among institutions)
4. Wrong route error: administration of a drug by a route are the P&T committee, infection control committee, use re-
other than that ordered by the physician. Also included view committee, product evaluation committee, patient care
are doses given via the correct route but at the wrong committee, and the committee for protection of human sub-
site (e.g., left eye instead of right). jects. Of particular importance to the drug control system are
5. Wrong rate error: administration of a drug at the the formulary and drug use review (DUR) functions of the
wrong rate, the correct rate being that given in the P&T committee (although DUR in many institutions may be
physician’s order or as established by hospital policy. under a use review or quality-assurance committee).
6. Wrong dosage form error: administration of a drug by
the correct route but in a different dosage form than Drug Use Review.28 Review of how drugs are prescribed and
that specified or implied by the physician. Example used is an important part of institutional quality-assurance
of this error type include use of an ophthalmic oint- and drug control systems. DUR programs may be performed
ment when a solution was ordered. Purposeful altera- retrospectively or, preferably, concurrently or prospectively.
tion (e.g., crushing of a tablet) or substitution (e.g., They may utilize patient outcomes or therapeutic processes
as the basis for judgments about the appropriateness of drug 4. Personal inspection of all patient-care areas should be
prescribing and use. Depending on the review methodology, made to determine if recalled products are present.
the pharmacist should be involved in 5. Quarantine of all recalled products obtained (marked
“Quarantined—Do Not Use”) until they are picked up
1. Preparing, in cooperation with the medical staff, drug by or returned to the manufacturer.
use criteria and standards. 6. Maintenance of a written log of all recalls, the actions
2. Obtaining quantitative data on drug use, i.e., informa- taken, and their results.
tion on the amounts and types of drugs used, prescrib-
ing patterns by medical service, type of patient, and so
Computerization.30 Many information handling tasks in the
forth. These data will be useful in setting priorities for
drug control system (e.g., collecting, recording, storing, re-
the review program. They also may serve as a measure
trieving, summarizing, transmitting, and displaying drug use
of the effectiveness of DUR programs, assist in ana-
information) may be done more efficiently by computers than
lyzing nosocomial infection and culture and sensitivity
by manual systems. Before the drug control system can be
data, and help in preparing drug budgets.
computerized, however, a comprehensive, thorough study of
3. Reviewing medication orders against the drug use cri-
the existing manual system must be conducted. This study
teria and standards.
should identify the data flow within the system and define
4. Consulting with prescribers concerning the results of
the functions to be done and their interrelationships. This in-
3 above.
formation is then used as the basis to design or prospectively
5. Participating in the followup activities of the review
evaluate a computer system; any other considerations, such as
program, i.e., educational programs directed at pre-
those of the hospital accounting department, are subordinate.
scribers, development of recommendations for the
The computer system must include adequate safe-
formulary, and changes in drug control procedures in
guards to maintain the confidentiality of patient records.
response to the results of the review process.
A backup system must be available to continue the
computerized functions during equipment failure. All trans-
It should be noted that the overall DUR program is a
actions occurring while the computer system is inoperable
joint responsibility of the pharmacy and the organized medical
should be entered into the system as soon as possible.
staff; it is not unilaterally a pharmacy or medical staff function.
Data on controlled substances must be readily retriev-
able in written form from the system.
Quality Assurance for Pharmaceutical Services.29 To ensure
that the drug control system is functioning as intended, there
Defective Drug Products, Equipment, and Supplies. The
should be a formalized method to (1) set precise objectives (in
pharmacist should be notified of any defective drug prod-
terms of outcome and process criteria and standards) for the
ucts (or related supplies and equipment) encountered by the
system; (2) measure and verify the degree of compliance with
nursing or medical staffs. All drug product defects should
these standards, i.e., the extent to which the objectives have
be reported to the USP–FDA–ASHP Drug Product Defect
been realized; and (3) eliminate any noncompliance situa-
Reporting Program.
tions. Such a quality-assurance program will be distinct from,
though related to, the DUR activities of the department.
Disposal of Hazardous Substances. Hazardous substances
(e.g., toxic or flammable solvents and carcinogenic agents)
Drug Recalls. A written procedure to handle drug product
must be disposed of properly in accordance with the require-
recalls should be developed. Any such system should have
ments of the Environmental Protection Agency or other appli-
the following elements:
cable regulations. The substances should not be poured indis-
criminately down the drain or mixed in with the usual trash.
1. Whenever feasible, notation of the drug manufactur-
Unreconstituted vials or ampuls and unopened bottles
er’s name and drug lot number should appear on out-
of oral medications supplied by the National Cancer Institute
patient prescriptions, inpatient drug orders or profiles,
(NCI) should be returned to the NCI’s contract storage and
packaging control records, and stock requisitions and
distribution facility.
their associated labels.
Other intact products should be returned to the original
2. Review of these documents (prescriptions, drug or-
source for disposition.
ders, and so forth) to determine the recipients (patients
Units of anticancer drugs no longer intact, such as re-
and nursing stations) of the recalled lots. Optimally,
constituted vials, opened ampuls, and bottles of oral medica-
this would be done by automated means.
tions, and any equipment (e.g., needles and syringes) used in
3. In the case of product recalls of substantial clinical their preparation require a degree of caution greater than with
significance, a notice should go to the recipients that less toxic compounds to safeguard personnel from acciden-
they have a recalled product. The course of action they tal exposure. The National Institutes of Health recommends
should take should be included. In the case of outpa- that all such materials be segregated for special destruction
tients, caution should be exercised not to cause undue procedures. The items should be kept in special containers
alarm. The uninterrupted therapy of the patients must be marked “Danger—Chemical Carcinogens.” Needles and
assured; i.e., replacement of the recalled drugs gener- syringes first should be rendered unusable and then placed
ally will be required. The hospital’s administration and in specially marked plastic bags. Care should be taken to
nursing and medical staffs should be informed of any re- prevent penetration and leakage of the bags. Excess liquids
calls having significant therapeutic implications. Some should be placed in sealed containers; the original vial is sat-
situations also may require notifying the physicians of isfactory. Disposal of all of the above materials should be by
patients receiving drugs that have been recalled. incineration to destroy organic material.
Alternate disposal for BCG vaccine products has been 17. American Society of Hospital Pharmacists. ASHP
recommended by the Bureau of Biologics (BOB). The BOB guidelines on pharmacist-conducted patient counsel-
suggests that all containers and equipment used with BCG ing. Am J Hosp Pharm. 1976; 33:644–5.
vaccines be sterilized prior to disposal. Autoclaving at 121 18. Lipman AG, Mullen HF. Quality control of medical
0
C for 30 minutes will sterilize the equipment. service representative activities in the hospital. Am J
At all steps in the handling of anticancer drugs and Hosp Pharm. 1974; 31:167–70.
other hazardous substances, care should be taken to safe- 19. Evans DM, Guenther AM, Keith TD, et al. Pharmacy
guard professional and support services personnel from practice in an operating room complex. Am J Hosp
accidental exposure to these agents. Pharm. 1979; 36:1342–7.
20. Mar DD, Hanan ZI, LaFontaine R. Improved emer-
gency room medication distribution. Am J Hosp
References Pharm. 1978; 35:70–3.
1. Ginnow WK, King CM Jr. Revision and reorganiza- minimum standard for pharmacies in institutions. Am
tion of a hospital pharmacy policy and procedure man- J Hosp Pharm. 1977; 34:1356–8.
ual. Am J Hosp Pharm. 1978; 35:698–704. 22. American Society of Hospital Pharmacists. ASHP guide-
2. Accreditation manual for hospitals 1980. Chicago: lines on the competencies required in institutional phar-
Joint Commission on Accreditation of Hospitals; 1979. macy practice. Am J Hosp Pharm. 1975; 32:917–9.
3. Publications, reprints and services. Washington, DC: 23. American Society of Hospital Pharmacists. ASHP
American Society of Hospital Pharmacists; current training guidelines for hospital pharmacy supportive
edition. personnel. Am J Hosp Pharm. 1976; 33:646–8.
4. American Society of Hospital Pharmacists. ASHP 24. American Society of Hospital Pharmacists. ASHP
guidelines for selecting pharmaceutical manufacturers competency standard for pharmacy supportive per-
and distributors. Am J Hosp Pharm. 1976; 33:645–6. sonnel in organized health care settings. Am J Hosp
5. American Society of Hospital Pharmacists. ASHP Pharm. 1978; 35:449–51.
guidelines for hospital formularies. Am J Hosp Pharm. 25. American Society of Hospital Pharmacists. ASHP
1978; 35:326–8. statement on clinical functions in institutional phar-
6. American Society of Hospital Pharmacists. ASHP macy practice. Am J Hosp Pharm. 1978; 35:813.
statement of guiding principles on the operation of the 26. American Society of Hospital Pharmacists. ASHP
hospital formulary system. Am J Hosp Pharm. 1964; statement on the pharmacy and therapeutics commit-
21:40–1. tee. Am J Hosp Pharm. 1978; 35:813–4.
7. American Society of Hospital Pharmacists. ASHP 27. American Society of Hospital Pharmacists. ASHP
guidelines for repackaging oral solids and liquids in statement on the hospital pharmacist’s role in infection
single unit and unit dose packages. Am J Hosp Pharm. control. Am J Hosp Pharm. 1978; 35:814–5.
1979; 36:223–4. 28. Antibiotic use review and infection control: evalu-
8. 21 CFR Parts 210 and 211. Current good manufactur- ating drug use through patient care audit. Chicago:
ing practices in manufacturing, processing, packing or InterQual, Inc.; 1978.
holding of drugs. April 1979. 29. Model quality assurance program for hospital pharma-
9. Sourcebook on unit dose drug distribution systems. cies, revised. Washington, DC: American Society of
Washington, DC: American Society of Hospital Hospital Pharmacists; 1980.
Pharmacists; 1978. 30. Sourcebook on computers in pharmacy. Washington,
10. American Society of Hospital Pharmacists. ASHP DC: American Society of Hospitals Pharmacists; 1978.
statement on unit dose drug distribution. Am J Hosp
Pharm. 1975; 32:835.
11. American Society of Hospital Pharmacists. ASHP Developed by the ASHP Council on Professional Affairs. Approved
guidelines for single unit and unit dose packages of by the ASHP Board of Directors, March 20, 1980. Revised
drugs. Am J Hosp Pharm. 1977; 34:613–4. November 1981.
guidelines for obtaining authorization for pharmacists’ This document contains numerous references to various official
notations in the patient medical record. Am J Hosp ASHP documents and other publications. Inclusion of the latter does
Pharm. 1979; 36:222–3. not constitute endorsement of their content by the Society; they are,
13. American Society of Hospital Pharmacists. ASHP however, considered to be useful elaborations on certain subjects
guidelines for the use of investigational drugs in insti- contained herein. To avoid redundancy with other ASHP documents,
tutions. Am J Hosp Pharm. 1979; 36:221–2. relevant references are cited in many sections of these guidelines.
14. American Society of Hospital Pharmacists. ASHP Most may be obtained from ASHP through its publications catalog
guidelines for institutional use of controlled sub-
stances. Am J Hosp Pharm. 1974; 31:582–8. Copyright © 1980, American Society of Hospital Pharmacists, Inc.
15. Recommendations of the National Coordinating All rights reserved.
Committee on Large Volume Parenterals. Washington,
DC: American Society of Hospital Pharmacists; 1980. The bibliographic citation for this document is as follows: American
16. National Coordinating Committee on Large Volume Society of Hospital Pharmacists. ASHP technical assistance bulletin
Parenterals. Recommendations for the labeling of large on hospital drug distribution and control. Am J Hosp Pharm. 1980;
volume parenterals. Am J Hosp Pharm. 1978; 35:49–51. 37:1097–103.

Repackaging Oral Solids and Liquids in
Single Unit and Unit Dose Packages
To maximize the benefits of a unit dose drug distribution transmission, moisture permeability, size, thickness
system, all drugs must be packaged in single unit or unit (alone or in laminate), recommended sealing tempera-
dose packages.a However, not all drugs are commercially ture, and storage requirements.
available in single unit (or unit dose) packages. Therefore, 8. Unit dose packages and labels should, to the extent
the institutional pharmacist must often repackage drugs possible, comply with the “ASHP Guidelines for
obtained in bulk containers (e.g., bottles of 500 tablets) Single Unit and Unit Dose Packages of Drugs.”1
into single unit packages so that they may be used in a 9. Whenever feasible, a responsible individual, other
unit dose system. than the packaging operator, should verify that (a) the
Certain precautions must be taken if the quality of packaging system (drug, materials, and machines) is
drugs repackaged by the pharmacist is to be maintained. set up correctly and (b) all procedures have been per-
The guidelines presented herein will assist the pharmacist in formed properly. Ultimate responsibility for all pack-
developing procedures for repackaging drugs in a safe and aging operations rests with the pharmacist.
acceptable manner: 10. Control records of all packaging runs must be kept.
These records should include the following informa-
1. The packaging operation should be isolated, to the ex- tion: (1) complete description of the product, i.e.,
tent possible, from other pharmacy activities. name, strength, dosage form, route of administra-
2. Only one drug product at a time should be repackaged tion, etc.; (2) the product’s manufacturer or supplier;
in a specific work area. No drug products other than (3) control number; (4) the pharmacy’s control number
the one being repackaged should be present in the im- if different from the manufacturer’s; (5) expiration dates
mediate packaging area. Also, no labels other than of the original container and the repackaged product;
those for the product being repackaged should be pres- (6) number of units packaged and the date(s) they were
ent in the area. packaged; (7) initials of the operator and checker (if
3. Upon completion of the packaging run, all unused any); (8) a sample of the label and, if feasible, a sample
stocks of drugs and all finished packages should be of the finished package, which should not be discarded
removed from the packaging area. The packaging until after the expiration date and which should be
machinery and related equipment should then be com- examined periodically for signs of deterioration; and
pletely emptied, cleaned, and inspected before com- (9) description (including lot number) of the packag-
mencing the next packaging operation. ing materials and equipment used.
4. All unused labels (if separate labels are used) should 11. It is the responsibility of the pharmacist to deter-
be removed from the immediate packaging area. The mine the expiration date to be placed on the package,
operator should verify that none remains in the pack- taking into account the nature of the drug repack-
aging machine(s). If labels are prepared as part of the aged, the characteristics of the package, and the
packaging operation, the label plate (or analogous storage conditions to which the drug may be sub-
part of the printing apparatus) should be removed or jected. This date must not be beyond that of the
adjusted to “blank” upon completion of the run. This original package.b
will help assure that the correct label is printed during 12. All drugs should be packaged and stored in a tem-
any subsequent run. There should be a procedure to perature- and humidity-controlled environment to
reconcile the number of packages produced with the minimize degradation caused by heat and moisture.
number of labels used (if any) and destroyed (if any) A relative humidity of 75% at 23 °C should not be
and the number of units or volume of drug set forth to exceeded. Packaging materials should be stored in
be packaged. accordance with the manufacturer’s instructions and
5. Before beginning a packaging run, an organoleptic evalu- any applicable regulations.
ation (color, odor, appearance, and markings) of the drug 13. Written procedures (both general and product specific)
product being repackaged should be made. The bulk governing repackaging operations should be prepared
container should also be examined for evidence of water and updated as required. Any deviation from these
damage, contamination, or other deleterious effects. procedures should be noted and explained on the con-
6. All packaging equipment and systems should be oper- trol record. Operators must understand the procedures
ated and used in accordance with the manufacturer’s (and operation of all packaging equipment) before
or other established instructions. There should be valid commencing the run.
justification and authorization by the supervisor for 14. Applicable FDA and USP requirements concerning
any deviation from those instructions on the part of the type of package required for specific drug products
the operator. must be followed.
7. The pharmacist should obtain data on the characteris- 15. Drugs and chemicals with high vapor pressures should
tics of all packaging materials used. This information be stored separately from other products to minimize
should include data on the chemical composition, light cross contamination.
References Developed originally by a joint working group of the American

Society of Hospital Pharmacists and the American Society of
1. American Society of Hospital Pharmacists. ASHP Consultant Pharmacists and representatives of the drug packag-
guidelines for single unit and unit dose packages of ing industry. The original document subsequently was approved
drugs. Am J Hosp Pharm. 1977; 34:613–4. officially by the Boards of Directors of ASHP and ASCP. FDA
2. Stolar MH. Expiration dates of repackaged drug prod- reviewed the original document and commended ASHP and ASCP
ucts. Am J Hosp Pharm. 1979; 36:170. Editorial. for developing the guidelines.
Copyright © 1983, American Society of Hospital Pharmacists,

a
A single unit package is one which contains one discrete pharma- Inc., and American Society of Consultant Pharmacists. All rights
ceutical dosage form, e.g., one tablet or one 5-mL volume of liquid. reserved.
A unit dose package is one which contains the particular dose of
drug ordered for the patient. A single unit package is a unit dose The bibliographic citation for this document is as follows: American
(or single dose) package if it contains that particular dose of drug Society of Hospital Pharmacists. ASHP technical assistance bulletin
ordered for the patient. on repackaging oral solids and liquids in single unit and unit dose
packages. Am J Hosp Pharm. 1983; 40:451–2.
b
For specific recommendations on expiration date policy, see
Reference 2.
Revised by the ASHP Board of Directors, November 16–17, 1978.


Single Unit and Unit Dose Packages of Drugs
Drug packages must fulfill four basic functions: Nonproprietary Name
(and proprietary name if to be shown)
1. Identify their contents completely and precisely. Dosage Form (if special or other than oral)
2. Protect their contents from deleterious environmental Strength
effects (e.g., photodecomposition). Strength of Dose and Total Contents Delivered
3. Protect their contents from deterioration due to han- (e.g., number of tablets and their total dose)
dling (e.g., breakage and contamination). Special Notes (e.g., refrigerate)
4. Permit their contents to be used quickly, easily, and Expiration Date
safely. Control Number
Modern drug distribution systems use single unit pack- 1. Nonproprietary and proprietary names. The nonpro-
ages to a great extent and, in fact, such packages are central prietary name and the strength should be the most
to the operation of unit dose systems, intravenous admixture prominent part of the package label. It is not neces-
services, and other important aspects of pharmacy practice. sary to include the proprietary name, if any, on the
These guidelines have been prepared to assist pharmaceuti- package. The name of the manufacturer or distributor
cal manufacturers and pharmacists in the development and should appear on the package. In addition, the name of
production of single unit and unit dose packages, the use of the manufacturer of the finished dosage form should
which has been shown to have substantial benefits. be included in the product labeling. The style of type
A single unit package is one that contains one discrete should be chosen to provide maximum legibility, con-
pharmaceutical dosage form, i.e., one tablet, one 2-mL vol- trast, and permanence.
ume of liquid, one 2-g mass of ointment, etc. A unit dose 2. Dosage form. Special characteristics of the dosage
package is one that contains the particular dose of the drug form should be a part of the label, e.g., extended re-
ordered for the patient. A single unit package is also a unit lease. Packages should be labeled as to the route of
dose or single dose package if it contains the particular dose administration if other than oral, e.g., topical use. In
of the drug ordered for the patient. A unit dose package a package containing an injection, the acceptable in-
could, for example, contain two tablets of a drug product. jectable route(s) of administration should be stated on
both outer and inner packages, i.e., both on the syringe
General Considerations unit and carton (if any).
3. Strength. Strength should be stated in accordance with
Packaging Materials. Packaging materials (and the package terminology in the American Hospital Formulary
itself) must possess the physical characteristics required to Service. The metric system should be used, with dosage
protect the contents from (as required) light, moisture, tem- forms formulated to provide the rounded-off figures in
perature, air, and handling. The material should not deterio- the USP table of approximate equivalents and expressed
rate during the shelf life of the contents. Packages should be in the smallest whole number. Micrograms should be
of lightweight, nonbulky materials that do not produce toxic used through 999, then milligrams through 999, then
fumes when incinerated. Materials that may be recycled or grams. Thus, 300 mg, not 5 gr, nor 325 mg, nor 0.3 g;
are biodegradable, or both, are to be preferred over those 60 mg, not 1 gr, nor 0.06 g, nor 64.5 mg, nor 65 mg; 400
that are not. Packaging materials should not absorb, adsorb, mcg, not 1/150 gr, nor 0.4 mg, nor 0.0004 g; mL (mil-
or otherwise deleteriously affect their contents. Information liliters) should be used instead of cc (cubic centimeters).
should be available to practitioners indicating the stability 4. Strength of dose and total contents delivered. The total
and compatibility of drugs with various packaging materials. contents and total dose of the package should be indi-
cated. Thus, a unit dose package containing a 600-mg
Shape and Form. Packages should be constructed so that dose as two 300-mg tablets should be labeled “600 mg
they do not deteriorate with normal handling. They should (as two 300-mg tablets).” Likewise, a 500-mg dose of
be easy to open and use, and their use should require little or a drug in a liquid containing 100 mg/mL should be
no special training or experience. Unless the package con- labeled “Delivers 500 mg (as 5 mL of 100 mg/mL).”
tains a drug to be added to a parenteral fluid or otherwise 5. Special notes. Special notes such as conditions of stor-
used in compounding a finished dosage form, it should al- age (e.g., refrigerate), preparation (e.g., shake well or
low the contents to be administered directly to the patient (or moisten), and administration (e.g., not to be chewed)
IPPB apparatus or fluid administration set) without any need that are not obvious from the dosage form designation
for repackaging into another container or device (except for are to be included on the label.
ampuls). 6. Expiration date. The expiration date should be promi-
nently visible on the package. If the contents must
Label Copy. Current federal labeling requirements must be be reconstituted prior to use, the shelf life of the fi-
adhered to, with attention also given to the items at right. nal product should be indicated. Unless stability data
The desired copy and format are as follows: warrant otherwise, expiration dates should fall during
January and July to simplify recall procedures.
7. Control number (lot number). The control number 2. An appropriate size needle may be an integral part
should appear on the package. of the device. The needle sheath should not be the
plunger. The plunger should be mechanically stable in
the barrel of the syringe.
Product Identification Codes. The use of product identi- 3. The device should be of such a design that it is patient
fication codes, appearing directly on the dosage form, is ready and assembly instructions are not necessary.
encouraged. 4. The sheath protecting the needle should be a non-
penetrable, preferably rigid material, to protect per-
Evidence of Entry. The package should be so designed that sonnel from injury. The size of the needle should be
it is evident, when the package is still intact, that it has never indicated.
been entered or opened. 5. The device should be of such a design that easy and
visible aspiration is possible. It should be as compact
as possible and of such a size that it can be easily
Specific Considerations handled.
Oral Solids
Parenteral Solutions and Additives
1. Blister package. A blister package should
1. The approximate pH and osmolarity of parenteral
a. Have an opaque and nonreflective backing (flat
solutions should be stated on the label. The amount
upper surface of package) for printing.
of overfill also should be noted. Electrolyte solutions
b. Have a blister (dome or bubble) of a transparent
should be labeled in both mEq (or millimole) and mg
material that is, preferably, flat bottomed.
concentrations. Solutions commonly labeled in terms
c. Be easily peelable.
of percent concentration, e.g., dextrose, should also be
d. If it contains a controlled substance, be num-
labeled in w/v terms.
bered sequentially for accountability purposes.
2. Parenteral fluid container labels should be readable
2. Pouch package. A pouch package should
when hanging and when upright or in the normal ma-
a. Have one side opaque and nonreflective for
nipulative position.
printing.
3. Drugs to be mixed with parenteral infusion solutions
b. Be easily deliverable, i.e., large tablets in large
should be packaged into convenient sizes that mini-
pouches, small tablets in small pouches.
mize the need for solution transfers and other manipu-
c. Tear from any point or from multiple locations.
lations.
d. If it contains a controlled substance, be num-
4. Partially filled piggyback-type containers should
bered sequentially for accountability purposes.
a. Be recappable with a tamperproof closure.
3. The packages should be such that contents can be de-
b. Have a hanger.
livered directly to the patient’s mouth or hand.
c. Have volume markings.
d. Be designed to minimize the potential for con-
Oral Liquids
tamination during use.
e. Contain a partial vacuum for ease of reconstitu-
1. The packages should be filled to deliver the labeled
tion.
contents. It is recognized that overfilling will be nec-
5. If an administration set is included with the container,
essary, depending on the shape of the container, the
it should be compatible with all large volume paren-
container material, and the formulation of the dosage
teral delivery systems.
form.
2. The label should state the contents as follows: Delivers
Other Dosage Forms—Ophthalmics, Suppositories, Oint
____mg (or g or mcg) in ____mL.
ments, etc. Dosage forms other than those specifically dis-
3. If reconstitution is required, the amount of vehicle to
cussed above should be adequately labeled to indicate their
be added should be indicated. These directions may
use and route of administration and should adhere to the
take the form of “fill to mark on container” in lieu of
above and other required package labeling and design criteria.
stating a specific volume.
4. Syringe-type containers for oral administration should
not accept a needle and should be labeled “For Oral
Use Only.” Approved by the ASHP Board of Directors, November 14–15, 1984.
5. Containers should be designed to permit administra- Revised by the ASHP Council on Clinical Affairs. Supersedes the
tion of contents directly from the package. previous version, which was approved on March 31–April 1, 1977.
Injectables Copyright © 1985, American Society of Hospital Pharmacists, Inc.

1. The device should be appropriately calibrated in milli-
liters and scaled from the tip to the fill line. Calibrated The bibliographic citation for this document is as follows: American
space may be built into the device to permit addition Society of Hospital Pharmacists. ASHP technical assistance bulletin
of other drugs. The label should state the contents as on single unit and unit dose packages of drugs. Am J Hosp Pharm.
follows: Delivers ____mg (or g or mcg) in ____mL. 1985; 42:378–9.
148 Education and Training–Positions

Developing Leadership Competencies (1518) proach to learning and service in which a supervising phar-
Source: Council on Education and Workforce Development macist oversees the services of students, residents, and other
To work with healthcare organization leadership to foster pharmacists providing direct patient care; further,
opportunities for pharmacy practitioners to move into lead- To support the assessment of the impact of these phar-
ership roles; further, macy practice and training models on the quality of learner
To encourage leaders to seek out and mentor pharmacy experiences and patient care outcomes.
practitioners in developing administrative, managerial, and This policy supersedes ASHP policy 1204.
leadership skills; further,
To encourage pharmacy practitioners to obtain the Education and Training in Health Care Informatics
skills necessary to pursue administrative, managerial, and (1317)
leadership roles; further, Source: Council on Education and Workforce Development
To encourage colleges of pharmacy and ASHP state To recognize the significant and vast impacts of health-
affiliates to collaborate in fostering student leadership skills system information systems, automation, and technology
through development of co-curricular leadership opportuni- changes on safe and effective use of medications; further,
ties, leadership conferences, and other leadership promotion To foster, promote, and lead the development of and
programs; further, participation in formal health care informatics educational
To reaffirm that residency programs should develop programs for pharmacists, pharmacy technicians, and stu-
leadership skills through mentoring, training, and leadership dent pharmacists.
opportunities; further,
To foster leadership skills for pharmacists to use on a Preceptor Skills and Abilities (1201)
daily basis in their roles as leaders in patient care. Source: Council on Education and Workforce Development
This policy supersedes ASHP policy 0509. To collaborate with pharmacy organizations on the devel-
opment of standards to enhance the quality of experiential
Pharmacy Technician Training and Certification (1519) education and pharmacy residency precepting; further,
Source: Council on Education and Workforce Development To provide tools, education, and other resources to de-
To support the position that by the year 2020, the comple- velop preceptor skills.
tion of a pharmacy technician training program accred-
ited by ASHP and the Accreditation Council for Pharmacy Qualifications of Pharmacy Technicians in Advanced
Education (ACPE) be required to obtain Pharmacy Roles (1203)
Technician Certification Board certification for all new Source: Council on Education and Workforce Development
pharmacy technicians entering the workforce; further, To recognize that highly trained and skilled pharmacy tech-
To foster expansion of ASHP-ACPE accredited phar- nicians working in advanced roles regularly perform com-
macy technician training programs. plex and critical medication-use procedures, and that a safe
This policy supersedes ASHP policies 1015 and 0702. and effective medication-use process depends significantly
on the skills, knowledge, and competency of those pharmacy
Cultural Competency and Cultural Diversity (1414) technicians to perform those tasks; further,
Source: Council on Education and Workforce Development To reaffirm that all pharmacy technicians should com-
To promote the development of cultural competency of plete an ASHP-accredited training program, be certified by
pharmacy educators, practitioners, residents, students, and the Pharmacy Technician Certification Board, and be li-
technicians; further, censed by state boards of pharmacy; further,
To educate providers on the importance of providing To advocate that beyond those requirements pharmacy
culturally congruent care to achieve quality care and patient technicians working in advanced roles should have addi-
engagement; further, tional training and should demonstrate ongoing competen-
To foster awareness of the impact that an ethnically cies specific to the tasks to be performed; further,
and culturally diverse workforce has on improving health To advocate that expansion of pharmacy technician
care quality. duties into expanded, advanced roles should include consid-
This policy supersedes ASHP policies 0314 and 0409. eration of potential risk to patients and that ongoing qual-
ity assurance metrics should be established to assure patient
Pharmacy Resident and Student Roles in New Practice safety.
Models (1316)
Source: Council on Education and Workforce Development Quality of Pharmacy Education and Expansion of
To promote pharmacy practice and training models that: (1) Colleges of Pharmacy (1108)
provide experiential and residency training in team-based Source: Council on Education and Workforce Development
patient care; (2) recognize and utilize the skills and knowl- To support the Accreditation Council for Pharmacy
edge of student pharmacists and residents in providing direct Education’s continuing role of promulgating accreditation
patient care services; (3) augment the patient care services standards and guidelines and engaging in sound accredita-
of pharmacists through expanded roles for residents as prac- tion processes to ensure quality in the education provided by
titioner learners; and (4) where appropriate, utilize an ap- colleges of pharmacy; further,
Education and Training–Positions 149
To acknowledge that, in addition to a robust curricu- in accordance with the Accreditation Council on Graduate
lum, access to quality experiential educational sites and the Medical Education (ACGME) standards and ASHP accredi-
availability of qualified faculty (including preceptors and tation standards for pharmacy residency programs.
specialty-trained clinical faculty) are essential determinants This policy was reviewed in 2014 by the Council on
of the ability to expand enrollment in existing or additional Public Policy and by the Board of Directors and was found
colleges of pharmacy; further, to still be appropriate.
To oppose expansion of enrollment in existing or
new colleges of pharmacy unless well-designed projections Interprofessional Education and Training (1014)
demonstrate that such enrollment increases are necessary to Source: Council on Education and Workforce Development
maintain a viable pharmacist workforce. To support interprofessional education as a component of
This policy supersedes ASHP policy 0607. didactic and experiential education in Doctor of Pharmacy
degree programs; further,
Residency Equivalency (1109) To support interprofessional education as a part of
Source: Council on Education and Workforce Development professional development for pharmacy practitioners and to
To acknowledge the distinct role of ASHP-accredited resi- collaborate with other disciplines to facilitate and promote
dency training in preparing pharmacists to be direct patient- programs that support this goal; further,
care providers; further, To encourage and support pharmacists’ collaboration
To recognize the importance of clinical experience in with other health professionals and health care executives in
developing practitioner expertise; further, the development of team-based, patient-centered care mod-
To affirm that there are no objective means to convert els; further,
or express clinical experience as equivalent to or a substitute To foster documentation and dissemination of out-
for the successful completion of an ASHP-accredited resi- comes achieved as a result of interprofessional education of
dency. health care professionals.
Pharmacy Internships (1110) Education and Workforce Development and by the Board of
Source: Council on Education and Workforce Development Directors and was found to still be appropriate.
To encourage the National Association of Boards of
Pharmacy to develop standardized pharmacy internship Pharmacy Student Experiences in Medically Underserved
hour requirements that would be used uniformly by all state Areas (0913)
boards of pharmacy; further, Source: Council on Education and Workforce Development
To support structured requirements, goals, and objec- To encourage colleges of pharmacy to require student learn-
tives for pharmacy internship experiences, in alignment with ing experiences in traditionally medically underserved areas
requirements for introductory and advanced pharmacy prac- and with diverse patient populations.
tice experiences; further, This policy was reviewed in 2013 by the Council on
To promote and expand new staffing models that fos- Education and Workforce Development and by the Board of
ter expanded roles for pharmacy interns, providing work Directors and was found to still be appropriate.
experiences that build upon their knowledge and help them
develop as future pharmacists. Pharmacy Expertise in the Preparation and Handling of
This policy supersedes ASHP policy 0802. Injectable Medications (0915)
Source: Council on Education and Workforce Development
State-Specific Requirements for Pharmacist Continuing To encourage colleges of pharmacy to include sterile com-
Education (1111) pounding and aseptic technique instruction in the didactic
Source: Council on Education and Workforce Development curriculum and during experiential education; further,
To support the standardization of state pharmacist continu- To support the development of postgraduate, curriculum-
ing education requirements; further, based sterile compounding training programs to foster an in-
To advocate that state boards of pharmacy adopt con- crease in the number of pharmacists with sterile compound-
tinuing professional development (CPD) as the preferred ing expertise.
model for maintaining pharmacist competence and structure This policy was reviewed in 2013 by the Council on
continuing education requirements as a component of CPD. Education and Workforce Development and by the Board of
Directors and was found to still be appropriate.
Innovative Residency Models (1112)
Source: Council on Education and Workforce Development Continuing Professional Development (0916)
To support the development of innovative residency models Source: Council on Education and Workforce Development
that meet ASHP accreditation requirements. To endorse and promote the concept of continuing profes-
sional development (CPD), which involves personal self-
Employment Classification and Duty Hours of Pharmacy appraisal, educational plan development, plan implementa-
Residents (1008) tion, documentation, and evaluation; further,
Source: Council on Public Policy To continue the development of a variety of mecha-
To advocate that pharmacy residents should be classified as nisms and tools that pharmacists can use to assess their CPD
exempt employees; further, needs; further,
To advocate that pharmacy residents be subject to duty To encourage individual pharmacists to embrace CPD
hour limits (similar to resident physicians) with respect to all as a means of maintaining their own professional compe-
clinical and academic activities during their training program tence; further,
150 Education and Training–Positions
To encourage pharmacy managers to promote CPD as use ASHP statements, guidelines, and professional policies
the model for ensuring the competence of their staff; further, as an integral part of training programs and courses.
To collaborate with other pharmacy organizations, This policy was reviewed in 2011 by the Council on
state boards of pharmacy, accrediting bodies, and regulatory Education and Workforce Development and by the Board of
bodies in the development of effective methods for imple- Directors and was found to still be appropriate.
menting CPD; further,
To strongly support objective assessment of the impact Communication Among Health-System Pharmacy Practi
of CPD on pharmacist competence; further, tioners, Patients, and Other Health Care Providers (0510)
To endorse the efforts of colleges of pharmacy and Source: Council on Educational Affairs
ASHP-accredited pharmacy residency programs to teach the To foster effective communication (with appropriate atten-
principles, concepts, and skills of CPD. tion to patients’ levels of general and health literacy) among
This policy was reviewed in 2013 by the Council on health-system pharmacy practitioners, patients, and other
Education and Workforce Development and by the Board of health care providers; further,
Directors and was found to still be appropriate. To develop programs to enable pharmacy students,
residents, and health-system pharmacy practitioners to self-
Pharmacy Residency Training (0917) assess their levels of health literacy and general communica-
Source: Council on Education and Workforce Development tion skills; further,
To continue efforts to increase the number of ASHP- To develop methods with which pharmacy students,
accredited pharmacy residency training programs and posi- residents, and health-system pharmacy practitioners can assess
tions available. the level of general and health literacy of patients; further,
This policy was reviewed in 2013 by the Council on To disseminate information about resources for students,
Education and Workforce Development and by the Board of residents, and health-system pharmacy practitioners to use
Directors and was found to still be appropriate. in working with patients and others having specific commu-
nication needs.
Collaboration Regarding Experiential Education (0804) This policy was reviewed in 2014 by the Council on
Source: Council on Education and Workforce Development Education and Workforce Development and by the Board of
To promote collaboration of health-system teaching sites Directors and was found to still be appropriate.
with the colleges of pharmacy (nationally or regionally), for
the purpose of fostering preceptor development, standard- Practice Sites for Colleges of Pharmacy (0315)
Source: Council on Educational Affairs
ization of experiential rotation schedule dates and evaluation
To encourage practitioner input in pharmacy education;
tools, and other related matters.
further,
To encourage that institutional and health-system
Education and Workforce Development and by the Board of
environments be used as sites for experiential training of
Directors and was found to still be appropriate.
pharmacy students: further,
To encourage colleges of pharmacy and health systems
Requirement for Residency (0701)
to define and develop appropriate organizational relation-
Source: House of Delegates Resolution
ships that permit a balance of patient care and service, as
To support the position that by the year 2020, the completion
well as educational and research objectives, in a mutually
of an ASHP-accredited postgraduate-year-one residency beneficial manner: further,
should be a requirement for all new college of pharmacy To include the administrative interests of both the health
graduates who will be providing direct patient care. system and the college of pharmacy in defining these organiza-
This policy was reviewed in 2011 by the Council on tional relationships to ensure compatibility of institutional (i.e.,
Education and Workforce Development and by the Board of health system or university) and departmental (i.e., pharmacy
Directors and was found to still be appropriate. department and department in the college) objectives; further,
To encourage pharmacists and pharmacy leaders to
Residency Programs (0704) recognize that part of their professional responsibility is the
Source: Council on Education and Workforce Development development of new pharmacy practitioners.
To strongly advocate that all pharmacy residency programs This policy was reviewed in 2012 by the Council on
become ASHP-accredited as a means of ensuring and con- Education and Workforce Development and by the Board of
veying program quality. Directors and was found to still be appropriate.
Education and Workforce Development and by the Board of Licensure for Pharmacy Graduates of Foreign Schools
Directors and was found to still be appropriate. (0323)
Source: Council on Legal and Public Affairs
ASHP Guidelines, Statements, and Professional Policies To support state licensure eligibility of a pharmacist who
as an Integral Part of the Educational Process (0705) has graduated from a pharmacy program accredited by the
Source: Council on Education and Workforce Development Accreditation Council for Pharmacy Education (ACPE) or
To encourage faculties in colleges of pharmacy and pre- accredited by an ACPE-recognized accreditation program.
ceptors of ASHP-accredited residency training programs to This policy was reviewed in 2012 by the Council on
Education and Training–Positions 151
Public Funding for Pharmacy Residency Training (0325) ited residency or have attained comparable skills through
Source: Council on Legal and Public Affairs practice experience.
To support legislation and regulation that ensures public This policy was reviewed in 2014 by the Council on
funding for accredited pharmacy residency programs consis- Education and Workforce Development and by the Board of
tent with the needs of the public and the profession; further, Directors and was found to still be appropriate.
To oppose legislation or regulation involving re-
imbursement levels for graduate medical education that Career Counseling (8507)
adversely affects pharmacy residencies at a rate dispropor- Source: Council on Educational Affairs
tionate to other residency programs. To urge colleges of pharmacy to develop career counseling
This policy was reviewed in 2012 by the Council on programs to make students aware of postgraduate career
Public Policy and by the Board of Directors and was found options, including residency training and career paths in
to still be appropriate. various types of practice; further,
To urge that career counseling occur in a structured
Residency Training for Pharmacists Who Provide Direct manner early in the curriculum and be continued throughout
Patient Care (0005) the curriculum; further,
Source: Council on Educational Affairs To urge practitioners in various organized health care
To recognize that optimal direct patient care by a pharmacist settings to make themselves available to colleges of phar-
requires the development of clinical judgment, which can macy for participation in both structured and unstructured
be acquired only through experience and reflection on that career counseling.
experience; further, This policy was reviewed in 2011 by the Council on
To establish as a goal that pharmacists who provide Education and Workforce Development and by the Board of
direct patient care should have completed an ASHP-accred Directors and was found to still be appropriate.
152 Education and Training–Endorsed Document
Definitions of Pharmacy Residencies and Fellowships

Pharmacy residencies (originally termed “internships”) be- Pharmacy publishes an annual listing of residencies and
gan in the early 1930s, primarily for the purpose of training fellowships conducted by its members. In 1985, ACCP
pharmacists for the management of pharmacy services in reported the availability of 51 such residencies and 83 such
hospitals. The first nonacademic residency program is be- fellowships.18 Another source reported 115 known fellow-
lieved to have been conducted by Harvey A. K. Whitney at ships in 1986.19 In that year, there were 12 clinical fel-
the University of Michigan Hospital.1 Approximately 10 lowships sponsored by the ASHP Research and Education
years later, the first residency program combined with for- Foundation in nine areas of specialization.
mal graduate studies was created.2 Developments in these By 1986, a lack of conformity had arisen in the use of
programs eventually led the American Society of Hospital the terms “residency” and “fellowship,” and considerable
Pharmacists to establish, in 1948, standards for pharmacy potential existed for program applicants to be misinformed
internships in hospitals.3 Those standards defined an intern- or misled regarding program purposes and content. In
ship as “a period of organized training in an accredited hospital 1986, at the recommendation of the ASHP Commission on
pharmacy under the direction and supervision of personnel Credentialing, ASHP invited six other national pharmacy
qualified to offer such training.” organizations to discuss the issue and develop consensus
Two types of internships were recognized, nonaca- definitions for the terms. The definitions and interpretations
demic and academic. The nonacademic internship consisted that follow resulted from that conference. These definitions
of a period of training in a hospital pharmacy. The academic and interpretations are viewed as accurate for current resi-
internship consisted of training in a hospital pharmacy and dencies and fellowships yet sufficiently broad and flexible to
study in an accredited graduate school associated with a col- allow the development of new types of programs. Education,
lege of pharmacy and leading to a Master of Science degree. practice, and research developments may generate changes
In 1962, following several revisions in the standards, in residencies and fellowships and ultimately stimulate revi-
ASHP established an accreditation process and accreditation sions in the definitions and interpretations.
standards for residencies in hospital pharmacy.4,5 In this action,
the term “internship” was replaced by “residency.” A residency Residency
was defined as “a postgraduate program of organized training .
. .” (and further detailed within the various standards). In 1985, Definition. A pharmacy residency is an organized, directed,
the concept that a resident’s training should be directed was postgraduate training program in a defined area of phamacy
incorporated into the definition.6–9 It was also acknowledged practice.
that a residency is practice oriented and that it is possible for a
residency to focus on a defined (specialized) area. Interpretation. Residencies exist primarily to train pharmacists
During the early 1970s, numerous residencies devel- in professional practice and management activities. Residencies
oped in clinical practice, leading to the establishment, in provide experience in integrating pharmacy services with the
1980, of accreditation standards for clinical pharmacy and comprehensive needs of individual practice settings and
specialized residency training.10,11 In 1986, the American provide indepth experiences leading to advanced practice
Pharmaceutical Association published a compilation of pro- skills and knowledge. Residencies foster an ability to con
grammatic essentials for community pharmacy residencies.12 ceptualize new and improved pharmacy services. Within a
In that same year, the American College of Apothecaries given residency program, there is considerable consistency
published specific guidelines for the accreditation of com- in content for each resident. In addition, accreditation standards
munity pharmacy residencies.13 and program guidelines produced by national pharmacy
Paralleling these developments and fostered by a associations provide considerable program content detail
growing sophistication and clinical thrust in institutional and foster consistency among programs.
pharmacy practice, postgraduate research-oriented programs A residency is typically 12 months or longer in
(generally termed “fellowships”) developed in the 1970s. duration, and the resident’s practice experiences are
These programs were conducted primarily in colleges of closely directed and evaluated by a qualified practitioner–
pharmacy and in academically based health centers to edu- preceptor. A residency may occur at any career point follow
cate and train individuals to conduct pharmacy research. A ing an entry-level degree in pharmacy. Individuals planning
1981 survey of fellowship programs reported the existence practice-oriented careers are encouraged to complete all for
of 58 fellowships in 19 topic areas.14 Two-thirds of these mal academic education before entry into a residency.
fellowships had existed for 3 years or less. The oldest pro-
gram had existed for less than 9 years. The ASHP Research Fellowship
and Education Foundation initiated clinical fellowships in
1978 and defined a pharmacy fellowship as “a directed, but Definition. A pharmacy fellowship is a directed, highly
highly individualized program [that] emphasizes research. individualized, postgraduate program designed to prepare
The focus of a pharmacy fellowship is to develop the the participant to become an independent researcher.
participant’s (the fellow’s) ability to conduct research in his
or her area of specialization.”15,16 Interpretation. Fellowships exist primarily to develop compe
ASHP publishes an annual directory of ASHP- tency in the scientific research process, including conceptual
accredited residency programs. In 1985, there were 184 izing, planning, conducting, and reporting research. Under
accredited programs.17 The American College of Clinical the close direction and instruction of a qualified researcher-
Education and Training–Endorsed Document 153
preceptor, the participant (the fellow) receives a highly 11. American Society of Hospital Pharmacists. ASHP
individualized learning experience that utilizes research accreditation standard for specialized residency train-
interests and knowledge needs as a focus for his or her ing (with guide to interpretation). Am J Hosp Pharm.
education and training. A fellowship graduate should be 1980; 37:1229–32.
capable of conducting collaborative research or functioning 12. American Pharmaceutical Association, Academy of
as a principal investigator. Pharmacy Practice. APhA community pharmacy resi-
Fellowships are typically offered through colleges of dency program: programmatic essentials. Am Pharm.
pharmacy, academic health centers, or specialized health- 1986; NS26:35–43.
care institutions. Fellowships are usually offered for prede- 13. American College of Apothecaries. Guidelines for
termined, finite periods of time, often exceeding 12 or even accreditation of community pharmacy residencies.
24 months. Individuals planning research-oriented careers Memphis, TN: American College of Apothecaries;
should expect to complete formal education in research 1986.
design and statistics either before or during a fellowship. A 14. Kaul AF, Powell SH, Cyr DA. Postgraduate pharmacy
fellowship candidate is expected to possess basic practice skills fellowships. Drug Intell Clin Pharm. 1981; 15:981–5.
relevant to the knowledge area of the fellowship. Such skills 15. ASHP Commission on Credentialing. Statement
may be obtained through practice experience or through of definition of pharmacy fellowships and resi-
an appropriate residency and should be maintained during dency. Bethesda, MD: American Society of Hospital
the program. Pharmacists; 1981.
16. McConnell W. Fellowship program in critical care
References pharmacy. In: Majerus TC, Dasta JF, eds. Practice
of critical care pharmacy. Rockville, MD: Aspen
1. Niemeyer G. Ten years of the American Society of Systems; 1985:59–68.
Hospital Pharmacists, 1942–1952: education and 17. American Society of Hospital Pharmacists. Residency
training. Bull Am Soc Hosp Pharm. 1952; 9:363–75. directory. Accredited pharmacy residency programs
2. American Society of Hospital Pharmacists. Approval and programs participating in the 1986 ASHP resident
program for internships in hospital pharmacy. Bull Am matching program. Bethesda, MD: American Society
Soc Hosp Pharm. 1955; 12:309–13. of Hospital Pharmacists; 1985.
3. American Society of Hospital Pharmacists. Standards 18. American College of Clinical Pharmacy. Residency
for internships in hospital pharmacies. Bull Am Soc and fellowship programs offered by members of the
Hosp Pharm. 1948; 5:233–4. American College of Clinical Pharmacy, 1986–87.
4. American Society of Hospital Pharmacists. Minimum Kansas City, MO: American College of Clinical
standard for pharmacy internship in hospitals. Bull Am Pharmacy; 1986.
Soc Hosp Pharm. 1955; 12:288–90. 19. Kaul AF, Janosik JE, Powell SH. Postgraduate phar-
5. American Society of Hospital Pharmacists. macy fellowships (1985–86). Drug Intell Clin Pharm.
Accreditation standard for residency in hospital pharmacy. 1986; 20:203–8.
Am J Hosp Pharm. 1963; 20:378–80.
6. American Society of Hospital Pharmacists.
Accreditation standard for pharmacy residency in a Developed by an ad hoc consortium made up of representatives
hospital. Am J Hosp Pharm. 1971; 28:189–90. from the American Association of Colleges of Pharmacy (AACP),
7. American Society of Hospital Pharmacists. the American College of Apothecaries (ACA), the American College
Accreditation standard for pharmacy residency in a of Clinical Pharmacy (ACCP), the American Pharmaceutical
hospital. Am J Hosp Pharm. 1973; 30:1129. Association (APhA), the American Society of Consultant
8. American Society of Hospital Pharmacists. ASHP Pharmacists (ASCP), the American Society of Hospital Pharmacists
accreditation standard for pharmacy residency in (ASHP), and the National Association of Retail Druggists (NARD);
a hospital (with guide to interpretation). Am J Hosp the consortium was convened by ASHP and met on August 4, 1986.
Pharm. 1979; 36:74–80. Approved by the ASHP Board of Directors, November 20, 1986, and
9. American Society of Hospital Pharmacists. ASHP subsequently approved by ACCP, APhA, ASCP, ACA, and AACP.
accreditation standard for hospital pharmacy train-
ing (with guide to interpretation). Am J Hosp Pharm. Copyright © 1987, American Society of Hospital Pharmacists, Inc.
1985; 42:2008–18. All rights reserved.
accreditation standard for residency training in clinical The bibliographic citation for this document is as follows: American
pharmacy (with guide to interpretation). Am J Hosp Society of Hospital Pharmacists. Definitions of pharmacy residen-
Pharm. 1980; 37:1223–8. cies and fellowships. Am J Hosp Pharm. 1987; 44:1142–4.
Ethics
156 Ethics–Positions
Ethics
Pharmacist Role in Capital Punishment (1531) Patient’s Right to Choose (0013)
Source: Council on Pharmacy Practice Source: Council on Legal and Public Affairs
To acknowledge that an individual’s opinion about capital To support the right of the patient or his or her representative
punishment is a personal moral decision; further, as allowed under state law to develop, implement, and make
To oppose pharmacist participation in capital punish- informed decisions regarding his or her plan of care; further,
ment; further, To acknowledge that the patient’s rights include being
To reaffirm that pharmacists have a right to decline to informed of his or her health status, being involved in care
participate in capital punishment without retribution. planning and treatment, and being able to request or refuse
This policy supersedes ASHP policy 8410. treatment; further,
To support the right of the patient in accord with state
Pharmacist’s Role on Ethics Committees (1403) law to (a) formulate advance directives and (b) have health
Source: Council on Pharmacy Practice care practitioners who comply with those directives.
To advocate that pharmacists should be included as members This policy was reviewed in 2014 by the Council on
of hospital and health-system ethics committees; further, Public Policy and by the Board of Directors and was found
To encourage pharmacists to actively seek ethics con- to still be appropriate.
sultations as appropriate; further,
To encourage pharmacists serving on ethics commit- ASHP Position on Assisted Suicide (9915)
tees to seek advanced training in health care ethics. Source: Council on Legal and Public Affairs
To remain neutral on the issue of health professional partici-
Ethical Use of Placebos in Clinical Practice (1116) pation in assisted suicide of patients who are terminally ill;
Source: Council on Pharmacy Practice further,
To affirm that the use of placebos in clinical practice is ethi- To affirm that the decision to participate in the use
cally acceptable only when patients have been informed of of medications in assisted suicide is one of individual con-
and agree to such use as a component of treatment; further, science; further,
To encourage hospitals and health systems to develop To offer guidance to health-system pharmacists who
policies and procedures to guide clinicians in making in- practice in states in which assisted suicide is legal.
formed decisions regarding the use of placebos; further, This policy was reviewed in 2013 by the Council on
To oppose the use of pharmacologically active sub- Pharmacy Practice and by the Board of Directors and was
stances or medications as placebos. found to still be appropriate.
This policy supersedes ASHP policy 0517.
Nondiscriminatory Pharmaceutical Care (9006)
Pharmacist’s Right of Conscience and Patient’s Right of Source: Council on Professional Affairs
Access to Therapy (0610) To adopt the following positions in regard to nondiscrimina-
Source: Council on Legal and Public Affairs tory pharmaceutical care:
To recognize the right of pharmacists, as health care provid-
ers, and other pharmacy employees to decline to participate • All patients have the right to privacy, respect, confi-
in therapies they consider to be morally, religiously, or ethi- dentiality, and high-quality pharmaceutical care.
cally troubling; further, • No patient should be refused pharmaceutical care or
To support the proactive establishment of timely and denied these rights based solely on diagnosis.
convenient systems by pharmacists and their employers that • Pharmacists must always act in the best interest
protect the patient’s right to obtain legally prescribed and of individual patients while not placing society as a
medically indicated treatments while reasonably accom- whole at risk.
modating in a nonpunitive manner the right of conscience;
further, This policy was reviewed in 2011 by the Council on
To support the principle that a pharmacist exercising Pharmacy Practice and by the Board of Directors and was
the right of conscience must be respectful of, and serve the found to still be appropriate.
legitimate health care needs and desires of, the patient, and
shall provide a referral without any actions to persuade, co-
erce, or otherwise impose on the patient the pharmacist’s
values, beliefs, or objections.
Ethics–Statements 157
ASHP Statement on Leadership

as a Professional Obligation
Position leaders, and the challenges presented by the leadership gap
defined by White.6 The Task Force report noted that leader-
The American Society of Health-System Pharmacists ship and management are different, stating that despite the
(ASHP) believes that all pharmacists have a professional synonymous use of “management” and “leadership” within
obligation to serve as leaders in the safe and effective use of the literature, hierarchy does not confer leadership, nor does
medications and encourages pharmacy practitioners, admin- leadership confer hierarchy. As Covey7 wrote, “Management
istrators, faculty members, preceptors, and students to ad- works in the system; leadership works on the system.” He
vance patient care and strengthen the pharmacy profession also further differentiated the concepts of leadership and
by embracing the responsibility to exert leadership in their management, saying, “Effective leadership is putting first
practices. ASHP urges all pharmacists to accept this respon- things first. Effective management is discipline, carrying it
sibility, actively seek the development of leadership skills, out.” Although the two terms are often used synonymously,
and exercise leadership when working with others, includ- leadership is a broader and more encompassing concept that
ing pharmacists, pharmacy technicians, pharmacy students extends to a wider array of situations, whereas management
and residents, administrators, other health care profession- has a more specific focus.
als, and patients. The most successful organizations facilitate the de-
ASHP encourages colleges of pharmacy to go beyond velopment of routine leadership roles and encourage par-
management coursework and integrate education on leader- ticipation in those roles. Frontline pharmacists must exhibit
ship as a practice philosophy throughout the pharmacy cur- themselves as leaders each time they step into the work-
riculum. All pharmacists share the responsibility to mentor place. The practice of effectively influencing the behavior
pharmacy students, pharmacy residents, other pharmacists, of physicians, nurses, pharmacy technicians, interns, support
staff, and others to optimize medication safety and patient
and pharmacy technicians. Pharmacists in formal leader-
outcomes constitutes successful leadership. Innovative prac-
ship roles have a specific responsibility to foster the de-
tice models can support the development of both clinical and
velopment of leadership skills in pharmacists, facilitate the
leadership skills. ASHP encourages these types of practice
development of practice models that provide regular oppor-
models and their development.
tunities to exercise leadership, and encourage pharmacists
The obligation to develop practitioners prepared for
to exercise leadership in practice. ASHP also encourages
professional leadership requires colleges of pharmacy to
hospital and health-system executives to support the devel-
adopt such values. Currently, leadership training is incon-
opment of leadership skills of all health care professionals.
sistently present in both academic and practice settings. The
Task Force report noted that pharmacy curricula commonly
Leadership in Practice offer elective management courses without addressing fun-
damental leadership skills in a proactive or longitudinal
The ASHP Statement on Professionalism includes leader- manner and that the concept of using management training
ship as 1 of 10 characteristics of a professional,1 and the to teach leadership skills has led to further gaps in how new
ASHP Statement on the Roles and Responsibilities of the pharmacists perceive leadership.5 The report emphasized the
Pharmacy Executive explains the formal leadership roles of need for increased focus on leadership training in colleges of
the pharmacy executive.2 Neither of these documents, how- pharmacy and recommended that these institutions incorpo-
ever, describes the professional obligation every pharmacist rate formalized leadership training throughout the curricu-
has to serve as a leader in the safe and effective use of medi- lum in a formal, longitudinal manner and not exclusively
cations. through management course work.
Definitions of leadership commonly focus on working White’s6 survey of student and new practitioners dem-
toward goals and exerting influence.3 For example, Nahata4 onstrated that they are likely to be mentored by frontline
stated that leadership “is about a vision, direction, strategies, pharmacists, supporting the critical need for expressions of
motivating, and inspiring.” The focus on goals and influence leadership. All pharmacists should take personal responsi-
guides understanding of the inherent requirement for leader- bility for leadership of the medication-use process and for
ship in pharmacy. The success of current pharmacy practice mentorship of students, residents, and colleagues. Although
models and the successful implementation of future models it is not the exclusive responsibility of formal pharmacy
rest on the ability of members of the profession to influence leaders such as pharmacy directors and managers, formal
others. In the complex and evolving health care environ- leaders must foster and support pharmacist leadership.
ment, leadership from pharmacists is required to promote The report of the American Association of Colleges
and advance the profession and our care for patients. Thus, of Pharmacy Argus Commission, Building a Sustainable
leadership is not an option—it is a professional obligation. System of Leadership Development for Pharmacy, also ar-
The ASHP Research and Education Foundation gued that leadership is a responsibility for all pharmacists.8
convened a Student and New Practitioner Leadership The report called for integration of leadership throughout
Task Force that generated a report titled Leadership as a pharmacy education and offered a number of specific rec-
Professional Obligation.5 This 2009 report addressed sev- ommendations. To support leadership development of stu-
eral issues regarding the current perceptions of leadership dents and practitioners, the report recommended greater fo-
in the pharmacy profession, methods for training pharmacy cus on fostering leadership education in pharmacy curricula,
158 Ethics–Statements
in residencies, and in practice sites. To cultivate high-quality 3. Holdford DA. Leadership theories and their lessons
candidates to fulfill the pharmacy leadership gap, the report for pharmacists. Am J Health-Syst Pharm. 2003;
also recommended expansion of didactic leadership training, 60:1780–6.
distance learning programs, the use of social media for net- 4. Nahata MC. Balancing leadership and management.
working and mentorship, and an increased focus on the full Am J Pharm Educ. 2001; 65:295–6.
spectrum of leadership. Colleges should also assess leader- 5. American Society of Health-System Pharmacists
ship potential during the application and selection process. Research and Education Foundation Center for
Pharmacists also have an obligation to exert lead- Health-System Pharmacy Leadership Student and
ership and participate in shaping the future of the profes- New Practitioner Leadership Task Force. Final re-
sion. Participation in professional societies such as ASHP port: leadership is a professional obligation (2009).
provides opportunities to shape the future of the profession www.ashpfoundation.org/MainMenuCategories/
and affords excellent opportunities for the development of CenterforPharmacyLeadership/AbouttheCenter/
leadership skills. Professional organizations such as ASHP StudentNewPractitionerLeadershipTaskForce/
also have an obligation to encourage the development of SNPFinalReport.aspx (accessed 2011 Mar 23).
leadership skills and support their development among their 6. White SJ. Will there be a pharmacy leadership crisis?
memberships. An ASHP Foundation Scholar-in-Residence report.
Am J Health-Syst Pharm. 2005; 62:845–55.
Conclusion 7. Covey SR. The 7 habits of highly effective people.
New York: Free Press; 1989.
Leadership is a professional obligation of all pharmacists 8. Kerr RA, Beck DE, Doss J, et al. Building a sustain-
and not the exclusive responsibility of pharmacists who hold able system of leadership development for pharmacy:
formal leadership roles or titles. All pharmacists should ac- report of the 2008–09 Argus Commission. Am J Pharm
cept the obligation to develop and exert leadership skills to Educ. 2009; 73(suppl):S5.
ensure the safe and effective use of medications. Pharmacy
schools, professional organizations, and employers should
encourage the development of these skills among students Approved by the ASHP Board of Directors on April 14, 2011, and
and practitioners and should provide both formal training by the ASHP House of Delegates on June 12, 2011. Developed
and opportunities for pharmacists to develop leadership ca- through the ASHP Council on Pharmacy Management.
pacity.
Ashley L. Mains, Pharm.D., and David R. Witmer, Pharm.D., are
gratefully acknowledged for drafting this statement.
References
ASHP statement on professionalism. Am J Health-Syst Inc. All rights reserved.
Pharm. 2008; 65:172–4.
2. American Society of Health-System Pharmacists. The bibliographic citation for this document is as follows: American
ASHP statement on the roles and responsibilities of Society of Health-System Pharmacists. ASHP statement on leader-
the pharmacy executive. Am J Health-Syst Pharm. ship as a professional obligation. Am J Health-Syst Pharm. 2011;
2009; 66:499–502. 68:2293–5.
ASHP Statement on Pharmacist’s

Decision-making on Assisted Suicide
Preamble Health Care Systems. Collaboration. Collaboration among
members of the health care team must occur at both the
Consistent with the intent of the Code of Ethics for patient care and the public policy levels. It is the pharma-
Pharmacists “to state publicly the principles that form cist’s responsibility to educate members of the health care
the fundamental basis of the roles and responsibilities of team about the pharmacotherapeutic options available in
pharmacists,” the American Society of Health-System treating the patient’s condition. Health care team mem-
Pharmacists issues this Statement on Pharmacist Decision- bers include the patient, members of the patient’s family,
making on Assisted Suicide. The practice of providing and caregivers.
competent patients with pharmaceutical means of ending Confidentiality. The patient’s right of confidential-
their lives raises issues of professional obligations to pa- ity and right to determine his or her therapy, including
tients and to other professionals involved in patient care. We end-of-life decisions, shall be respected, included, and
affirm the ASHP policy (9802) that supports the right of a considered in the decision process in health care systems.
pharmacist to participate or not in morally, religiously, or Pharmacists should maintain the confidentiality of all
ethically troubling therapies. patient information, regardless of whether they agree with
This Statement establishes a framework for pharma- the values underlying the patient’s choice of treatment or
cist participation in the legal and ethical debate about the ap- decision to forgo any particular treatment.
propriate care of patients at the end of life. This Statement Covenant with society. Health care is delivered in a
will help pharmacists resolve the growing questions about system in which each profession makes a contribution on
the ethical obligations of health care professionals to provide the patient’s behalf. An act in one part of the system has con-
care and alleviate suffering. It is hoped that this framework sequences in other parts of that system. Each profession has
and its use by pharmacists will virtually eliminate a patient’s a covenant with society, founded on a relationship of trust
request for assisted suicide. with the patient. The trust developed between each patient
When asked to evaluate and comment on legislative, and members of the health care team makes it important for
regulatory, or judicial actions or on organizational policies each professional to examine the moral and ethical issues of
of health systems regarding pharmaceutical care, pharma- patients’ requests for assistance in dying.
cists should use the principles expressed in this Statement in Barriers to care. Health care professionals must address
developing their responses. the following barriers to adequate end-of-life care:
Guiding Principles 1. Inadequate knowledge and use of pain- and symptom-

management therapies.
Professional Tradition. The basic tenet of the profession is 2. The paucity of published data related to the ingestion
to provide care and affirm life. The pharmacy profession is of lethal drugs and the outcomes thereof.
founded on a tradition of patient trust. The trust developed 3. Insufficient education of health care professionals
between each patient and members of the health care team about end-of-life and palliative care issues.
makes it important for each professional to examine the 4. Inadequate recognition that end-of-life care is the
moral and ethical issues of patients’ requests for assistance responsibility of the entire health care team.
in dying. Pharmacists should serve as advocates for the 5. Legal and regulatory issues that deter appropriate
patient throughout the continuum of care. provision of pain and symptom management.
Respect for Patients. Patient autonomy. Pharmacists should Professional Obligations. Conscientious objection. Pharmacists
ensure the rights of competent patients to know about all must retain their right to participate or not in morally,
legally available treatment options while communicating to religiously, or ethically troubling therapies. Procedures
patients and their caregivers (including family members if should be in place to ensure that employers are able to provide
appropriate) the overall duty of health care professionals to care to the patient and provide adequate services to the patient
preserve life. and caregiver. The employer has specific responsibilities, and
Confidentiality. Pharmacists should maintain the con- the employee cannot be a barrier to the employer’s ability to
fidentiality of all patient information, regardless of whether fulfill those obligations. Employers must reasonably accom-
they agree with the values underlying the patient’s choice of modate the employee pharmacist’s right to not participate in
treatment or decision to forgo any particular treatment. morally, religiously, or ethically troubling therapies.
Decision-making. Patients’ ability to exercise their Obligation to the patient. Pharmacists should support
ethical and legal right to choose or decline treatment is depen appropriate drug therapy to ensure that palliative care and
dent upon pharmacists informing patients and their health care aggressive pain management are available for all patients in
providers about the nature of pharmaceutical options. Those need. Pharmacists, as part of their professional responsibil-
options are constantly changing, given the dynamic aspect of ity, must offer to provide counseling services to the patient
the pharmaceutical marketplace and the evolving nature of and caregivers and be prepared to provide pharmaceutical
hospice care and available palliative treatments. care to the patient until the end of life.
Obligation to team members. The pharmacist, as a Assisted Suicide

member of a health care team responsible for the care of a
patient, is accountable for providing the team members with 1. Dixon KM, Kier KL. Longing for mercy, requesting
detailed information concerning efficacious use of pharma- death: pharmaceutical care and pharmaceutically assisted
ceutical and other therapies available that may affect the death. Am J Health-Syst Pharm. 1998; 55:578–85.
options open to the patient. 2. Hamerly JP. Views on assisted suicide: perspectives
As active members of an interdisciplinary team caring of the AMA and the NHO. Am J Health-Syst Pharm.
for patients, pharmacists must be central participants in all 1998; 55:543–7.
decisions relating to medication management of the patient. 3. Lee BC. Views on assisted suicide: the aid-in-dying
Pharmacists should respect the opinions and specific areas perspective. Am J Health-Syst Pharm. 1998; 55: 547–50.
of expertise of the other members of the health care team. 4. Meier DE, Emmons CA, Wallenstein S et al. A national
Pharmacist education. Pharmacists are often inad- survey of physician-assisted suicide and euthanasia in
equately trained in the care of dying patients. Therefore, the United States. N Engl J Med. 1998; 338: 1193–201.
pharmacists’ education at all levels (undergraduate, gradu- 5. Mullan K, Allen WL, Brushwood DB. Conscientious
ate, continuing education) should be sensitive to these objection to assisted death: can pharmacy address this
issues and offer the development of skills and knowledge in a systematic fashion? Ann Pharmacother. 1996;
concerning care of the dying. Pharmacists should make 30:1185–91.
a personal, professional commitment to learn more about 6. Rupp MT. Issues for pharmacists in assisted patient
end-of-life care. death. In: Battin MP, Lipman AG, eds. Drug use in
assisted suicide and euthanasia. Binghamton, NY:
Recommended Readings Haworth; 1996.
7. Rupp MT. Physician-assisted suicide and the issues it
Supreme Court Decisions raises for pharmacists. Am J Health-syst Pharm. 1995;
52:1455–60.
1. Washington v. Glucksberg, decided June 26, 1997. 8. Rupp MT, Isenhower HL. Pharmacists’ attitudes
2. Vacco v. Quill, decided June 26, 1977. toward physician-assisted suicide. Am J Hosp Pharm.
3. Angell M. The Supreme Court and physician-assisted 1994; 51:69–74.
suicide—the ultimate right. N Engl J Med. 1997; 336: 9. Stein GC. Assisted suicide: an issue for pharmacists.
50–3. Am J Health-Syst Pharm. 1998; 55:539. Editorial.
4. Annas GJ. The bell tolls for a constitutional right 10. Van der Maas PJ, van der Wal G, Haverkate I et al.
to physician-assisted suicide. N Engl J Med. 1997; Euthanasia, physician-assisted suicide, and other
337:1098–103. medical practices involving the end of life in the
5. Burt RA. The Supreme Court speaks: not assisted Netherlands, 1990–1995. N Engl J Med. 1996;
suicide but a constitutional right to palliative care. 335:1699–705.
N Engl J Med. 1997; 337:1234–6. 11. Van der Wal G, van der Maas PJ, Bosma JM et al.
6. Gostin LO. Deciding life and death in the courtroom: Evaluation of the notification procedure for physician-
from Quinlan to Cruzan, Glucksberg, and Vacco—a assisted death in the Netherlands. N Engl J Med. 1996;
brief history and analysis of constitutional protection 335:1706–11.
of the “right to die” JAMA 1997; 278:1523–8. 12. Vaux KL. Views on assisted suicide: an ethicist’s per-
7. Orentlicher D. The Supreme Court and physician- spective. Am J Health–Syst Pharm. 1998; 55:551–3.
assisted suicide: rejecting assisted suicide but embracing
euthanasia. N Engl J Med. 1997; 337:1236–9. End-of-Life Care
8. Palmer LI. Institutional analysis and physicians’ rights
after Vacco v. Quill, Cornell J Law Public Policy. 1. Foley KM. Competent care for the dying instead of
1998; 7:415–30. physician-assisted suicide. N Engl J Med. 1997;
336:54–8.
Professional Organization Position Statements/Policies 2. Quill TE, Lo B, Brock DW. Palliative options of last
resort: a comparison of voluntarily stopping eating
1. American Bar Association house of delegates. Report and drinking, terminal seda-tion, physician-assisted
of action taken at 1997 annual meeting. suicide, and voluntary active euthanasia. JAMA. 1997;
2. American Pharmaceutical Association. Code of Ethics 278:2099–104.
for Pharmacists. 3. Suicide prevention: efforts to increase research and
3. American Pain Society. Treatment of pain at the end of education in palliative care. Washington, DC: General
life. Accounting Office, 1998 Apr; report HEHS-98-128.
4. National League for Nursing. Life-terminating
choices: a framework for nursing decision-making. Miscellaneous
5. American Medical Association Policy on Physician-
Assisted Suicide, 1996. 1. Board of Directors report on the Council on Legal
6. American Nurses Association. Position statement on and Public Affairs, ASHP House of Delegates
assisted suicide. Session—1994.
7. American Geriatrics Society. Position statement on the 2. Board of Directors report on the Council on
care of dying patients. Professional Affairs, ASHP House of Delegates
8. National Hospice Organization. Session—1998.
3. Board of Directors report on the Council on Legal To support research on the needs of dying patients;
and Public Affairs, ASHP House of Delegates further,
Session—1998. To provide education to pharmacists on caring for
4. Statement of Attorney General Reno on Oregon’s dying patients, including education on clinical, managerial,
Death with Dignity Act. June 5, 1998. professional, and legal issues; further,
5. Schnabel J, Schnabel G. Pharmacy information. In: To urge the inclusion of such topics in the curricula of
Haley K, Lee M, eds. The Oregon Death With Dignity colleges of pharmacy.
Act: A Guidebook for Health Care Providers. Portland: This policy was reviewed in 2007 by the Council on
Oregon Health Sciences University, Center for Ethics Pharmacy Practice and by the Board of Directors and was
in Health Care; 1998 Mar. found to still be appropriate.
Pharmacist’s Right of Conscience and Patient’s Right of

This statement was reviewed in 2013 by the Council on Pharmacy Access to Therapy (0610)
Practice and by the Board of Directors and was found to still be Source: Council on Legal and Public Affairs
appropriate. To recognize the right of pharmacists, as health care provid-
ers, and other pharmacy employees to decline to participate
Approved by the ASHP Board of Directors, April 21, 1999, and in therapies they consider to be morally, religiously, or ethi-
by the ASHP House of Delegates, June 7, 1999. Developed by the cally troubling; further,
Council on Legal and Professional Affairs. To support the proactive establishment of timely and
convenient systems by pharmacists and their employers that
Copyright © 1999, American Society of Health-System Pharmacists, protect the patient’s right to obtain legally prescribed and
Inc. All rights reserved. medically indicated treatments while reasonably accom-
modating in a nonpunitive manner the right of conscience;
The bibliographic citation for this document is as follows: American further,
Society of Health-System Pharmacists. ASHP statement on pharmacist’s To support the principle that a pharmacist exercising
decision-making on assisted suicide. Am J Health-Syst. Pharm. the right of conscience must be respectful of, and serve the
1999; 56:1661–4. legitimate health care needs and desires of, the patient, and
shall provide a referral without any actions to persuade, co-
Relevant ASHP Policies erce, or otherwise impose on the patient the pharmacist’s
values, beliefs, or objections.
Pharmacist Support for Dying Patients (0307) This policy supersedes ASHP policy 9802.
Source: Council on Professional Affairs
To support the position that care for dying patients is part Pharmacist Role in Capital Punishment (1531)
of the continuum of care that pharmacists should provide to Source: Council on Pharmacy Practice
patients; further, To acknowledge that an individual’s opinion about capital
To support the position that pharmacists have a pro- punishment is a personal moral decision; further,
fessional obligation to work in a collaborative and compas- To oppose pharmacist participation in capital punish-
sionate manner with patients, family members, caregivers, ment; further,
and other professionals to help fulfill the patient care needs, To reaffirm that pharmacists have a right to decline to
especially the quality-of-life needs, of dying patients of all participate in capital punishment without retribution.
ages; further, This policy supersedes ASHP policy 8410.
ASHP Statement on Professionalism

Position idea that these individuals profess a common purpose.12 The
common purpose of pharmacists is eloquently stated in the
Pharmacy is a profession. Despite the challenges to profes- eight principles of the Code of Ethics for Pharmacists.13
sionalism presented by changes in health care, pharmacists Professing these principles creates responsibilities for
must embrace the responsibilities that stem from their pro- pharmacists. Foremost among these responsibilities is the
fession’s guiding principles. Among those responsibilities obligation to place the well-being of patients at the center of
are advancing the well-being and dignity of their patients, pharmacy practice. Many of the other principles flow from
acting with integrity and conscience, collaborating respect- the covenantal relationship between the pharmacist and
fully with health care colleagues, and seeking justice in the the patient. To provide the best possible care, pharmacists
distribution of health care resources. dedicate themselves to maintaining professional competence
The American Society of Health-System Pharmacists through lifelong learning and contemplation. Professional
(ASHP) encourages pharmacy practitioners, administrators, education and advancing standards of practice can only be
faculty members, preceptors, and students to advance patient achieved through a profession’s collective efforts; pharma-
care and strengthen the pharmacy profession by promoting cists therefore commit themselves to serve not only their pa-
professionalism in everyday practice. ASHP urges pharma- tients but also their profession. Finally, pharmacists commit
cists to dedicate themselves to serving the interests of their themselves to improving health care institutions not simply
patients and to practicing with compassion and respect for for the well-being of individual patients but for the benefit
patients and their families. Pharmacists should commit of society as a whole.
to working cooperatively with and with respect for other
health care providers and to seeking to improve the quality
Incorporating Professionalism
of health care received by the communities in which they
work and live. ASHP encourages pharmacists to serve as into Practice
mentors to students, residents, and colleagues in a manner
that fosters the adoption of high professional aspirations for ASHP encourages practitioners, administrators, faculty
pharmacy practice, high personal standards of integrity and members, preceptors, and pharmacy students to contemplate
competence, a commitment to serving humanity, habits of and to incorporate into their practices the guiding principles
analytical thinking and ethical reasoning, and a commitment set forth in the Code of Ethics for Pharmacists13 and the fol-
to lifelong learning. lowing 10 characteristics of a professional:
1. Knowledge and skills of the profession,

Background 2. Commitment to self-improvement of skills and knowl-
edge,
Between 1995 and 2005, the number of PubMed-indexed
3. Service orientation,
articles on professionalism quadrupled, from 50 to ap-
4. Pride in and service to the profession,
proximately 200 per year.1 Professional associations from
5. Covenantal relationship with the patient,
the American College of Physicians–American Society of
6. Creativity and innovation,
Internal Medicine to the American College of Dentistry have
7. Conscience and trustworthiness,
convened task forces, developed white papers and charters,
8. Accountability for his or her work,
and initiated programs to increase the professionalism of
9. Ethically sound decision-making, and
their members.2–6
10. Leadership.6
The rising interest in professionalism has been attrib-
uted to the perception that changes in health care delivery are
Practicing and aspiring hospital and health-system pharma-
eroding the professional standards of health care providers.2
cists should develop a personal plan for professional de-
Among the changes confronting the pharmacy profession are
velopment, encourage their colleagues to do the same, and
managed care’s continuing emphasis on cost containment7;
share the results. Continuing education should be viewed as
increased demand for systems that ensure the safety of medi-
an opportunity to enhance one’s practice rather than an obli-
cation use8; technology-driven changes in pharmacy’s core re
gation to be fulfilled in the most expedient manner.
sponsibilities, the most important of which is an expansion of
Much could be done to make practice sites more con-
the pharmacist’s role in patient care7,9,10; and a prolonged shor
ducive to professional behavior. Institutions can develop
tage of pharmacists.11 As such challenges mount, it is in the best
personnel recruitment, orientation, and evaluation systems
interest of our profession and the public we serve to reaffirm
that encourage professional development (e.g., by offer-
our foundational principles. Hospital and health-system phar
macists must therefore define for themselves the principles ing benefit packages that emphasize professional develop-
that will guide them in their unique practice settings. ment rather than salary or by incorporating characteristics
of professionalism into job descriptions).14 Administrators
and pharmacists can promote professionalism by improving
Guiding Principles and Responsibilities the pharmacy practice area to reduce environmental barri-
for Health-System Pharmacy ers to professionalism (e.g., cluttered, isolated, outdated, or
cramped working quarters).
The use of the term “profession” to describe a group of in-
dividuals pursuing an occupation or career is based on the
One of the fundamental services of a professional is References

recruiting, nurturing, and securing new practitioners to that
profession’s ideals and mission.15 For hospital and health- 1. National Center for Biotechnology Information.
system pharmacists, professional socialization is especially PubMed online database. www.ncbi.nih.gov/entrez/
important because the principles of institutional pharmacy query.fcgi (accessed 2006 Jun 16).
practice are not emphasized in typical pharmacy curricula. 2. ABIM Foundation, ACP–ASIM Foundation, and
Above all else, hospital and health-system pharmacists need European Federation of Internal Medicine. Medical
to prevent “inconsistent socialization,”16 in which the prin- professionalism in the new millennium: a physician
ciples of professionalism instilled in pharmacy students are charter. Ann Intern Med. 2002; 136:243–6.
undermined by a lack of professionalism in the role models 3. Yeager AL. Dental ethics for the 21st century: learn-
they encounter when they enter practice. Pharmacy depart- ing from the Charter on Medical Professionalism. J
ments can avoid inconsistent socialization by promoting a Am Coll Dent. 2002; 69:53–60.
culture of professionalism in the workplace through per- 4. Popp RL, Smith SC Jr. Cardiovascular professional-
sonnel recruitment and evaluation systems that emphasize ism and ethics in the modern era. J Am Coll Cardiol.
professional development.16 Regardless of the level of sup- 2004; 44:1722–3.
port they receive, however, hospital and health-system phar- 5. American Society of Health-System Pharmacists. 2001
macists must commit themselves fully to their mentorship ASHP Leadership Conference on Pharmacy Practice
responsibilities. Management Executive Summary. From management
ASHP urges practicing pharmacists to serve as men- to leadership: the building blocks of professionalism.
tors to students, residents, and colleagues in a manner that Am J Health-Syst Pharm. 2002; 59:661–5.
fosters the adoption of high professional aspirations for 6. Adapted from: American Pharmaceutical Association
pharmacy practice, high personal standards of integrity and Academy of Students of Pharmacy—American
competence, a commitment to serve humanity, habits of ana- Association of Colleges of Pharmacy Council of
lytical thinking and ethical reasoning, and a commitment to Deans Task Force on Professionalism. White paper on
lifelong learning. Practice sites should designate preceptors, pharmacy student professionalism. J Am Pharm Assoc.
implement preceptor training programs, encourage precep- 2000; 40:96–102.
tor adherence to the highest professional standards, solicit 7. Zacker C, Mucha L. Institutional and contingency ap-
student feedback on preceptorship programs, and reward proaches to the reprofessionalization of pharmacy. Am
those who participate.6 Hospitals and health systems should J Health-Syst Pharm. 1998; 55:1302–5.
also explore other ways to promote mentorship relation- 8. Pedersen CA, Schneider PJ, Scheckelhoff DJ. ASHP
ships among staff. Hospital and health-system pharmacists national survey of pharmacy practice in hospital set-
and students can participate in ASHP’s Virtual Mentoring tings: prescribing and transcribing—2004. Am J
Exchange.17 ASHP encourages pharmacists, particularly Health-Syst Pharm. 2005; 62:378–90.
new practitioners, to actively seek mentors. 9. Reeder CE, Dickson M, Kozma CM et al. ASHP na
Finally, hospital and health-system pharmacists can tional survey of pharmacy practice in acute care set
advance the cause of professionalism in health care by re- tings—1996. Am J Health-Syst Pharm. 1997; 54: 653–
invigorating the mission development processes of their 69.
institutions, encouraging those institutions to revise their 10. Knapp KK, Okamoto MP, Black BL. ASHP survey
mission statements to describe how they will address such of ambulatory care pharmacy practice in health sys
ethical issues as the treatment of patients, employees, and tems—2004. Am J Health-Syst Pharm. 2005; 62: 274–
staff; institutions’ responsibilities to their communities, to 84.
other institutions, and to their own futures; the need to honor 11. Knapp KK, Quist RM, Walton SM et al. Update on the
founding traditions and sustaining principles; and the com- pharmacist shortage: national and state data through
plex interactions of legal and ethical responsibilities and 2003. Am J Health-Syst Pharm. 2005; 62:492–9.
their obligations to meet legislatively and socially defined 12. Knowlton CH, Penna RP. Pharmaceutical care, 2nd ed.
needs.18 Bethesda, MD: American Society of Health-System
In 1976, Anderson15 called on hospital pharmacists to Pharmacists; 2003:4.
“create a code that reflects our relationships with all of the 13. Code of ethics for pharmacists. In: Hawkins BH, ed.
different people and conditions under which we practice.” Best practices for hospital and health-system phar-
The time has come for hospital and health-system pharma- macy. Bethesda, MD: American Society of Health-
cists to join forces with other health care providers and pa- System Pharmacists; 2005:103.
tients to engage what has been called “the new authorities 14. Hammer DP, Berger BA, Beardsley RS et al. Student
of health care”18 to attain the kind of health care system our professionalism. Am J Pharm Educ. 2003; 63:1–29.
patients deserve and our society demands. 15. Anderson RD. 1976 Harvey A.K. Whitney lecture:
the peril of deprofessionalization. Am J Hosp Pharm.
1977; 34:133–9 [reprinted in Am J Health-Syst Pharm.
Conclusion 2004; 61:2373–9].
16. Manasse HR Jr, Stewart JE, Hall RH. Inconsistent so-
The pharmacy profession’s guiding principles are elo- cialization in pharmacy—a pattern in need of change.
quently stated in the Code of Ethics for Pharmacists. Despite J Am Pharm Assoc. 1975; 15:616–21,658.
the challenges to professionalism presented by changes in 17. American Society of Health-System Pharmacists.
health care, pharmacists must embrace the responsibilities ASHP virtual mentoring exchange. www.ashp.org/
that stem from their profession’s guiding principles. virtualmentoring/index.cfm (accessed 2005 Jun 16).
18. Reiser SJ, Banner RS. The Charter on Medical Copyright © 2008, American Society of Health-System Pharmacists,
Professionalism and the limits of medical power. Ann Inc. All rights reserved.
Intern Med. 2003; 138:844–6.
Society of Health-System Pharmacists. ASHP statement on profes-
sionalism. Am J Health-Syst Pharm. 2008; 65:172–4.
Approved by the ASHP Board of Directors on January 12, 2007,
and by the ASHP House of Delegates on June 26, 2007. Developed
through the ASHP Council on Pharmacy Practice.
Ethics–Guideline 165
ASHP Guidelines on Pharmacists’

Relationships with Industry
In the practice of their profession, pharmacists should be for travel, lodging, and meal expenses. Token consulting or
guided only by the consideration of patient care. Pharmacists advisory arrangements cannot be used to justify compensat-
should neither accept nor retain anything of value that has the ing pharmacists for their time, travel, lodging, and other out-
potential to affect materially their ability to exercise judg- of-pocket expenses.
ments solely in the interests of patients. A useful criterion
in determining acceptable activities and relationships is this: Clinical Research
Would the pharmacist be willing to have these relationships
generally known? Notwithstanding this responsibility, phar- Pharmacists who participate in practice-based research of
macists may benefit from guidance in their relationships with pharmaceuticals, devices, or other programs should conduct
industry. To this end, the following suggestions are offered. their activities in accord with basic precepts of accepted
scientific methodology. Practice-based drug studies that are,
Gifts and Hospitality in effect, promotional schemes to entice the use of a product
or program are unacceptable.
Gifts, hospitality, or subsidies offered to pharmacists by
industry should not be accepted if acceptance might influence, Disclosure of Information
or appear to others to influence, the objectivity of clinical
judgment or drug product selection and procurement. To avoid conflicts of interest or appearances of impropriety,
pharmacists should disclose consultant or speaker arrange-
Continuing Education ments or substantial personal financial holdings with compa
nies under consideration for formulary inclusion or related
Providers of continuing education that accept industry fund- decisions. To inform audiences fully, speakers and authors
ing for programs should develop and enforce policies to should disclose, when pertinent, consultant or speaker and
maintain complete control of program content. research funding arrangements with companies.
Subsidies to underwrite the costs of continuing-education
conferences, professional meetings, or staff development Additional Issues
programs can contribute to the improvement of patient care
and are permissible. Payments to defray the costs of a con- The advice in this document is noninclusive and is not
ference should not be accepted directly or indirectly from intended to limit the legitimate exchange of prudent scien
industry by pharmacists attending the conference or pro- tific information.
gram. Contributions to special or educational funds for staff
development are permissible as long as the selection of staff
members who will receive the funds is made by the department This guideline was reviewed in 2001 by the Council on Legal and
of pharmacy. Public Affairs and by the ASHP Board of Directors and was found
It is appropriate for faculty at conferences or meetings to still be appropriate.
to accept reasonable honoraria and reimbursement for
reasonable travel, lodging, and meal expenses. However, Approved by the ASHP Board of Directors, November 20, 1991.
direct subsidies from industry should not be accepted to pay Developed by the ASHP Council on Legal and Public Affairs.
the costs of travel, lodging, or other personal expenses of
pharmacists attending conferences or meetings, nor should The language used in many of the guidance issues contained in this
subsidies be accepted to compensate for the pharmacists’ time. document was adapted, with permission, from documents devel-
Scholarships or other special funds to permit pharmacy oped by the American Medical Association (JAMA. 1991; 265:501)
students, residents, and fellows to attend carefully selected and the American College of Physicians (Ann Intern Med. 1990;
educational conferences may be permissible as long as the 112:624–6).
selection of students, residents, or fellows who will receive
the funds is made by the academic or training institution. Copyright © 1992, American Society of Hospital Pharmacists, Inc.
Consultants and Advisory Arrangements
Consultants who provide genuine services for industry may Society of Hospital Pharmacists. ASHP guidelines on pharmacists’
receive reasonable compensation and accept reimbursement relationships with industry. Am J Hosp Pharm. 1992; 49:154.
166 Ethics–Endorsed Document
Code of Ethics for Pharmacists
Preamble avoids discriminatory practices, behavior or work con-

ditions that impair professional judgment, and actions
Pharmacists are health professionals who assist individuals that compromise dedication to the best interests of
in making the best use of medications. This Code, prepared patients.
and supported by pharmacists, is intended to state publicly the
principles that form the fundamental basis of the roles and re- V. A pharmacist maintains professional competence.
sponsibilities of pharmacists. These principles, based on moral Interpretation: A pharmacist has a duty to maintain
obligations and virtues, are established to guide pharmacists in knowledge and abilities as new medications, devices,
relationships with patients, health professionals, and society. and technologies become available and as health in-
formation advances.
Principles
VI. A pharmacist respects the values and abilities of
I. A pharmacist respects the covenantal relationship colleagues and other health professionals.
between the patient and pharmacist. Interpretation: When appropriate, a pharmacist asks
Interpretation: Considering the patient-pharmacist for the consultation of colleagues or other health
relationship as a covenant means that a pharma- professionals or refers the patient. A pharmacist
cist has moral obligations in response to the gift of acknowledges that colleagues and other health pro-
trust received from society. In return for this gift, a fessionals may differ in the beliefs and values they
pharmacist promises to help individuals achieve op- apply to the care of the patient.
timum benefit from their medications, to be commit-
ted to their welfare, and to maintain their trust. VII. A pharmacist serves individual, community, and
societal needs.
II. A pharmacist promotes the good of every patient in Interpretation: The primary obligation of a pharma-
a caring, compassionate, and confidential manner. cist is to individual patients. However, the obliga-
Interpretation: A pharmacist places concern for the tions of a pharmacist may at times extend beyond
well-being of the patient at the center of professional the individual to the community and society. In these
practice. In doing so, a pharmacist considers needs situations, the pharmacist recognizes the responsi-
stated by the patient as well as those defined by health bilities that accompany these obligations and acts
science. A pharmacist is dedicated to protecting the accordingly.
dignity of the patient. With a caring attitude and a
compassionate spirit, a pharmacist focuses on serving VIII. A pharmacist seeks justice in the distribution of
the patient in a private and confidential manner. health resources.
Interpretation: When health resources are allocated,
III. A pharmacist respects the autonomy and dignity of a pharmacist is fair and equitable, balancing the
each patient. needs of patients and society.
Interpretation: A pharmacist promotes the right of
self-determination and recognizes individual self-
worth by encouraging patients to participate in deci- The endorsement of this document was reviewed in 2012 by the
sions about their health. A pharmacist communicates Council on Pharmacy Practice and by the Board of Directors and
with patients in terms that are understandable. In all was found to still be appropriate.
cases, a pharmacist respects personal and cultural
differences among patients. Copyright American Pharmacists Association. Adopted by the mem-
bership of the American Pharmaceutical Association on October
IV. A pharmacist acts with honesty and integrity in 27, 1994. Endorsed by the American Society of Health-System
professional relationships. Pharmacists House of Delegates on June 3, 1996 (ASHP Policy
Interpretation: A pharmacist has a duty to tell the truth 9607). Proceedings of the 47th annual session of the ASHP House of
and to act with conviction of conscience. A pharmacist Delegates. Am J Health-Syst Pharm. 1996; 53:1805. ASHP Reports.
Formulary Management
(Medication-Use Policy Development)
168 Formulary Management–Positions
Formulary Management
Pharmacogenomics (1104) from well-designed, independent studies that demonstrate
Source: Council on Therapeutics inferior efficacy or safety of the generic drug product.
To advocate that pharmacists take a leadership role in the This policy was reviewed in 2012 by the Council on
therapeutic applications of pharmacogenomics, which is es- Therapeutics and by the Board of Directors and was found
sential to individualized drug therapy; further, to still be appropriate.
To support research to validate and standardize genetic
markers and genetic testing for drug therapy and to support Expression of Therapeutic Purpose of Prescribing (0305)
research and other efforts that guide and accelerate the ap- Source: Council on Professional Affairs
plication of pharmacogenomics to clinical practice; further, To advocate that the prescriber provide or pharmacists have
To advocate for the inclusion of pharmacogenomic immediate access to the intended therapeutic purpose of
test results in medical and pharmacy records in a format prescribed medications in order to ensure safe and effective
that clearly states the implications of the results for drug medication use.
therapy and facilitates availability of the genetic informa- This policy was reviewed in 2012 by the Council on
tion throughout the continuum of care and over a patient’s Pharmacy Practice and by the Board of Directors and was
lifetime; further, found to still be appropriate.
To encourage pharmacists to educate prescribers and
patients about the use of pharmacogenomic tests and their Appropriate Dosing of Medications in Patient Popula-
appropriate application to drug therapy management; further, tions with Unique Needs (0228)
To encourage pharmacist education on the use of Source: Council on Professional Affairs
pharmacogenomics and advocate for the inclusion of phar- To advocate reforms in medication-use systems, including
macogenomics and its application to therapeutic decision- electronic systems, and health care provider education and
making in college of pharmacy curricula. training that facilitate optimal patient-specific dosing in
This policy supersedes ASHP policy 0016. populations of patients (e.g., pediatrics, geriatrics) with al-
tered pharmacokinetics and pharmacodynamics.
Medications Derived from Biologic Sources (0809) This policy was reviewed in 2011 by the Council on
Source: Council on Pharmacy Practice Pharmacy Practice and by the Board of Directors and was
To encourage pharmacists to take a leadership role in their found to still be appropriate.
health systems for all aspects of the proper use of medica-
tions derived from biologic sources, including preparation, Medication Formulary System Management (0102)
storage, control, distribution, administration procedures, Source: Council on Administrative Affairs
safe handling, and therapeutic applications; further, To declare that decisions on the management of a medication
To facilitate education of pharmacists about the proper formulary system (1) should be based on clinical, ethical,
use of medications derived from biologic sources. legal, social, philosophical, quality-of-life, safety, and phar-
(Note: Section 351(a) of the Public Health Service Act macoeconomic factors that result in optimal patient care,
[42 U.S.C. 262(a)] defines biological product as follows: a and (2) must include the active and direct involvement of
virus, therapeutic serum, toxin, antitoxin, vaccine, blood, physicians, pharmacists, and other appropriate health care
blood component or derivative, allergenic product, or analo- professionals; further,
gous product, or arsphenamine or derivative of arsphena- To declare that decisions on the management of a
mine [or any other trivalent organic arsenic compound], ap- medication formulary system should not be based solely on
plicable to the prevention, treatment, or cure of a disease or economic factors.
condition of human beings.) This policy was reviewed in 2010 by the Council on
This policy was reviewed in 2012 by the Council on Pharmacy Management and by the Board of Directors and
Pharmacy Practice and by the Board of Directors and was was found to still be appropriate.
Gene Therapy (0103)
Generic Substitution of Narrow Therapeutic Index Source: Council on Administrative Affairs
Drugs (0817) To declare that health-system decisions on the selection, use,
Source: Council on Therapeutics and management of gene therapy agents should be based on
To support the current processes used by the Food and Drug the same principles as a medication formulary system in that
Administration (FDA) to determine bioequivalence of ge- (1) decisions are based on clinical, ethical, legal, social, phil
neric drug products, including those with a narrow therapeu- osophical, quality-of-life, safety, and pharmacoeconomic fac
tic index, and to recognize the authority of the FDA to decide tors that result in optimal patient care and (2) such decisions
if additional studies are necessary to determine equivalence; must include the active and direct involvement of physicians,
further, pharmacists, and other appropriate health care professionals.
To oppose a blanket restriction on generic substitution This policy was reviewed in 2010 by the Council on
for any medication or medication class without evidence Pharmacy Management and by the Board of Directors and
Formulary Management–Positions 169
Role of Pharmacists and Business Leaders in Health Medical Devices (9106)

Care Services and Policies (9819) Source: Council on Legal and Public Affairs
Source: Council on Professional Affairs To support public and private initiatives to clarify and define
To support the principle that business leaders and health pro- the relationship among drugs, devices, and new technologies
fessionals must share responsibility and accountability for in order to promote safety and effectiveness as well as better
providing optimal health care services to patients; further, delivery of patient care.
To support the principle that business leaders should This policy was reviewed in 2012 by the House of
expect practicing pharmacists to formulate policies that af- Delegates and by the Board of Directors and was found to
fect the prerogative of pharmacists to make optimal care de- still be appropriate.
cisions on behalf of patients.
This policy was reviewed in 2013 by the Council on Therapeutic Interchange (8708)
Pharmacy Practice and by the Board of Directors and was Source: Council on Legal and Public Affairs
found to still be appropriate. To support the concept of therapeutic interchange of vari-
ous drug products by pharmacists under arrangements where
Standardization of Drug Medication Formulary Systems pharmacists and authorized prescribers interrelate on the
(9601) behalf of patient care.
Source: Council on Administrative Affairs This policy was reviewed in 2013 by the Council on
To support the concept of a standardized medication formulary Pharmacy Practice and by the Board of Directors and was
system among components of integrated health systems when found to still be appropriate.
standardization leads to improved patient outcomes; further,
To include in the formulary-standardization process the
direct involvement of the health system’s physicians, phar-
macists, and other appropriate health care professionals.
170 Formulary Management–Statements
ASHP Statement on the Pharmacy and Therapeutics

Committee and the Formulary System
Position staff bylaws, medical staff rules and regulations, and other
organizational policies.
American Society of Health-System Pharmacists (ASHP) The overarching purposes of the P&T committee are
believes that health systems should develop, organize, and policy development, communication and education, and for-
administer a formulary system that follows the principles mulary management.
below in order to optimize patient care by ensuring access to
clinically appropriate, safe, and cost-effective medications. Policy Development
Background The P&T committee formulates policies regarding evalua-

tion, selection, diagnostic and therapeutic use, and monitor-
A formulary is a continually updated list of medications and ing of medications and medication-associated products and
related information, representing the clinical judgment of devices. The P&T committee should establish and assist in
pharmacists, physicians, and other experts in the diagnosis programs and procedures that ensure safe and effective medi-
and treatment of disease and promotion of health.1 A formu- cation therapy (e.g., clinical care plans, treatment guidelines,
lary includes, but is not limited to, a list of medications and critical pathways, disease management protocols). Members
medication-associated products or devices, medication-use of the P&T committee, or their representatives from appro-
policies, important ancillary drug information, decision- priate specialties (including pharmacists), should participate
support tools, and organizational guidelines. The multiplicity in or direct the development and review of such programs or
of medications available, the complexities surrounding their procedures, which should be kept current.
safe and effective use, and differences in their relative value The P&T committee should participate in performance
make it necessary for health systems to have medication-use improvement activities related to procurement, prescrib-
policies that promote rational, evidence-based, clinically ap- ing, dispensing, administering, monitoring, and overall use
propriate, safe, and cost-effective medication therapy. The of medications. The P&T committee should advise the in-
formulary system is the ongoing process through which a stitution, including the pharmacy department, in the imple-
health care organization establishes policies on the use of mentation of effective medication distribution and control
drugs, therapies, and drug-related products and identifies procedures, incorporating technological advances when ap-
those that are most medically appropriate and cost-effective to propriate. The P&T committee should initiate, direct, and
best serve the health interests of a given patient population. review the results of medication-use evaluation programs
to optimize medication use and routinely monitor outcomes
(economic, clinical, and humanistic) of formulary decisions.
Pharmacy and Therapeutics Committee
Medication-use evaluation should result in performance-im-
provement initiatives to improve the medication-use process.
To be effective, medication-use policies must have the con-
The P&T committee should take actions to prevent,
currence of individuals involved in the medication-use proc-
monitor, and evaluate adverse drug reactions and medication
ess. Such consensus is achieved by developing medication-
errors in the health care setting, including those occurring
use policies through a properly organized and representative
with biological products and vaccines. Information from
pharmacy and therapeutics (P&T) committee or equivalent
these activities should be disseminated to the appropriate
body and ensuring that those policies are approved by the
health care personnel for informational and educational pur-
organized medical staff.
poses (e.g., newsletters, memoranda) and, when appropriate,
The P&T committee is composed of actively partici-
to the Food and Drug Administration (FDA).
pating physicians, other prescribers, pharmacists, nurses,
The P&T committee should establish clearly defined
administrators, quality-improvement managers, and other
policies and procedures related to manufacturer sales repre-
health care professionals and staff who participate in the
sentatives’ activities within the organization.
medication-use process. Customarily, P&T member appoint-
ments are based on guidance from the medical staff. The
P&T committee should serve in an evaluative, educational, Communication and Education
and advisory capacity to the medical staff and organizational
administration in all matters that pertain to the use of medica- The P&T committee ensures that mechanisms are in place to
tions (including investigational medications). The P&T com- communicate with health care professionals, patients, and pay-
mittee is a policy-recommending body to the medical staff ers about all aspects of the formulary system, including changes
and the administration of the organization on matters related made to the formulary or policies and how formulary system
to the safe and therapeutic use of medications. The P&T decisions are made. The P&T committee also recommends or
committee is responsible to the medical staff as a whole, and assists in the formulation of educational programs designed
its recommendations are subject to approval by the organized to meet the needs of professional staff, patients, families, and
medical staff as well as the administrative approval process. caregivers on matters related to medications and medication
The basic policies and procedures that govern the P&T com- use. The P&T committee should establish or plan suitable edu-
mittee’s administration of the formulary system should be cational programs on matters related to medication use for staff
incorporated, as appropriate, in the health system’s medical involved in the care of patients and the use of medications.
Formulary Management–Statements 171
Formulary Management The P&T committee, when considering formulary op-

tions, should evaluate coordination issues with local health
Health systems should develop, organize, and administer a care plans and other organizations’ formularies. At a mini-
formulary system that follows the principles below in order mum, appropriateness of therapeutic interchange should be
to optimize patient care by ensuring access to clinically ap- evaluated for any formulary decisions that may conflict with
propriate, safe, and cost-effective medications. known managed care or other health plan formularies.
The formulary should be published and updated regu-
Formulary System. The P&T committee is responsible for larly. It should also be readily available and accessible at
administering the formulary system. Although the basic or- all times, either manually or electronically, to all personnel
ganization of each health care setting and its medical staff involved in the care of patients and the use of medications.
may influence the specific functions and scope of the P&T Medications should be identified in the formulary by their
committee, key elements of a formulary system that should generic names, and prescribers should be strongly encour-
also be included are the evaluation of the clinical use of aged to order medications by their generic names.
medications (including outcomes), the development of poli- The P&T committee should clearly define terminology
cies and quality assurance activities for medication use and related to formulary status of medications (e.g., formulary,
administration, and the evaluation and monitoring of ad- nonformulary, not stocked at a given site, restricted by cri-
verse drug reactions and medication errors. The formulary teria specific to a given site), especially in multihospital or-
system shall be endorsed by the medical staff based on the ganizations, and disseminate this information to health care
recommendations of the P&T committee. The medical staff professionals involved in the medication-use process. The
should adapt the principles of the system to fit the needs of P&T committee should establish a procedure for appraisal
the particular organization and affiliated institutions and am- and use by the medical staff of medications not included in
bulatory care settings. The organization, often through the the formulary (i.e., nonformulary medication use).
pharmacy department, should make certain that all personnel The pharmacist shall be responsible for specifications
involved in the care of patients and the use of medications in for the quality, quantity, and source of supply of all medica-
all health-system components are informed about the exis- tions, chemicals, biologicals, and pharmaceutical prepara-
tence of the formulary system, how to access the formulary, tions used in the diagnosis and treatment of patients.
the procedures governing its operation, any changes in those
procedures, and other necessary information (e.g., changes
in drug product availability). This information may be fur- Conclusion
ther disseminated to other interested entities (e.g., affiliated
managed care organizations). ASHP believes that medication-use policies should be de-
veloped and implemented in organized health-care systems
Formulary. The P&T committee develops an evidence- to promote the rational, evidence-based, clinically appropri-
based formulary of medications and medication-associated ate, safe, and cost-effective use of medications. The P&T
products accepted for use in the organization. The commit- committee of a health system should develop, organize, and
tee also provides timely revision and maintenance for the administer a formulary system that follows the principles set
formulary and promotes the rational, clinically appropriate, forth in this statement in order to optimize patient care.
safe, and cost-effective use of medications via guidelines,
protocols, and other mechanisms. The P&T committee, on an References
ongoing basis, objectively appraises, evaluates, and selects
medications for addition to or deletion from the formulary. 1. Principles of a sound drug formulary system [con-
The formulary is based on the best clinical evidence avail- sensus statement]. In: Hawkins B, ed. Best practices
able and reflects the current clinical judgment of the medical for hospital & health-system pharmacy: positions
staff, pharmacists, and other health care experts. The selec- and guidance documents of ASHP. Bethesda, MD:
tion of items to be included in the formulary should be based American Society of Health-System Pharmacists;
on objective evaluation of their relative economic, clinical, 2006:110–3.
and humanistic outcomes. The decisions should not be based 2. U.S. Department of Health and Human Services.
solely on economic factors. The committee should identify Electronic orange book: approved drug products with
potential safety concerns for each medication considered for therapeutic equivalence evaluations. www.fda.gov/
inclusion in the formulary and should ensure those safety cder/ob/ (accessed 2008 Sep 24).
concerns are addressed if the medication is added to the for-
mulary or used in the health system.
The committee should minimize unnecessary duplica-
tion of the same basic drug type, drug entity, or drug product.
Optimizing the number of drug entities and products avail- This statement was reviewed in 2012 by the Council on Pharmacy
able from the pharmacy can produce substantial patient care Practice and by the Board of Directors and was found to still be
and financial benefits. These benefits are greatly increased appropriate.
through the use of generic equivalents (drug products con-
sidered identical or equivalent by FDA) and therapeutic Approved by the ASHP Board of Directors on January 23, 2008
equivalents (drug products differing in composition or basic and by the ASHP House of Delegates on June 10, 2008. Developed
drug entity that are considered to have similar pharmaco- through the ASHP Council on Pharmacy Practice. This statement
logic and therapeutic activities).2 The P&T committee must supersedes the ASHP Statement on Pharmacy and Therapeutics
set forth policies and procedures that govern the dispensing Committee dated November 20, 1991, and the ASHP Statement on
of generics and therapeutic equivalents. the Formulary System dated November 18, 1982.
Linda S. Tyler, Pharm.D., FASHP; Mirta Millares, Pharm.D., M.P.A., FASHP; Katharine Kiser, Pharm.D.; Thomas L. Kurt,
FCSHP, FASHP; Andrew L. Wilson, Pharm.D., FASHP; Lee C. M.D., M.P.H., FACPM, FACMMT, FAACT, FCP, FACE (ASCPT);
Vermeulen, Jr., B.S.Pharm., M.S.; J. Russell (Rusty) May, Pharm.D., Timothy R. Lanese, M.B.A., FASHP, FACHE; Rosario (Russ) J.
FASHP; Michael A. Valentino, M.H.S.A.; and Sabrina W. Cole, Lazzaro, M.S.; Melvin E. Liter, M.S., Pharm.D.; Patrick M. Malone,
Pharm.D., are gratefully acknowledged for drafting this statement. Pharm.D., FASHP; Candis M. Morello, Pharm.D., CDE, FCSHP;
The drafters have declared no potential conflicts of interest. Richard O’Brocta, Pharm.D., BCPS; Folakemi T. Odedina, Ph.D.;
James A. Ponto, M.S., BCNP, FASHP; Curt W. Quap, M.S.; Mike
ASHP also acknowledges the following organizations and indi Rouse, B.Pharm., M.P.S.; Marissa Schlaifer, M.S. (AMCP); Shelley
viduals for reviewing drafts of this statement: Academy of Managed Hoppe Schliesser, Pharm.D.; Michele F. Shepherd, Pharm.D., M.S.,
Care Pharmacy (AMCP); American Nurses Association (ANA); BCPS, FASHP; Jonalan Smith, Pharm.D. (ASCP); Allen J. Vaida,
American Society for Clinical Pharmacology and Therapeutics Pharm.D., FASHP (ISMP); William E. Wade, Pharm.D., FASHP,
(ASCPT); American Society of Consultant Pharmacists (ASCP); FCCP; Tom W. Woller, M.S., FASHP; and John L. Woon, Pharm.D.,
Institute for Safe Medication Practices (ISMP); Pharmacy Com FASHP. (Review does not imply endorsement.)
pounding Accreditation Board (PCAB); Daniel T. Abazia, Pharm.D.;
Philip Anderson, Pharm.D., FASHP; Lilian M. Azzopardi, Copyright © 2008, American Society of Health-System Pharmacists,
B.Pharm., M.Phil., Ph.D.; Kenneth R. Baker, J.D. (PCAB); James Inc. All rights reserved.
L. Besier, Ph.D., FASHP; J. Lyle Bootman, Ph.D., Sc.D.; David
G. Bowyer, B.S.; Maureen Brady, Pharm.D.; Margaret Chrymko, The bibliographic citation for this document is as follows: American
Pharm.D., FASHP; Joseph W. Cranston, Ph.D.; Steven Dzierba, Society of Health-System Pharmacists. ASHP statement on the
M.S., FASHP; Michael Gaunt, Pharm.D. (ISMP); Pamela C. pharmacy and therapeutics committee and the formulary system.
Hagan, M.S.N., R.N. (ANA); Raymond W. Hammond, Pharm.D., Am J Health-Syst Pharm. 2008; 65:2384–6.
BCPS, FCCP; Eric T. Hola, M.S.; Patricia Kienle, B.S.Pharm.,
Formulary Management–Statements 173
ASHP Statement on the Use of

Medications for Unlabeled Uses
The freedom and responsibility to make drug therapy deci- Lack of Practice Standards. Well-defined medical practice
sions that are consistent with patient-care needs is a funda- standards that differentiate between experimental therapies
mental precept supported by ASHP. This activity is a profes- and established practice will probably always be some-
sional duty of pharmacists not limited by language in Food what lacking, owing to the advancement of medical science
and Drug Administration (FDA)-approved product labeling. and the dynamic nature of medical practice. Standards of
The prescribing, dispensing, and administration of practice for certain drug therapies, particularly biotechno-
FDA-approved drugs for uses, treatment regimens, or pa- logically produced drugs, cancer chemotherapy, and AIDS
tient populations that are not reflected in FDA-approved treatments, are continually evolving. The dynamic nature of
product labeling often represent a therapeutic approach these drug therapies makes it difficult for professional so-
that has been extensively studied and reported in medical cieties to review scientific data expediently and to develop
literature. Such uses are not indicative of inappropriate us- standards that remain absolutely current.
age. Health-care professionals should appreciate the critical
Failure of Package Insert and FDA-Approved Labeling to
need for freedom in making drug therapy decisions and un-
Reflect Current Practice. For FDA-approved product label-
derstand the implications of unlabeled uses. ASHP supports
ing to be modified, scientific data must be submitted by a
third-party reimbursement for FDA-approved drug products
product’s manufacturer to FDA to support any additional
appropriately prescribed for unlabeled uses.
indication(s) and dosage regimen(s). Once they are submit-
ted, FDA must review the data and make a decision to permit
Definition of Unlabeled Use alteration of the package insert.
Knowing that unlabeled uses are permitted, and know-
The FDA approves drug products for marketing in the United ing that the accumulation and submission of scientific data
States. Such a product approved for marketing is often termed to FDA to modify labeling is a time-consuming and often ex-
an “FDA-approved drug.” FDA also approves each drug pensive process, some pharmaceutical manufacturers elect
product’s labeling (container label, package insert, and certain not to pursue labeling changes. Therefore, a product’s label-
advertising); the term “FDA-approved labeling” applies here. ing sometimes fails to represent the most current therapeutic
Drug uses that are not included in the indications or dosage information for a drug, and situations naturally occur when it
regimens listed in the FDA-approved labeling are defined as is appropriate to prescribe drugs for unlabeled uses.
“unlabeled uses.” For purposes of this document, unlabeled
use includes the use of a drug product in (1) doses, (2) patient
populations, (3) indications, or (4) routes of administration
Pharmacist’s Role
that are not reflected in FDA-approved product labeling.
ASHP believes that pharmacists in organized health-care
It is important to recognize that FDA cannot approve
settings bear a significant responsibility for ensuring optimal
or disapprove physician prescribing practices of legally mar-
outcomes from all drug therapy. With respect to unlabeled
keted drugs. FDA does regulate what manufacturers may
uses, the role of the pharmacist should be to
recommend about uses in their products’ labeling and what
manufacturers can include in advertising and promotion.
1. Fulfill the roles of patient advocate and drug informa-
The sometimes-used term “unapproved use” is a misno-
tion specialist.
mer, implying that FDA regulates prescribing and dispensing
2. Develop policies and procedures for evaluating drug
activities. This term should be avoided.1 Other terminology that
orders (prescriptions) and dispensing drugs for unla-
is sometimes used to describe unlabeled use includes “off-label
beled uses in their own work settings. Such policies
use,” “out-of-label use,” and “usage outside of labeling.”
and procedures might address the documentation of
According to FDA, unlabeled use encompasses a range
scientific support, adherence to accepted medical prac-
of situations that extend from inadequate to carefully con-
tice standards, or a description of medical necessity.
ceived investigations, from hazardous to salutary uses, and
3. Develop proactive approaches to promote informed
from infrequent to widespread medical practice. Accepted
decisionmaking by third-party payers for health-care
medical practice often involves drug use that is not reflected
services.
in FDA-approved drug-product labeling.2
Role of Drug Information Compendia

Health-Care Issues Related to
Unlabeled Use The Medicare Catastrophic Coverage Act of 1988 (now re
pealed) included the statements that “in carrying out the leg-
Access to Drug Therapies. The prescribing and dispensing islation, the Secretary [of Health and Human Services] shall
of drugs for unlabeled uses are increasing.3,4 In many clini- establish standards for drug coverage. In establishing such
cal situations, unlabeled use represents the most appropriate standards, which are based on accepted medical practice, the
therapy for patients. Failure to recognize this or, more im- Secretary shall incorporate standards from such current au-
portantly, regarding such use as “unapproved” or “experi- thoritative compendia as the Secretary may select.”5 Specific
mental” may restrict access to necessary drug therapies. compendia recommended were the AHFS Drug Information,
AMA Drug Evaluations, and USP Dispensing Information, have sometimes elected to cover only those indications in-
Volume I. Despite the repeal of the Act, some third-party cluded in FDA-approved drug-product labeling and have fre-
payers have adopted guidelines that endorse these three quently denied coverage for unlabeled uses of drug products.
compendia as authoritative information sources with respect ASHP believes that such coverage denials restrict
to unlabeled uses for drug products. patients from receiving medically necessary therapies that
represent the best available treatment options. A growing
Positions on Unlabeled Use number of insurance carriers are following the BC/BS and
HIAA guidelines that encourage the use of the three au-
FDA Position. A statement entitled “Use of Approved Drugs thoritative drug compendia, peer-reviewed literature, and
for Unlabeled Indications” was published in the FDA Drug consultation with experts in research and clinical practice to
Bulletin in April 1982 to address the issues of appropriate- make specific coverage decisions. ASHP supports informed
ness and legality of prescribing approved drugs for uses not decisionmaking that promotes third-party reimbursement
included in FDA’s approved labeling. This statement infor FDA-approved drug products appropriately prescribed
cluded the following: for unlabeled uses.
The Food, Drug and Cosmetic Act does not limit the References
manner in which a physician may use an approved
drug. Once a product has been approved for market- 1. Use of approved drugs for unlabeled indications. FDA
ing, a physician may prescribe it for uses or in treat- Drug Bull. 1982; 12:4–5.
ment regimens or patient populations that are not 2. Nightingale SL. Use of drugs for unlabeled indica-
included in approved labeling. Such “unapproved” tions. FDA Q Rep. 1986(Sep); 269.
or, more precisely, “unlabeled” uses may be appropri- 3. Mortenson LE. Audit indicates many uses of combi
ate and rational in certain circumstances, and may, in nation therapy are unlabeled. J Cancer Program
fact, reflect approaches to drug therapy that have been Manage. 1988; 3:21–5.
extensively reported in medical literature.1 4. Off-label drugs: initial results of a national survey.
Washington, DC: U.S. General Accounting Office.
Other Organizations. Other organizations that have pub- 1991:1–27.
lished positions on the issue of unlabeled uses of drug prod- 5. PL 100-360, 1988.
ucts are the Health Care Financing Administration (HCFA),6 6. Health Care Financing Administration. Medicare
the Blue Cross and Blue Shield Association of America carriers’ manual. Section 2050.5. Washington, DC: U.S.
(BC/BS),7 and the Health Insurance Association of America Department of Health and Human Services; 1987 Aug.
(HIAA).8 7. Statement on coverage recommendation for FDA-
The American Medical Association, American Society approved drugs. Chicago: Blue Cross and Blue
of Clinical Oncology, Association of American Cancer Shield Association; 1989 Oct 25.
Institutes, Association of Community Cancer Centers, 8. Statement of the Health Insurance Association of
Candlelighters Childhood Cancer Foundation, Memorial America (HIAA) on coverage for unapproved drugs
Sloan Kettering Cancer Center, National Cancer Institute, and drug-related costs. Presented to the National
and the National Institute of Allergy and Infectious Committee to Review Current Procedures for Approval
Diseases jointly developed a consensus statement and of New Drugs for Cancer and AIDS. 1989 Oct 25.
recommendations regarding use and reimbursement of 9. Cancer economics. Cancer Lett. 1989; Suppl(Jun):2–3.
unlabeled uses of drug products.9
These statements are consistent with the ASHP position.
Reimbursement Issues Approved by the ASHP Board of Directors, November 20, 1991,
and by the ASHP House of Delegates, June 1, 1992. Developed by
As a cost-containment measure, most third-party pay- the Council on Professional Affairs.
ers exclude coverage for experimental therapies. Drug
therapy coverage decisions are complicated, because often Copyright © 1992, American Society of Hospital Pharmacists, Inc.
it is difficult to differentiate among an accepted standard All rights reserved.
of practice, an evolving standard of practice, and investi-
gational therapies. Data demonstrating medical necessity The bibliographic citation for this document is as follows: American
and improved patient outcome are often difficult to retrieve. Society of Hospital Pharmacists. ASHP statement on the use of med-
Consequently, insurance carriers and managed care providers ications for unlabeled uses. Am J Hosp Pharm. 1992; 49:2006–8.
Formulary Management–Guidelines 175
ASHP Guidelines on Medication-Use Evaluation

Medication-use evaluation (MUE) is a performance improve Steps of the MUE Process
ment method that focuses on evaluating and improving medi
cation-use processes with the goal of optimal patient outcomes. While the specific approach varies with the practice setting
MUE may be applied to a medication or therapeutic class, dis- and patient population being served, the following common
ease state or condition, a medication-use process (prescribing, steps occur in the ongoing MUE process:
preparing and dispensing, administering, and monitoring), or
specific outcomes.1 Further, it may be applied in and among the • Establish organizational authority for the MUE pro-
various practice settings of organized health systems. cess and identify responsible individuals and groups.
MUE encompasses the goals and objectives of drug- • Develop screening mechanisms (indicators) for com-
use evaluation (DUE) in its broadest application, with an prehensive surveillance of the medication-use system.
emphasis on improving patient outcomes. Use of “MUE,” • Set priorities for in-depth analysis of important aspects
rather than “DUE,”2 emphasizes the need for a more mul- of medication use.
tifaceted approach to improving medication use. MUE has • Inform health care professionals (and others as neces-
a common goal with the pharmaceutical care it supports: sary) in the practice setting(s) about the objectives and
to improve an individual patient’s quality of life through expected benefits of the MUE process.
achievement of predefined, medication-related therapeutic • Establish criteria, guidelines, treatment protocols, and
outcomes.3,4 Through its focus on the system of medication standards of care for specific medications and medi-
use, the MUE process helps to identify actual and potential cation-use processes. These should be based on sound
medication-related problems, resolve actual medication- scientific evidence from the medical and pharmaceuti-
related problems, and prevent potential medication-related cal literature.
problems that could interfere with achieving optimum out- • Educate health care professionals to promote the use
comes from medication therapy. of criteria, guidelines, treatment protocols, and stan-
In organized health systems, MUE must be conducted dards of care.
as an organizationally authorized program or process that is • Establish mechanisms for timely communication
proactive, criteria based, designed and managed by an inter- among health care professionals.
disciplinary team, and systematically carried out. It is con- • Initiate the use of MUE criteria, guidelines, treatment
ducted as a collaborative effort of prescribers, pharmacists, protocols, and standards of care in the medication-use
nurses, administrators, and other health care professionals process.
on behalf of their patients. • Collect data and evaluate care.
• Develop and implement plans for improvement of the
MUE Objectives medication-use process based on MUE findings (if in-
dicated).
Some typical objectives of MUE include • Assess the effectiveness of actions taken, and docu-
ment improvements.
• Promoting optimal medication therapy. • Incorporate improvements into criteria, guidelines, treat-
• Preventing medication-related problems. ment protocols, and standards of care, when indicated.
• Evaluating the effectiveness of medication therapy. • Repeat the cycle of planning, evaluating, and taking
• Improving patient safety. action for ongoing improvement in medication-use
• Establishing interdisciplinary consensus on medica- processes.
tion-use processes. • Regularly assess the effectiveness of the MUE process
• Stimulating improvements in medication-use processes. itself and make needed improvements.
• Stimulating standardization in medication-use pro-
cesses. Selecting Medications and
• Enhancing opportunities, through standardization, to assess Medication-Use Processes for Evaluation
the value of innovative medication-use practices from both
patient-outcome and resource-utilization perspectives. Medications or medication-use processes should be selected
• Minimizing procedural variations that contribute to for evaluation for one or more of the following reasons:
suboptimal outcomes of medication use.
• Identifying areas in which further information and 1. The medication is known or suspected to cause ad-
education for health care professionals may be needed. verse reactions, or it interacts with another medication,
• Minimizing costs of medication therapy. These costs food, or diagnostic procedure in a way that presents a
may be only partly related to the direct cost of medi- significant health risk.
cations themselves. When medications are selected and 2. The medication is used in the treatment of patients
managed optimally from the outset, the costs of compli- who may be at high risk for adverse reactions.
cations and wasted resources are minimized, and over- 3. The medication-use process affects a large number of
all costs are decreased. patients or the medication is frequently prescribed.
• Meeting or exceeding internal and external quality stan- 4. The medication or medication-use process is a critical
dards (e.g., professional practice standards, accredita- component of care for a specific disease, condition, or
tion standards, or government laws and regulations). procedure.
176 Formulary Management–Guidelines
5. The medication is potentially toxic or causes discom- • Collecting, analyzing, and evaluating patient-specific
fort at normal doses. data to identify, resolve, and prevent medication-
6. The medication is most effective when used in a spe- related problems.
cific way. • Interpreting and reporting MUE findings and recom-
7. The medication is under consideration for formulary mending changes in medication-use processes.
retention, addition, or deletion. • Providing information and education based on MUE
8. The medication or medication-use process is one for findings.
which suboptimal use would have a negative effect on
patient outcomes or system costs.
Resources
9. Use of the medication is expensive.
Some resources helpful in designing and managing an MUE
Indicators Suggesting a process are listed here.
Need for MUE Analysis
• The primary professional literature and up-to-date ref-
Certain events (indicators) serve as “flags” of potential op- erence texts are key resources necessary for the devel-
portunities to improve medication use. Some are opment of MUE criteria. In general, local consensus
should be based on medical and pharmaceutical litera-
• Adverse medication events, including medication errors, ture recommendations.
preventable adverse drug reactions, and toxicity. • Published criteria, such as found in AJHP and ASHP’s
• Signs of treatment failures, such as unexpected readmis Criteria for Drug Use Evaluation (volumes 1–4), pro-
sions and bacterial resistance to anti-infective therapy. vide medication-specific criteria that may be adapted
• Pharmacist interventions to improve medication ther- for local use.
apy, categorized by medication and type of intervention. • Computer software programs, including proprietary
• Nonformulary medications used or requested. programs designed specifically for MUE functions,
• Patient dissatisfaction or deterioration in quality of life. may be helpful in managing data and reporting.
• External standards-setting bodies, such as the
Roles and Responsibilities Joint Commission on Accreditation of Healthcare
Organizations, publish medication-use indicators that
in the MUE Process
can help to identify portions of the medication-use sys-
tem that require improvement.
The roles of individual health care professionals in MUE
may vary according to practice setting, organizational goals,
and available resources. The organizational body (e.g., qual- Follow-up Actions in an MUE Process
ity management committee, pharmacy and therapeutics
committee) responsible for the MUE process should have, The MUE process itself should be reviewed regularly to iden
at a minimum, prescriber, pharmacist, nurse, and adminis tify opportunities for its improvement. The success of an MUE
trator representation. Other health care professionals should process should be assessed in terms of improved patient out-
contribute their unique perspectives when the evaluation and comes. Medication-use system changes that evolve from MUE
improvement process addresses their areas of expertise and findings should be developed by the departments and medi-
responsibility. Temporary working groups may be used for cal services with responsibility for providing care, rather than
specific improvement efforts. solely through a committee having oversight for MUE (e.g., a
pharmacy and therapeutics committee). Typical follow-up ac-
Pharmacist’s Responsibilities in MUE tions based on MUE findings include contact with individual
prescribers and other health care professionals, information
Pharmacists, by virtue of their expertise and their mission and education (newsletters, seminars, clinical care guidelines)
of ensuring proper medication use, should exert leadership for health care professionals, changes in medication-use sys-
and work collaboratively with other members of the health tems, and changes in medication-therapy monitoring processes.
care team in the ongoing process of medication-use evalua- MUE should be conducted as an ongoing interdisciplinary and
tion and improvement.5 Responsibilities of pharmacists in collaborative improvement process. Punitive reactions to qual-
the MUE process include ity concerns are often counterproductive. It is important to com-
municate and commend positive achievements (care that meets
• Developing an operational plan for MUE programs or exceeds expectations) and improvements.
and processes that are consistent with the health sys-
tem’s overall goals and resource capabilities. Pitfalls
• Working collaboratively with prescribers and others to
develop criteria for specific medications and to design Some common pitfalls to avoid in performing MUE activi-
effective medication-use processes. ties include the following:6
• Reviewing individual medication orders against medi-
cation-use criteria and consulting with prescribers and 1. Lack of authority. An MUE process that does not in-
others in the process as needed. volve the medical staff is likely to be ineffective.
• Managing MUE programs and processes. Authoritative medical staff support and formal organi-
zational recognition of the MUE process are necessary.
2. Lack of organization. Without a clear definition of the roles computerized information management resources.
and responsibilities of individuals involved (e.g., who will Deficiencies in information gathering and analysis
develop criteria, who will communicate with other depart- should be identified and priorities for upgrading infor-
ments, who will collect and summarize data, and who will mation support established.
evaluate data), an MUE process may not succeed.
3. Poor communication. Everyone affected by the MUE References
process should understand its importance to the health
system, its goals, and its procedures. The pharmacist 1. Nadzam DM. Development of medication-use indi-
should manage the MUE process and have the respon- cators by the Joint Commission on Accreditation of
sibility and authority to ensure timely communication Healthcare Organizations. Am J Hosp Pharm. 1991;
among all professionals involved in the medication- 48:1925–30.
use process. Criteria for medication use should be 2. American Society of Hospital Pharmacists. ASHP
communicated to all affected professionals prior to the guidelines on the pharmacist’s role in drug-use evalu-
evaluation of care. MUE activity should be a standing ation. Am J Hosp Pharm. 1988; 45:385–6.
agenda item for appropriate quality-of-care commit- 3. Hepler CD, Strand LM. Opportunities and responsibil-
tees responsible for aspects of medication use. ities in pharmaceutical care. Am J Hosp Pharm. 1990;
4. Poor documentation. MUE activities should be well 47:533–43.
documented, including summaries of MUE actions 4. American Society of Hospital Pharmacists. ASHP
with respect to individual medication orders and the statement on pharmaceutical care. Am J Hosp Pharm.
findings and conclusions from collective evaluations. 1993; 50:1720–3.
Documentation should address recommendations 5. Angaran DM. Quality assurance to quality improve-
made and follow-up actions. ment: measuring and monitoring pharmaceutical care.
5. Lack of involvement. The MUE process is not a Am J Hosp Pharm. 1991; 48:1901–7.
one-person task, nor is it the responsibility of a single 6. Todd MW. Drug use evaluation. In: Brown TR, ed.
department or professional group. Medication-use cri- Handbook of institutional pharmacy practice. 3rd
teria should be developed through an interdisciplinary ed. Bethesda, MD: American Society of Hospital
consensus process. Lack of administrative support can Pharmacists; 1992.
severely limit the effectiveness of MUE. The benefits
of MUE should be conveyed in terms of improving
patient outcomes and minimizing health-system costs. Approved by the ASHP Board of Directors, April 24, 1996.
6. Lack of follow-through. A one-time study or evalua- Developed by the ASHP Council on Professional Affairs.
tion independent of the overall MUE process will have Supersedes the ASHP Guidelines on the Pharmacist’s Role in
limited success in improving patient outcomes. The Drug-Use Evaluation, dated November 19, 1987.
effectiveness of initial actions must be assessed and
the action plan adjusted if necessary. It is important not Copyright © 1996, American Society of Health-System Pharmacists,
to lose sight of the improvement goals. Inc. All rights reserved.
7. Evaluation methodology that impedes patient care. Data
collection should not consume so much time that patient The bibliographic citation for this document is as follows:
care activities suffer. Interventions that can improve care American Society of Health-System Pharmacists. ASHP guide-
for an individual patient should not be withheld because lines on medication-use evaluation. Am J Health-Syst Pharm.
of the sampling technique or evaluation methodology. 1996; 53:1953–5.
8. Lack of readily retrievable data and information man-
agement. Existing data capabilities need to be as-
sessed and maximum benefit obtained from available
ASHP Guidelines on the Pharmacy and Therapeutics

Committee and the Formulary System
Purpose (AHA) issued joint statements on the legality of formu
laries.11,12 AMA and the American Pharmaceutical (later
These guidelines outline the recommended processes and Pharmacists) Association subsequently joined with ASHP
techniques for formulary system management and describe and AHA to revise the statements.13 In 1965, two signifi-
the pharmacist’s responsibilities and roles in managing cant events occurred: (1) Medicare listed formularies as a
the formulary system in partnership with other health care reimbursement eligibility requirement14 and (2) the Joint
professionals. These guidelines also provide assistance to Commission on the Accreditation of Hospitals (now known
pharmacists in the organization and operation of the phar- as the Joint Commission) included an active P&T commit-
macy and therapeutics (P&T) committee or equivalent body, tee in its accreditation requirements.15 Even with these ac-
evaluation of medications for formularies, and development tions, formularies were typically no more than lists of drugs
and implementation of strategies to manage medication use stocked by the pharmacy.
through the formulary system. A glossary of terms is pro- By the 1980s, literature describing the clinical and
vided in the appendix. economic value of well-designed formularies had emerged.
Evidence from the hospital setting was published first, soon
followed by evidence from the ambulatory care environ-
Formulary and Formulary System ment.10 This literature led to more widespread acceptance
of formularies. In 1986, the Pharmaceutical Research and
A formulary is a continually updated list of medications and Manufacturers Association officially accepted the concept of
related information, representing the clinical judgment of therapeutic interchange in hospitals and opposed its use in
physicians, pharmacists, and other experts in the diagno- other settings.10 As more evidence emerged, AMA’s views on
sis, prophylaxis, or treatment of disease and promotion of formularies for inpatient and outpatient settings became more
health. A formulary includes, but is not limited to, a list of closely aligned with those of ASHP. AMA’s official policy on
medications and medication-associated products or devices, drug formularies and therapeutic interchange was first pub-
medication-use policies, important ancillary drug informa- lished in 199416 and has since been updated several times.5
tion, decision-support tools, and organizational guidelines. Today, formulary systems are considered an essential tool
A formulary system is the ongoing process through which a for health care organizations. Formularies have grown from
health care organization establishes policies regarding the use simple drug lists to comprehensive systems of medication-
of drugs, therapies, and drug-related products and identifies use policies intended to ensure safe, appropriate, and cost-
those that are most medically appropriate and cost-effective effective use of pharmaceuticals in patient care.
to best serve the health interests of a given patient popula-
tion.1 Formulary systems are used in many different settings,
including hospitals, acute care facilities, home care settings, P&T Committee
and long-term-care facilities, as well as by payers such as
Medicare, Medicaid, insurance companies, and managed care The P&T committee is responsible for managing the formu-
organizations. Many organizations have policy statements on lary system. It is composed of actively practicing physicians,
other prescribers, pharmacists, nurses, administrators, quality-
the use of formularies.2–8 This document focuses on the use of
improvement managers, and other health care professionals
formulary systems in hospitals and health systems.
and staff who participate in the medication-use process.
Customarily, P&T committee member appointments are
Evolution of Formularies based on guidance from the medical staff. The P&T commit-
tee should serve in an evaluative, educational, and advisory
Formulary systems have evolved over time. Modern for- capacity to the medical staff and organizational administra-
mularies began as rudimentary drug lists developed by the tion in all matters pertaining to the use of medications (in-
military in the 1940s and came into more widespread use cluding investigational medications). The P&T committee
during the 1950s. Pharmacists, in conjunction with their or- should be responsible for overseeing policies and procedures
ganizations, developed policies to dispense generic equiva- related to all aspects of medication use within an institution.
lent drugs when a specific brand-name drug was prescribed. The P&T committee is responsible to the medical staff as
Protests from the National Pharmaceutical Council and the a whole, and its recommendations are subject to approval
American Medical Association (AMA) resulted in state laws by the organized medical staff as well as the administrative
prohibiting this activity. Community pharmacies complied, approval process. The P&T committee’s organization and
but hospital pharmacies resisted. In the late 1950s, the ASHP authority should be outlined in the organization’s medical
minimum standard for pharmacies in hospitals called for the staff bylaws, medical staff rules and regulations, and other
implementation of a formulary system.9 organizational policies as appropriate.
During the 1960s, the concept of a hospital formu- Other responsibilities of the P&T committee include med-
lary continued to grow. Hospitals developed policies that ication-use evaluation (MUE), adverse-drug-event monitoring
authorized pharmacists to make generic interchanges in an and reporting, medication-error prevention, and development
institutional formulary system based on prior consent from of clinical care plans and guidelines. Information about these
physicians.10 ASHP and the American Hospital Association activities is available in ASHP guidelines on the topics.17–20
P&T committees have been credited with increasing policies, the therapies offered by the organization, and the
practitioners’ knowledge about drug therapy, improving medications routinely stocked in the pharmacy. A formulary
the safety of drug therapy, and improving therapeutic out- also identifies those medications that are most medically ap-
comes.21 propriate and cost-effective to best serve the health interests
Consideration of patient care and unbiased reviews of of the health system’s patient population. The P&T commit
the biomedical literature are the cornerstone principles of tee should interpret the term medication broadly in the con-
formulary decision-making. A conflict of interest (COI), fi- text of care delivery to include alternative remedies (herbals
nancial or otherwise, may interfere with professionals’ ability and supplements), nonprescription drugs, blood derivatives,
to make evidence-based decisions,22 and even the appearance contrast media, and other diagnostic and treatment agents.26
of a potential COI can undermine a formulary decision. The The formulary system should include review and ap-
P&T committee has a responsibility to its patients and its or- proval of all policies related to the medication-use process.
ganization to identify and address COI issues in its decision- All medication-use policies, regardless of their origination,
making processes. Professionals participating in the P&T should flow through the P&T committee. The organiza-
committee should disclose financial relationships with phar- tion’s medical staff leadership (i.e., the body to which the
maceutical manufacturers, medical supply vendors, other P&T committee reports) should complete the final policy
health care provider organizations, and other commercial approval. Policy review and revision should occur as new
interests. Some health care organizations exclude heath care information becomes available and at regularly established
professionals with COIs from P&T committee membership, intervals (e.g., annually). Specific medication-use policies
whereas others allow participation in committee discussions should address
but prohibit voting on particular items. Practitioners request-
ing additions or changes to the formulary should disclose • How medications are requested for addition to or dele-
financial relationships with pharmaceutical companies and tion from the formulary,
other potential COIs to the P&T committee. • How medications are reviewed for addition to or dele-
Finally, the role of pharmaceutical company represen- tion from the formulary, including who performs the
tatives and medical science liaisons in a health care organi- reviews,
zation should be carefully considered. Organizational guide- • The process for developing, implementing, and moni-
lines should define appropriate relationships and interactions toring medication-use guidelines,
with such individuals. At a minimum, these guidelines • Methods for ensuring the safe prescribing, distribu-
should address the provision of pharmaceutical samples, tion, administration, and monitoring of medications,
indirect or direct funding support, and educational program- • Methods for selection of suitable manufacturers for
ming regarding formulary and nonformulary medications. specific medications (a pharmacist shall be respon-
Applications for formulary additions should be initiated and sible for specifications for the quality, quantity, and
completed independently by the requesting health care pro- source of supply of all medications, chemicals, bio-
vider and not by an industry representative or vendor. Refer logicals, and pharmaceutical preparations used in the
diagnosis and treatment of patients),27
to ASHP’s “Guidelines on Pharmacists’ Relationships with
Industry” for more information on appropriate interactions • The process for using nonformulary agents within the
institution,
with industry.23
• The process for managing drug product shortages,
• The process for developing an organization-specific
Managing the Formulary System MUE plan,
• Policies regarding specific medication-use processes
Health systems should develop, maintain, and implement (e.g., procurement, prescribing, distribution, adminis-
a formulary management process. Decisions on the man- tration, monitoring), and
agement of a formulary system should be founded on the • The process for disseminating medication-use policies
evidence-based clinical, ethical, legal, social, philosophical, and how users will be educated regarding the process.
quality-of-life, safety, and economic factors that result in op-
timal patient care.24,25 The process must include the active A formal process to review medication-use policies
and direct involvement of physicians, pharmacists, and other should be in place. This process may include the use of ex-
appropriate health care professionals. This evidence-based pert panels or subcommittees of the P&T committee. Expert
process should not be based solely on economic factors. panels should serve in an advisory role to the P&T commit
The formulary system should be standardized among com- tee, and their membership should include recognized experts
ponents of integrated health systems when standardization in their areas of practice. Such panels can be helpful in ap
leads to improved patient outcomes and safety. plying clinical study results to specific patient populations,
Management of a formulary system is a significant com and panel members can help educate groups of physicians,
ponent of a health care organization’s ongoing medication- who ultimately drive prescribing behaviors, about signifi
use policy development process. A comprehensive, well- cant formulary changes. User groups, representing those
maintained formulary that is tailored to the organization’s primarily affected by the policy, may also be helpful. The
patient care needs, policy framework, and medication-use P&T committee may also find subcommittees that address
systems ensures that the six critical processes identified by specific therapeutic areas to be beneficial (e.g., antimicro
the Joint Commission (selection and procurement, storage, bial, cancer chemotherapy, cardiovascular, adverse-drug-
ordering and transcribing, preparing and dispensing, admin- reaction, or biotechnology subcommittees).
istration, and monitoring) work in concert to ensure optimal The P&T committee should have formal interactions
outcomes.26 A well-managed formulary system ensures a (i.e., communication lines) with other committees whose
close relationship among the organization’s medication-use functions may affect the medication-use process. These
committees would include those responsible for develop- grade evidence when evaluating formulary requests; several
ing tools to facilitate medication use (e.g., forms or order tools are available for this purpose.28–32
set review committee, computerized prescriber-order-entry Published evidence and expert opinion are not the only
committee), those concerned with safety or performance resources available to aid in the formulary decision-making
improvement (e.g., quality-improvement or patient safety process. Internal data and prescribing and outcomes informa-
committees), those involved in developing patient care poli- tion may be helpful in formulary decision-making. When pub-
cies (e.g., medical and nursing committees), those involved lished data are not available, it may be appropriate to incorpo-
with investigational medications (e.g., investigational re- rate expert opinion into the review process. Experts in practice
view boards), and other committees whose actions may af- areas sometimes have access to unpublished data or reports
fect medication use (e.g., nutrition, equipment and supply, that may offer insight into difficult formulary decisions.
or finance committees). Recommendations from other com- The P&T committee should use formulary packets and
mittees, subcommittees of P&T, expert panels, and others dossiers prepared by pharmaceutical manufacturers with
should be submitted to the P&T committee for review. P&T the utmost caution, since the objectivity of these documents
committee decisions on recommendations should be com- may be challenged. The formulary decision-making process
municated to the recommending group in a timely fashion. should instead be guided by an independent review of evi-
dence published in the biomedical literature, application of
Evaluating Medications for expert opinion, and use of internal data and benchmarking
programs.
Inclusion in the Formulary
The information should be provided to the P&T com-
mittee in a written document with a standard format (e.g., a
The P&T committee should use a structured, evidence-based
drug monograph, drug review, drug-evaluation document).
process in the evaluation of medications for formulary con-
All information provided in the drug-evaluation document
sideration. The P&T committee should be provided with in-
should be referenced to the evidence or identified as a con-
formation that reflects a thorough, accurate, and unbiased re-
clusion supported by evidence. Any areas of consensus rec-
view and analysis of the evidence available in the scientific
ommendations or opinion should be clearly identified.
literature. The evaluation process should encourage objec-
tive consideration of clinical and care delivery information,
facilitate communication, foster positive patient outcomes, Types of Drug Reviews. There are four major types of drug
and support safe and effective medication ordering, dispens- reviews: new drug monographs, reevaluations of previous
ing, administration, and monitoring. Decisions made by the formulary decisions, therapeutic class reviews, and expe-
P&T committee should support improved patient care out- dited reviews of newly approved medications. Because of
comes across the continuum of care. the expertise and training of pharmacists (drug information
specialists in particular), pharmacists should play an integral
Evidence-Based Evaluation. Inclusion of a medication on part in the preparation and presentation of the drug review
a health system’s formulary should reflect that an evidence- document to the P&T committee.
based evaluation of the relative merits and risks of the medi- New drug monographs. When the Food and Drug
cation has been performed and that the institution’s P&T Administration (FDA) approves a new drug for market-
committee, with input from appropriate experts, has deter- ing that is relevant to the health system, a drug monograph
mined that the medication is appropriate for routine use in should be prepared for formulary consideration by the P&T
the management of the patient population at that institution. committee. New chemical entities warrant a thorough evalu-
Evidence-based medicine is a systematic approach to ation and a written drug monograph. A short (e.g., one-page)
the evaluation of biomedical literature and application to summary could be provided along with the full monograph.33
clinical practice and should be applied to formulary decision- Some organizations use an executive summary format. A
making for medication product selection.24 Evidence-based new drug that is significantly similar to other available ther-
decision-making standardizes and improves the quality of apeutic alternatives may be presented in a more abbreviated
patient care and promotes cost-effective prescribing.24,25 To manner (e.g., an abbreviated monograph) provided that the
practice evidence-based medicine, practitioners must be pro- P&T committee or experts agree that the drug is therapeuti-
ficient in retrieving, evaluating, and applying the biomedical cally equivalent to agents already available on the formulary.
literature to clinical practice. Addenda to original monographs used to reevaluate
Evidence-based decision-making incorporates the sys- previous formulary decisions. Formulary decisions may
tematic approach to reviewing, evaluating, and applying the need to be reassessed based on relevant new information
biomedical literature to guide formulary decisions. Various or in light of newly marketed drugs or dosage forms. New
types and strengths of evidence (e.g., meta-analyses, ran- data on safety, efficacy, stability, methods of administration,
domized clinical trials, case reports, association consensus cost, or pharmacoeconomics may warrant a reevaluation
statements) may be useful in the decision-making process. of the drug or dosage strengths or formulations stocked by
Although different types of evidence are available for ap- the health system. An addendum to the original monograph
plication, those with stronger evidence should be used to summarizing the new information should be developed for
drive formulary decisions (e.g., meta-analyses, randomized evaluation by the P&T committee. The P&T committee may
controlled trials). Other types of evidence have a role in the want to establish reassessment dates at the time of formulary
decision-making process, however, and may be appropri- review so that the committee can reassess the effect of a for-
ate when stronger evidence is not available. Observational mulary decision on quality or cost of care.
studies (i.e., case–control and cohort studies), case reports, Therapeutic class reviews. Review of an entire thera-
and consensus opinions may be valuable even when stronger peutic class of drugs should be performed at regular inter-
evidence is available. Some organizations find it useful to vals, which may be determined by the P&T committee or
influenced by regulatory agencies. A therapeutic class re- Pharmacoeconomic Assessments. Rigorous pharmacoeco-
view should include all formulary and nonformulary medi- nomic evaluations can and should be conducted in some cases
cations within the class and may include institutional utili- when reviewing new medications. These evaluations should
zation or outcomes data and newly published information. explicitly state the perspective of the analysis (e.g., patient,
Therapeutic class reviews may lead to formulary removal of health care provider, payer) and should include consider-
therapeutically equivalent drugs or a change in restriction or ation of all costs and consequences relevant to that perspec-
guideline status for a drug. tive. When new medications being considered are found to
Expedited reviews. A process should be available for the be therapeutically equivalent to existing alternatives (having
P&T committee to conduct an expedited review of a new drug, equivalent efficacy and safety), then the cost-minimization
new indication for a drug, or reevaluation of a previous for- approach is appropriate. In these circumstances, it is im
mulary decision. Criteria should be in place to describe when portant to consider costs associated with the medication
an expedited review is warranted. For example, approval of a and nonmedication-related costs (e.g., costs of administra
new chemical entity for a disease with no therapeutic alterna- tion, monitoring, prolonged hospital stay, and laboratory test
tive may warrant an expedited review to ensure availability of monitoring; costs to patients and providers).
the drug for patients who need it. Likewise, a significant new While cost-effectiveness analysis (evaluating the in-
safety concern may warrant an expedited review for addition cremental difference in investment necessary to produce
of restrictions or removal from the formulary. an incremental difference in clinical outcome) is another
potentially useful analytic approach, it is not often used for
Elements of a Drug-Evaluation Document. The drug- formulary decision-making because of its complexity and
evaluation document should present the evidence in a man- need for strong evidence or data. The academic value of
ner that is thorough, is consistent from medication to medi- this approach lies in its ability to show how little (or how
cation, and provides all necessary facts and analysis to the much) must be spent to achieve a particular margin of clini-
P&T committee to allow for an informed formulary deci- cal advantage when comparing an alternative that is more
sion. Document structure may vary, depending on the needs expensive but safer or more efficacious. No standards cur-
of the specific health system and P&T committee, but the rently exist to determine how much money is reasonable to
following elements are essential to all such documents: spend for any given improvement in out-come; however, it
is unreasonable to recommend alternatives of lower quality
• Brand and generic names and synonyms, simply to achieve cost savings. This approach can be used to
• FDA approval information, including date and FDA demonstrate how a decrease in clinical outcomes associated
rating, with the use of a less expensive agent can be offset by invest-
• Pharmacology and mechanism of action, ing the savings achieved in other interventions that produce
• FDA-approved indications, even greater total benefits.
• Potential non-FDA-approved (off-label) uses, Cost-utility evaluations (evaluating the incremental
• Dosage forms and storage, difference in investment necessary to produce an incremen-
• Recommended dosage regimens, tal difference in quality-of-life-adjusted clinical outcome
• Pharmacokinetic considerations, [e.g., incremental cost per quality-adjusted life years gained
• Use in special populations (e.g., children, elderly, pa- for one medication versus another]) may also be beneficial
tients with renal or liver failure), by serving to reflect patient preference in formulary deci-
• Pregnancy category and use during breast-feeding,
sion-making. However, the same concerns related to the use
• Comparisons of the drug’s efficacy, safety, conve-
of cost-effectiveness evaluations apply to this approach.34–36
nience, and costs with those of therapeutic alternatives
Decision analysis models incorporating local data can
(with evidence tables when feasible),
be employed when published pharmacoeconomic data are
• If information on comparative efficacy is minimal or
limited or unavailable. Probabilities for each outcome can
lacking, data on absolute efficacy (i.e., efficacy versus
be extracted from the published literature or drawn from lo-
placebo),
cal data sources, which would provide a more relevant local
• Clinical trial analysis and critique,
perspective on outcomes. Costs associated with medications
• Medication safety assessment and recommendations
and outcomes should reflect those of the health care system.
(adverse drug reactions; drug–drug and drug–food in-
teractions; specific therapy monitoring requirements; Pharmacoeconomic analyses published in the medi-
unusual administration, storage, or stability issues; and cal literature or provided in the manufacturer’s formulary
potential for medication errors, such as look-alike or dossier should be analyzed carefully before being included
sound-alike issues), and as part of the review process. Particular attention should be
• Financial analysis, including pharmacoeconomic as- paid to the assumptions made in these studies. In many situ-
sessments. ations, assumptions made to simplify economic studies are
not valid in particular institutions. Institution-specific costs
Formulary status recommendations (e.g., from drug are often different from the costs used in published studies,
information services or expert groups) may be included in and local data should be used when incorporating their re-
the drug evaluation document. In some organizations, recom- sults into medication reviews.37,38
mendations are not provided in the written document in order Even if a formal pharmacoeconomic evaluation is not
to promote an unbiased discussion by the P&T committee. included in a drug review document, a financial evaluation
Recommendations should consider the formulary status (ad- must be conducted, including consideration of nonmedication-
dition or rejection) of a medication, as well as the need for related costs and financial consequences to the pharmacy
restrictions, educational efforts, or policies and procedures to and to the organization as a whole.
ensure safe and appropriate use within the health system.
Formulary Exceptions. Exclusion of a medication from a • The prescriber has the option, at the time of prescrib-
formulary may affect coverage of and access to the medi- ing, to specify the brand or supplier of the drug to be
cation. In a closed formulary system, for example, only dispensed for that particular medication order if con-
medications listed on the formulary are covered under the sidered clinically justified.
patient’s drug benefit. Regardless of health-system setting, • The prescriber’s decision should be based on pharma-
the formulary system should include an exception process cologic or therapeutic considerations (or both) relative
that provides prescribers and patients with timely access to to that patient.
medications that are not on the formulary but are medically
necessary for the care of the patient. The underlying princi- Therapeutic Interchange. Therapeutic interchange is the
ple for such a process is that unique patient needs may not be authorized exchange of therapeutic alternatives in accor-
satisfied by use of the formulary medications. The formulary dance with previously established and approved written
exception process should generate information on nonfor- guidelines, policies, or protocols within a formulary sys-
mulary medication use that will enable the P&T committee tem.1 Therapeutic interchange provides pharmacists with
to evaluate trends in such use. Criteria for approval of non- the authorization to use a formulary therapeutic alternative
formulary medications should be developed (e.g., allergy to in place of a nonformulary medication or a non-preferred for-
or therapeutic failure of formulary alternative, condition not mulary medication without having to contact the prescriber.
treatable by formulary medications). Drugs appropriate for therapeutic interchange are drug prod-
ucts with different chemical structures that are expected to
Subformularies. Depending on state regulations, subfor- have similar therapeutic effects and safety profiles when
mularies may be developed and maintained, using the same administered to patients in therapeutically equivalent doses.
evidence-based process, to provide lists of appropriate and The authorization of a therapeutic interchange and notifica-
approved medications for furnishing by nonphysician pro- tion of the prescriber should occur according to the organi-
viders or to specific patient subsets, such as Medicare pa- zation’s policy. In some organizations, prescribers agree to
tients. Health systems must follow specific rules and regula- the therapeutic interchange process as part of their overall
tions provided under the U.S. Medicare Modernization Act agreement to follow the organization’s policies when they
of 2003 in their evaluation and inclusion of medications in a are granted prescribing privileges. Other organizations re-
Medicare formulary for those medications to be covered.39 quire that the prescriber be notified each time a medication is
interchanged. A process should be established for when the
prescriber wishes to opt out of the interchange. Adequate ed-
Strategies for Managing Medication Use ucational initiatives should be undertaken to ensure that ev-
eryone affected (prescribers, patients, pharmacists, nurses,
Common strategies for managing medication use via the for- and other health care professionals) is notified of the thera-
mulary include use of generic drugs, therapeutic interchange, peutic interchange. Guidelines on therapeutic interchange
guided-use policies, clinical practice guidelines, and policies are available elsewhere.41
for off-label prescribing and the use of research pharmaceu-
ticals. MUE is also important in managing medication use. Guided-Use Strategies. Medications may be added to the
formulary with additional processes in place to guide the use
Generic Drugs. Optimizing the number of medication enti- of the medications to improve therapeutic outcomes, prevent
ties and products available from the pharmacy can produce adverse events, or reduce costs. Examples of strategies to
substantial patient care and financial benefits. These benefits help guide the use of medications in addition to therapeutic
are greatly increased through the use of generic equivalents interchange may include the following.
(drugs considered bioequivalent by FDA [i.e., AB-rated drug Established-use criteria. Patients must meet the estab-
products40] and therapeutic equivalents (drug products dif- lished criteria before the medication is dispensed. A process
fering in composition or in their basic drug entity that are should be developed to cover situations in which the patient
considered to have very similar pharmacologic and therapeu- does not meet the established criteria, but the medication is
tic activities). The use of high-quality generic equivalents is nevertheless determined to be medically necessary. This strat-
encouraged in order to provide the best possible care at an egy may also be useful when medications are in short supply.
affordable cost. Use of generic drugs that have been deemed Restricting drug use to a service. A specific service
bioequivalent by FDA does not require review or approval must approve the use of the drug before dispensing. This
by the P&T committee, although a review of all new medica- strategy can be used when inappropriate use or severe ad-
tions for key safety issues (e.g., look-alike, sound-alike con- verse effects may occur, and it can also be employed for
cerns) should be conducted to prevent medication errors. For antimicrobial agents when inappropriate use or overuse can
some drug categories, such as those with a narrow therapeu- result in resistant organisms and pose a danger to the general
tic range, a more thorough evaluation of the bioequivalency patient population or the public.
data and approval of experts or the P&T committee should be Limiting use of the drug to specially trained individu-
considered before implementing a generic substitution. als. This strategy may be appropriate when the drug is in-
The P&T committee must establish policies and proce herently dangerous and should only be used by individuals
dures governing the dispensing of generic equivalents. These with specific training (e.g., restricting use of chemotherapy
policies and procedures should include the following points: agents to oncologists).
Designating medications for use in specific areas.
• The pharmacist is responsible for selecting from avail- Such policies can be helpful when administration of a medi-
able generic equivalents those drugs to be dispensed cation requires special equipment or staff with particular
pursuant to a prescriber’s order for a particular medi- skills to use the medication safely (e.g., limiting neuromus-
cation. cular blockers to operating rooms and critical care areas).
Approval of medical director (or designee) before their awareness of it and may create a sense of investment in
drug use. This strategy is particularly appropriate when the its goals. Process-of-care and outcomes data from the orga-
P&T committee has reviewed a high-cost medication and nization’s MUE activities (or, in some organizations, from
determined that the drug has little or no role in the care of such sources as the electronic medical records and com-
patients at that organization but a prescriber would like to puterized prescriber-order-entry systems) can also be used
use the medication on a nonformulary basis. to make informed decisions during the consensus process.
After the consensus process is completed, the guideline
Clinical Practice Guidelines. The implementation of should be reviewed and approved by the P&T committee.
medication-use policy decisions is a complicated process The dissemination and implementation of guidelines
that, when properly conducted, can decrease variability in in the practice environment must also be carefully executed.
practice and improve patient outcomes, including clinical Unlike active intervention tools that directly influence be-
and economic consequences of care. Many tools are used to havior, guidelines change behavior only when they are ac-
reduce practice variability, reduce cost, and improve quality, cessed, read, accepted, and put into practice. Exhaustive
including order sets, clinical pathways, treatment algorithms, communication about the availability of guidelines is neces
and clinical practice guidelines. While active intervention sary. The dissemination of guidelines in hardcopy format
tools, such as order sets, directly influence prescribing for is common, but electronic distribution (often in the form of
individual patients, clinical practice guidelines influence a library of guidelines available via the Internet) is more ef
prescriber behavior in a passive manner, primarily through ficient. Given the dynamic nature of the biomedical evidence
education. Like the medication formulary, clinical practice and the quickening pace of changes in practice, maintaining
guidelines should reflect current biomedical evidence, al- current practice guidelines is an important challenge. Every
though they may also include expert opinion of prescribers guideline should include a time frame for future review and
within a practice seting. Clinical practice guidelines are revision. If resources are not available to properly update
developed and disseminated by national and international and revise an older guideline, the guideline should be retired
organizations, but they can also be developed locally. Not and removed from circulation.
all guidelines are equally valuable, however. Policymakers
should not assume that guidelines, even those endorsed by Off-Label Use. The use of a drug prescribed for an indica-
respected organizations, are necessarily evidence based and tion not specifically approved by FDA is often referred to
should carefully review guidelines to ensure that they are truly as off-label use. Off-label use can include the use of phar-
evidence driven and current. Regardless of the source of the maceuticals outside of specified populations, for different
synthesis of biomedical evidence that forms the framework diseases or stages of diseases, or by different routes of ad-
for an individual guideline, a locally conducted consensus ministration. Other types of off-label use involve changes
development process, incorporating local expertise, must be to dosing or dosing schedules or in chronology or sequence
performed if a guideline is to be accepted and followed. of use.
Whether the medication formulary is a reflection of Before considering off-label use, supporting safety
existing clinical practice guidelines in a particular organiza- and efficacy evidence must be carefully evaluated and a
tion or vice versa, it is critical that the guidelines and formu- risk-benefit determination made, especially when alter
lary are consistent. If a specific medication is recommended natives with FDA-approved labeling are available for the
by a clinical practice guideline, it should in the majority of intended off-label use.42 When considering or reviewing
cases be on the formulary. As formulary changes are made, off-label use, the P&T committee should use an evidence-
agents may need to be removed from or replaced in exist- based process. The approach to evaluating evidence and
ing guidelines. Guidelines should avoid recommending use benefit developed by the U.S. Preventive Services Task
of nonformulary medications, and they can be useful in dis- Force is an example.43,44
couraging nonformulary medication use and guiding the ap- The following principles should guide the off-label use
propriate use of nonformulary products when necessary. of medications:
Guidelines are frequently developed to address com-
plex or particularly expensive medication therapies. However, 1. Off-label pharmaceutical prescribing should be based
complicated specialty therapies that will affect the care of on published evidence, and patient safety should be
very few patients may not justify the time and resources nec- the primary consideration.
essary to develop and maintain a guideline. Guidelines may 2. When the off-label use of an agent is expected to occur
be medication specific or disease oriented and may overlap frequently, the P&T committee should establish proto-
in their scope of coverage. cols guiding that use. The P&T committee should be
The development of a clinical practice guideline considered the arbiter of off-label use and should rely
should begin with the synthesis of all available biomedi- on the scientific evidence to guide its decisions.
cal evidence addressing the guideline topic. In many cases, 3. The ultimate responsibility for the safety and efficacy
guidelines from other organizations, both national and lo- of off-label use resides with the prescriber, who should
cal, can be used as a starting point for development. The be familiar with the evidence before considering off-
national guideline clearinghouse sponsored by the Agency label use, be aware of local protocols for use of the
for Healthcare Research and Quality is a useful source of agent, and, when necessary, consult with an appropri-
previously developed guidelines (www.guideline.gov). The ately knowledgeable pharmacist.
subsequent consensus process, eliciting feedback and input 4. Proper assessment of evidence for off-label use should
from local stakeholders, is critical. Stakeholders may not involve as comprehensive and balanced a review as
reach unanimous agreement about all dimensions of the possible. Selective use of studies to support a position
guideline, but their involvement in its development increases is strongly discouraged and, in the event of a negative
outcome, may not withstand the rigor of a thorough how an individual medication is used or evaluate medica-
peer review. tion management of a given disease state. All steps of the
medication-use process should be evaluated over time. The
Research Pharmaceuticals (Investigational Drugs). An in- P&T committee, or its equivalent, should be involved in the
vestigational drug is defined as a chemical or biological used MUE process.
in a clinical investigation and can include prescription and Concurrent evaluation (collecting data during care de-
nonprescription drugs, nutritional supplements, and herbal livery and sometimes as a component of the care process) is
preparations. Investigational drug study procedures must be usually preferred over retrospective methods because it al-
consistent with all applicable laws and regulations. Efforts lows organizations to select relevant outcomes for collection
should be made to ensure that the prescribing and distribu- rather than rely on out-comes routinely documented in pa-
tion of investigational drugs benefit from the safe medica- tient medical records. For example, quality-of-life measures
tion management systems used for other medications. More remain an infrequently documented measure in medical re-
information on the management of investigational drugs can cords. Only through concurrent evaluation can that outcome
be found in other ASHP guidelines.45,46 measure be reliably captured. Medications recently added to
the formulary should be evaluated, especially if there is the
MUE Process. Although distinctions have historically been potential for inappropriate use or adverse effects of concern.
made among the terms drug-use evaluation, drug-use review, This review should occur 6–12 months after their addition
and medication-use evaluation, they all refer to the systematic to the formulary. High-cost, high-use, and problemprone
evaluation of medication use employing standard, observa- medications are also good candidates for evaluation.
tional quality-improvement methods (e.g., traditional “plan–
do–check–act” approach). MUE is a quality-improvement Incorporating Patient Safety Issues
activity, but it can also be considered a formulary system in the Decision-Making Process
management technique.
MUE methods have traditionally involved establish- P&T committees have always addressed medication safety
ing evidence-based criteria for medication use and apply- issues. However, as medication errors have received in-
ing those criteria retrospectively to determine the degree to creased scrutiny and more is understood about the process
which a particular medication was used in discordance with failures that contribute to such errors, P&T committees have
established criteria. Interventions could then be used to im- more opportunities to address patient safety issues. The P&T
prove prescribing based on those data. As electronic medi- committee should systematically address patient safety as part
cal records have become increasingly important and more of its deliberations. Opportunities for including patient safety
widely available, MUE activities have matured from simple in P&T committee deliberations include the following:
paper-based medical record reviews to sophisticated analy-
ses drawing on multiple sources of data regarding medica- 1. When evaluating a medication for inclusion on the for-
tion use. A more expansive approach to MUE has been de- mulary, the P&T committee should consider adverse
scribed in which not only the use of individual medications effects, issues in preparation, sound-alike or look-
but the entire process of care for disease states is examined.47 alike potential, and dosing or administration issues.
The use of quasiexperimental research methods may provide Assessments should be conducted to identify potential
more meaningful information for quality-improvement pur- safety concerns posed by use of the medication. The
poses (e.g., economic, clinical, and humanistic outcomes of P&T committee should make recommendations for
greater relevance than arbitrarily set appropriateness criteria). managing identified risks.
MUE can be simply informative (collecting data to 2. Organizations, in collaboration with the appropriate
guide decision-making) or be used to measure the effect committees, should undertake projects to proactively
of interventions, such as the addition of a new agent to the assess risk in medication-use processes. The use of
formulary or the implementation of a new medication-use
high-risk medications or major system changes (e.g.,
policy. MUE activities can focus on any dimension of the
a new computer system, new equipment) offer oppor-
medication-use process (from medication acquisition to pa
tunities to perform proactive risk assessments. Failure
tient monitoring) that presents an opportunity for improve
mode and effects analysis (FMEA) can be used to
ment. While MUE often focuses on problem-prone, high-
structure these assessments. The Joint Commission,
risk, or high-cost medications, MUE can be used to examine
Institute for Healthcare Improvement, and National
any aspect of medication use that is problematic to the insti
Center on Patient Safety provide information about
tution conducting the evaluation.
conducting and examples of FMEA projects on their
A systematic plan to monitor, evaluate, and improve
websites (www.jointcommission.org/, www.ihi.org/,
medication use should be established within the organiza-
tion.17 Such a plan is an accreditation requirement for many and www.patientsafety.gov).
organizations (e.g., Joint Commission26). MUE should be 3. The P&T committee should consistently review
a part of the organization’s overall quality-improvement medication-event data, including data on near misses,
program. MUE activities should be conducted to examine and make recommendations to prevent future events.
the effect of medication-use policy decisions (particularly 4. The P&T committee should conduct targeted quality-
those made in the absence of convincing evidence from the improvement projects to improve the safety of specific
biomedical literature) but can also be conducted to inform medications or to evaluate the processes involved.
decision-making (again, particularly when making policy 5. When reviewing policies, the P&T committee should
decisions under conditions of uncertainty). Specific proj- ensure that the policies adequately address the poten-
ects to evaluate medication use can either involve assessing tial risk issues.
6. The P&T committee should champion evidence-based • Newsletters,

fail-safe techniques (e.g., bar-coding) to prevent medi- • Mailings,
cation events. • Prescriber detailing, and
7. The P&T committee should review information avail- • Pharmacy or institutional websites.
able on patient safety or events reported by other or-
ganizations to identify ways to prevent medication Pilot or demonstration projects may be beneficial in il-
events and disseminate the information to health care lustrating the value of a new medication-use policy and may
providers and, when appropriate, patients. generate data that could justify a decision or help communi-
cate why a specific policy is necessary.
Resources on medication safety should be routinely
reviewed to identify potential issues an organization could
Conclusion
address. Examples of resources include the Institute for
Safe Medication Practices (www.ismp.org), Medwatch
A formulary system is the multidisciplinary, evidence-based
(www.fda.gov/medwatch), FDA Patient Safety News (www.
process employed by an organization to select and use medi-
accessdata.fda.gov/scripts/cdrh/cfdocs/psn/), and the U.S.
cations that offer the best therapeutic outcomes while mini-
Pharmacopeia Patient Safety Program (www.usp.org/hqi/
mizing potential risks and costs for patients. Organizations
patientSafety/). employ the MUE process to continually improve how medi-
cations are used within the organization at all steps in the
Drug Product Shortages medication-use process. Medication use is an inherently
complex and dangerous process that requires constant evalu-
Health systems frequently need to address drug product short- ation. Organizations need to implement tools and processes
ages. Drug product shortages disrupt patient care and the pro- necessary to meet the goals of using medications effectively
cessing of medication orders, increasing the risks presented and safely. Professionals involved in the medication-use
by all aspects of the medication-use system, including pur- process need to know and understand how the organization’s
chasing, storage, pharmacy computer and automation sys- medication-use policies and processes can be incorporated
tems, ordering, preparation, administration, and monitoring. into their daily work so that medications are used appropri-
During a drug product shortage, the P&T committee ately and safely. Technology offers many opportunities to
plays an important role in setting organizational priorities. make those processes more effective. Communicating the
The P&T committee needs to develop strategies to address actions related to medication use is a constant challenge that
shortages in a timely manner, including designating appro- organizations need to address.
priate alternatives, identifying strategies for rationing avail-
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23. American Society of Hospital Pharmacists. ASHP alence evaluations. www.fda.gov/cder/ob/ (accessed
guidelines on pharmacists’ relationships with industry. 2008 Mar 27).
Am J Hosp Pharm. 1992; 49:154. 41. Gray T, Bertch K, Galt K, et al. Guidelines for thera-
24. Nakahiro S. Contemporary issues in formulary man- peutic interchange—2004. Pharmacotherapy. 2005;
agement. In: Millares M, ed. Applied drug information: 25:1666–80.
42. American Society of Hospital Pharmacists. ASHP Medication-Use Evaluation: A performance-improvement

statement on the use of medications for unlabeled method that focuses on evaluating and improving
uses. Am J Hosp Pharm. 1992; 49:2006–8. medication-use processes with the goal of optimal pa-
43. U.S. Preventive Services Task Force. Strength of rec- tient outcomes.17
ommendations rating guide. www.ahrq.gov/clinic/ Pharmacy and Therapeutics (P&T) Committee: An advi-
3rduspstf/ratings.htm (accessed 2008 Mar 27). sory committee that is responsible for developing, man-
44. U.S. Preventive Services Task Force. Current methods aging, updating, and administering a formulary system.1
of the U.S. Preventive Services Task Force: a review Therapeutic Alternatives: Drug products with different
of the process.www.ahrq.gov/clinic/ajpmsuppl/har- chemical structures but of the same pharmacologic or
ris2.htm#assessing (accessed 2008 Mar 27). therapeutic class and usually have similar therapeutic
45. American Society of Hospital Pharmacists. ASHP guide- effects and adverse-reaction profiles when adminis-
lines for pharmaceutical research in organized health- tered to patients in therapeutically equivalent doses.1
care settings. Am J Hosp Pharm. 1989; 46:129– 30. Therapeutic Interchange: Authorized exchange of thera-
46. American Society of Health-System Pharmacists. peutic alternatives in accordance with previously es-
ASHP guidelines on clinical drug research. Am J tablished and approved written guidelines or protocols
Health-Syst Pharm. 1998; 55:369–76. within a formulary system.1, 41
47. Vermeulen LC, Beis SJ, Cano SB. Applying outcomes Therapeutic Substitution: The act of dispensing a thera-
research in improving the medication-use process. Am peutic alternative for the drug product prescribed with-
J Health-Syst Pharm. 2000; 57:2277–82. out prior authorization of the prescriber. This is an il-
48. American Society of Health-System Pharmacists. legal act because only the prescriber may authorize an
ASHP guidelines on managing drug product short- exchange of therapeutic alternatives.1
ages. Am J Health-Syst Pharm. 2001; 58:1445–50.
Appendix—Glossary of Terms
Formulary: A continually updated list of medications and These guidelines were reviewed in 2012 by the Council on
related information, representing the clinical judgment Pharmacy Practice and by the Board of Directors and were found
of physicians, pharmacists, and other experts in the di- to still be appropriate.
agnosis, prophylaxis, or treatment of disease and pro-
motion of health. Approved by the ASHP Board of Directors on January 28, 2008.
Formulary System: An ongoing process whereby a health These guidelines supersede the ASHP Guidelines on Formulary
care organization, through its physicians, pharma- System Management dated November 20, 1991, the ASHP Technical
cists, and other health care professionals, establishes Assistance Bulletin on Drug Formularies dated November 14, 1990,
policies on the use of drug products and therapies and and the ASHP Technical Assistance Bulletin on the Evaluation of
identifies drug products and therapies that are the most Drugs for Formularies dated November 19, 1987. Developed
medically appropriate and cost-effective to best serve through the ASHP Council on Pharmacy Practice.
the health interests of a given patient population.1
Generic Substitution: The substitution of drug products ASHP gratefully acknowledges the expert panel that developed
that contain the same active ingredient or ingredients these guidelines: Linda S. Tyler, Pharm.D., FASHP; Mirta Millares,
and are chemically identical in strength, concentration, Pharm.D., FCSHP, FASHP; Andrew L. Wilson, Pharm.D., FASHP;
dosage form, and route of administration to the drug Lee C. Vermeulen, Jr., B.S.Pharm., M.S.; J. Russell (Rusty) May,
product prescribed.1 Pharm.D., FASHP; Michael A. Valentino, R.Ph. MHSA; and
Medication: Any prescription medications, herbal remedies, Sabrina W. Cole, Pharm.D.
vitamins, nutraceuticals, nonprescription drugs, vaccines,
or diagnostic and contrast agents used to diagnose, treat, Copyright © 2008, American Society of Health-System Pharmacists,
or prevent disease and other abnormal conditions and Inc. All rights reserved.
radioactive medications, respiratory therapy treatments,
parenteral nutrition, blood derivatives, intravenous solu- The bibliographic citation for this document is as follows: American
tions (plain or with electrolytes or drugs), or any product Society of Health-System Pharmacists. ASHP guidelines on the
designated by the Food and Drug Administration as a pharmacy and therapeutics committee and the formulary system.
drug (including investigational drugs).26 Am J Health-Syst Pharm. 2008; 65:1272–83.
188 Formulary Management–Endorsed Document
Principles of a Sound Drug Formulary System

These principles have been endorsed by the following appropriate and cost-effective to best serve the health inter-
organizations: ests of a given patient population.
• Academy of Managed Care Pharmacy Drug Formulary. A continually updated list of medications
• Alliance of Community Health Plans and related information, representing the clinical judgement
• American Medical Association of physicians, pharmacists, and other experts in the diagno-
• American Society of Health-System Pharmacists sis and/or treatment of disease and promotion of health.
• Department of Veterans Affairs, Pharmacy Benefits
Management Strategic Healthcare Group
Guiding Principles
• National Business Coalition on Health
• U.S. Pharmacopeia
Formulary system decisions are based on scientific and
economic considerations that achieve appropriate, safe, and
Preamble cost-effective drug therapy.
A coalition of national organizations representing health • Clinical decisions are based on the strength of scien-
care professionals, government, and business leaders tific evidence and standards of practice that include,
formed a working group (see Appendix III) to develop but are not limited, to the following:
a set of principles specifying the essential components • Assessing peer-reviewed medical literature, in-
that contribute to a sound drug formulary system. The cluding randomized clinical trials (especially
Coalition was formed in September 1999 in response to drug comparison studies), pharmacoeconomic
the widespread use of drug formularies in both inpatient studies, and outcomes research data.
and outpatient settings and the lack of understanding about • Employing published practice guidelines, devel-
formularies among the public. Also, proposed federal leg- oped by an acceptable evidence-based process.
islation that would provide a prescription drug benefit for • Comparing the efficacy as well as the type and
Medicare beneficiaries has brought increased attention to frequency of side effects and potential drug in-
the appropriate role and management of drug formulary teractions among alternative drug products.
systems within drug benefit programs. • Assessing the likely impact of a drug product on
The formulary system, when properly designed and im patient compliance when compared to alterna-
plemented, can promote rational, clinically appropriate, safe, tive products.
and cost-effective drug therapy. The Coalition has enumerated • Basing formulary system decisions on a thor-
these principles, however, because it recognizes that patient care ough evaluation of the benefits, risks, and po-
may be compromised if a formulary system is not optimally de tential outcomes for patients; risks encompass
veloped, organized, and administered. This document contains adverse drug events (adverse drug reactions and
“Guiding Principles” that the Coalition believes must be present medication errors, such as those caused by con-
for a drug formulary system to appropriately serve the patients it fusing product names or labels).
covers. The absence of one or more of these “Guiding Principles” • Economic considerations include, but are not limited,
should be cause for careful scrutiny of a formulary system. A glos- to the following:
sary (see Appendix I) and bibliography (see Appendix II) are • Basing formulary system decisions on cost fac-
included with the “Guiding Principles” to clarify terminology tors only after the safety, efficacy, and therapeu-
and to provide additional resources, respectively. tic need have been established.
The Coalition believes that the presence of consensus- • Evaluating drug products and therapies in terms
based Formulary System Principles can assist decision-mak- of their impact on total health care costs.
ers who must balance the health care quality and cost equation. • Permitting financial incentives only when they
Further, the Guiding Principles will be a valuable educational promote cost management as part of the deliv-
tool for national, state, and local public policy makers, health ery of quality medical care. Financial incen-
care system administrators, purchasers and third-party payers, tives or pressures on practitioners that may in-
practitioners, and consumers and patient advocates. These terfere with the delivery of medically necessary
parties all have an interest in designing formulary systems that care are unacceptable.
ensure patients have access to rational, clinically appropriate,
safe, and cost-effective therapy and which supports an afford- The formulary system encompasses drug selection, drug utili-
able and sustainable drug benefit program. zation review, and other tools to foster best practices in prescrib-
ing, dispensing, administration, and monitoring of outcomes.
Definitions
• The formulary system:
Drug Formulary System. An ongoing process whereby • Provides drug product selection and formulary
a health care organization, through its physicians, phar maintenance (see above).
macists, and other health care professionals, establishes • Provides drug use evaluation (also called drug
policies on the use of drug products and therapies, and iden utilization review) to enhance quality of care for
tifies drug products and therapies that are the most medically patients by assuring appropriate drug therapy.
Formulary Management–Endorsed Document 189
• Provides for the periodic evaluation and analysis • The formulary system should:
of treatment protocols and procedures to ensure • Inform physicians, pharmacists, other health
that they are up-to-date and are consistent with care professionals, patients, and payers about
optimum therapeutics. the factors that affect formulary system deci-
• Provides for the monitoring, reporting, and sions, including cost containment measures; the
analysis of adverse results of drug therapy (e.g., procedures for obtaining non-formulary drugs;
adverse drug reactions, medication errors) to and the importance of formulary compliance to
continuously improve the quality of care. improving quality of care and restraining health
care costs.
The Pharmacy and Therapeutics (P&T) Committee, or • Proactively inform practitioners about changes
equivalent body, comprised of actively practicing physicians, to the formulary or to other pharmaceutical man-
pharmacists, and other health care professionals, is the mech agement procedures.
anism for administering the formulary system, which includes • Provide patient education programs that explain
developing and maintaining the formulary and establishing how formulary decisions are made and the roles
and implementing policies on the use of drug products. and responsibilities of the patient, especially
the importance of patient compliance with drug
• The Pharmacy and Therapeutics Committee: therapy to assure the success of that therapy.
• Objectively appraises, evaluates, and selects • Disclose the existence of formularies and have
drugs for the formulary. copies of the formulary readily available and ac-
• Meets as frequently as is necessary to review and cessible.
update the appropriateness of the formulary sys- • Provide rationale for specific formulary deci-
tem in light of new drugs and new indications, sions when requested.
uses, or warnings affecting existing drugs.
• Establishes policies and procedures to educate The formulary system should include a well-defined process
and inform health care providers about drug for the physician or other prescriber to use a non-formulary
products, usage, and committee decisions. drug when medically indicated.
• Oversees quality improvement programs that
employ drug use evaluation. • The formulary system should:
• Implements generic substitution and therapeutic • Enable individual patient needs to be met with
interchange programs that authorize exchange of non-formulary drug products when demon-
therapeutic alternatives based upon written guide- strated to be clinically justified by the physician
lines or protocols within a formulary system. (Note: or other prescriber.
Therapeutic substitution, the dispensing of therapeu- • Institute an efficient process for the timely pro-
tic alternates without the prescriber’s approval, is il- curement of non-formulary drug products and
legal and should not be allowed—see Glossary.) impose minimal administrative burdens.
• Develops protocols and procedures for the use of • Provide access to a formal appeal process if a
and access to non-formulary drug products. request for a non-formulary drug is denied.
• Include policies that state that practitioners should
Physicians, pharmacists, and other health care professionals not be penalized for prescribing non-formulary
provide oversight of the formulary system. drug products that are medically necessary.
• Health care organization policies should ensure ap- Appendix I—Glossary

propriate oversight of the P&T Committee and its
decisions by the medical staff or equivalent body. Drug Formulary System: An ongoing process whereby a
health care organization, through its physicians, phar-
The formulary system must have its own policies, or adhere macists, and other health care professionals, establishes
to other organizational policies, that address conflicts of in- policies on the use of drug products and therapies, and
terest and disclosure by P&T committee members. identifies drug products and therapies that are the most
medically appropriate and cost effective to best serve
• Formulary system policies should: the health interests of a given patient population.
• Require P&T committee members to reveal, by Drug Formulary: A continually updated list of medica-
signing a conflict of interest statement, economic tions and related information, representing the clinical
and other relationships with pharmaceutical enti- judgement of physicians, pharmacists, and other ex-
ties that could influence Committee decisions. perts in the diagnosis and/or treatment of disease and
• Exclude product sponsor representatives from promotion of health.
P&T committee membership and from attending Pharmacy & Therapeutics (P&T) Committee: An advisory
P&T committee meetings. committee that is responsible for developing, managing,
• Require P&T committee members to adhere to the updating, and administering the drug formulary system.
formulary system’s policy on disclosure and partici- Generic Substitution: The substitution of drug products that
pation in discussion as it relates to conflict of interest. contain the same active ingredient(s) and are chemically
identical in strength, concentration, dosage form, and
The formulary system should include educational programs route of administration to the drug product prescribed.
for payers, practitioners, and patients concerning their roles Therapeutic Alternates: Drug products with differ-
and responsibilities. ent chemical structures but which are of the same
190 Formulary Management–Endorsed Document
pharmacological and/or therapeutic class, and usually 12. American Society of Hospital Pharmacists. ASHP
can be expected to have similar therapeutic effects and Technical Assistance Bulletin on the Evaluation of
adverse reaction profiles when administered to pa- Drugs for Formularies. Am J Hosp Pharm. 1988;
tients in therapeutically equivalent doses. 45:386–7.
Therapeutic Interchange: Authorized exchange of thera- 13. Covington TR and Thornton JL. The formulary sys-
peutic alternates in accordance with previously estab- tem: A cornerstone of drug benefit management, in
lished and approved written guidelines or protocols A Pharmacist’s Guide to Principles and Practices of
within a formulary system. Managed Care Pharmacy. Ito S and Blackburn S, eds.
Therapeutic Substitution: The act of dispensing a thera- Foundation for Managed Care Pharmacy, Alexandria
peutic alternate for the drug product prescribed VA. 1995:35–49.
without prior authorization of the prescriber. This is 14. Dillon MJ. Drug Formulary Management, in Managed
an illegal act because only the prescriber may autho- Care Pharmacy Practice. Navarro RP ed. Aspen
rize an exchange of therapeutic alternates. Publishers, Inc., Gaithersburg, MD. 1999:145–65.
Drug Utilization Review (Drug Use Review, DUR, and 15. Hejna CS and Shepherd MD. Pharmacy and thera-
Drug Use Evaluation): Process used to assess the peutics committee and formulary development, in
appropriateness of drug therapy by engaging in the A Pharmacist’s Guide to Principles and Practices of
evaluation of data on drug use in a given health care en Managed Care Pharmacy. Ito S and Blackburn S, eds.
vironment against predetermined criteria and standards. Foundation for Managed Care Pharmacy, Alexandria
VA. 1995:27–34.
Appendix II—Bibliography 16. National Committee for Quality Assurance. UM 10
procedures for pharmaceutical management. 2000
1. Academy of Managed Care Pharmacy, Concepts Standards for Accreditation of MCOs. 1999:58–60.
in Managed Care Pharmacy Series—Formulary 17. National Committee for Quality Assurance. UM 10
Management (Alexandria, VA: 1998). procedures for pharmaceutical management. 2000
2. American Medical Association. Board of Trustees Surveyor Guidelines for the Accreditation of MCOs.
Report PPP, Principles of Drug Utilization Review. In, 1999:173–82.
American Medical Association House of Delegates 18. PCMA Response to American Medical Association
Proceedings, 140th Annual Meeting. Chicago: Report, I-97, “Pharmaceutical Benefits Management
American Medical Association; June 1991; 225–7. Companies.” September 1998.
3. American Medical Association. Board of Trustees Report 19. Rucker TD and Schiff GD. Drug formularies: myths-
45, Drug Formularies and Therapeutic Interchange. In, information. Medical Care. 1990; 28:928–42.
American Medical Association House of Delegates Reprinted in Hospital Pharmacy, 1991; 26:507–14.
Proceedings, 47th Interim Meeting. New Orleans:
American Medical Association; December 1993; 155–8. Appendix III—Coalition Working Group
4. American Medical Association. Council on Ethical
and Judicial Affairs Report 2, Managed Care Cost Academy of Managed Care Pharmacy
Containment Involving Prescription Drugs. In, Judith A. Cahill, C.E.B.S., Executive Director
American Medical Association House of Delegates
Richard Fry, Senior Director, Pharmacy Affairs
Proceedings, 144th Annual Meeting. Chicago:
American Medical Association; June 1995; 207–13. American Medical Association
5. American Medical Association. Board of Trustees Joseph W. Cranston, Ph.D., Director-Science, Research and
Report 9, Pharmaceutical Benefits Management Technology
Companies. In, American Medical Association House American Society of Health-System Pharmacists
of Delegates Proceedings, 51st Interim Meeting. Dallas: William A. Zellmer, M.P.H., Deputy Executive Vice
American Medical Association; December 1997; 33–44. President
6. American Society of Consultant Pharmacists. Department of Veterans Affairs
Guidelines for the Development of Formulary Systems John E. Ogden, Director, Pharmacy Services
in Nursing Facilities; July 1996. Michael A. Valentino, Associate Chief Consultant for
7. American Society of Hospital Pharmacists. ASHP Pharmacy Benefits Management
Statement on the Formulary System. Am J Hosp
National Business Coalition on Health
Pharm. 1983; 40:1384–5.
Catherine Kunkle, Vice President
Guidelines on Formulary System Management. Am J U.S. Pharmacopeia
Hosp Pharm. 1992; 49:648–52. Jacqueline L. Eng, Senior Vice President, Program
9. American Society of Hospital Pharmacists. ASHP Development
Statement on the Pharmacy and Therapeutics Keith W. Johnson, Vice President and Director, New and
Committee. Am J Hosp Pharm. 1992; 49:2008–9. Off-Label Uses
10. American Society of Health-System Pharmacists. Thomas R. Fulda, Program Director, Drug Utilization
ASHP Guidelines on Medication-Use Evaluation. Am Review Programs
J Health-syst Pharm. 1996; 53:1953–5. Nancy B. Mabie, Assistant Director, Pharmacy Affairs
11. American Society of Hospital Pharmacists. ASHP Observer
Technical Assistance Bulletin on Drug Formularies. AARP
Am J Hosp Pharm. 1991; 48:791–3. David Gross, Senior Policy Advisor, Public Policy Institute
Formulary Management–Endorsed Document 191
Public Comment Requested oughly reviewed and considered by the Coalition Working
Group.
To ensure that knowledgeable and interested parties beyond These principles were endorsed by the ASHP Board of
the Coalition Working Group had an opportunity to contrib Directors on June 4, 2000.
ute to the Principles development process, a preliminary set of The endorsement of this document was reviewed in
principles was distributed for public comment to 50-plus or- 2011 by the Council on Pharmacy Practice and by the Board
ganizations in February 2000. Comments received were thor- of Directors and was found to still be appropriate.
194 Government, Law, and Regulation–Positions

Pharmacist Participation in Health Policy Development determining the quality of a drug product and its raw materi-
(1501) als; further,
Source: Council on Public Policy To urge Congress and state legislatures to provide ad-
To advocate that pharmacists participate with policymakers equate funding, or authority to impose user fees, to accom-
and stakeholders in the development of health-related poli- plish these objectives.
cies at the national, state, and community levels; further, This policy supersedes ASHP policy 0907.
To develop tools and resources to assist pharmacists in
fully participating in health policy development at all levels. Premarketing Comparative Clinical Studies (1506)
Source: Council on Public Policy
Pharmacist Recognition as a Healthcare Provider (1502) To advocate that the Food and Drug Administration have the
Source: Council on Public Policy authority to impose a requirement for comparative clinical
To advocate for changes in federal (e.g., Social Security trials.
Act), state, and third-party payment programs to define This policy supersedes ASHP policy 0514.
pharmacists as healthcare providers; further,
To affirm that pharmacists, as medication-use experts, Funding, Expertise, and Oversight of State Boards of
provide safe, accessible, high-quality care that is cost effec- Pharmacy (1507)
tive, resulting in improved patient outcomes; further, Source: Council on Public Policy
To recognize that pharmacists, as healthcare providers, To advocate appropriate oversight of pharmacy practice and
improve access to patient care and bridge existing gaps in the pharmaceutical supply chain through coordination and
healthcare; further, cooperation of state boards of pharmacy and other state and
To collaborate with key stakeholders to describe the federal agencies whose mission it is to protect the public
covered direct patient-care services provided by pharma- health; further,
cists; further, To advocate adequate representation on state boards
To advocate for sustainable compensation and stan- of pharmacy and related agencies by pharmacists who are
dardized billing processes used by payers for pharmacist knowledgeable about all areas of pharmacy practice (e.g.,
services by all available payment programs. hospitals, health systems, clinics, and nontraditional set-
This policy supersedes ASHP policy 1307. tings) to ensure appropriate oversight; further,
To advocate for dedicated funds for the exclusive use
Pharmaceutical Product and Supply Chain Integrity by state boards of pharmacy and related agencies including
(1503) funding for the training of state board of pharmacy inspec-
Source: Council on Public Policy tors and the implementation of adequate inspection sched-
To encourage the Food and Drug Administration (FDA) and ules to ensure the effective oversight and regulation of phar-
relevant state authorities to take the steps necessary to en- macy practice, the integrity of the pharmaceutical supply
sure that (1) all drug products entering the supply chain are chain, and protection of the public; further,
thoroughly inspected and tested to establish that they have To advocate that inspections be performed only by
not been adulterated or misbranded and (2) patients will not pharmacists competent about the applicable area of practice.
receive improperly labeled and packaged, deteriorated, out- This policy supersedes ASHP policy 0518.
dated, counterfeit, adulterated, or unapproved drug products;
further, Support for FDA Expanded Access (Compassionate Use)
To encourage FDA and relevant state authorities to de- Program (1508)
velop and implement regulations to (1) restrict or prohibit Source: Council on Public Policy
licensed drug distributors (drug wholesalers, repackagers, To advocate that the Food and Drug Administration (FDA)
and manufacturers) from purchasing legend drugs from un- Expanded Access (Compassionate Use) Program be the sole
licensed entities and (2) ensure accurate documentation at mechanism for patient access to drugs for which an investi-
any point in the distribution chain of the original source of gational new drug application (IND) has been filed, in order
drug products and chain of custody from the manufacturer to to preserve the integrity of the drug approval process and
the pharmacy; further, assure patient safety; further,
To advocate for the establishment of meaningful pen- To advocate for broader patient access to such drugs
alties for companies that violate current good manufacturing under the FDA Expanded Access Program; further,
practices (cGMPs) intended to ensure the quality, identity, To advocate that IND applicants expedite review and
strength, and purity of their marketed drug product(s) and release of drugs for patients who qualify for the program;
raw materials; further, further,
To advocate for improved transparency so that drug To advocate that the drug therapy be recommended by
product labeling include a readily available means to retrieve a physician and reviewed and monitored by a pharmacist to
the name and location of the facility that manufactured the assure safe patient care; further,
specific lot of the product; further, To advocate for the patient’s right to be informed of
To advocate that this readily retrievable manufacturing the potential benefits and risks via an informed consent pro-
information be available prospectively to aid purchasers in cess, and the responsibility of an institutional review board
Government, Law, and Regulation–Positions 195
to review and approve the informed consent and the drug publicly accessible central repository of PMI in a format that
therapy protocol. is suitable for ready export; further,
To advocate for laws and regulations that would re-
Approval of Biosimilar Medications (1509) quire all dispensers of medications to comply with FDA-
Source: Council on Public Policy established standards for unalterable content, format, and
To encourage the development of safe and effective biosimi- distribution of PMI.
lar medications in order to make such medications more af- This policy supersedes ASHP policy 1012.
fordable and accessible; further,
To encourage research on the safety, effectiveness, and Automatic Stop Orders (1405)
interchangeability of biosimilar medications; further, Source: Council on Pharmacy Practice
To support legislation and regulation to allow Food To advocate that the Centers for Medicare & Medicaid
and Drug Administration (FDA) approval of biosimilar Services (1) remove the requirement in the Hospital
medications; further, Conditions of Participation that all medication orders auto-
To support legislation and regulation to allow FDA ap- matically stop after an arbitrarily assigned period to include
proval of biosimilar medications that are also determined by other options to protect patients from indefinite, open-ended
the FDA to be interchangeable and therefore may be substi- medication orders, and (2) revise the remainder of the medi-
tuted for the reference product without the intervention of cation management regulations and interpretive guidelines
the prescriber; further, to be consistent with this practice; further,
To oppose the implementation of any state laws re- To affirm that the requirement for automatic stop or-
garding biosimilar interchangeability prior to finalization of ders for all medications is a potential source of medication
FDA guidance; further, errors and patient harm; further,
To oppose any state legislation that would require a To encourage pharmacists to participate in interprofes-
pharmacist to notify a prescriber when a biosimilar deemed sional efforts to establish standardized methods to assure ap-
to be interchangeable by the FDA is dispensed; further, propriate duration of therapy.
To require postmarketing surveillance for all biosimi- This policy supersedes ASHP policy 0904.
lar medications to ensure their continued safety, effective-
ness, purity, quality, identity, and strength; further, Federal and State Regulation of Compounding (1406)
To advocate for adequate reimbursement for biosimi- Source: Council on Public Policy
lar medications that are deemed interchangeable; further, To advocate that the applicable compendial standards of the
To promote and develop ASHP-directed education of United States Pharmacopeia be included in state and federal
pharmacists about biosimilar medications and their appro- laws and regulations that govern compounding by any health
priate use within hospitals and health systems; further, professional; further,
To advocate and encourage pharmacist evaluation and To advocate for mandatory state registration of com-
the application of the formulary system before biosimilar pounding facilities (e.g., pharmacies, physician offices, clin-
medications are used in hospitals and health systems. ics, ambulatory surgery centers) that provide products for
This policy supersedes ASHP policy 1409. specific patient prescriptions or in anticipation of specific
patient prescriptions or medication orders; further,
Development of Abuse-Resistant Narcotics (1512) To advocate for mandatory Food and Drug
Source: Council on Therapeutics Administration registration and current good manufacturing
To advocate that the Food and Drug Administration investi- practices requirements for outsourcing facilities that com-
gate the efficacy of abuse-resistant formulations in prevent- pound and sell products without patient-specific prescrip-
ing prescription drug abuse. tions across state lines; further,
To advocate for improved patient safety and care
Quality Patient Medication Information (1513) through education of regulatory inspectors, increased fre-
Source: Council on Therapeutics quency and improved effectiveness of compliance inspec-
To support efforts by the Food and Drug Administration tions, and enhancing interagency communications; further,
(FDA) and other stakeholders to improve the quality, consis- To advocate that state and federal agencies develop
tency, and simplicity of written patient medication informa- standardized definitions and nomenclature relating to ster-
tion (PMI); further, ile and nonsterile compounding, including but not limited
To encourage the FDA to work in collaboration with to definitions of compounding, manufacturing, repackaging,
patient advocates and other stakeholders to create evidence- and relabeling.
based models and standards, including establishment of a This policy supersedes ASHP policy 1308.
universal literacy level, for PMI; further,
To advocate that research be conducted to validate 340B Drug Pricing Program Sustainability (1407)
these models in actual-use studies in pertinent patient popu- Source: Council on Public Policy
lations; further, To affirm the intent of the federal drug pricing program (the
To advocate that FDA explore alternative models of “340B program”) to stretch scarce federal resources as far as
PMI content development and maintenance that will ensure possible, reaching more eligible patients and providing more
the highest level of accuracy, consistency, and currency; fur- comprehensive services; further,
ther, To advocate legislation or regulation that would op-
To advocate that the FDA engage a single third-party timize access to the 340B program in accordance with the
author to provide editorial control of a highly structured, intent of the program; further,
To advocate for clarification and simplification of the mised and that pharmacists are reimbursed for the clinical
340B program and any future federal discount drug pricing services provided.
programs with respect to program definitions, eligibility, and
compliance measures to ensure the integrity of the program; Expedited Pathways for FDA Drug Approval (1411)
further, Source: Council on Therapeutics
To encourage pharmacy leaders to provide appropriate To support the use of expedited pathways for Food and
stewardship of the 340B program by documenting the ex- Drug Administration (FDA) approval of new drugs that ex-
panded services and access created by the program; further, pand access to innovative therapies while protecting patient
To educate pharmacy leaders and health-system ad- safety; further,
ministrators about the internal partnerships and accountabil- To advocate for the development of unique labeling re-
ities and the patient-care benefits of program participation; quirements that would be used on an interim basis to identify
further, products approved by these pathways in order to increase
To educate health-system administrators, risk manag- awareness of data limitations and guide clinician use of these
ers, and pharmacists about the resources (e.g., information drugs until additional evidence becomes available; further,
technology) required to support 340B program compliance To advocate that the FDA be diligent in enforcing
and documentation; further, postmarketing commitments for drug products approved via
To encourage communication and education concern- expedited pathways, including utilizing its existing authority
ing expanded services and access provided by 340B partici- to enforce penalties when these requirements are not met;
pants to patients in fulfillment of its mission. further,
This policy supersedes ASHP policy 0506. To encourage research to evaluate the impact of ex-
pedited pathways on drug product development and patient
State Prescription Drug Monitoring Programs (1408) care, including drug development timelines and costs, over-
Source: Council on Public Policy all health care costs, patient access to care, and the effective-
To advocate for mandatory, uniform prescription drug moni- ness and safety of these therapies.
toring programs that collect real-time, relevant, and standard
information from all dispensing outpatient entities about FDA Oversight of Laboratory-Developed Tests (1412)
controlled substances and monitored prescriptions; further, Source: Council on Therapeutics
To advocate that the design of these programs should To advocate that the Food and Drug Administration be
balance the need for appropriate therapeutic management granted increased authority to regulate laboratory-developed
with safeguards against fraud, misuse, abuse, and diversion; tests as medical devices, including tests used for pharmaco-
further, genetic testing; further,
To advocate that such programs be structured as part of To support development of a risk-based framework
electronic health records and exchanges to allow prescribers, for regulatory oversight of laboratory-developed tests that
pharmacists, and other practitioners to proactively monitor promotes innovation while providing a mechanism to ensure
data for appropriate assessment; further, that test results are reliable, reproducible, and clinically rel-
To advocate for full interstate integration to allow for evant; further,
access by prescribers, pharmacists, and other qualified des- To encourage expanded availability of commercially
ignees across state lines; further,
marketed pharmacogenetic tests that would be available for
To advocate for federal and state funding to establish
use by laboratory and health care professionals to guide drug
and administer these programs; further,
therapy.
To promote research, education, and implementation
of best practices in prescription drug monitoring programs.
Regulation of Telepharmacy Services (1310)
To advocate that state governments adopt laws and regula-
Access to Oral Contraceptives Through an Intermediate
tions that standardize telepharmacy practices across state
Category of Drug Products (1410)
lines and facilitate the use of United States-based telephar-
Source: Council on Therapeutics
macy services; further,
To advocate that oral contraceptives be provided only under
To advocate that boards of pharmacy and state agen-
conditions that ensure safe use, including the availability of
cies that regulate pharmacy practice include the following
counseling to ensure appropriate self-screening and product
in regulations for telepharmacy services: (1) education and
selection; further,
training of participating pharmacists; (2) education, train-
To support expanded access to these products through
ing, certification by the Pharmacy Technician Certification
a proposed intermediate category of drug products, as de-
Board, and licensure of participating pharmacy technicians;
scribed by ASHP policy, that would be available from all
(3) communication and information systems requirements;
pharmacists and licensed health care professionals (includ-
(4) remote order entry, prospective order review, verifica-
ing pharmacists) who are authorized to prescribe medica-
tion of the completed medication order before dispensing,
tions; further,
and dispensing; (5) direct patient-care services, including
To advocate that the proposed reclassification of these
medication therapy management services and patient coun-
products be accompanied by coverage changes by third-
seling and education; (6) licensure (including reciprocity)
party payers to ensure that patient access is not compro-
of participating pharmacies and pharmacists; (7) service
arrangements that cross state borders; (8) service arrange-
ments within the same corporate entity or between different
corporate entities; (9) service arrangements for workload re-
lief in the point-of-care pharmacy during peak periods; (10) To advocate that all pharmacy functions be performed
pharmacist access to all applicable patient information; and under the general supervision of a licensed pharmacist and
(11) development and monitoring of patient safety, quality, that licensed pharmacists and technicians be held account-
and outcomes measures; further, able for the quality of pharmacy services provided.
To identify additional legal and professional issues in (Note: Licensure is the process by which an agency
the provision of telepharmacy services to and from sites lo- of government grants permission to an individual to engage
cated outside the United States. in a given occupation upon finding that the applicant has
This policy supersedes ASHP policy 0716. attained the minimal degree of competency necessary to en-
sure that the public health, safety, and welfare will be rea-
Regulation of Centralized Order Fulfillment (1311) sonably well protected. Certification is the process by which
Source: Council on Public Policy a nongovernmental agency or association grants recognition
To advocate changes in federal and state laws, regulations, to an individual who has met certain predetermined qualifi-
and policies to permit centralized medication order fulfill- cations specified by that agency or association.)
ment within health care facilities under common ownership. This policy supersedes ASHP policy 0815.
DEA Scheduling of Hydrocodone Combination Products Stable Funding for HRSA Office of Pharmacy Affairs
(1314) (1219)
Source: Council on Therapeutics Source: Council on Public Policy
To advocate that the Drug Enforcement Administration To advocate for a sustainable level of funding, including
(DEA) reschedule hydrocodone combination products to appropriations, sufficient to support the public health mis-
Schedule II based on their potential for abuse and patient sion of the Health Resources and Services Administration
harm and to achieve consistency with scheduling of other (HRSA) Office of Pharmacy Affairs; further,
drugs with similar abuse potential. To support initiatives of the Office of Pharmacy
Affairs, including the 340B Drug Pricing Program and inno-
DEA Scheduling of Controlled Substances (1315) vative pharmacy service models in HRSA-funded programs;
Source: Council on Therapeutics further,
To advocate that the Drug Enforcement Administration To encourage research on the potential impact of any
(DEA) establish clear, measurable criteria and a transparent proposed fees or alternative funding sources for the Office
process for scheduling determinations; further, of Pharmacy Affairs.
To urge the DEA to use such a process to re-evaluate This policy supersedes ASHP policy 0911.
existing schedules for all substances regulated under the
Controlled Substances Act to ensure consistency and incor- Globalization of Clinical Trials (1223)
porate current evidence concerning the abuse potential of Source: Council on Therapeutics
these therapies; further, To encourage the Food and Drug Administration (FDA) to
To monitor the effect of DEA scheduling of prod- use its existing authority to increase monitoring and inspec-
ucts under the Controlled Substances Act and other abuse- tion of foreign clinical trials to ensure the integrity and qual-
prevention efforts (e.g., prescription drug monitoring pro- ity of those studies; further,
grams) to assess the impact on patient access to these medi- To advocate that the FDA expand its oversight of clini-
cations and on the practice burden of health care providers. cal trials conducted abroad by continuing to pursue innova-
tive strategies, such as increased collaboration with foreign
Pharmacy Technicians (1216) regulatory agencies and changes in domestic regulatory pro-
Source: Council on Public Policy cesses that support timely submission of foreign clinical trial
To advocate that pharmacy move toward the following information; further,
model with respect to the evolving pharmacy technician To encourage the FDA to establish a standardized elec-
workforce as the optimal approach to protecting public tronic format and reporting standards that would be required
health and safety: (1) development and adoption of uniform for submission of data from foreign clinical trials; further,
state laws and regulations regarding pharmacy technicians, To support the ethical treatment of patients in foreign
(2) mandatory completion of an ASHP-accredited program clinical trials in accordance with international standards de-
of education and training as a prerequisite to pharmacy signed to protect human subjects; further,
technician certification, (3) mandatory certification by the To encourage public and private research to study the
Pharmacy Technician Certification Board as a prerequisite impact of the globalization of clinical trials on patient care.
to licensure by the state board of pharmacy, and (4) licensure
of pharmacy technicians by state boards of pharmacy grant- Medical Marijuana (1101)
ing the technician permission to engage in the full scope of Source: Council on Therapeutics
responsibilities authorized by the state; further, To oppose state legislation that authorizes the use of medi-
To advocate, with respect to certification, as an in- cal marijuana until there is sufficient evidence to support
terim measure until the optimal model is fully implemented, its safety and effectiveness and a standardized product that
that individuals be required either (1) to have completed an would be subject to the same regulations as a prescription
ASHP-accredited program of education and training or (2) drug product; further,
to have at least one year of full-time equivalent experience To encourage research to define the therapeutically
as pharmacy technicians before they are eligible to become active components, effectiveness, safety, and clinical use of
medical marijuana; further,
certified; further,
To advocate for the development of processes that such advertising is provided in an understandable format, at
would ensure standardized formulations, potency, and quality a level of health literacy that allows the intended audience
of medical marijuana products to facilitate research; further, to make informed decisions, and includes a description of
To encourage the Drug Enforcement Administration to the established patient-health care provider relationship as a
eliminate barriers to medical marijuana research, including critical source for information about the test and interpreta-
review of medical marijuana’s status as a Schedule I con- tion of test results; further,
trolled substance, and its reclassification, if necessary to fa- To encourage pharmacists to educate consumers and
cilitate research; further, clinicians on the appropriate use of direct-to-consumer clini-
To oppose the procurement, storage, preparation, or cal genetic tests for disease diagnosis and drug therapy man-
distribution of medical marijuana by licensed pharmacies or agement.
health care facilities for purposes other than research; further,
To oppose the smoking of marijuana in settings where Drug Product Shortages (1118)
smoking is prohibited; further, Source: Council on Public Policy
To encourage continuing education that prepares phar- To advocate that the Food and Drug Administration (FDA)
macists to respond to patient and clinician questions about have the authority to require manufacturers to report drug
the therapeutic and legal issues surrounding medical mari- product shortages and the reason(s) for the shortage, and to
juana use. make that information available to the public; further,
(Note: As defined by the Congressional Research To strongly encourage the FDA to consider, in its defi-
Service, the term medical marijuana refers to uses of botani- nition of “medically necessary” drug products, the patient
cal marijuana that qualify for a medical use exception under safety risks created by use of alternate drug products during
the laws of certain states and under the federal Investigational a shortage; further,
New Drug Compassionate Access Program. Botanical mari- To support government-sponsored incentives for man-
juana includes the whole or parts of the natural marijuana ufacturers to maintain an adequate supply of medically nec-
plant and therapeutic products derived therefrom, as op- essary drug products; further,
posed to drugs produced synthetically in the laboratory that To advocate laws and regulations that would (1) re-
replicate molecules found in the marijuana plant.) quire pharmaceutical manufacturers to notify the appropri-
ate government body at least 12 months in advance of vol-
Agricultural Use of Hormone and Prohormone Therapies untarily discontinuing a drug product, (2) provide effective
(1102) sanctions for manufacturers that do not comply with this
Source: Council on Therapeutics mandate, and (3) require prompt public disclosure of a no-
To advocate that the Food and Drug Administration and tification to voluntarily discontinue a drug product; further,
United States Department of Agriculture re-evaluate the ag- To encourage the appropriate government body to seek
ricultural use of hormone and prohormone therapies for pur- the cooperation of manufacturers in maintaining the supply
poses of animal growth promotion based on evidence dem- of a drug product after being informed of a voluntary deci-
onstrating potential adverse effects on human health; further, sion to discontinue that product.
To encourage additional research to better define the This policy supersedes ASHP policy 0319.
public health impact of using hormone therapies for agricul-
tural purposes. Poison Control Center Funding (1121)
Direct-to-Consumer Clinical Genetic Tests (1103) To advocate that poison control centers be considered an es-
Source: Council on Therapeutics sential emergency service; further,
To support research to validate and standardize genetic mark- To advocate for new and stable funding mechanisms
ers used in direct-to-consumer clinical genetic tests and guide for poison control centers to continue to provide these es-
the application of test results to clinical practice; further, sential and valuable services; further,
To encourage the Food and Drug Administration to To support the integration and coordination of poison
use existing authority to regulate these tests as medical de- control center services where appropriate.
vices and to work with the National Institutes of Health to
expedite establishment of a process to evaluate and approve Health Insurance Coverage for U.S. Residents (1001)
direct-to-consumer clinical genetic tests; further, Source: Council on Public Policy
To advocate that direct-to-consumer clinical genetic To advocate health insurance for all residents of the United
tests to support disease diagnosis or management of drug States, including coverage of medications and related phar-
therapy be provided to consumers only through the services macist patient-care services; further,
of appropriate health care professionals that order tests from
To advocate that the full range of available methods
laboratories that are certified under the Clinical Laboratories
be used to (1) ensure the provision of appropriate, safe, and
Improvement Amendments of 1988 (CLIA); further,
cost-effective health care services; (2) optimize treatment
To oppose advertising of direct-to-consumer clini-
outcomes; and (3) minimize overall costs without compro-
cal genetic tests unless such testing includes the established
mising quality; further,
patient-health care provider relationship as a mechanism to
To advocate that health insurers seek to optimize con-
provide information and interpretation of test results; further,
tinuity of care in their design of benefit plans.
To oppose advertising of direct-to-consumer clinical
genetic tests unless the following requirements are met: (1)
that the relationship between the genetic marker and the dis-
ease or condition being assessed is clearly presented, (2) that
the benefits and risks of testing are discussed, and (3) that
Risk Evaluation and Mitigation Strategies (1002) To encourage impartial private-sector entities to also
Source: Council on Public Policy conduct such studies.
To advocate for research on the impact of the Food and Drug This policy was reviewed in 2014 by the Council on
Administration’s Risk Evaluation and Mitigation Strategies Public Policy and by the Board of Directors and was found
(REMS) on patient safety, cost effectiveness, and pharmacy to still be appropriate.
workflow; further,
To advocate pharmacist involvement in the develop- Regulation of Home Medical Equipment Medication
ment and implementation of REMS; further, Products and Devices (1007)
To urge computer software vendors to assist pharma- Source: Council on Public Policy
cists in the identification of and compliance with REMS; To advocate for consistent regulatory oversight of all home
further, medical equipment, with the goals of continuity of care,
To advocate that any REMS that include constraint patient safety, and appropriate pharmacist involvement
on traditional drug distribution systems be consistent with whenever equipment is used for medication administration;
ASHP policy on restricted drug distribution. further,
This policy was reviewed in 2014 by the Council on To monitor the impact of the Centers for Medicare &
Public Policy and by the Board of Directors and was found Medicaid Services quality standards on the accreditation of
to still be appropriate. suppliers of medication-related durable medical equipment
and supplies.
FDA Authority on Recalls (1003) This policy was reviewed in 2014 by the Council on
Source: Council on Public Policy Public Policy and by the Board of Directors and was found
To strongly encourage the Food and Drug Administration to still be appropriate.
(FDA) to develop a standard recall notification process and
format to be used by all manufacturers to facilitate the timely Preservation of Antimicrobials for Medical Treatment
removal of recalled drugs; further, (1009)
To advocate that such notification should (1) come Source: Council on Therapeutics
from a single source, (2) clearly identify the recalled prod- To advocate that the Food and Drug Administration (FDA)
uct, (3) explain why the product is being recalled, (4) pro- eliminate future approval of antimicrobials for nontherapeu-
vide a way to report having the recalled product, (5) give tic uses in agricultural animals that represent a safety risk by
instructions on what to do with the recalled product, and (6) contributing to antibiotic resistance; further,
be provided concurrently to all entities in the supply chain; To encourage efforts to phase out and eliminate the
further, nontherapeutic uses of antimicrobials previously approved
To advocate that the FDA be given the authority to or- by the FDA; further,
der mandatory recalls of medications; further, To support the therapeutic use of antimicrobials in
To urge the FDA to require drug manufacturers and the animals only under the supervision of a veterinarian; further,
computer software industry to provide bar codes and data To encourage the FDA, Centers for Disease Control
fields for lot number, expiration date, and other necessary and Prevention, and other stakeholders to monitor and limit,
and appropriate information on all medication packaging, when effective alternatives are available, the therapeutic use
including unit dose, unit-of-use, and injectable drug packag- of antimicrobials that are essential to the treatment of criti-
ing, in order to facilitate compliance with recalls or with- cally ill human patients; further,
drawals and to prevent the administration of recalled prod- To advocate for the inclusion of pharmacists in antimi-
ucts to patients; further, crobial surveillance and related public health efforts based
To urge the FDA to encourage postmarketing reporting on pharmacists’ knowledge of antimicrobial drug products
of adverse events and product quality issues to enhance the and antimicrobial resistance.
recall system. This policy was reviewed in 2014 by the Council on
This policy was reviewed in 2014 by the Council on Therapeutics and by the Board of Directors was found to
Public Policy and by the Board of Directors and was found still be appropriate.
Use of Surrogate Endpoints for FDA Approval of Drug
Postmarketing Comparative Clinical and Pharmacoeco- Uses (1011)
nomic Studies (1004) Source: Council on Therapeutics
Source: Council on Public Policy To support the continued use of qualified surrogate endpoints
To advocate expansion of comparative clinical and phar- by the Food and Drug Administration (FDA) as a mecha-
macoeconomic studies on the effectiveness, safety, and cost nism to evaluate the effectiveness and safety of new drugs
comparison of marketed medications in order to improve and new indications for existing therapies, when measure-
therapeutic outcomes and promote cost-effective medication ment of definitive clinical outcomes is not feasible; further,
use; further, To support efforts by the FDA and other stakeholders
To advocate that such studies compare a particular to qualify surrogate endpoints; further,
medication with (as appropriate) other medications, medical To advocate that the FDA consistently enforce exist-
devices, or procedures used to treat specific diseases; further, ing requirements that drug product manufacturers complete
To advocate adequate funding for the Agency for postmarketing studies for drugs approved based on qualified
Healthcare Research and Quality and other federal agencies surrogate endpoints in order to confirm that the expected
to carry out such studies; further,
improvement in outcomes occurs, and to require that these to the pharmacy provider of the patient’s choice; (6) formu-
studies be completed in a timely manner. laries with sufficient flexibility to allow access to medically
This policy was reviewed in 2014 by the Council on necessary drugs; and (7) well-publicized, unbiased resources
Therapeutics and by the Board of Directors and was found to assist beneficiaries in enrolling in the most appropriate
to still be appropriate. plan for their medication needs.
(Note: Fully funded means the federal government will
Regulation of Interstate Pharmacy Practice (0909) make adequate funds available to fully cover the Medicare
Source: Council on Public Policy program’s share of prescription drug program costs; eli-
To advocate that state governments, including legislatures gible means the federal government may establish criteria
and boards of pharmacy, adopt laws and regulations that har- by which Medicare beneficiaries qualify for the prescription
monize the practice of pharmacy across state lines in order drug program.)
to provide a consistent, transparent, safe, and accountable This policy was reviewed in 2012 by the Council on
framework for pharmacy practice. Public Policy and by the Board of Directors and was found
This policy was reviewed in 2013 by the Council on to still be appropriate.
to still be appropriate. Federal Review of Anticompetitive Practices by Drug
Product Manufacturers (0814)
Regulation of Dietary Supplements (0811) Source: Council on Public Policy
Source: Council on Public Policy To strongly oppose anticompetitive practices by manufac-
To advocate that Congress grant authority to the Food and turers that adversely affect drug product availability and
Drug Administration (FDA) to (1) require that dietary sup- price; further,
plements undergo FDA approval for evidence of safety and To encourage appropriate federal review of these prac-
efficacy; (2) mandate FDA-approved dietary supplement tices.
labeling that includes disclosure of excipients; (3) mandate This policy was reviewed in 2012 by the Council on
FDA-approved patient information materials that describe Public Policy and by the Board of Directors and was found
safe use in a clear, standardized format, including the poten- to still be appropriate.
tial for interaction with medications and cautions for special
populations; and (4) establish and maintain an adverse-event FDA Authority to Prohibit Reuse of Brand Names (0719)
reporting system specifically for dietary supplements, and Source: Council on Public Policy
require dietary supplement manufacturers to report sus- To advocate for Food and Drug Administration authority to
pected adverse reactions to the FDA; further, prohibit reuse of brand names of prescription and nonpre-
To oppose direct-to-consumer advertising of dietary scription drugs when any active component of the product is
supplements unless the following criteria are met: (1) federal changed or after any other changes are made in the product
laws are amended to include all the requirements described that may affect its safe use.
above to ensure that dietary supplements are safe and ef- This policy was reviewed in 2011 by the Council on
fective; (2) evidence-based information regarding safety and Public Policy and by the Board of Directors and was found
efficacy is provided in a format that allows for informed de- to still be appropriate.
cision-making by the consumer; (3) the advertising includes
a recommendation to consult with a health care professional Minimum Effective Doses (0602)
before initiating use; (4) any known warnings or precautions Source: Commission on Therapeutics
regarding dietary supplement–medication interactions or di- To advocate that the Food and Drug Administration require
etary supplement-disease interactions are provided as part manufacturers to identify minimum effective doses for med-
of the advertising; and (5) the advertising is educational in ications and make this information available to health care
nature and includes pharmacists as a source of information. providers.
(Note: Dietary supplement as used in this policy is de- This policy was reviewed in 2010 by the Council on
fined by the Dietary Supplement Health and Education Act Therapeutics and by the Board of Directors and was found
of 1994, as amended; 21 U.S.C. 321.) to still be appropriate.
Public Policy and by the Board of Directors and was found Streamlined Licensure Reciprocity (0612)
to still be appropriate. Source: Council on Legal and Public Affairs
To advocate that state boards of pharmacy grant temporary
Medicare Prescription Drug Benefit (0813) licensure to pharmacists who are relocating from another
Source: Council on Public Policy state in which they hold a license in good standing, permit-
To strongly advocate a fully funded prescription drug pro- ting them to engage in practice while their application for
gram for eligible Medicare beneficiaries that maintains conti- licensure reciprocity is being processed; further,
nuity of care and ensures the best use of medications; further, To advocate that the National Association of Boards
To advocate that essential requirements in the program of Pharmacy collaborate with state boards of pharmacy to
include (1) appropriate product reimbursement; (2) afford- streamline the licensure reciprocity process.
ability for patients, including elimination of coverage gaps; This policy was reviewed in 2010 by the Council on
(3) payment for indirect costs and practice expenses related Public Policy and by the Board of Directors and was found
to the provision of pharmacist services, based on a study of to still be appropriate.
those costs; (4) appropriate coverage and payment for pa-
tient care services provided by pharmacists; (5) open access
Postmarketing Safety Studies (0515) Intermediate Category of Drugs (0220)

Source: Council on Legal and Public Affairs Source: Council on Legal and Public Affairs
To advocate that Congress grant the Food and Drug Adminis To support, with appropriate changes in federal statutes and
tration (FDA) authority to require the manufacturer of an regulations, the establishment of an intermediate category of
approved drug product or licensed biologic product to conduct drug products that do not require a prescription but are avail-
postmarketing studies on the safety of the product when the able only from pharmacists and licensed health care profes-
agency deems it to be in the public interest; further, sionals who are authorized to prescribe medications; further,
To advocate that Congress grant FDA broader author- To base such support on the following facts:
ity to require additional labeling or withdrawal of the prod-
uct on the basis of a review of postmarketing studies; further, 1. Some drug products that are potential candidates for
To advocate that Congress provide adequate funding switching from prescription-only to nonprescription
to FDA to fulfill this expanded mission related to postmar- status raise concerns about patient safety as nonpre-
keting surveillance. scription products; these products could be better
This policy was reviewed in 2014 by the Council on controlled, monitored, and evaluated by making them
Public Policy and by the Board of Directors and was found available only from pharmacists and licensed health
to still be appropriate. care professionals who are authorized to prescribe
medications; and
Mandatory Registry of Clinical Trials (0516) 2. Pharmacists have the education, training, and exper-
Source: Council on Legal and Public Affairs tise to help patients make appropriate therapeutic deci-
To advocate disclosure of the most complete information on sions associated with the use of such drug products;
the safety and efficacy of drug products; further, further,
To advocate that the Department of Health and Human
Services establish a mandatory registry for all Phase II, III, To support that the regulatory system for this inter-
and IV clinical trials that are conducted on drugs intended mediate category of drug products contain the following
for use in the United States; further, features:
To advocate that each clinical trial have a unique iden-
tifier; further, 1. Drug products appropriate for this intermediate
To advocate that all data from registered clinical trials category would be identified through the advice of
be posted electronically with unrestricted access, and that pharmacists, physicians, and other licensed health
such posting occur (1) after Food and Drug Administration professionals who are authorized to prescribe medi-
approval of the related new product but before marketing cations, on the basis of the medical conditions to be
begins and (2) as soon as possible for trials completed after treated and potential adverse effects (as indicated in
initial marketing. FDA-approved labeling);
This policy was reviewed in 2014 by the Council on 2. Pharmacists would be able to provide drugs in this in-
Public Policy and by the Board of Directors and was found termediate category directly to patients without a pre-
to still be appropriate. scription, on the basis of appropriate assessment and
professional consultation;
Importation of Pharmaceuticals (0413) 3. Licensed health professionals who currently have
Source: Council on Legal and Public Affairs prescribing authority would continue to have the
To advocate for the continuation and application of ability to prescribe medications in this intermediate
laws and regulations enforced by the Food and Drug category; and
Administration and state boards of pharmacy with 4. Data from postmarketing surveillance, epidemiologic
respect to the importation of pharmaceuticals in order to studies, and adverse-drug-reaction reporting would be
(1) maintain the integrity of the pharmaceutical supply collected to help determine a drug product’s eventual
chain and avoid the introduction of counterfeit products movement to nonprescription status, return to pre-
into the United States; (2) provide for continued patient scription-only status, or continuation in the intermedi-
access to pharmacist review of all medications and pre- ate category.
serve the patient-pharmacist-prescriber relationship; and
(3) provide adequate patient counseling and education, This policy was reviewed in 2011 by the Council on
particularly to patients taking multiple high-risk medica- Public Policy and by the Board of Directors and was found
tions; further, to still be appropriate.
To urge the FDA and state boards of pharmacy to
vigorously enforce federal and state laws in relation to Greater Access to Less Expensive Generic Drugs (0222)
importation of pharmaceuticals by individuals, distributors Source: Council on Legal and Public Affairs
(including wholesalers), and pharmacies that bypass a safe To support legislation and regulations that promote greater
and secure regulatory framework. patient access to less expensive generic drug products.
Public Policy and by the Board of Directors and was found Public Policy and by the Board of Directors and was found
to still be appropriate. to still be appropriate.
FDA’s Public Health Mission (0012) To support an ongoing dialogue between FDA and
Source: Council on Legal and Public Affairs ASHP for the purpose of exploring ways to advocate the best
To support the Food and Drug Administration’s public health use of FDA-regulated products by consumers and health
mission of ensuring the safety and effectiveness of drugs, care professionals.
biologics, and medical devices through risk assessment, ap- This policy was reviewed in 2014 by the Council on
propriate product approval, labeling approval, manufactur- Public Policy and by the Board of Directors and was found
ing oversight, and consultation with health professionals, to still be appropriate.
while deferring to state regulation and professional self-reg-
ulation on matters related to the use of drugs, biologics, and Generic Pharmaceutical Testing (9010)
medical devices; further, Source: House of Delegates Resolution
To support the allocation of sufficient federal re- To support and foster legislative and regulatory initiatives
sources to allow FDA to meet its defined public health mis- designed to improve and restore public and professional
sion; further, confidence in the drug approval and regulatory process in
To support the appointment of practicing pharmacists which all relevant data are subject to public scrutiny.
to FDA advisory committees as one mechanism of ensuring This policy was reviewed in 2010 by the Council on
that decisions made by the agency incorporate the unique Public Policy and by the Board of Directors and was found
knowledge of the profession of pharmacy for the further to still be appropriate.
benefit of the patient; further,
Government, Law, and Regulation–Statements 203
ASHP Statement on Criteria for an Intermediate

Category of Drug Products
Position products that would bridge the large gap between prescrip-
tion and nonprescription status.1,8,9 An intermediate drug
The American Society of Health-System Pharmacists category could improve patient access to medications that
(ASHP) supports the establishment of an intermediate cat- offer substantial public health benefit but present challenges
egory of drug products that would not require a prescription for safety or effectiveness if used under existing models for
but would be available from a pharmacist after appropriate nonprescription drug dispensing. Two concerns regarding
patient assessment and professional consultation.1 These the use of existing models are that (1) a product’s labeling
drug products would continue to be available by prescription information may be beyond most consumers’ capacity to
from licensed health care professionals who are authorized understand (or may be subject to misinterpretation) and (2)
to prescribe medications. Drug products appropriate for this monitoring procedures are not readily accessible to patients.
intermediate category should have proven public health ben- Pharmacists’ expertise, licensure, and education, which in-
efits and be identified by processes that include the input and cludes instruction on physiology, pharmacology, disease
advice of experts, such as pharmacists, physicians, and other management, and physical assessment, make pharmacists
licensed health care professionals. Identification of drug well qualified to help patients make appropriate therapeutic
products for inclusion in the intermediate category should decisions about the use of these drug products.
be based on the medical condition to be treated and potential The terms “behind-the-counter (BTC) drugs” and
adverse effects of the drug. Concerns that patients may not “pharmacist-only drugs” have also been used to describe the
be able to fulfill a substantial self-care role associated with proposed intermediate category of drug products. While an
these drug products will be alleviated by taking into consid- FDA-established BTC category does not currently exist, the
eration the benefits of pharmacist oversight of these drug term BTC has been used to refer to drug products such as
regimens. Data from postmarketing surveillance, epidemio- pseudoephedrine and levonorgestrel (marketed as Plan B)
logic studies, and adverse-drug-reaction reports should be that are available for purchase only at the pharmacy coun-
collected and analyzed to evaluate the ongoing safety and ter.10,11 Implementation of that restriction has largely been
effectiveness of drug products placed in this category. This a policing action (e.g., to restrict the amount of drug a pa-
information would be used to determine whether the prod- tient can obtain or to confirm the patient’s age). In some in-
uct would remain in the intermediate category, return to stances, these functions are completed by pharmacy support
prescription-only status, or move to nonprescription status. staff under the supervision of a pharmacist. ASHP recom-
mends the use of the terminology intermediate category of
drugs to describe drug products appropriate for this category
Background that would be used by patients in conjunction with clini-
cal assessment and consultation provided by pharmacists.
Rationale for Establishing an Intermediate Drug Distribution of the aforementioned nonprescription products
Category. Reclassification of prescription drug products to via an intermediate category model of dispensing could im-
nonprescription status (e.g., antifungal products used for prove appropriate use of those products.
the treatment of vaginitis, nonsedating antihistamines) has The purpose of this statement is to describe the cri-
been associated with improvements in patient autonomy, teria that should be used to identify drug products for in-
health care knowledge, and self-care behavior.2-4 However, clusion in an intermediate category. While the practice
proposals to reclassify some prescription drug products to implications of an intermediate drug category are briefly
nonprescription status have been denied because of con- described, that discussion is beyond the scope of this state-
cerns about safety and whether patients would be capable of ment. Pharmacoeconomic analyses should be conducted to
determining if they were suitable candidates for treatment. assess the overall impact and costs of an intermediate cate-
In 2008, for example, the Food and Drug Administration gory of drug products on patients, health systems, and health
(FDA) ruled a third time against making lovastatin, a hy- insurers, and new models of reimbursement for pharmacists’
droxymethylglutaryl-coenzyme A reductase inhibitor (or services should be developed. It should be noted that a few
statin), available without a prescription,5 although the pre- studies have demonstrated that overall costs to the health
dicted public health benefit of increasing the availability of system decrease when the cost of these medications is not
statins was estimated to range between 23,000 and 33,000 transferred solely to the patient.12,13 Alternative reimburse-
coronary heart disease events prevented per 1 million ment models, such as insurance coverage for these products,
treated for 10 years.6 ASHP supports inclusion of statins in would be necessary to optimize the use of the intermediate
an intermediate category of drug products that provides the category of drug products.
benefit of pharmacist oversight.7 Other drug products that
should be considered for the intermediate category include
injectable epinephrine to treat anaphylaxis; inhaled cortico- Criteria for an Intermediate
steroids, leukotriene modifiers, and inhaled ß-agonists used Category of Drug Products
in the treatment of asthma; s elect therapies for osteoporosis
and hypertension; and vaccines. Appropriate identification of drug products for inclusion
ASHP and other pharmacy organizations have long in the intermediate category should address the concerns
proposed the creation of an intermediate category of drug associated with a substantial self-care role for patients by
204 Government, Law, and Regulation–Statements
providing the benefits of pharmacist oversight of these drug tained between the pharmacist and the patient and that docu-
therapy regimens (e.g., assessing for appropriate indications, mentation of the care provided be available to the patient’s
contraindications, precautions, adverse drug events, drug other health care providers, upon approval of the patient to
interactions, and therapeutic response). ASHP believes drug provide such information. The exact nature and duration
products proposed for inclusion in the intermediate category of the patient–pharmacist relationship would depend on
should the condition being treated and the drug therapy selected.
A practice model that includes collaboration among the pa-
• Meet many of the criteria currently used to reclassify tient, the pharmacist, and the patient’s physician (or other
prescription drugs to nonprescription status (e.g., the primary care provider) would enhance the use of these drug
drug product has a well-established benefit:risk ratio products and result in improved patient outcomes.
and a wide safety margin), Increased pharmacist time for patient assessment,
• Have been marketed as a prescription product for a counseling, and documentation of services provided with
length of time and been used by a number of patients these drug products would require reimbursement for these
deemed sufficient by FDA to detect serious adverse cognitive services. In addition, other conditions and proce-
effects. Likewise, a product could be marketed as a dures would be necessary to ensure the safety and effective-
nonprescription product but would benefit from phar- ness of these therapies, including the following:
macist oversight because safety and effectiveness con-
cerns have arisen with its nonprescription use, • If the drug is to be used in conjunction with other
• Have evidence of effectiveness and safety for the dos- therapies, such as diet and exercise, information about
age and regimen recommended for the formulation in- those adjunct therapies should be readily available to
tended for intermediate classification, and the patient from the pharmacist or through recommen-
• Be used to prevent or treat a disease, symptom, or con- dation of the pharmacist or other health care provider.
dition that can be readily detected by the patient or iden- • Patient care services provided by the pharmacist
tified by the pharmacist or other health care provider. should be documented in the pharmacy record and
available for sharing with other health care providers.
Further, if the drug is used for a condition that requires lab- • Pharmacists and patients should provide information
oratory or other medical monitoring, the pharmacy should on actual or suspected adverse effects or drug interac-
be able to offer testing or have access to the results of that tions to programs such as MedWatch for the purposes
monitoring. Signs and symptoms of deterioration in health of drug safety surveillance.
and the need for medical attention should be identifiable by • Pharmacies should adopt standardized processes for
the pharmacist or patient, as should signs demonstrating the the use of medications in the intermediate category
effectiveness of the drug therapy. If the drug has the potential that would guide patient triage, treatment, and refer-
to rarely cause serious toxicity that can result in death or se- ral to a physician when necessary. The expertise of-
rious harm, there should be reliable early warning signs that fered by clinical practice guidelines and professional
can be readily detected and interpreted by the pharmacist or associations should serve as the basis for these pro-
patient. tocols, with appropriate modifications based on the
Antiinfective agents (systemic or other formulations) unique characteristics of the patient population at the
for which the emergence of resistance is a concern would not practice site.
be appropriate for the intermediate category. • Pharmacies should adhere to quality measures that
In applying these criteria, an independent decision would be developed to assess the care provided (simi-
should be made about each individual chemical entity, dos- lar to those offered by the Pharmacy Quality Alliance)
age form, and drug product because differences among vari- and engage in ongoing quality-improvement activi-
ous members of a drug class and dosage forms prevent using ties to assess and improve the quality of services pro-
therapeutic class as a basis for classifying groups of related vided.
drug products.
Because drug information is continually evolving, drug A detailed discussion of these topics is addressed by
products in the intermediate category may be reclassified as other ASHP position and guidance documents, including the
prescription or nonprescription medications as new effective- ASHP Statement on the Pharmacist’s Role in Primary Care14;
ness and safety information becomes available. Similarly, the ASHP Guidelines on Pharmacist-Conducted Patient
products could be permanently classified in the intermedi- Education and Counseling15; the ASHP Guidelines on the
ate category if ongoing evidence documents the necessity of Pharmacist’s Role in the Development, Implementation, and
pharmacist intervention to ensure safe and effective use. The Assessment of Critical Pathways16; the ASHP Guidelines
postmarketing surveillance of these medications through the on Documenting Pharmaceutical Care in Patient Medical
collaboration of FDA and product manufacturers should be Records17; and the ASHP Guidelines on Adverse Drug
supported, in part, by information reported by pharmacists Reaction Monitoring and Reporting.18
and patients to an established surveillance system, such as
MedWatch, or similar reporting mechanisms. Conclusion
Practice Implications An intermediate category of drug products would increase
patient access to and benefit from drug products that would
Implementation of the intermediate drug category would re- otherwise be available only by prescription. The use of ap-
quire that an ongoing relationship be established and main- propriate criteria for classifying drug products in an inter-
mediate drug category—in conjunction with pharmacist 12. West DS, Johnson JT, Hone SH. A 30-month evalua-
oversight of patient assessment, counseling, and monitor- tion of the effects on the cost and utilization of proton
ing—would improve public health without compromising pump inhibitors from adding OTC to drug benefit cov-
patient safety. erage in a state employee health plan. J Manag Care
Pharm. 2006; 12:25–32.
References 13. Trygstad TK, Hansen RA, Wegner SE. Evaluation of
product switching after a state Medicaid program be-
1. American Society of Health-System Pharmacists. gan covering loratadine OTC one year after market
ASHP policy position 0220: intermediate category availability. J Manag Care Pharm. 2006; 12:108–
of drugs. www.ashp.org/DocLibrary/BestPractices/ 20.
DistributionPositions.aspx (accessed 2008 Dec 3). 14. American Society of Health-System Pharmacists.
2. Brass EP. Implications of a switch from prescription to ASHP statement on the pharmacist’s role in primary
over-the-counter status for allergy drugs. Curr Allergy care. Am J Health-Syst Pharm. 1999; 56:1665–7.
Asthma Rep. 2004; 4:245–50. 15. American Society of Health-System Pharmacists.
3. Lipsky MS, Waters T. The “prescription-to-OTC ASHP guidelines on pharmacist-conducted patient
switch” movement. Its effects on antifungal vaginitis education and counseling. Am J Health-Syst Pharm.
preparations. Arch Fam Med. 1999; 8:297–300. 1997; 54:431–4.
4. Gurwitz JH, McLaughlin TJ, Fish LS. The effect of 16. American Society of Health-System Pharmacists.
an Rx-to-OTC switch on medication prescribing pat- ASHP guidelines on the pharmacist’s role in the de-
terns and utilization of physician services: the case of velopment, implementation, and assessment of critical
vaginal antifungal products. Health Serv Res. 1995; pathways. Am J Health-Syst Pharm. 2004; 61:939–
30:672–85. 45.
5. Merck and Company. Merck receives not approv- 17. American Society of Health-System Pharmacists.
able letter from FDA for OTC Mevacor (lovastatin) ASHP guidelines on documenting pharmaceutical care
20 mg. www.merck.com/newsroom/press_releases/ in patient medical records. Am J Health-Syst Pharm.
product/2008_0125a.html (accessed 2008 Feb 14). 2003; 60:705–7.
6. Brass EP, Allen SE, Melin JM. Potential impact on 18. American Society of Health-System Pharmacists.
cardiovascular public health of over-the-counter statin ASHP guidelines on adverse drug reaction monitor-
availability. Am J Cardiol. 2006; 97:851–6. ing and reporting. Am J Health-Syst Pharm. 1995;
7. American Society of Health-System Pharmacists. 52:417–9.
ASHP statement on the over-the-counter availability
of statins. Am J Health-Syst Pharm. 2005; 62:2420–
2. This statement was reviewed in 2012 by the Council on Therapeutics
8. National Association of Boards of Pharmacy. Groups and by the Board of Directors and was found to still be appropriate.
advocate various Plan B classifications as FDA delays
decision on OTC application. www.nabp.net/ftpfiles/ Developed through the ASHP Council on Therapeutics and ap-
newsletters/NABP/nabp022006.pdf (accessed 2008 proved by the ASHP Board of Directors on March 7, 2008, and by
Dec 3). the ASHP House of Delegates on June 10, 2008.
9. American Pharmacists Association. Report of the
APhA 2005 House of Delegates. Transition class of The assistance of Susan R. Dombrowski, B.S.Pharm., M.S., in draft-
drugs. J Am Pharm Assoc. 2005; 45:557. ing this statement is gratefully acknowledged.
10. Food and Drug Administration. Legal requirements
for the sale and purchase of drug products containing Copyright © 2009, American Society of Health-System Pharmacists,
pseudoephedrine, ephedrine, and phenylpropanol- Inc. All rights reserved.
amine. www.fda.gov/cder/news/methamphetamine.
htm (accessed 2008 Dec 3). The bibliographic citation for this document is as follows: American
11. Food and Drug Administration. Plan B: questions and Society of Health-System Pharmacists. ASHP statement on crite-
answers. www.fda.gov/cder/drug/infopage/planB/plan ria for an intermediate category of drug products. Am J Health-Syst
BQandA20060824.htm (accessed 2008 Dec 3). Pharm. 2009; 66:502–9.
ASHP Statement on the

Over-the-Counter Availability of Statins
The American Society of Health-System Pharmacists an absolute benefit in reducing risk of CHD for a given
(ASHP) believes that existing models for over-the-counter milligram-per-deciliter lowering of LDL-C. However, for
(OTC) dispensing do not provide the safeguards required individuals with lower LDL-C levels and fewer risk factors
to ensure the safe and effective use of 3-hydroxy-3-meth- for CHD, the benefits of lowering LDL-C level are less
ylglutaryl coenzyme A (HMG-CoA) reductase inhibitors dramatic.6
(“statins”) as part of a multimodal approach to preventing
coronary heart disease (CHD). ASHP supports the goal of Nonprescription Dispensing Models
more widespread use of CHD-preventive therapies, includ-
ing statin therapy, and encourages consideration of alter- The efficacy of statins in reducing LDL-C has prompted
native nonprescription dispensing models for statins that calls for more widespread use, including suggestions for a
would advance CHD prevention. reclassification of statins as an OTC medication. Although
Since 1985, ASHP has called for changes in federal ASHP does not support reclassification to OTC status as that
statutes and regulations to establish an intermediate category status is currently constructed, alternative nonprescription
of drug products that do not require a prescription but are models for dispensing these valuable medications should be
available only from pharmacists and other licensed health explored.
care professionals authorized to prescribe medications.1 To approve a reclassification to OTC status, FDA
ASHP believes consideration of OTC reclassification for reviewers must find that (1) a drug is safe and effective in
statins presents an opportunity to explore the creation of such its proposed use(s), (2) the benefits of the drug outweigh
a category of drugs. ASHP has suggested that the regulatory its risks, and (3) consumers will be able to use the drug’s
system for such an intermediate category of drug products labeling (e.g., its package insert) to safely use the medication
would allow pharmacists to provide drugs in this intermedi- in an OTC setting.7 ASHP believes a decision to approve
ate category directly to patients without a prescription, on the nonprescription dispensing models for statins should be
basis of appropriate assessment and professional consultation, based on evidence that, under the proposed model, the
while ensuring that licensed health professionals who target population would receive a clinical benefit in primary
currently have prescribing authority would continue to have prevention of CHD from the medication and patients
the ability to prescribe such medications. ASHP believes that can safely use the medication to achieve that clinical
under such a regulatory system, data from postmarketing benefit. To achieve the goal of safe and effective use, any
surveillance, epidemiologic studies, and adverse-drug- nonprescription dispensing model for statins should
reaction reporting should be collected to help determine a
drug product’s eventual movement to nonprescription sta-
tus, return to prescription-only status, or continuation in the
• Identify candidates for appropriate therapeutic inter-
ventions, including statin therapy, on the basis of cho-
intermediate category.1 ASHP believes statins are an ideal lesterol levels, other risk factors for CHD events, and
candidate for dispensing under such a model. the patient’s medical and family histories;
• Allow patients and health care providers to monitor
Background response to treatment, including adverse reactions; and
• Maximize the effectiveness of treatment by encouraging
ASHP supports the use of statins to lower cholesterol adherence to therapy and appropriate interactions with
and reduce morbidity and mortality in patients at risk for health care professionals.
cardiovascular events.2 Elevated cholesterol, specifically
low-density lipoprotein cholesterol (LDL-C), is an ASHP believes that before a patient begins statin
important risk factor for the development of CHD. ASHP therapy, a cardiac risk assessment should be performed by a
has recommended that evaluation and management of lipid competent health care professional in order to
disorders be guided by the recommendations of the National
Cholesterol Education Program (NCEP), the latest of which • Determine the patient’s LDL-C value, which can be
are contained in the Adult Treatment Panel III (ATP III) used as a baseline value if the patient is a candidate for
guidelines.3,4 Statins are considered the drug of choice for treatment;
most patients with dyslipidemia who require lipid-lowering • Assess the individual for other cardiovascular risk
therapy. They are effective in lowering elevated LDL-C, factors such as smoking, diabetes, hypertension, diet,
and studies have demonstrated that statins reduce the risk weight, amount of exercise, and family history of car-
of cardiovascular events in patients without known CHD diovascular disease; and
(primary prevention). In addition, statins have been shown • Develop the optimal treatment plan based on ATP III
to reduce cardiovascular events and mortality in patients guidelines and the assessment above.
with CHD (secondary prevention). Cardiovascular disease
is the leading cause of death for both men and women in Individuals with two or more risk factors or a family
the United States, and CHD is responsible for nearly 75% history of cardiovascular disease who have never been
of all deaths from cardiovascular disease.5 Individuals with evaluated should have a complete medical assessment
multiple cardiovascular risk factors and a low LDL-C derive and appropriate interventions by a physician. If statins are
an appropriate therapeutic option, they should be part of health care professionals.1 ASHP believes the regulatory
a multimodal approach to reducing the overall CHD risk, system for this intermediate category of drug products
which would include managing and treating modifiable should have the following features:
risk factors such as hypertension, smoking, obesity, diet,
and lack of exercise. Diet and exercise therapy should be a 1. Drug products appropriate for this intermediate
fundamental part of all cholesterol-lowering regimens. category would be identified through the advice of
pharmacists, physicians, and other licensed health
professionals who are authorized to prescribe medica
Current OTC Model tions, on the basis of the medical conditions to be
treated and potential adverse effects (as indicated in
Statins are not suitable for OTC status as that class is cur-
FDA-approved labeling);
rently regulated. One study has examined the use of statins
2. Pharmacists would be able to provide drugs in this
in a simulated OTC setting. The CUSTOM study8 was an
intermediate category directly to patients without a
open-label study designed to observe consumers’ initial and
prescription, on the basis of appropriate assessment
continued use of a statin to lower LDL-C. Although the re-
and professional consultation;
sults may indicate that some individuals in the study sample
3. Licensed health professionals who currently have
were able to use an OTC statin as directed, the study was, by
prescribing authority would continue to have the
the investigators’ own admission, not designed to evaluate
ability to prescribe medications in this intermediate
clinical outcomes and therefore not able to demonstrate effi-
category; and
cacy. The study certainly did not prove that the existing OTC
4. Data from postmarketing surveillance, epidemiologic
model would provide the level of counseling required to re-
studies, and adverse-drug-reaction reporting would
duce cardiovascular risk factors other than LDL-C levels.
be collected to help determine a drug product’s
However encouraging these results might seem, caution
eventual movement to nonprescription status, return
should be exercised in extrapolating such information to a
to prescription-only status, or continuation in the
larger population, especially information regarding safety.
intermediate category.1
Adverse drug effects should always be assessed, especially
if the medications that cause them are easily available to
Drugs that would raise safety and efficacy concerns if
the public. A system that relies on the voluntary reporting
used as nonprescription products could be better controlled,
of adverse drug effects by patients may be inadequate to
monitored, and evaluated if they were available only from
protect the public or detect subtle signals. It is imperative
pharmacists and licensed health care professionals who are au-
that the decision to reclassify a statin to a nonprescription
thorized to prescribe medications. Pharmacists have the educa-
status include a wide margin of safety. After statin therapy
tion, training, and expertise to help patients make appropriate
starts, ongoing evaluations should assess the patient’s
therapeutic decisions about the use of such products. ASHP
response, reassess risk factors, and monitor for and report
believes statins are a good candidate for dispensing under such
adverse events. The existing model for OTC medications
a model, much as is done in Great Britain, where simvastatin
would place the entire burden for performing this evaluation
was approved for “counterprescribing” in May 2004.9
and reassessment on the patient. Most patients are likely
to be unfamiliar with the system used to report an adverse
event, if the adverse event is even recognized. Although Conclusion
adverse events from prescription statins are rare, particularly
at lower doses, they can occur months or years after therapy ASHP supports nonprescription dispensing models for
is initiated. Since OTC status would encourage wider use statins that ensure their safe and effective use as part of a
of statins, these drugs might be used by individuals with multimodal approach to CHD prevention. Given the com-
multiple disease states or those taking potentially interacting plexities of therapies to prevent CHD, ASHP encourages
medications (e.g., cyclosporine, diltiazem, verapamil, macro consideration of alternatives to the current model of OTC
lide antibiotics, azole antifungals, or protease inhibitors). distribution for statins.
Because statins are a chronic therapy, new risks may be
introduced as the patient’s health varies, requiring vigilance References
on the part of the patient as well as health care providers.
ASHP believes, for these reasons, that reclassification 1. Policy Position 0220: Intermediate Category of Drugs.
of statins to OTC status as currently constructed is not In: Best practices for hospital and health-system phar-
advisable but that alternative nonprescription models for macy 2004–2005. Positions and practice documents of
dispensing these valuable medications should be explored. ASHP. Bethesda, MD: American Society of Health-
System Pharmacists; 2004:89.
2. ASHP Therapeutic Position Statement on the Use of
Alternative Nonprescription Models Statins in the Prevention of Atherosclerotic Disease in
Adults. Am J Health Syst Pharm. 2003; 60:593–8.
ASHP believes that there are alternatives to prescription- 3. Expert Panel on Detection, Evaluation, and Treatment
only status that would allow expanded use of statins of High Blood Cholesterol in Adults. Executive sum-
to reduce cardiovascular events in primary prevention mary of the Third Report of the National Cholesterol
patients. Since 1985, ASHP has had a policy urging changes Education Program (NCEP) Expert Panel on Detection,
in federal statutes and regulations to create an intermediate Evaluation, and Treatment of High Blood Cholesterol
category of drug products that do not require a prescription in Adults (Adult Treatment Panel III). JAMA. 2001;
but are available only from pharmacists and other licensed 285:2486–97.
4. National Cholesterol Education Program (NCEP) 9. Royal Pharmaceutical Society of Great Britain.
Expert Panel on Detection, Evaluation, and Treatment Concise version of practice guidance on the sale of
of High Blood Cholesterol in Adults (Adult Treatment OTC simvastatin. July 2004. Available at: http://www.
Panel III). Third Report of the National Cholesterol rpsgb.org. uk/pdfs/otcsimvastatincardguid.pdf (ac-
Education Program (NCEP) Expert Panel on cessed January 4, 2005).
Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults (Adult Treatment Panel III) final
report. Circulation. 2002; 106:3143–421.
This statement was reviewed in 2009 by the Council on
5. American Heart Association. 2002 heart and stroke
Therapeutics and by the Board of Directors and was found to still
statistical update. Available at: www.americanheart.
be appropriate.
org/presenter (accessed 2002 May 14).
6. Grundy SM, Cleeman JI, Merz CN et al. Implications
Approved by the ASHP Board of Directors on January 6, 2005,
of recent clinical trials for the National Cholesterol
and by the ASHP House of Delegates on June 14, 2005. Developed
Education Program Adult Treatment Panel III
through the ASHP Commission on Therapeutics.
Guidelines. Circulation. 2004; 110:227–39.
7. Food and Drug Administration, Center for Drug
Evaluation and Research, Endocrinologic and
Metabolic Drugs Advisory Committee, Questions
to the Committee (joint meeting of January 13–14, The bibliographic citation for this document is as follows: American
2005, to consider new drug application 21-213). Society of Health-System Pharmacists. ASHP statement on the
Available at: http://www.fda.gov/ohrms/dockets/ over-the-counter availability of statins. Am J Health-Syst Pharm.
ac/05/questions/2005-4086S2_02_FDA-Questions. 2005; 62:2420–2.
htm (accessed January 26, 2005).
8. Melin JM, Struble WE, Tipping RW et al. A consumer
use study of over-the-counter lovastatin (CUSTOM).
Am J Cardiol. 2004; 94:1243–8.
ASHP Statement on
Principles for Including Medications and
Pharmaceutical Care in Health Care Systems
Introduction Principle V. Pharmacists should have access to relevant patient
information to support their professional judgments and activi-
The United States government, individual state governments, ties. Pharmacists should be encouraged and permitted to make
and private health care systems are moving toward reforming additions to medical records for the purpose of adding their
the way that they provide health care to their citizens or ben- findings, conclusions, and recommendations. Pharmacists will
eficiaries. As they do so, policy makers must improve their respect the confidential nature of all patient information.
medication-use systems to address problems of access, qual-
ity, and cost of medicines and pharmaceutical care services. Principle VI. Health care systems must be designed to enable,
This document offers principles for achieving maximum foster, and facilitate communication and collaboration
value from the services of the nation’s pharmacists. among pharmacists and other care providers to ensure proper
Although pharmaceuticals and pharmaceutical care are coordination of patients’ medication therapies.
among the most cost-effective methods of health care available,
there is evidence that the public is not currently realizing the Principle VII. Quality assessment and assurance programs
full potential benefit from these resources. Illnesses related to related to individual patient care should be implemented
improper medication use are costing the health care systems at local levels through collaborative efforts of health care
in the United States billions of dollars per year in patient practitioners rather than through centralized bureaucracies.
morbidity and mortality. Pharmacists are prepared and eager Quality assessment and assurance procedures for medication
to help other health providers and patients prevent and resolve use (such as pharmacy and therapeutics committees, formulary
medication-related problems, and health care systems should systems, drug-use evaluation programs, and patient outcomes
facilitate and take advantage of pharmacists’ expertise. analyses) are most effective when the professionals who care for
These principles are offered to guide health policy covered patients are involved in the design and implementation
makers in their deliberations concerning the inclusion of of the procedures. Moreover, such programs must recognize
medications and pharmacists’ services in health care systems. local variations in epidemiology, demography, and practice
standards. Information related to quality assessment and
assurance activities must be held in confidence by all parties.
Principles
Principle VIII. Demonstration projects and evaluation studies
Principle I. Health care systems must make medications avail-
in the delivery of pharmaceutical care must be enabled, fos-
able to patients and provide for pharmaceutical care, which tered, and implemented. New services, quality assessment and
encompasses pharmacists’ health care services and health pro- assurance techniques, and innovative medication delivery sys-
motional activities that ensure that medications are used safely, tems are needed to improve the access to and quality of medi-
effectively, and efficiently for optimal patient outcomes. cation therapy and pharmaceutical care while containing costs.
Principle II. Careful distinction must be made between Principle IX. Health care policies that are intended to influ-
policies that affect pharmacist reimbursement and policies ence practices of those associated with pharmacy, such as the
that affect pharmacist compensation. Health care systems pharmaceutical industry or prescribers, should address those
must reimburse pharmacists for the medications they audiences directly rather than through policies that affect re-
provide patients (including the costs of drug products, the imbursement, compensation, or other activities of pharmacists.
costs associated with dispensing, and related administrative
costs). Health care systems also must compensate
pharmacists for the services and care that they provide to This statement was reviewed in 2012 by the Council on Public
patients, which result in improved medication use and which Policy and by the Board of Directors and was found to still be
may not necessarily be associated with dispensing. appropriate.
Principle III. Patients differ in their needs for pharmaceutical Approved by the ASHP Board of Directors, November 18, 1992,
care services. The method of compensating pharmacists and by the ASHP House of Delegates, June 7, 1993. Developed by
for their services must recognize the value of the different levels a committee of the Joint Commission of Pharmacy Practitioners and
and types of services that pharmacists provide to patients based subsequently reviewed and approved by the ASHP Council on Legal
on pharmacists’ professional assessments of patients’ needs. and Public Affairs.
Principle IV. Pharmacists must be enabled and encouraged Copyright © 1993, American Society of Hospital Pharmacists, Inc.
to use their professional expertise in making medication- All rights reserved.
related judgments in collaboration with patients and health
care colleagues. Health care systems must not erect barri- The bibliographic citation for this document is as follows: American
ers to pharmacists’ exercising professional judgments; nor Society of Hospital Pharmacists. ASHP statement on principles for
should health care systems prescribe specific services or including medications and pharmaceutical care in health care sys-
therapies for defined types of patients. tems. Am J Hosp Pharm. 1993; 50:756–7.
212 Medication Misadventures–Positions
Statutory Protection for Medication-Error Reporting approach to addressing medication errors while supporting
(1505) a nonthreatening reporting environment to encourage phar-
Source: Council on Public Policy macy staff and others to report actual and potential medica-
To collaborate with other healthcare providers, professions, tion errors in a timely manner; further,
and stakeholders to advocate and support state and federal To provide leadership in supporting a single, compre-
legislative and regulatory initiatives that provide liability hensive, hospital- or health-system-specific medication error
protection for the reporting of actual and potential medica- reporting program that (1) fosters a confidential, nonthreat-
tion errors by individuals and healthcare providers; further, ening, and nonpunitive environment for the submission of
To provide education on the role that patient safety or- medication error reports; (2) receives and analyzes these
ganizations play in liability protection. confidential reports to identify system-based causes of med-
This policy supersedes ASHP policy 0011. ication errors or potential errors; and (3) recommends and
disseminates error prevention strategies; further,
Support for Second Victims (1524) To provide leadership in encouraging the participation
Source: Council on Pharmacy Practice of all stakeholders in the reporting of medication errors to
To acknowledge that the patient is the primary victim in this program.
any medical error, unanticipated adverse patient event, or (Note: A just culture is one that has a clear and trans-
patient-related injury; further, parent process for evaluating errors and separating events
To acknowledge that involvement by healthcare per- arising from flawed system design or inadvertent human
sonnel in such events may cause them to become second error from those caused by reckless behavior, defined as a
victims; further, behavioral choice to consciously disregard what is known to
To recognize that a just culture and a healthy culture of be a substantial or unjustifiable risk.)
safety embrace a support system for second victims; further, This policy was reviewed in 2014 by the Council on
To encourage healthcare organizations to establish Pharmacy Practice and by the Board of Directors and was
programs to support second victims; further, found to still be appropriate.
To educate healthcare professionals (including those
in training), health organization administrators, and regula- Minimizing the Use of Abbreviations (0604)
tory agencies about the second-victim effect and available Source: Council on Administrative Affairs
resources. To support efforts to minimize the use of abbreviations in
health care; further,
Standardization of Small-Bore Connectors to Avoid To collaborate with others in the development of a
Wrong-Route Errors (1530) lexicon of a limited number of standard drug name abbre-
Source: Council on Pharmacy Practice viations that can be safely used in patient care.
To support the use of medication administration device con- This policy was reviewed in 2010 by the Council on
nectors and fittings that are designed to prevent misconnec- Pharmacy Management and by the Board of Directors and
tions and wrong-route errors; further, was found to still be appropriate.
To encourage healthcare organizations to prepare for
safe transition to use of medication delivery device connec- Drug Names, Labeling, and Packaging Associated with
tors and adapters that meet International Organization for Medication Errors (0020)
Standardization standards; further, Source: Council on Professional Affairs
To identify and promote the implementation of best To urge drug manufacturers and FDA to involve practic-
practices for preventing wrong-route errors. ing pharmacists, nurses, and physicians in decisions about
This policy supersedes ASHP policy 1018. drug names, labeling, and packaging to help eliminate (a)
look-alike and sound-alike drug names, and (b) labeling and
Just Culture (1115) packaging characteristics that contribute to medication er-
Source: Council on Pharmacy Practice rors; further,
To recognize that the principles of just culture promote an To inform pharmacists and others, as appropriate,
environment in health care organizations in which safety is about specific drug names, labeling, and packaging that have
valued, reporting of safety risks is encouraged, and a fair documented association with medication errors.
process is used to hold staff and leaders accountable; further, This policy was reviewed in 2014 by the Council on
To encourage hospitals and health systems to include Pharmacy Practice and by the Board of Directors and was
just culture as a component in organizational safety culture found to still be appropriate.
surveys and quality improvement initiatives.
Medication Errors and Risk Management (0021)
Just Culture and Reporting Medication Errors (1021) Source: Council on Professional Affairs
Source: Council on Pharmacy Practice To urge that pharmacists be included in health care orga-
To encourage pharmacists to exert leadership in establishing nizations’ risk management processes for the purpose of
a just culture in their workplaces and a nonpunitive systems (a) assessing medication-use systems for vulnerabilities
Medication Misadventures–Positions 213
to medication errors, (b) implementing medication-error Human Factors Concepts (9609)

prevention strategies, and (c) reviewing occurrences of Source: Council on Professional Affairs
medication errors and developing corrective actions. To encourage pharmacists to apply human factors concepts
This policy was reviewed in 2014 by the Council on (human errors related to inadequate systems or environ-
Pharmacy Practice and by the Board of Directors and was ment) in the prevention, analysis, and reporting of medi-
found to still be appropriate. cation errors; further,
To encourage research (in conjunction with other
Medication Misadventures (9805) groups, as appropriate) to identify human factors causes
Source: Council on Administrative Affairs of medication errors and opportunities for their prevention.
To affirm that pharmacists must assume a leadership role in This policy was reviewed in 2014 by the Council on
preventing, investigating, and eliminating medication mis- Pharmacy Practice and by the Board of Directors and was
adventures across the continuum of care. found to still be appropriate.
214 Medication Misadventures–Statements
ASHP Statement on Reporting Medical Errors
Position ing institution or practitioner or others involved in the

incident,
The incidence of death and serious harm caused by mistakes 4. A definition of “serious harm” that concentrates on
and accidents in health care is unacceptable.1 This serious long-term or irreversible patient harm, so as not to
public health problem merits top-priority national atten- overburden the reporting system,
tion. Addressing this issue will require major reforms and 5. National coordination and strong federal efforts to en-
sizable investment of resources throughout the health care sure compliance with standardized methods of report-
system, including the medication use process, which is a ing, analysis, and follow up, that emphasize process
particular focus of the American Society of Health-System improvement and avoid a culture of blame,
Pharmacists (ASHP). 6. Adequate resources devoted to report analysis, timely
ASHP believes that the following steps should be taken dissemination of advisories based on report analysis,
as part of a comprehensive national solution to the problem: and development of appropriate quality improvement
(1) The establishment of a standardized, uniform nationwide efforts, and
system (with the characteristics noted below) of mandatory 7. Periodic assessment of the system to ensure that it is
reporting of adverse medical events that cause death or seri- meeting its intent and not having serious undesired
ous harm, (2) continued development and strengthening of consequences.
systems for voluntary reporting of medical errors, and (3)
strengthening efforts to implement process changes that re- Experience associated with current mandatory state
duce the risk of future errors and improve patient care. reporting of adverse medical events and mandatory public
The fundamental purpose of reporting systems for health reporting of certain infectious diseases should be as-
medical errors is to learn how to improve the health care de- sessed, and the best practices of such programs should be
livery process to prevent these errors. Reporting of medical applied to the new system of mandatory reporting of adverse
errors must become culturally accepted throughout health medical events that cause death or serious harm.
care. A major investment of resources will be required in The primary goals of voluntary reporting of medical
the health care system to apply the lessons derived from the errors should be quality improvement and enhancement
reporting of medical errors. Marshaling those resources is of patient safety. Reports by frontline practitioners of er-
an urgent issue for the governing boards of health care in- rors and “near misses” are a strength of such programs
stitutions, health care administrators, health professionals, when report analysis and communication lead to preven-
purchasers of health care (including federal and state gov- tion of similar occurrences. The public interest will be
ernments), third party payers, public policy makers, creden- served if protection is granted to individuals who submit
tialing organizations, the legal profession, and consumers. reports to voluntary reporting programs. The Medication
Errors Reporting Program operated by the United States
Pharmacopeia in cooperation with the Institute for Safe
Requirements
Medication Practices is an important initiative that merits
strengthening; this program may be a model for voluntary
The primary goal of mandatory reporting of adverse medical
reporting of other types of medical error.
events that cause death or serious harm should be to foster
accountability for health care delivery process changes to pre-
vent errors or adverse medical events. If a patient dies or is se- Reference
riously harmed because of a mistake or accident in the health
care system, the practitioner or institution responsible for the 1. Institute of Medicine Division of Health Care Services
patient’s care should report the incident to a designated state Committee on Quality of Health Care in America.
health body. Further, states should be obligated to share infor- To err is human: building a safer health system.
mation based on these reports promptly with a national coor- Washington, DC: National Academy Press; 1999.
dinating body and with national programs that are designed
to improve the quality and enhance the safety of patient care.
ASHP’s support of a mandatory reporting system is This statement was reviewed in 2005 by the Council on Professional
contingent upon the system having the following character- Affairs and by the Board of Directors and was found to still be ap-
istics: propriate.
1. An overall focus on improving the processes used in Approved by the ASHP House of Delegates, June 5, 2000.
health care, with the proper application of technical
expertise to analyze and learn from reports, Copyright © 2000, American Society of Health-System Pharmacists,
2. Legal protection of confidentiality of patients, health Inc. All rights reserved.
care workers, and the information submitted to the
extent feasible while preserving the interest of public The bibliographic citation for this document is as follows: American
accountability, Society of Health-System Pharmacists. ASHP statement on report-
3. Nonpunitive in the sense that the submission of a re- ing medical errors. Am J Health-Syst Pharm. 2000; 57:1531–2.
port, per se, does not engender a penalty on the report-
Medication Misadventures–Statements 215
ASHP Statement on the Role

of the Medication Safety Leader
Position position is sometimes filled by a nurse or physician. The
medication safety leader may report to the organization’s
The American Society of Health-System Pharmacists (ASHP) risk-management department, its office of quality, or a senior
believes that medication safety is a fundamental responsibil- administrator (e.g., hospital vice president, chief medical of-
ity of all members of the profession of pharmacy. For a medi- ficer, chief executive officer). Reporting outside the phar-
cation safety program to succeed, however, it is essential that macy department may foster interdisciplinary approaches
there be an innovative leader to set a vision and direction, to medication safety. Medication safety leadership may en-
identify opportunities to improve the medication-use system, compass a single hospital or a group of organizations (e.g.,
and lead implementation of error-prevention strategies. The spanning a health system or at a corporate level of a larger
medication safety leader’s role includes responsibility for organization). Regardless of organization size, it is critical
leadership, medication safety expertise, influencing practice that the fundamentals of medication safety are the central
change, research, and education. ASHP believes that because component of the medication safety leader’s job function.
of their training, knowledge of the medication-use process, Although medication safety leaders may have other respon-
skills, and abilities, pharmacists are uniquely qualified to sibilities in smaller institutions, medication safety should re-
fill the roles and meet the responsibilities of the medication main their core responsibility, and they must be strategically
safety leader in hospitals and health systems. positioned and empowered to lead efforts to reduce the risks
of medication use.
The characteristics of a medication safety leader include
Background
1. A strong understanding of the facility’s internal systems
Hospital and health-system pharmacists have improved and processes developed through firsthand experience,
pharmacy systems over the past 60 years to reduce the risk observations, medication-use evaluations, interviews,
that medications could harm patients. Medication safety was and data analysis for a spectrum of patient populations
at the heart of such historic innovations in pharmacy ser- (e.g., pediatric, geriatric, cardiac, oncology).
vices as unit-dose systems, decentralized clinical pharmacy 2. Clinical expertise and a broad understanding of health
services, and intravenous admixture services. The crucial care systems and processes to facilitate accurate inter-
leadership role of pharmacists in medication safety has been pretation of clinical events.
summarized as follows: 3. Knowledge of and experience with all aspects of the
medication-use system, including procurement, pre-
Pharmacy leadership is the core of a successful medi- scribing, transcribing, preparation, distribution, ad-
cation safety program. Pharmacy leaders can play an ministration, documentation, and monitoring.
enormously important role in performance improve- 4. Strong analytical skills and an understanding of sta-
ment. They can be part of the senior leadership team’s tistics, population data, and the concepts of risk and
DNA because their impact and view go far beyond the prioritization.
walls of the pharmacy . . . . Pharmacists can play an 5. Knowledge of performance-improvement methodol-
important role as leaders to reduce patient safety risks, ogy and tools, including root cause analysis (RCA),
optimize the safe function of medication management failure mode and effects analysis (FMEA), cause-and-
systems, and align pharmacy services with national ini- effect diagramming, process-flow mapping, and meth-
tiatives that measure and reward quality performance.1 ods for monitoring projects and measuring the prog-
ress of performance-improvement initiatives.
The landmark Institute of Medicine (IOM) report To Err 6. Three or more years of posttraining health-system
Is Human: Building a Safer Health System2 generated practice experience.
major patient safety initiatives by government agencies, 7. Demonstrated leadership skills.
regulatory and accrediting bodies, professional and orga- 8. Excellent small- and large-group presentation skills.
nizational associations, and health care organizations. The 9. Excellent oral communication skills, especially the
Joint Commission National Patient Safety Goals (NPSGs)3 ability to communicate to all types of health care
are an example of a response to the original IOM report. providers as individuals as well as in small and large
The Pharmacy Practice Model Initiative4 and the National groups.
Quality Forum Safe Practice 185 incorporate medication 10. Excellent writing and editing skills.
safety principles to ensure optimal patient safety and out- 11. Strong personal belief that resolving the problem of
comes. medication errors is a systems issue and not an indi-
The medication safety leader (also referred to as a vidual health care provider issue.
medication safety officer, medication safety manager, or 12. Ability to function proactively rather than reactively.
medication safety coordinator, among other titles) is a clini- 13. Strong personal belief in the concept of a “just cul-
cal practitioner designated by an organization to serve as the ture”6 that enhances transparency, opens participation
authoritative expert in safe medication use. Traditionally, the to all health care professionals, and fosters a “lessons
medication safety leader has been a clinical pharmacist or learned” environment in an organization’s medication
manager within the department of pharmacy, although the error reporting system.
14. Understanding of concepts and application of safety Leadership. To provide leadership, the medication safety
principles, continuous quality improvement, and hu- leader will
man factors engineering.
15. Appropriate assertiveness. 1. Develop a vision of an ideal safe medication-use sys-
16. A passion for medication safety and improving patient tem for the organization.
outcomes. 2. Oversee the planning, creation, review, and refinement
17. Proven success in working with interdisciplinary of a medication safety plan.
teams and engaging diverse groups. 3. Proactively develop and lead implementation of error-
18. Strong personal belief in engaging patients as part of prevention strategies based on practice standards, lit-
the health care team. erature review, medication safety tools, and analysis of
19. Eagerness to learn from events outside one’s own fa- the organization’s medication safety data.
cility (e.g., through external sources of information) 4. Participate in the planning, design, and implementa-
to apply learning about what went wrong in order to tion of the organization’s medication-use technology
identify and remedy possible system weaknesses to and automation systems.
prevent patient harm.7 5. Build a culture of safety through “lesson learned”
education and communication across the entire or-
The scope of a medication safety leader’s responsibilities ganization.
reaches into every corner of the health care system and en- 6. Oversee processes to collect information on the or-
compasses many roles, such as educator, preceptor, mentor, ganization’s medication errors and system failures to
detective, compliance officer, risk manager, engineer, ac- ensure that they are captured and barriers to reporting
countant, statistician, computer analyst, and counselor. A are addressed.
typical day may include attending safety rounds, precepting 7. Ensure compliance with state and federal regulatory
pharmacy students and residents, writing policies, review- and legal requirements relating to medication safety
ing adverse drug reactions and medication error reports, and assist in the accreditation process by ensuring that
developing error-prevention strategies, leading process- the organization’s medication-use processes meet appli-
improvement teams, implementing action items, reviewing cable medication management standards and NPSGs.
smart pump libraries, ensuring safe use of automated medi-
cation dispensing systems, assessing the safety of replace- Medication Safety Expertise. In the role of medication
ment drug products during drug shortages, orienting new safety expert, the medication safety leader will
professional staff, assisting with medication reconciliation,
conducting tracers to ensure compliance with accredita- 1. Serve as an authoritative resource on medication
tion standards (e.g., Joint Commission medication manage- safety for the organization.
ment standards and NPSGs), working with practitioners to 2. Contribute the medication safety perspective for technol-
resolve acute events, attending medical staff meetings, and ogy initiatives.
educating the corporate board on the culture of safety. Most 3. Contribute the medication safety perspective to inter-
medication safety leaders quickly find themselves involved nal and external emergency-preparedness planning.
in many projects and committees as well as serving as the 4. Serve as an internal consultant to investigate medica-
contact person when nursing, pharmacy, or medical staff tion safety events or issues and develop recommenda-
have questions or problems. The medication safety leader tions for action.
needs a solid understanding of patient safety principles and 5. Serve as the chair of the medication safety committee,
must have the ability to prioritize work activities to have a whose duties may include setting the agenda, review-
positive impact on the safety of patient care. The medication ing general and specific error reports, and examining
safety leader should strive to acquire additional skills crucial the progress of projects and initiatives assigned to the
to success, such as presentation and communication skills, medication safety team.
as well as expertise in process-improvement methodologies 6. Be knowledgeable in the application and use of a va-
such as Six Sigma and Lean. Formalized training in medica- riety of quality-improvement methodologies and tools
tion safety can be achieved through residency, fellowship, (e.g., FOCUS-PDCA or Lean methodologies, RCA,
and certificate programs and other methods of continuing FMEA).
education. ASHP supports the expansion of pharmacy edu- 7. Collect, review, and analyze, as the leader of review
cation and postgraduate residency training to include an em- teams, the organization’s medication-use, medication
phasis on medication safety.8 error, adverse drug reaction, and continuous quality-
improvement data (e.g., markers of adverse drug
Responsibilities of events, smart pump event data, triggers and surveil-
lance information, automated dispensing system and
Medication Safety Leaders bedside bar-code scanning reports) and use appropri-
ate data analysis techniques to identify needed im-
Medication safety leaders must collaborate with all types
provements and develop high-leverage error-reduction
of health care professionals, support staff, and management
strategies.
and consider all components of the medication-use process
8. Predict and prepare to manage medication safety is-
in both inpatient and clinic settings in order to improve med-
sues caused by potential or actual drug product short-
ication safety. The medication safety leader’s role includes
ages and the use of replacement drug products.
responsibility for leadership, medication safety expertise,
9. Maintain knowledge of trends and developments in
influencing practice change, research, and education.
the patient safety field through continuous profes-
Medication Misadventures–Statements 217
sional development: reading articles, journals, and re- of smart pumps and automated medication dis-
lated material; attending appropriate seminars, confer- pensing systems),
ences, or educational programs; and using information • Education of health care providers, other perti-
from the Institute of Safe Medication Practices (ISMP) nent staff, and (as possible) patients to ensure
National Medication Error Reporting Program, the they are competent in safe medication-use prac-
Food and Drug Administration (FDA) MedWatch pro- tices, and
gram, and similar programs. • Provision of effective ongoing programs and
10. Participate at local and national levels in patient safety presentations related to safe medication use to
and medication safety organizations and initiatives. diverse audiences (e.g., nursing, pharmacy, re-
spiratory care, and medical staff).
Influencing Practice Change. To influence practice change, 2. Share information about actual or potential medication
the medication safety leader will errors or harm with safety organizations such as ISMP,
FDA, drug or product manufacturers, and state error
1. Collaborate with other departments (e.g., pharmacy, reporting programs.
risk management, patient safety), hospital or health- 3. Conduct medication-use safety research through well-
system senior leadership, frontline staff, and designed, externally validated studies and implement
nursing and medical staff leadership to iden- evidence-based practices for medication safety.
tify and prioritize safety issues and develop risk- 4. Contribute to the literature on medication safety.
reduction strategies using the methods listed above to 5. Provide medication safety education to pharmacy col-
identify opportunities to improve medication safety. leagues, students, and residents, as well as other health
2. Manage changes in the medication-use system to care professionals.
enhance medication safety, ensure that appropriate 6. Integrate medication safety into orientation and train-
measures are taken to address and resolve medication ing for all health care providers who participate in the
safety issues, and see that hospital staff and faculty are medication-use process.
supported in providing safe care for patients.
3. Work closely with others (e.g., the patient safety of-
ficer) to integrate medication safety into the overall Conclusion
strategic plan for patient safety and coordinate medi-
cation safety initiatives with organizational patient
ASHP believes that pharmacists, as experts on medication
safety initiatives.
use, are uniquely qualified to serve as medication safety
4. Participate in or lead multidisciplinary hospital and
leaders. Medication safety leaders articulate the vision and
health-system committees concerned with medication
direction for improving the safety of the medication-use sys-
errors, adverse drug events and reactions, near misses,
tem to prevent patient harm. The medication safety leader’s
policy review, safe medication use, new product re-
role includes responsibility for leadership through direction
view, and patient safety to identify risk points and pri-
and prioritization, medication safety expertise, influencing
oritize system improvements to reduce the potential
practice change, research, and education. Through analysis
for medication error and patient harm.
of the organization’s medication safety data and literature
5. Consult with and advise specific clinical teams and the
hospital and health system generally on opportunities review, the medication safety leader will lead development
and strategies to improve patient care. and implementation of proactive error-prevention strategies
6. Encourage organizationwide medication error report- and build a culture of safety across the organization.
ing through an established and accepted error report-
ing system that utilizes appropriate error detection References
methods (e.g., trigger tools) and through other appro-
priate avenues such as the pharmacy and therapeutics 1. Burgess LH, Cohen MR, Denham CR. A new leader-
committee, medication safety committee, and patient ship role for pharmacists: a prescription for change. J
safety committee. Patient Saf. 2010; 6:31–7.
7. Develop effective methods for spreading best medica- 2. Kohn LT, Corrigan JM, Donaldson MS, eds. To err is
tion-use practices throughout the organization. human: building a safer health system. Washington,
8. Use continuous quality-improvement principles to DC: National Academy Press; 1999.
assess and report on the status of efforts to improve 3. Joint Commission. Facts about the National Patient
medication safety. Safety Goals. www.jointcommission.org/facts_about_
9. Periodically review and update clinical decision- the_national_patient_safety_goals/ (accessed 2012
support tools to alert staff to high-risk situations and Nov 3).
educate staff as needed. 4. The consensus of the Pharmacy Practice Model
Summit. Am J Health-Syst Pharm. 2011; 68:1148–52.
Research and Education. To further research and education 5. National Quality Forum. Safe Practices for Better
regarding medication safety, the medication safety leader will Healthcare 2009 Update: a consensus report. www.
qualityforum.org/publications/reports/safe_prac-
1. Design and assist in the implementation of education and tices_2009.aspx (accessed 2012 Jan 31).
orientation programs in safe medication use, including 6. Marx D. Patient safety and the “just culture”: a primer
• Development of competency assessment for for health care executives. New York: Columbia
staff tasks related to medication safety (e.g., use University Press; 2001.
7. Desired entry characteristics for those to be trained
for medication-use safety coordinator positions. www. Approved by the ASHP Board of Directors on April 13, 2012, and
ashp.org/DocLibrary/Accreditation/Regulations- by the ASHP House of Delegates on June 10, 2012. Developed
Standards/RTPEntryCharactMedUseSafety.aspx (ac- through the ASHP Section of Inpatient Care Practitioners Section
cessed 2011 Nov 28). Advisory Group on Medication Safety and approved by the ASHP
8. American Society of Health-System Pharmacists. Council on Education and Workforce Development on February 21,
Required educational outcomes, goals, and objec- 2012.
tives for postgraduate year two (PGY2) pharmacy
residencies in medication-use safety. www.ashp.org/ This statement was drafted by Lynn Eschenbacher, Pharm.D.,
DocLibrary/Accreditation/Regulations-Standards/ M.B.A., who declared no potential conflicts of interest.
RTPObjMedicationSafety032608.aspx (accessed 2012
Feb 3). Michael R. Cohen, M.S., Sc.D., FASHP; Deborah Saine, M.S.,
FASHP; and Allen Vaida, Pharm.D., FASHP are gratefully acknowl-
Suggested Readings edged for their contributions to this statement.
1. Cohen MR, ed. Medication errors. Washington, DC: ASHP gratefully acknowledges the following individuals and or-
American Pharmacists Association; 2007. ganizations for reviewing drafts of this statement (review does not
2. Manasse HR, Thompson KK, eds. Medication safety: imply endorsement): American Osteopathic Association (AOA);
a guide for health care facilities. Bethesda, MD: Emily Alexander, Pharm.D., BCPS; Dean A. Bennett, CPHQ; Jorge
American Society of Health-System Pharmacists; Carrillo, Pharm.D., M.S.; Toby Clark, M.Sc., FASHP; John B.
2005. Crosby, J.D. (AOA); Jean Douglas, Pharm.D.; Michael S. Edwards,
3. Hepler CD, Segal R. Preventing medication errors and Pharm.D., M.B.A., BCOP, FASHP; Roy Guharoy, Pharm.D.;
improving drug therapy outcomes: a management sys- Becky Harvey, Pharm.D.; John Hertig, Pharm.D., M.S.; James
tems approach. Boca Raton, FL: CRC Press; 2003. M. Hoffman, Pharm.D., M.S., BCPS; Justin M. Julius, Pharm.D.;
4. Joint Commission Resources. Medication use: a sys- Ambra King, Pharm.D.; Joanne Kowiatek, M.P.M., FASHP; Donna
tems approach to reducing errors, 2nd ed. Oakbrook Luong, Pharm.D.; Jeannell Mansur, Pharm.D., FASHP; Elaine
Terrace, IL: Joint Commission Resources; 2008. Mebel, Pharm.D., M.S.; John F. Mitchell, Pharm.D., FASHP; David
5. Committee on Quality of Health Care in America, B. Moore, M.P.A., CPh; Ashley M. Overy, Pharm.D.; Stephanie
Institute of Medicine. Crossing the quality chasm: a Peshek, Pharm.D., M.B.A., FASHP; James Ponto, M.S., FASHP;
new health system for the 21st century. Washington, Curt W. Quap, M.S., FASHP; Marcus Ravnan, Pharm.D., FASHP,
DC: National Academy Press; 2001. FCSHP; Jennifer Schultz, Pharm.D., FASHP; Nancy R. Smestad,
6. Committee on Data Standards for Patient Safety, M.S.; Robert L. Stein, Pharm.D., J.D.; and Jody Jacobson Wedret,
Institute of Medicine. Patient safety: achieving a new B.S.Pharm., FASHP, FCSHP.
standard for care. Washington, DC: National Academy
Press; 2004. Copyright © 2013, American Society of Health-System Pharmacists,
7. Committee on the Work Environment for Nurses Inc. All rights reserved.
and Patient Safety, Board on Health Care Services,
Institute of Medicine. Page A, ed. Keeping patients The bibliographic citation for this document is as follows: American
safe: transforming the work environment of nurses. Society of Health-System Pharmacists. ASHP statement on the role
Washington, DC: National Academy Press; 2004. of the medication safety leader. Am J Health-Syst Pharm. 2013;
8. Committee on Identifying and Preventing Medication 70:448–52.
Errors, Board on Health Care Services, Institute of
Medicine. Aspden P, Wolcott JA, Bootman JL, et al.,
eds. Preventing medication errors. Washington, DC:
National Academy Press; 2007.
Web Resources
www.ashp.org
www.ismp.org
www.safemedication.com
www.asmso.org
www.ahrq.gov
www.fda.gov/cder/drugSafety.htm
www.ihi.org
www.jointcommission.org/standards_information/npsgs.
aspx
www.leapfroggroup.org
www.qualityforum.org
www.nccmerp.org
www.usp.org
www.patientsafety.gov
Medication Misadventures–Guidelines 219
ASHP Guidelines on Adverse Drug Reaction

Monitoring and Reporting
Pharmacists in organized health care systems should develop used in humans for prophylaxis, diagnosis, or ther-
comprehensive, ongoing programs for monitoring and report- apy, excluding failure to accomplish the intended
ing adverse drug reactions (ADRs).1 It is the pharmacist’s re- purpose.”
sponsibility and professional obligation to report any suspected
ADRs. ADR-monitoring and reporting programs encourage FDA: For reporting purposes, FDA categorizes a
ADR surveillance, facilitate ADR documentation, promote the serious adverse event (events relating to drugs or
reporting of ADRs, provide a mechanism for monitoring the devices) as one in which “the patient outcome is
safety of drug use in high-risk patient populations, and stimulate death, life-threatening (real risk of dying), hospital-
the education of health professionals regarding potential ADRs. ization (initial or prolonged), disability (significant,
A comprehensive, ongoing ADR program should include persistent, or permanent), congenital anomaly, or re-
mechanisms for monitoring, detecting, evaluating, document- quired intervention to prevent permanent impairment
ing, and reporting ADRs as well as intervening and providing or damage.”
educational feedback to prescribers, other health care profes-
sionals, and patients. Additionally, ADR programs should focus For perspective, it may be helpful to note events that are
on identifying problems leading to ADRs, planning for positive not classified as ADRs. A side effect is defined by ASHP
changes, and measuring the results of these changes. Positive as an expected, well-known reaction resulting in little or
outcomes resulting from an ADR program should be empha- no change in patient management (e.g., drowsiness or dry
sized to support program growth and development. mouth due to administration of certain antihistamines or
ASHP does not suggest that there is a predictable rate nausea associated with the use of antineoplastics). ASHP
of incidence or severity of ADRs. The number and severity further defines a side effect as an effect with a predictable
of ADRs reported in a given organization or setting would frequency and an effect whose intensity and occurrence are
vary with the organization’s size, type, patient mix, drugs related to the size of the dose. Additionally, drug withdrawal,
used, and the ADR definition used. drug-abuse syndromes, accidental poisoning, and drug-over-
dose complications should not be defined as ADRs.
Definitions While individual health care organizations may need
to apply ADR surveillance to different degrees for differ-
ASHP defines a significant ADR as any unexpected, unin- ent groups of patients, ASHP believes it would be greatly
tended, undesired, or excessive response to a drug that beneficial if a common definition of ADRs were used in all
settings to facilitate reporting, collective surveillance, and
1. Requires discontinuing the drug (therapeutic or diag- ADR-trend research.
nostic),
2. Requires changing the drug therapy, Program Features
3. Requires modifying the dose (except for minor dosage
adjustments), A comprehensive ADR-monitoring and reporting program
4. Necessitates admission to a hospital, should be an integral part of an organization’s overall drug-
5. Prolongs stay in a health care facility, use system. An ADR-monitoring and reporting program
6. Necessitates supportive treatment, should include the following features:
7. Significantly complicates diagnosis,
8. Negatively affects prognosis, or 1. The program should establish
9. Results in temporary or permanent harm, disability, or a. An ongoing and concurrent (during drug ther-
death. apy) surveillance system based on the reporting
of suspected ADRs by pharmacists, physicians,
Consistent with this definition, an allergic reaction (an nurses, or patients.5
immunologic hypersensitivity, occurring as the result of b. A prospective (before drug therapy) surveillance
unusual sensitivity to a drug) and an idiosyncratic reaction system for high-risk drugs or patients with a high
(an abnormal susceptibility to a drug that is peculiar to the risk for ADRs.
individual) are also considered ADRs. c. A concurrent surveillance system for monitor-
Several other definitions of ADRs exist, including ing alerting orders. Alerting orders include the
those of the World Health Organization (WHO),2 Karch and use of “tracer” drugs that are used to treat com-
Lasagna,3 and the Food and Drug Administration (FDA).4 mon ADRs (e.g., orders for immediate doses
of antihistamines, epinephrine, and corticoste-
WHO: “Any response to a drug which is noxious and roids), abrupt discontinuation or decreases in
unintended, and which occurs at doses normally used in dosage of a drug, or stat orders for laboratory
man for prophylaxis, diagnosis, or therapy of disease, or assessment of therapeutic drug levels.6,7
for the modification of physiological function.” 2. Prescribers, caregivers, and patients should be notified
regarding suspected ADRs.
Karch and Lasagna: “Any response to a drug that 3. Information regarding suspected ADRs should be re-
is noxious and unintended, and that occurs at doses ported to the pharmacy for complete data collection
220 Medication Misadventures–Guidelines
and analysis, including the patient’s name, the pa- 13. In settings where it is possible, a pharmacy-coordinated
tient’s medical and medication history, a description ADR team or committee, consisting of a physician,
of the suspected ADR, the temporal sequence of the nurse, quality improvement leader, an administrator, and
event, any remedial treatment required, and sequelae. a pharmacist is recommended.12–15 The team should be
4. High-risk patients should be identified and monitored. charged with adopting a definition for the organization,
High-risk patients include but are not limited to pe- promoting awareness of the consequences of ADRs,
diatric patients, geriatric patients, patients with organ establishing mechanisms for identifying and reporting
failure (e.g., hepatic or renal failure), and patients re- ADRs, reviewing ADR patterns or trends, and develop-
ceiving multiple drugs.6 ing preventive and corrective interventions.
5. Drugs likely to cause ADRs (“high-risk” drugs) 14. Continuous monitoring of patient outcomes and pat-
should be identified, and their use should be moni- terns of ADRs is imperative. Findings from an ADR-
tored. Examples of drugs that may be considered as monitoring and reporting program should be incorporated
high risk include aminoglycosides, amphotericin, an- into the organization’s ongoing quality improvement ac-
tineoplastics, corticosteroids, digoxin, heparin, lido- tivities. The process should include the following:
caine, phenytoin, theophylline, thrombolytic agents, a. Feedback to all appropriate health care staff,
and warfarin.6 b. Continuous monitoring for trends, clusters, or
6. The cause(s) of each suspected ADR should be evalu- significant individual ADRs,
ated on the basis of the patient’s medical and medica- c. Educational efforts for prevention of ADRs, and
tion history, the circumstances of the adverse event, d. Evaluation of prescribing patterns, patient moni-
the results of dechallenge and rechallenge (if any), al- toring practices, patient outcomes, and the ADR
ternative etiologies, and a literature review. program’s effect on overall and individual patient
7. A method for assigning the probability of a reported outcomes.
or suspected ADR (e.g., confirmed or definite, likely,
possible, and unlikely) should be developed to cat- An overall goal of the ADR process should be the achieve-
egorize each ADR. Algorithms8–10 may be useful in ment of positive patient outcomes.
establishing the causes of suspected ADRs. Subjective
questions and the professional judgment of a pharma-
cist can be used as additional tools to determine the
Benefits
probability of an ADR. Questions might include the
following: An ongoing ADR-monitoring and reporting program can
a. Was there a temporal relationship between the provide benefits to the organization, pharmacists, other
health care professionals, and patients. These benefits in-
onset of drug therapy and the adverse reaction?
clude (but are not limited to) the following:
b. Was there a dechallenge; i.e., did the signs and
symptoms of the adverse reaction subside when
the drug was withdrawn? 1. Providing an indirect measure of the quality of phar-
c. Can signs and symptoms of the adverse reaction maceutical care through identification of preventable
be explained by the patient’s disease state? ADRs and anticipatory surveillance for high-risk
d. Were there any laboratory tests that provide drugs or patients.
evidence for the reaction being an ADR? 2. Complementing organizational risk-management
e. What was the patient’s previous general experi- activities and efforts to minimize liability.
ence with the drug? 3. Assessing the safety of drug therapies, especially
f. Did symptoms return when the agent was read- recently approved drugs.
ministered? 4. Measuring ADR incidence.
8. A method for ranking ADRs by severity should be es- 5. Educating health care professionals and patients
tablished.11 about drug effects and increasing their level of
9. A description of each suspected ADR and the out- awareness regarding ADRs.
comes from the event should be documented in the 6. Providing quality-assurance screening findings for use
patient’s medical record. in drug-use evaluation programs.
10. Serious or unexpected ADRs should be reported to the 7. Measuring the economic impact of ADR prevention as
Food and Drug Administration (FDA) or the drug’s manifested through reduced hospitalization, optimal
manufacturer (or both).a and economical drug use, and minimized organiza-
11. All ADR reports should be reviewed and evaluated by tional liability.
a designated multidisciplinary committee (e.g., a phar-
macy and therapeutics committee).
12. ADR-report information should be disseminated to Role of the Pharmacist
health care professional staff members for educational
purposes. Good topics for medical staff education in- Pharmacists should exert leadership in the development,
clude preventing ADRs and appropriate and effective maintenance, and ongoing evaluation of ADR programs.
care for patients who experience ADRs. Educational They should obtain formal endorsement or approval of such
programs can be conducted as morning “report” dis- programs through appropriate committees (e.g., a pharmacy
cussions, newsletters, “grand rounds” presentations, and therapeutics committee and the executive committee of
algorithms for treatment, and multidisciplinary re- the medical staff) and the organization’s administration. In
views of drug-use evaluations. Patient confidentiality settings where applicable, input into the design of the pro-
should be preserved.
gram should be obtained from the medical staff, nursing staff, 9. Kramer MS, Leventhal JM, Hutchinson TA, et al. An
quality improvement staff, medical records department, and algorithm for the operational assessment of adverse
risk managers.8,16–18 The pharmacist should facilitate drug reactions. I. Background, description, and in-
structions for use. JAMA. 1979; 242:623–32.
1. Analysis of each reported ADR, 10. Naranjo CA, Busto U, Sellers EM, et al. A method for
2. Identification of drugs and patients at high risk for estimating the probability of adverse drug reactions.
being involved in ADRs, Clin Pharmacol Ther. 1981; 30:239–45.
3. The development of policies and procedures for the 11. Hartwig SC, Siegel J, Schneider PJ. Preventability and
ADR-monitoring and reporting program, severity assessment in reporting adverse drug reac-
4. A description of the responsibilities and interactions tions. Am J Hosp Pharm. 1992; 49:2229–32.
of pharmacists, physicians, nurses, risk managers, and 12. Accreditation Manual for Hospitals. Chicago:
other health professionals in the ADR program, Joint Commission on Accreditation of Healthcare
5. Use of the ADR program for educational purposes, Organizations; 1989:121, 180.
6. Development, maintenance, and evaluation of ADR 13. Keith MR, Bellanger-McCleery RA, Fuchs JE.
records within the organization, Multidisciplinary program for detecting and evaluat-
7. The organizational dissemination and use of informa- ing adverse drug reactions. Am J Hosp Pharm. 1989;
tion obtained through the ADR program, 46:1809–12.
8. Reporting of serious ADRs to the FDA or the manu- 14. Kimelblatt BJ, Young SH, Heywood PM, et al.
facturer (or both), and Improved reporting of adverse drug reactions. Am J
9. Publication and presentation of important ADRs to the Hosp Pharm. 1988; 45:1086–9.
medical community. 15. Nelson RW, Shane R. Developing an adverse drug re-
action reporting program. Am J Hosp Pharm. 1983;
Direct patient care roles for pharmacists should include 40:445–6.
patient counseling on ADRs, identification and documentation 16. Swanson KM, Landry JP, Anderson RP. Pharmacy-
in the patient’s medical record of high-risk patients, monitor- coordinated, multidisciplinary adverse drug reaction
ing to ensure that serum drug concentrations remain within ac- program. Top Hosp Pharm Manage. 1992; 12(Jul):49–
ceptable therapeutic ranges, and adjusting doses in appropriate 59.
patients (e.g., patients with impaired renal or hepatic function). 17. Flowers P, Dzierba S, Baker O. A continuous quality
improvement team approach to adverse drug reaction re-
porting. Top Hosp Pharm Manage. 1992; 12(Jul): 60–7.
References 18. Guharoy SR. A pharmacy-coordinated, multidisci-
plinary approach for successful implementation of an
1. American Society of Hospital Pharmacists. ASHP adverse drug reaction reporting program. Top Hosp
technical assistance bulletin on hospital drug Pharm Manage. 1992; 12(Jul):68–74.
distribution and control. Am J Hosp Pharm. 1980;
37:1097–103.
2. Requirements for adverse reaction reporting. Geneva, a
To report an adverse drug event to the FDA, use the MedWatch
Switzerland: World Health Organization; 1975. program. Reports can be mailed (MedWatch, 5600 Fishers Lane,
3. Karch FE, Lasagna L. Adverse drug reactions—a criti- Rockville, MD 20852–9787), faxed (800-FDA-0178), called in
cal review. JAMA. 1975; 234:1236–41. (800-FDA-1088), or reported by modem (800-FDA-7737). An
4. Kessler DA. Introducing MedWatch, using FDA form easy-to-use FDA form 3500 can be used. This form should be avail-
3500, a new approach to reporting medication and able from a pharmacy.
device adverse effects and product problems. JAMA.
1993; 269:2765–8. Approved by the ASHP Board of Directors, November 16, 1994.
5. Prosser TR, Kamysz PL. Multidisciplinary adverse Revised by the ASHP Council on Professional Affairs. Supersedes a
drug reaction surveillance program. Am J Hosp previous version dated November 16, 1988.
Pharm. 1990; 47:1334–9.
6. Koch KE. Adverse drug reactions. In: Brown TR, Copyright © 1995, American Society of Health-System Pharmacists,
ed. Handbook of institutional pharmacy practice. 3rd Inc. All rights reserved.
ed. Bethesda, MD: American Society of Hospital
Pharmacists; 1992. The bibliographic citation for this document is as follows: American
7. Koch KE. Use of standard screening procedures to Society of Health-System Pharmacists. ASHP guidelines on adverse
identify adverse drug reactions. Am J Hosp Pharm. drug reaction monitoring and reporting. Am J Health-Syst Pharm.
1990; 47:1314–20. 1995; 52:417–9.
8. Karch FE, Lasagna L. Toward the operational identifi-
cation of adverse drug reactions. Clin Pharmacol Ther.
1977; 21:247–54.
ASHP Guidelines on Preventing

Medication Errors in Hospitals
The goal of drug therapy is the achievement of defined thera- injectable products, radiopharmaceuticals, radiopaque con-
peutic outcomes that improve a patient’s quality of life while trast media, anesthetic gases, blood-fraction drugs, dialysis
minimizing patient risk.1 There are inherent risks, both known fluids, respiratory therapy agents, investigational drugs, drug
and unknown, associated with the therapeutic use of drugs (pre- samples, drugs brought into the hospital setting by patients,
scription and nonprescription) and drug administration devices. and other chemical or biological substances administered to
The incidents or hazards that result from such risk have been patients to evoke a pharmacological response.6
defined as drug misadventuring, which includes both adverse Through a systems-oriented approach, the pharmacist
drug reactions (ADRs) and medication errors.2 This document should lead collaborative, multidisciplinary efforts to prevent,
addresses medication errors—episodes in drug misadventuring detect, and resolve drug-related problems that can result in
that should be preventable through effective systems controls patient harm.1 An understanding of the risk factors associated
involving pharmacists, physicians and other prescribers, nurses, with medication errors should enable improved monitoring of
risk management personnel, legal counsel, administrators, pa- patients and medications associated with increased risk for seri-
tients, and others in the organizational setting, as well as regula- ous errors and should enable the development of organizational
tory agencies and the pharmaceutical industry. systems designed to minimize risk.7 The pharmacist should par-
This document suggests medication error prevention ticipate in appropriate organizational committees and work with
approaches that should be considered in the development of physicians, nurses, administrators, and others to examine and
organizational systems and discusses methods of managing improve systems to ensure that medication processes are safe.
medication errors once they have occurred. These guide-
lines are primarily intended to apply to the inpatient hos- Types of Medication Errors
pital setting because of the special collaborative processes
established in the setting [e.g., formulary system, pharmacy Medication errors include prescribing errors, dispensing
and therapeutics (P&T) committee, and opportunity for errors, medication administration errors, and patient compliance
increased interaction among health-care providers]. errors. Specific types of medication errors are categorized in
Recommendations for practice settings other than hos- Table 1, based on a compilation of the literature.3,7–18
pitals are beyond the scope of this document, although many A potential error is a mistake in prescribing, dispensing,
of the ideas and principles may be applicable. or planned medication administration that is detected and cor-
Medication errors compromise patient confidence in the rected through intervention (by another health-care provider
health-care system and increase health-care costs. The prob- or patient) before actual medication administration. Potential
lems and sources of medication errors are multidisciplinary errors should be reviewed and tabulated as separate events from
and multifactorial. Errors occur from lack of knowledge, sub- errors of occurrence (errors that actually reach patients) to iden-
standard performance and mental lapses, or defects or failures tify opportunities to correct problems in the medication use sys-
in systems.3,4 Medication errors may be committed by both tem even before they occur. Detection of potential errors should
experienced and inexperienced staff, including pharmacists, be a component of the hospital’s routine quality improvement
physicians, nurses, supportive personnel (e.g., pharmacy process. Documentation of instances in which an individual
technicians), students, clerical staff (e.g., ward clerks), ad- has prevented the occurrence of a medication error will help
ministrators, pharmaceutical manufacturers, patients and their identify system weaknesses and will reinforce the importance
caregivers, and others. The incidence of medication errors is of multiple checks in the medication use system.
indeterminate; valid comparisons of different studies on med-
ication errors are extremely difficult because of differences in Recommendations for Preventing
variables, measurements, populations, and methods.2 Medication Errors
Many medication errors are probably undetected. The
outcome(s) or clinical significance of many medication Organizational systems for ordering, dispensing, and admin-
errors may be minimal, with few or no consequences that istering medications should be designed to minimize error.
adversely affect a patient. Tragically, however, some medi- Medication errors may involve process breakdowns in more
cation errors result in serious patient morbidity or mortal than one aspect of a system. This section provides recommen-
ity.3 Thus, medication errors must not be taken lightly, and dations to the management staff (general and departmental)
effective systems for ordering, dispensing, and administer- of hospitals, as well as to individual prescribers, pharmacists,
ing medications should be established with safeguards to nurses, patients, pharmaceutical manufacturers, and others.
prevent the occurrence of errors. These systems should in-
volve adequately trained and supervised personnel, adequate Organizational and Departmental Recommendations.
communications, reasonable workloads, effective drug han- Organizational policies and procedures should be estab-
dling systems, multiple procedural and final product checks lished to prevent medication errors. Development of the
by separate individuals, quality management, and adequate policies and procedures should involve multiple depart-
facilities, equipment, and supplies. ments, including pharmacy, medicine, nursing, risk manage-
The pharmacist’s mission is to help ensure that patients ment, legal counsel, and organizational administration. The
make the best use of medications.5 This applies to all drugs following recommendations are offered for organizational
used by inpatients or ambulatory patients, including oral or management and clinical staff: 3,8,11–14,16,19–29
Table 1.
Types of Medication Errors3,7–18,a
Type Definition
Prescribing error Incorrect drug selection (based on indications, contraindications, known allergies, existing
drug therapy, and other factors), dose, dosage form, quantity, route, concentration, rate of
administration, or instructions for use of a drug product ordered or authorized by physician (or
other legitimate prescriber); illegible prescriptions or medication orders that lead to errors that
reach the patient
Omission errorb The failure to administer an ordered dose to a patient before the next scheduled dose, if any
Wrong time error Administration of medication outside a predefined time interval from its scheduled administration
time (this interval should be established by each individual health care facility)
Unauthorized drug errorc Administration to the patient of medication not authorized by a legitimate prescriber for the patient
Improper dose errord Administration to the patient of a dose that is greater than or less than the amount ordered by the
prescriber or administration of duplicate doses to the patient, i.e., one or more dosage units in
addition to those that were ordered
Wrong dosage-form errore Administration to the patient of a drug product in a different dosage form than ordered by the prescriber
Wrong drug-preparation errorf Drug product incorrectly formulated or manipulated before administration
Wrong administration-technique errorg Inappropriate procedure or improper technique in the administration of a drug
Deteriorated drug errorh Administration of a drug that has expired or for which the physical or chemical dosage-form
integrity has been compromised
Monitoring error Failure to review a prescribed regimen for appropriateness and detection of problems, or failure
to use appropriate clinical or laboratory data for adequate assessment of patient response to
prescribed therapy
Compliance error Inappropriate patient behavior regarding adherence to a prescribed medication regimen
Other medication error Any medication error that does not fall into one of above predefined categories
a
The categories may not be mutually exclusive because of the multidisciplinary and multifactorial nature of medication errors.
b
Assumes no prescribing error. Excluded would be (1) a patient’s refusal to take the medication or (2) a decision not to administer the dose
because of recognized contraindications. If an explanation for the omission is apparent (e.g., patient was away from nursing unit for tests or medication
was not available), that reason should be documented in the appropriate records.
c
This would include, for example, a wrong drug, a dose given to the wrong patient, unordered drugs, and doses given outside a stated set of
clinical guidelines or protocols.
d
Excluded would be (1) allowable deviations based on preset ranges established by individual health care organizations in consideration of
measuring devices routinely provided to those who administer drugs to patients (e.g., not administering a dose based on a patient’s measured
temperature or blood glucose level) or other factors such as conversion of doses expressed in the apothecary system to the metric system and (2)
topical dosage forms for which medication orders are not expressed quantitatively.
e
Excluded would be accepted protocols (established by the pharmacy and therapeutics committee or its equivalent) that authorize pharmacists
to dispense alternate dosage forms for patients with special needs (e.g., liquid formulations for patients with nasogastric tubes or those who have
difficulty swallowing), as allowed by state regulations.
f
This would include, for example, incorrect dilution or reconstitution, mixing drugs that are physically or chemically incompatible, and inadequate
product packaging.
g
This would include doses administered (1) via the wrong route (different from the route prescribed), (2) via the correct route but at the wrong site
(e.g., left eye instead of right), and (3) at the wrong rate of administration.
h
This would include, for example, administration of expired drugs and improperly stored drugs.
1. Using the principles of the formulary system, the ordering, dispensing, and administration. The system should
P&T committee (or its equivalent)—composed of ensure adequate written and oral communications among
pharmacists, physicians, nurses, and other health personnel involved in the medication use process to opti-
professionals—should be responsible for formulating mize therapeutic appropriateness and to enable medications
policies regarding the evaluation, selection, and thera- to be prescribed, dispensed, and administered in a timely
peutic use of drugs in organized health-care settings. fashion. All systems should provide for review and verifica-
2. Care and consideration must be given in hiring and tion of the prescriber’s original order (except in emergency
assigning personnel involved in medication ordering, situations) before a drug product is dispensed by a pharma-
preparation, dispensing, administration, and patient cist. Any necessary clarifications or changes in a medication
education. Policies and procedures should be developed order must be resolved with the prescriber before a medica-
that ensure adequate personnel selection, training, su- tion is administered to the patient. Written documentation
pervision, and evaluation. This would include the need of such consultations should be made in the patient’s medi-
to ensure proper interviewing, orientation, evaluation of cal record or other appropriate record. Nursing staff should
competency, supervision, and opportunities for continu- be informed of any changes made in the medication order.
ing professional and technical education. Changes required to correct incorrect orders should be re-
3. Sufficient personnel must be available to perform tasks garded as potential errors, assuming the changes occurred in
adequately. Policies and procedures should ensure that time to prevent the error from reaching the patient.
reasonable workload levels and working hours are es- 6. There should be an ongoing, systematic program of qual-
tablished and rarely exceeded. ity improvement and peer review with respect to the safe
4. Suitable work environments should exist for the prep- use of medications. A formal drug use evaluation (DUE)
aration of drug products. Potential error sources within program, developed and conducted through collaborative
the work environment, such as frequent interruptions, efforts among medicine, pharmacy, and nursing, should be
should be identified and minimized. integrated and coordinated with the overall hospital qual-
5. Lines of authority and areas of responsibility within ity improvement program. To prevent medication errors, a
the hospital should be clearly defined for medication portion of the DUE program should focus on monitoring
the appropriate use of any drugs associated with a high possible. When 24-hour pharmacy service is not feasible,
frequency of adverse events, including specific drug a pharmacist must be available on an “on-call” basis.
classes (such as antimicrobials, antineoplastic agents, 10. The pharmacy manager (or designee), with the assis-
and cardiovascular drugs) and injectable dosage forms tance of the P&T committee (or its equivalent) and the
(e.g., potassium products, narcotic substances, heparin, department of nursing, should develop comprehensive
lidocaine, procainamide, magnesium sulfate, and insu- policies and procedures that provide for efficient and
lin). The quality improvement program should include a safe distribution of all medications and related supplies
system for monitoring, reviewing, and reporting medica- to patients. For safety, the recommended method of dis-
tion errors to assist in identifying and eliminating causes tribution within the organized health-care setting is the
of errors (system breakdowns) and preventing their recur- unit dose drug distribution and control system.
rence. Table 2 lists common causes of medication errors, 11. Except in emergency situations, all sterile and nonsterile
i.e., areas where there may be system breakdowns. drug products should be dispensed from the pharmacy
7. Pharmacists and others responsible for processing department for individual patients. The storage of non-
drug orders should have routine access to appropriate emergency floor stock medications on the nursing units
clinical information about patients (including medica- or in patient-care areas should be minimized. Particular
tion, allergy, and hypersensitivity profiles; diagnoses; caution should be exercised with respect to drug products
pregnancy status; and laboratory values) to help evalu- that have commonly been involved in serious medica-
ate the appropriateness of medication orders. tion errors or whose margin of safety is narrow, such as
8. Pharmacists should maintain medication profiles for concentrated forms of drug products that are intended to
all patients, both inpatients and ambulatory patients, be diluted into larger volumes (e.g., concentrated lido-
who receive care at the hospital. This profile should caine and potassium chloride for injection concentrate).
include adequate information to allow monitoring of All drug storage areas should be routinely inspected by
medication histories, allergies, diagnoses, potential pharmacy personnel to ensure adequate product integ-
drug interactions and ADRs, duplicate drug therapies, rity and appropriate packaging, labeling, and storage. It
pertinent laboratory data, and other information. is important that drug products and other products for
9. The pharmacy department must be responsible for the external use be stored separately from drug products for
procurement, distribution, and control of all drugs used internal use.
within the organization. Adequate hours for the provi- 12. The pharmacy director and staff must ensure that all
sion of pharmaceutical services must be maintained; drug products used in the organizational setting are
24-hour pharmaceutical service is strongly recom- of high quality and integrity. This would include, for
mended in hospital settings. In the absence of 24-hour example, (1) selecting multisource products supported
pharmaceutical service, access to a limited supply of by adequate bioavailability data and adequate product
medications should be available to authorized nonphar- packaging and labeling, (2) maintaining an unexpired
macists for use in initiating urgent medication orders. product inventory, and (3) keeping abreast of compen-
The list of medications to be supplied and the policies dial requirements.
and procedures to be used (including subsequent re- 13. The use of a patient’s own or “home” medications
view of all activity by a pharmacist) should be devel- should be avoided to the fullest extent possible. Use
oped by the P&T committee (or its equivalent). Items of such medications should be allowed only if there is
should be chosen with safety in mind, limiting wher- a need for the patient to receive the therapy, the drug
ever possible medications, quantities, dosage forms, product is not obtainable by the pharmacy, and no al-
and container sizes that might endanger patients. The ternative therapy can be prescribed. If such medica-
use of well-designed night cabinets, after-hours drug tions are used, the prescribing physician must write
carts, and other methods would preclude the need for an appropriate order in the patient’s medical record.
non-pharmacists to enter the pharmacy. Access to the Before use, a pharmacist should inspect and identify
pharmacy by nonpharmacists (e.g., nurses) for removal the medication. If there are any unresolved questions
of doses is strongly discouraged; this practice should with respect to product identity or integrity, the medi-
be minimized and eliminated to the fullest extent cation must not be used.
14. All discontinued or unused drugs should be returned
Table 2. to the department of pharmacy immediately on dis-
Common Causes of Medication Errors continuation or at patient discharge. Discharged
Ambiguous strength designation on labels or in packaging patients must not be given unlabeled drug products
Drug product nomenclature (look-alike or sound-alike to take home, unless they are labeled for outpatient
names, use of lettered or numbered prefixes and use by the pharmacy in accordance with state and
suffixes in drug names) federal regulations. Discharged patients should be
Equipment failure or malfunction counseled about use of any medications to be used
Illegible handwriting after discharge.
Improper transcription 15. It is recommended that there be computerized phar-
Inaccurate dosage calculation
macy systems in place that enable automated checking
Inadequately trained personnel
for doses, duplicate therapies, allergies, drug interac-
Inappropriate abbreviations used in prescribing
Labeling errors tions, and other aspects of use. Where possible, the use
Excessive workload of technological innovations such as bar coding is rec-
Lapses in individual performance ommended to help identify patients, products, and care
Medication unavailable providers. Pharmacy-generated medication administra-
tion records or labels are recommended to assist nurses authority, procedures to alert nurses and others to new
in interpreting and documenting medication activities. drug orders that need to be processed, standard medica-
16. Adequate drug information resources should be avail- tion administration times, and approved abbreviations).
able for all health-care providers involved in the drug 4. Drug orders should be complete. They should include
use process. patient name, generic drug name, trademarked name
17. Standard drug administration times should be estab- (if a specific product is required), route and site of
lished for the hospital by the P&T committee (or its administration, dosage form, dose, strength, quantity,
equivalent), with input from the departments of nurs- frequency of administration, and prescriber’s name. In
ing and pharmacy. Policies and procedures should some cases, a dilution, rate, and time of administration
allow for deviations from the standard times when should be specified. The desired therapeutic outcome
necessary. Further, standard drug concentrations and for each drug should be expressed when the drug is
dosage charts should be developed to minimize the prescribed. Prescribers should review all drug orders
need for dosage calculations by staff. for accuracy and legibility immediately after they have
18. The P&T committee (or its equivalent) should develop prescribed them.
a list of standard abbreviations approved for use in 5. Care should be taken to ensure that the intent of medica-
medication ordering. There should be efforts to pro- tion orders is clear and unambiguous. Prescribers should
hibit or discourage the use of other abbreviations in a. Write out instructions rather than using nonstan-
medication ordering. dard or ambiguous abbreviations. For example,
19. A review mechanism should be established through write “daily” rather than “q.d.,” which could
the P&T committee specifying those responsible for be misinterpreted as q.i.d. (causing a drug to be
data collection and evaluation of medication error re- given four times a day instead of once) or as o.d.
ports. The review group should investigate causes of (for right eye).
errors and develop programs for decreasing their oc- b. Do not use vague instructions, such as “take as
currence. The review group should be composed of directed,” because specific instructions can help
representatives from pharmacy, nursing, medicine, differentiate among intended drugs.
quality assurance, staff education, risk management, c. Specify exact dosage strengths (such as milli-
and legal counsel. grams) rather than dosage form units (such as
20. The pharmacy department, in conjunction with nurs- one tablet or one vial). An exception would be
ing, risk management, and the medical staff, should combination drug products, for which the num-
conduct ongoing educational programs to discuss ber of dosage form units should be specified.
medication errors, their causes, and methods to pre- d. Prescribe by standard nomenclature, using the
vent their occurrence. Such programs might involve drug’s generic name (United States Adopted
seminars, newsletters, or other methods of information Name or USAN), official name, or trademarked
dissemination. name (if deemed medically necessary). Avoid the
following: locally coined names (e.g., Dr. Doe’s
Recommendations for Prescribers. Prescribing is an early syrup); chemical names [e.g., 6-mercaptopurine
point at which medication errors can arise. It has been esti- (instead of mercaptopurine) could result in a six-
mated that 1% of hospitalized patients suffer adverse events fold overdose if misinterpreted]; unestablished
as the result of medical mismanagement30 and that drug- abbreviated drug names (e.g., “AZT” could stand
related complications are the most common type of adverse for zidovudine, azathioprine, or aztreonam); ac-
event.7 The following recommendations for preventing ronyms; and apothecary or chemical symbols.
medication errors are suggested for physicians and other e. Always use a leading zero before a decimal
prescribers3,7,11–16,31: expression of less than one (e.g., 0.5 mL).
Conversely, a terminal zero should never be used
1. To determine appropriate drug therapy, prescribers (e.g., 5.0 mL), since failure to see the decimal
should stay abreast of the current state of knowledge could result in a 10-fold overdose. When pos-
through literature review, consultation with pharma- sible, avoid the use of decimals (e.g., prescribe
cists, consultation with other physicians, participation 500 mg instead of 0.5 g).
in continuing professional education programs, and f. Spell out the word “units” (e.g., 10 units regular
other means. It is especially crucial to seek informa- insulin) rather than writing “u,” which could be
tion when prescribing for conditions and diseases not misinterpreted as a zero.
typically experienced in the prescriber’s practice. g. Use the metric system.
2. Prescribers should evaluate the patient’s total status
and review all existing drug therapy before prescrib- 6. Written drug or prescription orders (including signa-
ing new or additional medications to ascertain possible tures) should be legible. Prescribers with poor hand-
antagonistic or complementary drug interactions. To writing should print or type medication or prescription
evaluate and optimize patient response to prescribed orders if direct order entry capabilities for computerized
drug therapy, appropriate monitoring of clinical signs systems are unavailable. A handwritten order should be
and symptoms and of relevant laboratory data is nec- completely readable (not merely recognizable through
essary. familiarity). An illegible handwritten order should be
3. In hospitals, prescribers should be familiar with the regarded as a potential error. If it leads to an error of oc-
medication ordering system (e.g., the formulary system, currence (that is, the error actually reaches the patient),
participation in DUE programs, allowable delegation of it should be regarded as a prescribing error.
7. Verbal drug or prescription orders (that is, orders that are procedures established for the organizational setting to
orally communicated) should be reserved only for those provide for the safe distribution of all medications and
situations in which it is impossible or impractical for the related supplies to inpatients and ambulatory patients.
prescriber to write the order or enter it in the computer. In particular, pharmacists should be familiar with all
The prescriber should dictate verbal orders slowly, elements that are designed into the system to prevent
clearly, and articulately to avoid confusion. Special cau- or detect errors. Actions by any staff that would (even
tion is urged in the prescribing of drug dosages in the unintentionally) defeat or compromise those ele-
teens (e.g., a 15-mEq dose of potassium chloride could ments should serve as “alerts” to the pharmacist that
be misheard as a 50-mEq dose). The order should be safety may be affected. Any necessary followup action
read back to the prescriber by the recipient (i.e., the (e.g., education or reeducation of staff) should ensue
nurse or pharmacist, according to institutional policies). promptly. Policies and procedures to be followed for
When read back, the drug name should be spelled to “hold” orders should be clear and understood by phar-
the prescriber and, when directions are repeated, no ab- macy, medical, and nursing staffs.
breviations should be used (e.g., say “three times daily” 5. Pharmacists should never assume or guess the intent of
rather than “t.i.d.”). A written copy of the verbal order confusing medication orders. If there are any questions,
should be placed in the patient’s medical record and the prescriber should be contacted prior to dispensing.
later confirmed by the prescriber in accordance with 6. When preparing drugs, pharmacists should maintain
applicable state regulations and hospital policies. orderliness and cleanliness in the work area and per-
8. When possible, drugs should be prescribed for admin- form one procedure at a time with as few interruptions
istration by the oral route rather than by injection. as possible.
9. When possible, the prescriber should talk with the pa- 7. Before dispensing a medication in nonemergency
tient or caregiver to explain the medication prescribed situations, the pharmacist should review an original
and any special precautions or observations that might copy of the written medication order. The pharmacist
be indicated, including any allergic or hypersensitivity should ensure that all work performed by supportive
reactions that might occur. personnel or through the use of automated devices is
10. Prescribers should follow up and periodically evaluate the checked by manual or technological means. All pro-
need for continued drug therapy for individual patients. cesses must conform with applicable state and federal
11. Instructions with respect to “hold” orders for medica- laws and regulations. Pharmacists should participate
tions should be clear. in, at a minimum, a self-checking process in read-
ing prescriptions, labeling (drug or ingredients and
Recommendations for Pharmacists. The pharmacist is pharmacist-generated labeling), and dosage calcula-
expected to play a pivotal role in preventing medication tions. For high risk drug products, when possible, all
misuse. The value of pharmacists’ interventions to prevent work should be checked by a second individual (pref-
medication errors that would have resulted from inappropri- erably, another pharmacist). Pharmacists must make
ate prescribing has been documented.7,32,33 Ideally, the phar- certain that the following are accurate: drug, labeling,
macist should collaborate with the prescriber in developing, packaging, quantity, dose, and instructions.
implementing, and monitoring a therapeutic plan to produce 8. Pharmacists should dispense medications in ready-
defined therapeutic outcomes for the patient.1 It is also to-administer dosage forms whenever possible. The unit
vital that the pharmacist devote careful attention to dispens- dose system is strongly recommended as the preferred
ing processes to ensure that errors are not introduced at that method of drug distribution. The need for nurses to ma-
point in the medication process. The following recommen- nipulate drugs (e.g., measure, repackage, and calculate)
dations are suggested for pharmacists3,4,8–10,14,16,18–20,28,29: prior to their administration should be minimized.
9. Pharmacists should review the use of auxiliary labels
1. Pharmacists should participate in drug therapy moni- and use the labels prudently when it is clear that such
toring (including the following, when indicated: the use may prevent errors (e.g., “shake well,” “for exter-
assessment of therapeutic appropriateness, medication nal use only,” and “not for injection”).
administration appropriateness, and possible duplicate 10. Pharmacists should ensure that medications are deliv-
therapies; review for possible interactions; and evalua- ered to the patient-care area in a timely fashion after
tion of pertinent clinical and laboratory data) and DUE receipt of orders, according to hospital policies and
activities to help achieve safe, effective, and rational procedures. If medication doses are not delivered or if
use of drugs. therapy is delayed for any reason pending resolution of
2. To recommend and recognize appropriate drug ther- a detected problem (e.g., allergy or contraindications),
apy, pharmacists should stay abreast of the current the pharmacist should notify the nursing staff of the
state of knowledge through familiarity with literature, delay and the reason.
consultation with colleagues and other health-care 11. Pharmacists should observe how medications are
providers, participation in continuing professional actually being used in patient-care areas to ensure that
education programs, and other means. dispensing and storage procedures are followed and to
3. Pharmacists should make themselves available to assist nurses in optimizing patient safety.
prescribers and nurses to offer information and advice 12. Pharmacy staff should review medications that are
about therapeutic drug regimens and the correct use of returned to the department. Such review processes
medications. may reveal system breakdowns or problems that
4. Pharmacists should be familiar with the medication resulted in medication errors (e.g., omitted doses
ordering system and drug distribution policies and and unauthorized drugs).
13. When dispensing medications to ambulatory patients tion. The administration of medication should bedocu-
(e.g., at discharge), pharmacists should counsel patients mented as soon as it is completed.
or caregivers and verify that they understand why a 6. When standard drug concentrations or dosage charts
medication was prescribed and dispensed, its intended are not available, dosage calculations, flow rates, and
use, any special precautions that might be observed, other mathematical calculations should be checked by a
and other needed information. For inpatients, phar- second individual (e.g., another nurse or a pharmacist).
macists should make their services available to 7. The drug distribution system should not be circum-
counsel patients, families, or other caregivers when vented by “borrowing” medications from one patient
appropriate. (or another hospital area) to give to a different patient
14. Pharmacists should preview and provide advice on or by stockpiling unused medications. If there are
the content and design of preprinted medication order apparent missing doses, it is important that the phar-
forms or sheets if they are used. macy be contacted for explanation or correction. There
15. Pharmacists should maintain records sufficient to enable may be an important reason why the dose was not sent
identification of patients receiving an erroneous product. to the patient-care area (e.g., allergy, contraindication,
and questionable dose), and resolution of the potential
Recommendations for Nurses. By virtue of their direct question or problem may be pending.
patient-care activities and administration of medications to 8. If there are questions when a large volume or number
patients, nurses—perhaps more than any other health-care of dosage units (e.g., more than two tablets, capsules,
providers—are in an excellent position to detect and report vials, or ampuls) is needed for a single patient dose,
medication errors. Nurses often serve as the final point in the the medication order should be verified. Consult with
checks-and-balances triad (physicians and other prescribers, the pharmacist and prescriber as appropriate.
pharmacists, and nurses) for the medication use process; 9. All personnel using medication administration devices
thus, they play an important role in risk reduction. The fol- (e.g., infusion pumps) should understand their opera-
lowing recommendations for preventing medication admin- tion and the opportunities for error that might occur
istration errors are suggested3,14,16,17,34: with the use of such devices.
10. Nurses should talk with patients or caregivers to ascer-
1. Nurses who practice in organized health-care settings tain that they understand the use of their medications
should be familiar with the medication ordering and use and any special precautions or observations that might
system (e.g., participation in DUE activities, order pro- be indicated. Any counseling needed should be provided
cessing, and standard medication administration times). before the first dose is administered, when possible.
2. Nurses should review patients’ medications with respect 11. When a patient objects to or questions whether a par-
to desired patient outcomes, therapeutic duplications, ticular drug should be administered, the nurse should
and possible drug interactions. Adequate drug informa- listen, answer questions, and (if appropriate) double
tion (including information on medication administra- check the medication order and product dispensed
tion and product compatibilities) should be obtained before administering it to ensure that no preventable
from pharmacists, nurses, other health-care providers, error is made (e.g., wrong patient, wrong route, and
the literature, and other means when there are questions. dose already administered). If a patient refuses to take
There should be appropriate followup communication a prescribed medication, that decision should be docu-
with the prescriber when this is indicated. mented in the appropriate patient records.
3. All drug orders should be verified before medication
administration. Nurses should carefully review origi- Recommendations for Patients and Personal Caregivers.
nal medication orders before administration of the first Patients (or their authorized caregivers or designees) have the
dose and compare them with medications dispensed. right to know about all aspects of their care, including drug
Transcriptions of orders should be avoided to the therapy. When patient status allows, health-care providers
extent possible and should be recognized as prime op- should encourage patients to take an active role in their drug
portunities for errors. Doses should not be administered use by questioning and learning about their treatment regi-
unless the meaning of the original order is clear and mens. Generally, if patients are more knowledgeable, anxiet-
unambiguous and there are no questions with respect ies about the uncertainty of treatments can be alleviated and
to the correctness of the prescribed regimen. Nurses errors in treatment may be prevented. The following sugges-
should check the identity and integrity (e.g., expira- tions are offered to help patients whose health status allows,
tion date and general appearance) of the medications and their caregivers, make the best use of medications3:
dispensed before administering them. When there are
discrepancies, the nurse should contact the pharmacy 1. Patients should inform appropriate direct health-care
department and determine the appropriate action. providers (e.g., physicians, nurses, and pharmacists)
4. Patient identity should be verified before the adminis- about all known symptoms, allergies, sensitivities, and
tration of each prescribed dose. When appropriate, the current medication use. Patients should communicate
patient should be observed after administration of the their actual self-medication practices, even if they
drug product to ensure that the doses were adminis- differ from the prescribed directions.
tered as prescribed and have the intended effect. 2. Patients should feel free to ask questions about any
5. All doses should be administered at scheduled times procedures and treatments received.
unless there are questions or problems to be resolved. 3. atients should learn the names of the drug products
Medication doses should not be removed from pack- that are prescribed and administered to them, as well
aging or labeling until immediately before administra- as dosage strengths and schedules. It is suggested that
patients keep a personal list of all drug therapy, includ- their causes studied in order to develop systems that mini-
ing prescribed drugs, nonprescription drugs, home mize recurrence.3,4,7,10,11,14,16,22,40 Several error monitoring
remedies, and medical foods. Patients should also main- techniques exist (e.g., anonymous self-reports, incident
tain lists of medications that they cannot take and the reports, critical incident technique, and disguised observation
reasons why. This information should be shared with technique) and may be applied as appropriate to determine
health-care providers. Patients should be assertive in the rates of errors.9,40,41 There are differences in the validity
communicating with health-care providers when any- of data obtained by the various error monitoring techniques
thing seems incorrect or different from the norm. or combined techniques. Program managers should deter-
4. After counseling from an authorized health-care pro- mine the best method for use in their organizations in consid-
vider about the appropriateness of the medication, pa- eration of utility, feasibility, and cost. Monitoring programs
tients should take all medications as directed. for medication errors should consider the following risk fac-
tors6,10,11,22,40,41:
Recommendations for Pharmaceutical Manufacturers and
Approval Organizations. Poor designs with respect to drug 1. Work shift (higher error rates typically occur during
product packaging and labeling, as well as selection of inap- the day shift).
propriate or confusing nomenclature, have been identified as 2. Inexperienced and inadequately trained staff.
factors that contribute to serious medication errors by 3. Medical service (e.g., special needs for certain patient
practitioners.4,35–37 Pharmaceutical manufacturers and ap- populations, including geriatrics, pediatrics, and on-
proval agencies should be responsive to efforts of practitioners cology).
to minimize errors. The following guidelines are recommended 4. Increased number or quantity of medications per patient.
for the pharmaceutical industry and regulatory authorities3,4,16,38 5. Environmental factors (lighting, noise, and frequent
interruptions).
1. Drug manufacturers and the Food and Drug Adminis 6. Staff workload and fatigue.
tration are urged to involve pharmacists, nurses, and 7. Poor communication among health-care providers.
physicians in decisions about drug names, labeling, 8. Dosage form (e.g., injectable drugs are associated with
and packaging. more serious errors).
9. Type of distribution system (unit dose distribution is
2. Look-alike or sound-alike trademarked names and
preferred; floor stock should be minimized).
generic names should be avoided.
10. Improper drug storage.
3. Similar proprietary appearances of packaging and la-
11. Extent of measurements or calculations required.
beling should be avoided, because look-alike products
12. Confusing drug product nomenclature, packaging, or
contribute to medication errors.
labeling.
4. The use of lettered or numbered prefixes and suffixes in
13. Drug category (e.g., antimicrobials).
trademarked names is generally discouraged. Lettered
14. Poor handwriting.
prefixes or suffixes could be mistaken for instructions or
15. Verbal (orally communicated) orders.
strength. Commonly used medical abbreviations should
16. Lack of effective policies and procedures.
never be used in trademarked names (e.g., “HS” could 17. Poorly functioning oversight committees.
stand for half-strength or a bedtime dose). Numbers
as part of trademarked names could be mistaken for Managing Medication Errors. Medication errors result
quantities to be administered. Coined abbreviations from problematic processes, but the outcomes of medica-
that could be misinterpreted (e.g., MTX, U, and HCTZ) tion errors could range from minimal (or no) patient risk to
should not be used in trademarked names. life-threatening risk. Classification of the potential serious-
5. Special instructions should be highlighted on labeling, ness and clinical significance of detected medication errors
such as the need for dilution before administration. should be based on predefined criteria established by the
6. The most prominent items on the product label should P&T committee (or its equivalent). The error classification
be information in the best interest of safety (e.g., prod- should be based on the original order, standard medication
uct name and strength). Less prominence should be dispensing and administration procedures, dosage forms
given to company names or logos. available, acceptable deviation ranges, potential for adverse
7. Drug manufacturers are encouraged to make dosage consequences and patient harm, and other factors.6,32,41
forms available commercially in unit dose and unit- Classification of medication errors should allow for bet-
of-dispensing containers, as well as bulk packaging, to ter management of followup activities upon medication error
facilitate their appropriate use in all practice settings. detection. A simple classification of medication errors is the
8. Drug manufacturers must communicate with health-care following: (1) clinically significant (includes potentially fatal
providers (i.e., pharmacists, physicians, and nurses) when or severe, potentially serious, and potentially significant er-
changes are made in product formulations or dosage forms. rors) or (2) minor.7,33 Hartwig, Denger, and Schneider defined
seven medication error severity levels, as follows41:
Monitoring and Managing
Medication Errors Level 0—Nonmedication error occurred (potential
errors would be classified here).
Monitoring Medication Errors. Ongoing quality improve- Level 1—An error occurred that did not result in
ment programs for monitoring medication errors are needed. patient harm.
The difficulty in detecting errors has long been recognized Level 2—An error occurred that resulted in the need
as one of the barriers to studying the problem effectively.39 for increased patient monitoring but no change in vital
Medication errors should be identified and documented and signs and no patient harm.
Level 3—An error occurred that resulted in the need for 5. When appropriate, the supervisor and the staff mem-
increased patient monitoring with a change in vital signs bers who were involved in the error should confer on
but no ultimate patient harm, or any error that resulted how the error occurred and how its recurrence can be
in the need for increased laboratory monitoring. prevented. Medication errors often result from prob-
Level 4—An error occurred that resulted in the need lems in systems rather than exclusively from staff
for treatment with another drug or an increased length performance or environmental factors 2,3,44; thus, error
of stay or that affected patient participation in an in- reports should not be used for punitive purposes but to
vestigational drug study.a achieve correction or change.
Level 5—An error occurred that resulted in permanent 6. Information gained from medication error reports and
patient harm. other means that demonstrates continued failure of in-
Level 6—An error occurred that resulted in patient dividual professionals to avoid preventable medication
death. errors should serve as an effective management and
educational tool in staff development or, if necessary,
Medication error classifications could also be based on modification of job functions or staff disciplinary action.
probability and severity scales analogous to those used in 7. Supervisors, department managers, and appropriate
ADR reporting programs.42,43 committees should periodically review error reports and
Determination of the causes of medication errors should determine causes of errors and develop actions to pre-
be coupled with assessment of the severity of the error. While vent their recurrence (e.g., conduct organizational staff
quality management processes should include programs to de- education, alter staff levels, revise policies and proce-
crease the incidence of all medication errors, effort should be dures, or change facilities, equipment, or supplies).
concentrated on eliminating the causes of errors associated with 8. Medication errors should be reported to a national mon-
greater levels of severity. There should be established mecha- itoring program so that the shared experiences of phar-
nisms for tracking drugs or drug classes that are involved in macists, nurses, physicians, and patients can contrib-
medication errors. Correlations between errors and the method ute to improved patient safety and to the development
of drug distribution should also be reviewed (e.g., unit dose, of valuable educational services for the prevention
floor stock, or bulk medications; premixed or extemporane- of future errors. Reports of medication errors can be
ously compounded products; and oral or injectable products). made by telephone to the United States Pharmacopeial
These processes will help identify system problems and stimu- Convention, Inc. (USP) Medication Errors Reporting
late changes to minimize the recurrence of errors. Program (1-800-23ERROR). Reports can be submit-
Quality improvement programs should provide guid- ted to USP on a confidential basis if the reporter so
ance for patient support, staff counseling and education, chooses. Other reporting programs may also be in
and risk management processes when a medication error is existence or under development. Reporting programs
detected. Incident reporting policies and procedures and ap- are intended to track trends and inform practitio-
propriate counseling, education, and intervention programs ners, regulators, and the pharmaceutical industry of
should be established in all hospitals. Risk management pro- potential product and system hazards that have a docu-
cesses for medication errors should include pharmacists, phy- mented association with medication errors.
sicians, and nurses, in addition to risk management special-
ists, legal counsel, and others as appropriate. The following References
actions are recommended upon error detection3,7,10,11,16,17,27,43:
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cedures. For clinically significant errors, an immediate 1. Am J Hosp Pharm. 1989; 46:929–44.
oral notice should be provided to physicians, nurses, 3. Davis NM, Cohen MR. Medication errors: causes and
and pharmacy managers. A written medication error prevention. Huntingdon Valley, PA: Neil M. Davis
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should be determined and documented include what 5. Zellmer WA. ASHP plans for the future. Am J Hosp
happened, where the incident occurred, why the in- Pharm. 1986; 43:1921. Editorial.
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was involved. Appropriate product evidence (e.g., ment on the pharmacist’s responsibility for distribution
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a
statement on the pharmacy and therapeutics commit- The mention of investigational drugs in the definition of level 4 er-
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25. Barker KN, Pearson RE, Hepler CD, et al. Effect of an any error involving an investigational drug should automatically
automated bedside dispensing machine on medication be classified as a level 4 error. However, in discussing this issue
errors. Am J Hosp Pharm. 1984; 41:1352–8. at its September 1992 meeting, the ASHP Council on Professional
26. American Society of Hospital Pharmacists. ASHP Affairs noted that it is the effect on the patient (for a medication
guidelines for selecting pharmaceutical manufacturers of any type) that really should determine what level of error is in-
and suppliers. Am J Hosp Pharm. 1991; 48:523–4. volved. Approved by the ASHP Board of Directors, June 23, 1993,
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ASHP Guidelines on Preventing Medication Errors

with Chemotherapy and Biotherapy
Purpose and Definitions These guidelines provide wide-ranging recommen-
dations for preventing errors with chemotherapy agents in
The purposes of these guidelines are to define best practices healthcare organizations, with an emphasis on hospitals,
for the safe use of chemotherapy and biotherapy agents and infusion centers, and ambulatory care clinics that offer di-
to assist practitioners in improving their medication-use rect pharmacy services. Nevertheless, it is strongly recom-
systems to prevent medication errors and patient harm from mended that the guidance also be adopted by other settings,
these agents. Although the guidelines are intended primar- including physician office practices, home care, and patients
ily to address use of chemotherapy and biotherapy agents self-administering oral and injectable therapies at home.
in cancer treatment, some recommendations may be more Other guidance on the safe use of chemotherapy in the am-
broadly applicable across the medication-use system. These bulatory setting has been published by the American Society
guidelines supplement ASHP’s Guidelines on Preventing of Clinical Oncology (ASCO) and the Oncology Nursing
Medication Errors in Hospitals and address error prevention Society (ONS).4 These recommendations cover known
within diverse healthcare settings.1 Further, these guidelines procedural, technical, and behavioral elements that could
provide updated general guidance to include a standard defi- systematically reduce a healthcare organization’s vulner-
nition of a “medication error” and applicable aspects of rec- abilities to errors. Given use of an electronic medical record
ommendations from the National Coordinating Council on (EMR) increased from 3.8% of hospitals in 2007 to 8% in
Medication Error Reporting and Prevention (NCC MERP). 2011, and computerized provider order entry (CPOE) use
NCC MERP’s definition of a medication error is: increased from 4% of hospitals in 2005 to 34% of hospi-
tals in 2011,5 additional information on the unique consid-
any preventable event that may cause or lead to in- erations of using CPOE for chemotherapy ordering has been
appropriate medication use or patient harm while the included in these guidelines.
medication is in the control of the healthcare provider, Strict adherence to good practice recommendations is
patient, or consumer. Such events may be related to not sufficient. Because the complexities of chemotherapy
professional practice, healthcare products, procedures, use afford unlimited opportunities for system failures, con-
and systems, including prescribing; order communica- tinuous diligence to verify accuracy is critical by all persons
tion; product labeling, packaging, and nomenclature; responsible for medication-use functions for chemotherapy.
compounding; dispensing; distribution; administra- These guidelines focus on the medication-use responsibili-
tion; education; monitoring; and use.2 ties shared by and unique to specific professional healthcare
disciplines, progressing from general to specific applica-
For the purposes of these guidelines, chemotherapy and tions. The structure of the guidelines, by necessity, includes
biotherapy agents are defined as any medication that (1) is the repetition of some material, repeated and enhanced in
listed in section 10:00 of the American Hospital Formulary specific sections and recommendations for different health-
Service3 (AHFS) pharmacologic–therapeutic classification care professionals. With the growth in use and number of
system; (2) has at least one FDA-labeled indication to pre- oral chemotherapy agents on the market, a greater responsi-
vent or treat cancer, even if not listed in AHFS 10:00; or (3) is bility for care management is now placed on the patient. It is
an investigational medication being used to prevent or treat essential that applicable sections of these guidelines extend
cancer. This definition includes medications administered by to patients so they can participate in protecting their own
any route. For simplicity, the term “chemotherapy” is used safety.
throughout these guidelines to refer to any chemotherapy or The guidelines contain the following major sections:
biotherapy medication that is used for cancer treatment.
The variety of therapies used in the treatment of cancer 1. Recommendations for healthcare organizations,
will only increase as advances are made, and healthcare or- 2. Recommendations for multidisciplinary monitoring of
ganizations will confront the challenge of defining the prod- medication use and verification,
ucts that require special procedures for safe use. Given the 3. Recommendations for prescribing systems and pre-
complexity of cancer care, it is recommended that such a list scribers,
be as inclusive as possible. While these guidelines focus on 4. Recommendations for medication preparation and dis-
the safe use of chemotherapy in treating cancer patients, in pensing systems and roles for pharmacists,
some situations chemotherapy agents may be used for non- 5. Recommendations for medication administration sys-
malignant diseases. In general, these additional safety pro- tems and roles for nurses,
cedures should apply for all uses of a chemotherapy agent, 6. Recommendations for patient education,
regardless of indication. Although they are specific to use of 7. Recommendations for manufacturers and regulatory
chemotherapy for cancer treatment, many of the principles agencies, and
of these guidelines also apply to cancer supportive care (e.g., 8. Recommendations for identifying and managing med-
treatment for pain and nausea). Finally, for organizations ication errors.
that conduct clinical research, investigational chemotherapy
agents should be included in all safety systems established Because of the complexity of and differences in practice
for FDA-approved chemotherapy agents. settings and organizational arrangements, aspects of these
guidelines may be more applicable to some practice set- Recommendations for Healthcare
tings than others. Pharmacists, physicians, nurses, and other Organizations
healthcare providers should use their professional judgment
in assessing and adapting the guidance to their own settings. Optimal and comprehensive patient care, especially for pa-
These guidelines focus on safe use of a specific type of high- tients receiving chemotherapy, requires the participation of
risk medications at various stages of the medication-use multiple healthcare disciplines. Systems are necessary to
process and should be augmented as appropriate by other coordinate the functions throughout the medication-use pro-
clinical and practice guidance, including ASHP statements cess of prescribing, preparing, dispensing, and administering
and guidelines. of chemotherapy, and for educating and counseling patients.
Healthcare organizations where multiple disciplines
Background are represented should establish committees with represen-
tatives from each discipline to develop policies and pro-
Although the rate of medication errors for chemotherapy ad- cedures for the medication-use process and to oversee its
ministered in the inpatient setting is not well documented, operation. These policies and procedures should include edu-
estimates of the frequency of errors with adult and pediat- cational and competency requirements for persons with medi-
ric chemotherapy in the ambulatory setting have been pub- cation-use responsibilities; general system requirements that
lished. In one study, the overall chemotherapy error rate was minimize vulnerabilities to errors; and periodic auditing of
8.1 errors per 100 clinic visits.6 For adults, errors were as- physicians’, pharmacists’, and nurses’ proficiency with the
sociated with 7.1% of clinic visits, and errors were associ- system. Further, near misses and errors involving both com-
ated with 18.8% of pediatric clinic visits. Errors occurred mercial and investigational chemotherapy agents should be
across all phases of the medication-use system, but admin- analyzed in all settings, and problems in the procedures that
istration (56%) and ordering (36%) errors were most com- place patients at risk should be resolved.
mon. Another study found a substantially lower rate (3%)
of errors in chemotherapy orders in the outpatient infusion Education, Competency, and Credentialing. All practice
center at a major cancer center.7 The error rate with oral che- settings should establish policies and procedures ensuring
motherapy agents is less well studied, but serious medica- that healthcare providers who prescribe, prepare, dispense,
tion errors can occur with these therapies across all phases of and administer chemotherapy and monitor patients receiving
the medication-use system.8,9 Taylor and colleagues10 docu- those medications are competent to perform those functions.
mented a 9.9% error rate with oral chemotherapy given to For pharmacists and nurses, specific education and experi-
pediatric patients with acute lymphoblastic leukemia. In this ence or board certification in a practice specialty may be in-
study, the errors occurred at the prescribing and administra- cluded in the institution’s credentialing process.
tion steps. Employers should evaluate prospective employees’
Regardless of the exact rate of medication errors for training and previous practice experiences for knowledge
chemotherapy agents, the safe use of these therapies pres- and mastery of the skills that are essential prerequisites for
ents unique challenges that demand additional safety sys- working with chemotherapy. Prerequisites for preparing
tems. Chemotherapy agents often have a narrow therapeutic and administering chemotherapy should include discipline-
index, and they are used in complex, multidrug regimens. appropriate training in how to safely handle chemotherapy
Complex dose calculations and adjustments are required, agents to protect themselves, co-workers, and patients.
such as dosing per body surface area (BSA) and frequent Competency to appropriately educate patients and moni-
adjustment according to renal function, toxicity, and other tor adherence with prescribed therapy should be assessed.
clinical parameters. Chemotherapy agents can cause seri- Deficiencies in applicants’ training and experience must
ous toxicities at FDA-approved dosages and with FDA- be identified and remedied before new employees assume
approved administration schedules. Advocates for safe med- patient-care responsibilities. Ongoing training for new and
ication use, including oncology pharmacy specialists, have current employees should emphasize collaboration among
recommended that healthcare organizations improve their healthcare providers to ensure optimal patient care, out-
medication-use systems specifically to prevent medication comes, and worker safety.
All healthcare providers who prescribe, prepare, dis-
errors with chemotherapy.11-14
pense, and administer chemotherapy and monitor patients
Chemotherapy-related medication-error prevention
receiving those medications should be oriented in their prac-
remains a priority. Increasingly, many chemotherapy agents
tice setting before commencing patient-care responsibilities.
are administered outside the inpatient or ambulatory care
Orientation should include an introduction of new employ-
setting. A growing number of patients are self-administering
ees to all the departments, service providers, and functions
oral chemotherapy agents at home.15 Thus, error-prevention
that affect patient care. Each provider’s roles and respon-
strategies should be applicable to the diverse settings in
sibilities should be identified, and expectations should be
which chemotherapy agents are used.
clarified about how healthcare providers from different
Surveys have indicated a need for improvement in
disciplines will communicate and work collaboratively with
medication-use systems for chemotherapy agents. One sur-
respect to the chemotherapy medication-use process.
vey of major United States cancer centers indicated that the
Further, healthcare organizations should require that
safety systems routinely used for infused chemotherapy
all personnel who prescribe, prepare, dispense, administer,
agents are rarely applied to oral chemotherapy agents.16
and handle hazardous drugs or contaminated materials, and
Another survey replicated this finding and indicated that
all persons who may be exposed to hazardous drugs or con-
many other recommended safety practices for chemotherapy
taminated materials in the course of their duties, complete
agents are not followed.17
job-appropriate training and evaluation. Employees should patient. Medication profiles for cancer patients should, at a
demonstrate competence, knowledge, and proficiency in minimum, include the following information:
techniques and procedures for safely handling (preventing
exposure to oneself, other persons, and the environment, and 1. Patient’s name and a unique identifying code or num-
managing accidental exposure) and disposing of hazardous ber.
drugs. Those competencies should be reassessed annually or 2. A brief medical history that identifies a patient’s can-
more frequently if performance problems occur. It is the re- cer diagnosis.
sponsibility of medication-use system administrators and su- 3. Known drug-related adverse events, allergies, and
pervisory personnel to know the current government restric- medication-, nutrient-, and food-related sensitivities.
tions that limit or prohibit some healthcare providers from 4. Vital statistics that may affect treatment intensity, par-
preparing and administering chemotherapy medications. ticularly those needed to calculate medication doses,
Healthcare providers who participate in the chemother- including height, weight, BSA, age, sex, and pertinent
apy medication-use process and those who monitor patients laboratory values (e.g., serum creatinine, creatinine
receiving chemotherapy should be knowledgeable and have clearance, liver transaminases).
current information available about each of the following 5. Data about all prescription, over-the-counter, and
factors, relative to their scope of practice and job duties, on complementary and alternative medications used by a
the chemotherapy used in their practice settings: patient, including:
• All relevant dates, including when the
1. Names of chemotherapy drug formulations. medication(s) were:
2. Indications and uses, and whether they comply with • prescribed (if it differs from the date they
the FDA-approved labeling or approved compendia were prepared and administered),
or are part of an investigational protocol. • prepared and dispensed (if it differs from
3. Routes of administration. the date the medications were adminis-
4. Administration schedules. tered), and
5. Appropriate dosages, including dose adjustments for • administered (use planned date for patient
toxicity and, when applicable, constraints for the max- self-administered agents);
imum dose of medication that can be safely given dur- • Drug identity;
ing a single administration, over a course of treatment, • Drug dosage and reason(s) for any dose adjust-
or cumulatively over a lifetime. ments, as appropriate;
6. Appropriate storage conditions. • Total drug dosage administered per unit interval
7. Potential adverse effects. (e.g., day, week, treatment cycle);
8. Potential drug interactions. • Administration route;
9. Procedures to use for handling hazardous substances.
• Administration schedule as a function of the
treatment plan (e.g., every 3 hours, days 1, 8, and
10. Strategies for identifying and mitigating the risks of 15, with the specific treatment dates);
extravasation. • Rate of administration (when relevant);
• Prescribed duration of use (e.g., number of doses
Every practice setting where cancer patients receive che- to administer; number of treatment hours, days,
motherapy should provide opportunities for continuing pro- or weeks); and
fessional and technical education related to chemotherapy • The product manufacturer’s identity, product
management. A portion of the annual continuing education lot numbers, and (when practicable) expiration
programs for healthcare providers specializing in oncology dates for drugs dispensed from that facility.
should be related to chemotherapy agents and their uses. 6. Additional ingredients and diluting agents and the
Providers who use drug-delivery devices (e.g., intrave- amounts used in extemporaneously compounded
nous pumps and infusion controllers) to administer chemo- medications.
therapy agents should be required to demonstrate competen- 7. Primary references that describe the treatment regi-
cies related to the clinical application, function (general use, men.
operational limits, alarms), and care of these devices; prob- 8. An up-to-date treatment history, including:
lems that may occur with the devices; and troubleshooting. • The treatment cycle or course number for each
treatment repetition,
Communication and Access to Information. Many errors • The dates on which a patient last received treat-
occurring in the medication-use process are caused or aggra- ment,
vated by inadequate patient-specific information. Patients’ • How previous treatment was tolerated, and
medical records should be organized and made readily ac- • The cumulative amount of drug previously ad-
cessible for use by all providers who prescribe, dispense, ministered for medications with established
and administer chemotherapy to enable independent con- absolute cumulative dosage limits (e.g., anthra-
firmation that all prerequisite criteria have been met before cyclines, bleomycin) or constraints against re-
commencing treatment. In some cases, individual disciplines peated administration as a function of time.
may keep additional patient records that supplement the pa-
tient’s primary medical record. For example, it has histori- Other settings, such as ambulatory, home, specialty, and
cally been the responsibility of pharmacists and pharmacies managed care organizations are vulnerable to the same com-
to maintain patient-specific medication profiles and records munication and interpretation errors that occur in hospitals.
of medications that were prescribed and dispensed for each These settings and organizational arrangements, however,
could introduce additional opportunities for errors of omis- independent double checks of the content. (An “independent
sion and duplication when treatments and other services are double check” is a process in which two qualified individu-
provided at multiple locations and by more than one partici- als separately check, alone and apart from each other, an
pating provider or group of providers. In hospitals and inte- item or action, and then compare results to ensure the de-
grated health systems, patient-specific medical information sired outcomes.19) These forms should include the revision
has traditionally been communicated through a single com- date, as appropriate, to allow everyone involved to identify
prehensive medical record. In contrast, providers in private and validate that they are using the most current version.
practice, home care, and managed care organizations gener- Standardized medication-order forms, including pre-
ally cannot rely on the availability of a comprehensive medi- scriptions for oral therapies administered by patients, sim-
cal record, because medication prescribing, preparing, and plify and expedite medication ordering by requiring pre-
administering may occur at geographically separate facilities. scribers to supply only patient-specific information, such as
Local policies should be developed to ensure that or-
ders for a patient’s chemotherapy medications are transmit- 1. Patient’s name and unique identifying number (e.g.,
ted accurately and completely, that medication reconciliation medical record number) or date of birth according to
takes place at all transitions in care, and that patient confi- institutional policies regarding patient identification.
dentiality is protected.18 Electronic means of communica- 2. Date and time the order was generated.
tion are recommended to transmit up-to-date, accurate, and 3. Time and date treatments are to be administered.
comprehensive patient-specific medical information among 4. Cycle and day number.
providers. Thus, data entered into this electronic system by 5. Current patient-specific laboratory values (as defined
any one provider are immediately available to all. Until a by institutional policy regarding the timeframe for
single unifying network becomes available for all healthcare which laboratory test results are considered acceptable
providers, portable printed and electronic records (including to use to determine whether chemotherapy can be initi-
an accurate, updated patient medication list) that ensure pa- ated).
tient safety and confidentiality must be devised. 6. Patient-specific dosing parameters (i.e., height,
weight, dosing weight, BSA).
Schedule Coordination. Because oncology patients often 7. Medication generic name.
receive care from more than one healthcare provider, their 8. Planned medication dosages and administration
primary provider, care coordinator, or patient navigator rates as a function of patient-specific factors and the
should coordinate patient care with other providers and fa- calculated doses and rates to be administered.
cilities. Efficient organizational systems should have some- 9. Route of administration (including the venous ac-
one to coordinate a patient’s healthcare needs with their vari- cess device type, if applicable).
ous healthcare providers’ schedules. 10. Patient’s allergies and medication and nutrient sensi-
tivities.
Standardize Medication Ordering. To the extent possible, 11. Prescriber’s name and signature.
medication prescribing, preparation, dispensing, and admin- 12. Prescriber’s telephone, pager, or fax number (or an-
istration should be standardized. Healthcare organizations other means to communicate with the prescriber).
should adopt and incorporate national standards into their
practice. Patient-care facilities should develop and use stan- Preprinted forms should specify, by protocol number or
dardized preprinted medication-order forms or forms that publication reference, the treatment that is to be adminis-
are retrievable from a computerized database for requesting tered.11,20,21
frequently used chemotherapy treatments and treatment- For investigational chemotherapy treatments, stan-
related services. Well-designed standardized, regimen-spe- dardized forms should also include the study name, protocol
cific, medication-order forms decrease potential errors by number, and patient-specific study number, as applicable.
organizing treatment information in a clear, consistent, and Color-coded forms, for example, may be used to designate
uniform format. As discussed further below, CPOE provides different types of treatment, such as commercially marketed
standardization opportunities and other potential benefits. chemotherapy and investigational medications.
Standardized forms should be developed collabora- Standardized order forms eliminate many of the issues
tively with input from the healthcare providers who pre- related to misinterpreting medication orders that are com-
scribe, prepare, and administer chemotherapy medications. monly associated with nonstandardized orders; however,
Forms should be preprinted with the entire treatment plan healthcare providers must be aware that interpretation errors
and include items such as generic drug names, specifica- may still result from illegible handwriting. Multipurpose
tions for drug dosage and dosage modifications as a function preprinted forms that list chemotherapy medications alpha-
of patient-specific variables, and administration routes and betically may also contribute to prescribing errors when two
schedules. Forms should include the entire treatment plan, similar drug names appear in close proximity. Since lined
including oral medications that may be filled by an outside paper can obscure the details of a prescriber’s orders, pre-
provider and patient self-administered. Prescription forms printed forms should be printed on unlined paper.
should also include space for prescribers to note laboratory Self-replicating forms (e.g., carbon copies, no-carbon
test results that affect dosages, administration rates, and required paper) can produce copies that are difficult to read,
treatment duration. These forms may also permit prescrib- and these forms should be avoided. Further, poor quality fax
ers to schedule laboratory tests and request other services transmissions of these order sets should also be avoided.
for comprehensive patient care. A multidisciplinary process Providers who prepare and administer medications on the
should be in place for the development, implementation basis of a copy of a prescriber’s order should be wary of am-
and maintenance of these standard order forms, including biguous notations, artifact markings, and omissions on the
copy. Each facility should restrict chemotherapy ordering workflow. Some institutional chemotherapy policies dictate
(e.g., access to medication-order forms) to providers with a final review and approval (informally known as “OK to
the appropriate clinical privileges. Healthcare organizations Give” or final sign-off) of the chemotherapy order by an at-
that depend on standardized forms should review all forms tending physician or other senior clinician.
on a regularly defined schedule and must ensure that only Clinical decision support is another important consid-
the most current versions of standardized forms are available eration for CPOE.26 Clinical decision support can guide the
and that obsolete forms are recalled and destroyed. prescriber through various phases of the ordering process
and include specific chemotherapy considerations based on
CPOE. CPOE should be implemented to further enhance individual patient parameters, such as laboratory values, co-
the safety of the chemotherapy-use process. CPOE offers an morbid conditions, hydration requirements, and the need for
opportunity to introduce new safety features into the chemo- supportive care medications (e.g., antiemetics). Appropriate
therapy prescribing process, but implementation of CPOE alerts, such as allergies, drug interactions, duplicate therapies,
for chemotherapy providers appears to lag other areas.5,22,23 and maximum doses, should be incorporated as appropriate
CPOE provides many of the same safety and conve- and be consistent with the institution’s overall plan for im-
nience features as preprinted orders, such as order legibility, plementing clinical decision support alerts. The duration of
standardization across practitioners, chemotherapy schedul- the order set, a cycle or specific weeks of therapy, should be
ing and sequencing, and inclusion of support care medica- standardized, and clear criteria to treat or continue treatment
tions and some patient demographics. CPOE also provides must be documented for the patient to continue treatment.
additional benefits that are not available with a paper sys- Users should plan for improvements and alterations to
tem. For example, the ability to control user access to vari- the CPOE system after implementation. Changes should be
ous sections of the system can be very useful in managing considered by a multidisciplinary team and include provider
prescriber privileges, especially to limit which staff may feedback as well as data from continuous monitoring of the
order chemotherapy or prescribe specific investigational order entry process, including safety reporting and near-miss
drugs. CPOE improves efficiency by allowing data to be data. Continuous review and improvement are multidisci-
accessed by different providers in different locations at the plinary processes and need to include both clinicians and
same time, and it serves as a guide for the ordering provider information systems staff.28
via clinical decision support features and serves to structure Implementing CPOE for chemotherapy is an impor-
workflow (i.e., specific steps in subsequent preparation, distant step, and CPOE should be leveraged to provide guid-
pensing, and administration). CPOE provides benefits over ance for prescribers ordering chemotherapy. By definition,
a paper system, including additional safety checks not pos- the prescriber is entering orders directly into the system, and
sible with paper, but diligence by the prescriber and careful
safety can be improved because there is usually no interme-
independent checks of the resulting orders are still essential
diary who must interpret the orders and enter them into an-
when using CPOE for chemotherapy.
other information system. Since CPOE clearly reflects and
CPOE for chemotherapy must be implemented with
communicates the intent of the prescriber, properly planned
great care. CPOE represents a major change in an organi-
CPOE should give prescribers the ability to select a specific
zation’s chemotherapy use process and workflow, and it
regimen or protocol that delineates the necessary informa-
may introduce new errors that may not have existed in the
tion to produce a clear and accurate drug regimen.28 These
traditional handwritten process.24 In a well-established and
custom ordering screens are typically called “order sets” or
mature chemotherapy-use system, one must be certain that
“templates,” and they are essential to safely using CPOE for
the dramatic changes produced by CPOE do not threaten the
chemotherapy.23
safety of the chemotherapy-use process during the imple-
Depending on the system and resources devoted to
mentation period.
order sets, additional information (e.g., requirements for
To gain the benefits of CPOE, there are several key
laboratory values, supportive care, dose reductions, or
principles of implementation and continued development
that must be considered, such as standardization, reduction dose-limiting parameters) may be part of the order sets.
in ambiguity, safety over convenience, and an evaluation of Information such as dosing (e.g., mg/kg or mg/m2, diluents,
workflow effects.25,26 When feasible, formal process rede- or concentration, if appropriate) should be part of the order
sign methods should be applied before implementing CPOE set to facilitate dose verification by the pharmacist. The sys-
for chemotherapy. Given the patient safety risks involved, a tem may also be able to prevent ordering the wrong route
formal failure modes and effects analysis (FMEA) should of administration or append a warning message to specific
be considered, as such an approach has been successfully orders, averting such potentially deadly mistakes as inadver-
used.23,27 When reviewing the capabilities of a CPOE sys- tently prescribing vincristine intrathecally.
tem, pertinent patient data must be available to all providers. Transitioning complex order sets from paper to a
These data include provider notes, laboratory values, flow CPOE system poses various challenges. Care must be taken
sheets that show prior chemotherapy and medications admin- in designing ordering templates, because an undetected
istered, and consent forms, among others. Workflow should design error may result in multiple mistakes. Prescribers
be considered when determining how data are displayed and and investigators (in the case of an investigational proto-
in what order the data are presented. This workflow begins col ordering set) should be involved in the checking of the
at the point the order is entered by the prescriber, followed template, and ideally they should be asked to sign off on
by pharmacist review, nurse review, drug administration, the particular ordering screens before they are put into wide
and the documentation of the effect on the patient. The num- use. The building of these orders sets is not a simple pro-
ber and type of checks required to verify the order should be cess, especially pediatric order sets and investigational drug
reviewed with consideration of the CPOE capabilities and regimens.29
Cancer chemotherapy often includes a complicated Verbal Orders for Chemotherapy Medications. Except for
sequencing of drugs and scheduling of the regimen. Growth discontinuing treatment, medication-use systems should not
factors need to be scheduled at the proper time to be effective permit healthcare providers to use or accept verbal orders
and not interfere with the mechanism of action of the che- to commence or modify a chemotherapy medication.11,12,30
motherapy or biotherapy regimen. Unfortunately, if there is Verbal communication for chemotherapy orders, whether
a delay in the scheduled administration times, some systems face-to-face or over the telephone, circumvent an essential
may not allow a simple click or two to reschedule multiple checkpoint in the order-verification process, whether they are
days and doses, in contrast to older methods in which a pre- communicated directly to persons who prepare medications
scriber could just write “delay chemotherapy by 6 hours.” or received and reported by one or more intermediaries.31
If possible, the CPOE system and electronic health
record should allow for an electronic check and documen- Stat Orders for Chemotherapy Medications. It is rarely
tation of the independent checks by the pharmacist, nurse, necessary to begin chemotherapy treatment as quickly as
and any others involved in the chemotherapy use process. possible (i.e., “stat”). In general, stat orders for chemo-
A notation in the system alerting the nurse or prescriber that therapy may compromise essential order-verification safe-
the order is under review by the pharmacist is very helpful. guards and are almost never appropriate. Except for urgently
Systems should allow senior physician final approval (i.e., required treatments, chemotherapy medication preparation
“OK to give” or final sign-off) before action is taken by the and administration should be scheduled when staffing is
pharmacy. adequate to ensure that appropriate safety checks are per-
Careful thought is necessary and critical when using formed during compounding, verification, and administra-
a CPOE system, and the potential for error still exists. Prior tion. It is essential that patient care is not compromised un-
to order entry, the prescriber must consider whether a dose der any circumstances.
reduction is needed based on a change in laboratory values
or organ function. If an investigational protocol is involved, Standardize Dosage Calculation. Medication-use systems
the prescriber must select the correct cycle or dose level, if should establish whether drug dosages should be routinely
dose escalation is necessary. CPOE systems may be able to calculated as a function of actual, ideal (lean), or adjusted
guide the prescriber, but they cannot make the correct choice body weight and develop standardized criteria that direct
for him or her. Another potential source of error is the auto- dosage calculation as a function of this weight. ASCO has
calculation feature of some systems. The system can utilize produced guidelines for dosing chemotherapy in obese pa-
the latest height and weight to calculate BSA or use the patients that suggest using actual body weight if the intent is
tient’s weight to calculate the proper dose. However, an in- cure.32 Institutions should consider this information when
correct height or weight entry can result in a dosing error. It deciding on dose calculation standards. Institutions should
is easy for prescribers to miss small but significant changes also define policies for other situations, such as in pediat-
that could result from data entry errors. Systems may be able ric or hematopoietic stem cell transplant patients, where
to prevent data entry error by displaying an alert when data adjusted-weight dosing is used, or when cure is not the goal.
differ from a previous entry by a certain percentage or final Investigational protocols may specify treatment parameters
dose amount. different from institutional parameters. In all cases, the treat-
Emergency contingency plans for how to commu- ment plans and medication orders should indicate whether
nicate chemotherapy orders in the event the CPOE is not patients’ actual or ideal body weight was used in calculating
available (e.g., power outage, system failure) should be drug dosages and identify the equation from which dosages
developed and tested. Whenever possible, the contingency were calculated.
plan should replicate the CPOE process (e.g., paper orders Methods should be standardized for calculating BSA
replicating CPOE screens) as much as possible to minimize and ideal body weight, rounding calculated results (e.g., drug
introduction of new risks. Training and awareness of the dosages and administration rates), and changing dosages and
emergency contingency plan should be part of the orienta- administration rates in response to changes in patients’ weight
tion and annual competency plan for all providers. and stature. For dosage and administration rates calculated
Implementation of a CPOE system presents many new from pharmacokinetic data, the mathematical equations that
challenges for the health (or patient) care team. Although describe how calculated values were derived should appear
remotely entering orders in a CPOE system may be conve- in the treatment plans and medication orders.
nient for some, it may also reduce the face-to-face contact
of writing in the chart during rounds or while on the patient- Standardize the Content of Medication Orders. Standards
care unit, reducing the opportunity for personal interactions should be established for the content of an acceptable medi-
between healthcare professionals. While CPOE has been cation order, requirements for patient-specific measure-
shown to prevent prescribing errors, it is not a panacea, and ments, and data that must be included on medication-order
diligence and independent checks are still essential to a safe forms.33,34 The following standards are recommended:
chemotherapy process using CPOE. Knowing some of its
pitfalls in advance will aid in the design and use of all the 1. All orders for patient-care services should be clearly
features available in a CPOE system, especially for high- dated and timed.
risk therapies such as chemotherapy. The success of CPOE 2. When ordering chemotherapy medications, the ge-
depends on having high-level administrative, clinical, finan- neric drug name (as approved by the United States
cial, and information technology support. It is critical front- Adopted Names [USAN] program) should be used.
line staff have a significant role in the development, imple- Brand names are not acceptable unless they aid in
mentation, and monitoring of CPOE.28 identifying combination drug products or a particular
drug formulation (e.g., to distinguish between liposo- Therefore, a medication order that complies with these rec-
mal and nonliposomal product formulations). ommendations would appear as follows for a patient with
3. The dosage form should be specified. a BSA of 2 m2: Methotrexate injection 100 mg/m2/dose =
4. Orders for medications should include the patient- 200 mg in 100 mL 5% dextrose injection/dose, administer
specific data from which drug doses are calculated by continuous intravenous infusion over 24 hours, every 48
(height, weight, BSA, laboratory test results). When hours for three doses days 1, 3, and 5. Start at 0800 on April
drug dosages and schedules are modified for current 1, 2014.
or anticipated pathologies, treatment plans and medi-
cation orders should explicitly identify the factors on Establish Dosage Limits and Acceptable Routes of
which treatment modifications are based. If the order Administration. Medication-use systems should include
is for chemotherapy as part of the clinical trial, identi- utilization limits for chemotherapy medications. Constraints
fying information for the protocol should be included should be developed to limit maximum chemotherapy
in the order. drug dosages and administration routes and schedules.
5. Drug dosages and calculated doses should be ex- Multidisciplinary peer review should be completed before
pressed in metric notation. The word units should established drug administration limits are exceeded.11,12
never be abbreviated in medication orders where drug These constraints should include the maximum amount of
dosages and administration rates are expressed in bio- a chemotherapy drug that may be administered as a single
logical activity units (e.g., aldesleukin, asparaginase, dose, the maximum amount that may be administered during
bleomycin). Leading zeros (e.g., 0.3 mg) should be a defined time interval (including maximum administration
used for numbers less than one. Trailing zeros should rates for parenterally administered medications and maxi-
never be used. mum dose per day for oral therapy), and the routes by which
6. Medication orders should specify the drug dosage each drug should be administered.35 For example, some in-
and calculated dose according to the “container stitutions cap the dose of vincristine at 2 mg or limit the
rule” (i.e., the specified and calculated dose is the lifetime dose of doxorubicin to 550 mg/m2 in patients with
amount prepared in and administered from a single normal cardiac function.
container).20 Constraints for dosage and administration rate may be
7. Administration vehicle solutions and volumes should defined by treatment regimens and protocols and may vary
be specified, unless standard solutions and volumes among protocols. In contrast, the types of treatments admin-
have been established. istered in some practice settings may be consistently simi-
8. The administration route should be specified. lar, permitting the establishment of absolute maximum dose
9. The administration rate should be specified, when rel- limits within that practice setting.
evant. Limits should also be established for the maximum
10. The administration schedule and the duration of treat- amount of a chemotherapy drug that may be administered
ment should be specified. Treatment plans and medi- during one treatment course or cycle and, when appropriate,
cation orders should specify the interval between the maximum amount of drug that may be administered to a
repeated doses, the days on which each dose is to be single patient within his or her lifetime.11 In addition, dosage
given within a treatment cycle or course, and the total limits should be established for chemotherapy medications
length of a treatment cycle or course. used in specific combination regimens (defined for each
11. The dates and times when drug administration is to drug) in which clinical toxicities may be exacerbated by
commence, or the temporal sequence in which each combining agents with overlapping adverse-effect profiles.
medication is to be administered, should be specified. Chemotherapy drug-use limits should appear promi-
When 1200 is written as 12 a.m. or 12 p.m., it may nently in printed treatment descriptions (e.g., protocol
be incorrectly interpreted. Directions indicating events summaries, care maps, schematic treatment diagrams) and
for 1200 should be written as 12:00 noon or 12:00 on printed medication-order forms and computer-based
midnight, or expressed in the 24-hour system. medication-order templates. Active clinical decision sup-
12. The medical record should contain a justification for port that alerts healthcare providers whenever an order for
the chemotherapy treatment plan (e.g., a reference chemotherapy medications exceeds defined limits would be
to FDA product labeling, the primary literature, in- ideal.36 For patients who receive chemotherapy medications
stitutionally approved guidelines, national consensus for which cumulative dosage limits have been established,
guidelines, or an investigational protocol); similar in- cumulative dosage data should be constantly updated in
formation may be included in the medication order to their permanent medical records and in any supplementary
provide additional clarification. records. Patients’ cumulative dosage data should be audited
13. Although healthcare providers have traditionally used and independently confirmed by healthcare providers when
abbreviations, acronyms, and nicknames to describe verifying orders for chemotherapy medications.11,37
chemotherapy medications and treatment regimens, In each healthcare organization, the medication-use
the practice is potentially dangerous and should be system should include a multidisciplinary committee that
avoided. Abbreviations for drug names, scheduling oversees matters related to medication-use limits. The com-
information, and directions for medication use should mittee should proactively develop and establish policies and
be prohibited in medication orders. Nonstandard ab- procedures for resolving disagreements related to patient
breviations, Latin abbreviations, and apothecaries’ treatment among providers; whether medications should be
weights and measures should not be used in orders for prepared, dispensed, and administered if a discrepancy can-
chemotherapy medications. Whenever possible, mea- not be resolved; and how medication-use-related disputes
surement units should be expressed in metric notation. are to be resolved. Committee membership should comprise
all providers who have responsibilities in the medication-use administered by other routes (e.g., intravenous, sub-
process in the organization.11 cutaneous, intramuscular) in the pharmacy. Upon de-
livery to the unit, intrathecal medications should be
Investigational Chemotherapy Medications. Cancer pa- stored separately from medications with other routes
tients often receive investigational (i.e., experimental) anti- of administration.
cancer treatments at facilities participating in clinical trials. 4. Providers administering intrathecal chemotherapy
Consideration must be given to ensure that the same safety should do so in a setting that has been designated
precautions and checks that are used for FDA-approved che- for that procedure. An independent double check by
motherapy therapies apply similarly to prescribing, prepar- two qualified individuals should be completed prior
ing, dispensing, and administering oral and parenteral inves- to administration.
tigational medications and monitoring patients who receive
those therapies. Recommendations for Multidisciplinary
Facility administrators should ensure that adequate
staff is maintained to support an investigational drug pro-
Monitoring of Medication Use and
gram.31 Ideally, nurses and pharmacists should be involved Verification
early in the process of developing clinical protocols involv-
ing the use of commercially marketed and investigational Independent medication-order verification is an essential
chemotherapy medications.38 Early involvement helps en- safeguard that ensures the accuracy and appropriateness of
sure that chemotherapy regimens are expressed in a fash- medical treatment. It is imperative that healthcare provid-
ion to mitigate errors, and investigational medications are ers resolve any questions related to medication orders be-
prepared and administered in accordance with local policies fore treatment commences. Providers should recognize that
and procedures. Nurses and pharmacists should be voting medication-order verification and other system safeguards
members on regulatory and review committees that evaluate ensure patients’ safety.11,20,37 Lack of information about pa-
the scientific and ethical treatment of patients receiving che- tients and their medications has been described as the most
motherapy medications and monitor investigational thera- frequent cause of medication errors.24,39 In order to indepen-
pies (e.g., institutional review boards).11 dently verify prescribers’ orders for medications, all persons
Because a protocol governs and supplies the rules for who prepare and administer chemotherapy medications and
drug use in clinical trials, an up-to-date copy of the study those who monitor patients who have received chemothera-
protocol should be available for review at all sites where pies should also have access to complete, up-to-date copies
medications are prepared and administered. All staff should of treatment protocols and patient-specific data, including
be informed through inservice education programs before home medication lists.11,30,37 Drug information and reference
new protocols are implemented. Inservice programs and materials should be readily available to all persons who pro-
study-related information should be provided by persons as- vide patient care.
sociated with the investigational study (e.g., principal inves- Each healthcare provider has a responsibility to share
tigator, associate investigators, protocol chairperson, study- information with other providers and consultants to ensure
coordinating personnel). If an investigational protocol is to patient safety and an optimal treatment outcome. Policies
be conducted at more than one site within a health system, that regulate treatment verification standards should de-
procedures should be developed to ensure that up-to-date scribe how prescribers, medically responsible and senior au-
information is available at all study sites where patients re- thorizing physicians, pharmacists and pharmacy technicians,
ceive protocol-directed care. nurses, and other persons who are responsible for transcrib-
Procedures for supplying healthcare providers with ing and transmitting medication orders should interact and
information about patients’ dose assignments, drug dosage, communicate information.
and schedule modifications should also be devised. A sepa- Providers who prescribe, prepare, dispense, and ad-
rate procedure should be established allowing independent minister chemotherapy medications should perform inde-
dose-checking activity among all disciplines involved in the pendent double checks at defined points in the chemotherapy
medication-use process for investigational drugs. use process. Treatment-verification systems may incorporate
computerized medication-order safety checks but should
Intrathecal Administration. Administration of chemo- also include independent manual double checks.11,31 Ideally,
therapy via the intrathecal route is necessary for certain computerized systems (e.g., CPOE) are used to calculate and
treatment regimens. Given the high risk associated with verify dosages and the rate and route of administration for
intrathecal administration (e.g., vincristine intrathecal ad- chemotherapy drug orders and to screen medication orders
ministration is fatal), specific considerations apply to intra- for compliance with dosage limits. In addition to facilitat-
thecal administration of chemotherapy: ing chemotherapy-order processing, computer software can
also serve as a double check on prescribers’ orders. Systems
1. Prescribing should be limited to providers with institu- requiring pharmacists to transcribe prescribers’ medication
tional privileges to prescribe chemotherapy. orders into a computerized or manual drug-ordering system
2. Drug labels should clearly indicate that the chemo- should have a second person, preferably a pharmacist, re-
therapy is only intended for intrathecal administration, check all order-processing documents and product labeling
including ancillary labels. Vinca alkaloid drugs must before a drug product is dispensed. In situations in which a
contain label warnings to avoid intrathecal administra- pharmacist is not available, a prescriber or nurse may serve
tion. as the second check.
3. Medications that will be administered intrathecally Providing medications to patients includes five dis-
should be placed in separate bags from medications crete steps: prescribing, preparation, dispensing, adminis-
tration, and monitoring. The ideal verification system has pleting all relevant orders of a treatment regimen at the same
ten established checkpoints to ensure that an chemotherapy time. Requiring all treatment details in advance ensures that
drug is accurately prescribed, prepared, dispensed, and ad- orders can be checked for completeness and accuracy and
ministered to the patient for whom it was intended (Figure compliance with planned treatment.
1). Different individuals should complete each check so that Institutions should establish policies regarding
no single person bears responsibility for checking his or her whether chemotherapy may be prescribed by physicians-in-
own work. training (e.g., medical fellows) and nonphysician healthcare
providers with prescribing privileges (e.g., nurse practitio-
Prescribing Chemotherapy Medications (Checkpoint 1). ners, physician assistants). If the institution allows prescrip-
Healthcare providers who prescribe, prepare, and adminis- tions by these individuals, these orders should be verified
ter chemotherapy drugs should be familiar with the entire by at least one medically responsible person, other than the
treatment regimen. A prescriber should order all the medica- prescriber, who is knowledgeable about medical oncology.
tions necessary for the entire treatment regimen, including When orders for chemotherapy drugs must be coun-
hydration and supportive care orders, at the same time and tersigned by a second medically responsible individual, the
prior to administration of any of the medications. When pre- person who countersigns the medication orders should criti-
scribing chemotherapy regimens based on a patient’s weight cally evaluate each order for a chemotherapy treatment. This
(or BSA, which relies on weight), weight data and trends is checkpoint 1. The orders should be compared with patient-
in patient weight should be evaluated to be sure the correct specific data and verified against original reference sources
information is used. In CPOE, order sets may assist in com- that describe the treatment regimen (e.g., a published article,
Figure 1. Medication-order verification system. These established checkpoints ensure a chemotherapy medication is accurately prescribed,
prepared, dispensed, administered, and monitored.
validated standard reference text, investigational protocol). For patients who receive treatment in clinical trials in which
If the patient is taking part in an investigational study, veri- more than one primary or ancillary treatments are prescribed
fication of enrollment onto the trial and of informed consent (e.g., dose- and duration-escalating studies), treatment as-
should be reviewed. signment and dosage and administration schedule modifica-
tions should be confirmed with at least one person directly
Preparing Chemotherapy Medications (Checkpoints 2–4). associated with the clinical trial, other than the prescriber
Checkpoint 2 requires persons receiving a prescriber’s order (e.g., the principal investigator, an associate investigator,
for chemotherapy medications to review the original medi- research nurses or pharmacists, a study coordinator or chair-
cation orders and independently verify them against pub- person). The prescriber should be consulted when expected
lished standards (e.g., product package labeling, reports treatment modifications were not ordered or when nonstan-
published in professional journals, treatment protocols, dard modifications were prescribed.
standard reference textbooks) and determine appropriate- Instructions for diluents, drug administration sequence
ness based on patient-specific information. The dose per and duration, number of doses, and starting date and time
container and the total course dose should be verified at should be checked. To ensure that appropriate ancillary and
this checkpoint. supportive medications that facilitate chemotherapy drug de-
Because erroneous information sometimes appears in livery and those required by protocol have been prescribed
published information, orders for noninvestigational chemo- and are complete and accurate (e.g., premedications, hydra-
therapy medications should be verified against the primary tion, cytoprotectant and “rescue” medications, antiemetics,
reference in which the specific treatment was described hematopoietic growth factors), their orders should be re-
(e.g., published reports, study protocols, meeting proceed- viewed and confirmed. Discrepancies between prescribed
ings). If a primary reference is not available, the treatment medications and planned treatment should be brought to the
regimen should be confirmed with a resource that previously prescriber’s attention and resolved before medication prepa-
had been validated as accurately describing the planned ration proceeds.
treatment (locally compiled handbooks, guides, and com- At checkpoint 3, after treatment orders have been
pendia) or at least two alternative publications, including verified, all work related to medication-order processing
reviews and reference textbooks.11,34 Investigational drug and preparation accuracy should be routinely documented
doses and administration schedules must be verified against in a standardized format, either on paper or electronically.
a study protocol that was approved by all relevant regula- Drug preparation work sheets (sometimes referred to as
tory agencies and study sponsors (e.g., institutional review work cards or admixture or compounding logs, sheets, and
board, National Cancer Institute, FDA). Protocol amend- cards) identify the drug products prepared for each patient
ments should be distributed immediately and be readily and the persons who prepared and checked the medications.
available for reference. In addition, order templates should Although layout and design may vary among work sheets,
be updated as soon as possible, especially for drug dose or and data may be organized as a continuous log in which
preparation changes. each drug product appears on separate, consecutive lines or
Although preprinted order forms and CPOE preclude as a separate record for each patient, all work sheets should
the necessity of repeatedly verifying drug names, dosages, detail the techniques used in preparing the drug products.
routes, and schedules, all medication orders should be eval- They should also identify special preparation and dispens-
uated for completeness, compliance with the planned regi- ing information, such as the indication of special product
men, and, during repeated courses, deviations from previous containers, requirements for filtration, the need for special
treatments by following these recommendations: diluents, intermediate dilution steps, and how and when
administration sets should be attached to the drug product
1. The date a patient was last treated and the next planned container. Order processing, drug preparation, and process-
treatment date should be compared to ensure that an ing records should be confirmed by a second individual
appropriate interval has elapsed since treatment was (preferably a pharmacist).11,12 The calculations written on
last administered. preparation work sheets should be independently verified by
2. Measurements from which a patient’s medication dos- a second healthcare provider who did not prepare the work
age and administration rate are calculated should be sheet. Independent verification should include checking the
confirmed (e.g., height, weight, BSA). Institutions work sheet for completeness and accuracy of content, with
should develop policies and procedures regarding particular attention given to special preparation instructions.
when patient-specific data (e.g., height, weight, BSA) A checklist, whether paper or electronic, that identifies the
should be re-measured. It is important to review trends necessary elements in chemotherapy drug preparation may
in height and weight as a double check to ensure there be a helpful reference (Figure 2).11 Technology can serve as
were no errors in documentation. a surrogate checklist, if practitioners follow procedures in
3. Appropriate laboratory test and physical assessment using appropriately developed and applied software.
values should be evaluated and primary treatment ref- At checkpoint 4, drug products should be checked, af-
erences should be consulted to determine whether they ter preparation, against both the preparation work sheet and
are within acceptable ranges or if treatment modifica- the original order by an individual who was not involved in
preparing the work sheet. Checklists may also be helpful for
tions are indicated.
this step.11
4. A patient’s allergy, drug sensitivity, and adverse drug
effect histories and his or her current medication pro- Dispensing Chemotherapy Medications (Checkpoint 5).
file should be evaluated for potential drug interactions Checkpoint 5 requires persons dispensing medications to
with planned chemotherapy treatment. patients or caregivers for outpatient use to verify a patient’s
Figure 2. Chemotherapy drug preparation checklists.
Checklist for Initial Setup of Chemotherapy Drug Work Card

This form should be completed on paper or electronically by the pharmacist checking the work card. Place check mark (or N/A)
in each space after each check is completed. Your check marks and initials at the bottom of this work sheet are your personal
assurance that you checked all these items for accuracy in the setup and transcription of information onto the work card. Each drug
requires a separate checklist.
Patient ___________________ Drug _______________
Start date _____________
Administration time _____________
Stop date _____________
Duration _____________
Correct drug name _____________
Number of doses ______
Dose _____________
Drug concentration _____________
Drug volume _____________
Diluent _____________
Volume of diluent ______Overfill _____Drug in overfill ____
Expiration time _____________
Special delivery devices (tubing, cassette, container, etc.)
Correct route of administration _________________________
Correct line type, as appropriate ______________________
Correct mixing instructions (special directions, e.g., “Do Not Filter”) _____________
Auxiliary label information (e.g., “Do Not Refrigerate,” “Use In-line Filter,” “For Intrathecal Use Only”) ___________
Correct total volume _____________
Pharmacist’s initials ______________ Date ______________
This record should remain with the work card for the duration of the order and be saved for the supervisor for review after
discontinuation of the order.
Supervisor’s initials _______________ Date ______________
Continued on next page
identity when a medication is dispensed. Patients who self- tional medications, diluent, and vehicle solutions), route of
administer their medications or personal caregivers should administration, and schedule are correct.
visually examine the medication, confirm whether its ap- At checkpoint 7, healthcare providers should exam-
pearance meets their expectations, and compare its instruc- ine the medication container and note whether the content’s
tions with information they received from their healthcare general appearance is what was expected. Many parenteral
providers (e.g., a chemotherapy calendar). chemotherapy products have distinctive colors, and prod-
uct coloration should be confirmed before administration.
Dispensing and Administering Chemotherapy Medications At checkpoint 8, patients who self-administer their
(Checkpoints 6–9). At checkpoint 6, before starting treat- medications (or receive it from personal caregivers) should
ment, each chemotherapy medication should be checked in- carefully read the container’s label to confirm the product’s
dependently against the prescriber’s orders by at least two identity and review its instructions for use (schedule of dos-
individuals who are trained and competent to administer ing, whether to take with or without food) each time they
chemotherapy medications. All dosage- and administration- take a medication.
rate-related calculations should be independently verified. At checkpoint 9, patients should be encouraged to ask
This includes any infusion pump rate settings, which should questions about their treatment before its administration and
be checked at the initiation of each container of the infu- compare its appearance and medication label with informa-
sion, periodically throughout the infusion, and whenever a tion they received about the treatment. Patient identification
new nurse assumes care for the patient. Healthcare providers using two identifiers should occur prior to chemotherapy
should routinely confirm that the medication will be admin- administration. Whenever possible, barcode-driven admin-
istered to the intended patient by comparing a patient’s name istration should be used.40
and unique identifying code or number with medication la- In ambulatory care practice, it is common for patients
bels (e.g., alpha–numeric characters or bar codes) and that to receive parenteral chemotherapy medications in a setting
a drug product’s identity, ancillary components (e.g., addi- where a physician and a nurse (or other healthcare profes-
Figure 2 (continued)
Checklist for Preparing and Labeling Chemotherapy Drugs

For each order you check, verify that each element is correct with a check mark.
Patient ________________________ Drug ____________
Date _____________
Label check
Patient name is same as on front of work card __________
Drug name on label matches drug name written on back of work card ____________
Dose on label matches dose written on back of work card_____________
Diluent on label matches diluent written on back of work card _____________
Volume of diluent on label matches volume of diluent on back of work card _______
Correct date to prepare _____________
Expiration date and time _____________
Correct time (expiration date not greater than administration time) _____________
For each drug/additive
Correct drug used ________Proper protocol supply ____
Drug concentration in each vial _____________
Additives, such as sodium bicarbonate solution, for which large stock bottles are used (which remain in hood) are visually checked,
lot number is verified, and technician is asked to verify volume used ____________
Drug volume for dose verified ____________
Drug lot number on each vial matches lot number written on work card _____________
Calculations are checked _____________
Drug has not expired _____________
For each diluent
Correct diluent ______Volume of diluent _____
Diluent has not expired _____________
Special instructions followed
Air purged from bag ____
Tubing affixed/primed to end of line ________
Diluent for reconstitution _______
Correct container _____Proper overfill ___Drug in overfill ___
Final miscellaneous steps
Chemotherapy work card checklist is in card pocket _____
Solution is inspected for impurities/floaters_____________
Label is initialed (on left-hand side of label just below last additive or drug) after being affixed to correct admixture _____________
Total volume to be infused _____ Red chemo i.v. seal _____
“Caution chemo” label ____ Other auxiliary labeling ____
Zip-lock bag __________
Work card is initialed _____________
Pharmacist’s initials ___________ Date _____________

Supervisor’s initials ___________ Date _____________
sional) complete all tasks related to prescribing, preparing, failure at one of the prior checkpoints. However, a vigilant
administering, and monitoring treatment without a pharma- healthcare team might discover a potential error sooner if
cist’s participation. Under these circumstances, the healthcare they are knowledgeable about the expected adverse effects
providers involved should perform independent double checks and are vigilant for either exaggerated or unexpected ad-
and be involved in the entire process. The person preparing verse effects.
chemotherapy medications should work from written orders. For all chemotherapy agents administered at a health-
care institution, the patient’s clinical status should be as-
Monitoring (Checkpoint 10). Chemotherapy agents are usu- sessed on each day of chemotherapy administration. Vital
ally expected to produce adverse events, so it is sometimes signs should be taken and a standardized assessment for pos-
difficult to detect possible medication errors resulting from sible toxicities should be performed.
For oral chemotherapy agents, assurance that patients scribed (e.g., for sore mouth, for nausea, for chronic lym-
understand how to take their chemotherapy medicine should phocytic leukemia).
be assessed initially and then at each patient encounter. An When chemotherapy treatment (ordering, preparing,
assessment for adherence should be performed at each clinic and administering) is coordinated at a single location, it is
visit. Patients should be taught how to recognize and report the prescriber’s responsibility (or in the conduct of clini-
expected and unexpected toxicities. cal trials, it is the principal investigator’s responsibility) to
provide information about the treatment (e.g., protocols,
publication reprints) to those who prepare and administer
Recommendations for Prescribing medications and monitor patient outcomes. It remains the
Systems and Prescribers prescriber’s responsibility to answer questions and provide
information to other healthcare providers when treatment is
Chemotherapy prescribing is complicated by numerous implemented in a place that is geographically separate from
medical publications that report indications, dosages, and the prescriber’s location. Prescribers, clinical investigators,
administration schedules inconsistent with FDA-approved and medically responsible staff should provide to healthcare
product labeling. Chemotherapy treatments frequently in- providers who prepare and administer chemotherapy medi-
volve off-label uses based on preliminary reports, promis- cations a complete printed (or electronically reproduced)
ing information from abstracts, and compendia information. copy of the treatment regimen.
Prescribers must exercise great care in correctly interpreting
this information and clearly communicating orders for che- General Guidelines for Prescribing Chemotherapy
motherapy medications with other healthcare providers. Medications.11,13,20,41 The following are general guidelines
Health-system administrators should require orders for for prescribing chemotherapy drugs:
all chemotherapy medications and other high-risk drugs pre-
scribed by physicians-in-training or nonphysician prescrib- 1. Instructions for medication regimens should be ex-
ers to be countersigned by a senior physician with expertise plicit, complete, clear, and easy to follow. Treatment
in the specialty to safeguard against errors in interpretation regimens should be described accurately and consis-
and prescribing. Healthcare providers seeking privileges for tently in all written, published, or circulated materials
prescribing chemotherapy drugs should complete an orienta- in which chemotherapy medication use is described.
tion to local policies and procedures related to prescribing 2. The patient’s medical record should contain a justifi-
chemotherapy before they are permitted to order them for cation for the chemotherapy treatment plan (e.g., FDA
patient care. product labeling, a primary literature reference, in-
Healthcare providers should locally develop standard- stitutionally approved guidelines, national consensus
ized dosage and administration schedule modifications for guidelines, or an investigational protocol).
each chemotherapy medication. Treatment modifications 3. Medication-use systems should require healthcare
may be appropriate for patients with the following character- providers to use standardized vocabulary and nomen-
istics: (1) preexisting pathologies that predispose a patient to clature for describing treatment with chemotherapy
adverse effects from treatment with particular chemothera- medications. “Tall Man” lettering should be used for
pies (e.g., withholding or decreasing bleomycin dosages in written and electronic orders.
patients with preexisting pulmonary dysfunction or cardio- 4. Prescribers should use uniform and consistent nota-
tions to express quantifiable amounts (dosage, con-
toxic agents in patients with congestive heart failure); (2) a
centration, volume, and time).
history of severe, prolonged, or cumulative adverse effects
5. Prescribers should never trail a whole number with a
after previous chemotherapy treatments; (3) impaired physi-
decimal point followed by a zero (e.g., write “5 mg,”
ological function that predisposes patients to altered phar-
not “5.0 mg”).
macodynamic responses (e.g., renal or hepatic impairment);
6. When writing amounts less than one, the expression
(4) low or decreased performance status; and (5) patients on
should be written with a leading zero preceding the
multiple medications with a potential for a drug interaction
decimal point (e.g., “0.125 mg”).
with a particular chemotherapy. 7. All treatment plans and medication orders should
Healthcare providers should also establish for their identify the dosage (as a function of body weight,
institutions standardized guidelines for prescribing drugs BSA, or other dosing factors) and the calculated dose.
that are routinely administered concomitantly with chemo- Total course dose should be included in circumstances
therapy medications. Medication-use guidelines for sup- in which a single infusion container is designed to pro-
portive care and ancillary agents (e.g., antiemetics, hydra- vide multiple days of treatment (e.g. 7-day cladridine
tion, chemoprotectants) should be made accessible to all infusion).
healthcare providers who prescribe, prepare, and administer 8. When treatment day enumeration is arbitrary, day 1
chemotherapy drugs and for persons who perform clinical typically describes the day treatment commences. In
monitoring. contrast, hematopoietic progenitor-cell transplanta-
When generating medication orders in a setting where tion regimens often include day 0, and significant
preprinted ordering forms, CPOE, and other electronic and treatment-related events before and after a progenitor-
mechanical means (e.g., e-prescribing) are not available, cell graft is administered are distinguished by negative
prescribers should legibly print the names of medications, (minus) and positive (plus) prefixes, respectively.
dosages, routes of administration, and administration sched- 9. All medications that are a part of the treatment regimen
ules in plain block letters and Arabic numerals. Medication (e.g., oral chemotherapies) should be included, indi-
orders should include the indications for which they are pre- cating where the product will be filled or dispensed.
10. Recommendations for proper medication storage c. whether alternate day dosing is appropriate
should also be included. Cancer patients must often based on the pharmacokinetic and pharmacody-
travel long distances to receive care, so guidance and namic properties of the medication. The goal of
support (provision of coolers and ice packets for re- alternate day dosing is to fulfill the total weekly
frigerated medications) to properly store medications dose rather than giving the exact daily dose
when in transit as well as at home. (e.g., if an agent is to be given 175 mg daily
for 2 weeks, but the drug is only available in 50
In some cases, CPOE can be used to promote best practices mg capsules, consider alternate day dosing by
(e.g., eliminating the use of trailing and leading zeros [items giving 200 mg on one day and 150 mg on the
4 and 5 above]). next day). If alternate day dosing is used, then
instructions that say “take X tablets on odd days
Specific Recommendations for Parenterally Administered and X tablets on even days” should be avoided,
Medications.20 Healthcare providers should adhere to the as two consecutive odd days may occur when
following guidelines for parenteral chemotherapy drugs: transitioning from one month to another. For ex-
ample: January 31 and February 1.
1. In treatment plans and orders, doses should be ex- 4. Only the quantity needed to cover the administration
pressed as the total amount of medication to be admin- period until the next clinical evaluation should be or-
istered from a single container (i.e., the total amount of dered.
medication per syringe, bag, or other container). 5. If appropriate, instructions should address how medi-
2. For medication admixtures that can be prepared in cations are to be taken with respect to food ingestion
more than one way, practitioners should institute and indicate whether particular types of food may af-
a priori, standard, and consistent methods directing how fect medication activity.
each medication will be prepared and administered. 6. Oral chemotherapy medication orders should be in-
3. When a medication with extended stability is adminis- cluded with parenteral chemotherapy orders to allow
tered from a single container for more than 24 hours, for appropriate screening and safety checks.
a prescriber’s order for treatment should specify the 7. Oral chemotherapy medication orders should be in-
amount of medication to be administered during each cluded on the patient’s home medication list to allow
24-hour interval.20 For example, a medication order for appropriate screening and safety checks.
for a patient with a BSA of 2 m2 should read: Drug 8. Oral chemotherapy medication orders should be com-
XYZ (8 mg/m2/day × 3 days) 48 mg in 150 mL 0.9% municated to the pharmacist for appropriate screening
sodium chloride injection by continuous intravenous and safety checks.
infusion over 72 hours. Start on 04/01/2001 at 0800 9. Patient instructions should address what to do if a dose
(total dose/cycle = 48 mg). is missed.
10. Patients should be provided with explicit instructions
Specific Recommendations for Orally Administered regarding what adverse effects to expect, which ones
Chemotherapy Medications.20,42 Prescribing orally admin- require a telephone call to a provider, and who and
istered chemotherapy agents presents unique challenges for where to call.
healthcare providers due to the greater responsibility placed 11. Instructions should describe safe handling, storage,
upon patients to manage their own care and patients’ percep- and disposal of oral chemotherapy.
tion that these agents may be less dangerous than parentally 12. Essential ancillary medications and supportive care
administered agents. Healthcare providers should adhere to that accompany a chemotherapy treatment regimen
the following recommendations when oral medications are should be explicitly identified.
the prescribed chemotherapy treatment or when oral chemo- 13. Refills on oral chemotherapy medications should be
therapy is included as part of the treatment regimen: discouraged, when feasible.
14. Patients should be appropriately educated regarding
1. In treatment plans and medication orders, drug doses access and cost issues (e.g., regarding specialty phar-
and schedules should be described as the amount of macies, prior authorization, out-of-pocket costs, and
medication to be taken per dose, not as a total daily options for pharmaceutical manufacturer or copay as-
dose that is to be taken in divided doses. sistance).
2. In treatment plans, medication orders, and instructions
to a patient, the number of doses to be administered or Recommendations for Medication
taken should be clearly identified.
3. Doses for solid orally administered dosage forms
Preparation and Dispensing Systems
should specify whether and how doses are to be and Roles for Pharmacists
rounded to the nearest capsule or tablet strength. If the
calculated dose can’t be provided based on the avail- For each practice setting, persons representing the vari-
able dosage forms, the following alternatives can be ous healthcare disciplines that prescribe, prepare, and
considered: administer chemotherapy medications should participate
a. whether tablet formulations should be broken (if in planning and managing local medication-use systems.
not a hazardous drug);
b. whether an alternative dosage method or formu- Standardized Medication Preparation Guidelines. Health-
lation is appropriate; or care providers should establish standardized guidelines for
reconstituting, diluting, admixing, packaging, and labeling
commonly used chemotherapy and other medications that evaluation systems for all practitioners who have direct pa-
are routinely administered with chemotherapy. Each prac- tient contact.
tice facility should also establish a standardized method for Pharmacists should engage the support of medical and
labeling multidose vials and reconstituted drug products. nursing administrators and supervisors to encourage their
Standardized medication preparation guidelines should be staff (particularly those in professional training programs)
prominently displayed (e.g., as a chart) for easy accessibility to complete chemotherapy medication-error awareness pro-
in areas where orders are processed and medications pre- grams.30 Educational programs should be discipline specific.
pared. Policies should be developed for prescribing of oral Program content should include medication-error case sce-
chemotherapy that are not being dispensed by the health sys- narios, problem-solving to prevent and mitigate medication
tem. Instructions for patient counseling, safe handling, and errors, and discussion about the effects that medication errors
disposal should be included in these policies. have on patients’ quality of life and the health system.11,31
Policies and procedures should be developed for situ-
ations in which medications are prepared at facilities that Standardized Drug Procurement and Storage. Pharmacists
are geographically removed from where treatment is admin- who select and procure drugs should strive to minimize or
istered. Procedural protocols should describe requirements eliminate look-alike drug product containers and limit the
for medication packaging, storage conditions during trans- availability of different vial sizes for parenteral medica-
portation, duration of transport, and handling after delivery. tions whenever possible.12 Frequent additions to the variety
Medication couriers should receive training in organiza- of available drug products and changes among alternative
tional policies for handling medications and should immedi- manufacturers’ drug products can contribute to medication-
ately report when conditions and handling practices deviate use errors and should be avoided. If it is necessary to change
from procedural standards. In addition, handling procedures manufacturers, healthcare organizations should develop a
should ensure patient confidentiality and provide guidelines process to ensure staff are educated about the new product
for emergency situations, such as hazardous-drug spills. and that computer systems have the appropriate manufac-
Persons who prepare and dispense chemotherapy med- turer’s information. When practical, drug products with
ications should ensure timely drug delivery to patients and similar names and packaging should not be stored next to
patient-care areas after receiving written orders. If dispens- each other. Medication-use systems that involve a formulary
ing is delayed for any reason, healthcare providers awaiting should separate nonformulary products from those that are
the medications should be notified.11 on the formulary. Healthcare providers should familiarize
themselves with chemotherapy drugs that are not on formu-
Quality Assurance and Improvement. In collaboration with lary before prescribing, preparing, and administering them.
healthcare providers who prescribe and administer medica-
tions, pharmacists and persons who prepare and dispense Standardized Medication Preparation and Dispensing.
chemotherapy should take the initiative in developing and Chemotherapy medications should be dispensed in ready-to-
managing quality-assurance and quality improvement pro- administer dosage forms whenever possible. Generally, che-
grams for their medication-use systems. These programs motherapy for intermittent parenteral administration should
should include surveillance and reporting systems, FMEAs, be prepared so that each medication container has only one
and root-cause analysis, when appropriate, that track po- dose. The risk of incorrect medication use is increased when
tential and actual medication errors, evaluate the proximal the amount of drug dispensed in a single container exceeds
causes of errors among processes and systems, and identify the amount to be administered during a 24-hour period. It
preventive measures.11,43 The major advantage of multidis- is essential that individuals and committees responsible for
ciplinary participation is that each discipline’s perspectives developing and overseeing medication-use systems establish
and methods for conceptualizing system flaws and solutions guidelines on whether prescribers may order chemotherapy
can be incorporated in designing strategies for preventing preparations to be administered from a single container for
medication errors. Confidential reporting is essential to the more than 24 hours. In all practices where parenteral drugs
success of a medication-error surveillance and reporting with extended stability (more than 24 hours) are sanctioned,
system. Only by understanding what causes and contributes it is imperative that the duration of their use is clearly la-
to errors can the number of errors be reduced. In design- beled and that healthcare providers are trained to correctly
ing a medication-error surveillance and reporting system, prescribe, prepare, and administer them.20
strategic emphasis should be placed on understanding why When preparing a chemotherapy admixture, a quantity
errors occur and not on blaming or censuring personnel.44 of medication that most closely approximates the prescribed
Further, proactive assessment of the chemotherapy-use pro- dose should be segregated from other drug supplies. For
cess should be conducted. treatment regimens that include two or more drugs, espe-
cially when medications are to be administered by different
Orientation on Medication-Error Reduction. Pharmacy routes, the medications should be physically segregated dur-
supervisors and managers should develop an orientation ing preparation and when administered. Compounded medi-
program about medication errors commonly associated with cations should be prepared one at a time, using standardized
chemotherapy medications for training of pharmacy person- techniques whenever possible.
nel who prepare and dispense chemotherapy. Pharmacists The chemotherapy preparation process should include
should develop ongoing interprofessional educational pro- an independent double check by two separate individuals
grams that focus awareness on potential medication errors of the correct drug, diluents, administration containers, and
with chemotherapy medications, strategies for preventing volume measurements before the solutions are transferred
errors, and local and national medication-error reporting and to the final administration container. A person other than
the individual who selected the components of the prepa-
ration (drug and diluent) and measured the volume of di- Labels for oral dosage forms, rectal suppositories, and
luent solutions used to reconstitute the medications should topically applied unit-dose products should include all of the
visually confirm the correct product(s) and measurement(s) following information:
before the solutions are transferred from the measuring de-
vice to the drug vial for reconstituted drugs and to the fi- 1. Patient’s name, unique identifying code or number,
nal administration container. Post hoc or proxy methods for and location within a treatment facility (when appli-
checking medication preparation, including pulling back cable).
syringe plungers to demonstrate the volume of fluid that 2. Date (with or without specifying time) the medication
was injected into the secondary container, should not be was dispensed.
used as the sole method for verifying chemotherapy prod- 3. Generic drug name.
uct preparation. Verification may be accomplished by direct 4. Dosage form and strength.
visual inspection; remote monitoring through telepharmacy 5. Amount of medication per dose (when the container
applications (with pictures); or by weighing syringes, other dispensed holds more than one dose).
transfer devices, and intermediate product containers before 6. Administration route.
fluid transfer is completed. Whenever possible, methods that 7. Detailed instructions to the patient for self-administer-
allow direct observation of product preparation should be ing the medication (including a dosing calendar when
used. The actual original medication vials and diluents that appropriate).
were used during preparation must be present for inspection 8. Supplemental administration instructions (e.g., start-
during the verification process. ing and completion dates and times; number of doses
Technologies to automate the preparation of sterile to administer; cautionary information about when
products, including chemotherapy, are emerging. Some ro- medications are to be taken in relation to food inges-
botic technologies enclose and automate the entire production and other medications; and instructions and warn-
tion process, and these products may provide a variety of ings regarding administration route, handling precau-
benefits to institutions with a sufficient volume of chemo- tions, storage conditions, and container closures).
therapy to justify their substantial cost. A more common 9. The quantity dispensed within each container (the
technology organizes information, manages workflow, adds
number of tablets, capsules, or suppositories, pack-
new checks, and documents parenteral drug therapy prepara-
aged in a single container).
tion through a combination of computer software, barcodes,
and cameras. In these systems, the components of a chemo-
Labels for injectable dosage form containers should include
therapy preparation are verified with bar code technology
all of the following information:
and pictures before preparation, and pictures of the prepara-
tion are stored. These systems add additional double checks
1. Patient’s name, unique identifying code or number,
with the barcode technology and improve documentation of
and location within a treatment facility (when appli-
the preparation and other relevant information such as prod-
cable).
uct lot number. In some settings, the photos taken through
2. Generic drug name.
this technology enable the pharmacist to check chemother-
3. The amount of medication per container and, when a
apy preparation outside the sterile area. Like other technolo-
product container holds more than one dose (e.g., mul-
gies, automation for parenteral therapies must be carefully
implemented to be certain the new technology is not elimi- tiple doses for intermittent administration), the amount
nating checks in the process. For example, bar coding the of medication per dose).20
components of a chemotherapy dose does not eliminate the 4. How much overfill is added to a container when ex-
need to check the components of the chemotherapy before cess medication and fluid volumes are added to dis-
they are admixed. place air from the tubing lumen (“dead space”) in ad-
ministration sets.
Standardized Medication Labeling. Strict procedures 5. Route of administration (for example, medications
should be established for standardizing medication labeling. prescribed for administration other than by the intrave-
A uniform, systematic labeling method should be used, espe- nous route—especially those for intrathecal adminis-
cially when multiple drugs are prepared for a single patient. tration— should bear ancillary labels that distinctively
Medication labels should be mechanically printed (not hand- identify the intended administration route).
written). Chemotherapy medications should be labeled im- 6. The name and amount of all drug additives in a chemo-
mediately after preparation. Oral medications should also be therapy admixture.
sealed with child-resistant or poisoning-prevention closures. 7. Diluent (vehicle fluid) name.
Chemotherapy agents are administered parenterally 8. The volume of fluid to be administered. Adding over-
by many routes other than the intravenous route (e.g., in- fill to the container should be discouraged, but when
trathecally, intrahepatically, intrapleurally, intraarterially). unavoidable, both the volume to administer and the
Inadvertent administration by the wrong route can result in overfill volume should be specified. Proper education
serious or fatal consequences (e.g., administering vincristine for nurses administering these products is essential to
intrathecally is fatal). Medication-use systems should in- ensure that patients do not receive additional drug.
clude policies and procedures that clearly distinguish medi- 9. Administration rate and duration. Ideally, both ad-
cations administered by the intravenous route from those ministration rate and duration should be specified.
intended for administration by other routes. Auxiliary labels Because administration rates can be calculated from
may facilitate distinguishing among medications that are ad- the volume to be administered and duration of admin-
ministered by particular delivery methods. istration, duration is the essential component.
10. Supplemental administration instructions, such as start- The following roles are recommended for pharmacist
ing and completion dates and times; prohibitions about participation:
when medications are not to be administered in rela-
tion to other medications; and instructions and warn- 1. Educating healthcare providers about medication
ings regarding administration (e.g., information about errors.
special requirements for administration sets, including 2. Independently verifying medication dosages, routes of
inline filtration, warnings to avoid intrathecal admin- administration, and schedules.
istration with vinca alkaloid drugs, and hazardous- 3. Participating in multidisciplinary efforts to establish
drug warning labels). drug-specific utilization constraints that limit maxi-
11. When it is necessary to prepare more than one medi- mum doses, administration rates, and administration
cation intended for sequential administration, the con- schedules for chemotherapy medications.
tainer labels should be numbered. The sequence in 4. Participating in multidisciplinary efforts to standard-
which each container is to be used and the total num- ize the prescribing vocabulary and the development,
ber of containers (e.g., bag 1 of 3, bottle 3 of 7) should implementation, and maintenance of standardized or-
be indicated. der sets.
12. Date (with or without specifying time) the medication 5. Participating in multidisciplinary efforts to educate pa-
was ordered or prepared. Investigational compounds, tients, their families, and personal caregivers.
in particular, should be labeled with the date and time 6. Participating in multidisciplinary efforts to develop
they were prepared. adherence programs and monitor patient adherence to
13. Expiration date and time after which a medication prescribed regimens, including recommendations for
should no longer be used (i.e., beyond-use date and supportive care to treat and or mitigate adverse events
time). associated with chemotherapy agents.
14. Cautionary warnings as required for hazardous drug 7. Participating in multidisciplinary efforts to assist pa-
products.45 tients with accessing medications (e.g., prior authori-
15. Storage specifications. zation, manufacturer assistance programs, copay assis-
16. The name (with or without specifying location or tele- tance programs, coping with drug shortages).
phone number) of the institution, pharmacy, or prac- 8. Improving communication among healthcare provid-
tice from which a medication was dispensed and the ers and among healthcare providers, patients, and
prescriber’s identity. caregivers.
9. Working with pharmaceutical or equipment manufac-
Credentialing Pharmacists for Chemotherapy Medication- turers on medication-specific safety strategies.
Use Programs. Pharmacy managers and supervisors should
require pharmacist employees to complete training and dem- Drug Information Resources and Education for Providers.
onstrate competencies related to chemotherapy medication Pharmacists should help ensure the availability of up-to-date
use, evaluating medication orders, preparing chemotherapy references on the appropriate use of chemotherapy drugs for
medications, safe handling procedures, error surveillance all healthcare providers involved in medication use.11,31 Drug
and reporting programs, and local policies as a prerequisite information resources should provide information about:
to pharmacist credentialing. Healthcare organizations should
periodically reassess pharmacist employees’ competencies • Drug products’ FDA-approved labeling, compendia-
related to their responsibilities, increasing the frequency of supported indications, and investigational uses.
reassessment if performance problems occur.14 • Drug-specific precautionary warnings and information
about adverse effects, particularly dosage- and schedule-
Roles for Pharmacists. Among primary healthcare provid- limiting effects.
ers, pharmacists generally are best positioned to ensure that • Potential interactions with other drugs, disease states,
medications are used rationally and safely and increase oth- and foods.
ers’ awareness about medication errors and how to prevent • Administration methods, including drug admixture
them. Pharmacists should participate in all aspects of patient stability and compatibility data.
care related to chemotherapy treatment, including develop- • Usual adult and pediatric dosages.
ing policies for safe and appropriate medication use and • Dosage recommendations for single- and multiple-
other services consistent with pharmacist patient care.11,30 treatment courses.
Pharmacists should participate with other primary health- • Treatment modifications for persons with concurrent
care providers in multidisciplinary groups that develop, im- pathologies or end-organ impairment.
plement, and periodically reevaluate practice-specific proce- • Safety Data Sheets.
dures and processes for verifying chemotherapy medication • Pharmacokinetically based dosing and monitoring
orders, resolving procedural questions related to confirming guidelines.
and processing medication orders, and evaluating and re-
solving disputes among healthcare providers. Information and guidelines for handling chemotherapy ex-
Each organization should establish a minimum accept- travasations and hypersensitivity reactions, including the
able level of pharmacist participation in the error-prevention use of antidotes, should be developed by a multidisciplinary
elements of patient care, such as proactively reviewing med- team and be readily available.
ication orders, screening laboratory results, providing drug Pharmacists should develop and provide discipline-
information and patient counseling, and reviewing drug stor- specific educational materials about chemotherapy medi-
age conditions.11,46 cation use to healthcare providers who prescribe, prepare,
and administer chemotherapy medications. The instructional interviewing patients, their family members, or other home-
tools developed for each professional healthcare discipline based caregivers (e.g., completing medication-use and al-
should complement the materials developed for the other lergy histories, screening blood pressure, performing ongo-
disciplines.11 ing treatment response assessment, dispensing medications),
When new chemotherapies, treatment regimens, or pharmacists should provide medication education and coun-
treatment protocols are introduced, pharmacists should as- seling. They should verify that patients and their caregivers
sume a continuous, proactive leadership role in developing understand the following:
educational programs and materials for healthcare providers,
patients, and caregivers.11,31 Pharmacists should assess the 1. The purpose of the medication and its intended use.
competency of individuals assigned primary responsibility 2. The appropriate use and safe handling of medications
for chemotherapy education to confirm their ability to effec- (e.g., don’t place oral chemotherapy agents in a pill
tively communicate medication-related information. box, keep away from children) and administration de-
For patients whose care is transferred from oncologists vices.
to nonspecialist practitioners, oncology pharmacy specialists 3. Appropriate temperature and safe storage conditions.
should develop and provide drug monographs, medication- 4. Special precautions to prevent exposure to hazardous
use summaries, and other treatment-related materials de- materials that may be present in patients’ clothing,
scribing how oral and parenteral chemotherapy medications linens, body fluids, and excreta during and after treat-
and treatment regimens are to be accomplished.12,30 The ment.
need is especially acute among organizations and practition- 5. The potential interactions with other medications and
ers who provide local care for patients enrolled in clinical foods.
trials or receiving investigational chemotherapy treatments. 6. The critical need for good medication adherence prac-
tices.
Treatment Protocols. Oncology pharmacy specialists should 7. What to do if a dose is missed.
participate in developing treatment protocols for standard 8. Dosing calendars or other supplemental information to
treatments and clinical investigations. In practice settings improve adherence.
where chemotherapy medications and treatment regimens are 9. Common and possible adverse effects associated with
used routinely, pharmacists should initiate the development the medication.
of tools that standardize the way medications are ordered, 10. Methods for preventing, managing, and reporting ad-
thereby facilitating accurate and appropriate prescribing, or- verse effects.
der interpretation and verification, and medication process- 11. What to do if potentially serious adverse effects occur,
ing and dispensing.31,47 Pharmacists should lead initiatives to including when to contact a provider, who to contact,
standardize drug preparation procedures, including reconsti- and how to reach them.11,36
tution, dilution, and drug admixture methods for commonly 12. How to properly dispose of the medication, container,
used parenteral chemotherapy medications.12 and supplies.
13. Access and cost issues (specialty pharmacies, prior
CPOE. Pharmacists should work with information systems authorization, out-of-pocket costs, options for phar-
personnel, computer programmers, and software vendors maceutical manufacturer or copay assistance, drug
to develop CPOE systems. System requirements should in- shortages).
clude mechanisms for standardizing medication orders, de-
creasing opportunities for error by minimizing data entry, Pharmacists should provide educational materials to patients
and screening orders for medication doses and administra- and suggest supplemental and alternative information re-
tion schedules that exceed established limits. Pharmacists sources, such as the National Cancer Institute information
should advocate for and participate in establishing maxi- services department (1-800-4-CANCER and www.cancer.
mum safe chemotherapy dosage and scheduling limits with gov), the American Cancer Society, libraries, and book-
physicians, nurses, and other primary healthcare providers. stores.11 If pharmacists are not available to provide chemo-
Pharmacists should guide the appropriate use of clinical therapy patient education, they should assist in competency
decision support in CPOE systems for chemotherapy and assessment of those assigned primary responsibility for that
the medication management process. education.
Vocabulary and Nomenclature. Pharmacists are uniquely Advocates for Patients’ Rights. Pharmacists should encour-
qualified to lead multidisciplinary efforts to develop and image patients and their caregivers to participate in their own
plement clear, detailed, standardized vocabulary and nomen- care and advise patients how to protect themselves from
clature for chemotherapy treatment regimens, medication medication errors. Pharmacists should advise patients that
orders, and administration instructions. Pharmacists should they are entitled to satisfactory answers from their health-
participate in the early stages of protocol development for care providers. Pharmacists should encourage patients to
standard treatments and clinical investigations to ensure that double-check the details of their treatment, including drug
pharmacotherapeutic regimens are clearly described, easily names and dosages, and to request dosage recalculation if
understood, and incorporate standardized language, content, their biological measurements change. Pharmacists who par-
abbreviations, and units of measure.11,20,30 ticipate in developing treatment plans and protocols should
ensure that consent-for-treatment forms contain accurate,
Patient Education and Counseling. Pharmacists should complete information to secure patients’ informed consent.
ensure that educational materials used for patient education Pharmacists should help to prepare treatment consent forms;
are comprehensive and routinely updated. When meeting or provide patients with an accurate and detailed description
of their treatment plan in clear, unambiguous, and easily • Independent double check of the final product and in-
understood language and answers to their questions about fusion pump settings.
the treatment and alternative treatment options; and assess • Accurate documentation of medication use and effects
patients’ understanding of expected and possible outcomes. on patient care.
Pharmacists should also describe their role as primary care • Strict compliance with regulations and practice stan-
providers and the care they provide.11,12 dards.
• Patient education regarding medication safety.
Clinical Intervention, Analysis, and Performance
Improvement. In addition to dispensing medications, phar- Credentialing Nurses for Chemotherapy Medication-Use
macists can help improve the quality of patient care by Programs. Organizational policies and procedures should
implementing a proactive clinical intervention program and require nurse employees to complete training and demon-
documenting healthcare providers’ deviations from planned strate nursing care-related competencies, such as adminis-
chemotherapy treatments. Longitudinal data collection, tering chemotherapy medications, caring for patients who
analysis, and reporting can reveal system flaws that con- have received chemotherapy medications, and knowl-
tributed to (or failed to prevent) prescribing errors, suggest edge of local policies. Specialty certification (e.g., ONS
targets for quality improvement, and validate pharmacists’ Oncology Certified Nurse credential, ONS Chemotherapy
interventions. and Biotherapy Provider Card) is highly encouraged. Nurses
Pharmacists should proactively work with other pri- may be required to complete additional training and compe-
mary care providers to establish medication-use reporting tency assessments before they are permitted to administer
and surveillance programs. Committees established for this experimental medications. Training usually combines didac-
purpose should include representatives from medical, nurs- tic and supervised practical instruction. Didactic instruction
ing, pharmacy, and risk-management disciplines. Programs generally includes training about specific chemotherapy
should continually evaluate local medication-use systems to agents, appropriate dosages and dosage ranges, adverse ef-
identify potential problems and solutions related to medica- fects and clinical toxicities, administration techniques, and
tion use and prevent medication errors.11,43 Such programs in safe handling. Technical experience in administering che-
institutions should seek endorsement from appropriate local motherapy medications requires demonstrating competence
multidisciplinary committees (e.g., pharmacy and therapeu- with administering intravenous medications. Healthcare or-
tics, medical executive, and clinical practice committees). ganizations should periodically (at least annually, but more
frequently if performance problems occur) reassess nurses’
Feedback for Pharmaceutical Manufacturers and competencies related to their responsibilities.
Regulators. Pharmacists should work with pharmaceutical
manufacturers and the FDA to eliminate ambiguous, confus- Standardized Medication Administration Practices. In col-
ing, and potentially misleading drug product and treatment laboration with the multidisciplinary team, nurses within an
information from published resources (e.g., product pack- organization should standardize chemotherapy administra-
aging, package inserts, official compendia, and promotional tion practices. It should be determined whether intravenous
information). Pharmacists working in the pharmaceutical chemotherapy agents should be infused as a primary or sec-
manufacturing industry should proactively identify prevent- ondary infusion across the organization. Institutions should
able causes of product-user errors and adverse effects as- establish cut-off times to initiate nonurgent chemotherapy
sociated with product labeling, packaging, and promotion.48 administration in relation to the need for adequate staffing.
Pharmacists’ voluntary participation in national reporting Medication safety technologies should be implemented
programs can increase the awareness of medication errors to enhance the chemotherapy administration process. ASHP
and promote error prevention throughout the healthcare encourages health systems to adopt bar-code-enabled medi-
system. These aggregate data promote changes in product cation administration (BCMA) technology to improve pa-
identity, packaging, labeling, commercial information, and tient safety and the accuracy of medication administration
marketing practices that are subject to manufacturers’ con- and documentation.39 Infusion pumps that provide dose and
trol and governmental regulation.11,41 infusion-rate warnings (often called “smart pumps”) should
also be implemented. Because of unique challenges from
chemotherapy (e.g., BSA-based dosing), some organiza-
Recommendations for Medication tions’ pumps may not immediately provide warnings for
Administration Systems and chemotherapy, and care must be taken to make enhance-
Roles for Nurses ments to the technology to accommodate chemotherapy.
Appropriate use of both of these technologies provides new
Nurses are often the last link in the chain of healthcare pro- checks in the chemotherapy administration process.
viders who provide treatment with chemotherapy medica-
tions. To safeguard patients from mistakes that have poten- Standardized Tools for Recording Medication Admin-
tially lethal consequences, evidence-based systems have istration. Nurses with a variety of experiences have devised
evolved that promote safety and include4: and contributed to designing tools to facilitate the preven-
tion of drug administration errors, such as standardized work
• Requirements for credentialing persons who adminis- sheets used to calculate medication dosages and administra-
ter chemotherapy medications. tion rates and checklists of pertinent laboratory results and
• Tools and methods to facilitate documentation and physiological measurements. Treatment flow sheets pro-
identification of correct medication use. vide easily interpretable information about when a patient’s
• Independent verification of medication orders. previous treatments were administered, whether dosages
and medication delivery deviated from planned treatment, Examples of inappropriate practice include borrowing medi-
and the cumulative amount of medication administered. cations from a patient’s drug supply to give to another patient
Thoughtfully designed treatment flow sheets may become and preparing agents without the proper facilities or staff.
part of a patient’s permanent medical record and can be an Medication administration schedules should be followed as
invaluable resource for patient care. closely as possible; providers and caregivers should strive
to comply with treatment plans. Drug administration should
Checking Orders and Equipment for Administering Chemo- be documented promptly after it is completed, and providers
therapy Medications. Medication orders for chemotherapy administering chemotherapy medications should rigorously
require documentation of independent double-checks by comply with local requirements for documenting treatment.
two individuals prior to administration.4 These individuals To prevent the inadvertent duplication of treatment, it is rec-
should be different than the individual who prepared the ommended that one individual assume the primary responsi-
product. In addition, nurses should evaluate and confirm the bility for each patient during a work period (shift or tour of
functional integrity of vascular access devices (and devices duty). When one individual cannot assume primary respon-
for other administration routes), medication pumps, and sibility for each patient during a work period, appropriate
other devices that control medication delivery. For adjust- hand-off communication is essential.
able and programmable mechanical and electronic devices,
mechanical adjustments or electronic programming for de- Nurses and Patient Education. Nurses who administer che-
livering the correct dose at the appropriate rate should be motherapy medications have a prominent role in educating
independently verified with another healthcare provider who patients about their chemotherapy. Nurses should encour-
is knowledgeable about the delivery device before it is used age patients and their personal caregivers to ask questions
to administer medications. about their treatment. Patient education guidelines may be
included in treatment maps and clinical care plans.
Recording and Tracking Chemotherapy Use. After medica-
tions have been administered, it is a nurse’s responsibility to
manually or electronically record the activity. The documen- Recommendations for Patient Education
tation should be in a standardized format and include the
patient’s name, the names of all medications administered, Well-informed patients (and their authorized caregivers) are
dosages, administration routes, rates of administration, the the vital last link in the safety chain to prevent errors related
date and time administration began, the duration of admin- to chemotherapy medications. Patients are entitled to know
istration or time that treatment was completed, and whether all pertinent facts about the medications they receive during
adverse effects were observed or reported by the patient dur- their treatment. Healthcare providers charged with educat-
ing or after administration. Communications with patients, ing patients should have demonstrated competency to ac-
other healthcare providers, and personal caregivers should curately perform this function. Healthcare providers have
be documented in an objective, chronological narrative an obligation to encourage patients to ask questions and to
style, reporting the dates and times the events occurred, the provide answers.
names of involved persons, and how questions and problems The following suggestions are offered to help patients
were resolved. and their caregivers ensure optimal outcomes from the can-
cer therapy medications.
Clinical Intervention, Analysis, and Performance Improve-
ment. Nurses and other personnel should immediately report Multifocal Medication Education. Patients need multifo-
to medically responsible personnel and their supervisors any cal education about the purpose, adverse effects, sched-
instance in which medications were used incorrectly and the ules, routes of administration, and descriptions (e.g., colors,
events attributable to the error. In response to discovering shapes) for all the medications they will receive during their
a medication-use error, a provider’s primary responsibil- treatment. This includes the chemotherapy regimen, includ-
ity is to ensure the patient’s safety. Subsequently, the error ing both oral and intravenous therapy, and all ancillary and
and related circumstances should be recorded in accordance supportive medications, such as antiemetics and medica-
with specific policies and procedures. Medication-use error tions that hasten bone marrow recovery. In order to ensure
reports (also called occurrence, safety, or incident reports) patients receive the appropriate education to manage their
should be written in an objective, chronological, narrative therapy or its side effects, it is imperative that roles of the
style without editorial remarks and speculative comments. various healthcare professionals are defined and that respon-
Comprehensive occurrence reports are useful in discovering sibility for primary patient education versus reinforcement
and evaluating system flaws and may provide the impetus of key information is clearly delineated. When patients are
for improving medication-use systems. well informed and the information they receive is reinforced
To prevent medication errors, nurses and other person- by nurses, pharmacists, and other caregivers, they are bet-
nel who administer chemotherapy medications must com- ter prepared to detect a misinterpreted medication order and
ply with policies and procedures that define standards of assertively question conflicting information.49 Healthcare
practice. It is important, however, to periodically reevaluate professionals should be sensitive to the emotional aspects of
practice standards in order to assess how well a medication- patients with cancer when planning medication education.
use system functions, make appropriate changes, and, ulti- Education should take place at a time when a patient is able
mately, improve patient safety and the quality of care. to listen and understand. Medication education should not be
Healthcare providers administering chemotherapy attempted when patients are sedated or confused as a result
medications should not deviate from guidelines for order- of medications or immediately after receiving their cancer
ing, preparing, and administering chemotherapy agents. diagnosis.
Patients should participate in their care by asking Recommendations for Manufacturers
questions about their cancer treatment and related medica- and Regulatory Agencies
tions and by confirming the regimen with their nurse be-
fore receiving treatment. Healthcare providers should make Pharmaceutical manufacturers have a responsibility to exer-
educational materials available in counseling and treatment cise care in designing product packaging and labeling, deter-
areas to encourage patients to learn more about their cancer mining dosage strengths and dosage forms, and in promot-
therapies. ing their products, as these features may contribute to errors
in prescribing, product selection, preparation, and adminis-
Health-System Procedures Education. Patients should un- tration. Companies that market chemotherapy agents should
derstand the health system’s plan for chemotherapy medi- develop and support educational programs that encourage
cation-error prevention. They should become familiar with safe and accurate prescribing, preparation, administration,
their providers’ routine procedures for checking medication handling, storage, and disposal of their products. The fol-
orders so that they can understand the safeguards that have lowing guidelines address some of the major areas.
been established and why delays may occur before their
treatment can be started. For example, patients can remind Product Naming, Packaging, Labeling, and Drug Dosage
Strengths/Forms. Companies should avoid trademark-
the person administering chemotherapy to compare medi-
ing drug names that look or sound similar to those of other
cation labels with a patient’s identity and can verify their
drug products. Proprietary drug names for new products and
height and weight each time they are measured.
product formulations should not be similar to existing ge-
neric and proprietary names. Manufacturers should avoid
Patient Participation in a Medication-Use System. Patients appending letters and numbers to drug names, as this prac-
(or their caregivers) should be knowledgeable about their tice can result in potential confusion with dosage strengths,
medications and the ways in which the medications are to medication quantities, and the amount of medication to be
be administered according to their treatment plan. In some administered.
circumstances, patients should be encouraged to take respon- Product packaging and labeling should provide clear,
sibility for some of their care to help improve their quality easily distinguished features to identify a drug and the
of life. Examples include self-administering medications, amount of drug per dosage unit (e.g., tablet, capsule, wa-
maintaining the patency of vascular access devices, giving fer) and within a product container (e.g., vials, bags, bot-
themselves a subcutaneous injection, and troubleshooting a tles, prefilled syringes). It is particularly important that a
problem with the portable infusion pump. Patients should drug product’s USAN-approved generic name appear more
demonstrate their ability to perform these functions if they prominently than other information on the product label.
are included in the therapy plan. Competency and readi- Drug names should be printed on both the front and back
ness for self-administration should be assessed for patients of the containers and packaging of parenteral drugs; “Tall
Man” characters should be used to distinguish between
prescribed oral chemotherapy.
similar drug names. Container labels for drugs that are in
Each patient should be given a detailed treatment cal-
solution and for those that require reconstitution or dilution
endar that clearly identifies his or her treatment plan. They
before they are used should identify the total drug content in
should be encouraged to keep their calendar with them to mass units (or biological activity units) rather than concen-
compare the expected treatment with what is being dis- tration.49 Product packaging and labeling that include both
pensed and administered. mass and concentration values should be designed to display
mass units more prominently. Product packaging should in-
Patients’ Responsibilities. Patients should be taught and clude a bar code on inner and outer packaging.
empowered to detect and to seek help in managing ad- Labels should be unique and well designed.
verse effects that may occur during their cancer treatment. Distinguishing colors and contrasting hues facilitate identi-
Healthcare providers should be promptly informed about ad- fying and distinguishing drug products and products in dif-
verse effects experienced during a chemotherapy cycle be- ferent strengths and concentrations. Warnings and special
fore the next cycle commences. Patients should keep a list of or unique instructions should be prominently displayed on
the medications that they may self-administer to treat these product packaging and labeling. Unique labeling and pack-
adverse effects. Patients should be encouraged and taught aging techniques should be used to prevent product misiden-
how to report medication errors and near misses that occur tification and to warn about dosing errors and unique char-
as a result of self-administration. Safe handling, storage, and acteristics that predispose medication users to potentially
serious or life-threatening toxicities. Examples include the
disposal of oral chemotherapy should be taught to the patient
unique way that the Platinol-AQ brand of cisplatin injection
or their caregiver.
(Bristol-Myers Squibb, Princeton, NJ) is packaged to pre-
It is important for healthcare providers to be able to
vent misidentification with carboplatin and the cautionary
determine potential interactions between a patient’s nonche-
statements on vials containing vincristine sulfate injection
motherapy medications and the chemotherapy they are to re- that warn against using the entire contents of a vial for a
ceive. Therefore, patients should be requested to provide to single patient (on bulk packages) and that intrathecal admin-
their healthcare team members a list of all medications they istration may be fatal.
are using, including over-the-counter preparations, dietary A statement that declares a drug’s approved routes of
supplements, and other complementary and alternative med- administration is optional and may or may not appear on prod-
icines. In general, use of any medication should be discussed uct packaging. If the agent is approved for administration by
with their healthcare providers before initiating therapy. only one route, it must be clearly indicated.
Appropriate storage temperatures or conditions should (clinic, local pharmacy, specialty pharmacy), it is difficult
be clearly visible on drug labeling and packaging. to establish a comprehensive medication list for screening of
Drug labeling and packaging must identify the manu- drug interactions, therapeutic duplications, and other impor-
facturer’s product lot or control number. tant aspects of medication management. Delays in therapy
Drugs that must be reconstituted and diluted before could result when patients must wait for medications to be
clinical use should include reconstitution instructions that shipped to their home from a specialty pharmacy. Receiving
identify appropriate diluents and volumes. prescriptions by mail does not allow for a face-to-face in-
A manufacturer’s drug product preparation date (for teraction between the patient and the pharmacist, where pa-
experimental drugs) or an expiration date should be clearly tient concerns and educational deficits may be identified. In
visible on the product label. addition, specialty pharmacies may not have access to the
Special instructions (e.g., “Shake Well,” “Do Not patient’s complete health record and this may compromise
Shake,” “Albumin Required”) and instructions for dilution the specialty pharmacist’s ability to properly verify the or-
should appear on product labeling. In cases where important der. Given these challenges, when patients can only obtain
information will not fit on a product label, a package insert, chemotherapy through a restricted drug distribution system,
or “pull-away” label may be required as part of the labeling pharmacists and other providers should proactively provide
and packaging. relevant information to patients and specialty pharmacies
In the case of oral chemotherapy agents, careful con- to coordinate care. Follow up, such as phone calls, should
sideration should be given to dosage forms and strengths be conducted to verify that the patient receives the chemo-
provided. Often patients must combine multiple strengths therapy and understands proper use. The ASHP Task Force
of a medication to receive their prescribed dosage, thereby on Caring for Patients Served by Specialty Suppliers pro-
increasing the opportunity for a medication error. Many on- vided recommendations for effectively managing restricted-
cology patients have difficulty swallowing and cannot take distribution drugs and other aspects of working with spe-
solid dosage forms. Manufacturers should be responsive to cialty suppliers.50 The National Comprehensive Cancer
dosing practice patterns and other patient-specific needs of Network (NCCN) has also commented on specialty pharma-
oncology patients that become apparent after medications cies and their effects on patient care and medication safety
are released into the market. regarding chemotherapy.53
Product changes should be widely communicated to
prescribers, pharmacists, nurses, and other healthcare pro- Regulatory Oversight. Regulatory agencies have a respon-
viders involved in drug prescribing, preparation, and admin- sibility to review product packaging, labeling, and adver-
istration. tising to ensure that their content accurately reflects safety
Package inserts and product information that describe and efficacy data and conforms with language that has been
medical indications, medication doses, administration approved by the FDA. A key component in those reviews
schedules, safe handling, disposal, and product use should should be that the product packaging and labeling facilitate
not include abbreviations. This is especially important for safe and appropriate use and prevent users from making er-
drugs used in complex treatment regimens. rors in selecting, preparing, and administering a drug prod-
uct. Pharmacists should be consulted in screening propri-
Educational Materials and Programs. Pharmaceutical man- etary drug names, product packaging, and labeling before
ufacturers and drug product sponsors should be encouraged drug products are approved for commercial use.
to provide educational materials and programs that promote
and encourage safe use of their drug products. Programs
should clearly explain the indications appearing on FDA- Recommendations for Identifying and
approved labeling, dosages, methods for preparation, ad- Managing Medication Errors
ministration routes and schedules, and safe handling and
disposal. Treatment descriptions should be standardized and Medication-use errors with chemotherapy are distinguished
consistent with guidelines designed to prevent medication- from errors with other types of drugs in two important ways,
use errors.20 Medication names and administration informa- both of which relate to the inherent toxicity of chemotherapy
tion should not be abbreviated in educational and promo- agents. Individually and categorically, the therapeutic index
tional materials. for chemotherapy drugs is less than that for any other class
of drugs. Adverse effects are an expected pharmacodynamic
Restricted Drug Distribution. Chemotherapy agents, par- consequence attendant with chemotherapy use, and clini-
ticularly newer oral chemotherapy agents, may be subject cal toxicities may occur and persist at substantially lower
to restricted distribution. Restricted drug distribution prod- dosages and schedules than are therapeutically used. The
ucts are available only through a select distribution program second characteristic that distinguishes chemotherapy from
in which only prescribers and patients registered with the many other types of drugs is that subtherapeutic doses (“un-
program are able to prescribe, administer, and receive the derdoses”) of chemotherapy can severely complicate further
product.50 Restricted distribution can occur due to decisions treatment. Subtherapeutic doses of chemotherapy medica-
made by pharmaceutical manufacturers or as a result of Risk tions may not only fail to provide a therapeutic benefit but
Evaluation and Mitigation Strategies (REMS).51 There are may also compromise patients’ ultimate response to therapy
circumstances in which properly implemented constraints by delaying effective treatment until adverse effects are re-
on the traditional drug distribution system are appropri- solved or contributing to cumulative, long-term patient harm
ate.52 The primary safety concern is that restricted distribu- from adverse effects. It should be noted that chemotherapy
tion may adversely affect continuity of care. For example, treatments are almost always repeated, and the effect of a
when patients receive medications from various sources medication-use error may not be apparent until long after
the error occurs. Consequently, if treatment plans and medi- or committee so that system and process improvement
cation orders are not verified during each treatment cycle, can occur in the setting of investigational studies.
errors may be compounded during repeated cycles and go 8. Encourage practitioners to report medication errors
undetected throughout an entire treatment course. With the to a national medication-error tracking program. This
increased responsibility placed upon patients to manage oral allows other providers to learn how medication errors
therapies, it is likely that medication errors will occur with occur and how they can be prevented. Reporting
self-administration. Patients should be educated and encour- mechanisms for medication-use systems should
aged to report medication errors to their healthcare provid- be standardized by policy. Mechanisms must be
ers, who in turn should report the error through the insti- developed for ongoing, interprofessional analysis
tutional reporting system. Patient reported errors should be and use of information that is reported to medica-
handled with the same concern and diligence as an error that tion-error databases.54
occurred in the hospital, clinic, or physician’s office.
In addition to the actions already set forth in the ASHP Categorizing Medication Errors. In practice settings where
Guidelines on Preventing Medication Errors in Hospitals,1 a variety of disciplines provide patient care, serious potential
the following actions are recommended after detecting a and actual errors should be reported to an oversight commit-
medication error6: tee composed of representatives of all the disciplines that
provide care. By standardizing the way medication errors
1. Implement monitoring and interventions for control- are reported, comparisons between reports and databases
ling injurious effects and ensuring patient safety. are facilitated, error trends are more easily identified, and
2. Determine whether an error could have previously system-based solutions can be developed.55 Continuous
occurred during prior treatment in the same patient oversight by a multidisciplinary quality-assurance commit-
and in other patients. Medication preparation work tee promotes continuity and permits all primary patient-care
sheets or logs and drug administration records should providers to evaluate system flaws and develop and improve
be evaluated. Unexpected toxicities and an apparent the quality of processes and systems that safeguard patient
or unaccountable lack of therapeutic and adverse ef- care.43 Medication-use oversight committees are advised to
fects should be investigated when it is suspected that a review medication-error reports from systems other than
medication error has occurred. their own and evaluate their local medication-use system for
3. Seek the advice of healthcare professionals from vari- design characteristics that may permit similar errors.30,38
ous disciplines. The diverse perspective of providers The ASHP Guidelines on Preventing Medication
in other disciplines may facilitate discovering and un- Errors in Hospitals1 recommend adopting a system for cat-
derstanding the circumstances that allowed a medica- egorizing medication-error severity, such as the one devel-
tion error to occur. oped by Myers and Hartwig, et al.54,55 Although this system
4. Determine whether an immediate temporary or stop- is generally applicable to errors of occurrence with chemo-
gap change in policy or procedure is necessary to pre- therapy drugs, it categorizes errors by severity and priori-
vent recurrence of an error while the proximal cause is tizes them without consideration for the frequency at which
being analyzed. repeated errors occur. Accordingly, errors with the highest
5. Provide immediate professional counseling and sup- severity ranking receive the greatest efforts toward reme-
port for employees implicated in causing or contrib- diation. In contrast, potential errors are assigned a “zero”
uting to an error that results in serious patient harm. ranking, the lowest severity level, as they do not reach pa-
Counseling and support should be offered to all per- tients. By relegating potential errors to the lowest priority
sonnel who learn that they have been involved in a category, this outcome severity-based system risks trivial-
medication error without regard for how recently the izing system-design flaws. Errors discovered before they
error occurred. reach patients could cause devastating consequences, yet
6. Establish procedures to inform and follow up with pa- serious nascent errors are often transformed into potential
tients and their families about a medication error. errors only by serendipitous discovery. Therefore, potential
7. Understand that reporting medication errors and ad- errors should be distinguished from errors of occurrence and
verse drug reactions is a responsibility that should be subcategorized based on their potential to cause harm.54,55
shared by all healthcare providers. However, health However, potential errors should not be taken less seriously
systems may designate a person or committee to be than errors of occurrence. When serious potential errors are
specifically responsible for reporting and investigat- discovered, the systems and processes that contributed to the
ing medication errors and adverse drug reactions. In errors should be evaluated and their proximal causes iden-
investigational drug studies, a study’s principal in- tified. The greatest efforts toward remediation of potential
vestigator must report serious adverse events to the errors and errors of occurrence should be concentrated on
trial’s sponsors (the drug manufacturer and the inves- eliminating the causes of errors that could have and had, re-
tigational new drug application holder) and to the in- spectively, the greatest adverse effects on patients’ health.
stitutional review board that oversees study conduct. NCC MERP’s definition for medication errors includes
Investigational drug sponsors are required to report to any event that may cause or lead to inappropriate medication
the FDA serious adverse effects associated with inves- use.2 The definition is complemented by the NCC MERP
tigational agents, even if they are caused by a medi- Taxonomy of Medication Errors, a comprehensive expand-
cation-use error. While reporting of medication errors able tool intended for use in developing databases and ana-
in investigational studies to the institutional review lyzing medication-error reports.56 The Taxonomy provides
board and the FDA occur, it is imperative they also standardized language and structure for recording and track-
be reported through the institutional reporting system ing medication-error-related data for errors of occurrence
and potential errors. NCC MERP permits interested persons 9. Weingart SN, Spencer J, Buia S, et al. Medication
to adopt it as it is presented or adapt it for use in a particular safety of five oral chemotherapies: a proactive risk as-
practice setting. sessment. J Oncol Pract. 2011; 7:2–6.
10. Taylor JA, Winter L, Geyer LJ, et al. Oral outpatient
Conclusion chemotherapy medication errors in children with acute
lymphoblastic leukemia. Cancer. 2006; 107:1400–06.
The use of chemotherapy and biotherapy agents presents 11. Cohen MR, Anderson RW, Attilio RM, et al.
healthcare organizations with distinct safety challenges that Preventing medication errors in cancer chemotherapy.
require additional precautions to prevent medication errors. Am J Health-Syst Pharm. 1996; 53:737–46.
These guidelines provide best practices for the safe use of 12. Attilio RM. Caring enough to understand: the road to
chemotherapy and biotherapy agents to help practitioners oncology medication error prevention. Hosp Pharm.
improve their medication-use systems to prevent medication 1996; 31:17–26.
errors and patient harm from these agents. The guidelines 13. Beckwith MC, Tyler LS. Preventing medication errors
describe the medication-use responsibilities shared by and with antineoplastic agents, part 1. Hosp Pharm. 2000;
unique to specific professional healthcare disciplines, pro- 35:511–23.
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guidelines focus on the safe use of chemotherapy in treatment with antineoplastic agents, part 2. Hosp Pharm. 2000;
of cancer patients, in general the recommendations apply for 35:732–47.
all uses of a chemotherapy agent, regardless of indication. 15. Weingart SN, Brown E, Bach PB, et al. NCCN Task
These wide-ranging recommendations focus on preventing Force Report: Oral chemotherapy. J Natl Compr Canc
errors with chemotherapy agents in hospitals and ambula- Netw. 2008; 6(Suppl 3):S1–S14.
tory care clinics that offer direct pharmacy services, but the 16. Weingart SN, Flug J, Brouillard D, et al. Oral chemo-
guidance may also be useful in other settings. Because of therapy safety practices at US cancer centers: ques-
the complexity of and differences between practice settings tionnaire survey. BMJ. 2007; 334:407.
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address a specific aspect of the medication-use process and press]
should be augmented as appropriate by other clinical and 19. Institute for Safe Medication Practices [ISMP].
practice guidance. Independent double checks: undervalued and misused.
ISMP Medication Safety Alert - Acute Care. June 13,
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41. USP Quality Review. National council focuses on guidelines supersede ASHP Guidelines on Preventing Medication
coordinating error reduction efforts. Rockville, MD: Errors with Antineoplastic Agents dated April 19, 2002.
United States Pharmacopeial Convention, 1997 Jan.
42. Goodin S, Griffith N, Chen B, et al. Safe handling of Barry Goldspiel, Pharm.D., BCPS, BCOP, FASHP, FISOPP, is Chief,
oral chemotherapeutic agents in clinical practice: rec- Clinical Pharmacy Specialist Section, Clinical Center Pharmacy
ommendations from an international pharmacy panel. Department, National Institutes of Health, Bethesda, MD. James
J Oncol Prac. 2011; 7:7–12. M. Hoffman, Pharm.D., M.S., BCPS, is Medication Outcomes
and Safety Officer, Pharmaceutical Sciences, St. Jude Children’s
Research Hospital, Memphis, TN. Niesha L. Griffith, M.S., FASHP, Nurses (AMSN); American Nurses Association (ANA);
is Director of Pharmacy and Infusion Services, Arthur G. James Society of Hospital Pharmacists of Australia (SHPA); Carol
Cancer Hospital and Richard J. Solove Research Institute, The Bickford, Ph.D., RN-BC, CPHIMS (ANA); Jeff Brittain,
Ohio State University, Columbus. Susan Goodin, Pharm.D., BCOP, Pharm.D., BCPS; Melissa Dinolfo, Pharm.D., BCOP; Paul S.
FASHP, FCCP, is Executive Director, Statewide Affairs, Rutgers Driver, Pharm.D., BCPS, FASHP; Glenn T. Etow, Pharm.D.;
Cancer Institute of New Jersey, New Brunswick, and Professor of Jennifer Hagen, Pharm.D.; John Hamiel, Pharm.D.; Mark
Medicine, Division of Medical Oncology, Robert Wood Johnson Holdsworth, Pharm.D., BCOP; Lisa M. Holle, Pharm.D., BCOP
Medical School, New Brunswick. Robert DeChristoforo, M.S., (HOPA); Sean Keefe, Pharm.D., BCOP; Jim Lile, Pharm.D.; Neil
FASHP, is Chief, Clinical Center Pharmacy Department, National J. MacKinnon, M.S.Pharm., Ph.D.; Shannon Manzi, Pharm.D.;
Institutes of Health. CAPT Michael Montello, Pharm.D., M.B.A., Patrick McDonnell, Pharm.D.; Cham Nguyen, Pharm.D.; Robert S.
is Associate Branch Chief for Clinical Trials Technology and Oakley, M.S., FASHP; Karen M. O’Leary, B.S.Pharm. (SHPA); N.
Pharmacist Consultant, Clinical Investigations Branch, National Pauline Thomas Parks, M.S.; Nisha Pherwani, Pharm.D., BCOP;
Cancer Institute (NCI) Cancer Therapy Evaluation Program, Judy Pi, Pharm.D., BCOP; Carol Rollins, M.S., Pharm.D., BCNSP;
Bethesda, and Project Officer, NCI Cancer Trials Support Unit, Andrea N. Sikora, Pharm.D.; Sue Stott, B.S. (AMSN); Thomas
Bethesda. Judy L. Chase, Pharm.D., FASHP, is Director, Clinical V. Thomas, Pharm.D.; Dennis Tribble, Pharm.D.; Siu-Fun Wong,
Pharmacy Services, University of Texas M. D. Anderson Cancer Pharm.D., FASHP, FCSHP; Arlene Wright; Daisy Yang, Pharm.D.;
Center, Houston. Sylvia Bartel, M.P.H., is Director of Pharmacy and and Maria L. Zarambo, Pharm.D.
Clinical Support Services, Dana-Farber Cancer Institute, Boston,
MA. Jharana Tina Patel, Pharm.D., is Quality Assurance Officer, The authors have declared no potential conflicts of interest.
Clinical Center, National Institutes of Health.
The Hematology/Oncology Pharmacy Association (HOPA) is grate- Inc. All rights reserved.
fully acknowledged for reviewing and endorsing these guidelines.
The bibliographic citation for this document is as follows: Goldspiel
ASHP also gratefully acknowledges the following organiza- B, Hoffman JM, Griffith NL, et al. ASHP guidelines on preventing
tions and individuals for reviewing these guidelines (review medication errors with chemotherapy and biotherapy. Am J Health-
does not imply endorsement): Academy of Medical-Surgical Syst Pharm. 2015; 72:e6–35.
Medication Therapy and
Patient Care
258 Medication Therapy and Patient Care: Organization and Delivery of Services–Positions
Organization and Delivery of Services

Patient Adherence Programs as Part of Health implementing the models of care that optimize outcomes for
Insurance Coverage (1504) patients and the healthcare organization; further,
Source: Council on Public Policy To encourage the development of complexity index
To advocate for the pharmacist’s role in patient medication tools and resources to support the identification of high-risk,
adherence programs that are part of health insurance plans; high-cost, and other patient cohorts to facilitate patient-care
further, provider panel determinations and workload balancing; fur-
To advocate those programs that (1) maintain the direct ther,
patient pharmacist relationship; (2) are based on the pharma- To promote collaboration among members of the in-
cist’s knowledge of the patient’s medical history, indication terprofessional healthcare team to develop meaningful mea-
for the prescribed medication, and expected therapeutic out- sures of individual patient and population care outcomes;
come; (3) use a communication method desired by the pa- further,
tient; (4) are consistent with federal and state regulations for To advocate for education to prepare pharmacists for
patient confidentiality; and (5) permit dispensing of partial their role in population health management.
fills or overfills of prescription medications in order to syn-
chronize medication refills and aid in medication adherence. Standardization of Doses (1525)
This policy supersedes ASHP policy 0116. Source: Council on Pharmacy Practice
To recognize that standardization of medication doses re-
Complementary and Alternative Medicine in Patient duces medication errors and improves information technol-
Care (1511) ogy interoperability, operational efficiency, and transitions
Source: Council on Therapeutics of care; further,
To promote awareness of the impacts of complementary To encourage development of universal standardized
and alternative (CAM) products on patient care, particularly doses for specific patient populations; further,
drug interactions, medication safety concerns, and the risk To encourage healthcare organizations to adopt stan-
of contamination and variability in active ingredient content; dardized doses and to promote publication and education
further, about best practices.
To advocate for the documentation of CAM products
in the health record to improve patient safety; further, Standardization of Oral Liquid Medication
To advocate for the inclusion of information about Concentrations (1401)
CAM products and their characteristics in medication- Source: Council on Pharmacy Practice
related databases; further, To advocate for the development of nationally standardized
To provide education on the impacts of CAM products drug concentrations for oral liquid medications; further,
on patient care in healthcare organizations; further, To encourage all health care providers and organiza-
To foster the development of up-to-date and readily tions to standardize concentrations of oral liquid medica-
available resources about CAM products. tions; further,
To promote effective instruction of patients and care-
Impact of Insurance Coverage Design on Patient Care givers on how to properly measure and administer oral liq-
Decision (1520) uid medications.
Source: Council on Pharmacy Management
To advocate that all health insurance policies be designed Documentation of Patient-Care Services in the
and coverage decisions made in a way that preserves the pa- Permanent Health Record (1419)
tient–practitioner relationship; further, Source: Council on Pharmacy Management
To oppose provisions in health insurance policies that To advocate for public and organizational policies that sup-
interfere with established drug distribution and clinical ser- port pharmacist documentation of patient-care services in
vices designed to ensure patient safety, quality, and continu- the permanent patient health record to ensure accurate and
ity of care; further, complete documentation of the care provided to patients and
To advocate for the inclusion of hospital and health- to validate the impact of pharmacist patient care on patient
system outpatient and ambulatory care services in health in- outcomes and total cost of care; further,
surance coverage determinations for their patients. To advocate that electronic health records be designed
This policy supersedes ASHP policy 1017. with a common documentation space to accommodate all
health care team members and support the communication
Pharmacist’s Role in Population Health Management needs of pharmacy.
(1523) This policy supersedes ASHP policy 0407.
Source: Council on Pharmacy Management
To recognize the importance of medication management in Standardization of Intravenous Drug Concentrations
patient-care outcomes and the vital role of pharmacists in (1306)
population health management; further, Source: Council on Pharmacy Practice
To encourage healthcare organizations to engage To develop nationally standardized drug concentrations and
pharmacists and pharmacy leaders in identifying appropri- dosing units for commonly used high-risk drugs that are
ate patient cohorts, anticipating their healthcare needs, and
Medication Therapy and Patient Care: Organization and Delivery of Services–Positions 259
given as continuous infusions to adult and pediatric patients; Transitions of Care (1208)
further, Source: Council on Pharmacy Management
To encourage all hospitals and health systems to use To recognize that continuity of patient care is a vital require-
infusion devices that interface with their information sys- ment in the appropriate use of medications; further,
tems and include standardized drug libraries with dosing To strongly encourage pharmacists to assume profes-
limits, clinical advisories, and other patient-safety-enhanc- sional responsibility for ensuring the continuity of care as
ing capabilities; further, patients move from one setting to another (e.g., ambulatory
To encourage interprofessional collaboration on the care to inpatient care to home care); further,
adoption and implementation of standardized drug concen- To encourage the development, optimization, and
trations and dosing units in hospitals and health systems. implementation of information systems that facilitate shar-
This policy supersedes ASHP policy 0807. ing of patient-care data across care settings and providers;
further,
Medication Overuse (1312) To advocate that payers and health systems provide
Source: Council on Therapeutics sufficient resources to support effective transitions of care;
To define medication overuse as use of a medication when further,
the potential risks of using the drug outweigh the potential To encourage the development of strategies to address
benefits for the patient; further, the gaps in continuity of pharmacist patient care services.
To recognize that medication overuse is inappropriate This policy supersedes ASHP policy 0301.
and can result in patient harm and increased overall health
care costs; further, Pharmacist Prescribing in Interprofessional Patient
To advocate that pharmacists take a leadership role in Care (1213)
interprofessional efforts to minimize medication overuse. Source: Council on Pharmacy Practice
To define pharmacist prescribing as follows: patient assess-
Drug-Containing Devices (1313) ment and the selection, initiation, monitoring, adjustment,
Source: Council on Therapeutics and discontinuation of medication therapy pursuant to diag-
To recognize that use of drug-containing devices (also nosis of a medical disease or condition; further,
known as combination devices) has important clinical and To advocate that health care delivery organizations es-
safety implications for patient care; further, tablish credentialing and privileging processes that delineate
To advocate that use of such devices be documented the scope of pharmacist prescribing within the hospital or
in the patient’s medical record to support clinical decision- health system and to ensure that pharmacists who prescribe
making; further, are competent and qualified to do so.
To encourage pharmacists to participate in interprofes-
sional efforts to evaluate and create guidance on the use of Pharmacist’s Role in Team-Based Care (1215)
these products through the pharmacy and therapeutics com- Source: Council on Pharmacy Practice
mittee process to ensure patient safety and promote cost- To recognize that pharmacist participation in interprofes-
effectiveness; further, sional health care teams as the medication-use expert in-
To advocate that the Food and Drug Administration creases the capacity and efficiency of teams for delivering
(FDA) and device manufacturers increase the transparency high-quality care; further,
of the FDA approval process for drug-containing devices, To advocate to policymakers, payers, and other stake-
including access to data used to support approval; further, holders for the inclusion of pharmacists as care providers
To encourage research that evaluates the clinical and within team-based care; further,
safety implications of drug-containing devices to inform To assert that pharmacists are responsible for coor-
product development and guide clinical practice. dinating the care they provide with that provided by other
members of the health care team and are accountable to the
Qualifications and Competencies Required to Prescribe patient and to the health care team for the outcomes of that
care; further,
Medications (1202)
To urge pharmacists on health care teams to collabo-
rate with other team members in establishing quality mea-
To affirm that prescribing is a collaborative process that
sures for care provided by those teams.
includes patient assessment, understanding of the patient’s
diagnoses, evaluation and selection of available treatment
Collaborative Drug Therapy Management (1217)
options, monitoring to achieve therapeutic outcomes, patient
education, and adherence to safe and cost-effective prescrib-
To pursue the development of federal and state legislative
ing practices; further,
and regulatory provisions that authorize collaborative drug
To affirm that safe prescribing of medications, per-
therapy management by pharmacists; further,
formed independently or collaboratively, requires compe-
To advocate expansion of federal and state legislative
tent professionals who complement each others’ strengths at
each step; further, and regulatory provisions that optimize pharmacists’ ability
To explore the creation of prescribing standards that to provide the full range of professional services within their
would apply to all who initiate or modify medication orders scope of expertise; further,
or prescriptions and that would facilitate development of To acknowledge that as part of these advanced collabor-
competencies and training of prescribers; further, ative practices, pharmacists, as active members in team-based
To encourage research on the effectiveness of current care, must be responsible and accountable for medication-
educational processes designed to train prescribers. related outcomes; further,
To support affiliated state societies in the pursuit of To encourage pharmacists to define practices and asso-
state-level collaborative drug therapy management authority ciated measures of effectiveness that support their account-
for pharmacists. ability for patient outcomes; further,
This policy supersedes ASHP policy 9812. To promote pharmacist accountability as a fundamen-
tal component of pharmacy practice to other health care pro-
Medication Adherence (1222) fessionals, standards-setting and regulatory organizations,
Source: Council on Therapeutics and patients.
To recognize that improving medication adherence should
be a key component of strategies to improve the quality and Pharmacists’ Role in Medication Reconciliation (1117)
safety of patient care only when adherence improvement Source: Council on Pharmacy Practice
efforts include the following as required elements: (1) as- To affirm that an effective process for medication reconcilia-
sessing the appropriateness of therapy, (2) providing patient tion reduces medication errors and supports safe medication
education, and (3) ensuring patient comprehension of infor- use by patients; further,
mation necessary to support safe and appropriate use of pre- To advocate that pharmacists, because of their distinct
scribed therapies; further, knowledge, skills, and abilities, should take a leadership role
To advocate that pharmacists, because of their distinct in interdisciplinary efforts to develop, implement, monitor,
knowledge, skills, and abilities, should take a leadership role and maintain effective medication reconciliation processes;
in multidisciplinary efforts to develop, implement, monitor, further,
and maintain effective strategies for improving medication To encourage community-based providers, hospitals,
adherence; further, and health systems to collaborate in organized medication
To recognize that clinicians, patients, and caregivers reconciliation programs to promote overall continuity of pa-
share accountability for the outcomes of medication thera- tient care; further,
pies, and that the central role patients and their caregivers To declare that pharmacists have a responsibility to ed-
have in disease management includes responsibility for fol- ucate patients and caregivers on their responsibility to main-
lowing instructions for safe and effective medication use; tain an up-to-date and readily accessible list of medications
further, the patient is taking and that pharmacists should assist pa-
To encourage development, evaluation, and dissemi- tients and caregivers by assuring the provision of a personal
nation of models that improve adherence, including those medication list as part of patient counseling, education, and
that combine existing strategies that have demonstrated ef- maintenance of an individual medical record.
fectiveness; further, This policy supersedes ASHP policy 0620.
To discourage practices that inhibit education of or
lead patients to decline education and clinical information Medication Therapy Management (1005)
regarding their medication therapy; further, Source: Council on Public Policy
To support the development of mechanisms to docu- To support medication therapy management (MTM) ser-
ment medication adherence interventions, including infor- vices as defined in Section 3503 of the Patient Protection
mation technology solutions; further, and Affordable Care Act (PL 111-148); further,
To advocate for payment models that facilitate an ex- To affirm that MTM is a partnership between the pa-
panded role for pharmacists in medication adherence efforts. tient (or a caregiver) and a pharmacist, in collaboration with
other health care professionals, that promotes the safe and
Patient-Reported Outcomes Tools (1107) effective use of medications.
Source: Council on Therapeutics This policy was reviewed in 2014 by the Council on
To advocate for expanded use of validated patient-reported Public Policy and by the Board of Directors and was found
outcomes (PRO) tools in clinical research and direct patient to still be appropriate.
care; further,
To support development of validated PRO tools that Patient Access to Pharmacy Services in Small and Rural
are sensitive to differences in cultural and health literacy; Hospitals (1022)
further, Source: Council on Pharmacy Practice
To encourage additional research on PRO tools, in- To advocate that critical-access hospitals (CAHs) and small
cluding studies to assess their correlation to overall patient and rural hospitals meet national medication management
outcomes; further, and patient safety standards, regardless of size or location;
To educate clinicians and patients about the appropri- further,
ate use of PRO tools. To provide resources and tools to assist pharmacists
who provide services to CAHs and small and rural hospitals
Pharmacist Accountability for Patient Outcomes (1114) in meeting standards related to safe medication use.
Source: Council on Pharmacy Practice This policy was reviewed in 2014 by the Council on
To affirm that pharmacists are obligated by their covenantal Pharmacy Practice and was found to still be appropriate.
relationship with patients to ensure that medication use is
safe and effective; further, Scope and Hours of Pharmacy Services (1023)
To declare that pharmacists, pursuant to their authority Source: Council on Pharmacy Practice
over a specialized body of knowledge, are autonomous in To support the principle that all patients should have 24-hour
exercising their professional judgment and accountable as access to a pharmacist responsible for their care, regardless
professionals and health care team members for safe and ef- of hospital size or location; further,
fective medication therapy outcomes; further,
Medication Therapy and Patient Care: Organization and Delivery of Services–Positions 261
To advocate alternative methods of pharmacist review To encourage the development of hospital-specific

of medication orders (such as remote review) before drug or health-system-specific standard administration times
administration when onsite pharmacist review is not avail- through an interdisciplinary process coordinated by the
able; further, pharmacy; further,
To support the use of remote medication order review To encourage information technology vendors to adopt
systems that communicate pharmacist approval of orders these principles in system design while allowing flexibility
electronically to the hospital’s automated medication distri- to meet site-specific patient needs.
bution system; further, This policy was reviewed in 2011 by the Council on
To promote the importance of pharmacist access to per- Pharmacy Management and by the Board of Directors and
tinent patient information, regardless of proximity to patient. was found to still be appropriate.
Pharmacy Practice and was found to still be appropriate. Universal Influenza Vaccination (0601)
Source: Commission on Therapeutics
Health-System Use of Medications and Administration To advocate universal administration of influenza vaccina-
Devices Supplied Directly to Patients (0806) tions to the United States population.
Source: Council on Pharmacy Management This policy was reviewed in 2010 by the Council on
To encourage hospitals and health systems not to permit ad- Therapeutics and by the Board of Directors and was found
ministration of medications brought to the hospital or clinic by to still be appropriate.
the patient or caregiver when storage conditions or the source
cannot be verified unless it is determined that the risk of not Integrated Team-Based Approach for the Pharmacy
using such a medication exceeds the risk of using it; further, Enterprise (0619)
To support care models in which medications are pre- Source: Council on Professional Affairs
pared for patient administration by the pharmacy and are ob- To advocate a high level of coordination of all components
tained from a licensed, verified source; further, of the pharmacy enterprise in hospitals and health systems
To encourage hospitals and health systems not to perfor the purpose of optimizing (1) the value of drug therapy
mit the use of medication administration devices with which and (2) medication-use safety; further,
the staff is unfamiliar (e.g., devices brought in by patients) To encourage pharmacy department leaders to develop
unless it is determined that the risk of not using such a de- and maintain patient-centered practice models that integrate
vice exceeds the risk of using it; further, into a team all components of the pharmacy enterprise, in-
To advocate adequate reimbursement for preparation, cluding general and specialized clinical practice, drug-use
order review, and other costs associated with the safe provi- policy, product acquisition and inventory control, product
sion and administration of medications and use of related preparation and distribution, and medication-use safety and
devices. other quality initiatives.
Pharmacy Management and by the Board of Directors and Pharmacy Practice and by the Board of Directors and was
was found to still be appropriate. found to still be appropriate.
Pharmacist’s Leadership Role in Anticoagulation Health Care Quality Standards and Pharmacy Services
Therapy Management (0816) (0502)
Source: Council on Therapeutics Source: Council on Administrative Affairs
To advocate that pharmacists provide leadership in the inter- To advocate that health care quality improvement programs
disciplinary development, implementation, maintenance, ef- adopt standard quality measures that are developed with the
fectiveness monitoring, and assurance of continuity of care involvement of pharmacists, are evidence-based, and pro-
of anticoagulation management programs; further, mote the demonstrated role of pharmacists in improving pa-
To advocate that pharmacists be responsible for coor- tient outcomes.
dinating the individualized care of patients within antico- This policy was reviewed in 2014 by the Council on
agulation management programs; further, Pharmacy Practice and by the Board of Directors and was
To encourage pharmacists who participate in anticoag- found to still be appropriate.
ulation programs to educate patients, caregivers, prescribers,
and staff about anticoagulant medication uses, drug interac- Health-System Facility Design (0505)
tions, adverse effects, the importance of adhering to therapy, Source: Council on Administrative Affairs
and recommended laboratory testing and other monitoring. To advocate the development and the inclusion of contempo-
This policy was reviewed in 2012 by the Council on rary pharmacy specifications in national and state health care
Therapeutics and by the Board of Directors and was found design standards to ensure adequate space for safe provision
to still be appropriate. of pharmacy products and patient care services; further,
To promote pharmacist involvement in the design-
Standard Drug Administration Schedules (0707) planning and space-allocation decisions of health care
Source: Council on Pharmacy Management facilities.
To support the principle that standard medication ad- This policy was reviewed in 2014 by the Council on
ministration times should be based primarily on optimal Pharmacy Management and by the Board of Directors and
pharmacotherapeutics, with secondary consideration of was found to still be appropriate.
workload, caregiver preference, patient preference, and lo-
gistical issues; further,
Mandatory Tablet Splitting for Cost Containment (0525) To construct such mechanisms in a manner that will
Source: Council on Professional Affairs (1) provide a system for monitoring trends in the quality of
To oppose mandatory tablet splitting for cost containment in pharmacy services to patients, (2) increase recognition of the
ambulatory care; further, value of pharmacy services, and (3) provide a basis for mak-
To encourage pharmacists, when voluntary tablet ing improvements in the process and outcomes of pharmacy
splitting is considered, to collaborate with patients, care- services; further,
givers, and other health care professionals to determine To facilitate a dialogue with and education of national
whether tablet splitting is appropriate on the basis of the patient satisfaction database vendors on the role and value of
patient’s ability to split tablets and the suitability of the clinical pharmacy services.
medication (e.g., whether it is scored or is an extended- This policy was reviewed in 2010 by the Council on
release product); further, Pharmacy Management and by the Board of Directors and
To urge pharmacists to promote dosing accuracy and was found to still be appropriate.
patient safety by ensuring that patients are educated on how
to properly split tablets; further, Pharmacist Validation of Information Related to Medi-
To encourage further research by the United States cations (9921)
Pharmacopeia and the Food and Drug Administration on the Source: Council on Professional Affairs
impact of tablet splitting on product quality. To support consultation with a pharmacist as a primary
This policy was reviewed in 2014 by the Council on means for consumers to validate publicly available informa-
Pharmacy Practice and by the Board of Directors and was tion related to medications.
Performance Improvement (0202) found to still be appropriate.
Source: Council on Administrative Affairs
To encourage pharmacists to establish performance im- Collaborative Drug Therapy Management Activities (9801)
provement processes within their practice settings that mea- Source: House of Delegates Resolution
sure both operational and patient outcomes; further, To support the participation of pharmacists in collaborative
To encourage pharmacists to use contemporary per- drug therapy management, which is defined as a multi-
formance improvement techniques and methods for ongoing disciplinary process for selecting appropriate drug therapies,
improvement in their services; further, educating patients, monitoring patients, and continually
To support pharmacists in their development and im- assessing outcomes of therapy; further,
plementation of performance-improvement processes. To recognize that pharmacists participate in collab-
This policy was reviewed in 2011 by the Council on orative drug therapy management for a patient who has a
Pharmacy Management and by the Board of Directors and confirmed diagnosis by an authorized prescriber; further,
was found to still be appropriate. To recognize that the activities of a pharmacist in
collaborative drug therapy management may include, but
Pharmacy Benefits for the Uninsured (0101) not be limited to, initiating, modifying, and monitoring a
Source: Council on Administrative Affairs patient’s drug therapy; ordering and performing laboratory
To support the principle that all patients have the right to and related tests; assessing patient response to therapy;
receive care from pharmacists; further, counseling and educating a patient on medications; and
To declare that health system pharmacists should play administering medications.
a leadership role in ensuring access to pharmacists’ services This policy was reviewed in 2012 by the Council on
for indigent or low-income patients who lack insurance Pharmacy Practice and by the Board of Directors and was
coverage and for patients who are underinsured; further, found to still be appropriate.
To advocate better collaboration among health sys-
tems, community health centers, state and county health Medication Administration by Pharmacists (9820)
departments, and the federal Health Resources and Services Source: Council on Professional Affairs
Administration (HRSA) in identifying and addressing the To support the position that the administration of medi-
needs of indigent and low-income patients who lack insur- cines is part of the routine scope of pharmacy practice;
ance coverage and of patients who are underinsured. further,
This policy was reviewed in 2010 by the Council on To support the position that pharmacists who adminis
Pharmacy Management and by the Board of Directors and ter medicines should be skilled to do so; further,
was found to still be appropriate. To support the position that pharmacists should be
participants in establishing procedures in their own work
Patient Satisfaction (0104) settings with respect to the administration of medicines
Source: Council on Administrative Affairs (by anyone) and monitoring the outcomes of medication
To encourage pharmacists to establish mechanisms within administration.
their practice settings that measure the level of satisfaction This policy was reviewed in 2012 by the Council on
patients have with pharmacy services and with the outcomes Pharmacy Practice and by the Board of Directors and was
of their drug therapy; further, found to still be appropriate.
Medication Therapy and Patient Care: Organization and Delivery of Services–Statements 263
ASHP Statement on Confidentiality of Patient

Health Care Information
The American Society of Health-System Pharmacists and stored in such a way that the subjects’ rights of privacy
(ASHP) believes that all medical information is sensitive and confidentiality are protected. IRBs have a responsibility
and should be given the utmost protection. ASHP supports to determine when informed consent is necessary and to es-
the adoption into federal law of a minimum standard for pro- tablish procedures for obtaining informed consent. Patients
tection of individually identifiable patient health informa- should receive a statement describing the parties who may
tion and believes that states should retain the ability to adopt have access to patient-identifiable information (e.g., insti-
standards that are more stringent than federal law. tutional personnel, business associates, researchers, person-
ASHP believes that patients should have the right to nel from study sponsors, employees of government agencies
access and review their medical records and the ability to that monitor compliance with regulations). Patient authori-
correct factual errors in those records. Patients should also zation requirements under the privacy regulations of HIPAA
have the right to know who has access to their medical re- must be followed, and patients always have the right to with-
cords and to authorize how their medical information will draw their consent at any time.
be used. ASHP believes that there is no potential for a breach
The Health Insurance Portability and Accountability of patient confidentiality when patient information is aggre-
Act of 1996 (HIPAA) requires health systems to have writ- gated for use in legitimate research or statistical measure-
ten policies and procedures in place to guard against the ment and is not uniquely identifiable. Therefore, specific
unauthorized collection, use, or disclosure of individually authorization by individual patients for access to this infor-
identifiable patient health information and provide notice of mation is not needed.
such policies to their patients. All health-system personnel ASHP believes that pharmacy residency programs and
should be trained to understand and comply with those pri- other training programs must implement policies and proce-
vacy standards. dures to ensure the confidentiality of patient medical records
ASHP strongly believes that pharmacists must have while allowing pharmacy students and residents access to
access to patient health records in order to provide quality these records in the course of their training and presentation
care and ensure the safe use of medications. Within health of their research.
systems, all authorized practitioners should be encouraged
to communicate freely with each other while maintaining
patient confidentiality and privacy. This includes pharma-
cists practicing across the continuum of practice settings in This statement was reviewed in 2013 by the Council on Public
order to maintain continuity of care. Pharmacists recognize Policy and by the Board of Directors and was found to still be ap-
that with access to the patient’s health record comes the propriate.
pharmacist’s professional responsibility to safeguard the pa-
tient’s rights to privacy and confidentiality. Uniquely identi- Developed through the ASHP Council on Public Policy and ap-
fiable patient information should not be exchanged without proved by the ASHP Board of Directors on February 22, 2008, and
the patient’s authorization for any reason not directly related by the ASHP House of Delegates on June 10, 2008.
to treatment, payment, health care operations, or research
conducted under an appropriately constituted institutional This statement supersedes the ASHP Statement on the Confidential-
review board (IRB). ASHP advocates strict governmental ity of Patient Health Care Information dated April 21, 1999.
protections, with appropriate civil or criminal penalties for
violations, to prevent disclosure of individually identifiable Copyright © 2009, American Society of Health-System Pharma-
patient information outside the health system (i.e., to an un- cists, Inc. All rights reserved.
authorized third party) for any purposes not directly related
to treatment, payment, health care operations, or research The bibliographic citation for this document is as follows: Ameri-
conducted under an appropriately constituted IRB. can Society of Health-System Pharmacists. ASHP statement on
Pharmacists participate extensively in research on confidentiality of patient health care information. Am J Health-Syst
drugs. ASHP believes that all research data must be recorded Pharm. 2009; 66:411–2.
264 Medication Therapy and Patient Care: Organization and Delivery of Services–Statements
ASHP Statement on the Health-System Pharmacist’s

Role in National Health Care Quality Initiatives
Position help align medication use in hospitals and health systems
with the national health care quality agenda, health-system
The American Society of Health-System Pharmacists (ASHP) pharmacists should
believes that pharmacists who practice in hospitals and health
systems (“health-system pharmacists”) have a critical leader- • Become familiar with the organizations that influence
ship role in national health care quality-improvement initia- the national health care quality agenda and monitor
tives. Health-system pharmacists possess the knowledge of those organizations for changes in medication-use-
drug therapy and medication-use systems required to suc- related quality measures.
cessfully implement quality-assurance and improvement pro- • Participate in the development, implementation, and
grams. These pharmacists should use their authority over and evaluation of national and state health care quality-
accountability for medication management systems to align improvement initiatives related to medication use.
medication use in hospitals and health systems with the na- • Collaborate with other health care professionals to
tional health care quality agenda. evaluate medication-use practices in their organiza-
tions and develop and implement programs that opti-
mize patient outcomes, improve medication use, and
Background align with the national health care quality agenda, in-
cluding expanding the scope and reach of pharmacists’
Major reports from the Institute of Medicine (IOM) have services when appropriate.
demonstrated that the quality and safety environment across
the health care industry needs significant transformation.
• Collect, analyze, and report data that measure health
care quality related to medication use, and support the
The Urgent Need to Improve Health Care Quality1 suggested public availability of those data.
that the quality of the health care system in the United States
could be accurately measured and that the quality of care
• Integrate and align information systems in their orga-
nizations with the national health care quality agenda.
was being compromised by the underuse, overuse, and mis-
use of health care entities. Crossing the Quality Chasm2 built
• Educate other health care practitioners, health care ex-
ecutives, and the public about medication-related health
a compelling case that the American health care delivery care quality-improvement initiatives and the critical
system requires major restructuring and proposed goals for role pharmacists have in those initiatives (e.g., by pub-
improving six key dimensions of health care quality: safety, lishing articles about innovative pharmacy services that
timeliness, effectiveness, efficiency, equity, and patient cen- improve patient outcomes or medication use).
teredness (the “STEEP” framework). To achieve these aims,
IOM called for fundamental reforms, including new pay-
• Encourage national pharmacy organizations to sup-
port, guide, and provide education related to the na-
ment methodologies, public reporting, and transparency of tional health care quality agenda.
quality-improvement data.
Since the release of these reports, health care policy-
makers, providers, purchasers, payers, consumers, and others Conclusion
have responded in ways that are beginning to change the U.S.
health care delivery system. These changes are influenced The number of mandatory and voluntary health care qual-
by a growing number of private and public organizations, ity measures related to the use of medications is large and
including the Joint Commission, Centers for Medicare and growing. As medication-use experts, health-system pharma-
Medicaid Services (CMS), National Quality Forum, National cists have a responsibility to become knowledgeable about
Priorities Partnership, Agency for Healthcare Research and national health care quality-improvement initiatives and to
Quality, Institute for Healthcare Improvement, and American align their practices accordingly. Because health-system phar-
Health Quality Association, among others. These organiza- macists possess knowledge of drug therapy and medication-
tions, alone or in collaboration, identify health care quality use systems and have authority over and accountability for
measures to set the national health care quality agenda. These medication management systems, they have a fundamental
quality measures are collected and reported through both leadership role in the development, implementation, and
mandatory and voluntary reporting systems, and the outcome evaluation of health care quality-improvement initiatives.
measurements of a health system may be linked to reimburse-
ment (e.g., through CMS pay-for-performance programs). References
1. Chassin MR, Galvin RW. The urgent need to improve

Responsibilities of
health care quality. Institute of Medicine National
Health-System Pharmacists Roundtable on Health Care Quality. JAMA. 1998;
280:1000–5.
Many national health care quality measures are related to 2. Institute of Medicine Committee on Quality of Health
medication use.3 Health-system pharmacists are strategically Care in America. Crossing the quality chasm: a new
positioned to integrate practices and procedures that support health system for the 21st century. Washington, DC:
these quality measures into the medication-use system. To National Academy Press; 2001:43–56.
3. Bohenek WS, Grossbart SR. Pharmacists’ role in American Pharmacists Association (APhA); South Carolina Soci-
improving quality of care. Am J Health-Syst Pharm. ety of Health-Systems Pharmacists (SCSHSP); John A. Armitstead,
2008; 65:1566–70. M.S., FASHP; Cathy Baker, Pharm.D.; Frank Briggs, Pharm.D.,
M.P.H.; Kimberly K. Daugherty, Pharm.D., BCPS; Jeanne Ezell,
M.S., FASHP; Linda Gore Martin, Pharm.D., M.B.A., BCPS; Jody
This policy was reviewed in 2013 by the Council on Pharmacy Jacobson Wedret, FASHP, FCSHP; Patricia Kienle, M.P.A., FASHP;
Practice and by the Board of Directors and was found to still be Julie Kuhle, B.S.Pharm.; Greg Polk, M.B.A.; James A. Ponto, M.S.,
appropriate. BCNP, FASHP; Mike Rouse, B.Pharm.(Hons), M.P.S. (ACPE);
Marissa Schlaifer, M.S. (AMCP); Sue Skledar, M.P.H., FASHP;
Approved by the ASHP Board of Directors on April 17, 2009, and Darren M. Triller, Pharm.D.; and Bradley White, Pharm.D., R.N.
by the ASHP House of Delegates on June 16, 2009. Developed (SCSHSP).
Copyright © 2010, American Society of Health-System Pharma-
The contributions of Wayne S. Bohenek, Pharm.D., M.S., FASHP, cists, Inc. All rights reserved.
and Jamie S. Sinclair, M.S., to this statement are gratefully ac-
knowledged. The following organizations and individuals are ac- The bibliographic citation for this document is as follows: Ameri-
knowledged for reviewing draft versions of this statement (review can Society of Health-System Pharmacists. ASHP statement on the
does not imply endorsement): Academy of Managed Care Pharmacy health-system pharmacist’s role in national health care quality ini-
(AMCP); Accreditation Council for Pharmacy Education (ACPE); tiatives. Am J Health-Syst Pharm. 2010; 67:578–9.
ASHP–SHM Joint Statement

on Hospitalist–Pharmacist Collaboration
Position many as 89% considering the hospitalist model to be supe
rior to the historical model of hospital care being provided
The American Society of Health-System Pharmacists by primary care physicians or by specialists working on ro
(ASHP) and the Society for Hospital Medicine (SHM) be- tations.7,8 Numerous studies demonstrate the value of hospi-
lieve that the rapidly emerging hospitalist model of inpatient talists in improving quality of care, decreasing hospital costs
care offers new and significant opportunities to optimize pa- and length of stay, and reducing hospital readmissions.9–21
tient care through collaboration among hospitalists, hospital As early as 1921, hospital pharmacists in the American
pharmacists (hereinafter, “pharmacists”), and other health Pharmaceutical Association (now the American Pharmacists
care providers. The emerging model of care allows for Association) had formed a committee to address their dis-
deeper professional relationships among health care provid- tinct concerns. During the 1930s, hospital pharmacists be-
ers and promotes a shared interest in and responsibility for gan to organize state organizations and to adhere to a set
direct patient care, indirect patient care, and service activi- of minimum standards of practice. In 1942, the American
ties. ASHP and SHM encourage hospitalists, pharmacists, Society of Hospital Pharmacists (now the American Society
and health care executives to seek out ways to foster col- of Health-System Pharmacists [ASHP]) was formed to es-
laboration between hospitalists and pharmacists. tablish minimum standards of pharmaceutical services in
The purpose of this consensus statement is to promote hospitals, provide interchange among pharmacists, promote
an understanding of the ways hospitalists and pharmacists new pharmaceutical techniques, and aid the medical profes-
can jointly optimize the care provided to patients in hospi- sion in extending the economic and rational use of medica-
tals, examine opportunities for improving hospitalist–phar- tions.22 As of 2005, there were approximately 50,000 phar-
macist alliances that enhance patient care, suggest future macists practicing in U.S. hospitals.23
directions for collaboration, and identify aspects of such col- The modern mission of hospital pharmacy departments
laboration that warrant further research. is to ensure optimal outcomes from the use of medicines.24
Although the focus of hospital pharmacy has traditionally
been on the safe dispensing of medications, direct patient
Background care by pharmacists (clinical pharmacy) has always been
a component of hospital pharmacy practice. Following the
Increases in health care spending and the expanding influ- rise of pharmaceutical care in the 1980s,25 these pharmacist
ence of managed care in the late 1980s and early 1990s services have expanded greatly. It has been estimated that
resulted in calls for more efficient health care. The move- 35–40% of hospital pharmacists are devoted to providing
ment toward greater efficiency resulted in more emphasis clinical services.23 A systematic review in 2006 documented
on ambulatory care, fewer hospital admissions, shortened improved outcomes when clinical pharmacists interacted
hospital stays, and an overall increase in the acuity of illness with the health care team on patient rounds, interviewed
of hospitalized patients. The emphasis on ambulatory care patients, reconciled medications, and provided discharge
increased the number and complexity of physician office counseling and follow-up.26 These findings support those of
visits, and the changing characteristics of office- and hos- other studies in which specific clinical pharmacy services
pital-based care placed significant demands on primary care were associated with improved therapeutic and economic
physicians and contributed to the rise of hospital medicine. outcomes.27–31
In 1996, the term “hospitalist” was introduced to the
health care lexicon.1 A hospitalist was defined as an inpatient
physician who manages the care of hospitalized patients and Opportunities for Collaboration Between
facilitates the transfer of their care back to the primary care Pharmacists and Hospitalists
physician. The Society of Hospital Medicine has since de-
fined a hospitalist as a physician whose primary professional Pharmacists and hospitalists have shared interests that pro-
focus is the general medical care of hospitalized patients vide strong incentives for collaboration. All health care pro-
and whose activities may include patient care, teaching, re- fessionals share, first, a commitment to and responsibility
search, and leadership related to hospital medicine.2 for providing safe and effective patient care. Physicians,
The past decade has seen rapid growth in the number pharmacists, and other health care providers have long col-
of hospitalists and the use of hospitalists by U.S. hospitals.3 laborated in providing direct patient care. The emerging
In 2005, 70% of hospitals with more than 200 beds used hospitalist model of care offers more opportunities for col-
hospitalist services, and there were over 16,000 hospitalists laboration because pharmacists and hospitalists also share
in practice.4 An estimated 20,000 hospitalists were practic- interest in and responsibility for indirect patient care and
ing at over 2,600 U.S. hospitals in 2007.5 service activities—developing the institutional policies, pro-
Initially, many physicians expressed concern about the cesses, and infrastructure that support patient care.
potential for hospitalists to interfere in the relationship be Direct patient care activities typically performed by
tween the patient and the primary care physician, as well as hospitalists include obtaining patient histories, conduct-
about the potential negative impact on continuity of care.6 ing physical examinations, making diagnoses, developing
However, subsequent studies demonstrated increasing ac treatment plans, monitoring patients’ responses to therapy,
ceptance of hospitalists by primary care physicians, with as performing follow-up hospital visits, participating in family
meetings, and providing discharge instructions.32 Specific professional education and research offer the opportunities
clinical pharmacy services that have been associated with to improve patient care provided not just by a single hospital
improved health care outcomes include providing drug in- but by other facilities as well.
formation, managing medication protocols and adverse drug
reactions, participating in medical rounds, gathering admis- Opportunities to Improve Collaboration
sion medication histories, interviewing patients, reconciling
patient medications, and providing discharge counseling and ASHP and SHM believe that there are opportunities for im-
follow-up.26–31 proving collaboration between hospitalists and pharmacists.
Pharmacists should be involved in the care of hospital- Barriers to collaboration include real and perceived profes-
ized patients and can collaborate with hospitalists in numer- sional boundaries, poor integration of technology systems,
ous ways, including inadequate pharmacist and hospitalist staffing, time con-
straints, inadequate funding and resources, lack of third-
• Providing consultative services that foster appropri- party compensation for clinical pharmacy services, and the
ate, evidence-based medication selection (e.g., during competing obligations weighing on both professions.
rounds), Real and perceived professional boundaries can be ad-
• Providing drug information consultation to physicians, dressed by clear communication and by enhanced interdis-
nurses, and other clinicians, ciplinary educational opportunities for all members of the
• Managing medication protocols under collaborative health care team.35–38 ASHP and SHM believe that, while
practice agreements, hospitalists should serve as the primary leaders of hospital
• Assisting in the development of treatment protocols, care teams, all health care professionals should be willing to
• Monitoring therapeutic responses (including labora- assume a leadership role in treating patients and, when ap-
tory test results), propriate, accept leadership by other team members. Like all
• Continuously assessing for and managing adverse members of the care team, pharmacists require timely access
drug reactions, to hospitalists for consultation, as well as access to patient
• Gathering medication histories, information. The vital flow of information and communi-
• Reconciling medications as patients move across the cation among health care providers should be conducive to
continuum of hospital care, and collaborating and improving patient outcomes. ASHP and
• Providing patient and caretaker education, including SHM believe that properly applied, well-integrated technol-
discharge counseling and follow-up. ogies (e.g., electronic medical records and personal digital
assistants with clinical decision support systems, including
Both hospitalists and pharmacists have a responsibility for drug information) can enhance communication among all
ensuring continuity as patients move across settings of care. members of the health care team.
In addition to their direct patient care activities, hos- Hospitalists and pharmacists can work together to
pitalists add value through their efforts in hospital service overcome limitations created by inadequate funding and
activities, student and resident education, and research. staffing by providing evidence to health care executives
Typical service activities include participating in quality- of the value of clinical pharmacist positions and pharma-
improvement and safety initiatives, developing institutional cist–hospitalist collaboration. This evidence should exam-
guidelines and protocols for the treatment of specific dis- ine the impact of these positions and such collaboration on
eases, serving on hospital committees (e.g., the pharmacy therapeutic, safety, humanistic, and economic outcomes.
and therapeutics [P&T] committee), and working with oth- Collaboration among all members of the health care team
ers to introduce new technologies to the hospital setting.33,34 would also be encouraged by reforming the current fee-for-
Pharmacists also participate in hospital service activi- service reimbursement practices to base payment for care
ties, student and resident education, and research. For ex- delivery on overall treatment goals (e.g., a payment rate
ample, pharmacists serve on the P&T committee and are based on diagnosis).
directly involved in managing the formulary system that
guides an institution’s medication use. As medication ex-
perts, pharmacists contribute to the development and imple- Conclusion
mentation of patient care guidelines and other medication-
use policies. Pharmacist expertise is also integral to many An interdisciplinary approach to health care that includes
quality-improvement efforts (e.g., surgical infection prophy- physicians, pharmacists, nurses, and other health care profes-
laxis) and to technology initiatives (e.g., bedside medication sionals will improve the quality of patient care. Hospitalists
scanning and computerized prescriber-order-entry systems). and pharmacists need to collaborate with each other and
Pharmacist provision of inservice education on medications with other health care professionals to optimize outcomes in
and medication use is invaluable for all health care providers. hospitalized patients. ASHP and SHM believe that hospital-
These overlapping responsibilities provide hospitalists ist–pharmacist alliances should be encouraged and that the
and pharmacists with opportunities to collaborate on activi- systems and technologies that enable collaboration, and the
ties that can have a profound effect on care in the hospital. incentives for such collaboration, should be enhanced.
Hospitalists and pharmacists can work together to ensure
that care is evidence-based, cost-effective, and adherent References
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ter the institution’s education and research initiatives. Health Med. 1996; 335:514–7.
2. Society of Hospital Medicine. Definition of a hospitalist. sured by HMOs: comparison of care by hospitalists
www.hospitalmedicine.org/Content/NavigationMenu/ and traditional academic providers. Pediatr Res. 2000;
AboutSHM/DefinitionofaHospitalist/Definition_ 47:204A. Abstract.
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J Med. 2000; 109:648–53. 25. American Society of Hospital Pharmacists. ASHP
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9. Wachter RM, Katz P, Showstack J, et al. Reorganizing pharmacists and inpatient medical care: a systematic
an academic medical service: impact on cost, qual- review. Arch Intern Med. 2006; 166:955–64.
ity, patient satisfaction, and education. JAMA. 1998; 27. Bond CA, Raehl CL, Franke T. Interrelationships
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10. Diamond HS, Goldberg E, Janosky JE. The effect of and length of stay in United States hospitals: summary
full-time faculty hospitalists on the efficiency of care and recommendations for clinical pharmacy services
at a community teaching hospital. Ann Intern Med. and staffing. Pharmacotherapy. 2001; 21:129–41.
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pneumonia care. J Gen Intern Med. 1998; 13:774–7. 2002; 22:134–47.
12. Craig DE, Hartka L, Likosky WH, et al. Implementation 29. Bond CA, Raehl CL. Clinical pharmacy services, phar-
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14. Rifkin WD, Connor DS, Silver A, et al. Comparison Pharmacists on rounding teams reduce preventable ad-
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Med. 2001; 16(suppl):S215. ist model for medical students’ education. Acad Med.
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a rural health system. Am J Med. 2000; 108:621–6. Hospitalists’ perceptions of their residency training
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tion, and satisfaction. Am J Manag Care. 2000; 6:549– 35. Committee on the Health Professions Education
55. Summit. Health professions education: a bridge to
18. Bellet PS, Whitaker RC. Evaluation of a pediatric hos- quality. Washington, DC: National Academy Press;
pitalist service: impact on length of stay and hospital 2003.
charges. Pediatrics. 2000; 105:478–84. 36. Cooper H, Carlisle C, Gibbs T, et al. Developing an
19. Landrigan C, Srivastava R, Muret-Wagstaff S, et al. evidence base for interdisciplinary learning: a system-
Outcomes of hospitalization in pediatric patients in- atic review. J Adv Nurs. 2001; 31:228–37.
37. Horsburgh M, Lamdin R, Williamson E. Multipro- macists Research and Education Foundation through a sponsorship
fessional learning: the attitudes of medical, nursing, from sanofi-aventis, Inc.
and pharmacy students to shared learning. Med Educ.
2001; 35:876–83. Daniel J. Cobaugh, Pharm.D., FAACT, DABAT (Corresponding
38. Crawford GB, Price SD. Team working: palliative care Author, ASHP); Alpesh Amin, M.D., MBA, FACP (Correspond-
as a model of interdisciplinary practice. Med J Aust. ing Author, SHM); Thomas Bookwalter, Pharm.D. (ASHP, SHM);
2003; 179:S32–4. Mark Williams, M.D., FACP (SHM), Patricia Grunwald, Pharm.D.
(ASHP); Cynthia LaCivita, Pharm.D. (ASHP); and Bruce Hawkins,
B.A., B.S. (ASHP) are gratefully acknowledged for drafting this
statement.
This statement was reviewed in 2012 by the Council on Pharmacy
Practice and by the Board of Directors and was found to still be Copyright © 2008, American Society of Health-System Pharma-
appropriate. cists, Inc. All rights reserved.
Approved by the ASHP Council on Pharmacy Practice on Sep- The bibliographic citation for this document is as follows: American
tember 24, 2007, by the ASHP Board of Directors on September Society of Health-System Pharmacists. ASHP–SHM joint statement
27, 2007, by the SHM Board of Directors on September 26, 2007. on hospitalist–pharmacist collaboration. Am J Health-Syst Pharm.
Developed through the American Society of Health-System Phar- 2008; 65:260–3.
ASHP Statement on Pharmaceutical Care

The purpose of this statement is to assist pharmacists in under- Care. Central to the concept of care is caring, a personal
standing pharmaceutical care. Such understanding must pre- concern for the well-being of another person. Overall
cede efforts to implement pharmaceutical care, which ASHP patient care consists of integrated domains of care including
believes merit the highest priority in all practice settings. (among others) medical care, nursing care, and pharmaceu-
Possibly the earliest published use of the term pharma- tical care. Health professionals in each of these disciplines
ceutical care was by Brodie in the context of thoughts about possess unique expertise and must cooperate in the patient’s
drug use control and medication-related services.1,2 It is a overall care. At times, they share in the execution of the various
term that has been widely used and a concept about which types of care (including pharmaceutical care). To pharma-
much has been written and discussed in the pharmacy pro- ceutical care, however, the pharmacist contributes unique
fession, especially since the publication of a paper by Hepler knowledge and skills to ensure optimal outcomes from the
and Strand in 1990.3–5 ASHP has formally endorsed the con- use of medications.
cept.6 With varying terminology and nuances, the concept At the heart of any type of patient care, there exists a
has also been acknowledged by other national pharmacy or- one-to-one relationship between a caregiver and a patient.
ganizations.7,8 Implementation of pharmaceutical care was In pharmaceutical care, the irreducible “unit” of care is one
the focus of a major ASHP conference in March 1993. pharmacist in a direct professional relationship with one
Many pharmacists have expressed enthusiasm for the patient. In this relationship, the pharmacist provides care
concept of pharmaceutical care, but there has been substan- directly to the patient and for the benefit of the patient.
tial inconsistency in its description. Some have character- The health and well-being of the patient are paramount.
ized it as merely a new name for clinical pharmacy; others The pharmacist makes a direct, personal, caring commitment
have described it as anything that pharmacists do that may to the individual patient and acts in the patient’s best interest.
lead to beneficial results for patients. The pharmacist cooperates directly with other professionals
ASHP believes that pharmaceutical care is an important and the patient in designing, implementing, and monitoring
new concept that represents growth in the profession beyond a therapeutic plan intended to produce definite therapeutic
clinical pharmacy as often practiced and beyond other activities outcomes that improve the patient’s quality of life.
of pharmacists, including medication preparation and dispens-
ing. All of these professional activities are important, however, Outcomes. It is the goal of pharmaceutical care to improve
and ASHP continues to be a strong proponent of the necessity an individual patient’s quality of life through achievement
for pharmacists’ involvement in them. In practice, these activi- of definite (predefined), medication-related therapeutic out-
ties should be integrated with and culminate in pharmaceutical comes. The outcomes sought are
care provided by individual pharmacists to individual patients.
In 1992, ASHP’s members urged the development of 1. Cure of a patient’s disease.
an officially recognized ASHP definition of pharmaceutical 2. Elimination or reduction of a patient’s symptomatology.
care.9 This statement provides a definition and elucidates 3. Arresting or slowing of a disease process.
some of the elements and implications of that definition. 4. Prevention of a disease or symptomatology.
The definition that follows is an adaptation of a definition
developed by Hepler and Strand.3 This, in turn, involves three major functions: (1) identifying
potential and actual medication-related problems, (2) resolving
Definition actual medication-related problems, and (3) preventing
potential medication-related problems. A medication-related
The mission of the pharmacist is to provide pharmaceutical problem is an event or circumstance involving medication
care. Pharmaceutical care is the direct, responsible provision therapy that actually or potentially interferes with an optimum
of medication-related care for the purpose of achieving defi- outcome for a specific patient. There are at least the following
nite outcomes that improve a patient’s quality of life. categories of medication-related problems3:
Principal Elements • Untreated indications. The patient has a medical prob-

lem that requires medication therapy (an indication for
The principal elements of pharmaceutical care are that it is medication use) but is not receiving a medication for
medication related; it is care that is directly provided to the that indication.
patient; it is provided to produce definite outcomes; these out- • Improper drug selection. The patient has a medication
comes are intended to improve the patient’s quality of life; and indication but is taking the wrong medication.
the provider accepts personal responsibility for the outcomes. • Subtherapeutic dosage. The patient has a medical
problem that is being treated with too little of the cor-
Medication Related. Pharmaceutical care involves not only rect medication.
medication therapy (the actual provision of medication) but • Failure to receive medication. The patient has a
also decisions about medication use for individual patients. medical problem that is the result of not receiving a
As appropriate, this includes decisions not to use medication medication (e.g., for pharmaceutical, psychological,
therapy as well as judgments about medication selection, sociological, or economic reasons).
dosages, routes and methods of administration, medication • Overdosage. The patient has a medical problem that is
therapy monitoring, and the provision of medication-related being treated with too much of the correct medication
information and counseling to individual patients. (toxicity).
• Adverse drug reactions. The patient has a medical pharmacy organizations. Pharmaceutical care is applicable
problem that is the result of an adverse drug reaction and achievable by pharmacists in all practice settings. The
or adverse effect. provision of pharmaceutical care is not limited to pharmacists
• Drug interactions. The patient has a medical problem in inpatient, outpatient, or community settings, nor to phar-
that is the result of a drug–drug, drug–food, or drug– macists with certain degrees, specialty certifications, residen-
laboratory test interaction. cies, or other credentials. It is not limited to those in academic
• Medication use without indication. The patient is tak- or teaching settings. Pharmaceutical care is not a matter of
ing a medication for no medically valid indication. formal credentials or place of work. Rather, it is a matter of a
direct personal, professional, responsible relationship with a
Patients may possess characteristics that interfere with patient to ensure that the patient’s use of medication is optimal
the achievement of desired therapeutic outcomes. Patients may and leads to improvements in the patient’s quality of life.
be noncompliant with prescribed medication use regimens, or Pharmacists should commit themselves to continuous
there may be unpredictable variations in patients’ biological care on behalf of individual patients. They bear responsibility
responses. Thus, in an imperfect world, intended outcomes for ensuring that the patient’s care is ongoing despite work-
from medication-related therapy are not always achievable. shift changes, weekends, and holidays. An important implica-
Patients bear a responsibility to help achieve the desired tion is that a pharmacist providing pharmaceutical care may
outcomes by engaging in behaviors that will contribute need to work as a member of a team of pharmacists who pro-
to—and not interfere with—the achievement of desired out- vide backup care when the primary responsible pharmacist
comes. Pharmacists and other health professionals have an is not available. Another is that the responsible pharmacist
obligation to educate patients about behaviors that will con- should work to ensure that continuity of care is maintained
tribute to achieving desired outcomes. when a patient moves from one component of a health-care
system to another (e.g., when a patient is hospitalized or dis-
Quality of Life. Some tools exist now for assessing a patient’s charged from a hospital to return to an ambulatory, community
quality of life. These tools are still evolving, and pharmacists status). In the provision of pharmaceutical care, professional
should maintain familiarity with the literature on this sub communication about the patient’s needs between responsible
ject.10,11 A complete assessment of a patient’s quality of life pharmacists in each area of practice is, therefore, essential.
should include both objective and subjective (e.g., the patient’s ASHP believes that the development of recognized methods
own) assessments. Patients should be involved, in an informed of practicing pharmaceutical care that will enhance such com-
way, in establishing quality-of-life goals for their therapies. munication is an important priority for the profession.
Pharmaceutical care can be conceived as both a pur-
Responsibility. The fundamental relationship in any type pose for pharmacy practice and a purpose of medication use
of patient care is a mutually beneficial exchange in which processes. That is, a fundamental professional reason that
the patient grants authority to the provider and the provider pharmacists engage in pharmacy practice should be to de-
gives competence and commitment to the patient (accepts liver pharmaceutical care. Furthermore, the medication use
responsibility).3 Responsibility involves both moral trust- systems that pharmacists (and others) operate should be de-
worthiness and accountability. signed to support and enable the delivery of pharmaceutical
In pharmaceutical care, the direct relationship between care by individual pharmacists. ASHP believes that, in orga-
an individual pharmacist and an individual patient is that of a nized health-care settings, pharmaceutical care can be most
professional covenant in which the patient’s safety and well- successfully provided when it is part of the pharmacy de-
being are entrusted to the pharmacist, who commits to hon- partment’s central mission and when management activity is
oring that trust through competent professional actions that focused on facilitating the provision of pharmaceutical care
are in the patient’s best interest. As an accountable member by individual pharmacists. This approach, in which empow-
of the health-care team, the pharmacist must document the ered frontline staff provide direct care to individual patients
care provided.4,7,12,13 The pharmacist is personally account- and are supported by managers, other pharmacists, and sup-
able for patient outcomes (the quality of care) that ensue port systems, is new for many pharmacists and managers.
from the pharmacist’s actions and decisions.1 An important corollary to this approach is that pharma-
cists providing pharmaceutical care in organized health-care
Implications settings cannot provide such care alone. They must work in
an interdependent fashion with colleagues in pharmacy and
The idea that pharmacists should commit themselves to the other disciplines, support systems and staff, and managers.7
achievement of definite outcomes for individual patients is an It is incumbent on pharmacists to design work systems and
especially important element in the concept of pharmaceutical practices that appropriately focus the efforts of all activities
care. The expectation that pharmacists personally accept re- and support systems on meeting the needs of patients. Some
sponsibility for individual patients’ outcomes that result from patients will require different levels of care, and it may be use-
the pharmacists’ actions represents a significant advance in ful to structure work systems in light of those differences.16,17
pharmacy’s continuing professionalization. The provision of ASHP believes that the provision of pharmaceutical care and
pharmaceutical care represents a maturation of pharmacy as a the development of effective work systems to document and
clinical profession and is a natural evolution of more mature support it are major priorities for the profession.
clinical pharmacy activities of pharmacists.14 In the provision of pharmaceutical care, pharmacists
ASHP believes that pharmaceutical care is fundamental use their unique perspective and knowledge of medication
to the profession’s purpose of helping people make the best therapy to evaluate patients’ actual and potential medication-
use of medications.15 It is a unifying concept that transcends related problems. To do this, they require direct access to
all types of patients and all categories of pharmacists and clinical information about individual patients. They make
judgments regarding medication use and then advocate op- 3. Hepler CD, Strand LM. Opportunities and responsibil-
timal medication use for individual patients in cooperation ities in pharmaceutical care. Am J Hosp Pharm. 1990;
with other professionals and in consideration of their unique 47:533–43.
professional knowledge and evaluations. Pharmaceutical 4. Penna RP. Pharmaceutical care: pharmacy’s mission
care includes the active participation of the patient (and des- for the 1990s. Am J Hosp Pharm. 1990; 47:543–9.
ignated caregivers such as family members) in matters perti- 5. Pierpaoli PG, Hethcox JM. Pharmaceutical care: new
nent to medication use. management and leadership imperatives. Top Hosp
The acknowledgment of pharmacists’ responsibility Pharm Manage. 1992; 12:1–18.
for therapeutic outcomes resulting from their actions does 6. Oddis JA. Report of the House of Delegates: June 3
not contend that pharmacists have exclusive authority and 5, 1991. Am J Hosp Pharm. 1991; 48:1739–48.
for matters related to medication use. Other health-care 7. American Pharmaceutical Association. An APhA
professionals, including physicians and nurses, have valua white paper on the role of the pharmacist in compre-
ble and well-established, well-recognized roles in the medi hensive medication use management; the delivery
cation use process. The pharmaceutical care concept does of pharmaceutical care. Washington, DC: American
not diminish the roles or responsibilities of other health Pharmaceutical Association; 1992 Mar.
professionals, nor does it imply any usurping of authority 8. Commission to Implement Change in Pharmaceutical
by pharmacists. Pharmacists’ actions in pharmaceutical Education. A position paper. Entry-level education
care should be conducted and viewed as collaborative. The in pharmacy: a commitment to change. AACP News.
knowledge, skills, and traditions of pharmacists, however, 1991; Nov (Suppl):14
make them legitimate leaders of efforts by health-care teams 9. Oddis JA. Report of the House of Delegates: June 1
to improve patients’ medication use. and 3, 1992. Am J Hosp Pharm. 1992; 49:1962–73.
Pharmaceutical care requires a direct relationship be- 10. Gouveia WA. Measuring and managing patient out-
tween a pharmacist and an individual patient. Some pharma- comes. Am J Hosp Pharm. 1992; 49:2157–8.
cists and other pharmacy personnel engage in clinical and 11. MacKeigan LD, Pathak DS. Overview of health-
product-related pharmacy activities that do not involve a related quality-of-life measures. Am J Hosp Pharm.
direct relationship with the patient. Properly designed, these 1992; 49:2236–45.
activities can be supportive of pharmaceutical care, but 12. Galinsky RE, Nickman NA. Pharmacists and the man-
ASHP believes it would be confusing and counterproduc- date of pharmaceutical care. DICP Ann Pharmacother.
tive to characterize such activities as pharmaceutical care. 1991; 21:431–4.
ASHP believes that clinical and product-related pharmacy 13. Angaran DM. Quality assurance to quality improve-
activities are essential, however, and are as important as the ment: measuring and monitoring pharmaceutical care.
actions of pharmacists interacting directly with patients. Am J Hosp Pharm. 1991; 48:1901–7.
Pharmaceutical educators must teach pharmaceutical 14. Hepler CD. Pharmaceutical care and specialty prac-
care to students.18 Providers of continuing education should tice. Pharmacotherapy. 1993; 13:64S–9S.
help practicing pharmacists and other pharmacy personnel to 15. Zellmer WA. Expressing the mission of pharmacy
understand pharmaceutical care. Students and pharmacists practice. Am J Hosp Pharm. 1991; 48:1195. Editorial.
should be taught to conceptualize and execute responsible 16. Smith WE, Benderev K. Levels of pharmaceutical
medication-related problem-solving on behalf of individual care: a theoretical model. Am J Hosp Pharm. 1991;
patients. Curricula should be designed to produce graduates 48:540–6.
with sufficient knowledge and skills to provide pharmaceu- 17. Strand LM, Cipole RJ, Morley PC,, et al. Levels of
tical care competently.8,18 Initiatives are under way to bring pharmaceutical care: a needs-based approach. Am J
about these changes.8 Practicing pharmacists must commit Hosp Pharm. 1991; 48:547–50.
their time as preceptors and their workplaces as teaching 18. O’Neil EH. Health professions education for the future:
laboratories for the undergraduate and postgraduate educa- schools in service to the nation. San Francisco, CA:
tion and training necessary to produce pharmacists who can Pew Health Profession Commission; 1993.
provide pharmaceutical care.8
Research is needed to evaluate various methods and
systems for the delivery of pharmaceutical care.
Pharmaceutical care represents an exciting new vision This statement was reviewed in 1998 by the Council on Professional
for pharmacy. ASHP hopes that all pharmacists in all prac- Affairs and the ASHP Board of Directors and was found to still be
tice settings share in this vision and that the pharmaceuti- appropriate.
cal care concept will serve as a stimulus for them to work
toward transforming the profession to actualize that vision. Approved by the ASHP Board of Directors, April 21, 1993, and
by the ASHP House of Delegates, June 9, 1993. Developed by the
References ASHP Council on Professional Affairs.
1. Brodie DC. Is pharmaceutical education prepared Copyright © 1993, American Society of Hospital Pharmacists, Inc.
to lead its profession? The Ninth Annual Rho Chi All rights reserved.
Lecture. Rep Rho Chi. 1973; 39:6–12.
2. Brodie DC, Parish PA, Poston JW. Societal needs for The bibliographic citation for this document is as follows: American
drugs and drug-related services. Am J Pharm Educ. Society of Hospital Pharmacists. ASHP statement on pharmaceuti-
1980; 44:276–8. cal care. Am J Hosp Pharm. 1993; 50:1720–3.
Medication Therapy and Patient Care: Organization and Delivery of Services–Guidelines 273
ASHP Guidelines on Documenting Pharmaceutical

Care in Patient Medical Records
Purpose the acute situation has settled. For less urgent and routine
recommendations, timely documentation is also preferred,
The professional actions of pharmacists that are intended to because delays in response to telephone calls or pager
ensure safe and effective use of drugs and that may affect messages may lead to miscommunicated or undocumented
patient outcomes should be documented in the patient medical re- recommendations. Unofficial, temporary, or removable
cord (PMR). These guidelines describe the kinds of information notes placed in the PMR do not provide a standard of accept
pharmacists should document in the PMR, how that information able communication or documentation and therefore are
should be documented, methods for obtaining authorization for discouraged. Documentation that is not a part of the PMR
pharmacist documentation, and the important role of training and (e.g., documentation in pharmacy records) may provide a
continuous quality improvement (CQI) in documentation. degree of risk reduction; however, such documentation does
not provide important information to other care providers
and can interrupt continuity of care when the patient is dis-
Background charged or transferred.
Pharmaceutical care is the direct, responsible provision of
medication-related care for the purpose of achieving defi- Documenting Pharmaceutical Care
nite outcomes that improve a patient’s quality of life.1 A
core principle of pharmaceutical care is that the pharmacist Pharmacists should be authorized and encouraged to make
accepts professional responsibility for patient outcomes.2 notations in the PMR for the purpose of documenting their
Integrating pharmaceutical care into a patient’s overall findings, assessments, conclusions, and recommendations.2
health care plan requires effective and efficient communica- ASHP believes that all significant clinical recommendations
tion among health care professionals. As an integral mem- and resulting actions should be documented in the appropriate
ber of the health care team, the pharmacist must document section of the PMR. The pharmacy department should establish
the care provided. Such documentation is vital to a patient’s policies and procedures for documenting information in the
continuity of care and demonstrates both the accountability PMR. Such policies and procedures will help pharmacists
of the pharmacist and the value of the pharmacist’s services. exercise good judgment in determining what information to
Moreover, because clinical services (e.g., those incident to a document in the PMR and how to present it.
physician’s services) are generally considered reimbursable Examples of information a pharmacist may need to docu-
only when they are necessary for the medical management ment in the PMR include, but are not limited to, the following:
of a patient and when the service provided and the patient’s
response are carefully documented, thorough documentation 1. A summary of the patient’s medication history on
may increase the likelihood of reimbursement. Early imple- admission, including medication allergies and their
mentation of such documentation practices may help health- manifestations.
system pharmacies cope with documentation requirements in 2. Oral and written consultations provided to other health
the event pharmacists’ clinical services become reimbursable. care professionals regarding the patient’s drug therapy
The PMR’s primary purpose is to convey information selection and management.
for use in patient care; it serves as a tool for communication 3. Physicians’ oral orders received directly by the
among health care professionals. Information in the PMR pharmacist.
may also be used in legal proceedings (e.g., as evidence), 4. Clarification of drug orders.
education (e.g., for training students), research (e.g., for 5. Adjustments made to drug dosage, dosage frequency,
evaluating clinical drug use), and quality assurance evalu- dosage form, or route of administration.
ations (e.g., to ascertain adherence to practice standards).3 6. Drugs, including investigational drugs, administered.
Clinical recommendations made by a pharmacist on 7. Actual and potential drug-related problems that warrant
behalf of the patient, as well as actions taken in accordance surveillance.
with these recommendations, should be documented in a 8. Drug therapy-monitoring findings, including
permanent manner that makes the information available to a. The therapeutic appropriateness of the patient’s
all the health care professionals caring for the patient. ASHP drug regimen, including the route and method of
believes that, to ensure proper coordination of patients’ administration.
medication therapies, health care systems must be designed b. Therapeutic duplication in the patient’s drug
to enable, foster, and facilitate communication and collabora regimen.
tion among health care providers.2 Health care systems must c. The degree of patient compliance with the pre-
not erect barriers to that communication or to the exercise of scribed drug regimen.
the professional judgment of health care providers. d. Actual and potential drug–drug, drug–food,
Although telephone calls and other oral communication drug–laboratory test, and drug–disease interactions.
may be necessary for immediate interventions, they do not e. Clinical and pharmacokinetic laboratory data
allow for the dissemination of information to care provid pertinent to the drug regimen.
ers who are not a part of the conversation. Such interventions f. Actual and potential drug toxicity and adverse
should be documented in the PMR as soon as possible after effects.
274 Medication Therapy and Patient Care: Organization and Delivery of Services–Guidelines
g. Physical signs and clinical symptoms relevant to 4. Identify the committees in the organization whose
the patient’s drug therapy. recommendations or decisions will be required to establish
9. Drug-related patient education and counseling pro- authority for pharmacists to document pharmaceutical
vided. care in the PMR. Determine the necessary sequence
of these approvals. Committees typically involved
Documentation by pharmacists should meet established include the pharmacy and therapeutics (P&T) com-
criteria for legibility, clarity, lack of judgmental language, mittee, the executive committee of the medical staff,
completeness, need for inclusion in the PMR (versus an al- a quality-assurance committee (e.g., the CQI commit-
ternative form of communication), appropriate use of a stan- tee), and the medical records committee.
dard format (e.g., SOAP [subjective, objective, assessment, 5. Determine the accepted method and format for submit-
and plan] or TITRS [title, introduction, text, recommenda- ting a proposal requesting authority to document phar-
tion, and signature]), and how to contact the pharmacist maceutical care in the PMR. In some organizations, a
(e.g., a telephone or pager number).4 written proposal may be required. If so, determine the
The authority to document pharmaceutical care in the PMR desired format (length, style, and necessary justifica-
comes with a responsibility to ensure that patient privacy and tion) and deadlines for proposal submission. An oral
confidentiality are safeguarded and the communication is con- presentation to the deciding bodies may be required. If
cise and accurate. Local, state, and federal guidelines and laws so, determine in advance the desired presentation format
(including the Health Insurance Portability and Accountability and supporting materials desired by these bodies.
Act of 1996 [HIPAA]) and risk management sensitivities should 6. Draft a written plan describing
be considered. Nonjudgmental language should be used, with a. Examples of information to be documented in the
care taken to avoid words that imply blame (e.g., error, mistake, PMR. It may be helpful to describe how this impor-
misadventure, and inadvertent) or substandard care (e.g., bad, tant information may be lost or miscommunicated
defective, inadequate, inappropriate, incorrect, insufficient, poor, if it is not documented in the PMR.
problem, and unsatisfactory).3 Facts should be documented ac- b. The locations within the PMR where documentation
curately, concisely, and objectively; such documentation should will be made and any special format or forms
reflect the goals established by the medical team. proposed. New forms will have to comply with
Documentation of a formal consultation solicited by HIPAA regulations and will require review and
a physician or other health care provider may include direct approval by specific organizational or medical
staff committees. To achieve the goal of effec-
recommendations or suggestions as appropriate. However,
tive communication among all the members of
unsolicited informal consultations, clinical impressions,
the health care team, compartmentalization of the
findings, suggestions, and recommendations should generally
PMR should be avoided.
be documented more subtly, with indirect recommendations
c. The persons who will be documenting pharma
presented in a way that allows the provider to decline the
ceutical care in the PMR (i.e., pharmacists,
suggestion without incurring a liability. For example, the
residents, or students). If pharmacy residents or
phrase “may want to consider” creates an opportunity for the
students will be making notations in the PMR,
suggestion to be acted upon or not, depending on presenting
procedures regarding authority and cosignatures
clinical factors.
will also have to be described.
7. Review the draft plan with the chair of the P&T commit-
Obtaining Authorization to Document tee, the director of nursing, the director of medical records,
Pharmaceutical Care and other appropriate administrative personnel, such as the
organization’s risk management officer and legal counsel.
The authority to document pharmaceutical care in the PMR is 8. Seek the endorsement and recommendation of the
granted by the health care organization in accordance with or- P&T committee.
ganizational and medical staff policies. Although documenting 9. In appropriate sequence, seek the endorsement or deci
pharmaceutical care in the PMR is a pharmacist’s professional sion of any other committees necessary for ultimate
responsibility, physicians and other health care professionals approval. Monitor the proposal’s course through the
may not be accustomed to or open to this practice. various committees and provide assistance, clarifica-
The following steps are recommended for obtaining tion, or additional data as necessary.
authorization to document pharmaceutical care in the PMR: 10. When the final approving body grants PMR documen-
tation authority, participate in the required policy
1. Determine the existing organizational and medical development and the communication of the new pol-
staff policies regarding authority for documentation in icy to the individuals or departments in the organiza-
the PMR. These policies may provide specific guidance tion that will be affected by the change (e.g., nurses,
on how to proceed. the medical staff, the quality-assurance staff, and the
2. Ascertain whether other nonphysician and nonnurse medical records department).
providers in the organization or affiliated organizations
have been granted authority to document patient care Training and CQI
activities in the PMR. If so, consult them regarding the
process used to establish the authority. Pharmacist documentation in the PMR is a skill that requires
3. Identify physicians in the organization who are ongoing training and evaluation.4 A temporary committee
willing to support documentation of pharmaceutical may be formed to manage the initial training required
care in the PMR. to implement pharmacist documentation in the PMR. That
committee may consider offering presentations by physicians MD: American Society of Hospital Pharmacists;
or other members of the health care team to provide their per- 1992:38–41.
spective on how to effectively communicate using the PMR. 4. Lacy CF, Saya FG, Shane RR. Quality of pharmacists’
The information in those presentations may be reinforced by documentations in patients’ medical records. Am J
workshops on documentation skills. Presentation and work- Health-Syst Pharm. 1996; 53:2171–5.
shop topics may include the choice of communication method 5. Matuschka P. Improving documentation of preop-
(i.e., when documentation in the PMR is preferred to erative antimicrobial prophylaxis. Am J Health-Syst
other means of communication), the documentation for- Pharm. 1998; 55:993–4.
mat (e.g., SOAP or TITRS), documentation etiquette, and 6. Lau A, Balen RM, Lam R,, et al. Using a personal digi-
legal requirements.4 Documentation skills should be demon- tal assistant to document clinical pharmacy services in
strated before a pharmacist is allowed to make notations in an intensive care unit. Am J Health-Syst Pharm. 2001;
the PMR.4 The ASHP Clinical Skills Program is another tool 58:1229–32.
for training pharmacists to use the PMR.3 7. Gordon W, Malyuk D, Taki J. Use of health-record
Documentation of pharmaceutical care should also be abstracting to document pharmaceutical care activities.
one of the many functions addressed in CQI efforts. Pharmacy Can J Hosp Pharm. 2000; 53:199–205.
department CQI efforts should include the development of
quality indicators that can be used to evaluate pharmacist
documentation in the PMR.4 Other CQI efforts might analyze
and improve systemwide policies and procedures for docu-
menting medication use.5 Periodic review of organizational These guidelines were reviewed in 2008 by the Council on Pharmacy
policies and procedures will allow for their revision in response Practice and by the Board of Directors and were found to still be ap-
to changes in health care and advances in technology, includ- propriate.
ing the availability of an electronic PMR.6,7
Approved by the ASHP Board of Directors, February 20, 2003.
Revised by the ASHP Council on Professional Affairs. Supercedes
References the ASHP Guidelines for Obtaining Authorization for Documenting
Pharmaceutical Care in Patient Medical Records dated November 16,
1. Hepler CD, Strand LM. Opportunities and responsibil- 1988.
ities in pharmaceutical care. Am J Hosp Pharm. 1990;
47:533–43. Copyright © 2003, American Society of Health-System Pharmacists,
2. American Society of Hospital Pharmacists. ASHP Inc. All rights reserved.
statement on pharmaceutical care. Am J Hosp Pharm.
1993; 50:1720–3. The bibliographic citation for this document is as follows: American
3. Shepherd MF. Professional conduct and use of patient Society of Health-System Pharmacists. ASHP guidelines on
medical records. In: ASHP Clinical Skills Program, documenting pharmaceutical care in patient medical records.
module 1: reviewing patient medical charts. Bethesda, Am J Health-Syst Pharm. 2003; 60:705–7.
ASHP Guidelines on Pharmacist-Conducted

Patient Education and Counseling
Purpose Concerns about improper medication use contributed

to the provision in the Omnibus Budget Reconciliation
Providing pharmaceutical care entails accepting responsibil- Act of 1990 (OBRA ’90) that mandated an offer to coun-
ity for patients’ pharmacotherapeutic outcomes. Pharmacists sel Medicaid outpatients about prescription medications.
can contribute to positive outcomes by educating and coun- Subsequently, states enacted legislation that generally ex-
seling patients to prepare and motivate them to follow their tends the offer-to-counsel requirement to outpatients not
pharmacotherapeutic regimens and monitoring plans. The covered by Medicaid. Future court cases may establish that
purpose of this document is to help pharmacists provide ef- pharmacists, in part because of changing laws, have a public
fective patient education and counseling. duty to warn patients of adverse effects and potential interac-
In working with individual patients, patient groups, tions of medications. The result could be increased liability
families, and caregivers, pharmacists should approach educa- for pharmacists who fail to educate and counsel their pa-
tion and counseling as interrelated activities. ASHP believes tients or who do so incorrectly or incompletely.10
pharmacists should educate and counsel all patients to the
extent possible, going beyond the minimum requirements Pharmacists’ Knowledge and Skills
of laws and regulations; simply offering to counsel is incon-
sistent with pharmacists’ responsibilities. In pharmaceutical In addition to a current knowledge of pharmacotherapy,
care, pharmacists should encourage patients to seek education pharmacists need to have the knowledge and skills to pro-
and counseling and should eliminate barriers to providing it. vide effective and accurate patient education and counsel-
Pharmacists should also seek opportunities to partici- ing. They should know about their patients’ cultures, es-
pate in health-system patient-education programs and to sup- pecially health and illness beliefs, attitudes, and practices.
port the educational efforts of other health care team members. They should be aware of patients’ feelings toward the health
Pharmacists should collaborate with other health care team system and views of their own roles and responsibilities for
members, as appropriate, to determine what specific informa- decision-making and for managing their care.11
tion and counseling are required in each patient care situation. Effective, open-ended questioning and active listen-
A coordinated effort among health care team members will ing are essential skills for obtaining information from and
enhance patients’ adherence to pharmacotherapeutic regimens, sharing information with patients. Pharmacists have to adapt
monitoring of drug effects, and feedback to the health system. messages to fit patients’ language skills and primary lan-
ASHP believes these patient education and counseling guages, through the use of teaching aids, interpreters, or cul-
guidelines are applicable in all practice settings—including tural guides if necessary. Pharmacists also need to observe
acute inpatient care, ambulatory care, home care, and long-term and interpret the nonverbal messages (e.g., eye contact, fa-
care—whether these settings are associated with integrated cial expressions, body movements, vocal characteristics) pa-
health systems or managed care organizations or are freestand- tients give during education and counseling sessions.12
ing. The guidelines may need to be adapted; for example, for Assessing a patient’s cognitive abilities, learning style,
use in telephone counseling or for counseling family members and sensory and physical status enables the pharmacist to
or caregivers instead of patients. Patient education and counsel- adapt information and educational methods to meet the pa-
ing usually occur at the time prescriptions are dispensed but tient’s needs. A patient may learn best by hearing spoken
may also be provided as a separate service. The techniques and instructions; by seeing a diagram, picture, or model; or by
the content should be adjusted to meet the specific needs of the directly handling medications and administration devices. A
patient and to comply with the policies and procedures of the patient may lack the visual acuity to read labels on prescrip-
practice setting. In health systems, other health care team mem- tion containers, markings on syringes, or written handout ma-
bers share in the responsibility to educate and counsel patients terial. A patient may be unable to hear oral instructions or may
as specified in the patients’ care plans. lack sufficient motor skills to open a child-resistant container.
In addition to assessing whether patients know how to
Background use their medications, pharmacists should attempt to under-
stand patients’ attitudes and potential behaviors concerning
The human and economic consequences of inappropriate medication use. The pharmacist needs to determine whether
medication use have been the subject of professional, public, a patient is willing to use a medication and whether he or she
and congressional discourse for more than two decades.1–5 intends to do so.13,14
Lack of sufficient knowledge about their health problems
and medications is one cause of patients’ nonadherence to Environment
their pharmacotherapeutic regimens and monitoring plans;
without adequate knowledge, patients cannot be effective Education and counseling should take place in an environ-
partners in managing their own care. The pharmacy profes- ment conducive to patient involvement, learning, and ac-
sion has accepted responsibility for providing patient educa- ceptance—one that supports pharmacists’ efforts to establish
tion and counseling in the context of pharmaceutical care caring relationships with patients. Individual patients, groups,
to improve patient adherence and reduce medication-related families, or caregivers should perceive the counseling envi-
problems.6–9 ronment as comfortable, confidential, and safe.
Education and counseling are most effective when con- what the patient expects, and ask the patient to describe
ducted in a room or space that ensures privacy and opportunity or show how he or she will use the medication.
to engage in confidential communication. If such an isolated Patients returning for refill medications should be
space is not available, a common area can be restructured to asked to describe or show how they have been using
maximize visual and auditory privacy from other patients or their medications. They should also be asked to de-
staff. Patients, including those who are disabled, should have scribe any problems, concerns, or uncertainties they
easy access and seating. Space and seating should be adequate are experiencing with their medications.
for family members or caregivers. The design and placement of 3. Provide information orally and use visual aids or dem-
desks and counters should minimize barriers to communication. onstrations to fill patients’ gaps in knowledge and un-
Distractions and interruptions should be few, so that patients derstanding. Open the medication containers to show
and pharmacists can have each other’s undivided attention. patients the colors, sizes, shapes, and markings on oral
The environment should be equipped with appropriate solids. For oral liquids and injectables, show patients
learning aids, e.g., graphics, anatomical models, medication the dosage marks on measuring devices. Demonstrate
administration devices, memory aids, written material, and the assembly and use of administration devices such as
audiovisual resources. nasal and oral inhalers. As a supplement to face-to-face
oral communication, provide written handouts to help
Pharmacist and Patient Roles the patient recall the information.
If a patient is experiencing problems with his or
Pharmacists and patients bring to education and counseling her medications, gather appropriate data and assess the
sessions their own perceptions of their roles and responsibil- problems. Then adjust the pharmacotherapeutic regi-
ities. For the experience to be effective, the pharmacist and mens according to protocols or notify the prescribers.
patient need to come to a common understanding about their 4. Verify patients’ knowledge and understanding of med-
respective roles and responsibilities. It may be necessary ication use. Ask patients to describe or show how they
to clarify for patients that pharmacists have an appropriate will use their medications and identify their effects.
and important role in providing education and counseling. Observe patients’ medication-use capability and accu-
Patients should be encouraged to be active participants. racy and attitudes toward following their pharmaco-
The pharmacist’s role is to verify that patients have suffi- therapeutic regimens and monitoring plans.
cient understanding, knowledge, and skill to follow their phar-
macotherapeutic regimens and monitoring plans. Pharmacists Content
should also seek ways to motivate patients to learn about their
treatment and to be active partners in their care. Patients’ role The content of an education and counseling session may in-
is to adhere to their pharmacotherapeutic regimens, monitor clude the information listed below, as appropriate for each
for drug effects, and report their experiences to pharmacists or patient’s pharmacotherapeutic regimen and monitoring
other members of their health care teams.12,15 Optimally, the plan.8,9,20 The decision to discuss specific pharmacothera-
patient’s role should include seeking information and present- peutic information with an individual patient must be based
ing concerns that may make adherence difficult. on the pharmacist’s professional judgment.
Depending on the health system’s policies and proce-
dures, its use of protocols or clinical care plans, and its cre- 1. The medication’s trade name, generic name, common
dentialing of providers, pharmacists may also have disease synonym, or other descriptive name(s) and, when ap-
management roles and responsibilities for specified catego- propriate, its therapeutic class and efficacy.
ries of patients. This expands pharmacists’ relationships with 2. The medication’s use and expected benefits and action.
patients and the content of education and counseling sessions. This may include whether the medication is intended
to cure a disease, eliminate or reduce symptoms, arrest
Process Steps or slow the disease process, or prevent the disease or
a symptom.
Steps in the patient education and counseling process will 3. The medication’s expected onset of action and what to
vary according to the health system’s policies and proce- do if the action does not occur.
dures, environment, and practice setting. Generally, the 4. The medication’s route, dosage form, dosage, and ad-
following steps are appropriate for patients receiving new ministration schedule (including duration of therapy).
medications or returning for refills12–21: 5. Directions for preparing and using or administering
the medication. This may include adaptation to fit pa-
1. Establish caring relationships with patients as appro- tients’ lifestyles or work environments.
priate to the practice setting and stage in the patient’s 6. Action to be taken in case of a missed dose.
health care management. Introduce yourself as a phar- 7. Precautions to be observed during the medication’s
macist, explain the purpose and expected length of the use or administration and the medication’s potential
sessions, and obtain the patient’s agreement to partici- risks in relation to benefits. For injectable medications
pate. Determine the patient’s primary spoken language. and administration devices, concern about latex al-
2. Assess the patient’s knowledge about his or her health lergy may be discussed.
problems and medications, physical and mental capa- 8. Potential common and severe adverse effects that may
bility to use the medications appropriately, and attitude occur, actions to prevent or minimize their occurrence,
toward the health problems and medications. Ask open- and actions to take if they occur, including notifying the
ended questions about each medication’s purpose and prescriber, pharmacist, or other health care provider.
9. Techniques for self-monitoring of the pharmacotherapy.
10. Potential drug–drug (including nonprescription), 5. Johnson JA, Bootman JL. Drug-related morbidity and
drug–food, and drug–disease interactions or contrain- mortality: a cost-of-illness model. Arch Intern Med.
dications. 1995; 155:1949–56.
11. The medication’s relationships to radiologic and labo- 6. Summary of the final report of the Scope of Pharmacy
ratory procedures (e.g., timing of doses and potential Practice Project. Am J Hosp Pharm. 1994; 51:2179–82.
interferences with interpretation of results). 7. Hepler CD, Strand LM. Opportunities and responsibil-
12. Prescription refill authorizations and the process for ities in pharmaceutical care. Am J Hosp Pharm. 1990;
obtaining refills. 47:533–42.
13. Instructions for 24-hour access to a pharmacist. 8. Hatoum HT, Hutchinson RA, Lambert BL. OBRA 90:
14. Proper storage of the medication. patient counseling—enhancing patient outcomes. US
15. Proper disposal of contaminated or discontinued medi- Pharm. 1993; 18(Jan):76–86.
cations and used administration devices. 9. OBRA ’90: a practical guide to effecting pharmaceuti-
16. Any other information unique to an individual patient cal care. Washington, DC: American Pharmaceutical
or medication. Association; 1994.
10. Lynn NJ, Kamm RE. Avoiding liability problems. Am
These points are applicable to both prescription and nonpre- Pharm. 1995; NS35(Dec):14–22.
scription medications. Pharmacists should counsel patients 11. Herrier RN, Boyce RW. Does counseling improve
in the proper selection of nonprescription medications. compliance? Am Pharm. 1995; NS35(Sep):11–2.
Additional content may be appropriate when pharma- 12. Foster SL, Smith EB, Seybold MR. Advanced coun-
cists have authorized responsibilities in collaborative disease seling techniques: integrating assessment and inter-
management for specified categories of patients. Depending vention. Am Pharm. 1995; NS35(Oct):40–8.
on the patient’s disease management or clinical care plan, 13. Bond WS, Hussar DA. Detection methods and strate-
the following may be covered: gies for improving medication compliance. Am J Hosp
Pharm. 1991; 48:1978–88.
1. The disease state: whether it is acute or chronic and its 14. Felkey BG. Adherence screening and monitoring. Am
prevention, transmission, progression, and recurrence. Pharm. 1995; NS35(Jul):42–51.
2. Expected effects of the disease on the patient’s normal 15. Herrier RN, Boyce RW. Establishing an active patient
daily living. partnership. Am Pharm. 1995; NS35(Apr):48–57.
3. Recognition and monitoring of disease complications. 16. Boyce RW, Herrier RN, Gardner M. Pharmacist-
patient consultation program, unit I: an interactive
Documentation approach to verify patient understanding. New York:
Pfizer Inc.; 1991.
Pharmacists should document education and counseling in 17. Pharmacist-patient consultation program, unit II: coun-
patients’ permanent medical records as consistent with the seling patients in challenging situations. New York:
patients’ care plans, the health system’s policies and proce- Pfizer Inc.; 1993.
dures, and applicable state and federal laws. When pharma- 18. Pharmacist-patient consultation program, unit III: counsel-
cists do not have access to patients’ medical records, educa- ing to enhance compliance. New York: Pfizer Inc.; 1995.
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patient profiles, on the medication order or prescription data. Am Pharm. 1991; NS31(Jul):65–70.
form, or on a specially designed counseling record. 20. Herrier RN, Boyce RW. Communicating risk to pa-
The pharmacist should record (1) that counseling was tients. Am Pharm. 1995; NS35(Jun):12–4.
offered and was accepted and provided or refused and (2) the 21. APhA special report: medication administration prob-
pharmacist’s perceived level of the patient’s understanding.9 As lem solving in ambulatory care. Washington, DC: Ameri-
appropriate, the content should be documented (for example, can Pharmaceutical Association; 1994.
counseling about food–drug interactions). All documentation
should be safeguarded to respect patient confidentiality and
privacy and to comply with applicable state and federal laws.10 This guideline was reviewed in 2011 by the Council on Pharmacy
Practice and by the ASHP Board of Directors and was found to still
be appropriate.
References
Approved by the ASHP Board of Directors, November 11, 1996.
1. Smith MC. Social barriers to rational drug therapy. Am Revised by the ASHP Council on Professional Affairs. Supersedes
J Hosp Pharm. 1972; 29:121–7. the ASHP Statement on the Pharmacist’s Role in Patient-Education
2. Priorities and approaches for improving prescrip- Programs dated June 3, 1991, and ASHP Guidelines on Pharmacist-
tion medicine use by older Americans. Washington, Conducted Patient Counseling dated November 18, 1992.
DC: National Council on Patient Information and
Education; 1987. Copyright © 1997, American Society of Health-System Pharmacists,
3. Manasse HR Jr. Medication use in an imperfect world: Inc. All rights reserved.
drug misadventuring as an issue of public policy, part
1. Am J Hosp Pharm. 1989; 46:929–44. The bibliographic citation for this document is as follows: American
4. Manasse HR Jr. Medication use in an imperfect world: Society of Health-System Pharmacists. ASHP guidelines on
drug misadventuring as an issue of public policy, part pharmacist-conducted patient education and counseling. Am J Health-
2. Am J Hosp Pharm. 1989; 46:1141–52. Syst Pharm. 1997; 54:431–4.
ASHP Guidelines on the Pharmacist’s Role

in the Development, Implementation,
and Assessment of Critical Pathways
Purpose
Summary of guidelines. Because pharmacotherapy
The purpose of these guidelines is (1) to describe the pharma- is a central component of many critical pathways,
cist’s role in the development, implementation, and assessment pharmacists should take leadership roles in their
of critical pathways (CPs) and (2) to help pharmacists prepare development, implementation, and assessment.
for that responsibility. Because pharmacotherapy is a central Pharmacists can improve the development of crit-
component of many CPs, pharmacists should take leadership ical pathways by ensuring the evidence-based selection
roles in the development, implementation, and assessment of of medications, establishing measures for monitoring
CPs. By assuming leadership roles, pharmacists can help im- patients for drug efficacy and adverse effects, and evaluat
prove patient outcomes, contribute to cost-effective patient ing the proposed critical pathway for patient safety.
care, and promote multidisciplinary approaches to patient care Pharmacists can improve the implementation of
and performance improvement. Although pharmacist involve- critical pathways by documenting processes and out
ment in the early stages of CP development is crucial to suc- comes, ensuring proper patient selection and medica
cess, CP development is generally cyclical, and pharmacists tion use, monitoring patients for drug efficacy and
should seek opportunities to become involved at any stage in adverse effects, and providing for continuity of care.
the cycle of CP development, implementation, and assessment. Pharmacists can improve the assessment of critical
pathways by measuring and analyzing processes and
Background outcomes, disseminating the results of those analy-
ses, and reviewing the critical pathways’ pharmaco-
The development of CPs has been stimulated by the desire to therapy to keep pace with changes in best practices.
improve patient outcomes by applying evidence-based clini-
cal practice guidelines; increased interest in measuring and
improving the quality of health care, including continuous- disease or procedure.37 Pharmacists perform the following
quality-improvement (CQI) initiatives; and managed care and functions in a typical CP: oversee the selection of medica-
other market-driven health care reforms. CPs can be defined as tions by using an evidence-based approach, develop the cri-
patient care management plans that delineate key steps along teria for medication selection or dosages, monitor patients
an optimal treatment timeline to achieve a set of predetermined for drug efficacy and adverse effects (or establish param-
intermediate and ultimate goals for patients who have clearly eters for monitoring), and ensure continuity of care across
defined diagnoses or require certain procedures.1 CPs have also the health system. The following describes common steps in
been called care guides, clinical pathways, clinical care plans, the development, implementation, and assessment of CPs.3
and care maps.2 CPs derive from the industrial engineering con-
cept of critical paths3 and were originally associated with inpa- 1. Select diagnoses and procedures. Diagnoses and proce
tient acute care and used primarily by nurses. CPs have evolved dures selected for CP development usually include those
to incorporate the spectrum of patient care providers and set- with high process variability, high cost, high patient volume,
tings and to include CQI concepts.4 CPs and similar tools are and high risk. CPs can be developed for common or spe-
developed in many facilities for many purposes.5–20 Although cialized diagnoses (e.g., myocardial infarction, diabetes
dismissed by some critics as “cookbook medicine,” CPs have in mellitus) or procedures (e.g., transurethral prostatectomy,
some cases been shown to improve patient outcomes21–26 and to coronary artery bypass grafting), for diagnoses that are
reduce health care expenses.27–36 ASHP believes that carefully likely to cause changes in health status (e.g., uncontrolled
developed and skillfully managed CPs can improve the care of asthma), and for diseases requiring complicated phar-
patients across the spectrum of health-system settings, as well macotherapeutic regimens (e.g., AIDS). The criteria for
as improve the allocation of scarce health care resources. selection should be developed with input from adminis
trative and clinical leaders to ensure institutionwide
Typical CP Process acceptance and should be based on scientific evidence.
2. Appoint a development team. The development team
Each health system will use a process of CP development, should include key health care providers from all
implementation, and assessment that meets its own needs organizational components involved in the CP. The
within its own structure, culture, practice settings, and poli- importance of a multidisciplinary approach to CP
cies and procedures, but these processes do share common development cannot be overemphasized. If possible,
elements. Typically, once a disease or procedure is selected consideration should be given to including a patient
for CP development, a multidisciplinary team analyzes its representative on the CP development team. Although
current management (including process variances, costs, and insurance carriers and managed care providers may
outcomes), evaluates the scientific literature, and develops a not have representatives on the development team,
plan of care. The planned actions for each discipline on the their protocols or guidelines should be evaluated by
health care team are mapped on a timeline for the specific the team for inclusion in the CP as appropriate.
3. Conduct a search of the scientific literature. A litera- expected outcomes. In some practice settings,
ture and database search conducted early in the pro- the patient may be an active partner in CP
cess will help identify measures for assessing current decision-making and implementation.
processes and outcomes and will help ensure an evi- c. Patient safety
dence-based approach to the CP. • Identify potential risks to the patient that
4. Document current processes and outcomes. The may arise from use of the CP. For example,
current processes, costs, variances, and outcomes need the CP could be subjected to the institu-
to be documented, usually through flow charting of the tion’s failure-mode and effects analysis,
current process, retrospective chart review, and bench- or the medication safety self-assessment
marking. Benchmarking may be internal or external to tool of the Institute for Safe Medication
the health system. Depending on the health system’s Practices could be used to assess the safety
resources, benchmarking may rely on chart review or of the practices outlined in the CP.38
may use computerized databases that compare physi- d. Monitoring
cians’ use of resources, health-system costs, and out- • Identify measures of conformance and
comes for specific diagnosis-related groups. This step variance so that the CP and the resulting
identifies the health system’s practice and compares it outcomes can be continuously improved.
with published clinical guidelines that are preferably Variances are deviations from the CP that
consensus based (e.g., guidelines from the Agency for may be positive or negative, avoidable or
Healthcare Research and Quality or the American Heart unavoidable, consequential or inconse-
Association). The team developing the CP should use quential. Sources of variances include pa-
an evidence-based approach to identify, discuss, and tient responses to medications, physician
resolve the gaps between clinical guidelines and current decisions, and system breakdowns.
local practice. Input from the practitioners who will be e. Documentation
involved in the CP is crucial to the success of this process • Develop a single, multidisciplinary work
evaluation and CP development in general. sheet or other tool that describes the CP’s
5. Develop the CP. Multidisciplinary, standardized develop- actions and time frames and provides
ment of the CP ensures integration of care and elimina- spaces for documenting that actions were
tion of duplication and oversights. The CP should state its performed.12 Describe how this tool will
goals, define actions essential to achieving those goals, be used and how data will be collected.
provide for patient education, outline assessment of 6. Obtain approval for the CP and educate participants. To
patient safety, identify measures of conformance and ensure global acceptance among all health care provider
outcomes, and describe required documentation. The ac- groups, the CP should be approved by appropriate com-
tions and resources required for implementation should mittees, especially those of the medical staff. The impact
be discussed and agreed upon by all disciplines involved. of CP implementation on practitioner workloads will re-
a. Goals and outcomes quire careful consideration, and departmental policies or
• Define the specific goals or measurable procedures may need to be modified. The pharmacy and
outcomes of the CP (e.g., decreased length therapeutics (P&T) committee should review pharmaco-
of stay, decreased ventilator time, reduced therapeutic issues associated with the CP early enough
overall patient cost, decreased pain scores, during development that therapeutic concerns can be
early ambulation). addressed as they arise rather than after the CP is imple-
• Select the areas of focus or categories of ac- mented. After the CP is approved, all health care team
tions essential to achieving the goals and out- members involved in the care of the patients affected
comes. To ensure consistency and continuity, by the CP should be educated about the anticipated
these areas of focus should be standardized outcomes, specific actions and time frames, and profes-
for all CPs developed within a health system; sional responsibilities associated with the CP.
examples of focus areas are treatments, medi- 7. Implement the CP. After the necessary education and train-
cations, and patient education and counseling. ing of providers, the CP is available for use. Starting the CP
• Determine the appropriate time frame. This as a pilot project for a small number of patients may pro-
will vary according to the disease or proce- vide valuable initial assessments that will facilitate wider
dure being addressed and the practice set- implementation. Staff members should be designated to
ting (e.g., emergency room, ambulatory care identify patients suitable for the CP and to guide their en-
clinic, acute care hospital). The time frame rollment and the CP’s use. Patients enrolled in a CP are as-
may be specified in minutes, hours, days, or signed to a health care team whose members have specific
phases. A workload assessment may be re- responsibilities for actions and time frames.
quired to develop appropriate time frames. 8. Assess the CP. Because not all consequences of a CP
• Define the activity for the focus area under are foreseeable, CPs require periodic assessment.
the appropriate time frame (e.g., “phar- Assessments after a few days or weeks of use may
macist provides medication-use education gauge only the feasibility of the CP and not its success
and counseling on discharge day”). in achieving desired goals, but they should identify
b. Patient education unexpected problems that may require modifications
• Modify the CP, using lay terms in the patient’s to the CP. Surveys of health care practitioners may be
primary language, to educate the patient about useful in such initial assessments. Assessments after a
activities to be performed, time frames, and few months of use may provide an initial perspective
on the CP’s success but may not be sufficient to fully item for the P&T committee meeting and for other multi-
evaluate outcomes. Assessments after longer periods disciplinary clinical and departmental meetings.
should produce evidence supporting the CP’s original 4. Monitor pharmacy, nursing, quality management, health-
goals. Regular analysis of the results and variances, system, health care, and management literature for ideas
as well as new information (e.g., new indications for on CP development, implementation, and assessment.
medications) and technologies (e.g., new pharmaco- CPs from other institutions may be used as examples of
therapy), provides data for a root-cause analysis and and frameworks for mapping care, but they should not be
continuous improvement of the CP. adopted directly, because acceptance and use are greater
9. Disseminate the results of the assessment. The results when CPs are developed or adapted by their users.
of the assessment should be shared not just with health- 5. Identify opportunities for contributing, through the
system managers or members of the CP development or provision of pharmaceutical care, to the health sys-
oversight committees but with all staff involved in the tem’s patient care delivery and improvement efforts.
CP. Widespread dissemination allows for more sugges-
tions for improvement from all members of the health Initiating Involvement. Pharmacists should begin their in-
care team and encourages acceptance of any alterations volvement in the CP process in ways most appropriate to their
in the CP required by the assessment. Publishing the re- health system’s structure, culture, practice settings, and poli-
sults in a journal, sharing the experience with a practice cies and procedures. Involvement may vary substantially from
network, or presenting the results at a meeting expands one health system to another, but in general pharmacists should
the general pool of knowledge concerning CPs.
1. Develop relationships with nursing, medical, dietary,
Pharmacist Involvement laboratory, quality management, risk management,
respiratory care, and other personnel through routine
These guidelines suggest actions to help prepare pharma- meetings, nursing and medical forums, and other
cists and pharmacy departments for involvement in the multidisciplinary opportunities. These relationships
development, implementation, and assessment of CPs at should be used to promote pharmacists’ contributions
various levels of care and in different practice settings. The to collaborative patient care. The pharmacy depart-
applicability of these guidelines depends on a pharmacist’s ment should support the use of CPs as an effective way
or pharmacy department’s current level of involvement in to integrate and align services, processes, and costs.
patient care and CPs. Pharmacists should focus on incorpo- 2. Support or initiate the implementation of a multidis-
rating contemporary pharmaceutical care principles (e.g., as- ciplinary team for CP development and oversight and
sessing medication orders, developing pharmacotherapeutic ensure that the pharmacy department and the P&T com-
regimens and monitoring plans, educating and counseling mittee are represented on the oversight committee.
patients, calculating doses according to pharmacokinetic 3. Seek leadership roles on the health system’s CP oversight
principles, conducting medication-use evaluations [MUEs], committee and development teams but be willing to
and managing anticoagulation therapy) in the development, accept subordinate roles. For example, pharmacists
implementation, and assessment of CPs.39–42 should be willing to lead or assist with literature evalu-
ation for the health system’s CP development teams.
Preparing for Involvement in CP Development. Pharmacists 4. Identify qualities required for the pharmacist’s role
should learn about their health system’s approach to CP devel- and develop a consistent process for selecting the most
opment and assess their readiness for involvement. They should appropriate pharmacists to participate on the various
CP development teams.
1. Review the health system’s current strategic plan 5. Ensure the ongoing involvement of the P&T committee
with respect to CPs. Because CPs are inherently colin the CP process. The P&T committee can facilitate
laborative, pharmacists should try to understand this the process by
strategic plan from the perspective of other health care • Reviewing and endorsing the pharmacotherapy
providers, seeking advice from them when necessary. proposed for inclusion in each CP.
When reviewing the strategic plan, pharmacists should • Establishing a standing P&T subcommittee or
also consider the needs of specific patient populations liaison position to assist CP development teams.
served by their institutions. The subcommittee or liaison would have the
2. Educate the pharmacy staff on the purposes and pro- opportunity to educate the CP team about the
cesses of CP development and the contents of CPs. The formulary process, the process for MUE, the appro
patient care decisions required in CPs demand clinical priate use of restricted medications, and other
knowledge, and the pharmacotherapy involved should critical medication-use issues.
be based on evidence in the scientific literature. This • Publishing CPs and information about the health
clinical knowledge is fundamental to the CP. An effec- system’s experiences with CPs in the P&T com-
tive contributor to the CP process needs to first acquire mittee newsletter.
the clinical knowledge on which the CP is based and • Developing the drug therapy portion of the CP
then use CQI, teamwork, negotiation, and administra- assessment into an MUE.
tive skills to develop, implement, and assess the CP. 6. Emphasize to pharmacists, other health care providers,
3. Discuss CP experiences with pharmacy colleagues within and health-system administrators pharmacists’ respon-
and outside the health system. Pharmacists should create a sibility for implementing CP steps that involve phar-
forum within the health system for ongoing dialogue about macotherapeutic regimens and monitoring, medication
CPs; for example, CPs could be made a regular agenda distribution, and patient education and counseling.
7. Initiate, after appropriate approvals, the development diagnosis-related-group classification) and comparing
of the pharmacotherapeutic components of CPs. these results with the health system’s experience.
8. Offer to evaluate and adapt the pharmacotherapeutic 2. Ensuring that an internal system of CP tracking and
components of existing protocols and guidelines for therapeutic review is in place for the rapid insertion
CPs under development. Maintain a pharmacotherapy of new, more effective therapies into the CP and that
database to facilitate CP updates when new medications CPs are integrated into the institution’s CQI processes.
and pharmacotherapeutic alternatives become available. 3. Assisting the development of patient satisfaction surveys.
9. Develop patient education and counseling materials 4. Monitoring the results of the CPs and using them to
for the pharmacotherapeutic components of CPs and perform MUEs.42 Since patients enrolled in CPs are
develop plans for pharmacists or other members of the receiving predetermined pharmacotherapeutic regi-
health care team to provide education and counseling mens and monitoring, this is an excellent opportunity
to patients. to perform disease- and outcome-oriented MUEs. The
10. Advocate the development and use of preprinted med- pharmacist should review the variances and outcomes
ication orders (hard copy or electronic) and consistent associated with the CP, determine the effects of phar-
use of terminology (e.g., generic drug names, decimals macotherapy, and use this analysis to modify the CP.
and units of measurement, and standardized terms and The pharmacotherapeutic component must be specific
abbreviations) within the CP. enough (e.g., specifying the medication and dosage)
11. Be proactive in anticipating alternative processes or that its influence on the outcomes can be determined
drug regimens that may be required in unusual circum- with confidence.
stances, such as drug shortages. 5. Ensuring that CPs are updated when there are changes in
institutional practices (e.g., formulary changes) or when
Maintaining Involvement. Pharmacists’ continued involvement external practices change (e.g., guidelines are revised,
in CPs will depend on their ability to demonstrate their dosage or monitoring recommendations are revised).
contributions to patient care delivery and improvement to
the CP oversight committee and development teams and Ensuring the Continuity of a CP. Many CPs require conti-
to the health system’s administration. To accomplish this,
nuity of care across various levels of care and practice set-
pharmacists can
tings. Such CPs should specify referral patterns among the
levels of care and practice settings. To help accomplish this,
1. Monitor the literature of pharmacy, nursing, quality
pharmacists can
management, health systems, health care, and manage-
ment for ideas on CP development, implementation,
1. Ensure that members of all organizational components
and assessment.
are included in the development and assessment of the
2. Identify new areas for CP development on the basis of
CP as appropriate for the particular disease or proce-
medication-use data (e.g., medication error data and
dure. Included might be personnel in the emergency
MUE findings).
department, the operating room, the intensive care unit,
3. Incorporate CPs into the pharmacy department’s cul-
ture by building responsibilities and performance ex- the step-down unit, the general nursing unit, the rehabil-
pectations for CP development, implementation, and itation unit, the long-term-care facility, the ambulatory
assessment into pharmacists’ job descriptions. care clinic, the laboratory, and the home care service.
4. Identify and train pharmacy staff on their roles and 2. Develop relationships with ambulatory care, home care,
responsibilities for implementing the pharmaceutical and long-term-care pharmacists and other health care
care components of CPs. providers to foster the seamless provision of pharmaceu-
5. Provide objective clinical input that is based on scien- tical care by inviting pharmacist members of managed
tific evidence. care organizations to participate in CP development,
6. Ensure consistent use of terminology (e.g., generic drug exchanging CPs with the managed care organizations,
names, decimals and units of measurement, and stan- and creating work teams to ensure the continuity of care.
dardized terms and abbreviations), rational medication 3. Organize interdisciplinary sharing of information
use, and appropriate monitoring. This could be done by (e.g., recent laboratory test results) and documentation
the P&T committee or by a pharmacist who coordinates that are useful to all health care providers.
and reviews the pharmacotherapeutic efforts of all CPs. 4. Develop a plan to communicate and monitor both
7. Maintain good working relationships with CP devel- internal and external CPs so that pharmacists have a
opment teams. The pharmacist member should be con- full understanding of the CP process and can evaluate
fident, assertive, cooperative, and effective in commu- and adjust the CP as necessary when new therapeutic
nicating with other health care providers. modalities emerge. Optimize this by using electronic
8. Develop and maintain clinical and management skills and Internet technology to rapidly insert new pharma-
through ongoing self-education. cotherapies into CPs when appropriate and evaluate
which pharmacotherapies are included in which CPs
Contributing to the CQI Aspects of CPs. The pharmacist to ensure consistency in medication management.
should ensure that the pharmaceutical care actions of the CP 5. Initiate dialogue among pharmacists to ensure the
contribute to patient satisfaction, desired clinical outcomes, continuity of the individual patient’s CP. For example,
and financial goals by when a patient is admitted, the hospital pharmacist
should, if necessary and with the patient’s permission,
1. Monitoring the literature for best-practice results re- contact the patient’s community pharmacist or man-
lating to specific disease states (as defined by federal aged care company to obtain information as allowed
under local, state, and federal laws (e.g., the Health 5. Koch KE. Opportunities for pharmaceutical care with
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34. Uchiyama K, Takifuji K, Tani M,, et al. Effectiveness can Society of Health-System Pharmacists. ASHP guidelines on
of the clinical pathway to decrease length of stay and the pharmacist’s role in the development, implementation, and
cost for laparoscopic surgery. Surg Endosc. 2002; assessment of critical pathways. Am J Health-Syst Pharm. 2004;
16:1594–7. 61:939–45.
35. Wilson SD, Dahl BB, Wells RD. An evidence-based
clinical pathway for bronchiolitis safely reduces anti-
biotic overuse.Am J Med Qual. 2002; 17:195–9.
ASHP Guidelines on a Standardized Method

for Pharmaceutical Care
Need for a Standardized Method • Designing a monitoring plan,
• Developing a pharmacotherapeutic regimen and cor-
The purpose of this document is to provide pharmacists with a responding monitoring plan in collaboration with the
standardized method for the provision of pharmaceutical care patient and other health professionals,
in component settings of organized health systems. Since the • Initiating the pharmacotherapeutic regimen,
introduction of the pharmaceutical care concept1 and the de- • Monitoring the effects of the pharmacotherapeutic
velopment of the ASHP Statement on Pharmaceutical Care,2 regimen, and
considerable variation in pharmacists’ provision of pharma- • Redesigning the pharmacotherapeutic regimen and
ceutical care has been noted. ASHP believes pharmacists need monitoring plan.
a standardized method for providing pharmaceutical care.
This document describes a standardized method based These major functions have been adapted, in part, from the
on functions that all pharmacists should perform for indi- pharmacotherapy series of the ASHP Clinical Skills Program
vidual patients in organized health systems. The use of this and the final report of the ASHP Model for Pharmacy
method would foster consistency in the provision of phar- Practice Residency Learning Demonstration Project.
maceutical care in all practice settings. It would support
continuity of care both within a practice setting (e.g., among Collecting and Organizing Pertinent Patient-Specific Infor
pharmacists on different work shifts caring for an acutely ill mation. Information should be collected and used as a patient-
inpatient) and when a patient moves among practice settings specific database to prevent, detect, and resolve the patient’s
(e.g., when an inpatient is discharged to home or ambula- medication-related problems and to make appropriate medica-
tory care). Further, a standardized method would establish tion-therapy recommendations. The database should include the
consistent documentation so that patient-specific and medi- following sections, each containing specific types of informa-
cation-related information could be shared from pharmacist tion to the extent that it is relevant to medication therapy:
to pharmacist and among health professionals.
The need to identify the functions involved in phar- Demographic
maceutical care and the critical skills necessary to provide Name
it was discussed at the San Antonio consensus conference Address
in 1993.3 Functions for the provision of pharmaceutical care Date of birth
were identified by the practitioner task force of the Scope Sex
of Pharmacy Practice Project.4 Those functions have been Religion and religious affiliation
defined in more detail in the pharmacotherapy series of the Occupation
ASHP Clinical Skills Program.5–9
These Guidelines are not specific to any practice set- Administrative
ting. ASHP believes this standardized method can be used in Physicians and prescribers
acute care (hospitals), ambulatory care, home care, long-term Pharmacy
care, and other practice settings. Functions can be tailored as Room/bed numbers
appropriate for a given practice setting. It is recognized that Consent forms
the degree of standardization and tailoring appropriate for a Patient identification number
given work site will depend on the practice environment, the
organization of services (e.g., patient-focused or department- Medical
focused), working relationships with other health profession- Weight and height
als, the health system’s and patient’s financial arrangements, Acute and chronic medical problems
and the health system’s policies and procedures. ASHP be- Current symptoms
lieves the use of the systematic approaches encouraged by Vital signs and other monitoring information
these guidelines will assist pharmacists in implementing and Allergies and intolerances
providing pharmaceutical care in their work sites. Past medical history
Laboratory information
Functions of Pharmaceutical Care Diagnostic and surgical procedures
ASHP believes that a standardized method for the provision Medication therapy
of pharmaceutical care should include the following: Prescribed medications
Nonprescription medications
• Collecting and organizing patient-specific information, Medications used prior to admission
• Determining the presence of medication-therapy Home remedies and other types of health products used
problems, Medication regimen
• Summarizing patients’ health care needs, Compliance with therapy
• Specifying pharmacotherapeutic goals, Medication allergies and intolerances
• Designing a pharmacotherapeutic regimen, Concerns or questions about therapy
Assessment of understanding of therapy Determining the Presence of Medication-Therapy Problems.

Pertinent health beliefs Conclusions should be drawn from the integration of
medication-, disease-, laboratory test-, and patient-specific in-
Behavioral/lifestyle formation. The patient’s database should be assessed for any
Diet of the following medication-therapy problems:
Exercise/recreation
Tobacco/alcohol/caffeine/other substance use or abuse • Medications with no medical indication,
Sexual history • Medical conditions for which there is no medication
Personality type prescribed,
Daily activities • Medications prescribed inappropriately for a particular
medical condition,
Social/economic • Inappropriate medication dose, dosage form, schedule,
Living arrangement route of administration, or method of administration,
Ethnic background • Therapeutic duplication,
Financial/insurance/health plan • Prescribing of medications to which the patient is allergic,
• Actual and potential adverse drug events,
Objective and subjective information should be obtained di- • Actual and potential clinically significant drug–drug,
rectly from patients (and family members, other caregivers, drug–disease, drug–nutrient, and drug–laboratory test
and other health professionals as needed). A physical assess- interactions,
ment should be performed as needed. In addition, informa- • Interference with medical therapy by social or recre-
tion can be obtained by reviewing the patient’s health record ational drug use,
and other information sources. • Failure to receive the full benefit of prescribed
Information in the patient’s health record should be un- medication therapy,
derstood, interpreted, and verified for accuracy before deci- • Problems arising from the financial impact of medication
sions are made about the patient’s medication therapy. With therapy on the patient,
access to the patient’s health record comes the professional • Lack of understanding of the medication therapy by
responsibility to safeguard the patient’s rights to privacy the patient, and
and confidentiality. The Privacy Act of 1974,10 professional • Failure of the patient to adhere to the medication regimen.
practice policies,11,12 and policies and procedures of orga-
nized health systems provide guidance for the pharmacist in The relative importance of problems must be assessed on the
judging the appropriate use of patient-specific information. basis of specific characteristics of the patient or the medi-
The patient (as well as family members, caregivers, cation. Checklists, work sheets, and other methods may be
and other members of the health care team as needed) should used to determine and document the presence of medica-
be interviewed. This is necessary for the pharmacist to estab- tion-therapy problems. The method should be proactive and
lish a direct relationship with the patient, to understand the should be used consistently from patient to patient.
patient’s needs and desired outcome, to obtain medication-
related information, and to clarify and augment other avail- Summarizing Patients’ Health Care Needs. The patient’s
able information. Pharmacists in many practice settings, overall needs and desired outcomes and other health pro-
including ambulatory care, may need to perform physical fessionals’ assessments, goals, and therapy plans should be
assessments to collect data for assessing and monitoring considered in determining and documenting the medication-
medication therapy. related elements of care that are needed to improve or pre-
Information, including clinical laboratory test results, vent deterioration of the patient’s health or well-being.
gathered or developed by other members of the health care
team may not be in the patient’s health record. Therefore, Specifying Pharmacotherapeutic Goals. Pharmacotherapeu
to ensure that the patient information is current and com- tic goals should reflect the integration of medication-,
plete, other sources should be checked. Other sources may disease-, laboratory test-, and patient-specific information,
include medication profiles from other pharmacies used by as well as ethical and quality-of-life considerations. The
the patient. goals should be realistic and consistent with goals speci-
Although it is ideal to have a comprehensive database fied by the patient and other members of the patient’s health
for all patients, time and staffing limitations may necessi- care team. The therapy should be designed to achieve defi-
tate choices regarding the quantity of information and the nite medication-related outcomes and improve the patient’s
number of patients to follow. Choices could be determined quality of life.
by the health system’s policies and procedures, by clinical
care plans, or by disease management criteria in the patient’s Designing a Pharmacotherapeutic Regimen. The regimen
third-party health plan. should meet the pharmacotherapeutic goals established with
Systems for recording patient-specific data will vary, the patient and reflect the integration of medication-, dis-
depending on pharmacists’ preferences and practice settings. ease-, laboratory test-, and patient-specific information;
Electronic documentation is recommended. Some informa- ethical and quality-of-life considerations; and pharmacoeco-
tion may already be in the patient’s health record. Therefore, nomic principles. It should comply with the health system’s
when authorized, the additional information gathered by the medication-use policies, such as clinical care plans and dis-
pharmacist should be recorded in the patient’s health re- ease management plans. The regimen should be designed for
cord so that it can be shared with other health professionals. optimal medication use within both the health system’s and
Abstracted summaries and work sheets may also be useful. the patient’s capabilities and financial resources.
Designing a Monitoring Plan for the Pharmacotherapeu The provision of pharmaceutical care requires monitoring
tic Regimen. The monitoring plan should effectively evalu- the regimen’s effects, revising the regimen as the patient’s
ate achievement of the patient-specific pharmacothera- condition changes, documenting the results, and assuming
peutic goals and detect real and potential adverse effects. responsibility for the pharmacotherapeutic effects.
Measurable, observable parameters should be determined
for each goal. Endpoints should be established for assess- References
ing whether the goal has been achieved. The needs of the
patient, characteristics of the medication, needs of other 1. Hepler CD, Strand LM. Opportunities and responsibil-
health care team members, and policies and procedures of ities in pharmaceutical care. Am J Hosp Pharm. 1990;
the health care setting will influence the monitoring plan. 47:533–43.
Developing a Pharmacotherapeutic Regimen and Corre statement on pharmaceutical care. Am J Hosp Pharm.
sponding Monitoring Plan. The regimen and plan developed 1993; 50:1720–3.
in collaboration with the patient and other health profession- 3. Implementing pharmaceutical care. Proceedings of an
als should be systematic and logical and should represent a invitational conference conducted by the American
consensus among the patient, prescriber, and pharmacist. The Society of Hospital Pharmacists and the ASHP
approach selected should be based on consideration of the Research Foundation. Am J Hosp Pharm. 1993; 50:
type of practice setting, its policies and procedures, practice 1585–656.
standards, and good professional relations with the prescriber 4. Summary of the final report of the Scope of Pharmacy
and patient. The regimen and monitoring plan should be doc- Practice Project. Am J Hosp Pharm. 1994; 51:2179–
umented in the patient’s health record to ensure that all mem- 82.
bers of the health care team have this information. 5. Shepherd MF. Clinical skills program pharmaco-
therapy series module 1. Reviewing patient medical
Initiating the Pharmacotherapeutic Regimen. Depending charts. Bethesda, MD: American Society of Hospital
on the regimen and plan, the pharmacist could, as appropri- Pharmacists; 1992.
ate, implement all or portions of the pharmacotherapeutic 6. Mason N, Shimp LA. Clinical skills program pharma-
regimen. Actions should comply with the health system’s cotherapy series module 2. Building a pharmacist’s
policies and procedures (e.g., prescribing protocols) and patient data base. Bethesda, MD: American Society of
correspond to the regimen and plan. Orders for medications, Hospital Pharmacists; 1993.
laboratory tests, and other interventions should be clear and 7. Mason N, Shimp LA. Clinical skills program–mod-
concise. All actions should be documented in the patient’s ule 3. Constructing a patient’s drug therapy problem
health record. list. Bethesda, MD: American Society of Hospital
Pharmacists; 1993.
Monitoring the Effects of the Pharmacotherapeutic Regi 8. Jones WN, Campbell S. Clinical skills program phar-
men. Data collected according to the monitoring plan should macotherapy series module 4. Designing and recom-
be sufficient, reliable, and valid so that judgments can be mending a pharmacist’s care plan. Bethesda, MD:
made about the effects of the pharmacotherapeutic regimen. American Society of Hospital Pharmacists; 1994.
Changes in patient status, condition, medication therapy, or 9. Frye CB. Clinical skills program pharmacotherapy
nonmedication therapy since the monitoring plan was de- series module 5. Monitoring the pharmacist’s care
veloped should be considered. Missing or additional data plan. Bethesda, MD: American Society of Hospital
should be identified. Achievement of the desired endpoints Pharmacists; 1994.
should be assessed for each parameter in the monitoring 10. PL 93-579. 5 U.S.C.A. 552a (88 Stat. 1896).
plan. A judgment should be made about whether the phar- 11. ASHP guidelines for obtaining authorization for doc-
macotherapeutic goals were met. Before the pharmacothera- umenting pharmaceutical care in patient medical re-
peutic regimen is adjusted, the cause for failure to achieve cords. Am J Hosp Pharm. 1989; 46:338–9.
any of the pharmacotherapeutic goals should be determined. 12. Principles of practice for pharmaceutical care.
Washington, DC: American Pharmaceutical Association;
Redesigning the Pharmacotherapeutic Regimen and 1995.
Monitoring Plan. Decisions to change the regimen and plan
should be based on the patient’s outcome. When clinical cir-
cumstances permit, one aspect of the regimen at a time should
be changed and reassessed. Recommendations for pharmaco-
therapeutic changes should be documented in the same man- Approved by the ASHP Board of Directors, April 24, 1996.
ner used to document the original recommendations. Developed by the ASHP Council on Professional Affairs.
Pharmacist’s Responsibility Copyright © 1996, American Society of Health-System Pharmacists,

An essential element of pharmaceutical care is that the phar-
macist accepts responsibility for the patient’s pharmacother- The bibliographic citation for this document is as follows: American
apeutic outcomes. The same commitment that is applied to Society of Health-System Pharmacists. ASHP guidelines on a stan-
designing the pharmacotherapeutic regimen and monitoring dardized method for pharmaceutical care. Am J Health-Syst Pharm.
plan for the patient should be applied to its implementation. 1996; 53:1713–6.
288 Medication Therapy and Patient Care: Specific Practice Areas–Positions
Specific Practice Areas

Naloxone Availability (1510) Pharmacist’s Role in Urgent and Emergency Situations
Source: Council on Therapeutics (1527)
To recognize the potential public health benefits of naloxone Source: Council on Pharmacy Practice
for opioid reversal; further, To affirm that pharmacists should participate in planning
To support efforts to safely expand access to naloxone; and providing emergency treatment team services; further,
further, To advocate that pharmacists participate in decision-
To advocate that individuals other than licensed making about the medications and supplies used in medical
healthcare professionals be permitted access to naloxone af- emergencies; further,
ter receiving education; further, To advocate that pharmacists serve in all emergency
To foster education on the role of naloxone in opioid responses, and that those pharmacists receive appropriate
reversal and its proper administration, safe use, and appro- training and maintain appropriate certifications.
priate follow-up care; further,
To support state efforts to authorize pharmacists’ pre- Safe Use of Radiopharmaceuticals (1402)
scribing authority for naloxone for opioid reversal. Source: Council on Pharmacy Practice
To affirm that radiopharmaceuticals require the same stan-
Safety and Effectiveness of Ethanol Treatment for dards for safe medication use as other medications, includ-
Alcohol Withdrawal Syndrome (1514) ing but not limited to standards for procurement, storage and
Source: Council on Therapeutics control, prescribing, preparation, dispensing, administration,
To oppose the use of oral or intravenous ethanol for the pre- documentation, clinical and regulatory monitoring, disposal,
vention or treatment of alcohol withdrawal syndrome (AWS) and formulary consideration; further,
because of its poor effectiveness and safety profile; further, To advocate that pharmacy departments, in coopera-
To support hospital and health-system efforts that pro- tion with departments of nuclear medicine, radiology, and
hibit the use of oral or intravenous ethanol therapies to treat radiation safety, provide oversight of radiopharmaceuticals
AWS; further, to assure safe use; further,
To educate clinicians about the availability of alterna- To advocate for incorporation of information on ra-
tive therapies for AWS. diopharmaceuticals into college of pharmacy curricula and
This policy supersedes ASHP policy 1010. increased pharmacy continuing education on radiopharma-
ceuticals.
Chemotherapy Parity (1516)
Source: Council on Therapeutics Safe Use of Fentanyl Transdermal System Patches
To advocate that all insurance payers design plans so that (1404)
patient cost sharing for chemotherapy be equivalent regard- Source: Council on Pharmacy Practice
less of route of administration; further, To advocate for enhanced consumer education and prod-
To continue to foster the development of best prac- uct safety requirements for fentanyl transdermal system
tices, including adherence monitoring strategies, and edu- patches; further,
cation on the safe use and management of chemotherapy To encourage manufacturers of fentanyl transdermal
agents regardless of route of administration. system patches to collaborate with pharmacists and other
stakeholders to identify and implement packaging, labeling,
Documentation of Penicillin Allergy as a Component of and formulation changes that prevent accidental exposure
Antimicrobial Stewardship (1517) and facilitate safe disposal.
To advocate involvement of pharmacists in the clarification Education About Performance-Enhancing Substances
of penicillin allergy, intolerance, and adverse drug events; (1305)
further, Source: Council on Pharmacy Practice
To advocate for documentation of penicillin allergy, To encourage pharmacists to engage in community outreach
intolerance, reactions, and severity in the medical record to efforts to provide education to athletes on the risks associated
facilitate optimal antimicrobial selection; further, with the use of performance-enhancing substances; further,
To recommend the use of penicillin skin testing in ap- To encourage pharmacists to advise athletic authori-
propriate candidates when clinically indicated to optimize ties and athletes on the dangers of performance-enhancing
antimicrobial selection. substances and other products that are prohibited in competi-
tion; further,
Prescription Drug Abuse (1526) To advocate for the role of the pharmacist in all aspects
Source: Council on Pharmacy Practice of sports doping control.
To affirm that pharmacists have leadership roles in recogni- This policy supersedes ASHP policy 0710.
tion, prevention, and treatment of prescription drug abuse;
further, Pharmacists’ Role in Immunization (1309)
To promote education on prescription drug abuse, mis- Source: Council on Public Policy
use, and diversion-prevention strategies. To affirm that pharmacists have a role in improving public
health and increasing patient access to immunizations by
Medication Therapy and Patient Care: Specific Practice Areas–Positions 289
promoting and administering appropriate immunizations to accreditation and quality improvement entities as the sole
patients and employees in all settings; further, indicator to assess the appropriateness of prescribing for ge-
To collaborate with key stakeholders to support the riatric patients based on known limitations in the evidence
public health role of pharmacists and student pharmacists evaluating the association between use of medications listed
in the administration of adult and pediatric immunizations; in such criteria and subsequent adverse drug events; further,
further, To advocate for the development, refinement, and vali-
To advocate that states grant pharmacists and appro- dation of new criteria that consider drug-, disease-, and pa-
priately supervised student pharmacists the authority to ini- tient-specific factors and demonstrate the ability to decrease
tiate and administer all adult and pediatric immunizations; the occurrence of adverse drug events in geriatric patients;
further, further,
To advocate that pharmacists and student pharmacists To support research to assess the clinical application of
who have completed a training and certification program ac- existing and proposed criteria, including assessment of their
ceptable to state boards of pharmacy and meeting the stan- correlation to patient outcomes and strategies for implemen-
dards established by the Centers for Disease Control and tation; further,
Prevention may provide such immunizations; further, To encourage inclusion of validated criteria in clinical
To advocate that state and federal health authorities decision support systems and other information technologies
establish centralized databases for documenting administra- to facilitate prescribing for geriatric patients; further,
tion of immunizations that are accessible to all health care To acknowledge that such criteria are intended as a
guide and should not replace the clinical judgment of phar-
providers; further,
macists and other clinicians.
To advocate that state and federal health authorities
require pharmacists and other immunization providers to
Tobacco and Tobacco Products (1224)
report their documentation to these centralized databases, if
available; further,
To discourage the use, distribution, and sale of tobacco and
To strongly encourage pharmacists to educate all pa-
tobacco products in and by pharmacies; further,
tients, their caregivers, parents, guardians, and health care
To advocate for tobacco-free environments in hospi-
providers about the importance of immunizations for disease tals and health systems; further,
prevention; further, To seek, within the bounds of public law and policy,
To encourage pharmacists to seek opportunities for to eliminate the use and distribution of tobacco and tobacco
involvement in disease prevention through community im- products in meeting rooms and corridors at ASHP-sponsored
munization programs; further, events; further,
To advocate for the inclusion of pharmacist-provided To promote the role of pharmacists in tobacco-cessa-
immunization training in college of pharmacy curricula. tion counseling and medication therapy management; further,
This policy supersedes ASHP policies 1220 and 0213. To join with other interested organizations in state-
ments and expressions of opposition to the use of tobacco
Pharmacist’s Role in Accountable Care Organizations and tobacco products.
(1214) This policy supersedes ASHP policy 0713.
Source: Council on Pharmacy Practice
To recognize that pharmacist participation in collaborative Safe and Effective Use of IV Promethazine (1105)
health care teams improves outcomes from medication use Source: Council on Therapeutics
and lowers costs; further, To recognize intravenous (IV) promethazine as a treatment
To advocate to health policymakers, payers, and other alternative in limited clinical circumstances; further,
stakeholders for the inclusion of pharmacists as health care To support health-system efforts to restrict use of IV
providers within accountable care organizations (ACOs) and promethazine by encouraging alternate routes of adminis-
other models of integrated health care delivery; further, tration or use of therapeutic alternatives when appropriate;
To advocate that pharmacist-provided care (including further,
care coordination services) be appropriately recognized in To encourage health systems to establish medication-
reimbursement models for ACOs; further, use processes that reflect nationally recognized best prac-
To advocate that pharmacists be included as health tices to limit the potential for patient harm when IV pro-
care providers in demonstration projects for ACOs; further, methazine use is medically necessary.
To encourage comparative effectiveness research and
measurement of key outcomes (e.g., clinical, economic, Pain Management (1106)
quality, access) for pharmacist services in ACOs; further, Source: Council on Therapeutics
To encourage pharmacy leaders to develop strategic To advocate fully informed patient and caregiver participa-
plans for positioning pharmacists in key roles within ACOs. tion in pain management decisions as an integral aspect of
patient care; further,
Criteria for Medication Use in Geriatric Patients (1221) To advocate that pharmacists actively participate in
Source: Council on Therapeutics the development and implementation of health-system pain
To support medication therapy management, including as- management policies and protocols; further,
sessment of physiologic and pharmacokinetic factors, as a To support the participation of pharmacists in pain
central component of providing safe and effective drug ther- management, which is a multidisciplinary, collaborative
apy to geriatric patients; further, process for selecting appropriate drug therapies, educating
To oppose use of the Beers criteria or similar criteria patients, monitoring patients, and continually assessing out-
by the Centers for Medicare & Medicaid Services and other comes of therapy; further,
290 Medication Therapy and Patient Care: Specific Practice Areas–Positions
To advocate that pharmacists lead efforts to prevent and flush of peripheral and central venous lines in neonatal
inappropriate use of pain therapies, including engaging in patients; further,
strategies to detect and address patterns of abuse and misuse; To advocate that hospitals and health systems use
further, manufacturer-prepackaged heparin flush products to im-
To encourage the education of pharmacists, pharmacy prove the safe use of heparin in neonatal patients.
students, and other health care providers regarding the prin- This policy was reviewed in 2013 by the Council on
ciples of pain management and methods to minimize drug Therapeutics and by the Board of Directors and was found
diversion. to still be appropriate.
Pharmacist Support for Dying Patients (0307)
Pharmacist’s Role in Providing Care for an Aging Source: Council on Professional Affairs
Population (0902) To support the position that care for dying patients is part
Source: Council on Pharmacy Practice of the continuum of care that pharmacists should provide to
To encourage expansion of geriatric health care services; patients; further,
further, To support the position that pharmacists have a pro-
To foster expanded roles for pharmacists in caring for fessional obligation to work in a collaborative and compas-
geriatric patients; further, sionate manner with patients, family members, caregivers,
To support successful innovative models of team- and other professionals to help fulfill the patient care needs,
based, interdisciplinary geriatric care; further, especially the quality-of-life needs, of dying patients of all
To increase training of pharmacists in caring for geriat- ages; further,
ric patients within college of pharmacy curricula, in ASHP- To support research on the needs of dying patients;
accredited postgraduate-year-one residencies, and through the further,
expansion of the number of ASHP-accredited postgraduate- To provide education to pharmacists on caring for
year-two geriatric pharmacy residency programs. dying patients, including education on clinical, managerial,
This policy was reviewed in 2013 by the Council on professional, and legal issues; further,
Pharmacy Practice and by the Board of Directors and was To urge the inclusion of such topics in the curricula of
found to still be appropriate. colleges of pharmacy.
Pharmacist Role in the Health Care (Medical) Home Pharmacy Practice and by the Board of Directors and was
(0908) found to still be appropriate.
To advocate to health policymakers, payers, and other stake- Interventions to Reduce High-Risk Behavior in Intra
holders for the inclusion of pharmacists as a care provider venous Drug Users (9711)
within the health care (medical) home model; further, Source: House of Delegates Resolution
To ensure that there are appropriate reimbursement ASHP supports the use of needle and syringe exchange
mechanisms for the care that pharmacists provide (includ- programs, drug abuse treatment, and community outreach
ing care coordination services) within the health care home programs for substance abusers to reduce the risk of trans-
model; further, mission of the human immunodeficiency virus (HIV), hepa-
To advocate to the Centers for Medicare & Medicaid titis B virus, and hepatitis C virus in intravenous drug users.
Services that pharmacists be included in demonstration proj-
ects for the health care home model; further,
To encourage comparative effectiveness research and
measurement of key outcomes (e.g., clinical, economic,
quality, access) for pharmacist services in the health care
Primary and Preventive Care (9407)
home model.
Source: Council on Professional Affairs
To support primary and preventive care roles for pharma-
cists in the provision of pharmaceutical care; further,
To collaborate with physician, nursing, and health-
system administrator groups in pursuit of these goals.
Safe and Effective Use of Heparin in Neonatal Patients
(0912)
To support the development and use of nationally standard-
ized concentrations of heparin when used for maintenance
Medication Therapy and Patient Care: Specific Practice Areas–Statements 291
ASHP Statement on the

Pharmacist’s Role in Antimicrobial Stewardship
and Infection Prevention and Control
Position 3. Surveillance systems to track the occurrence and

transmission of infections.
The American Society of Health-System Pharmacists 4. Surveillance systems to track the use of antimicrobials
(ASHP) believes that pharmacists have a responsibility to and the development of antimicrobial resistance.
take prominent roles in antimicrobial stewardship programs 5. Promotion of evidence-based practices and interven-
and participate in the infection prevention and control pro- tions to prevent the development of infections.
grams of health systems. This responsibility arises, in part,
from pharmacists’ understanding of and influence over an- Responsibilities of Pharmacists
timicrobial use within the health system. Further, ASHP be-
lieves that the pharmacist’s ability to effectively participate Pharmacists’ responsibilities for antimicrobial stewardship
in antimicrobial stewardship and infection prevention and and infection prevention and control include promoting the
control efforts can be realized through clinical endeavors optimal use of antimicrobial agents, reducing the transmis-
focused on proper antimicrobial utilization and member- sion of infections, and educating health professionals, pa-
ship on multidisciplinary work groups and committees
tients, and the public.
within the health system. These efforts should contribute to
the appropriate use of antimicrobials, ultimately resulting
Promoting Optimal Use of Antimicrobial Agents. An im-
in successful therapeutic outcomes for patients with infec-
portant clinical responsibility of the pharmacist is to ensure
tious diseases, and reduce the risk of infections for other
patients and health care workers. the optimal use of antimicrobial agents throughout the health
system. Functions related to this responsibility may include
Background 1. Encouraging multidisciplinary collaboration within the
health system to ensure that the prophylactic, empiri-
Antimicrobial stewardship is utilized in practice settings
cal, and therapeutic uses of antimicrobial agents result
of health systems to improve patient outcomes while mini-
in optimal patient outcomes. These activities may in-
mizing the unintended consequences of antimicrobial use.
clude antimicrobial-related patient care (e.g., aiding in
The goals of antimicrobial stewardship programs include
appropriate selection, optimal dosing, rapid initiation,
attenuating or reversing antimicrobial resistance, pre-
and proper monitoring and de-escalation of antimicro-
venting antimicrobial-related toxicity, and reducing the
bial therapies) as well as the development of restricted
costs of inappropriate antimicrobial use and health care-
antimicrobial-use procedures, therapeutic interchange,
associated infections. Guidelines published by the Infectious
Diseases Society of America and the Society for Healthcare treatment guidelines, and clinical care plans.2
Epidemiology of America and endorsed by ASHP and other 2. Working within the pharmacy and therapeutics com-
organizations describe an evidence-based approach to anti- mittee (or equivalent) structure, which may include in-
microbial stewardship in health systems and the important fectious disease-related subcommittees, to ensure that
role pharmacists with infectious diseases training have in the number and types of antimicrobial agents available
leading stewardship efforts.1 are appropriate for the patient population served. Such
Identifying and reducing the risks of developing, ac- decisions should be based on the needs of special pa-
quiring, and transmitting infections among patients, health tient populations and microbiological trends within the
care workers, and others are an important part of improving health system. High priority should be given to devel-
patient outcomes. In order to maximize outcomes, antimicro- oping antimicrobial-use policies that result in optimal
bial stewardship should be used in combination with infection therapeutic outcomes while minimizing the risk of the
prevention and control practices.1 Most health systems main- emergence of resistant strains of microorganisms.
tain an infection prevention and control program directed 3. Operating a multidisciplinary, concurrent antimi-
by a multidisciplinary committee. The specific program and crobial stewardship program that uses patient out-
responsibilities of the infection prevention and control com- comes to assess the effectiveness of antimicrobial-
mittee (or its equivalent) may differ among health systems. use policies throughout the health system.
Typically, the infection prevention and control com- 4. Generating and analyzing quantitative data on anti-
mittee develops organizational policies and procedures ad- microbial drug use to perform clinical and economic
dressing outcome analyses.
5. Working with the microbiology laboratory personnel
1. The management and provision of patient care and to ensure that appropriate microbial susceptibility tests
employee health services regarding infection or infec- are reported on individual patients in a timely man-
tion prevention and control. ner, and collaborating with the laboratory, infectious
2. The education of staff, patients, family members, diseases specialists, and infection preventionists in
and other caregivers in the prevention and control compiling susceptibility reports (at least annually) for
of infections.
292 Medication Therapy and Patient Care: Specific Practice Areas–Statements
distribution to prescribers within the health system to mulary restriction and preauthorization, enhances the effec-
guide empirical therapy. tiveness of educational activities in the patient care setting.1
6. Utilizing information technology to enhance antimi- Specific activities may include
crobial stewardship through surveillance, utilization
and outcome reporting, and the development of clini- 1. Providing clinical conferences, newsletters, and other
cal decision-support tools. types of educational forums for health professionals
7. Facilitating safe medication management practices on topics such as antimicrobial use and resistance,
for antimicrobial agents by utilizing efficient and ef- decontaminating agents (disinfectants, antiseptics,
fective systems to reduce potential errors and adverse and sterilants), aseptic technique and procedures, and
drug events. sterilization methods.
2. Educating and counseling inpatients, ambulatory care
Reducing the Transmission of Infections. Pharmacists patients, home care patients, and their families and
should participate in efforts to prevent or reduce the trans- caregivers in the following areas: adherence to pre-
mission of infections among patients, health care workers, scribed directions for antimicrobial use, storage and
and others within all of the health system’s applicable prac- handling of medications and administration devices,
tice settings. This may be accomplished through and other infection prevention and control procedures
(e.g., medical waste disposal).
1. Participating in the infection prevention and control 3. Participating in public health education and awareness
committee (or its equivalent). programs aimed at controlling the spread of infectious
2. Establishing internal pharmacy policies, procedures, diseases by
and quality-control programs to prevent contamination a. Promoting prudent use of antimicrobials,
of drug products prepared in or dispensed by the phar- b. Providing immunization access for children and
macy department. This is of paramount importance adults, an
in the preparation and handling of sterile products.3 c. Promoting appropriate infection prevention and
Other considerations include (but are not limited to) control measures (e.g., proper hand hygiene
provisions for cleaning pharmaceutical equipment techniques).
(e.g., laminar-airflow hoods and bulk-compounding 4. Providing exposure to antimicrobial stewardship and
equipment) and establishment of appropriate per- infection prevention and control practices through
sonnel policies (e.g., limiting the activities of staff experiential and didactic training for practicing
members who exhibit symptoms of a viral respiratory health-system pharmacists, students, residents, and
illness or other infectious condition). research fellows.
3. Encouraging the use of single-dose packages of sterile
drug products rather than multiple-dose containers, ex- Education and Training of Pharmacists
cept in sterile environments.
4. Recommending proper labeling, dating, and storage of ASHP recognizes that the current shortage of pharmacists
sterile products and multiple-dose sterile-product con- with advanced training in infectious diseases and the limited
tainers (if used). number of training opportunities may require pharmacists
5. Encouraging routine immunization (e.g., influenza without such training to assume some of the responsibilities
vaccination) of hospital staff and others who impact described above. ASHP supports the expansion of pharmacy
the patient care environment, and promoting periodic education and postgraduate residency training on infectious
screening for selected transmissible diseases (e.g., tu- diseases in order to develop an adequate supply of pharma-
berculosis) in accordance with health-system policy cists trained to deliver these essential services.
and federal, state, or local regulations.
6. Promoting adherence to standard precautions by
health care workers, patients, and others who impact Conclusion
the patient care environment.4
7. Collaborating in the development of guidelines for ASHP believes that pharmacists have a responsibility to
take prominent roles in antimicrobial stewardship and in-
risk assessment, treatment, and monitoring of patients
fection prevention and control programs in health systems.
and health care workers who have been in contact with
Pharmacists should participate in antimicrobial stewardship
persons with a transmissible infectious disease. and infection prevention and control efforts through clinical
8. Striving for zero tolerance of health care-associated endeavors focused on proper antimicrobial utilization and
infections, including surgical site infections, catheter- membership on relevant multidisciplinary work groups and
associated bloodstream infections, catheter-associated committees within the health system.
urinary tract infections, and ventilator-associated
pneumonia.
References
Educational Activities. The pharmacist’s role includes
providing education and information about antimicrobial 1. Dellit TH, Owens RC, McGowen JE, et al. Infectious
stewardship and infection prevention and control to health Diseases Society of America and the Society for
professionals, patients, and members of the public who Healthcare Epidemiology of America guidelines for
come in contact with the health system’s practice settings. developing an institutional program to enhance antimi-
Incorporating active intervention techniques, such as for- crobial stewardship. Clin Infect Dis. 2007; 44:159–77.
2. American Society of Health-System Pharmacists. Kollef M, Shapiro S, Fraser V, et al. A randomized trial of
ASHP guidelines on the pharmacist’s role in the de- ventilator circuit changes. Ann Intern Med. 1995; 123:
velopment, implementation, and assessment of critical 168–74.
pathways. Am J Health-Syst Pharm. 2004; 61:939–45. MacDougall C, Polk RE. Antimicrobial stewardship pro-
3. American Society of Health-System Pharmacists. grams in health care systems. Clin Microbiol Rev.
ASHP guidelines on quality assurance for pharmacy- 2005 Oct; 18(4):638–56.
prepared sterile products. Am J Health-Syst Pharm. Sepkowitz KA. Occupationally acquired infections in
2000; 57:1150–69. health care workers. Ann Intern Med. 1996; 125:826–
4. Siegel JD, Rhinehart E, Jackson M, et al. 2007 guideline 34,917–28.
for isolation precautions: preventing transmission of in- Shlaes DM, Gerding DN, John JF Jr., et al. SHEA and IDSA
fectious agents in healthcare settings, June 2007. www. Joint Committee on the Prevention of Antimicrobial
cdc.gov/ncidod/dhqp/pdf/guidelines/Isolation2007.pdf Resistance: guidelines for the prevention of antimi-
(accessed 2009 Feb 18). crobial resistance in hospitals. Clin Infect Dis. 1997;
25:584–99.
Suggested Readings
Centers for Disease Control and Prevention. Guideline for

disinfection and sterilization in healthcare facilities, This statement was reviewed in 2013 by the Council on Pharmacy
2008. Accessed 15 December 2008. www.cdc.gov/ Practice and by the Board of Directors and was found to still be
ncidod/dhqp/pdf/guidelines/Disinfection_Nov_2008. appropriate.
pdf.
Centers for Disease Control and Prevention [CDC]. Approved by the ASHP Board of Directors on April 17, 2009, and
Guidelines for environmental infection control in by the ASHP House of Delegates on June 16, 2009. Developed
health-care facilities: recommendations of CDC and through the ASHP Council on Pharmacy Practice. This statement
the Healthcare Infection Control Practices Advisory supersedes the ASHP Statement on the Pharmacist’s Role in Infec-
Committee (HICPAC). MMWR. 2003; 52(No. RR- tion Control dated June 3, 1998.
10):1–48.
Diekema DJ, Doebbeling BN. Employee health and infec- Curtis D. Collins, Pharm.D., M.S., is gratefully acknowledged for
tion control. Infect Control Hosp Epidemiol. 1995; drafting this statement.
16:292–301.
Gardner P, Schaffner W. Immunization of adults. N Engl J Copyright © 2010, American Society of Health-System Pharma-
Med. 1993; 328:1252–8. cists, Inc. All rights reserved.
Goldmann DA, Weinstein RA, Wenzel RP, et al. Strategies
to prevent and control the emergence and spread of The bibliographic citation for this document is as follows: ASHP
antimicrobial-resistant microorganisms in hospitals. Statement on the Pharmacist’s Role in Antimicrobial Stewardship
A challenge to hospital leadership. JAMA. 1996; 275: and Infection Prevention and Control. Am J Health-Syst Pharm.
234–40. 2010; 67:575–7.

in Clinical Pharmacogenomics
Position genetic variability, must also be understood. As awareness
of individual genetic variation grows due to improved ac-
The American Society of Health-System Pharmacists cess to lower-cost testing and availability of evidence-based
(ASHP) believes that pharmacogenomic testing can im- consensus guidelines in pharmacogenomics,4 the develop-
prove medication-related outcomes across the continuum of ment of patient-individualized therapeutic regimens should
care in all health-system practice settings. These improve- include an assessment of patients’ pharmacogenomic pro-
ments include reduction in suboptimal clinical outcomes, files in addition to allergy and adverse reaction history,
decreased cost of treatment, better medication adherence, drug interactions, dietary and lifestyle factors, patterns of
more appropriate selection of therapeutic agents, decreased adherence, and other therapeutic drug-monitoring param-
length of treatment, and enhanced patient safety.1-3 Because eters.5 The FDA provides a list of drugs for which pharma-
of their distinct knowledge, skills, and abilities, pharmacists cogenomic markers are included in the drug labeling,6 and
are uniquely positioned to lead inter-professional efforts the Clinical Pharmacogenetics Implementation Consortium
to develop processes for ordering pharmacogenomic tests (CPIC) has published ASHP-endorsed therapeutic guide-
and for reporting and interpreting test results. They are also lines for multiple drug-gene pairs.7,8
uniquely qualified to lead efforts to guide optimal drug se- The pharmacist’s patient-care functions include appro-
lection and drug dosing based on those results. Pharmacists priate and cost-conscious medication selection and monitor-
therefore have a fundamental responsibility to ensure that ing, which now increasingly include pharmacogenomic pro-
pharmacogenomic testing is performed when needed and file assessment. The purpose of this statement is to describe
that the results are used to optimize medication therapy.1 pharmacists’ responsibilities and accountabilities in the field
Pursuant to this leadership role, pharmacists share account- of pharmacogenomics.
ability with other hospital and health-system leaders, such as
physicians, laboratory professionals, and genetic counselors, Pharmacists’ Responsibilities
for the ongoing implementation and application of pharma-
cogenomics across the continuum of care. Because test re- Pharmacists’ responsibilities for pharmacogenomics include
sults will have implications throughout a patient’s lifetime, promoting the optimal use and timing of pharmacogenomic
all pharmacists should have a basic understanding of phar- tests; interpreting clinical pharmacogenomic test results; and
macogenomics in order to provide appropriate patient-care educating other pharmacists, fellow health care profession-
recommendations. Some advanced pharmacist functions in als, patients, and the public about the field of pharmacoge-
applying clinical pharmacogenomics may require special- nomics. The following are responsibilities that should be
ized education, training, or experience. ASHP encourages part of any clinical pharmacogenomics service:
pharmacist education on the use of pharmacogenomics and
advocates inclusion of pharmacogenomics and its applica- • Advocating for the rational and routine use of phar-
tion to the therapeutic decision-making process in college macogenomic testing.
of pharmacy curricula and Board of Pharmacy Specialties • Providing test result interpretation and clinical guid-
certification programs. ance for return of results to providers and patients
in collaboration with other health care professionals
Background (e.g., physicians, laboratory professionals, and genetic
counselors).
Clinical pharmacogenomics uses genetic information to • Optimizing medication therapy based on pharmacoge-
guide optimal drug selection and drug dosing for patients nomic test results.
to maximize therapeutic effects, improve outcomes, and • Educating and providing information on the clinical
minimize toxicity.2 Pharmacogenomic testing can be per- application of pharmacogenomics to health profes-
formed reactively or preemptively. Reactive testing gener- sionals, patients, and members of the public.
ally occurs when a patient is experiencing adverse effects • Supporting and participating in research, consortia,
unexplained by dose or drug-drug or drug-disease interac- and networks that guide and accelerate the application
tions, or when the use of a high-risk drug is anticipated and of pharmacogenomics to clinical practice.
the patient’s genotype is obtained in anticipation of starting
therapy. In contrast, preemptive testing occurs when patients Using these responsibilities as a guide, ASHP has developed
are screened for multiple pharmacogenomic variants prior to the following recommendations for pharmacists’ functions
developing an indication for specific pharmacotherapy. in pharmacogenomics.
Application of pharmacogenomic information re-
quires an understanding of how genetic variations impact Pharmacists’ Functions
the pharmacokinetic and pharmacodynamic properties of a
drug in specific diseases and patient populations, as well as A pharmacist’s functions in clinical pharmacogenomics will
an understanding of molecular pathways. The influence of vary, depending on education, training, experience, and the
factors such as age, sex, diet, pathophysiologic conditions, needs of the practice setting. All pharmacists should have a
and current medication use, as well as their relationship to basic understanding of pharmacogenomics in order to pro-
vide patient care that incorporates pharmacogenomic rec- • Applying collaborative drug therapy management
ommendations. Elements of a basic understanding of phar- principles to a clinical pharmacogenomics service,
macogenomics should enable pharmacists to perform the including advocating for the reimbursement of phar-
following functions: macogenomic tests and pharmacist interpretation by
health insurance plans.
• Recommending or scheduling pharmacogenomic test- • Developing and planning pharmacogenomic-specific
ing to aid in the process of drug and dosage selection. advanced training opportunities for pharmacists and
• Designing a patient-specific drug and dosage regimen other health care professionals.
based on the patient’s pharmacogenomic profile that • Actively contributing to the body of knowledge in
also considers the pharmacokinetic and pharmacody- pharmacogenomics by publishing articles on the topic
namic properties of the drug. These factors should be in the biomedical literature.
combined in the regimen design along with other per- • Designing and conducting pharmacogenomic re-
tinent patient-specific factors such as comorbidities, search.
other drug therapy, demographics, and laboratory data
to optimize patient outcomes.
Conclusion
• Educating patients, pharmacists, and other health care
professionals about pharmacogenomic principles and
ASHP believes that pharmacists have a responsibility to take
appropriate indications for clinical pharmacogenomic
a prominent role in the clinical application of pharmaco-
testing, including the cost-effective use of pharma-
genomics. This emerging science should be spearheaded in
cogenomic testing.9
many institutions by pharmacists to promote safe, effective,
• Communicating pharmacogenomic-specific drug ther-
and cost-efficient medication practices.
apy recommendations to the health care team, includ-
ing documentation of interpretation of results in the
patient’s health record.10 References
Pharmacists with specialized education, training, or experience 1. Swen JJ, Nijenhuis M, de Boer A, et al. Pharmaco-
in pharmacogenomics should also assume the following ad- genetics: from bench to byte—an update of guidelines.
ditional functions: Clin Pharmacol Ther. 2011; 89(5):662–73.
2. Manolio TA, Chisholm RL, Ozenberger B, et al.
• Developing pharmacogenomic-specific clinical de- Implementing genomic medicine in the clinic: the fu-
cision support tools in electronic health record sys- ture is now. Genet Med. 2013; 15(4):258–67.
tems that guide prescribers on the appropriate use and 3. Wu AC, Fuhlbrigge AL. Economic evaluation of
dosing of medicines based on a patient’s pharmaco- pharmacogenetic tests. Clin Pharmacol Ther. 2008;
genomic profile.11-13 84(2):272–4.
• Developing a process, including patient-specific edu- 4. Relling MV, Klein TE. CPIC: Clinical Pharmaco-
cational materials, to explain to patients the impor- genetics Implementation Consortium of the Pharmaco-
tance and significance of their pharmacogenomic test genomics Research Network. Clin Pharmacol Ther.
results, not only in the short term but also over the pa- 2011; 89(3):464–7.
tient’s lifetime. 5. ASHP policy position 1104: Pharmacogenomics. In:
• Developing institutional guidelines and processes Hawkins B, ed. Best practices for hospital and health-
for implementation of a clinical pharmacogenomic system pharmacy: positions and guidance documents
service. of ASHP. 2013–2014 ed. Bethesda, MD: American
• Establishing a process for communicating patient- Society of Health-System Pharmacists; 2013:162.
specific results, including documentation of the results http://www.ashp.org/DocLibrary/BestPractices/
in the patient’s health record. FormularyPositions.aspx (accessed 2014 Jun 19).
• Establishing a mechanism for revisable reporting (re- 6. Table of Pharmacogenomic Biomarkers in Drug
interpretation of findings based on evolving science) Labeling. http://www.fda.gov/drugs/scienceresearch/
over the course of the patient’s care with the institution researchareas/pharmacogenetics/ucm083378.htm (ac-
and beyond. cessed 2014 Jun 19).
• Developing processes to document improved patient 7. Clinical Pharmacogenetics Implementation Consortium
outcomes and economic benefits resulting from clini- [CPIC]. Drug-Gene Pairs. www.pharmgkb.org/page/
cal pharmacogenomics. cpicGeneDrugPairs (accessed 2014 Jun 19).
• Serving as an expert consultant on a clinical pharma- 8. American Society of Health-System Pharmacists.
cogenomics service. Endorsed Documents. http://www.ashp.org/menu/
• Contributing to the evaluation and implementation of PracticePolicy/PolicyPositionsGuidelinesBestPractices/
clinical pharmacogenomic testing as an integral part of BrowsebyDocumentType/EndorsedDocuments.aspx
medication therapy. (accessed 2014 Jun 19).
• Promoting collaborative relationships with other 9. Feero WG, Kuo GM, Jenkins JR, et al. Pharmacist ed-
health care professionals and departments involved in ucation in the era of genomic medicine. J Am Pharm
drug therapy to encourage the development and appro- Assoc. 2012; 52:e113–e121.
priate use of pharmacogenomic principles in patient 10. Hicks JK, Crews KR, Hoffman JM, et al. A clinician-
care. driven automated system for integration of pharma-
cogenetic interpretations into an electronic medical FCCP, BCPS (AQ-Cardiology) are gratefully acknowledged for
record. Clin Pharmacol Ther. 2012; 92(5):563–6. drafting this statement. Mary V. Relling, Pharm.D., and Kristine R.
11. Welch BM, Kawamoto K. Clinical decision sup- Crews, Pharm.D., BCPS, are gratefully acknowledged for their re-
port for genetically guided personalized medicine: view of and contributions to the statement.
a systematic review. J Am Med Inform Assoc. 2013;
20(2):388–400. The following individuals are gratefully acknowledged for review-
12. Pulley JM,, et al. Operational implementation of ing this statement (review does not imply endorsement): Manju T.
prospective genotyping for personalized medicine: Beier, Pharm.D., CGP; Gillian C. Bell, Pharm.D.; Larisa H. Caval-
the design of the Vanderbilt PREDICT project. Clin lari, Pharm.D., BCPS; J. Kevin Hicks, Pharm.D., Ph.D.; Shannon
Pharmacol Ther. 2012; 92(1):87–95. Manzi, Pharm.D.; Darius Mason, Pharm.D., BCPS; Teresa Vo,
13. Bell GC, Crews KR, Wilkinson MR, et al. Development Pharm.D.; and Kristin Weitzel, Pharm.D., CDE, FAPhA.
and use of active clinical decision support for preemp-
tive pharmacogenomics. J Am Med Inform Assoc. Copyright © 2015, American Society of Health-System Pharma-
2013. DOI: 10.1136/anuajnl-2013-001993 [Epub ahead cists, Inc. All rights reserved.
of print].
The bibliographic citation for this document is as follows: Ameri-
can Society of Health-System Pharmacists. ASHP statement on the
Developed through the ASHP Section of Clinical Specialists and pharmacist’s role in clinical pharmacogenomics. Am J Health-Syst
Scientists Section Advisory Group on Emerging Sciences, and ap- Pharm. 2015; 72:579–81.
proved by the ASHP Board of Directors on April 10, 2014, and by
the ASHP House of Delegates on June 1, 2014.
Cyrine-Eliana Haidar, Pharm.D., BCPS, BCOP; James M. Hoff-

man, Pharm.D., M.S., BCPS; and Samuel G. Johnson, Pharm.D.,

in Clinical Pharmacokinetic Monitoring
The American Society of Health-System Pharmacists of drug therapy, concurrent diseases and drug therapy,
(ASHP) believes that clinical pharmacokinetic monitoring and other pertinent patient factors (e.g., demographics,
is a fundamental responsibility of all pharmacists provid- laboratory data) that improve the safety and effectiveness
ing pharmaceutical care. Clinical pharmacokinetic moni- of drug therapy and promote positive patient outcomes.
toring is an integral component of pharmaceutical care for 2. Recommending or scheduling measurements of drug
selected patients based on their specific pharmacotherapy, concentrations in biological fluids (e.g., plasma, serum,
disease states and related factors, and treatment goals. ASHP blood, cerebrospinal fluid) or tissues in order to facilitate
believes that clinical pharmacokinetic monitoring is essential the evaluation of dosage regimens.
to achieving positive outcomes for these patients across the 3. Monitoring and adjusting dosage regimens on the basis
continuum of care and in all practice settings of health systems. of pharmacologic responses and biological fluid and
Examples of such outcomes include decreased mortality, tissue drug concentrations in conjunction with clinical
decreased length of treatment, decreased length of hospital signs and symptoms or other biochemical variables.
stay, decreased morbidity (either improved symptoms of 4. Evaluating unusual patient responses to drug therapy
disease or improved recuperation), and decreased adverse for possible pharmacokinetic and pharmacologic
effects from drug therapy. explanations.
5. Communicating patient-specific drug therapy informa-
Background tion to physicians, nurses, and other clinical practitio-
ners and to patients orally and in writing, and including
Clinical pharmacokinetics is the process of applying phar- documentation of this in the patient’s health record.
macokinetic principles to determine the dosage regimens 6. Educating pharmacists, physicians, nurses, and other
of specific drug products for specific patients to maximize clinical practitioners about pharmacokinetic principles
pharmacotherapeutic effects and minimize toxic effects. and appropriate indications for clinical pharmacokinetic
Application of these principles requires an understanding monitoring, including the cost-effective use of drug
of the absorption, distribution, metabolism, and excretion concentration measurements.
characteristics of specific drug products in specific diseases 7. Developing quality assurance programs for document-
and patient populations. The influence of factors such as age, ing improved patient outcomes and economic benefits
sex, diet, pathophysiologic conditions, and concomitant use of resulting from clinical pharmacokinetic monitoring.
other drug products must also be understood. The develop- 8. Promoting collaborative relationships with other
ment of patients’ individualized dosage regimens should be individuals and departments involved in drug therapy
based on integrated findings from monitoring both the drug monitoring to encourage the development and appro-
concentration-versus-time profiles in biological fluids and priate use of pharmacokinetic principles in pharma-
the pharmacologic responses to these drug products. ceutical care.
Within the pharmaceutical care process, pharmacists’
clinical functions include appropriate and cost-conscious Pharmacists with specialized education, training, or
therapeutic drug monitoring and provision of clinical experience may have the opportunity to assume the follow-
pharmacokinetic assessments. Clinical pharmacokinetic ing additional responsibilities:
monitoring is necessary when the range between minimal
effectiveness and toxicity is narrow and the results of 1. Designing and conducting research to expand clini-
the drug assay provide significant information for clinical pharmacokinetic knowledge and its relationship to
cal decision-making. In the absence of drug concentra- pharmacologic responses, exploring concentration–
tion measurements, patient-specific characteristics and response relationships for specific drugs, and con-
physiological markers should be used to provide clinical tributing to the evaluation and expansion of clinical
pharmacokinetic assessments and make dosage-regimen pharmacokinetic monitoring as an integral part of
recommendations. pharmaceutical care.
2. Developing and applying computer programs and
Responsibilities point-of-care information systems to enhance the
accuracy and sophistication of pharmacokinetic mod-
The following responsibilities should be part of clinical eling and applications to pharmaceutical care.
pharmacokinetic services or monitoring conducted by 3. Serving as an expert consultant to pharmacists with a
pharmacists: general background in clinical pharmacokinetic moni-
toring.
1. Designing patient-specific drug dosage regimens
based on the pharmacokinetic and pharmacologic Readers are referred to ASHP’s more thorough publica-
characteristics of the drug products used, the objectives tions on the subject of clinical pharmacokinetic monitoring,
including Clinical Pharmacokinetics Pocket Reference and by the ASHP Council on Professional Affairs. Supersedes
Concepts in Clinical Pharmacokinetics: A Self-Instructional a previous version approved by the House of Delegates on
Course. June 5, 1989.

This statement was reviewed in 2013 by the Council on Pharmacy Inc. All rights reserved.
Practice and by the Board of Directors and was found to still be
appropriate. The bibliographic citation for this document is as follows: American
Society of Health-System Pharmacists. ASHP statement on the
Approved by the ASHP Board of Directors, November 15, 1997, pharmacist’s role in clinical pharmacokinetic monitoring. Am J
and by the ASHP House of Delegates, June 3, 1998. Revised Health-Syst Pharm. 1998; 55:1726–7.

in Hospice and Palliative Care
Position cancer in the United States are cared for by a hospice. Hospices
across the country are caring for increasing numbers of patients
The American Society of Health-System Pharmacists with cardiac disease, AIDS, renal disease, end-stage pulmonary
(ASHP) believes that pharmacists have a pivotal role in the disease, dementia, amyotrophic lateral sclerosis, Parkinson’s
provision of hospice and palliative care and that pharmacists disease, and other degenerative neurologic diseases.
should be integral members of all hospice interdisciplinary Hospice care is covered by Medicare Part A, private
teams. Pharmacists practicing in U.S. health systems have health insurance, and Medicaid in most states for patients
been active in defining and providing palliative care since who meet certain criteria. Any Medicare beneficiary who has
the introduction of hospice through a demonstration project a terminal illness with a prognosis of less than six months is,
supported by the National Cancer Institute and conducted in if the disease runs its normal course as certified by the at-
New Haven, Connecticut, between 1974 and 1977.1 tending physician and the hospice medical director, eligible
Palliative care has been defined by the World Health for the hospice Medicare benefit.5 Ninety-one percent of
Organization (WHO) as “the active total care of patients U.S. hospices have met Medicare certification requirements
whose disease is not responsive to curative treatment.”2 to provide this benefit to Medicare beneficiaries at no
WHO notes that control of pain, other symptoms, and psy- cost to the beneficiaries. Many hospices receive charitable
chological, social, and spiritual problems is paramount. The contributions to cover the cost of care for terminally ill
goal of palliative care is achievement of the best quality of patients who cannot afford to pay for their care.
life for patients and their families. Palliative care should be provided in conjunction with
Pharmaceutical care is defined as the direct, respon- curative care at the time of diagnosis of a potentially terminal
sible provision of medication-related care for the purpose of illness. Palliative care alone may be indicated when attempts
achieving definite outcomes that improve a patient’s quality at a cure are judged to be futile. Admissions to hospice and
of life.3 Medication therapy is the cornerstone of most—but palliative care programs often come too late for optimal
not all—symptom control in palliative care. The goals of services to be provided.6 The mean length of stay is 50 days,
palliative care and pharmaceutical care are consistent, with and the median is 25 days.4 Many hospice patients die within
the latter being a necessary component of good palliative care. days to a week after admission to a program.
Hospice is a philosophy and program that delivers pal- A nationwide Gallup survey conducted in 1996 indi-
liative care. Hospice care is provided by an interdisciplinary cated that 9 out of 10 adults, if terminally ill and with six
team, which provides expert medical care, pain management, months or less to live, would prefer to be cared for at home.
and emotional and spiritual support expressly tailored to the A majority of adults would be interested in a comprehensive
patient’s wishes. Emotional and spiritual support are also ex- program of care, such as hospice. When asked to name their
tended to the family of the patient. In U.S. hospice programs, greatest fear associated with death, most respondents cited
care is usually provided in the patient’s home or in a home- being a burden to family and friends. Pain was the second
like setting operated by a hospice program. Hospice and pal- most common fear. Effective hospice programs address
liative care share the same core values and philosophies. these concerns.
The purpose of this statement is to describe pharmacist’s Pharmaceutical services provided by pharmacists in
responsibilities and to promote understanding of the various U.S. hospices were surveyed qualitatively and quantitatively
ways in which pharmacists provide or contribute to the pro- in 1979 and 1991.7,8
vision of care to patients who might be nearing the end of life. While many pharmacists continue to serve hospice
programs as volunteer consultants to the interdisciplinary
Background team, a growing number of those who work with hospice
programs are now considered integral staff and are paid for
Currently, there are over 3100 operational or planned hos- their services. Inhouse pharmacies have increased since the
pice programs in the 50 states, the District of Columbia, mid-1990s, and the number continues to grow. A hospice
Puerto Rico, and Guam.4 According to the National Hospice that can support its own pharmacy typically has an average
and Palliative Care Organization, 42% of hospices were free- daily census of 200 patients. Most pharmacists who provide
standing in 2000 and 33% were affiliated with hospitals, pharmaceutical services to hospice programs are not employed
22% with home health agencies, and 9% with hospital systems. directly by the hospices but by a provider of pharmaceutical ser-
Over 700,000 patients were served in 2000, and that number vices, such as a home health pharmacy or hospital. Many are
is growing annually. In that same year, 73% of hospices were employees of pharmacies that have contracts with hospices to
nonprofit, 20% were for-profit institutions, and 7% were run provide drug products and services. In recent years, specialized
by government. hospice pharmacy services have been developed in several parts
In 2000, 2.4 million Americans died from all causes. of the United States, and such programs are growing rapidly.
Hospices admitted approximately 700,000 patients. Of those,
600,000 died while under hospice care. Patients are discharged The Hospice Interdisciplinary Team. According to Medicare
from hospices typically because of stabilization of disease, hospice regulations, a hospice interdisciplinary team should
moving to an area or facility not served by a hospice, and pa- include a doctor of medicine or osteopathy, a registered
tient and family preference. Over half of patients who die of nurse, a social worker, and a pastoral or other counselor.
Many other professionals and support persons often serve Avoidance of admissions to hospitals or long-term-care
on such teams. In addition, Medicare regulations state that facilities through improved symptom control is a highly
the hospice must “employ a licensed pharmacist; or have a desirable and cost-effective outcome of pharmaceutical care
formal agreement with a licensed pharmacist to advise the for hospice and palliative care patients.
hospice on ordering, storage, administration, disposal, and
recordkeeping of drugs and biologicals.” According to the The Pharmacist’s Responsibilities
two published surveys of pharmacist activities in hospices,
the hospice pharmacist typically is a full member of the High-quality hospice and palliative care requires both traditional
interdisciplinary team.7,8 and expanded pharmacist activities, including a variety of
By regulation, a patient’s plan of care must be reviewed clinical, educational, administrative, and support responsibilities:
and updated at specified intervals. If a hospice has more
than one team, then it must designate the team by which a 1. Assessing the appropriateness of medication orders
particular patient will be cared for. Hospice teams typically and ensuring the timely provision of effective medi-
meet for one or two hours two to four times a month to review cations for symptom control. Pharmacists maintain
patients’ care, status, and needs. Treatment plan modifica- patient medication profiles and monitor all prescrip-
tions, determinations of need for additional services, and tion and nonprescription medication use for safety
planning for consultations with specialists, changes in care and effectiveness. Pharmacists provide patients with
settings, imminent death, and other important events are essential medications within a time frame that ensures
discussed. Education and training are often provided at these continuous symptom control (especially pain relief)
meetings as well. and avoids the need for emergency medical services.
The hospice medical director is a doctor of medicine 2. Counseling and educating the hospice team about
or osteopathy who is responsible for the medical component medication therapy. Pharmacists attend hospice team
of the patient’s care. The director also serves as a consul- meetings to advise other team members about medi-
tant to the patient’s primary care physicians and the hospice cation therapy, including dosage forms, routes of
program staff. Pharmacists coordinate pharmacotherapy by administration, costs, and availability of various drug
making recommendations for appropriate therapy, educating products. This is done through regularly scheduled
patients and the hospice team about medications, monitoring educational sessions. Pharmacists develop and main-
therapeutic responses, and performing other medication- tain a library of contemporary references about medi-
related functions. Adjusting drug therapy in accordance with cations, dietary supplements, and alternative and
treatment algorithms is a new role for pharmacists in some complementary therapies. Pharmacists advise mem-
hospice and palliative care settings. bers of the hospice team about the potential for toxicity
A registered nurse coordinates the implementation of from and interactions with dietary supplements and
each patient’s plan of care. After certified nursing assistants, alternative and complementary therapies.
who may provide personal care on a daily basis, nurses make 3. Ensuring that patients and caregivers understand
the largest number of home visits. Social workers are respon- and follow the directions provided with medications.
sible for the psychosocial care of patients and their families, Pharmacists ensure that all medication labeling is
and they arrange bereavement care for families after patients complete and understandable by patients and their
die. The volunteer director recruits, trains, and coordinates caregivers. Hospice pharmacists communicate with
volunteers—another essential component of hospice care. patients, either through the team or in person, about
Volunteers provide needed relief for family caregivers and a the importance of adhering to the prescribed drug regi
broad range of services to patients and their families. men. Pharmacists explain the differences among
Chaplains address spiritual and existential issues. addiction, dependence, and tolerance and dispel patient
Hospice chaplaincy is typically nondenominational and is and caregiver misconceptions about addiction to opiate
often provided in coordination with patients’ own clergy. agonists. Pharmacists ensure the availability of devices
Other frequent participants in team meetings include nurs- and equipment to permit accurate measurement of liq-
ing assistants, home health aides, dietitians, physical therapists, uid dosage forms by patients and their caregivers.
occupational therapists, speech therapists, and hospice admin- Pharmacists counsel patients about the role and potential
istrative personnel. Students and postgraduate trainees from a toxicity of alternative and complementary therapies.
variety of professions, including pharmacy, often attend as well. When needed, hospice pharmacists visit patients’
homes to communicate directly with patients and their
Value of the Pharmacist’s Care. Most hospice and palliative caregivers and to make necessary assessments.
care is reimbursed through a capitation plan. Therefore, fees 4. Providing efficient mechanisms for extemporaneous
for service generally do not apply. Pharmacists can improve compounding of nonstandard dosage forms. Hospice
the cost-effectiveness of pharmacotherapy for symptom pharmacists communicate with pharmaceutical manu-
control in hospice care through patient-specific monitor- facturers to determine the availability of nonstandard
ing for drug therapy outcomes, recommending alternative dosage forms. Medication-compounding needs in
drug products and dosage forms, minimizing duplicative hospice care include the preparation of dosage forms
and interacting medications, compounding medications to ease administration (e.g., concentrated sublingual
extemporaneously, improving drug storage and transportation, solutions, topical medications), flavoring medications
and educating staff, patients, and families about the most to promote compliance, eliminating or adjusting ingre-
efficient ways of handling and using medications. Systems for dients that patients cannot tolerate, and preparing or
documenting these activities and determining cost-effectiveness changing drug concentrations. Whenever possible,
and the cost–benefit and cost–utility ratios of medica- pharmacists compound formulations for which stabil-
tions used in the care of terminally ill patients are needed. ity and bioavailability data are available.
5. Addressing financial concerns. Hospice benefits usually in patient records should include drug therapy recommenda-
cover medications. However, patients may lack insur- tions, monitoring of medication effects, patient and family
ance coverage or benefits may not cover medications education and counseling activities, and other activities as
that are not considered strictly palliative. Pharmacists indicated. Medication profiles should be maintained and
communicate with pharmaceutical manufacturers to should include information about prescription and nonpre-
obtain medications through patient assistance programs. scription drug products, dietary supplements, and alterna-
6. Ensuring safe and legal disposal of all medications tive and complementary therapies. Pharmacists also should
after death. Medications dispensed to patients are maintain detailed formulation files for all extemporaneously
“owned” by the patients and, in most states, cannot compounded dosage forms. Other records should be main-
be used for other patients. Medications remaining in tained in compliance with applicable federal and state laws
patients’ homes fall under a variety of hazard catego- and regulations.
ries. Pharmacists are able to assist families with the
removal of the medications from the home in compli- References
ance with federal and state drug control and environ-
mental protection laws and regulations. 1. Lipman AG. Drug therapy in terminally ill patients.
7. Establishing and maintaining effective communica- Am J Hosp Pharm. 1975; 32:270–6.
tion with regulatory and licensing agencies. Because 2. World Health Organization Expert Committee. Cancer
hospice patients often require large quantities of con- pain relief and palliative care. Technical report series 804.
trolled substances, open communication with both Geneva, Switzerland: World Health Organization; 1990.
state and federal controlled-substance agencies is 3. American Society of Hospital Pharmacists. ASHP
important. Pharmacists ensure compliance with laws statement on pharmaceutical care. Am J Hosp Pharm.
and regulations pertaining to medications. 1993; 50:1720–3.
4. National Hospice and Palliative Care Organization.
Pharmacists’ Scope of Practice NHPCO facts and figures on hospice care in America.
www.nhpco.org (accessed 2002 Apr 11).
The pharmacist may have a range of practice privileges that 5. Gage B, Miller SC, Coppola K et al. Important ques-
vary in their level of authority and responsibility. Pharmacists tions for hospice in the next century. www.aspe.hhs.
who participate in hospice and palliative care should meet the gov/daltcp/Reports/impques.htm#execsum (accessed
health care organization’s competency requirements to ensure 2001 Nov 27).
that they provide appropriate quality and continuity of patient 6. Lipman AG. Evidence-based palliative care. J Pharm
care. They should demonstrate required knowledge and skills, Care Pain Symptom Control. 1999; 7(4):1–9.
which may be obtained through practice-intensive continuing 7. Berry JI, Pulliam CC, Caiola SM et al. Pharmaceutical
education and pharmacy practice and specialty residencies. services in hospices. Am J Hosp Pharm. 1981;
The specific practice of pharmacists should be defined 38:1010–4.
within a scope-of-practice document or a similar tool or pro- 8. Arter SG, Berry JI. The provision of pharmaceuti-
tocol developed by the health care organization. The scope- cal care to hospice patients: results of the National
of-practice document defines activities that pharmacists Hospice Pharmacist Survey. J Pharm Care Pain
would provide within the context of collaborative practice as Symptom Control. 1993; 1(1):25–42.
a member of the interdisciplinary team, as well as limitations
where appropriate. The document should indicate referral and Suggested Readings
communication guidelines, including the documentation of
patient encounters and methods for sharing patient infor- 1. Lipman AG, Berry JI. Pharmaceutical care of ter-
mation with collaborating medical providers. minally ill patients. J Pharm Care Pain Symptom
Also included in the scope-of-practice document should Control. 1995; 3(2):31–56.
be references to activities that will review the quality of care 2. Arter SG, Lipman AG. Hospice care: a new opportu-
provided and the methods by which the pharmacist will main- nity for pharmacists. J Pharm Pract. 1990; 3:28–33.
tain continuing professional competency for functions encom- 3. Lipman AG. Pain management in the home care and
passed by the scope-of-practice document. A process should hospice patient. J Pharm Pract. 1990; 3:1–11.
be in place, and responsible parties identified, to review and 4. Wilkins C. Pharmacy and hospice: a personal experi-
update the scope-of-practice document as appropriate. ence. Consult Pharm. 1988; 3:462–5.
5. Arter SG, DuBe J, Mahoney J.Hospice care and the
Documentation of Services pharmacist. Am Pharm. 1987; NS27:616–24.
6. Murphy DH. The delicate art of caring: treating the
As members of the interdisciplinary health care team, phar- whole person. Am Pharm. 1984; NS24:388–90.
macists should have access to patients’ health records and 7. Quigley JL, Quigley MA, Gumbhir AK. Pharmacy
authority to make entries necessary for the team’s coordi- and hospice: partners in patient care. Am Pharm. 1982;
nated care of the patient. With access to the patient’s health NS22:420–3.
record comes the pharmacist’s professional responsibility 8. Berry JI. Pharmacy services in hospice organizations.
to safeguard the patient’s rights to privacy and confidentiality. Hosp Formul. 1982; 17:1333–8.
Patients should be informed that pharmacists, as well as 9. Mullan PA. Pharmacy and hospice: opportunities for
other members of the team, have access to their records. service. Am Pharm. 1982; NS22:424–6.
Pharmacists should routinely sign patient-review records 10. Oliver CH. Pharmacy and hospice: talk with the dying
at interdisciplinary team meetings. Pharmacist documentation patient. Am Pharm. 1982; NS22:429–33.
11. DuBe JE. Hospice care and the pharmacist. US Pharm.
1981; Apr:25–38. Approved by the ASHP Board of Directors in April 2002 and ASHP
12. Gable FB. Death with dignity: the pharmacist’s role in House of Delegates in June 2002. Developed through the ASHP
hospice care. Apothecary. 1980; Sep/Oct:62–7. Council on Professional Affairs.
13. Hammel MI, Trinca CE. Patient needs come first at
Hillhaven hospice: pharmacy services essential for Copyright © 2002, American Society of Health-System Pharmacists,
pain control. Am Pharm. 1978; NS18:655–7. Inc. All rights reserved.
14. Nee D. Pharmacy practice in a hospice setting. Fla
Pharm Today. 1995; Apr:19–23. The bibliographic citation for this document is as follows: American
Society of Health-System Pharmacists. ASHP statement on the
pharmacist’s role in hospice and palliative care. Am J Health-Syst
Pharm. 2002; 59:1770–3.
ASHP Statement on the Pharmacist’s Role in

Medication Reconciliation
Position immediate. Organizations such as the Institute for Healthcare
Improvement, the Agency for Healthcare Research and
The American Society of Health-System Pharmacists Quality, and the Joint Commission launched initiatives for
(ASHP) believes that an effective process for medication performance improvement and established higher expecta-
reconciliation reduces medication errors and supports safe tions through new regulatory standards for improved com-
medication use by patients. ASHP encourages hospitals and munication between providers and patients and across health
health systems, including community-based providers and care systems.
managed care systems, to collaborate in organized, multi- In 2005, the Joint Commission made medication
disciplinary medication reconciliation programs to promote reconciliation a focus of one of its National Patient Safety
continuity of patient care. ASHP further believes that phar- Goals. The initial goal included a number of detailed and
macists, because of their distinct knowledge, skills, and specific requirements, which made implementation chal-
abilities, are uniquely qualified to lead interdisciplinary ef- lenging and resulted in numerous findings of noncompliance
forts to establish and maintain an effective medication rec- during survey. In response, the Joint Commission affirmed
onciliation process in hospitals and across health systems. the importance of the goal but suspended it in 2009 and 2010
Pharmacists should lead or assume key roles in the follow- for extensive revision. After a comprehensive literature re-
ing essential components of medication reconciliation: de- view and analysis of data collected by surveyor teams, a
veloping policies and procedures, implementing and con- modified goal was released in 2011, and scoring of the goal
tinuously improving medication reconciliation processes, began in July 2011.6 The revised goal sets an expectation
training and assuring the continuing competency of those for maintaining accurate medication information at critical
involved in medication reconciliation, providing operational risk points in the medication-use process while allowing
and therapeutic expertise in the development of information organizations latitude to define processes and encouraging
systems that support medication reconciliation, and advo- performance improvement.
cating for medication reconciliation programs in the com- The purpose of this statement is to describe pharma-
munity. Pursuant to their leadership role, pharmacists share cists’ responsibilities and accountabilities in medication rec-
accountability with other hospital and health-system leaders onciliation practices.
for the ongoing success of medication reconciliation pro-
cesses across the continuum of care. Pharmacists’ Responsibilities
Background When performed by pharmacists, medication reconcili-

ation can reduce the frequency and severity of hospital
The term “medication reconciliation” is defined by the Joint medication errors that could potentially result in patient
Commission as “the process of comparing the medications a harm.7 Pharmacists have demonstrated high rates of patient
patient is taking (and should be taking) with newly ordered interventions; interventions per patient; and documentation
medications” in order to resolve discrepancies or potential of medications, medication interactions, drug-related admis-
problems.1 The goals of medication reconciliation are to sions, and previous drug failures.8
obtain and maintain accurate and complete medication in- ASHP and the American Pharmacists Association be-
formation for a patient and use the information within and gan a collaborative effort in 2007 and 2008 to create a shared
across the continuum of care to ensure safe and effective vision for the role of the pharmacist in medication recon-
medication use. Although it is sometimes associated with ciliation processes.9 That vision recognizes that pharmacists
survey and accreditation activities, medication reconcili- should take a leadership role in improving medication recon-
ation is an important component of patient safety and has ciliation, acting as both advocates and medication experts, to
demonstrated effectiveness in preventing adverse drug provide information to and educate patients and health care
events. When organizations do not consistently and reliably providers. Specifically, pharmacists’ responsibilities were
reconcile patient medications across the continuum of care, described as including but not being limited to
medication errors and adverse drug events occur: approxi-
mately half of all hospital-related medication errors and 20% • Providing leadership in designing and managing pa-
of all adverse drug events have been attributed to poor com- tient-centered medication reconciliation systems,
munication at the transitions and interfaces of care. 2,3 • Educating patients and health care professionals about
In 1999, the Institute of Medicine report To Err Is Human: the benefits and limitations of the medication recon-
Building a Safer Health System4 identified medication errors ciliation process, and
as the most common type of health-system error, contributing • Serving as patient advocates throughout transitions of
to several thousand deaths each year. The fiscal impact of these care.
errors is also significant. With reported costs of $2595–4685
per adverse drug event, drug-related morbidity and mortal- Using this vision as a guide, ASHP has developed the fol-
ity were estimated to cost over $177 billion in 2000 alone.5 lowing recommendations for pharmacists’ functions in med-
Reports and studies such as these had a profound im- ication reconciliation activities.
pact on the medical community, and the call for action was
Pharmacists’ Functions forming medication reconciliation), (c) providing education

and performing assessments to ensure the competency of
Although medication reconciliation is required at key transi- those who document and perform medication reconciliation
tions of care, activities associated with medication reconcili- activities, and (d) providing didactic or simulated training
ation should be considered part of ongoing care provided to for medication history and reconciliation procedures.
a patient. Beyond active participation in medication recon-
ciliation activities, pharmacists have five fundamental func- Information Systems Development. As more organizations
tions in medication reconciliation: developing policies and adopt computerized provider order entry, electronic medical
procedures regarding medication reconciliation processes, records, and other information systems, pharmacists should
implementing and continuously improving those processes, ensure that the systems support medication reconciliation
training and assuring the continuing competency of those in- throughout the continuum of care. Consideration should be
volved in medication reconciliation, providing operational given to establishing methods for data extraction from the
and therapeutic expertise in the development of information medical record that allow for internal and external reporting
systems that support medication reconciliation, and advocat- of measures related to medication reconciliation.
ing for medication reconciliation programs in the commu-
nity. The extent of pharmacist involvement in these func- Advocacy. Pharmacists should provide information about
tions will depend on the resources available. medication reconciliation to health care providers, patients,
and the community, and they should evaluate the effective-
Policy and Procedure Development. Pharmacists should ness of these advocacy efforts on the medication reconcili-
provide leadership and participate in establishing policies ation process. Activities may include clinical grand rounds,
and procedures that encourage (a) provision of patient care professional conferences, patient counseling, and mass
services that include medication reconciliation processes, communications such as newsletters and public service an-
(b) implementation and operation of an evidence-based nouncements. These efforts should (a) demonstrate the ef-
medication reconciliation system that optimizes available fectiveness of sound medication reconciliation processes
resources, (c) education of organization staff on the impor- in improving patient safety and reducing health care costs,
tance of medication reconciliation as a patient safety initia- (b) emphasize the importance of timely and accurate com-
tive, and (d) promotion of medication reconciliation as a munication of medication information between patients and
focus of performance-improvement activities. their health care providers, (c) clarify and describe the im-
portant role of technology and electronic medical records
Implementation and Performance Improvement. Pharma- that support medication reconciliation documentation and
cists should lead or participate in organizational implemen- reconciliation, (d) provide strategies for preventing medi-
tation of and performance-improvement efforts regarding cation adverse events related to overuse, misuse, omission,
medication reconciliation activities. These activities may in- duplication, or other discrepancies found during medication
clude but are not limited to (a) establishing a medication rec- reconciliation processes, (e) highlight the importance of
onciliation implementation task force or redesign team, (b) completing a full and accurate medication history, includ-
creating a vision and expectations for medication reconcili- ing supplement use, prior to prescribing or administering a
ation activities, (c) securing executive-level commitment to new medication, and (f) describe opportunities for pharma-
or sponsorship of medication reconciliation resource needs, cist extenders, such as pharmacy technicians and students, to
(d) identifying barriers that are preventing, or potential bar- participate in medication reconciliation activities.
riers that may prevent, safe and effective medication recon-
ciliation procedures within their practice model, as well as Resource Constraints. Although the literature demonstrates
possible solutions, (e) guiding workflow development that the important role of pharmacists in successful medica-
integrates operational and clinical needs, (f) establishing tion reconciliation processes across the continuum of care,
roles and responsibilities of health care providers in medi- significant resources are needed to perform medication
cation reconciliation processes, including pharmacy techni- reconciliation skillfully and efficiently, which suggests op-
cians, pharmacy students, and other medical support per- portunities for expanding the roles of pharmacy residents,
sonnel, (g) ensuring that competency-based training for all students, and technicians. When properly trained, these indi-
personnel involved in medication reconciliation procedures viduals can participate in the documentation of medication
is established, (h) creating or assisting in the development of histories, which should then be reviewed by the pharmacist
standardized documentation templates for medication lists for accuracy prior to medication reconciliation, as described
and reconciliation, (i) ensuring that established procedures in the ASHP Pharmacy Practice Model Initiative Summit
meet regulatory requirements and organizational policy, and Recommendations.10 In one study, potential errors due to
(j) developing a method for ongoing medication reconcilia- incomplete or incorrect information, illegible orders, and
tion system evaluation. serious drug interactions were reduced by 82% by having
pharmacy technicians obtain medication histories.11
Training and Competency Assurance. Pharmacists should When confronted with limited resources, pharmacists
lead or participate in (a) identifying all health care provid- should at a minimum participate in and guide interdisciplin-
ers and support staff involved in medication reconciliation ary efforts to develop and define policies and procedures for
activities, (b) creating competency training and skills as- their organizations, standardize workflows for electronic doc-
sessment that are specific to each staff member’s roles and umentation, promote safe practices to the community, and,
responsibilities in medication reconciliation (e.g., conduct- most importantly, engage health care leadership in efforts to
ing a medication interview, taking a medication history, per- ensure medication reconciliation processes are successful.
Conclusion ashp.org/s_ashp/docs/files/MedRec_ASHP_APhA_
Wkgrp_MtgSummary.pdf (accessed 2012 Feb 1).
An effective process for medication reconciliation re- 10. American Society of Health-System Pharmacists.
duces medication errors and supports safe medication use. Pharmacy Practice Model Initiative Summit recom-
Pharmacists are uniquely qualified to lead interdisciplinary mendations. Recommendation D3a. February 1,
efforts to establish and maintain an effective medication rec- 2011. www.ashp.org/DocLibrary/PPMI/Summit-
onciliation process in hospitals and across health systems Recommendations.aspx (accessed 2012 Feb 1).
and should lead or assume key roles in the essential compo- 11. Michels R, Meisel S. Program using pharmacy techni-
nents of medication reconciliation. Because of their crucial cians to obtain medication histories. Am J Health-Syst
role, pharmacists share accountability with other hospital Pharm. 2003; 60:1982–6.
and health-system leaders for the ongoing success of medi-
cation reconciliation processes across the continuum of care.
Approved by the ASHP Board of Directors on April 13, 2012, and
References by the ASHP House of Delegates on June 10, 2012. Developed
1. Joint Commission. National Patient Safety Goals ef-
fective January 1, 2012. NPSG.03.06.01. www.jointcom- This statement was drafted by Michelle M. Thoma, Pharm.D., who
mission.org/assets/1/6/NPSG_Chapter_Jan2012_HAP. declared no potential conflicts of interest.
pdf (accessed 2012 Feb 2).
2. Barnsteiner JH. Medication reconciliation: transfer of ASHP gratefully acknowledges the following individuals and organi-
medication information across settings: keeping it free zations for reviewing drafts of this statement (review does not imply
from error. J Infus Nurs. 2005; 28(suppl 2):31–6. endorsement): Academy of Managed Care Pharmacy (AMCP); Paul
3. Rozich J, Roger R. Medication safety: one organi- Barrett, Pharm.D., M.P.A., BCPS, FASHP; Julie Cooper, Pharm.D.,
zation’s approach to the challenge. J Clin Outcomes BCPS; Jean Douglas, Pharm.D.; Michael S. Edwards, Pharm.D.,
Manag. 2001; 8:27–34. M.B.A., BCOP, FASHP; Kristine M. Gleason, B.S.Pharm.; Kayla
4. Kohn LT, Corrigan JM, Donaldson MS, eds. To err is Hansen, Pharm.D., M.S.; Becky Harvey, Pharm.D.; John Hertig,
human: building a safer health system. Washington, Pharm.D., M.S.; Justin Julius, Pharm.D.; Nishaminy Kasbekar,
DC: National Academy Press; 1999. Pharm.D., FASHP; Carlo Lupano, B.S.Pharm., M.B.A., CCP; Ash-
5. Bates DW, Spell N, Cullen DJ, et al. The cost of ad- ley M. Overy, Pharm.D.; Fred J. Pane, B.S.Pharm., FASHP; Bar-
verse drug events in hospitalized patients. JAMA. bara Petroff, M.S., FASHP; James Ponto, M.S., FASHP; Curt W.
1997; 277:307–11. Quap, M.S., FASHP; Elizabeth Sampsel, Pharm.D., M.B.A., BCPS
6. Joint Commission. 2011 National Patient Safety (AMCP); Jamie S. Sinclair, M.S., FASHP; Richard L. Stambaugh,
Goals. www.jointcommission.org/standards_informa- Pharm.D., M.S., BCPS; Robert L. Stein, Pharm.D., J.D.; and Jeffrey
tion/npsgs.aspx. (accessed 2011 Dec 13). Stroup, Pharm.D., BCPS, AAHIVE.
7. Gleason KM, Groszek JM, Sullivan C, et al. Recon-
ciliation of discrepancies in medication histories and Copyright © 2013, American Society of Health-System Pharma-
admission orders of newly hospitalized patients. Am J cists, Inc. All rights reserved.
Health-Syst Pharm. 2004; 61:1689–95.
8. Gurwich EL. Comparison of medication histories The bibliographic citation for this document is as follows: Ameri-
acquired by pharmacists and physicians. Am J Hosp can Society of Health-System Pharmacists. ASHP statement on the
Pharm. 1983; 40:1541–2. pharmacist’s role in medication reconciliation. Am J Health-Syst
9. Chen D, Burns A. ASHP–APhA Medication Recon- Pharm. 2013; 70:453–6.
ciliation Initiative Workgroup Meeting, February
12, 2007: summary and recommendations. www.

in Primary Care
Position The purposes of this statement are to promote under-

standing of the various ways in which pharmacists provide or
The American Society of Health System Pharmacists contribute to the provision of primary care in integrated health
(ASHP) believes that pharmacists have a role in meeting the systems and to clarify future directions for pharmacists in
primary care needs of patients by fulfilling their responsi- efforts to expand patient care services in primary care.
bilities to provide pharmaceutical care and, in states where
it is authorized, through their expanded responsibilities in Background
collaborative drug therapy management.
Pharmaceutical care is the direct, responsible provision Changes in the nation’s health care system, especially the
of medication-related care for the purpose of achieving definite growth of managed care and integrated health systems, are
outcomes that improve a patient’s quality of life.1 Pharmacists stimulating adoption of primary care as a way of meeting
establish relationships with patients to ensure the appropriate- basic health care needs and managing access to specialty
ness of medication therapy and patients’ understanding of services. Integrated health systems are organized to deliver
their therapy, and to monitor the effects of that therapy. In col- acute, intermediate, long-term, home, and ambulatory care.
laborative drug therapy management, pharmacists enter agree- They are intended to seamlessly provide care across practice
ments with physicians and other prescribers that may authorize settings through appropriate use of individual health profes-
pharmacists, for patients who have a confirmed diagnosis, to sionals and teams.13 Integrated systems offer opportunities
select appropriate medication therapies and regimens and for pharmacists and other health care providers to detect
adjust them on the basis of patients’ responses. and respond to the medication-related needs of patients in
National and international organizations, states, and transition between settings (e.g., from inpatient to ambulatory
health care organizations, among others, may have differing care). As integrated systems expand to offer more intensive
or overlapping definitions of primary care. Primary care is ambulatory care services and cover broader geographic areas,
a concept intended to improve the quality of care received primary care will become more prominent. Improving patients’
by everyone in the United States.2 For the purposes of this access to and continuity of care, implementing disease manage-
document, primary care is defined as the provision of inte- ment, and focusing on quality-related outcomes contribute to
grated, accessible health care services by clinicians who are optimizing drug costs within the total costs of patient care.14
accountable for addressing a majority of personal health care Pharmacists involved in primary care contribute to all of these.
needs, developing a sustained partnership with patients, and Pharmacists participate in primary care services in a
practicing in the context of family and community. Primary variety of practice settings within integrated health systems,
care services should be comprehensive, coordinated, and including the acute (inpatient), physician office, clinic, phar-
continuously provided over time by individuals or a team macy, long-term, and home settings. A growing number of
of health care professionals according to the patient’s needs. acute care hospitals have pharmacists participating in patient
Services should be accessible to patients by telephone or at care activities in ambulatory care clinics and hospital-based
sites of care provision. Clinicians who provide these services home health care services.15 Along with other providers,
are responsible for the quality of care, the satisfaction of pharmacists are expanding and further defining practice
patients, and the efficient use of resources, as well as for models to meet the pharmaceutical and primary care needs
their own ethical behavior.3 of patients throughout the continuum of care.
Practice elements of pharmaceutical care and collabora-
tive drug therapy management are consistent with the intents Responsibilities
and evolving forms of primary care. ASHP supports the
development of definitions and working models of primary Pharmacists involved in primary care participate with other
care that recognize and incorporate the services of pharmacists team members in the management of patients for whom medi-
for meeting primary care needs of patients. In general, phar- cations are a focus of therapy. Pharmacists’ responsibility is to
macists contribute to the provision of primary care through the optimize patients’ medication therapy. Primary care pharmaceu-
delivery of pharmaceutical care and in collaboration with other tical services should be designed to support the various compo-
health care providers.4–9 Furthermore, pharmacists may directly nents of the medication-use process (ordering, dispensing, ad-
provide a limited range of primary care functions in addition to ministering, monitoring, and educating) as individual steps or as
those encompassed by pharmaceutical care, either indepen- they relate to one another in the continuum of care. Pharmacists
dently or in collaboration with other members of a primary care should evaluate all components of the medication-use process
team.10,11 High-quality, coordinated, and continuous medication to optimize the potential for positive patient outcomes.
management for patients should be measurable as a result of the
provision of pharmaceutical care within a primary care de- Functions. In general, pharmacists who participate in
livery model. The benefits to patients are valuable access to providing primary care to individual patients perform the
medication information, the prevention and resolution of med- following functions in collaboration with physicians and
ication-related problems, improved outcomes, and increased other members of the primary care team:
satisfaction.12 Pharmacists are able to use medication-related
encounters with patients to provide information and either • Perform patient assessment for medication-related
resolve or make a referral for other health care needs. factors.
• Order laboratory tests necessary for monitoring include counseling (e.g., abuse of alcohol, tobacco, and other
outcomes of medication therapy. drugs; use of seat belts) and ordering screening procedures
• Interpret data related to medication safety and (e.g., blood lipids and glucose, fecal occult blood). The com-
effectiveness. plexity of services provided varies according to patient need
• Initiate or modify medication therapy care plans on the and support from within the integrated health system.
basis of patient responses. Areas of primary care pharmacy practice that have
• Provide information, education, and counseling to previously been demonstrated to be cost-effective and to improve
patients about medication-related care. outcomes include participation on primary care teams and
• Document the care provided in patients’ records. primary care clinics for medication monitoring and refill in
• Identify any barriers to patient compliance. the management of general or specific pharmacotherapy (e.g.,
• Participate in multidisciplinary reviews of patients’ for asthma, hypertension, dyslipidemia, anticoagulation,
progress. dermatologic diseases, diabetes, and psychotherapeutics).16–23
• Communicate with payers to resolve issues that may
impede access to medication therapies. Documentation of Pharmacists’ Care. Pharmacists in each
• Communicate relevant issues to physicians and other setting should routinely document the quantity and qual-
team members. ity of services provided and the estimated effect on patient
outcomes. Pharmacists must safeguard patients’ rights to
Expanded Functions. Expanded primary care functions of privacy and confidentiality. Patient information should be
pharmacists include all the functions previously described shared only with members of the health care team and others
as well as: with authorized access as needed for the care of patients.
Methods for referral to other health care providers and
• Provide individualized health promotion and disease documentation of care provided should be defined and must
prevention, including administration of immunizations occur as a routine part of the daily functions of a pharma-
where this is legally and organizationally authorized. cist’s practice. When more than one pharmacist is involved
• Perform limited physical assessment and supervise in delivering care, practice standards for the group should
medication therapy with appropriate collaborative be adopted and should serve as a guide for all. Pharmacists
drug therapy management authority. must also establish methods of communication among them-
selves in order to provide and ensure continuity of pharma-
Pharmacists’ Scope of Practice. The pharmacist may have a ceutical care on behalf of patients served.
range of practice privileges that vary in their extent of authority
and responsibility. Pharmacists who participate in collaborative Value of Pharmacist’s Care. Methods for obtaining compen-
primary care practice should meet the health care organization’s sation or economic and professional credit for value-added
competency requirements to ensure that they provide appropri- services must continue to be addressed. Structures designed to
ate quality and continuity of patient care. They should dem- measure the practitioner’s effectiveness as part of an innova-
onstrate required knowledge and skills that may be obtained tive team should be instituted. The pharmacy profession should
through practice-intensive continuing education and pharmacy embrace these activities in the form of well-structured research.
practice and specialty residencies. The specific practice of phar- Integrated health systems will need to receive adequate
macists who participate in collaborative primary care should be support to expand the availability of pharmacists to provide
defined within a scope-of-practice document or a similar tool pharmaceutical care as an essential component of primary care.
developed by the health care organization. The scope-of-
practice document defines activities that pharmacists would
provide within the context of collaborative primary care prac- References
tice, as well as limitations where appropriate. The document
should indicate referral and communication guidelines, includ- 1. American Society of Health System Pharmacists.
ing the documentation of patient encounters and methods for ASHP statement on pharmaceutical care. Am J Hosp
sharing patient information with collaborating medical provid- Pharm. 1993; 50:1720–3.
ers. Also included should be references to activities that will 2. Rubin E. Beyond the rhetoric: ensuring the availability
review the quality of care provided and the methods by which of primary care. Report of an AHC/FASHP retreat. Am
the pharmacist will maintain continuing professional compe- J Pharm Educ. 1993; 57:191–3.
tency for functions within the scope-of-practice document. A 3. Donaldson MS, Yordy KD, Lohr KN, et al., eds.
process should be in place to review and update the scope-of- Primary care: America’s health in a new era.
practice document as appropriate. Committee on the Future of Primary Care, Division
of Health Services, Institute of Medicine. Washington,
Description of Services Provided. The services offered by DC: National Academy Press; 1996.
the pharmacist range from consulting with the health care 4. Koecheler JA, Abramowitz PW, Swim SE, et al.
team to providing direct support of the patient while working Indicators for the selection of ambulatory patients who
in collaboration with the health care team. The pharmacist warrant pharmacist monitoring. Am J Hosp Pharm.
provides medication therapy outcomes management as part 1989; 46:729–32.
of the patient’s ongoing care. The level of intensity of services 5. Lobas LH, Lepinski PW, Abramowitz PW. Effects of
varies as the patient’s needs change. For chronic illnesses, pharmaceutical care on medication cost and quality of
services may range from health maintenance care to active patient care in an ambulatory-care clinic. Am J Hosp
management of treatment; for acute illnesses, services may Pharm. 1992; 49:1681–8.
range from facilitating access to medical care to providing 6. Chrischelles EQ, Helling DK, Aschoff CR. Effect of
initial management. In this context, health maintenance may clinical pharmacy services on the quality of family
practice physician prescribing and medication costs. 18. Alsuwaidan S, Malone DC, Billups SJ, et al.
Drug Intell Clin Pharm. 1989; 23:417–21. Characteristics of ambulatory care clinics and pharma-
7. Monson R, Bond CA, Schuna A. Role of the clinical cists in Veterans Affairs medical centers. Am J Health-
pharmacist in improving drug therapy: clinical phar- Syst Pharm. 1998; 55:68–72.
macists in outpatient therapy. Arch Intern Med. 1981; 19. Libby EA, Laub JJ. Economic and clinical impact of
141:1441–4. a pharmacy-based antihypertensive replacement pro-
8. Bond CA, Monson R. Sustained improvement in gram in primary care. Am J Health-Syst Pharm. 1997;
drug documentation, compliance, and disease con- 54:2079–83.
trol: a four-year analysis of an ambulatory care model. 20. Konzem SL, Morreale AP, Kaplan LA. Pharmacist-
Arch Intern Med. 1984; 114:1159–62. managed primary care dermatology clinic. Hosp
9. Jameson J, VanNoord G, Vanderwoud K. The impact Pharm. 1996; 31:823–5,834.
of a pharmacotherapy consultation on the cost and out- 21. Wilson Norton JL, Gibson DL. Establishing an outpa-
come of medical therapy. J Fam Pract. 1995; 41:469– tient anticoagulation clinic in a community hospital.
72. Am J Health-Syst Pharm. 1996; 53:1151–7.
10. Dong BJ, Echaves SA, Brody RV, et al. Pharmacist 22. Lacro JP, Kodsi A, Dishman B, et al. Primary care role
provision of preventive health services in a hyperten- of psychopharmacists in an ambulatory care setting.
sion clinic. Am J Health-Syst Pharm. 1997; 54:564–6. Calif J Health-Syst Pharm. 1995; 7:9–10.
11. Furmaga EM. Pharmacist management of a hyperlip- 23. Galt KA. Cost avoidance, acceptance, and outcomes
idemia clinic. Am J Hosp Pharm. 1993; 50:91–5. associated with a pharmacotherapy consult clinic in a
12. Galt KA, Skrabal MA, Abdouch I, et al. Using pa- Veteran’s Affairs medical center. Pharmacotherapy.
tient expectations and satisfaction data to design a 1998; 18:1103–11.
new pharmacy service model in a primary care clinic.
J Manage Care Pharm. 1997; 3:531–40.
Vision statement. American Society of Health-System
Pharmacists. Am J Health-Syst Pharm. 1996; 53:174. Approved by the ASHP Board of Directors, April 21, 1999, and
14. Chamberlain MA. The vertically integrated phar- by the ASHP House of Delegates, June 7, 1999. Developed by the
macy department. Am J Health-Syst Pharm. 1998; Council on Professional Affairs.
55:669–75.
15. Raehl CL, Bond CA, Pitterle ME. Ambulatory phar- Kimberly A. Galt, Pharm.D., FASHP, Richard F. Demers, and
macy services affiliated with acute care hospitals. Richard N. Herrier, Pharm.D., are gratefully acknowledged for
Pharmacotherapy. 1993; 13:618–25. drafting this document.
16. Chandler C, Barriuso P, Rozenberg-Ben- Dror K, et
al. Pharmacists on a primary care team at a Veterans Copyright © 1999, American Society of Health-System
Affairs medical center. Am J Health-Syst Pharm. Pharmacists, Inc. All rights reserved.
1997; 54:1280–7.
17. Oke TO. Primary health care services with a func- The bibliographic citation for this document is as follows: American
tional ambulatory care clinical pharmacy in a low in- Society of Health-System Pharmacists. ASHP statement on the
come housing project clinic. J Natl Med Assoc. 1994; pharmacist’s role in primary care. Am J Health-Syst Pharm. 1999;
86:465–8. 56:1665–7.

in Substance Abuse Prevention, Education,
and Assistance
Position 12.5% (17.4% for men; 8.0% for women)3 and of other drug
dependence (“drug addiction”), excluding tobacco, at 2.6%
The American Society of Health-System Pharmacists (3.3% for men; 2.0% for women).4 Studies suggest that the
(ASHP) believes that pharmacists have the unique knowl- prevalence of drug abuse among health professionals ap-
edge, skills, and responsibilities for assuming an important pears to be similar to that in the general population.5-7 Given
role in substance abuse prevention, education, and assistance. their access, however, health professionals abuse prescrip-
Pharmacists, as health care providers, should be actively in- tion drugs more often and “street” drugs less often than does
volved in reducing the negative effects that substance abuse the general population.
has on society, health systems, and the pharmacy profession. Substance abuse frequently coexists with and compli-
Further, ASHP supports efforts to rehabilitate pharmacists cates other psychiatric disorders, and it is a common and
and other health-system employees whose mental or physi- often unrecognized cause of physical morbidity. Intravenous
cal impairments are caused by substance abuse. drug abuse is a major factor in the spread of human immu-
nodeficiency virus (HIV) and hepatitis. Alcohol is a major
factor in cirrhosis of the liver, and tobacco is a key contribu-
Background tor to emphysema and lung cancer. Collectively, substance
abuse contributes significantly to morbidity and mortality in
The term “substance abuse” is commonly used to describe our population and to the cost of health care.
the hazardous or addictive use of psychoactive substances Substance abuse is also a serious workplace problem.
with either addictive, typically depressing or stimulating, or The 2012 NSDUH reported that approximately 14.6 mil-
perception distorting properties. The American Psychiatric lion Americans reporting past month illicit drug use were
Association’s Diagnostic and Statistical Manual of Mental currently employed full- or part-time.2 Substance abuse by
Disorders, 5th edition (DSM-5) includes substance use dis- employees of health care organizations leads to reduced
orders, typically considered addictions with severity catego- productivity, increased absenteeism, drug diversion, and,
ries, and substance-induced disorders, typically intoxica- almost certainly, increased accidents and medication misad-
tion or withdrawal, in its “Substance-Related and Addictive ventures. Consequently, it affects the quality of patient care,
Disorders” chapter.1 Examples include alcohol, tobacco, liability, and operational and health care costs.
“street” drugs (e.g., marijuana, lysergic acid diethylamide The abuse, or non-medical use, of prescription medi-
[LSD], phencyclidine [pcp], cocaine, methamphetamine, cations has also become a prevalent issue. Nonmedical use
methylenedioxymethamphetamine [MDMA], inhalants, of prescription drugs among youths aged 12 to 17 and young
gammahydroxybutyrate [GHB], heroin, K2/Spice, salvia, adults aged 18 to 25 in 2012 was the second most prevalent
bath salts), and the nonmedical use or the overuse of psy- illicit drug use category, with marijuana being first.2 The sur-
choactive and other prescription and nonprescription drugs vey also found that over half of all prescription drug abusers
(e.g., hydrocodone, oxycodone, ketamine, methadone, dex- had obtained the prescription medication “from a friend or
tromethorphan). relative for free” as compared to the 3.9% who had obtained
Substance abuse is a major societal problem. The the medication from a drug dealer or other stranger.
2012 National Household Survey on Drug Use and Health Pharmacists have unique, comprehensive knowledge
(NSDUH), a primary source of statistical information on about the safe and effective use of medications and about
drug abuse in the U.S. population, estimated that (a) 23.9 mil- the adverse effects of their inappropriate use. The provi-
lion Americans (or 9.2% of the population 12 years of age or sion of pharmaceutical care to individual patients involves
older) had used an illicit drug* in the past month, (b) 2.8 mil- pharmacists assessing the appropriateness of pharmacother-
lion Americans were classified with dependence or abuse of apy, counseling, and monitoring medication-use outcomes.
both illicit drugs and alcohol, (c) 4.5 million had dependence Health-system pharmacists have responsibilities for ensur-
or abuse of illicit drugs but not alcohol, and (d) 14.9 million ing a safe and effective medication-use system, including le-
Americans were dependent on alcohol.2 A 2001-2002 study gal and organizational responsibilities for medication distri-
conducted using DSM-IV criteria in the U.S. suggested of bution and control across the continuum of practice settings
substance abuse/dependence disorders suggested a lifetime within health care organizations. With this combination of
prevalence of alcohol use disorders of 30.3%, of drug use knowledge and organizational responsibilities, pharmacists
disorders of 10.3%, of alcohol dependence (alcoholism) of are prepared to serve in leadership and service roles in sub-
stance abuse prevention and education and assist in a variety
of patient care, employee health, and community activities.
*The National Survey on Drug Use and Health obtains informa-
tion on nine categories of illicit drug use: use of marijuana, cocaine, Responsibilities
heroin, hallucinogens, and inhalants, as well as the nonmedical use
of prescription-type pain relievers, tranquilizers, stimulants, and The scope of substance abuse responsibilities of pharmacists
sedatives. varies with the health care organization’s mission, policies
and procedures, patient population, and community. The re- 2. Providing recommendations about the appropriate use
sponsibilities listed below should be adapted to meet local of mood-altering substances to health care providers
needs and circumstances. Each responsibility is intended to and the public, including those persons recovering
be applicable to any substance of abuse; therefore, specific from substance dependency and their caregivers.9
substances are generally not mentioned. Pharmacists should 3. Fostering the development of undergraduate and
be involved in substance abuse prevention, education, and graduate college of pharmacy curricula and pharmacy
assistance by performing the following activities: technician education on the topic of substance abuse
prevention, education, and assistance.10
Prevention 4. Providing substance abuse education to fellow phar-
macists, other health care professionals, and other em-
1. Participating in or contributing to the development of ployees of their health care organization.
substance abuse prevention and assistance programs 5. Instructing drug abuse counselors in drug treatment
within health care organizations. A comprehensive programs about the pharmacology of abused sub-
program should consist of (a) a written substance stances and medications used for detoxification.
abuse policy; (b) an employee education and aware- 6. Promoting and providing alcohol risk-reduction edu-
ness program; (c) a supervisor training program; cation and activities.
(d) an employee assistance program; (e) peer support 7. Maintaining professional competency in substance
systems, such as pharmacist recovery networks; and abuse prevention, education, and assistance through
(f) drug testing.8 formal and informal continuing education.
2. Participating in public substance abuse education and 8. Providing post-graduate training in addictions, pain
prevention programs (e.g., in primary and secondary management, and palliative care where feasible.
schools, colleges, churches, and civic organizations) 9. Conducting research on substance abuse and addic-
and stressing the potential adverse health conse- tion.
quences of the misuse of legal and use of illegal drugs. 10. Educating patients about the correct storage, handling,
3. Opposing the sale of alcohol and tobacco products by and proper disposal of prescription medications.
pharmacists and in pharmacies.
4. Establishing a multidisciplinary controlled-substance Assistance
inventory system, in compliance with statutory and
regulatory requirements, that discourages diversion 1. Assisting in the identification of patients, coworkers,
and enhances accountability. Where helpful, for ex- and other individuals who may be having problems
ample, procedures might require the purchase of con- related to their substance abuse, and referring them to
trolled substances in tamper-evident containers and the appropriate people for evaluation and treatment.
maintenance of a perpetual inventory and ongoing 2. Participating in multidisciplinary efforts to support
surveillance system. and care for the health care organization’s employ-
5. Working with local, state, and federal authorities in ees and patients who are recovering from substance
controlling substance abuse, including participation in dependency.
state prescription drug monitoring programs, encour- 3. Supporting and encouraging the recovery of health
aging participation in appropriate prescription disposal professionals with alcoholism or other drug addictions.
programs, complying with controlled-substance re- Major elements of an employer’s support program
porting regulations, and cooperating in investigations might include (a) a willingness to hire or retain em-
that involve the misuse of controlled substances, espe- ployees; (b) participating in monitoring and reporting
cially diversion from a health care organization. requirements associated with recovery or disciplinary
6. Working with medical laboratories to (a) identify contracts; (c) maintaining an environment supportive
substances of abuse by using drug and poison con- of recovery; (d) establishing behavioral standards and
trol information systems, (b) establish proper speci- norms among all employees that discourage the abuse
men collection procedures based on knowledge of of psychoactive substances, including alcohol; and
the pharmacokinetic properties of abused substances, (e) participating in peer assistance programs.
and (c) select proper laboratory tests to detect the sus- 4. Collaborating with other health care providers in the
pected substances of abuse and to detect tampering development of the pharmacotherapeutic elements of
with samples. drug detoxification protocols.
7. Discouraging prescribing practices that enable or 5. Providing pharmaceutical care to patients being treated
foster drug abuse behavior (e.g., prescribing a larger for substance abuse and dependency.
quantity of pain medication than is clinically needed 6. Maintaining knowledge of professional support
for treatment of short-term pain). groups (e.g., state- and national-level pharmacist re-
8. Collaboration with outpatient and ambulatory care covery networks) and other local, state, and national
providers to prevent substance abuse after discharge. organizations, programs, and resources available for
preventing and treating substance abuse (see “Other
Education Resources”).
7. Refusing to allow any student or employee, includ-
1. Providing information and referral to support groups ing health professionals, to work, practice, or be on-
appropriate to the needs of people whose lives are site for rotations within the health care organization
affected by their own or another person’s substance while his or her ability to safely perform his or her
abuse or dependency. responsibilities is impaired by drugs, including al-
cohol. The refusal should follow the organization’s 2. AACP Special Committee on Substance Abuse
policies and procedures, the principles of ethical and and Pharmacy Education. American Association of
responsible pharmacy practice, and statutory require- Colleges of Pharmacy guidelines for the development
ments. Practice should not be precluded after appro- of addiction and related disorders policies for colleges
priate treatment and monitoring, if approved by the and schools of pharmacy. http://www.aacp.org/career/
treatment provider or contract monitor (or both, when grants/Documents/Guidelines%20for%20the%20
applicable). Development%20of%20Addiction%20and%20
Related%20Disorders%20Policies%20for%20
References Schools%20and%20Colleges%20of%20Pharmacy.
pdf (accessed 2014 Jun 24).
1. American Psychiatric Association. Diagnostic 3. Tucker DR, Gurnee MC, Sylvestri MF, et al.
and statistical manual of mental disorders. 5th ed. Psychoactive drug use and impairment markers in
Arlington, VA: American Psychiatric Association; pharmacy students. Am J Pharm Educ. 1988; 52:42–7.
2013. http://www.dsm.psychiatryonline.org/ (ac- 4. Miederhoff PA, Voight FB, White CE. Chemically im-
cessed 2014 Jun 26). paired pharmacists: an emerging management issue.
2. Substance Abuse and Mental Health Services Top Hosp Pharm Manage. 1987; 7(Nov):75–83.
Administration. Results from the 2012 National 5. Kriegler KA, Baldwin JN, Scott DM. A study of al-
Survey on Drug Use and Health: Summary of national cohol and other drug use behaviors and risk factors in
findings; NSDUH Series H-46, HHS publication no. health profession students. J Am Coll Health. 1994;
(SMA) 13-4795.Rockville, MD: Substance Abuse and 42:259–65.
Mental Health Services Administration; 2013. 6. Haberman P. Alcoholism in the professions. Troy, MI:
3. Hasin DS, Stinson FS, Ogburn E, et al. Prevalence, Performance Resource; 1991.
correlates, disability, and comorbidity of DSM-IV 7. Bissell L, Royce JE. Ethics for addiction profession-
alcohol abuse and dependence in the United States. als. Center City, MN: Hazelden Foundation; 1994.
Arch Gen Psychiatry. 2007; 64:830–42. 8. Colvin R. Prescription drug addiction: the hidden epi-
4. Comton WM, Thomas YF, Stinson FS, et al. demic. Omaha, NE: Addicus; 2002.
Prevalence, correlates, disability, and comorbidity of 9. Crosby L, Bissell L. To care enough: intervention
DSM-IV drug abuse and dependence in the United with chemically-dependent colleagues. Minneapolis:
States. Arch Gen Psychiatry. 2007; 64:566–76. Johnson Institute; 1989.
5. McAuliffe WE, Santangelo SL, Gingras J, et al. Use 10. Johnson VE. Intervention: how to help someone who
and abuse of controlled substances by pharmacists and doesn’t want help. A step-by-step guide for fami-
pharmacy students. Am J Hosp Pharm. 1987; 44:311– lies and friends of chemically-dependent persons.
7. Minneapolis: Johnson Institute; 1989.
6. Sullivan E, Bissell L, Williams E. Chemical depen- 11. Rinaldi RC, Steindler EM, Wilford BB, et al.
dency in nursing: the deadly diversion. Menlo Park, Clarification and standardization of substance abuse
CA: Addison-Wesley; 1988. terminology. JAMA. 1988; 259:555–7.
7. Bissell L, Haberman PW, Williams RL. Pharmacists 12. Brown ME, Trinkoff AM, Christen AG, et al.
recovering from alcohol and other drug addictions: an Impairment issues for health care professionals: review
interview study. Am Pharm. 1989; NS29(6):19–30. and recommendations. Subst Abus. 2002; 23S:155–65.
[Erratum, Am Pharm. 1989; NS29(9):11.] 13. Dole EJ, Tommasello AC. Recommendations for
8. Substance Abuse and Mental Health Services implementing effective substance abuse education in
Administration. Making your workplace drug-free: pharmacy practice. Subst Abus. 2002; 23S:263–71.
a kit for employers. DHHS publication no. SMA07- 14. Lafferty L. Hunter TS, Marsh WA. Knowledge, at-
4230. Rockville, MD: Substance Abuse and Mental titudes and practices of pharmacists concerning pre-
Health Services Administration; 2007. http://store. scription drug abuse. J Psychoactive Drugs. 2006;
samhsa.gov/shin/content//SMA07-4230/SMA07- 38(3):229–32
4230.pdf (accessed 2014 Jun 24). 15. Baldwin JN, Scott DM, Agrawal S, et al. Assessment
9. Davis NH. Dispensing and prescribing cautions for of alcohol and other drug use behaviors in health pro-
medical care during recovery from alcohol and drug fessions students. Subst Abus. 2006; 27(3):25–35.
addiction. J Pharm Pract. 1991; 6:362–8. 16. American Pharmacists Association. Pharmacists’ role
10. DeSimone EM, Kissack JC, Scott DM, et al. Curricular in addressing opioid abuse, addiction, and diversion. J
guidelines for pharmacy: substance abuse and addic- Am Pharm Assoc. 2014; 54:e5–e15.
tive disease. http://www.aacp.org/resources/educa- 17. Lord S, Downs G, Furtaw P, et al. Nonmedical use
tion/Documents/CurricularGuidelinesforPharmacy- of prescription opioids and stimulants among student
SubstanceAbuseandAddictiveDisease.pdf (accessed pharmacists. J Am Pharm Assoc. 2009; 49:519–28.
2014 May 27). 18. American Pharmacists Association. Addiction and
substance abuse in the pharmacy professions: From
Other Resources discovery to recovery. Pharmacy Today. 2013;
19(8):62–72.
1. Hogue MD, McCormick DD, eds. Points of light: 19. Merlo LJ, Cummings SM, Cottler LB. Recovering
a guide for assisting chemically dependent health substance-impaired pharmacists’ views regarding oc-
professional students. Washington, DC: American cupational risks for addiction. J Am Pharm Assoc.
Pharmaceutical Association; 1996. 2012; 52:480–91.
20. Baldwin JN. Substance abuse care. In: Allen LV, ed. e. Cocaine Anonymous (CA); for individuals with
Remington: the science and practice of pharmacy. 22nd cocaine dependencies. Telephone, 310-559-5833;
ed. London, UK: Pharmaceutical Press; 2013:2613–9. Website, www.ca.org.
21. Kenna GA, Baldwin JN, Trinkoff A, et al. Substance f. International Doctors in Alcoholics Anonymous
use disorders in health care professionals. In: Johnson (IDAA) includes pharmacists in recovery regard-
BA, ed. Addiction medicine: science and practice. less of degree (a national group that has an annual
New York, NY: Springer; 2011:1375–98. conference and recovery resources for doctoral
22. Baldwin JN, Scott DM, DeSimone EM, et al. Substance degree health professionals). Website is www.
use attitudes and behaviors at three pharmacy colleges. idaa.org. IDAA Executive Director contact is ex-
Subst Abus. 2011; 32:27–35. ecutive@idaa.org.
23. National Clearinghouse for Alcohol and Drug g. Nar-Anon; for helping people affected by an-
Information (NCADI). The clearinghouse is a feder- other’s drug misuse. Telephone, 800-477-6291;
ally funded service that assists in finding information e-mail wso@nar.anon.org.
on all aspects of substance abuse. Many publications h. Narcotics Anonymous (NA); provides informa-
and educational materials are available free of charge tion and support to recovering substance abusers.
from NCADI. Telephone, 800-729-6686; Website, Telephone, 818-773-9999; Website, www.na.org.
http://store.samhsa.gov/home 28. Advocacy and professional substance abuse educa-
24. Center for Substance Abuse Prevention (CSAP) tion:
Workplace Helpline (for employers). Telephone, 800- a. Pharmacist Recovery Networks (PRNs) exist in
967-5752; e-mail, dwp@samhsa.hhs.gov. most states in the U.S. to assist pharmacists (and
25. National Association of State Alcohol and Drug Abuse often also pharmacy technicians and sometimes
Directors (NASADAD). The association coordinates pharmacy students) with addictions or in addiction
and encourages cooperative efforts between the fed- recovery. The www.usaprn.org website includes
eral government and state agencies on substance information about these programs by state as well
abuse. NASADAD serves as a resource on state drug as information about other recovery-related re-
programs and can provide contacts in each state. sources.
Website, www.nasadad.org. b. The Pharmacy Section (cosponsored by APhA
26. Community organizations are available to help with and APhA Academy of Students of Pharmacy) of
drug or alcohol problems. Treatment counselors may the University of Utah School on Alcoholism and
be valuable in developing assistance policies and in Other Drug Dependencies was a one-week semi-
providing professional education about treatment nar held each summer until 2014 (options are be-
and referral systems. Community drug abuse pre- ing considered to establish the School at another
vention organizations may be helpful in prevention site beginning in 2015) for learning to deal with
efforts, including community drug education. Check substance abuse problems as they affect the pro-
your local telephone directory under headings such as fession. Consult www.usaprn.org for updates and
Alcoholism Information and Treatment, Drug Abuse current status of the School.
Information and Treatment, and Counselors.
27. Twelve-step groups (usually available locally un-
less otherwise noted; listed telephone numbers and Approved by the ASHP Board of Directors on April 10, 2015, and
Websites are for national headquarters): by the ASHP House of Delegates June 7, 2015. Developed through
a. Adult Children of Alcoholics (ACA); for adults the ASHP Council on Pharmacy Practice. This statement supersedes
who, as children, lived with alcoholic parents. a previous version dated June 2, 2013.
Telephone, 562-595-7831; Website, www.adult-
children.org. Jeffrey N. Baldwin, Pharm.D. and Chelsea Leeper, Pharm.D., are
b. Al-Anon; provides information on alcoholism and gratefully acknowledged for revising this statement.
alcohol abuse and refers callers to local Al-Anon
support groups established to help people affected Copyright © 2015. American Society of Health-System Pharmacists,
by others’ alcohol misuse. Telephone, 757-563- Inc. All rights reserved.
1500; Website, www.al-anon.org.
c. Alateen; for adolescents affected by alcoholics. Note: This statement had not been published in the American Jour-
Website, www.al-anon.alateen.org/for-alateen. nal of Health-System Pharmacy (AJHP) when ASHP Best Practices
d. Alcoholics Anonymous (AA); provides infor- 2015–2016 went to press. Some minor editorial differences may ex-
mation and support to recovering alcoholics. ist between this document and the official one that will eventually
Telephone, 212-870-3400; Website, www.alco- appear in AJHP and subsequent editions of this publication.
holics anonymous.org.
ASHP Statement on Pharmacy Services to the

Emergency Department
Position ventory control, cost containment, and participation on
resuscitation teams but have since expanded to include
The American Society of Health-System Pharmacists clinical pharmacy services.9 The effectiveness of clini-
(ASHP) believes every hospital pharmacy department cal pharmacy services has been well documented in other
should provide its emergency department (ED) with the settings. The participation of pharmacists in intensive care
pharmacy services that are necessary for safe and effective units and on internal medicine teams has improved patient
patient care. Although the nature of these services will vary outcomes by reducing preventable ADEs by 66% and 78%,
with each institution’s needs and resources, the pharmacist’s respectively.10-12 Similar effectiveness with pharmacist
role may include participation on emergency medicine teams has also been
documented.13 Despite this evidence, the 2005 ASHP na-
• Working with emergency physicians, emergency tional survey found that only 3.5% of the hospitals surveyed
nurses, and other health care professionals to develop had a pharmacist assigned to the ED for any period of time,
and monitor medication-use systems that promote safe and only 5% had a formal policy requiring that pharmacists
and effective medication use in the ED, especially for review and approve medication orders before administra-
high-risk patients and procedures, tion in EDs.14
• Collaborating with emergency physicians, emergency
nurses, and other health care professionals to promote Pharmacy Services in the ED
medication use in the ED that is evidence based and
aligned with national quality indicators, All health care professionals share a commitment to and
• Participating in the selection, implementation, and responsibility for providing safe and effective patient care.
monitoring of technology used in the medication-use These shared objectives provide strong incentives for col-
process, laboration. Pharmacists and other health care professionals
• Providing direct patient care as part of the interdisci- can collaborate in developing and monitoring medication-
plinary emergency care team, use systems that promote safe and effective medication use
• Participating in or leading emergency-preparedness ef- in the ED, including medication use in high-risk ED patients
forts and quality-improvement initiatives, and procedures. By working together, pharmacists and other
• Educating patients, caregivers, and health care profes- health care professionals can ensure that medication use in
sionals about safe and effective medication use, and the ED is evidence based, cost-effective, and adherent to
• Conducting or participating in ED-based research. national guidelines; develop and implement emergency-
preparedness plans and quality-improvement efforts; and, in
ASHP supports the expansion of pharmacy education many cases, foster the institution’s education and research
and postgraduate residency training to include an emphasis initiatives. The department of pharmacy should assume a
on emergency care. leadership role in ensuring these collaborations.
The purposes of this statement are to promote under- When making decisions regarding pharmacy services
standing of the pharmacist’s contributions to the care of pa- to the ED, hospital leadership should consider the ED’s need
tients in the ED and to suggest future roles for pharmacists for medication therapy management services, medication-
in providing that care. allergy assessment and clarification, medication-interaction
assessment, reporting of and intervention on medication er-
Background rors and ADEs, timely provision of drug information, and
participation in formulary decision making. Institutions
EDs across the nation treat approximately 114 million pa- should also keep in mind the Joint Commission’s pharma-
tients annually.1 EDs are overcrowded because of a high cist first-review requirement15 and national patient safety
percentage of uninsured patients, increased patient volume, goals,16 the hospital’s quality indicators related to medica-
increased complexity of patients in the ED, and a hospital tion selection, timing, and delivery; the potential effects of
bed shortage that frequently results in the boarding of inpa- patient flow and technology on medication safety in the ED;
tients in the ED. The combination of interruptions, intense and contributions pharmacists can make to continuity of
pressure, and a fast-paced environment can lead to medicare from ED admission through hospital discharge.
cation errors and fewer error interceptions.1 The Institute
of Medicine (IOM) has estimated that as many as 98,000 Patient Care. The IOM report, Hospital-Based Emergency
people die each year as a result of medical errors and that Care: At the Breaking Point, recommends the inclusion of
adverse drug events (ADEs) occurred in 3.7% of hospitaliza- clinical pharmacists on the ED care team to ensure patients’
tions.2 Hafner et al.3 reported a similar frequency of ADEs medication needs are appropriately met, to lead system
in the ED. Chin et al.4 found that 3.6% of patients received changes in order to reduce or eliminate medication errors,
an inappropriate medication in the ED and 5.6% were pre- and to evaluate the cost effectiveness of medication therapy
scribed an inappropriate medication at discharge. for the patient and hospital.1 As part of the interdisciplinary
Pharmacy services in the ED have been documented ED care team, pharmacists can provide care to critically ill
since the 1970s.5-8 These services initially focused on inpatients by
• Participating in resuscitation efforts, • Assisting in the development, implementation, and as-

• Providing consultative services that foster appropriate sessment of various technologies used throughout the
evidence-based medication selection, ED’s medication-use process,
• Providing consultation on patient-specific medication • Conducting failure mode and effects analysis and root-
dosage and dosage adjustments, cause analysis on error-prone aspects of the medica-
• Providing drug information consultation to emergency tion-use process,
physicians, emergency nurses, and other clinicians, • Participating in ED-based and hospitalwide commit-
• Monitoring for patient allergies and drug interactions, tees (e.g., pharmacy and therapeutics, infection con-
• Monitoring patient therapeutic responses (including trol, disaster) whose decisions affect medication use in
laboratory values), the ED,
• Continuously assessing for and managing adverse drug • Maintaining compliance with standards of national ac-
reactions, and crediting bodies, such as the Joint Commission, and
• Gathering or reviewing medication histories and rec- • Assisting in surveillance and reporting of adverse drug
onciling patients’ medications. reactions.
In addition, pharmacists can provide care to ambulatory pa- Education. The pharmacy department should support the
tients in the ED by pharmacist’s role in providing education and information to
health care professionals, patients, and the public in ED ser-
• Modifying medication regimens based on collabora- vice areas. Specific activities could include
tive-practice agreements for the management of spe-
cific patient populations that return to the ED, • Conducting educational forums for health care profes-
• Providing vaccination screening, referral, and adminis- sionals and students on topics such as emergency pre-
tration, paredness, disaster management, poisoning prevention
• Offering patient and caregiver education, including and treatment, immunizations, and use of medications
discharge counseling and follow-up, and in the ED and emergency situations,
• Providing information on obtaining medications • Providing health literacy-sensitive education to pa-
through patient assistance programs, care funds, and tients and caregivers regarding medication use, dis-
samples. ease-state management, and prevention strategies, and
• Offering ED-based educational opportunities to phar-
The boarding of patients in the ED until an inpatient bed macy students and residents.
becomes available poses challenges for patients, caregivers,
and health care professionals. The department of pharmacy The ED offers an enormous number of services, activi-
should work with the health care professionals involved in ties, and opportunities to train future pharmacists in all as-
the care of these patients to provide a seamless medication- pects of the medication-use process. Students and residents
use process. could participate in longitudinal experiences in ED-based
services such as clinics, community services (e.g., health
Emergency-Preparedness Planning. ASHP believes that all fairs), and satellite pharmacies and could study topics as
hospital and health-system pharmacists must assertively ex- varied as cultural follow-up, ADE monitoring and reporting,
ercise their responsibilities to prepare for and respond to di- or toxicology services. Introductory experiences could focus
sasters.17 ASHP has insisted that emergency-response plan- on student training on specific skills or competencies, such
ners at the federal, regional, state, and local levels call on as taking medication histories, medication reconciliation, or
pharmacists to participate in the full range of planning issues discharge counseling. Residency training of pharmacists in
related to pharmaceuticals. Hospital emergency-prepared- emergency care would provide more rewarding educational
ness plans, including ED components, must be developed experiences, foster pharmacist involvement in emergency-
with the assistance of departments of pharmacy. Pharmacists medicine research, and ultimately improve the quality of
should play a pivotal role in emergency-preparedness plan- patient care. Such residencies should meet ASHP-accredited
ning and as members of the health care team that provides residency quality standards.20 Achievement of the goals, ob-
care to victims. Ensuring the efficacy and safety of the med- jectives, and expected outcomes of such training would be
ication-use process is a natural role for pharmacists because supported by around-the-clock or on-call clinical pharmacist
treatment of disaster victims almost always involves the use services in the ED.
of pharmacologic agents.18,19
ED-Based Research. Research on and publications about
Quality-Improvement Initiatives. The department of phar- ED pharmacy, though plentiful, usually focus on specific
macy can collaborate with other health care professionals clinical settings, such as toxicology, drug interactions, and
on a variety of quality-improvement initiatives in the ED, infectious disease epidemiology. The literature lacks a broad
including representation of the varied scope and range of ED pharmacy
practices. ASHP believes that there should be more research
• Guiding the development of evidence-based treatment and publications regarding medication use in the ED and
protocols, algorithms, and clinical pathways that are ED-based pharmacy activities. Studies that generate data on
congruent with nationally accepted practice guidelines therapeutic, safety, humanistic, and economic outcomes of
and quality indicators, pharmacist-mediated process changes are urgently needed.
Professional Development of in the intensive care unit. JAMA. 1999; 282:267–70.

[Erratum, JAMA. 2000; 283:1293.]
Pharmacists in Emergency Care
11. Kane SL, Weber RJ, Dasta JF. The impact of criti-
cal care pharmacists on enhancing patient outcomes.
ASHP believes there should be an increase in the number of
Intensive Care Med. 2003; 29:691–8.
ED-based training opportunities for pharmacists, pharmacy
12. Kucukarslan SN, Peters M, Mlynarek M, et al.
students, and residents. Schools and colleges of pharmacy
Pharmacists on rounding teams reduce preventable ad-
are encouraged to provide ED-based educational oppor-
verse drug events in hospital general medicine units.
tunities for students. Hospitals and health systems are en-
Arch Intern Med. 2003; 163:2014–8.
couraged to support ED-based educational programs that
13. Ling JM, Mike LA, Rubin J, et al. Documentation
produce experts in the field. Postgraduate training of phar-
of pharmacist interventions in the emergency depart-
macists will provide a pipeline of clinicians, educators, lead-
ment. Am J Health-Syst Pharm. 2005; 62:1793–7.
ers, and scientists who are experts in and committed to qual-
14. Pedersen CA, Schneider PJ, Scheckelhoff DJ. ASHP
ity emergency care.
national survey of pharmacy practice in hospital set-
tings: dispensing and administration—2005. Am J
Conclusion Health-Syst Pharm. 2006; 63:327–45.
15. Medication Management Standard MM.4.10—pre-
Every pharmacy department should provide the ED with paring and dispensing. In: Comprehensive accredi-
the pharmacy services required to ensure safe and effec- tation manual for hospitals. Oakbrook Terrace, IL:
tive patient care. These services must be tailored to match Joint Commission on the Accreditation of Healthcare
each institution’s needs and resources; therefore, pharmacy Organizations: 2006:MM-10.
departments must decide the best way to safely provide 16. Joint Commission. National patient safety goals.
medications to ED patients. ASHP supports the expansion www.jointcommission.org/PatientSafety/National
of pharmacy education and postgraduate residency training PatientSafetyGoals (accessed 2007 May 25).
to include emphasis on emergency care in order to develop 17. American Society of Health-System Pharmacists.
an adequate supply of pharmacists who are trained to deliver ASHP statement on the role of health-system phar-
these essential pharmacy services. macists in emergency preparedness. Am J Health-Syst
Pharm. 2003; 60:1993–5.
References 18. Burda AM, Sigg T. Pharmacy preparedness for inci-
dents involving weapons of mass destruction. Am J
1. Institute of Medicine of the National Academies. Health-Syst Pharm. 2001; 58:2274–84.
Hospital-based emergency care: at the breaking point. 19. Setlak P. Bioterrorism preparedness and response:
www.iom.edu/CMS/3809/16107/35007.aspx (ac- emerging role for health-system pharmacists. Am J
cessed 2006 Sep 5). Health-Syst Pharm. 2004; 61:1167–75.
2. Kohn LT, Corrigan JM, Donaldson MS, eds. To err is 20. American Society of Health-System Pharmacists.
human: building a safer health system. Washington, ASHP residency accreditation regulations and stan-
DC: National Academy Press; 1999:26. dards. www.ashp.org/Import/ACCREDITATION/
3. Hafner JW Jr, Belknap SM, Squillante MD, et al. Residency Accreditation/RegulationsStandards.aspx
Adverse drug events in emergency department pa- (accessed 2008 Sep 24).
tients. Ann Emerg Med. 2002; 39:258–67.
4. Chin MH, Wang LC, Jin L, et al. Appropriateness of
Developed through the ASHP Council on Pharmacy Practice and
medication selection for older persons in an urban
approved by the ASHP Board of Directors on September 28, 2007,
academic emergency department. Acad Emerg Med.
and by the ASHP House of Delegates on June 10, 2008.
1999; 6:1232–42.
5. Elenbaas RM, Waeckerle JF, McNabney WK. The
Roshanak Aazami, Pharm.D.; Elizabeth A. Clements, Pharm.D.;
clinical pharmacist in emergency medicine. Am J
Daniel J. Cobaugh, Pharm.D., FACCT, DABAT; and Frank P.
Hosp Pharm. 1977; 34:843–6.
Paloucek, Pharm.D., are gratefully acknowledged for drafting this
6. Schwerman E, Schwartau N, Thompson CO, et al. The
statement. The ASHP Section of Clinical Specialists and Scientists
pharmacist as a member of the cardiopulmonary resus-
Section Advisory Group on Emergency Care is also gratefully ac-
citation team. Drug Intell Clin Pharm. 1973; 7:299–
knowledged for reviewing drafts and providing advice on the devel-
308.
opment of this statement.
7. Kasuya A, Bauman JL, Curtis RA, et al. Clinical phar-
macy on-call program in the emergency department.
The drafters have declared no conflict of interest.
Am J Emerg Med. 1986; 4:464–7.
8. Powell MF, Solomon DK, McEachen RA. Twenty-
Copyright © 2009, American Society of Health-System Pharma-
four hour emergency pharmaceutical services. Am J
cists, Inc. All rights reserved.
Hosp Pharm. 1985; 42:831–5.
9. Fairbanks RJ, Hays DP, Webster DF, et al. Clinical
pharmacy services in an emergency department. Am J The bibliographic citation for this document is as follows: Ameri-
Health-Syst Pharm. 2004; 61:934–7. can Society of Health-System Pharmacists. ASHP statement on
10. Leape LL, Cullen DJ, Clapp MD, et al. Pharmacist par- pharmacy services to the emergency department. Am J Health-Syst
ticipation on physician rounds and adverse drug events Pharm. 2008; 65:2380–3.
ASHP Statement on Racial and Ethnic

Disparities in Health Care
Position important that it is one of only two overarching goals for the
Healthy People 2010 objectives.3
Health disparities continue to be a major public health prob- Culture has been defined by IOM as “the accumulated
lem confronting the U.S. health care system. These dispari- store of shared values, ideas (attitudes, beliefs, values, and
ties arise from a complex set of factors, including social norms), understandings, symbols, material products, and
and economic inequality, cultural and linguistic barriers, practices of a group of people.”1 Ethnicity refers to “a shared
and persistent racial and ethnic discrimination. Evidence culture and way of life, especially as reflected in language,
continues to emerge, however, that some health dispari- folkways, religious and other institutional forms, material
ties are attributable to differences in the quality of health culture such as clothing and food, and cultural products such
care provided to different racial and ethnic groups. The as music, literature, and art.” 1 An ethnic group is a collection
American Society of Health-System Pharmacists (ASHP) of people “socially distinguished or set apart, by others or by
believes that all patients, regardless of race, ethnicity, sex, itself, primarily on the basis of cultural or national-origin
age, sexual orientation, religion, physical or mental dis- characteristics.”1 Like ethnicity, race has been described as
ability (or impairment), education, socioeconomic status, a sociocultural concept used to distinguish groups of people
diagnosis, or limitations in access, have the right to high- (in this case, those who share certain physical characteris-
quality health care that reflects knowledge of, sensitivity tics) and treat them differently.
to, and respect for their differences. ASHP recognizes the need to address all forms of
Pharmacists who practice in hospitals and health sys- health disparities and believes that health-system pharma-
tems (“health-system pharmacists”), working individually cists can take an important step in addressing these broader
and in coordination with interested organizations and other disparities by assuming a leadership role in the national cam-
health care professionals, can play a leading role in build- paign to eliminate racial and ethnic disparities in health care.
ing culturally competent systems of care to reduce racial and Health-system pharmacists, like other health profession-
ethnic disparities in health care by als, have espoused a tradition of nondiscriminatory health
care practice.4,5 Because medication therapy management is
• Increasing awareness of these disparities among health central to many of the health disparities cited by IOM (e.g.,
care providers, health-system administrators, legisla- treatment for pain, HIV infection, diabetes, end-stage renal
tors, regulators, third-party payers, and the public, disease, kidney transplantation),1 health-system pharmacists
• Promoting a more diverse and culturally competent have opportunities to directly address these disparities. As
health care work force and environment, health-system administrators and members of multidisci-
• Ensuring effective communication with patients and plinary health care teams, health-system pharmacists have
among providers, an important role to play in implementing the institutional
• Fostering consistent use of multidisciplinary teams changes necessary to eliminate racial and ethnic disparities
and evidence-based guidelines for patient care, in health care. ASHP believes that health-system pharma-
• Collecting and reporting data on health care access, cists have a professional and moral responsibility to address
utilization, and outcomes by racial and ethnic minori- racial and ethnic disparities in health care.
ties and measuring progress toward reducing health
care disparities, and General Principles
• Researching, identifying, and disseminating best prac-
tices for providing culturally competent care and re- The following three principles should guide the actions of
ducing disparities in health care. health-system pharmacists in efforts to eliminate racial and
ethnic disparities in health care: (1) all patients have the right
Background to high-quality care, (2) medication-use practices should re-
flect knowledge of, sensitivity to, and respect for the race
The Institute of Medicine (IOM) defines racial and ethnic and culture of the patient, and (3) health-system pharmacists
disparities in health care as “racial or ethnic differences in have a vital role to play in eliminating racial and ethnic dis-
the quality of healthcare that are not due to access-related parities in health care.
factors or clinical needs, preferences, and appropriateness
of intervention.”1 IOM states that “evidence of racial and All Patients Have the Right to High-Quality Care. A long-
ethnic disparities in healthcare is . . . remarkably consistent standing policy position of ASHP holds that “all patients
across a range of illnesses and healthcare services.” More have the right to . . . high-quality pharmaceutical care.”4
than 600 articles documenting racial or ethnic variations in ASHP believes that all patients have the right to receive care
health care have been published in the past three decades.2 from pharmacists and that health-system pharmacists should
With the majority of U.S. population growth between now play a leadership role in ensuring patient access to pharma-
and 2050 expected to come from racial and ethnic minor- cists’ services.6 The Code of Ethics for Pharmacists issued
ity Americans and immigrants, our health care system must by the American Pharmacists Association states that the
soon learn how to address the effects that race and ethnicity pharmacist “places concern for the well-being of the patient
can have on health care. Eliminating health disparities is so at the center of professional practice” and “seeks justice in
the distribution of health resources.”5 Racial and ethnic dis- can increase awareness of health disparities by encouraging
parities in health care are antithetical to the core principles their health care organizations to make the elimination of
of pharmacy and must be eliminated. disparities in health care a key component of the organiza-
tion’s mission. They can help their institutions foster an en-
Medication-Use Practices Should Reflect Knowledge of, vironment that promotes input from and involvement by all
Sensitivity to, and Respect for the Race and Culture of members of the organization in addressing this component
the Patient. Culture strongly influences how a person inter- of the organizational mission. In addition, pharmacists can
acts with the world. Failing to account for the patient’s race help develop inhouse and community programs to promote
or cultural beliefs and values in health care decisions can cultural understanding and appreciation of the importance
lead to negative health consequences. Providers may miss of diversity. They can also partner with community groups,
screening opportunities because they are unfamiliar with governmental agencies, health care provider organizations,
the prevalence of conditions among racial or ethnic groups. payers, and others to increase awareness of specific diseases
They may fail to consider different responses to medications among certain populations and encourage innovation and
that exist in different populations. Potential harmful interac- creativity in evaluating and disseminating approaches to
tions between medications and traditional remedies used by eliminating disparities in health care.
the patient may be overlooked. Finally, miscommunication
due to cultural, linguistic, or literacy differences between Create a More Diverse Health Care Work Force. Increased
providers and patients regarding symptoms, medications, racial and ethnic diversity among health care professionals
supplements, or the use of devices may lead to faulty di- may be associated with improved access to care for racial
agnoses, unnecessary laboratory testing, medication-related and ethnic minority patients, greater patient choice of and
errors, decreased adherence to therapy, or missed opportuni- satisfaction with health care professionals, more effective
ties for early detection and preventive measures.7 patient–clinician communication, and enhanced educa-
The Code of Ethics for Pharmacists states that “in all tional experiences for students in the health professions.9
cases” the pharmacist “respects personal and cultural dif- Racial and ethnic diversity in the health care work force
ferences among patients.”5 Clinicians who want to provide has been well correlated with the delivery of quality care
the best care for their patients must understand the role of to diverse patient populations. For minority patients, racial
culture and its potential impact on health outcomes and the concordance between patient and physician is associated
provider–patient relationship. with greater patient satisfaction and higher self-rated qual-
ity of care.10 Spanish-speaking patients, for example, re-
Health-System Pharmacists Have a Vital Role to Play port more satisfaction with care from Spanish-speaking
in Eliminating Racial and Ethnic Disparities in Health providers.11
Care. In their roles as medication-use experts, patient care In 2002, the American Hospital Association’s Com
providers, and health-system administrators, health-system mission on Workforce for Hospitals and Health Systems
pharmacists have the knowledge, skills, and opportunities to reported that although the national labor force is becoming
contribute to efforts to eliminate racial and ethnic disparities more diverse, hospital employees remain disproportionately
in health care. female and Caucasian.12 The Commission recommended
working aggressively to develop a work force that more
fully represents changing U.S. demographics. IOM has also
Pharmacists’ Roles in cited a continuing shortage of minorities among health care
Eliminating Disparities professionals.9
ASHP is committed to developing a diverse work
IOM has made recommendations to eliminate racial and eth- force of health-system pharmacists.13 In June 2003,
nic disparities in health care.1 The IOM recommendations the ASHP Board of Directors established the Ad Hoc
most relevant to health-system pharmacists are listed in the Committee on Ethnic Diversity and Cultural Competence,
appendix. ASHP would add to that list that pharmacists can which has recommended six major goals and developed
and should engage in research on disparities in health care. long-term strategic action plans for each goal.14 ASHP
ASHP encourages all health care professionals and adminis- members are encouraged to participate in these efforts and
trators to embrace these recommendations and urges health- to monitor their progress at ASHP’s Health Disparities
system pharmacists to take the following actions to help Web Resource Center (www.ashp.org/s_ashp/cat1c.asp?
eliminate health care disparities. CID=4266&DID=7523).
Increase Awareness of Disparities. One elemental barrier to Promote Culturally Competent Care and Services. Many
eliminating racial and ethnic disparities in health care may cultures take a different approach to health than is found in
be a lack of awareness of their existence and their impact on allopathic (“western”) medicine. Perceptions of illness and
society. Polls show that a significant majority of Americans disease vary by culture, and culture may influence a person’s
believe that African Americans receive the same quality of health-seeking behavior, approach to seeking out health care
health care as whites,1,8 despite ample evidence to the con- providers, and treatment preferences. As allopathic medi-
trary.1 Efforts to eliminate racial and ethnic disparities in cine increasingly emphasizes evidence-based approaches,
health care must begin with the acknowledgment that there health care practitioners will more frequently confront the
is a problem. Health-system pharmacists should lead efforts cultural divide between the demands of their profession and
to increase awareness of health disparities among health the closely held beliefs of their patients. Cultural compe-
care providers, health-system administrators, legislators, tency is rapidly becoming a quality and risk management
regulators, third-party payers, and the public. Pharmacists issue for hospitals and health systems. ASHP is committed
to developing a culturally sensitive, competent, and respect- care.21–23 Health care providers rely heavily on the use of the
ful work force.15 written word to communicate, a circumstance that contrib-
The Department of Health and Human Services (HHS) utes to health care disparities.1 When interpretation services
states that a culturally competent health care practitioner is are used, practitioners should ensure their quality. Fluency
in language is not necessarily sufficient to provide adequate
• Knowledgeable about cultural differences and their interpretation of the complex concepts involved in medical
impact on attitudes and behaviors, decision-making. Interpretation by family members also
• Sensitive, understanding, nonjudgmental, and respect- raises issues of patient confidentiality and autonomy.
ful in dealings with peoples whose culture is different Communication with patients needs to be cultur-
from one’s own, and ally and linguistically appropriate. For example, although
• Flexible and skillful in responding and adapting to dif- Spanish is the primary language of many cultures, simply
ferent cultural contexts and circumstances.16 translating educational material into Spanish may not pro-
vide the cultural context to make the education effective.
HHS’s Office of Minority Health has developed a set Health-system pharmacists should also utilize their
of standards for culturally and linguistically appropriate ser- medication-use expertise to help their institutions and com-
vices in health care to provide a consistent and comprehen- munities develop culturally and linguistically appropriate
sive approach to cultural and linguistic competence in health public education campaigns. These campaigns could address
care.17 These standards offer a framework for implementing health risks prevalent in racial and ethnic minority popula-
services and organizational structures to help health care or- tions served by the hospital and explain preventive measures
ganizations and providers, including pharmacists, respond and health care services available to those populations.
to the cultural and linguistic issues presented by diverse Health care professionals also need to recognize that
populations. ASHP believes these standards should be used racial and cultural differences may affect communication
to assess staff competence and to guide organizations’ edu- among providers. Health-system pharmacists should take
cational programming and strategic planning. Education on steps to ensure that provider-to-provider communication is
cultural competency issues is encouraged in preceptor train- effective and reflects the respect for colleagues expressed in
ing sessions, residency standards, and leadership orientation the Code of Ethics for Pharmacists.5
at ASHP and affiliate levels. The Accreditation Council for
Pharmaceutical Education now requires that schools and Utilize Multidisciplinary Teams and Evidence-Based Guide
colleges of pharmacy include cultural competency in their lines. Multidisciplinary team approaches to health care im-
curricula.18 Approaches to the subject could include stand- prove health outcomes for majority and minority patients
alone courses in health disparities and cultural competence, being treated for a range of diseases.1 ASHP believes phar-
inclusion of traditional healers in the educational process, macists should be integral participants in the development of
and infusion of the concept of cultural competence through- multidisciplinary action plans for patient care, disease man-
out the curriculum (e.g., through case studies that include agement plans, and health management plans.24 Evidence-
diverse populations). ASHP believes that experiential learn- based guidelines “offer the advantages of consistency, pre-
ing should also include practice experiences with racial and dictability, and objectivity,”1 but their use must be balanced
ethnic minorities, medically underserved populations, and with the need for clinical flexibility, especially when there is
patient populations whose cultures incorporate the use of evidence of different outcomes or responses among racial or
traditional healers and complementary or alternative medi- ethnic groups.
cine (e.g., folk medicine, home remedies).
The Code of Ethics for Pharmacists states that “A Collect and Monitor Data on Health Disparities. Standardized
pharmacist maintains professional competence.”5 ASHP be- collection of data regarding access to medications, drug
lieves that cultural competence is among the competencies utilization, and medical and cost-effectiveness outcomes
that pharmacists, residents, fellows, students, and techni- from medication therapy management by racial and ethnic
cians have an obligation to develop and maintain. minorities would promote research on disparities in health
care and help institutions monitor the progress of their efforts
Ensure Effective Communication with Patients and Among to eliminate those disparities.25 Pharmacists should be active
Providers. The Code of Ethics for Pharmacists states that “a partners with health care administrators and other health pro-
pharmacist communicates with patients in terms that are un fessionals in developing measures of progress against health
derstandable.”5 ASHP guidelines recommend that pharma- care disparities in institutional performance measures, which
cists “know about their patients’ cultures, especially health should be a key component of the organization’s mission.26
and illness beliefs, attitudes, and practices,” and “adapt mes-
sages to fit patients’ language skills and primary languages, Research Disparities in Health Care. Health-system phar-
through the use of teaching aids, interpreters, or cultural macists can research, identify, and disseminate best prac-
guides if necessary.”19 Persons with the most health problems tices for providing culturally competent care and reducing
and the greatest need for self-management skills often have disparities in health care. Priority areas for research include
the poorest health literacy. Health-system pharmacists pro- racial and ethnic groups’ access to medications, drug utili-
viding direct patient care should be able to assess the health zation, and medical and cost-effectiveness outcomes from
literacy of patients and provide appropriate education.20 medication therapy management. Pharmacists must keep
Lack of interpretation services or culturally and lin- pace with research regarding disparities in health care, pro-
guistically appropriate health education materials is as- grams to provide culturally competent care to patients, and
sociated with patient dissatisfaction, poor comprehension new educational approaches to improving patient care. It is
and compliance, and ineffective or lower quality of patient also important that pharmacy develop researchers to investi-
gate health care disparities and cutting-edge practitioners to 12. American Hospital Association Commission on Work
translate those research findings into practice. force for Hospitals and Health Systems. In our hands:
how hospital leaders can build a thriving workforce.
Conclusion www.aha.org/aha/key_issues/workforce/commission/
InOurHands.html (accessed 2004 Dec 10).
ASHP believes racial and ethnic disparities in health care are 13. ASHP policy position 0409: cultural diversity among
antithetical to the core principles of pharmacy. All patients health care providers. In: Hawkins B, ed. Best prac-
have the right to high-quality health care that reflects knowl- tices for hospital and health-system pharmacy: posi-
edge of, sensitivity to, and respect for their differences. tions and guidance documents of ASHP. Bethesda,
Health-system pharmacists, working individually and in MD: American Society of Health-System Pharmacists;
coordination with interested organizations and other health 2006:253.
care professionals, can and must play a vital role in efforts to 14. Report of the ASHP Ad Hoc Committee on Ethnic
eliminate racial and ethnic disparities in health care. Diversity and Cultural Competence. Am J Health-Syst
Pharm. 2005; 62:1924–30.
15. ASHP policy position 0314: cultural competence. In:
References Hawkins B, ed. Best practices for hospital and health-
system pharmacy: positions and guidance documents
1. Smedley BD, Stith AY, Nelson AR, eds. Unequal treat- of ASHP. Bethesda, MD: American Society of Health-
ment: confronting racial and ethnic disparities in health System Pharmacists; 2006:75.
care. Washington, DC: National Academy Press; 2003. 16. Department of Health and Human Services Admini-
2. Rubenstein LS. Racial disparities and health: Physicians stration on Aging. Achieving cultural competence: a
for Human Rights testimony to Congressional Black guidebook for providers of services to older Americans
Caucus. March 18, 2003. www.phrusa.org/research/ and their families. www.aoa.gov/prof/adddiv/cultural/
methics/caucus_0303.html (accessed 2006 Dec 1). CC-guidebook.pdf (accessed 2004 Dec 10).
3. U.S. Department of Health and Human Services.
17. U.S. Department of Health and Human Services. Final
Healthy People 2010. www.healthypeople.gov/default.
report: national standards for culturally and linguisti-
htm (accessed 2005 Nov 4).
cally appropriate services in health care (2001). www.
4. ASHP policy position 9006: nondiscriminatory phar-
omhrc.gov/omh/programs/2pgprograms/finalreport.
maceutical care. In: Hawkins B, ed. Best practices
pdf (accessed 2004 Dec 10).
for hospital and health-system pharmacy: positions
18. Accreditation standards and guidelines for the profes-
and guidance documents of ASHP. Bethesda, MD:
sional program in pharmacy leading to the doctor of
American Society of Health-System Pharmacists;
pharmacy degree. Chicago: Accreditation Council for
2006:82.
Pharmaceutical Education; 2006.
5. American Pharmacists Association. Code of
Ethics for Pharmacists. www.pharmacist.com/AM/
ASHP guidelines on pharmacist-conducted patient
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2008 Jan 7).
20. ASHP policy position 0510: communication among
6. ASHP policy position 0101: pharmacy benefits for the
health-system pharmacy practitioners, patients, and
uninsured. In: Hawkins B, ed. Best practices for hos-
other health care providers. In: Hawkins B, ed. Best
pital and health-system pharmacy: positions and guid-
practices for hospital and health-system pharmacy: po-
ance documents of ASHP. Bethesda, MD: American
sitions and guidance documents of ASHP. Bethesda,
Society of Health-System Pharmacists; 2006:161.
MD: American Society of Health-System Pharmacists;
7. Brach C, Fraser I. Can cultural competency reduce ra-
2006:74.
cial and ethnic health care disparities? A review and
21. Erizinger S. Communication between Spanish-
conceptual model. Med Care Res Rev. 2000; 57(suppl
speaking patients and their doctors in medical encoun-
1):181–217.
ters. Cult Med Psychiatry. 1991; 15:91–101.
8. Harvard Forums on Health. Americans speak out on
disparities in health care. www.phsi.harvard.edu/ 22. Carrasquillo O, Orav EJ, Brennan TA, et al. Impact of
health_reform/poll_media_report_disparities.pdf (ac- language barriers on patient satisfaction in an emer-
cessed 2004 Dec 10). gency department. J Gen Intern Med. 1999; 14:82–7.
9. Committee on Institutional and Policy-Level Strategies 23. Perez-Stable EJ, Napoles-Springer A, Miramontes JM.
for Increasing the Diversity of the U.S. Healthcare The effects of ethnicity and language on medical out-
Workforce. In the nation’s compelling interest: ensur- comes of patients with hypertension or diabetes. Med
ing diversity in the health care workforce. Washington, Care. 1997; 35:1212–9.
DC: National Academy Press; 2004. 24. ASHP policy position 9804: multidisciplinary action
10. Saha S, Komaromy M, Koepsell TD, et al. Patient- plans for patient care. In: Hawkins B, ed. Best prac-
physician racial concordance and the perceived qual- tices for hospital and health-system pharmacy: posi-
ity and use of health care. Arch Intern Med. 1999; tions and guidance documents of ASHP. Bethesda,
159:997–1004. MD: American Society of Health-System Pharmacists;
11. Morales LS, Cunningham WE, Brown JA, et al. Are 2006:161.
Latinos less satisfied with communication by health 25. Ver Ploeg M, Perrin E, eds. Eliminating health dispari-
care providers? J Gen Intern Med. 1999; 14:409–17. ties: measurement and data needs. Washington, DC:
National Academy Press; 2004.
26. The Commonwealth Fund. Enhancing public hospi- Cross-Cultural Education in the Health Professions
tals’ reporting of data on racial and ethnic disparities Recommendation 6-1. Integrate cross-cultural education
in care. www.cmwf.org/publications/publications_ into the training of all current and future health professionals.
show.htm?doc_id=452681&#doc452681 (accessed 2007
Jan 31). Data Collection and Monitoring
Recommendation 7-1. Collect and report data on healthcare
access and utilization by patients’ race, ethnicity, socioeco-
Appendix—Institute of Medicine nomic status, and, where possible, primary language.
Recommendations Most Pertinent Recommendation 7-2. Include measures of racial and eth-
to Hospital and Health-System nic disparities in performance measurement.
Pharmacy Practice1 Recommendation 7-3. Monitor progress toward the elimi-
nation of healthcare disparities.
Recommendation 7-4. Report racial and ethnic data by OMB
General Recommendations categories, but use subpopulation groups where possible.
Recommendation 2-1. Increase awareness of racial and eth-
nic disparities in healthcare among the general public and
key stakeholders. Developed through the ASHP Council on Pharmacy Practice and
Recommendation 2-2. Increase healthcare providers’ approved by the ASHP Board of Directors on April 16, 2007, and
awareness of disparities. by the ASHP House of Delegates on June 24, 2007.
Legal, Regulatory, and Policy Interventions Copyright © 2008, American Society of Health-System Pharma-
Recommendation 5-3. Increase the proportion of underrep- cists, Inc. All rights reserved.
resented U.S. racial and ethnic minorities among healthcare
professionals. The bibliographic citation for this document is as follows: American
Society of Health-System Pharmacists. ASHP statement on racial
Health-System Interventions and ethnic disparities in health care. Am J Health-Syst Pharm. 2008;
Recommendation 5-6. Promote the consistency and equity 65:728–33.
of care through use of evidence-based guidelines.
Recommendation 5-9. Support the use of interpretation ser- This statement was reviewed in 2011 by the Council on Pharmacy
vices where community need exists. Practice and by the Board of Directors and was found to still be
Recommendation 5-11. Implement multidisciplinary treat- appropriate.
ment and preventive care teams.
Patient Education and Empowerment

Recommendation 5-12. Implement patient education pro-
grams to increase patients’ knowledge of how to best access
care and participate in treatment decisions.
ASHP Statement on the Role of Health-System

Pharmacists in Emergency Preparedness
The United States has experienced and remains vulnerable Advice to Hospital and Health-System
to many events that cause large numbers of casualties. The
Pharmacy Directors
tragic events of September 11, 2001, and the subsequent
anthrax exposures and deaths also awakened the nation to
Every hospital and health-system pharmacy director (or
the threat of homeland terrorist attacks.
designee) should
As the United States began to enhance counterterrorism
measures in response to the homeland terrorist attacks of
1. Become well informed about the local history of and
September 11, 2001, it became clear that hospital and health-
potential for natural disasters and industrial accidents,
system pharmacists have an essential role in emergency
as well as the threat of terrorist attacks with WMD,
preparedness.
including potential agents that could be used and the
related diagnostic and treatment issues;
Position 2. Become thoroughly informed of federal, regional, state,
local, and institutional plans for emergency-prepared-
The American Society of Health-System Pharmacists ness, especially those related to the distribution, con-
(ASHP) believes that hospital and health-system pharmacists trol, and use of pharmaceuticals;
must assertively exercise their responsibilities in preparing 3. Ensure that the pharmaceutical components of the in-
for and responding to disasters, and the leaders of emergency stitution’s emergency plans are coordinated with the
planning at the federal, regional, state, and local levels overall local preparedness plans involving other in-
must call on pharmacists to participate in the full range of stitutions, community pharmacies, and wholesalers, as
issues related to pharmaceuticals. For the purposes of this well as coordinated with federal, regional, and state
Statement, disasters include natural disasters (e.g., floods, plans;
hurricanes, tornadoes, earthquakes, and forest fires); indus- 4. Ensure that the appropriate pharmaceuticals and related
trial accidents (e.g., explosions, fires, chemical releases, equipment and supplies are in stock at the institution,
radiation escape from nuclear power plants, and airplane or consistent with the overall local emergency-prepared-
train crashes); and terrorist attacks with weapons of mass ness plan, which should account for the interim
destruction (WMD), including biological and chemical between the occurrence of a disaster and the receipt of
agents and radiological, nuclear, and explosive devices. federal or state assistance;
5. Ensure that information about the appropriate use of
General Principles pharmaceuticals in response to a disaster is available
to the health professionals in the institution;
1. On the basis of their education, training, experience, 6. Ensure that the institution does not engage in stockpil-
and legal responsibilities, pharmacists should have a ing of pharmaceuticals without regard to local emergency-
key role in the planning and execution of (a) pharma- preparedness plans that are designed to meet the needs
ceutical distribution and control and (b) drug therapy of the whole community; and
management of patients during disasters. 7. Ensure that pharmacy personnel are trained to imple-
2. The expertise of the pharmacist should be sought in (a) ment the institution’s emergency plans.
developing guidelines for the diagnosis and treatment
of casualties and exposed individuals, (b) selecting
pharmaceuticals and related supplies for national and Advice to Hospital and
regional stockpiles and local emergency inventories in Health-System Pharmacists
emergency-preparedness programs, (c) ensuring proper
packaging, storage, handling, labeling, and dispensing Every hospital and health-system pharmacist should
of emergency supplies of pharmaceuticals, (d) ensuring
appropriate deployment of emergency supplies of phar- 1. Become well informed about the local history of and
maceuticals, and (e) ensuring appropriate education and potential for natural disasters and industrial accidents,
counseling of individuals who receive pharmaceuticals as well as the threat of terrorist attacks with WMD,
from an emergency supply in response to a disaster. including potential agents that could be used and the
3. Pharmacists should be in a position to advise public related diagnostic and treatment issues;
health officials on appropriate messages to convey to 2. Become thoroughly informed of local and institutional
the public about the use of essential pharmaceuticals plans for emergency preparedness, especially those
in response to disasters, giving consideration to issues related to the distribution, control, and use of pharma-
such as adverse effects, contraindications, the effec- ceuticals;
tiveness of alternative pharmaceuticals, and the poten- 3. Share with professional colleagues and patients
tial development of drug-resistant infectious agents. evidence-based information on pharmaceuticals used
4. In the event of a disaster, pharmacists should be called to respond to disasters;
on to collaborate with physicians and other prescrib- 4. Act assertively to prevent and allay panic and irratio-
ers in managing the drug therapy of individual victims. nal responses to disasters;
5. Strongly discourage individuals from developing qualified pharmacists to participate in emergency-

personal stockpiles of pharmaceuticals for use in the preparedness planning;
event of chemical, biological, or nuclear terrorism; 2. Advise their members of information unique to the
6. Consider volunteering in advance of a disaster to assist state regarding pharmacists’ participation in emergency-
in (a) distributing emergency supplies of pharmaceu- preparedness planning and deployment efforts; and
ticals, (b) dispensing and administering medications 3. Establish a volunteer network of health-system
and immunizations, and (c) managing the drug therapy pharmacists for deployment in the event of a terrorist
of individual victims; and attack.
7. Develop and maintain first-aid skills and complete and
maintain basic cardiac life support (BCLS) certifica- Commitments Made by ASHP
tion. BCLS certification may be required for adminis-
tering injectable medications, such as vaccines. In support of the efforts of health-system pharmacists in
emergency preparedness and counterterrorism, ASHP will
Advice to Hospital and Health-System
Administrators 1. Maintain an electronic communications network of
hospital pharmacy department directors that can be
Hospital and health-system administrators should used to transmit urgent information related to emer-
gency preparedness and counterterrorism;
1. Ask the pharmacy director to participate in preparing 2. Disseminate promptly to ASHP members important
the institution’s emergency-preparedness plan and to new information related to pharmacist involvement in
consider participating in the development of local, state, emergency preparedness and counterterrorism;
regional, and federal emergency-preparedness plans; 3. Disseminate to ASHP members and others in the
2. Consult with the pharmacy director to coordinate the health care community timely evidence-based infor-
institution’s participation in the building of emergency mation about pharmaceuticals used when responding
pharmaceutical supplies for use in the community; to disasters; and
3. Refrain from building institutional stockpiles of phar- 4. Meet with government officials and others when nec-
maceuticals that are not coordinated with the local plan; essary to clarify promptly important issues that af-
4. Encourage local preparedness-planning officials to fect the involvement of health-system pharmacists in
involve pharmacists in the full range of issues related emergency preparedness and counterterrorism.
to pharmaceuticals; and
5. Encourage and enable pharmacy personnel employed by
the institution to participate in local, state, regional, and This statement was reviewed in 2013 by the Council on Pharmacy
federal emergency-preparedness planning and to vol- Practice and by the Board of Directors and was found to still be
appropriate.
unteer for community service in the event of a disaster.
Approved by the ASHP Board of Directors on February 21, 2003,

Advice to and by the ASHP House of Delegates on June 1, 2003. Developed
Emergency-Preparedness Planners through the ASHP Council on Professional Affairs. Supersedes
the ASHP Statement on the Role of Health-System Pharmacists in
Emergency-preparedness planners at the federal, regional, Counterterrorism approved by the ASHP Board of Directors, No-
state, and local levels should vember 27, 2001, and revised and approved (as the ASHP Statement
on the Role of Health-System Pharmacists in Emergency Prepared-
1. Consult with qualified pharmacists in all areas in ness) by the ASHP House of Delegates and the ASHP Board of Di-
which the pharmacist’s expertise would contribute to rectors, June 2, 2002.
the creation and execution of workable plans;
2. Inform pharmacists, through national and state phar- Copyright © 2003, American Society of Health-System Pharmacists,
macy organizations, of plans for deployment of emer- Inc. All rights reserved.
gency pharmaceutical supplies so that appropriate
plans can be made at the local level; and The bibliographic citation for this document is as follows: American
3. Consult with qualified pharmacists on messages that Society of Health-System Pharmacists. ASHP statement on the role
should be conveyed to the public about the appropriate of health-system pharmacists in emergency preparedness. Am J
use of pharmaceuticals in the event of a disaster. Health-Syst Pharm. 2003; 60:1993–5.
Advice to State Societies of

Health-System Pharmacists
State societies of health-system pharmacists should
1. Offer their assistance to state and local emergency-

preparedness planning officials, especially in identifying
ASHP Statement on the Role of Health-System

Pharmacists in Public Health
Position One concept underlying many public health activities
is prevention, which is commonly categorized into three
Pharmacists who practice in hospitals and health systems types: primary prevention (reducing the actual incidence
(health-system pharmacists) play a vital role in maintain- and occurrence of diseases, injuries, and disability), second-
ing and promoting public health. The American Society of ary prevention (decreasing the severity or progression of
Health-System Pharmacists (ASHP) believes that all health- the disease, injury, and disability), and tertiary prevention
system pharmacists have a responsibility to participate in (treatment or rehabilitation to return the disease, injury, or
global, national, state, regional, and institutional efforts to disability to the initial or baseline state).5 Public health ef-
promote public health and to integrate the goals of those forts on the macro and micro levels can fall anywhere along
initiatives into their practices. Furthermore, health-system the prevention spectrum and can reinforce each other. For
pharmacists have a responsibility to work with public health example, Healthy People 2010 (a macro-level public health
planners to ensure their involvement in public health policy policy) aims to reduce the number of hospital admissions
decision-making and in the planning, development, and im- attributable to drug therapy management problems (primary
plementation of public health efforts. prevention).6 Policies implemented by individual hospitals
The primary objectives of this statement are to (1) (on the micro level) will allow clinicians to quickly identify
increase awareness of health-system pharmacists’ contribu- such adverse drug events (ADEs) and prevent them from
tions to public health, (2) describe the role of health-system worsening (secondary prevention), as well as treat the af-
pharmacists in public health planning and promotion, and fected patients (tertiary prevention). Pooling and evaluat-
(3) identify new opportunities for health-system pharma- ing these clinical experiences can lead to the development
cists’ involvement in future public health initiatives. This of dispensing guidelines or utilization studies that could be
statement does not provide an exhaustive review of health- used as a primary prevention tool on the macro level.
system pharmacists’ public health activities. Its intent is to The health-system pharmacist’s role in public health,
stimulate dialogue about the role that health-system phar- and the distinction between individualized patient care and
macists can play in providing care that improves public public health efforts, can be illustrated by several examples.
health in the United States. Providing optimal pharmacotherapy to a single patient has
great value. Nonetheless, lessons learned from the manage-
ment of individual patients can have an even greater impact
Background when they result in practice guidelines or health policies
that affect the larger population. Such policy development
Public health has been defined simply as “what we as a requires careful evaluation and synthesis of health informa-
society do to assure the conditions in which people can be tion using epidemiologic principles. Similarly, identification
healthy.”1 In contrast to medicine, public health initiatives of a specific ADE is an important patient care service rou-
“emphasize the prevention of disease and the health needs tinely performed by health-system pharmacists. The phar-
of the population as a whole.”2 macoepidemiologic study of ADEs across a population, cou-
Public health services have been characterized as oc- pled with action to prevent or mitigate such events, can have
curring on two levels: the planning (“macro”) level and the a significant impact on public health. Counseling a patient
implementation (“micro” or “provider”) level.3 Macro-level on the proper use of a medication helps that patient. When
public health services focus on the well-being of the popula- that knowledge is systematically evaluated and used to de-
tion as a whole and emphasize the assessment and prioritiza- velop better behavioral outcomes, general public health can
tion of a community’s health-related needs as well as plan- be improved. Finally, a health-system pharmacist who dis-
ning to address those needs. Such services include working penses medications as a member of an emergency-response
with community representatives in identifying health-related team has a limited impact on public health. However, the
community problems; setting community health priorities; same health-system pharmacist working with emergency-
formulating community health programs and policies; man- preparedness planners to develop policies and programs that
aging, administering, and evaluating community health- ensure proper utilization of the full range of pharmacy ser-
promotion programs; educating the community in ways vices during a disaster can have an enormous effect on the
that promote public health; and researching, presenting, and health of the affected population.
publishing information about public health activities.3 These
macro-level activities are carried out by public health pro-
fessionals with varying backgrounds, degrees, and interests. Public Health Activities of
Micro-level public health services include all the ac- Health-System Pharmacists
tivities required to implement public health initiatives. Many
of these services are performed on a provider-to-patient or a In 1981, the American Public Health Association (APHA)
program-to-population basis, usually with a specific health- outlined the public health role of the pharmacist in a pio-
related outcome in mind.4 Examples of such services include neering statement.7 This succinct policy position, building
disease screening, immunization, counseling for at-risk pop- on a previous APHA publication,8 declared that pharmacists
ulations, and tobacco-cessation programs. were an underutilized resource in promoting public health
and described an array of functions that could be performed Over the past two decades, the expanding role of
by pharmacists, from providing direct personal health care health-system pharmacists in patient care has allowed them
services to planning for health care for communities or to support public health efforts by designing and providing
wider geographic areas. In 2004, the American Association disease management programs. ASHP urges health-system
of Colleges of Pharmacy recognized the important role phar- pharmacists to build on this foundation by leading their
macists can play in public health by including population- institutions’ efforts to provide population-based care. By
based care and public health in its Center for Advancement in working with their health care colleagues through such insti-
Pharmaceutical Education (CAPE) Educational Outcomes.9 tutional mechanisms as the pharmacy and therapeutics com-
These outcomes also emphasized the pharmacist’s role in mittee and using tools such as medication-use evaluation,
the public health components of “health improvement, well- health-system pharmacists can contribute to population-
ness, and disease prevention” and the need for pharmacist specific, evidence-based disease management programs tai-
involvement to ensure the “availability of effective, quality lored to fit the needs of the institutions and communities they
health and disease prevention services,” as well as the ur- serve. Health-system pharmacists can participate in quality
gency to “develop public health policy.”9 reviews and ensure that evidence-based treatments are used
The public health duties that an individual health- for all patients to help alleviate health care disparities.
system pharmacist performs will vary, based on the individ-
ual’s experience, abilities, training, and work setting. ASHP Disease Prevention and Medication Safety. Health-system
believes that all health-system pharmacists, working alone pharmacists can be involved in disease prevention and con-
or in collaboration with health care colleagues and admin- trol in many ways. For example, they can help develop insti-
istrators, can contribute to the promotion of public health. tutional screening programs to check immunization status and
ASHP believes that health-system pharmacists have specific identify undiagnosed medical conditions (e.g., hypertension,
public-health-related responsibilities in infection control10; diabetes, hyperlipidemia, depression). The health-system
substance abuse prevention, education, and treatment11; im- pharmacist’s role in medication safety and error prevention
munization12; tobacco cessation13; and emergency prepared-
is in keeping with the national public health goals outlined
ness and response.14 The following are examples of other
in the federal government’s Healthy People 2010 initiative,
activities that health-system pharmacists can engage in to
which include reducing the number of hospital admissions re-
promote public health:
sulting from drug therapy mismanagement and fostering pro-
grams to intercept counterfeit medications.6 Medication rec-
• Providing population-based care,
onciliation programs are one example of the tools pharmacists
• Developing disease prevention and control programs
can encourage their facilities to use to achieve these goals.
(including medication safety programs) in their insti-
tutions and communities,
Health Education. Health-system pharmacists can promote
• Developing health-education policies and programs
public health by developing patient education programs
within their institutions that address the needs of pa-
tients, other health care professionals, community on safe and effective medication use17 and other public
leaders, and the public, health-related topics, such as tobacco cessation, exercise,
and healthy nutrition. Pharmacists should support the edu-
• Collaborating with state and local authorities, includ-
cation and training of the population at an early age, such
ing local and state health departments and boards of
health, to address local and regional health care needs as through school health programs, to help children develop
(including environmental hazard and emergency- good health behaviors that can continue into adulthood.
preparedness programs), Furthermore, health-system pharmacists can improve so-
ciety’s use of medications by educating their health care
• Advocating for sound legislation, regulations, and
public policy regarding disease prevention and man- colleagues about safe and effective medication use. Health-
agement, and system pharmacists can also use their knowledge and exper-
• Engaging in population-based research and initiating tise to educate community leaders (e.g., legislators, regula-
campaigns to disseminate new knowledge. tors, public officeholders, school officials, religious leaders)
about and involve them in public health initiatives.
Population-Based Care. The Institute of Medicine, in Cross-
ing the Quality Chasm: A New Health System for the 21st Public Health Policy. Health-system pharmacists should
Century, presented the problems of health care quality in the be encouraged to participate in public health policy devel-
United States and provided recommendations for change.15 opment, from local boards of health to national programs.
Subsequent follow-up reports, including Priority Areas for By linking disease prevalence, drug utilization, and the de-
National Action: Transforming Health Care Quality, have terminants of disease, health-system pharmacists can place
provided additional direction related to population-based prevention within a larger context. Drugs play a central
care.16 The CAPE Educational Outcomes recommended that role in health, and health policy, especially policy directed
pharmacists engage in both patient-centered and population- at chronic disease, must be formulated with a better under-
based care, suggesting that a core competency of pharma- standing of the relationship of drug therapy to the many
cists is the ability to develop “population-specific, evidence- other factors that affect disease outcomes. Since medication
based disease management programs and protocols based use increases as patients age, health-system pharmacists will
upon analysis of epidemiologic and pharmacoeconomic face increasing responsibilities to ensure appropriate and
data, medication use criteria, medication use review and risk cost-effective medication use as the average age of the U.S.
reduction strategies.”9 population rises.
Health-system pharmacist participation in emergency serve on institutional review boards, data monitoring and
planning and service delivery is critical. Requirements for safety committees, and expert medication advisory commit-
new and enlarged inventories of specialized pharmaceuti- tees. Experiential and didactic training for practicing health-
cals to provide prophylaxis and treatment to communities system pharmacists, students, residents, and research fellows
during emergencies are growing. The Centers for Disease should include exposure to research in public health policy,
Control and Prevention’s Strategic National Stockpile (SNS) pharmacoepidemiology, pharmacoeconomics, health-related
program, for example, includes 12-hour push packages, ven- quality of life, and evidence-based medicine. Health-system
dor-managed inventory, “chempacks,” vaccines, and medi- pharmacists should also work directly with public health
cal supplies.18 Hospital and health-system pharmacies are policymakers and other key stakeholders, such as profes-
essential in planning for accommodation of supplies, such sional organizations, medical centers, academic institutions,
as antibiotics and antidotes needed in the initial 24 hours governmental agencies, and third-party payers, to promote
following a crisis, before state and federal assets become optimal pharmacotherapy.
available. Community-based planning efforts for mass im-
munization, prophylaxis, and treatment, including pandemic Future Roles
response to biological, chemical, radiological, or explosive
agents, are an ongoing process, as is planning for utilization Revolutionary progress in basic biomedical sciences, in-
of the SNS. Medication management is a critical component cluding human genomics, stem-cell biology, immunology,
of all these contingencies, yet many of the plans do not ad- biomedical engineering, and bioinformatics, has provided
dress pharmacy participation. Involvement of health-system an unprecedented supply of information for improving hu-
pharmacists is critically important to reliably address medi- man health. The rapidly emerging fields of population ge-
cation issues. netics and pharmacogenomics highlight the significance of
ASHP encourages pharmacists to serve on National molecular techniques in the clinical diagnostic laboratory
Disaster Medical System assistance teams (http://ndms.dhhs. and the potential for application in patient-directed pharma-
gov), the National Pharmacy Response Team (www.ndms. cotherapy. Medication-prescribing decisions will increas-
dhhs.gov/nprt.html), or local units of the Medical Reserve ingly rely on the results of genotyping of drug-metabolizing
Corps (www.medicalreservecorps.gov) to assist in distribut- enzymes. New technology and practices will allow health-
ing emergency supplies of pharmaceuticals, dispensing and system pharmacists to reduce treatment failures and pre-
administering medications and immunizations, and manag- vent adverse drug reactions through the proper application
ing the drug therapy of individual victims.14 The develop- of pharmacogenetic principles.19 Advances in informatics
ment, implementation, and revision of local emergency op- will permit aggregation and application of population- and
erations plans, which include public health management of patient-specific clinical data in ways that will encourage de-
emergencies, require pharmacist input. Health-system phar- velopment of population-specific, evidence-based disease
macists need to be actively involved in planning for procure- management programs. As medication-use experts, health-
ment, distribution, and dispensing of medications, as well as system pharmacists will need to apply these new tools not
ongoing management of patient medication issues. simply to improve patient-specific pharmacotherapy but to
Pharmacists should also work with health-system ad- advance public health. Similarly, innovations in medication
ministrators to develop policies and initiatives that heighten delivery technology will allow more complex therapies to
awareness of the applicable laws and best management be administered outside institutional settings. Patients, care-
practices in the proper handling and disposal of hazardous givers, and health professionals will require education about
drugs. the safe use of such technologies, as will the legislators and
As medication-use experts and experienced health- other officials responsible for regulating their use.
system administrators, health-system pharmacists can and
should contribute to the development of public-health-
related legislation and regulation and should be involved in Conclusion
public program oversight and administration. Legislators,
regulators, and program managers at all levels of govern- Health-system pharmacists play a vital role in maintain-
ment should be educated to utilize this expertise. Health- ing and promoting public health. ASHP believes that all
system pharmacists, as individuals and through their profes- health-system pharmacists have a responsibility to partici-
sional associations, state and local boards of health, and state pate in global, national, state, regional, and institutional ef-
boards of pharmacy, are encouraged to participate in legisla- forts to promote public health and to integrate them into
tive, regulatory, and oversight processes. their practices and that health-system pharmacists should
be involved in public health policy decision-making and
in the planning, development, and implementation of pub-
Research and Training. To assume a greater responsibil-
lic health efforts. Health-system pharmacists can improve
ity in public health, health-system pharmacists must receive
public health by providing population-based care; devel-
adequate education and training. Pharmacy curricula should
oping disease prevention and control programs; providing
include advanced coursework in public health and research
health education; collaborating with state and local author-
design. Health-system pharmacists need to be proficient in
ities to address local and regional health care needs, includ-
research methodology, pharmacoepidemiology, and bio-
ing emergency preparedness and response; advocating for
statistics and their applications to public health decision-
sound legislation, regulations, and public policy regarding
making. Knowledge and experience in the design, conduct,
disease prevention and management; and engaging in pub-
and interpretation of clinical studies (both observational and
lic health research.
experimental) are essential. Health-system pharmacists have
the opportunity to participate in collaborative research and
References 19. Spear BB, Health-Chiozzi M, Huff J. Clinical appli-

cations of pharmacogenetics. Trends Mol Med. 2001;
1. Committee for the Study of the Future of Public 7:201–4.
Health. The future of public health. Washington, DC:
National Academies Press; 1988:1. Other Resources
2. Higher education for public health. New York:
Milbank Memorial Fund; 1976. Pharmacists looking for further involvement in public health
3. Bush PJ, Johnson KW. Where is the public health have many options. First, training and competence in public
pharmacist? Am J Pharm Educ. 1979; 43:249–53. health disciplines are invaluable in understanding the field
4. Bush PJ, ed. The pharmacist role in disease prevention of public health and its applications to pharmacy practice.
and health promotion. Bethesda, MD: ASHP Research Accredited schools of public health offer traditional didac-
and Education Foundation; 1983:3. tic classes, and some have courses or continuing educa-
5. Ives TJ, DerMarderosian AH. Pharmacists and public tion available on-line that will give the beginner a clearer
health. In: Hendrickson R, Beringer P, DerMarderosian understanding of the four traditional areas of public health
AH, et al., eds. Remington: the science and practice of practice: health administration and policy, health educa-
pharmacy. 21st ed. Philadelphia: Lippincott Williams tion, biostatistics, and epidemiology. Pharmacists who
& Wilkins; 2006:51. wish to pursue a degree in public health can also do so on-
6. Office of Disease Prevention and Health Promotion. line at a growing number of schools of public health (www.
Healthy People 2010. www.healthypeople.gov/docu- asph.org/document.cfm?page=718).
ment/HTML/Volume2/17Medical.htm (accessed 2007 Pharmacists with an interest in federal public health
Dec 27). initiatives can start with one of three main points of access.
7. American Public Health Association. APHA policy The first is the Centers for Disease Control and Prevention
8024: the role of the pharmacist in public health. Am J (www.cdc.gov), the largest repository of documents, pro-
Public Health. 1981; 71:213–6. gram descriptions, and contacts in the realm of prevention.
8. Cain RM, Kahn JS. The pharmacist as a member of the Major efforts aimed at disease surveillance, infectious dis-
health team. Am J Public Health. 1971; 61:2223–8. ease control, immunization, health education, chronic dis-
9. Center for Advancement in Pharmaceutical Education ease maintenance, and disease-related data management
(CAPE) Educational Outcomes 2004. www.aacp.org/ provide an ample and readily available source of informa-
Docs/MainNavigation/Resources/6075_CAPE2004. tion. The second major source of information is the Office
pdf (accessed 2007 Nov 27). of Disease Prevention and Health Promotion (http://odphp.
10. American Society of Health-System Pharmacists. osophs.dhhs.gov), which provides access to Healthy People
ASHP statement on the pharmacist’s role in infection 2010, a health information clearinghouse, national dietary
control. Am J Health-Syst Pharm. 1998; 55:1724–6. guidelines, and information about health observances.
11. American Society of Health-System Pharmacists. Finally, the Agency for Healthcare Research and Quality
ASHP statement on the pharmacist’s role in substance (www.ahrq.gov) provides information on evidence-based
abuse prevention, education, and assistance. Am J clinical practice, the Guide to Clinical Preventive Services
Health-Syst Pharm. 2003; 60:1995–8. (www.ahrq.gov/clinic/pocketgd.htm), and quality measure-
12. American Society of Health-System Pharmacists. ment of health care. Virtually the entire realm of public
ASHP guidelines on the pharmacist’s role in immuni- health within the U.S. Public Health Service can be accessed
zation. Am J Health-Syst Pharm. 2003; 60:1371–7. or linked via these three websites.
13. American Society of Health-System Pharmacists. State government websites provide public health in-
ASHP therapeutic position statement on smoking ces- formation for their respective states. State entities serve as
sation. Am J Health-Syst Pharm. 1999; 56:460–4. the main policymaking entity for public health priorities and
14. American Society of Health-System Pharmacists. strategies, provide a conduit for federal public health dol-
ASHP statement on the role of health-system phar- lars, and are the main repository of health information and
macists in emergency preparedness. Am J Health-Syst data for the state. States often organize a range of advisory
Pharm. 2003; 60:1993–5. groups, task forces, and planning committees whose output
15. Committee on Quality of Health Care in America. shapes their public health agenda. These entities also pro-
Crossing the quality chasm: a new health system for vide input and direction for state legislative bodies to ad-
the 21st century. Washington, DC: National Academy dress, legislate, and fund.
Press; 2001. On the local level, boards of health serve as the main
16. Adams K, Corrigan JM, eds. Priority areas for national government entities involved in public health. Aside from
action: transforming health care quality. Washington, their usual routine of immunizations and restaurant inspec-
DC: National Academies Press; 2003. tions, these boards serve as the policymakers for disaster re-
17. American Society of Health-System Pharmacists. sponse and provision of primary care to underserved popula-
ASHP guidelines on pharmacist-conducted patient tions. They receive federal and state dollars that are used to
education and counseling. Am J Health-Syst Pharm. fund public health efforts. They are closest to the general pop-
1997; 54:431–4. ulation both in their makeup and in their efforts at improving
18. Centers for Disease Control and Prevention. Strategic the public’s health. Pharmacists interested in learning more
National Stockpile. www.bt.cdc.gov/stockpile/ (ac- about public health and the types of activities that community
cessed 2007 Nov 20). public health agencies are involved in can register for a free
interactive tutorial at www.nynj-phtc.org/orientation.
Below is a list of websites that provide information • Food and Drug Administration (www.fda.gov)
related to public health. • Health Resources and Services Administration (www.
hrsa.gov)
Public Health Organizations • National Institutes of Health (www.nih.gov)
• Agency for Healthcare Research and Quality (www.
• World Health Organization (www.who.int) ahrq.gov)
• Pan American Health Organization (www.paho.org) • Environmental Protection Agency (www.epa.gov)
• American Public Health Association (www.apha.org)
• Association of State and Territorial Health Officials
(www.astho.org) Developed through the ASHP Council on Pharmacy Practice and
• National Association of County and City Health approved by the ASHP Board of Directors on January 12, 2007, and
Officials (www.naccho.org) by the ASHP House of Delegates on June 24, 2007.
• Public Health Foundation (www.phf.org)
• Association of Schools of Public Health (www.asph. Copyright © 2008, American Society of Health-System Pharma-
org) cists, Inc. All rights reserved.
Federal Health Agencies The bibliographic citation for this document is as follows: Ameri-
can Society of Health-System Pharmacists. ASHP statement on the
• U.S. Department of Health and Human Services role of health-system pharmacists in public health. Am J Health-Syst
(www.dhhs.gov) Pharm. 2008; 65:462–7.
• Office of the Surgeon General, Public Health Priorities
(www.surgeongeneral.gov/publichealthpriorities. This statement was reviewed in 2011 by the Council on Pharmacy
html) Practice and by the Board of Directors and was found to still be
• Centers for Disease Control and Prevention (www.
appropriate.
cdc.gov)
ASHP Statement on the Use of Dietary Supplements
Position Evidence of variability in dietary supplement content2–8

has spurred efforts to standardize products. Current federal
The American Society of Health-System Pharmacists (ASHP) regulations regarding the manufacture of dietary supple-
believes that the widespread, indiscriminate use of dietary ments are not adequate.9 Some manufacturers voluntarily
supplements presents substantial risks to public health and that follow good manufacturing practices (GMPs) devised by
pharmacists have an opportunity and a professional responsibil- their own trade groups (e.g., the National Nutritional Foods
ity to reduce those risks. ASHP recognizes that patients may Association GMP Certification Program10), and the U.S.
choose to use legally available dietary supplements, but be- Pharmacopeia (USP) has created voluntary standards for a
lieves that the decision to use substances that may be pharmaco- handful of dietary supplements.11 Manufacturers that wish to
logically active should always be based on reliable information carry the “USP approved” seal on their product labels have
about their safety and efficacy. The current regulatory frame- to subject their products to testing by USP. The creation of
work governing dietary supplements does not provide con- these voluntary programs reflects a widespread concern, even
sumers or health care providers with sufficient information on on the part of dietary supplement manufacturers, that produc-
safety and efficacy to make informed decisions. Furthermore, tion processes must be regulated. Although FDA has had the
standards for product quality are currently inadequate. ASHP authority to establish dietary supplement GMPs for almost a
recognizes the concerns raised by the dietary supplement decade, it issued its first proposed rule on the topic in 2003. 12
industry regarding regulating dietary supplements as non- DSHEA does not require FDA to review evidence of
prescription drugs because of the industry’s inability to patent the efficacy or safety of dietary supplements, so manufactur-
product ingredients. Still, ASHP urges Congress to amend ers have no burden to prove that their products are effective or
the Dietary Supplement Health and Education Act of 1994 safe. Although dietary supplement labeling cannot claim acti
(DSHEA) to require that the Food and Drug Administration vity in the treatment of a specific disease or condition, claims
(FDA) develop a regulatory scheme to ensure that dietary that suggest an effect on the “structure or function of the body”
supplements are safe and effective. ASHP believes that dietary are allowed.1 For example, dietary supplements containing
supplements, at a minimum, should (1) receive FDA approval echinacea can be labeled as supporting immune health (as a
for evidence of safety and efficacy, (2) meet manufacturing “function”) but cannot be labeled as preventing or ameliorat-
standards for identity, strength, quality, purity, packaging, and ing colds (treating a disease). Regardless of this distinction be-
labeling, and (3) undergo mandatory postmarketing reporting tween function and treatment, consumers are bombarded by the
of adverse events, including drug interactions. lay press (and even some scientific literature) with what can
ASHP strongly encourages in vitro and clinical studies only be described as specific-disease indications for dietary
of interactions between dietary supplements and medica- supplements (e.g., glucosamine for osteoarthritis, black cohosh
tions. Because of the demonstrated risk of these interactions, for menopausal symptoms, and St. John’s wort for depression).
ASHP discourages the concurrent use of dietary supple- The health claims allowed in dietary supplement
ments and drug therapy, especially those therapies for which labeling by current interpretation of DSHEA create further
failure may have irreversible consequences (e.g., immuno- confusion for consumers. FDA’s attempt to hold these health
suppressive therapy, cancer chemotherapy, treatment for claims to the same scientific standard required for conven-
human immunodeficiency virus infection, anticoagulation tional foods was struck down in Pearson v. Shalala, so FDA
therapy, and hormonal contraceptive therapy). must permit dietary supplement labels to carry “qualified”
ASHP believes that the criteria used to evaluate dietary health claims based on equivocal scientific evidence.13
supplements for inclusion in health-system formularies should Although DSHEA does require that dietary supple-
be as rigorous as those established for nonprescription drugs ments be safe, it does not require prospective testing to en-
and that the self-administered use of dietary supplements sure safety. To remove a product from the market, FDA must
during a health-system stay may increase risks to patients and prove that the product is unsafe. Under DSHEA, some dietary
liabilities to health care professionals and institutions. supplements that were banned from the U.S. market because
ASHP urges pharmacists and other health care practitioners of concerns about their safety have been allowed to return
to integrate awareness of dietary supplement use into everyday (e.g., sassafras tea, dehydroepiandrosterone). Demonstrably
practice and encourages pharmacists to increase efforts to pre- unsafe products have made their way onto the market, and
vent interactions between dietary supplements and drugs. ASHP fatal adverse reactions have been reported.14,15
also supports the education of pharmacists and other health care Establishing the safety record of dietary supplements
practitioners in the taxonomy, formulation, pharmacology, and has been complicated by the lack of systematically collected
pharmacokinetics of dietary supplements and believes that such data about their adverse reactions. The MedWatch system
education should be required in college of pharmacy curricula. has been used to a limited extent to report adverse events
related to dietary supplement use, but, nine years after the
Background passage of DSHEA, FDA is still developing an adverse-
reaction-reporting system for dietary supplements. Despite
Dietary supplements are defined in DSHEA as products the limited data, however, the number of case reports of in-
“intended to supplement the diet” that contain vitamins, teractions between dietary supplements and medications is
minerals, herbs or other botanicals, amino acids; “a dietary growing.16–21 The safety of dietary supplements for special
substance for use by man to supplement the diet by increas- populations (e.g., children, pregnant women, people with
ing the total daily intake”; or “a concentrate, metabolite, impaired organ or immunologic function) has also not been
constituent, extract, or combinations of these ingredients.”1 demonstrated.
Dangers to Public Health who use alternative therapies for a specific symptom or
disease are also receiving care and prescription medications
It has been estimated that 40% of the U.S. population uses from a physician or surgeon.35 In a more recent nationwide
dietary supplements often and that almost twice as many survey, almost 20% of adults taking prescription drugs
have used at least 1 of the estimated 29,000 dietary supple- reported that they were taking at least one dietary supplement,
ments on the market.22 Out-of-pocket expenditures on dietary not including vitamin or mineral supplements.36
supplements total approximately $18 billion annually.23 Such Pharmacists and other health care practitioners therefore
widespread and indiscriminate use of dietary supplements have an opportunity to reduce the risks associated with
presents five dangers to the public health: dietary supplement use. Health care providers face un-
familiar challenges in this effort, however, because much of
1. Some dietary supplements are inherently unsafe when the information they typically use to establish pharmaceuti-
ingested orally (e.g., chaparral, ephedra, comfrey, cal treatment regimens is lacking for dietary supplements.
tiractricol, aristolochic acid, pennyroyal).24–28 Product content is not standardized, therapeutic goals are
2. Lax regulation of dietary supplement manufacturing vague, and evidence of efficacy and safety is absent or
presents the risk of contamination or adulteration with ambiguous. ASHP believes that pharmacists, as medication-
harmful substances, including carcinogens,29–32 and use experts and accessible members of the health care team,
of dangerous variability in active ingredient content are uniquely qualified and positioned to counsel patients
among products.2–8 using or considering the use of dietary supplements. Despite
3. The use of dietary supplements may compromise, de- their professional responsibility to provide patients with
lay, or supplant treatment with therapies of proven ef- sound advice, pharmacists (like other health care providers) are
ficacy.16–21,25 frustrated by the lack of reliable information about the safety
4. Dietary supplements may present dangers to special and efficacy of dietary supplements. Pharmacists have shown
populations (e.g., children, pregnant women, patients that they can improve medication safety by identifying and
undergoing surgery, patients with impaired organ or preventing adverse drug events,37 and they could play a similar
immunologic function). role in preventing adverse events due to dietary supplement
5. Spending on dietary supplements represents an enormous use if they had sound, evidence-based professional resources.
health-related expenditure of unsubstantiated value.33
Incorporate Awareness of Dietary Supplement Use into
Since the mid-19th century, the federal government has Practice. ASHP urges pharmacists and other health care
exercised its responsibility to protect Americans from haz- practitioners to integrate awareness of dietary supplement
ardous or adulterated foods and medicines. ASHP believes use into everyday practice. ASHP believes that all health
that, with the passage and implementation of DSHEA, the systems should have an institutional policy regarding the
federal government has abandoned its duty to create a regu- use of dietary supplements. Such policies should allow phar-
latory scheme for dietary supplements that adequately macists and other health care practitioners to exercise their
protects the health of consumers. Under DSHEA, consumers professional judgment and try to balance patient autonomy
and health care practitioners are not provided with the infor- and institutional concerns.
mation they need to use dietary supplements safely. To
reduce the dangers posed by the current regulatory framework, Patient Counseling. Although most consumers of alternative
Congress should amend DSHEA to therapies also take prescription medications,35 one survey
found that 72% of respondents who used alternative thera-
1. Require that dietary supplements undergo FDA approval pies did not report that use to their health care providers.38
for evidence of safety and efficacy, Pharmacists and other health care practitioners must there-
2. Mandate FDA-approved dietary supplement labeling fore routinely inquire about a patient’s current or planned use
that describes safe use in a clear, standardized format, of dietary supplements, providing examples so that patients
including the potential for interaction with medications understand what is meant (e.g, asking “Do you use dietary
and cautions for special populations, supplements, such as St. John’s wort or gingko?”).39 This
3. Require FDA to promulgate and enforce GMPs for information will allow pharmacists and other health care
dietary supplements, practitioners to counsel the patient about dietary supplement
4. Require that dietary supplements meet FDA-established use and monitor for adverse reactions and drug interactions.
standards for identity, strength, purity, and quality, and When counseling patients about dietary supplements,
5. Empower FDA to establish and maintain an adverse- the concept of caveat emptor (buyer beware) must be empha-
event-reporting system specifically for dietary supple- sized because the content and safety of dietary supplements
ments, and require dietary supplement manufacturers are not well regulated. ASHP believes that all pharmacists,
to report suspected adverse reactions to FDA. at a minimum, should be familiar with the pharmacology
and pharmacokinetics of common dietary supplements that
Implications for Practice might contraindicate concurrent use with a therapeutic regimen
(i.e., proven and potential pharmacokinetic and pharmaco-
Although examples of persons rejecting potentially life-saving dynamic interactions with prescription and nonprescription
medical interventions in favor of alternative therapies can be medications) to the extent that sound evidence exists. To
found in the medical and lay press,34 the presumption that most provide informed counsel to patients using or considering
users of dietary supplements reject traditional treatments the use of dietary supplements, pharmacists further need to
is unfounded. One survey found that most individuals be familiar with the following:
• The typical uses of common dietary supplements and the the content of dietary supplements brought into health systems.
scientific literature regarding their efficacy and safety, In addition, discontinuing supplement use may be advis-
• The proven and potential interactions between common able as part of the diagnostic workup, and the possibility
dietary supplements and prescription and nonprescrip- that supplement use may have contributed to hospitalization
tion medications, should be considered.
• The methods of therapeutic monitoring for common If an institution decides, as a matter of patient auto
dietary supplements, including signs and symptoms of nomy, to allow the use of dietary supplements, such use
potential adverse effects and toxicities, should require a prescribed order for the specific dietary
• The proven and potential effects of certain disease states on supplement in the patient medical record and pharmacist
supplement absorption, distribution, and elimination, and review and verification of the order. Health systems should
• The safety of using dietary supplements before or after be aware that the use of dietary supplements may expose
surgery. patients to risks, and the health system and staff should take
steps to reduce potential liability (e.g., require patients to sign
Despite the shortcomings of the data on dietary sup- a liability waiver for dietary supplement use) and decrease
plements, the limited references on the topic that are avail- those risks.
able should be consulted.40–45
Patients stabilized on a combination of a supplement and Conclusion
medication should be cautioned not to suddenly discontinue the
use of either without first consulting with the prescriber. The Current regulation of the manufacture and labeling of dietary
potential for adverse effects from an interaction exists both when supplements fails to address substantial risks to the public
a dietary supplement is discontinued and when it is initiated. health. As the activity of some dietary supplements has be-
Dietary supplement sales have a very high potential come apparent, so have their dangers and the shortcomings
for profit. Despite the expectation that pharmacies should of the current regulatory framework. These laws and regula-
receive a profit from the sale of products, professional ethics tions should be revised, with the primary goal of providing
mandate that any recommendations or purchasing suggestions consumers and health care practitioners with the informa-
be made with the well-being of the customer or patient as the tion they need to use dietary supplements safely and effec-
primary concern. Pharmacists should also review promotional tively. In short, dietary supplements should be regulated
and reference materials promulgated in or by their work- in a manner that ensures that they are safe and effective.
places to ensure that these materials are evidence based and Regardless of the shortcomings of the current regulatory
not misleading or deceptive. The scientific literature about framework, pharmacists have an opportunity and a profes-
the safety and efficacy of dietary supplements is updated sional responsibility to reduce the risks presented by dietary
continually. Pharmacists have a responsibility to continually supplement use.
monitor that literature and incorporate the evolving knowledge
into their care for and advice to patients. References
Inclusion in Formularies. ASHP believes that the criteria 1. Dietary Supplement Health and Education Act of 1994
used to evaluate dietary supplements for inclusion in health- (SB 784). http://thomas.loc.gov/ (accessed 2003 Apr 1).
system formularies should be as rigorous as those estab- 2. Gurley BJ, Wang P, Gardner SF. Ephedrine-type al-
lished for prescription and nonprescription drugs. The Joint kaloid content of nutritional supplements containing
Commission on Accreditation of Healthcare Organizations Ephedra sinica (Ma-huang) as determined by high
(JCAHO) has recommended that medical staff weigh the pa- performance liquid chromatography. J Pharm Sci.
tient care implications of dietary supplements with the same 1998; 87:1547–53.
rigor applied to prescription and nonprescription medica 3. Harkey MR, Henderson GL, Gershwin ME, et al.
tions,46 and all JCAHO medication management standards Variability in commercial ginseng products: an analysis
apply to dietary supplements, as well as prescription and of 25 preparations. Am J Clin Nutr. 2001; 73:1101–6.
nonprescription drugs.47 ASHP believes that the decision 4. Parasrampuria J, Schwartz K, Petesch R. Quality con-
to include any product in a health-system formulary trol of dehydroepiandrosterone dietary supplement
should be based on comparative data regarding efficacy, products. JAMA. 1998; 280:1565. Letter.
adverse effects, cost, and potential therapeutic advantages 5. Feifer AH, Fleshner NE, Klotz L. Analytical accuracy
and deficiencies.48 The lack of definitive evidence of efficacy and reliability of commonly used nutritional supple-
and safety and the demonstrated variability in product ments in prostate disease. J Urol. 2002; 168:150–4.
content make most dietary supplements unsuitable for inclu- 6. De los Reyes GC, Koda RT. Determining hyperforin
sion in health-system formularies.49 More research is needed and hypericin content in eight brands of St. John’s
to determine the relative effectiveness of dietary supple- wort. Am J Health-Syst Pharm. 2002; 59:545–7.
ments and their safety for all patient populations, especially 7. Glisson JK, Rogers HE, Abourashed EA, et al. Clinic
drug–supplement interactions. at the health food store? Employee recommendations
The shortcomings that make most dietary supplements and product analysis. Pharmacotherapy. 2003; 23:64–72.
unsuitable for inclusion in formularies also argue strongly 8. Gurley BJ, Gardner SF, Hubbard MA. Content versus
against their self-administered use by patients during a health- label claims in ephedra-containing dietary supple-
system stay. ASHP believes that the use of self-administered ments. Am J Health-Syst Pharm. 2000; 57:963–9.
medications should be avoided to the extent possible50 and 9. Fontanarosa PB, Rennie D, DeAngelis CD. The need
that pharmacists should identify all drug products before for regulation of dietary supplements—lessons from
their use.15 There is currently no way to definitively determine ephedra. JAMA. 2003; 289:1568–70. Editorial.
10. National Nutritional Foods Association. NNFA GMP aristolochic acid. http://vm.cfsan.fda.gov/~dms/ds-
certification program overview. www.nnfa.org/ser- botl2.html (accessed 2003 Apr 1).
vices/science/gmp.htm (accessed 2003 Dec 12). 31. De Smet PA. Toxicological outlook on the quality
11. U.S. Pharmacopeia. U.S. Pharmacopeia dietary supple- assurance of herbal remedies. In: De Smet PA, Keller
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(accessed 2004 May 13). drugs. Vol. 1. Berlin: Springer-Verlag; 1992:1–72.
12. Food and Drug Administration. Current good manu- 32. De Smet PA. The safety of herbal products. In: Jonas
facturing practice in manufacturing, packing, or WB, Levin JS, eds. Essentials of complementary
holding dietary ingredients and dietary supplements. and alternative medicine. Philadelphia: Lippincott
Proposed rule. Fed Regist. 2003; 68:12157–263. Williams & Wilkins; 1999:108–47.
13. Pearson v. Shalala, 164 F.3d 650 (D.C. Cir. 1999). 33. De Smet PA. Health risks of herbal remedies. Drug
14. Food and Drug Administration. Illnesses and injuries Saf. 1995; 13:81–93.
associated with the use of selected dietary supplements. 34. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in
www. cfsan.fda.gov/~dms/ds-ill.html (accessed 2003 alternative medicine use in the United States, 1990–
Feb 14). 1997: results of a follow-up national study. JAMA.
15. Palmer ME, Haller C, McKinney PE, et al. Adverse 1998; 280:1569–75.
events associated with dietary supplements: an obser- 35. Astin JA. Why patients use alternative medicine: re-
vational study. Lancet. 2003; 361:101–6. sults of a national study. JAMA. 1998; 279:1548–53.
16. Williamson EM. Drug interactions between herbal and 36. Kaufman DW, Kelly JP, Rosenberg L, et al. Recent
prescription medicines. Drug Saf. 2003; 26:1075–92. patterns of medication use in the ambulatory adult
17. Fugh-Berman A. Herb–drug interactions. Lancet. population of the United States: the Slone survey.
2000; 355: 134–8. JAMA. 2002; 287:337–44.
18. Yue QY, Bergquist C, Gerdén B. Safety of St. John’s wort 37. Leape LL, Cullen DJ, Clapp M, et al. Pharmacist par-
(Hypericum perforatum). Lancet. 2000; 355:576–7. Letter. ticipation on physician rounds and adverse drug events
19. Brazier NC, Levine MA. Drug–herb interaction in the intensive care unit. JAMA. 1999; 282:267–70.
among commonly used conventional medicines: a 38. Eisenberg DM, Kessler RC, Van Rompay MI, et al.
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2003; 10:163–9. to conventional therapies among adults who use both:
20. Izzo AA, Ernst E. Interactions between herbal medi- results from a national survey. Ann Intern Med. 2001;
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Drugs. 2001; 61:2163–75. 39. Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and
21. Piscitelli SC, Burstein AH, Chaitt D, et al. Indinavir perioperative care. JAMA. 2001; 286:208–16.
concentrations and St. John’s wort. Lancet. 2000; 40. Chambliss WG, Hufford CD, Flagg ML, et al. Assessment
355:547–8. Letter. [Erratum, Lancet. 2001;357:1210.] of the quality of reference books on botanical dietary
22. Office of the Inspector General. Dietary supplement supplements. J Am Pharm Assoc. 2002; 42:723–34.
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24. Food and Drug Administration. Dietary supplements: Randomized trial of an internet curriculum on herbs
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25. De Smet PA. Herbal remedies. N Engl J Med. 2002; 43. Sweet BV, Gay WE, Leady MA, et al. Usefulness
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26. Blumenthal M, ed. The complete German Commission Pharmacother. 2003; 37:494–9.
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28. Shekelle PG, Hardy ML, Morton SC, et al. Efficacy 46. Rich DS. Ask the Joint Commission: understanding
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29. Slifman NR, Obermeyer WR, Musser SM, et al. accreditation manual for hospitals, 2004 update.
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Digitalis lanata. N Engl J Med. 1998; 339:806–11. tation of Healthcare Organizations; 2004:MM1–20.
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49. Ansani NT, Ciliberto NC, Freedy T. Hospital policies Approved by the ASHP Board of Directors on April 14, 2004, and
regarding herbal medicines. Am J Health-Syst Pharm. by the ASHP House of Delegates on June 20, 2004. Developed
2003; 60:367–70. through the ASHP Council on Professional Affairs. Supersedes
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technical assistance bulletin on hospital drug distribu-
tion and control. Am J Hosp Pharm. 1980; 37:1097– Copyright © 2004, American Society of Health-System Pharmacists,
1103. Inc. All rights reserved.
ASHP guidelines: minimum standard for pharma- The bibliographic citation for this document is as follows: American
cies in hospitals. Am J Health-Syst Pharm. 1995; Society of Health-System Pharmacists. ASHP statement on the use
52:2711–7. of dietary supplements. Am J Health-Syst Pharm. 2004; 61:1707–11.
This statement was reviewed in 2014 by the Council on Pharmacy

Practice and by the Board of Directors and was found to still be
appropriate.
Medication Therapy and Patient Care: Specific Practice Areas–Guidelines 333
ASHP Guidelines on Emergency Medicine

Pharmacist Services
Emergency medicine (EM) is an ever-changing, rapidly ED, whether corresponding duties are required of EMPs in
evolving practice specialty. The formal emergency de- other areas of the hospital, and the extent of time provided
partment (ED) has its roots in the 1950s, when full-time for administrative duties and obligations outside the ED.
emergency services were established in the United States.1 Finally, it should be noted that the many services described
Since then, the rate of mortality from accidental and trau- in these guidelines could not be provided by a single EMP.
matic injuries has significantly declined as a result of the When used in these guidelines, the phrase “the EMP” should
development of regional trauma centers and improved train- not be interpreted to imply that a single EMP could or should
ing in the care of trauma patients.2,3 The first descriptions be expected to provide every service detailed herein.
of pharmacy services provided in the ED appeared in the The target audience for these guidelines includes
1970s.4–6 These early reports detail services primarily related EMPs, health-system administrators, physicians, emergency
to medication distribution. Since that time, the literature has nurses and other emergency clinical staff, accreditors, and
detailed the development of EM pharmacy services as they regulators. In addition, pharmacists and health-system ad-
evolved to address changing needs in the ED.7–23 In recent ministrators may find these guidelines helpful in establish-
years, the number of EM pharmacists (EMPs) has dramati- ing new pharmacy services in the ED. Because some of these
cally increased,24 likely as a result of several factors, includ- readers may not require as much detail as others, the services
ing an increased focus on preventing medication errors in are briefly summarized in Appendix A. Those seeking more
the ED and the EMP’s role in error prevention, changing information should consult the appended list of recom-
medication management standards from regulatory and ac- mended readings, references, and resources (Appendix B).
crediting agencies, and emerging literature on a variety of
critical illnesses that emphasizes the need for early, goal- Essential Direct Patient Care
directed therapy. Furthermore, initial research indicates that
ED health care providers highly value the services provided
Roles of EMPs
by EMPs.25
The essential direct patient care roles of EMPs include opti-
mizing medication use through participation in direct patient
Purpose care rounds, medication order review, medication therapy
monitoring, participation in procedures that utilize high-
In 2008, ASHP published a statement on services that the risk medications, resuscitation, medication procurement and
pharmacy department should provide to the ED.26 These preparation, provision of medication information, and docu-
guidelines extend beyond the scope of that document and mentation of associated interventions.
are intended to define the role of the EMP, to suggest goals
for providing services to meet institution-specific needs, and Direct Patient Care Rounds. Because the large majority of
to establish a definition of best practices for the ED. These medication errors occur in the prescribing and administration
guidelines are based on the primary literature, therapeutic phases of the medication-use process, it is critical for EMPs
and practice guidelines, national standards, and the consen- to be involved in direct patient care activities, including
sus of experts in the field of EM pharmacy practice. medication selection and the prescribing process.22,27–29 For
Two levels of EMP services are described: essential the purposes of these guidelines, rounding is broadly defined
services, which should be the basis of the practice specialty, as conducting bedside patient care evaluations; working as
and desirable services, which would optimize pharmacother- a visible, well-integrated member of the multidisciplinary
apy outcomes through the highest level of practice, teaching, ED team; and participating in traditional rounding services
and research and should be considered in addition to essen- when applicable (e.g., in EDs with EM residency programs
tial services. The services are further delineated by either a for physicians). When conducting patient care rounds, EMPs
direct patient care or an administrative focus. should focus on providing direct patient care; they will be
The services provided by EMPs will depend on the most effective in doing this when physically present in the
level of services provided by the ED. Optimal EMP cover- ED. EMPs, in collaboration with other ED providers, should
age would provide consistent pharmacy services through a be accountable for ensuring optimized medication therapy
physical presence in the ED 24 hours per day, seven days regimens and therapeutic outcomes based on emerging litera-
per week. However, such coverage is not possible in every ture, treatment guidelines, and quality measures established
institution, nor may it be ideal based on institutional needs. by accrediting bodies. Depending on the number of patients
Coverage and services provided by EMPs will therefore seen in the ED and the number of pharmacists dedicated to
vary from institution to institution and should be designed the ED, EMPs should create a triage system to focus their
to best meet the needs of the institution’s emergency and patient care efforts on patients with critical illnesses or urgent
pharmacy departments. In concert with ED and pharmacy needs, on high-risk patient populations, or on specific classes
administrators and providers, each EMP should use his or of medications most associated with medication errors.
her professional judgment to individually weigh the factors
that determine which services should be provided. These Medication Order Review. Medication order review in the
factors include the patient populations served, the number of ED must comply with federal, state, and local regulations and
pharmacists and time dedicated to services provided to the accreditation requirements. The Joint Commission’s stan-
334 Medication Therapy and Patient Care: Specific Practice Areas–Guidelines
dards state that all medication orders should undergo prospec- departments. An alert system should be developed to no-
tive order review by a pharmacist prior to administration of tify the EMP to any medication orders requiring immediate
the medication to the patient, with three exceptions: (1) in an pharmacist intervention, while all other routine medication
emergency situation, (2) if a delay in administration would orders would be sent to the central pharmacy for review,
harm the patient, and (3) if a licensed independent practitioner processing, and preparation.
is present to oversee the ordering, preparation, and adminis-
tration of the medication.30 Although many medication orders Medication Therapy Monitoring. The development and
in the ED fall under the above exceptions, the level of assess- assessment of monitoring parameters related to medication
ment during medication order review should be consistent therapy are essential steps in the medication-use process; they
with that provided for patients elsewhere in the hospital. The will determine whether the therapy selected was safe and ef-
process through which ED medication orders are reviewed fective, was suboptimal, or failed and whether changes to the
should be determined by each institution based on its needs, regimen are needed. Research on pharmacist participation in
staffing structure, and systems, as well as the interpretation monitoring medication therapy has demonstrated improved
of requirements by regulatory and accrediting organizations. clinical outcomes in a variety of settings, including the treat-
The role of an EMP in medication order review will ment, management, and monitoring of chronic disease states
vary, depending on the number of patient visits per day, par- such as diabetes mellitus, hypertension, and hyperlipidemia,
ticularly during peak patient utilization; the hours of EMP and from therapeutic medication monitoring of antimicrobial
coverage; and the method of medication order entry. The and anticoagulant therapy in the hospital setting.34–37
role of an EMP should not focus on the medication order re- Several medication classes administered in the ED
view process alone but rather should parallel the role of other exert an immediate therapeutic effect and therefore can
pharmacy specialists providing direct patient care services be monitored shortly after administration. EMPs should
within the institution.24,31–33 A process should be developed be familiar with the pharmacokinetic parameters of medi-
to ensure that other pharmacists are accountable to review cations commonly administered in the ED, as well as the
those orders that are not reviewed by an EMP.3 Medication recommended monitoring parameters associated with each
order review by EMPs may be performed in a manner other therapeutic agent. Monitoring should also be provided for
than traditional medication order review. When at the bed- medications the patient has taken prior to arrival in the
side, an EMP is able to quickly complete a review of medi- ED, whether administered by emergency medical services
cation orders and make medication selection and dosing or by the patient as part of a home medication regimen.
recommendations based on patient-specific factors. Having Medication therapy monitoring should include both subjec-
a physical presence in the ED provides EMPs with the infor- tive (e.g., patient-reported pain score) and objective (e.g.,
mation needed to prioritize patient orders based on need and blood pressure, heart rate) elements.
time demands. To allow EMPs to review medication orders EMPs should provide recommendations for moni-
while maintaining a physical presence in the ED, institutions toring parameters for both the effectiveness and safety of
should consider employing portable hand-held technology medications administered in the ED. Much of this assess-
for use by the ED patient care team, including EMPs. ment can be completed by EMPs and used in combination
The majority of medication orders in the ED are one- with information gathered from the patient’s medical record.
time orders, so an EMP’s intervention is most valuable if EMPs should subsequently suggest revisions to medication
performed prior to medication administration. Ideally, all regimens based on the results of monitoring parameters and
orders for high-risk medications would receive prospec- the established goals for therapy. In addition, EMPs should
tive review, but optimal medication use in the ED requires incorporate medication therapy monitoring parameters in
a balance between ensuring patient safety and preventing the development of treatment protocols used in the ED, and
delays in patient care. EMPs should develop a triage sys- they may provide education to other health care providers
tem to focus the medication order review process on high- regarding appropriate monitoring of medication therapies.
risk medications, high-risk patient populations, and emer-
gent situations. When evaluating medication orders, EMPs Patient Care Involving High-Risk Medications and
should focus on key factors such as appropriateness of the Procedures. A number of high-risk medications and proce-
medication and dose, potential medication interactions, and dures are utilized in the ED. A procedure may be considered
patient-specific factors (e.g., age, weight, medication aller- high risk for a variety of reasons. Procedures performed on
gies, disease states, current clinical condition).30 If time and patients considered at high risk due to critical illness or in-
other patient care activities allow, EMPs may be involved in stability may qualify, or the procedure may involve medica-
the review process of routine medication orders, including tions with a narrow therapeutic index or with serious poten-
cost-saving initiatives, formulary compliance, and therapeu- tial for adverse effects (i.e., high-alert medications).38 EMPs
tic substitutions. should be present at the bedside to assist in the delivery of
In an institution with computerized provider order patient care involving high-risk medications or procedures.
entry (CPOE), centrally located or designated pharmacists Participation should include assisting in the appropriate se-
could work collaboratively with the EMP to assist in the lection of medications and corresponding doses, preparation
medication order review process for routine ED medication of medications, and patient monitoring.
orders, as well as admitting orders for boarded patients. If EMPs should also participate in efforts to improve
time permits, EMP participation in CPOE medication data- the safety of procedures that utilize high-risk medications.
base maintenance should also be considered. In an institution EMPs should evaluate current processes associated with the
that relies on written medication orders, a process should be use of high-risk medications and should assist in the develop-
developed to address the medication order review process ment of processes and systems to improve current practices
through collaboration between the pharmacy and emergency and prevent potential harm and errors. The EMP’s role may
include assisting in the development of policies and proto- (BLS), AHA Advanced Cardiac Life Support (ACLS), AHA
cols, with a focus on appropriate medication selection, use, Pediatric Advanced Life Support (PALS), American College
monitoring, and management. Several recommendations for of Surgeons Advanced Trauma Life Support, American
reducing errors associated with high-risk medications and Academy of Clinical Toxicology Advanced HAZMAT Life
procedures have been suggested.29,39–41 For example, use of Support (AHLS), and board certification as a Diplomate of
medication infusion systems with smart infusion technology the American Board of Applied Toxicology (DABAT). At a
software and double checks on high-alert medications may minimum, all EMPs should achieve and maintain up-to-date
be considered.39,40 In addition, EMPs should provide edu- certification in BLS, ACLS, and PALS.
cation and training related to high-risk medications to ED
health care providers. Medication Procurement and Preparation. Medication
procurement in the ED presents challenges that differ sig-
Resuscitation. EMPs should be present during all resusci- nificantly from those in other areas of the hospital. Because
tations in the ED. Initial evaluations of the role of EMPs of the urgent treatment needs of patients in the ED, several
in the resuscitation of trauma patients have revealed im- critical medications must be readily available. EMPs should
proved patient safety by decreasing preventable adverse be an integral part of the medication procurement and prepa-
medication events and expedited time to medication ad- ration process for medications used in the ED, as dispensing
ministration.7,42–44 The role of EMPs in resuscitation may medications is one of the five stages of the medication-use
vary, depending on such factors as the clinical scenario or process that EMPs can impact to prevent medication errors.29
the practice setting, but may involve preparing medications EMPs may serve as consultants to the pharmacy department
for immediate administration; ensuring appropriate medica- and ED regarding the development or revision of processes
tion selection and dose; ensuring appropriate administration associated with medication procurement, or they may play a
of medications; obtaining medications that are not readily more active role in medication procurement and preparation.
available in the ED; making recommendations for alterna- The options available for medication procurement
tive routes of administration when appropriate; answering vary widely among EDs and depend on such factors as
medication information questions; assisting physicians with patient volume and acuity, the physical limitations of the
differential diagnosis, particularly when related to a poten- ED, and processes established by the pharmacy depart-
tial medication-related cause; and completing resuscitation ment. Medications may be available in automated dispens-
documentation.45,46 In addition, EMPs should ensure that ing cabinets, in emergency kits, from the inpatient central
processes are in place to maintain an appropriate and readily pharmacy department, or from a satellite pharmacy within
available supply of emergency medications in the ED. the ED. A satellite pharmacy with compounding ability may
Toxicologic emergencies present resuscitation sce- best serve the needs of an ED by providing prompt prepara-
narios in which the knowledge of EMPs is highly valuable. tion of medications, though this is not considered a require-
Pharmacist involvement in toxicologic emergencies has ment. While a sterile room for preparation of intravenous
been described for more than 30 years.47,48 EMPs should medications may not be a possibility for most EDs, a laminar
be familiar with the recognition and treatment of patients flow hood would aid in the preparation of most intravenous
experiencing a toxicologic emergency, including recogni- medication requests. In an ED with no satellite pharmacy,
tion of characteristic physical signs and symptoms noted in the central pharmacy should have processes in place to as-
the physical examination, laboratory parameters, and other sist with rapid preparation and delivery of medications.26 In
diagnostic evaluations (e.g., toxidromes), that can result this model, EMPs should work with the central pharmacy to
from a wide range of substances, including prescription and ensure understanding of urgent medication needs. Finally,
over-the-counter medications, illicit drugs, natural occur- EMPs should be competent and responsible for preparation
ring poisons (e.g., those from plants, mushrooms, or enven- of medications needed for emergency use at the bedside
omations), and various chemicals.49 When a patient with a as an exception to the United States Pharmacopeia 797
suspected toxicologic emergency presents to the ED, EMPs standards.51 Competency should include methods of com-
should assist in obtaining a thorough and accurate medica- pounding, knowledge of potential medication interactions,
tion history and a history of present illness, as well as in intravenous medication compatibility, rates of administra-
identifying potential causative agents; should assist in the tion, and skill in using references on these topics.
selection and administration of specific antidotes and other A full review of medications used in the ED, includ-
supportive therapies; may assist in the preparation of anti- ing commonly used medications, high-risk medications, and
dotes; and should provide recommendations for monitor- antidotes, should be performed regularly (e.g., annually or
ing antidote effectiveness and safety. These services should as required by institution policy). EMPs should be involved
be provided in collaboration with clinical and medical toxi- in the decision-making process regarding which medica-
cologists, when available, or local and regional poison con- tions will be made available immediately within the ED.52
trol centers. Finally, EMPs should serve as a resource to the Medications identified as appropriate and necessary for fre-
pharmacy department in ensuring that an adequate inventory quent use in the ED should be stored in automated dispensing
of toxicologic antidotes is available in the institution.50 cabinets or another location as designated safe by the institu-
In preparing to become a member of the resuscitation, with appropriate alerts to prevent medication errors.52
tion team, EMPs should seek out training and certifica- EMPs may assist in the evaluation and management of these
tion in the conditions applicable to their practice settings. medications, including monitoring for appropriate usage,
Several training opportunities and certification programs are inventory levels, and medication storage according to both
available, including but not limited to the American Stroke hospital and regulatory body requirements. Optimization of
Association National Institutes of Health Stroke Scale, available medications should be based on changes in pre-
American Heart Association (AHA) Basic Life Support scribing practices, guideline or protocol recommendations,
medication availability, and formulary changes. Inventory Health care institutions should support EMPs by pro-
and storage replacement should be maintained by technician viding the means to document interventions. Different media
support and should not be the responsibility of EMPs. have been used to document interventions, including per-
Finally, EMPs should be involved with the institution’s sonal digital assistants, software programs on institutional
formulary review and process-improvement committees to intranets, and manual paper systems.59–64 Electronic systems
assist with medication reviews of new formulary agents and offer more complete, readily retrievable documentation and
for revisions to the current formulary regarding medications shorter entry times than manual systems, without the risk of
used in the ED. Further, data from medication-use evalua- loss associated with paper records.65,66 In addition, electronic
tions, safety monitoring, and monitoring for adherence to na- documentation systems offer the benefit of associating cost
tional quality indicators should be used to assist in evaluating avoidance with the documented intervention.19 Although de-
medication procurement and preparation processes. termining true cost avoidance can be difficult, there is re-
search available to provide some guidance for quantifying
Medication Information. The most common cause of medi- the cost avoidance of pharmacist interventions.6,10,56,57,67–69
cation errors is a lack of information related to medication In addition to these benefits, electronic documentation of
therapy.53 Provision of medication information is therefore a EMP interventions may improve communication with other
vital role in the practice of all pharmacists, including EMPs. health care providers caring for the patient after admission
Numerous studies in the ED demonstrate that medication in- (e.g., “hand-off”) if the documentation system allows the
formation is an important service provided by EMPs.9,10,25,54 documentation to follow the patient.
A survey of pharmacy departments revealed that only 50.4%
of respondents provide medication information services to Desirable Direct Patient Care Roles
the ED.54 In addition, ED health care providers report that of EMPs
they are more likely to utilize the resources of a pharmacist
when that pharmacist is located in the ED rather than the Desirable direct patient care roles of EMPs include the care
central pharmacy department.25 These statistics suggest a of boarded patients, obtaining medication histories, and
strong role in medication information for the EMP. medication reconciliation.
The medication information needs of the ED cover a
broad spectrum of clinical scenarios and may include ques- Care of Boarded Patients. ED overcrowding is a common
tions related to medication selection, dose, and administra- occurrence.70,71 Not only are more patients seeking primary
tion; adverse medication reactions; intravenous compatibil- care services in the ED, but a significant number of EDs
ity; medication interactions; and identification of unknown have closed over the past decade, increasing ED patient vol-
medications.55 EMPs should ensure that access to appropri- umes.72,73 Because there are many obstacles and processes
ate primary, secondary, and tertiary references is available that hinder the timely transfer of admitted patients from the
as needed to respond to medication information requests. ED to an inpatient bed,74 overcrowding in the ED often re-
EMPs must be able to quickly and accurately retrieve the sults in bottlenecks that force EDs to provide care to patients
answers to medication information questions using readily for long periods of time while they await admission or physi-
available resources, programs for personal digital assis- cal transfer to an inpatient bed or to another institution for a
tants, textbooks, or electronic resources to provide urgently different level of care (“boarding”).75 The needs of a boarded
needed medication information. patient can vary from simple requests for as-needed medica-
tions to such complex needs as critical care management.
Documentation. Research on pharmacist interventions in the Processes should be developed, based on institutional
inpatient setting has demonstrated improvement in patient resources, to designate the pharmacist who will be account-
outcomes through optimized pharmacotherapy regimens, able for providing care to boarded patients (i.e., an EMP
improved monitoring of medication therapy, and avoidance or the pharmacist assigned to the area to which the patient
of adverse medication events.36 In addition, pharmacist par- will be admitted). The EMP’s primary role in ensuring the
ticipation in patient care has been shown to significantly safety and effectiveness of the medication-use process of the
reduce the costs associated with medication therapy.56,57 ED should not be compromised to provide care for boarded
Research has detailed EMP interventions in the ED, describ- patients if alternatives exist. When staffing levels are insuf-
ing improvements to the medication-use process and patient ficient (e.g., when only a single EMP is present in the ED)
care by EMPs recommending improvements in medication or when the boarding area is physically separated from the
therapy, serving as a medication information resource, and ED, the responsibility of caring for boarded patients should
improving patient safety.4,5,9,11,13,18,20,22,58 Several of these be assigned to the inpatient pharmacist. (Ideally, to ensure
publications have shown dramatic cost avoidance.8,17,19,21,23 continuity of care, the inpatient pharmacist would be the
More detailed studies on the role of EMPs in managing spe- same pharmacist responsible for providing care to the pa-
cific disease states and a definitive evaluation of improve- tient after admission.) The services provided to boarded pa-
ment in patient outcomes are needed. tients by EMPs will depend on the level of services offered
EMPs should be diligent in documenting interven- by the institution. At a minimum, EMPs should review the
tions provided during patient care and other activities (e.g., medication profile of critical patients, with a focus on high-
education). They should regularly review intervention docu- risk medications, medication dosing and procurement, and
mentation to identify trends, which may indicate a need to monitoring, as necessary. When it is necessary to initiate an
educate ED health care providers or change medication-use admitting order for a boarded patient, the responsible phar-
procedures. Finally, cost-avoidance documentation may pro- macist should review medications administered in the ED
vide the justification needed for further expansion of EMP and those taken prior to arrival at the ED to prevent duplica-
services. tions in therapy.
Medication Histories and Medication Reconciliation. tial for harm; and documentation and review of medication
Research on medication reconciliation has identified sev- errors, adverse medication events, and near misses.22,27,28,90
eral barriers to obtaining an accurate medication history in Medication errors that occur in the ED should be re-
the ED.76–82 In many cases, ED staff are required to contact viewed by EMPs in collaboration with other health care pro-
multiple sources, including primary care physician offices, viders and hospital executives to identify potential sources
pharmacies, and family members, to obtain a medication his- of error, contributing factors related to the error, and poten-
tory, and even these burdensome efforts may not result in an tial solutions for preventing similar errors. Performance of
accurate home medication list. There have been significant a root cause analysis could identify potential error trends or
changes in medication reconciliation practices, with the most system failures and contribute to the development of safe
recent recommendations from The Joint Commission that medication practices and processes for prevention of future
complete medication reconciliation needs only be performed events. In addition, a review of medication errors should
by the receiving unit for patients admitted to the hospital and result in education and future policy or guideline develop-
that “screening” reconciliations be performed in the ED, un- ment. Finally, EMPs should be responsible for the develop-
less otherwise requested by the treating physician.30 ment and provision of education to ED health care providers
Although research has shown that pharmacists are the on the source of the error, the risks associated with the error,
providers who obtain the most accurate home medication and ways to prevent similar errors in the future.
list,83–85 dedicating a pharmacist solely to medication recon-
ciliation is not the best allocation of pharmacist resources in Quality-Improvement Initiatives. As a practitioner in the
the ED. EMPs should assist in the development and imple- ED setting, an EMP is able to recognize those aspects of
mentation of a risk-stratification protocol for identifying and patient care, medication safety, compliance with hospital
determining which ED patients need a medication history. In and regulatory policies, and adherence to national practice
general, medication histories may be obtained for patients recommendations and guidelines that could be improved.
with known or suspected toxicologic emergencies, with EMPs or other pharmacy representatives should be exten-
known or suspected adverse events from home medications, sively involved with quality-improvement initiatives in the
or with complicated medication histories that will influence ED. Involvement with a multidisciplinary committee of ED
ED clinical decision-making. health care providers and hospital administrators will pro-
Auxiliary pharmacy staff (pharmacy students hired vide EMPs with an avenue for improving the quality of care
through work/study programs and pharmacy technicians) in the ED.
can also be effective in obtaining accurate home medication EMPs should participate in ongoing efforts to optimize
histories; when possible, they should be incorporated into pharmacotherapy regimens through medication-use evalua-
medication reconciliation procedures.86–89 Quality reviews tions and through the development and implementation of
of medication histories completed by pharmacy technicians medication-use guidelines and pathways. A medication-use
should be conducted to assess accuracy and to provide guid- evaluation may be beneficial in reviewing medications com-
ance for further training opportunities. monly used in the ED, as well as those medications associ-
ated with errors.91,92 The results of a medication-use evalu-
Essential Administrative Roles of EMPs ation can be used to further guide education for other ED
health care providers.
The administrative duties of EMPs will vary, depending on
such factors as the availability of other EMPs to provide di- Leadership Duties and Professional Service. The leader-
rect patient care activities in the ED or to distribute commit- ship role of EMPs should include responsibilities to both
tee involvement among other EMPs. The essential admin- the pharmacy department and ED. Involvement in adminis-
istrative roles of EMPs include involvement in medication trative processes of both departments allows EMPs to serve
and patient safety initiatives, quality-improvement activi- as a liaison between the groups to support joint endeavors.
ties, professional leadership, and emergency preparedness. This role would ideally include participation in departmen-
For EMPs to succeed in fulfilling their administrative tal meetings, medication-use committees, quality-improve-
responsibilities without compromising patient care in the ment and process-improvement committees, medication
ED, pharmacy management must provide support that will safety committees, and research meetings for both de-
allow EMPs to participate in committee meetings, pursue partments. Involvement in such meetings ensures that the
related projects, and develop proposals with action plans. needs of both departments are met and provides EMPs with
Ideally, another pharmacist would be made available to pro- an avenue for improving both patient care and medication
vide coverage for direct patient care activities in the ED. use. In addition, involvement in ED-specific research proj-
ects increases pharmacy involvement, pharmacy publica-
Medication and Patient Safety. EMPs play an important role tion and recognition, and grant funding potential.
in monitoring and ensuring patient and medication safety Membership and active participation in local, state,
in the ED. The environment of the ED is naturally at high and national professional pharmacy organizations are essen-
risk for patient and medication safety lapses. EMPs should tial for the continued growth of the practice of EM phar-
encourage and assist in maintaining a safe environment for macy. As a relatively young area of practice, EM pharmacy
medication and patient safety, which should be continuously is continually developing and growing. One way to support
reviewed for potential process improvements. This review can this development and strengthen the presence of EM phar-
include proactive and continuous monitoring of medication macy is through participation in professional organizations.
practices; identification of errors and high-risk medications At the local level, EMPs may collaborate to develop a local
for monitoring; addressing hazardous conditions with poten- support network for training and research and can provide
new practitioners with avenues for learning. At the state
level, legislative and professional advocacy may help edu- medications, improvement in quality and effective medica-
cate government officials and other health care professionals tion use, and patient and medication safety. Education may
about EM pharmacy practice. At the national level, collabo- include formal sessions (e.g., in-service or didactic presenta-
ration among EMPs increases the strength as a group, serves tion at a conference) or participation in courses such as BLS,
to challenge existing programs to improve, assists new pro- ACLS, or PALS. Participation in formal education sessions
grams in their development, and allows collaboration as a may strengthen the relationship with other ED health care
group to affect the stature, practice, and further development providers and serves as a method of continuous learning for
of EM pharmacy practice. A final source of support for the EMPs. Informal education may also be provided through in-
development of the profession is involvement with national teraction in the ED, particularly at the bedside, which is a
EM organizations. Traditionally designed for physicians, time-efficient, effective tool for education of staff.
nurses, and emergency medical technicians, EM organiza- Participation in the didactic and experiential education
tions provide an avenue for education, networking, and pub- of doctor of pharmacy students is also a desirable activity
lication for EMPs. that supports the development of the profession. Precepting
pharmacy residents in EM learning experiences supports
Emergency Preparedness. As experts in pharmacology and the overall development of direct patient care practitioners
toxicology, EMPs have the skills and knowledge to serve and provides exposure to the practice of EM pharmacy. To
as active participants in emergency situations, such as natu- support the continued development of EM pharmacy ser-
ral disasters; disease outbreaks; biological, radiological, or vices, the development of EM residency training programs
chemical exposures; and acts of terrorism. It is essential is highly desirable. With the expansion of EM pharmacy ser-
that EMPs, in conjunction with the department of phar- vice locations and hours and the increasing role of EMPs
macy, participate in emergency preparedness planning.93,94 in administrative activities, the need for additional qualified
Planning and involvement should occur at a minimum at the pharmacists increases. New EMPs should focus on develop-
institutional level, with participation potentially expanding ing current services with plans to develop advanced (e.g.,
to include local, state, and national emergency preparedness postgraduate year two) residency training programs after the
efforts. Knowledge of local, state, and national emergency program is established and the practice experience is signifi-
preparedness plans, programs, and support systems is para- cant. Additionally, education and development of currently
mount in the development of institution-specific emergency practicing pharmacists are desirable, as education and de-
preparedness plans. These plans and programs should be velopment of existing pharmacists will provide additional
used to develop recommendations and policies regarding EMP coverage.
decontamination, medication acquisition, stockpiles, stor- Having medication therapy expertise, EMPs are
age, distribution, and use.93 uniquely qualified to provide medication education and
Actively participating in emergency preparedness information to patients and their caregivers in the ED and
events will strengthen the knowledge and skills EMPs need should play a key role in the delivery of medication informa-
to effectively lead in emergency situations. EMPs and ex- tion. In some cases, the education of ED patients and their
ecutives in the pharmacy department should work together families and caregivers may be independently considered
in the development of pharmacy-specific plans to coincide among the essential roles of the EMP. EMPs may develop
with institution-specific plans. Education of ED and phar- a system of triage for patient education so that counseling is
macy staff related to emergency preparedness should be focused on patients who will be discharged from the ED with
among the responsibilities of EMPs. a new or high-risk medication or on patients whose visit to
To further develop strengths in emergency prepared- the ED was the result of a medication adverse event or error.
ness, EMPs should seek out training and certification in In addition to developing a triage system for identifying the
emergency preparedness, such as certification for AHLS, patients with the greatest need for education, EMPs may also
Basic Disaster Life Support, Advanced Disaster Life rely on other ED health care providers to identify patients
Support, and the National Incident Management System. in need of medication education. The medication education
provided to patients and caregivers in the ED is diverse and
Desirable Administrative Roles of EMPs may include information related to the use of a new device,
the importance of medication adherence, or a potential ad-
Education of pharmacists and other health care providers, verse medication event. Education can include oral or written
pharmacy students and residents, and ED patients and their materials and should be documented in the patient’s medical
caregivers and participation in research are desirable admin- record. EMPs should confirm patient and caregiver under-
istrative roles for EMPs. standing of the medication education provided.
Education. The role of EMPs in education can be variable Research and Scholarly Activity. The Institute of Medicine
and broad, and it has been mentioned in conjunction with has described three aspects of emergency care research.95
other responsibilities throughout these guidelines. It is desir- These aspects include EM research, defined as research con-
able for EMPs to participate in the education of other health ducted in either the prehospital or ED setting by EM spe-
care providers, including pharmacists and pharmacy staff, cialists; trauma and injury control research, defined as the
pharmacy students, pharmacy residents, physicians, medi- research of the acute management of traumatic injury; and
cal residents, midlevel practitioners, nurses, and emergency research contributions that affect the ED but are attributed
medical support personnel. The types and levels of educa- to other practice specialties. EM research can be further
tion will vary with patient care and administrative workload. subdivided into basic science, clinical, and health services
Provision of education to ED health care staff should, research. A number of research priorities in the prehospital
at a minimum, include information on the appropriate use of and ED settings have been described.96–100
There is also an urgent need for research in EM phar- 7. Patanwala AE, Hays D. Pharmacist’s activities on a
macy, both for pharmacotherapy and pharmacy practice. trauma response team in the emergency department.
Such research would be facilitated by the development of a Am J Health-Syst Pharm. 2010; 67:1536–8.
practice-based research network, which is a group of practi- 8. Fairbanks RJ, Hays DP, Webster DF, et al. Clinical
tioners located locally, regionally, or nationally that collabo- pharmacy services in an emergency department. Am J
rates on pursuits of scholarly activity.101 Practice research Health-Syst Pharm. 2004; 61:934–7.
networks can be effective, as a larger group of researchers 9. Wymore ES, Casanova TJ, Broekemeier RL, et al.
represents a larger patient population that is more diverse Clinical pharmacist’s daily role in the emergency de-
than a single medical center. Practice-based research net- partment of a community hospital. Am J Health-Syst
works have been successful in other areas of practice and Pharm. 2008; 65:395–6, 398–9.
among a wide variety of health care practitioners, including 10. Whalen FJ. Cost justification of decentralized pharma-
interdisciplinary health care teams. ceutical services for the emergency room. Am J Hosp
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scribed and can be applied to the ED setting.102,103 EMPs 11. Culbertson V, Anderson RJ. Pharmacist involvement
may participate in ongoing clinical and practice-based re- in emergency room services. Contemp Pharm Pract.
search being conducted in the institution, including identi- 1981; 4:167–76.
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pharmacy services provided to an emergency depart-
EMPs provide many vital services within the ED. The cen- ment. Can J Hosp Pharm. 1992; 45:113–5.
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providing optimized pharmacotherapy regimens and thera- Ann Pharmacother. 1992; 26:476–80.
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pharmacy department and other health care providers, as 18. Mialon PJ, Williams P, Wiebe RA. Clinical pharmacy
well as patients and their caregivers, and EMPs may partici- services in a pediatric emergency department. Hosp
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19. Ling JM, Mike LA, Rubin J, et al. Documentation
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1999; 33:206–10. dures: Whenever possible, EMPs should be present at the
99. Becker LB, Weisfeldt ML, Weil MH, et al. The patient’s bedside to assist in the delivery of patient care that
PULSE initiative: scientific priorities and strategic utilizes high-risk medications or procedures. EMPs should
planning for resuscitation research and life saving review the use of high-risk medications in the ED and should
therapies. Circulation. 2002; 105:2562–70. assist in the development of processes and procedures to
100. Hoyt DB, Holcomb J, Abraham E, et al. Working improve patient safety and avoid errors. In addition, EMPs
group on trauma research program summary re- should provide education to ED health care providers related
port: National Heart Lung Blood Institute (NHLBI), to the use of high-risk medications.
National Institute of General Medical Sciences
(NIGMS), and National Institute of Neurological Resuscitation: EMPs should be present during all resuscita-
Disorders and Stroke (NINDS) of the National tions in the ED, including trauma, cardiopulmonary arrest,
Institutes of Health (NIH), and the Department of and toxicologic emergencies. In the resuscitation setting,
Defense (DOD). J Trauma. 2004; 57:410–5. EMPs should prepare medications for immediate adminis-
101. Lipowsi EE. Pharmacy practice-based networks:
tration, ensure the appropriate administration and dose of
Why, what, who, and how. J Am Pharm Assoc. 2008; medications, obtain medications that are not readily avail-
48:142–52. able in the ED, make recommendations for alternative routes
of medication administration, answer medication informa-
statement on pharmaceutical research in organized tion questions, assist with differential diagnosis, and com-
health-care settings. Am J Hosp Pharm. 1991; plete resuscitation documentation. EMPs should be familiar
48:1781. with the recognition and treatment of toxicologic emergen-
103. Fagan SC, Touchette D, Smith JA, et al. The state cies and should assist in identifying causative agents, with
of science and research in clinical pharmacy. the selection and administration of antidotes and other sup-
Pharmacotherapy. 2006; 26:1027–40. portive therapies, and with recommendations for monitor-
ing antidote therapy in conjunction with toxicologists and
Appendix A—Summary of poison control centers. EMPs should seek training programs
relevant to the conditions treated in their EDs.
Recommendations
Medication procurement and preparation: Although the role
Essential Direct Patient Care Roles of EMPs
of EMPs will vary, depending on the needs and resources
Direct patient care rounds: It is critical for EMPs to be ac-
of the institution, EMPs should be an integral part of the
countable for and involved in direct patient care activities,
medication procurement and preparation process in the ED.
including medication selection and the prescribing process.
EMPs should be involved in selecting medications stocked
EMPs should focus on providing direct patient care and will
in the ED, should ensure safe storage and usage of these
be most effective in doing this when physically present in
medications, should ensure timely turnaround for medica-
the ED, working as visible and well-integrated members of
tions obtained from the central pharmacy, and may assist
the multidisciplinary ED team.
in the preparation of urgently needed medications. EMPs
should be involved with the institution’s formulary review
Medication order review: Review of medication orders in
and process-improvement committees to assist with formu-
the ED should provide the same level of assessment provided
lation of policies regarding medications used in the ED.
to patients elsewhere in the hospital. The role of an EMP
in medication order review will vary, depending on site-
Medication information: Medication information is a vital
specific factors. The EMP should develop a triage system
role of EMPs. The medication information needs of the ED
to focus the medication order review process on high-risk
cover a broad spectrum of clinical scenarios and patient
medications, high-risk patient populations, and emergent
cases. EMPs should ensure access to appropriate primary,
situations. The EMP must not be the sole party responsible
secondary, and tertiary references as needed to respond to
for ensuring that medication order review occurs in the ED;
medication information requests and must be able to quickly
the pharmacy department should ensure that adequate pro-
and accurately retrieve the answers to medication informa-
cesses are in place to ensure that all medication orders are
tion questions using those resources.
reviewed in compliance with federal, state, and local regula-
tions and accreditation requirements. Each institution should
Documentation: EMPs should document interventions pro-
strive to identify the optimal balance between accountability
vided in the ED to allow measurement of improvement in
for prospective medication order review and direct patient
patient outcomes and potential cost avoidance. EMPs should
care activities in the ED.
regularly review intervention documentation to identify
trends, which may indicate a need to educate ED health care
Medication therapy monitoring: EMPs should ensure that
providers or change medication-use procedures. Health care
medication therapy administered in the ED is safe and ef-
institutions should support EMPs by providing means to Desirable Administrative Roles of EMPs
document those interventions. Education: It is desirable that EMPs provide education to
fellow pharmacists; other health care providers; pharmacy
Desirable Direct Patient Care Roles of EMPs students and residents; and ED patients, their families, and
Care of boarded patients: Based on institutional resources, caregivers.
processes should be developed to identify the pharmacist
accountable for providing care to boarded patients. These Research and scholarly activity: There is an urgent need for
processes should not compromise the EMP’s primary role research in EM pharmacy, both for pharmacotherapy and
in ensuring safe and effective use of medications for new pharmacy practice. EMPs can be valuable researchers in the
patients presenting to the ED. When possible, responsibil- ED and should be encouraged to participate in the comple-
ity for the care of boarded patients should be assigned to tion of research projects and scholarly activities. The estab-
the pharmacist who will be responsible for providing care to lishment of pharmacy practice research networks to facili-
the patient after admission to ensure continuity of care. At tate the completion of pharmacy-based research projects in
a minimum, the responsible pharmacist should review the the ED setting should also be encouraged.
medication profile of critical patients, review any high-risk
medications, assist with medication dosing, assist with med- Appendix B—Recommended Readings,
ication procurement, and provide monitoring as necessary.
References, and Resources
Medication histories and medication reconciliation: EMPs
The following list represents suggested readings that would
may assist in the development of a risk-stratification proto-
be useful to readers and should be considered in addition to
col for determining which medication histories will be ob-
those references and resources provided in the guidelines.
tained in the ED. In general, a focus on patients with known
The suggested readings are categorized into applicable cate-
or suspected toxicologic emergencies, with known or sus-
gories and are then listed in alphabetical order by the primary
pected adverse events from home medication regimens, or
author. For additional resources related to specific areas of
with complicated medication histories that will influence
emergency medicine pharmacist (EMP) service develop-
ED clinical decision-making should be considered.
ment, implementation, and best practices, please refer to the
ASHP Section of Clinical Specialists and Scientists Section
Essential Administrative Roles of EMPs
Advisory Group on Emergency Care Internet Resource Center
Medication and patient safety: In collaboration with physi-
(www.ashp.org/EmergencyCare.aspx). In addition to these
cians, nurses, and hospital executives, EMPs should assist in
resources and references, interested parties should seek out
reporting medication errors, reviewing reported medication
relevant resources and references related to local, regional,
errors, and identifying error trends. EMPs should further as-
state, and national regulatory and accrediting agencies.
sist in developing safe medication practices and processes
for prevention of errors, assist in implementing system im-
Internet Resources
provements, and provide staff education when needed.
1. American Society of Health-System Emergency Medi-
cine Pharmacist Practice Internet Resource Center.
Quality-improvement initiatives: EMPs or other pharmacy
www.ashp.org/EmergencyCare.aspx
representatives should be extensively involved with quality-
2. American Society of Health-System Pharmacy Medica-
improvement initiatives in the ED. EMPs should participate
tion Reconciliation Toolkit. www.ashp.org/Import/
in ongoing efforts to optimize pharmacotherapy regimens
PRACTICEANDPOLICY/PracticeResourceCenters/
through medication-use evaluation and development of
PatientSafety/ASHPMedicationReconciliationToolkit_1.
medication-use guidelines and pathways.
asp
3. Institute for Healthcare Improvement: Prevent Adverse
Leadership duties and professional service: The leadership
Drug Events (Medication Reconciliation). www.ihi.org/
duties and professional service of EMPs may include in-
IHI/Programs/Campaign/ADEsMedReconciliation.
volvement at the hospital level, which provides EMPs with
htm
an avenue for improving both patient care and medication
use. Involvement with local, state, and national professional
Primary Literature
pharmacy organizations, as well as with other professional
Initial descriptions of EMP services
health care organizations, will allow for collaboration, lead-
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the role of the EMP as an integral member of the ED health observations on 24-hour pharmacotherapy services in
care team. the emergency department. Ann Pharmacother. 1992;
26:476–80.
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preparedness should include education, training, and certi- in emergency room services. Contemp Pharm Pract.
fication; knowledge of federal, state, and local emergency 1981; 4:164–76.
preparedness and response policies; involvement with in- 3. Elenbaas RM. Role of the pharmacist in providing
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education of pharmacy and ED staff. 4. Elenbaas RM, Waeckerle JF, McNabney WK. The
clinical pharmacist in emergency medicine. Am J
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Quality-improvement initiatives
ASHP guidelines on medication-use evaluation. Am J Developed through the ASHP Section of Clinical Specialists and
Health-Syst Pharm. 1996; 53:1953–5. Scientists Advisory Group on Emergency Care and approved by the
92. American Society of Health-System Pharmacists. ASHP Board of Directors on July 8, 2011.
ASHP guidelines on the pharmacist’s role in the de-
velopment, implementation, and assessment of critical
pathways. Am J Health-Syst Pharm. 2004; 61:939–45.
Heather Draper Eppert, Pharm.D., BCPS, and Alison Jennett Copyright © 2011, American Society of Health-System Pharma-
Reznek, Pharm.D., BCPS, are gratefully acknowledged for author- cists, Inc. All rights reserved.
ing these guidelines. The authors and ASHP gratefully acknowledge
Roshanak (Roshy) Aazami, Pharm.D., BCPS, Emergency Medicine The bibliographic citation for this document is as follows: Ameri-
Pharmacist, Cedars-Sinai Medical Center, for her substantial contri- can Society of Health-System Pharmacists. ASHP guidelines on
bution and dedication to the completion of these guidelines. emergency medicine pharmacist services. Am J Health-Syst Pharm.
2011; 68:e81–95.
ASHP Guidelines on Pharmacist Involvement

in HIV Care
Background and Purpose and adverse effects, evaluating regimens for potential drug-
drug interactions, and identifying opportunities for regimen
The epidemic of human immunodeficiency virus (HIV) in- simplification are associated with better viral load reduc-
fection in the United States has changed dramatically since tions and CD4 cell responses, improved ART adherence,
its initial recognition in 1981.1 Early in the epidemic, the in- simpler regimens, and reductions in medication errors.12-16
cidence of HIV reached over 130,000 new cases per year, To address emerging challenges, pharmacists will need to
and death as a result of acquired immunodeficiency syn- apply their traditional expertise within an interdisciplinary
drome (AIDS) was an almost certain prognosis for those in- healthcare framework in multiple practice settings (inpa-
fected.2 Significant advances in the strategies to prevent HIV tient, community, and ambulatory care) as well as identify
transmission and in the medical care of patients with HIV and establish new roles in evolving areas of care including
infection led to significant reductions in both HIV trans- HIV testing and diagnosis, medication therapy manage-
mission events and AIDS-related deaths over time. Among ment (MTM), transitions of care, patient retention, acute
these advancements was an understanding of HIV infection HIV treatment, pre-exposure prophylaxis (PrEP), and ini-
pathophysiology, identification of HIV transmission modes, tiating ART in key populations, such as those with acute
development of public health interventions targeting behav- opportunistic infections, hepatitis co-infections, and solid
ioral changes in high-risk populations, and identification of organ transplantation. In developing these roles, it will be
novel HIV medication targets leading to advances in HIV essential for pharmacists to remain highly engaged in the
treatment and eventually combination-antiretroviral therapy rapidly changing field of HIV using reliable resources such
(ART). Because the application of ART in particular can sig- as aidsinfo.gov, the U.S. Department of Health and Human
nificantly suppress HIV replication, restoring a patient’s im- Services HIV management guidelines, and other resources
mune function, it has resulted in a significant decline in HIV- that are listed in the Appendix.
related mortality. As a result, patients on long-term therapy In 2003, ASHP published a statement on the phar-
that maintain viral suppression can now manage their infec- macist’s role in the care of patients with HIV infection.17
tion as a chronic illness and are likely to experience a near- These current guidelines extend beyond the scope of that
normal life expectancy.3 document and are intended to provide guidance for all phar-
Despite remarkable advances in HIV treatment and macists and other healthcare professionals involved in the
prevention, the HIV epidemic in the United States has per- care of patients with HIV. Pharmacists may also find these
sisted. While the annual incidence of AIDS and AIDS-related guidelines helpful in establishing or expanding their services
deaths initially declined following the introduction of ART in an HIV practice setting. Using primary literature, thera-
in 1995, the annual number of new HIV infections, AIDS peutic and practice guidelines, national standards, and the
diagnoses, and AIDS-related deaths has remained constant consensus of experts in the field of HIV pharmacy practice,
since 2000.4 From 2000 to 2011, there were 45,000–55,000 these guidelines describe the available evidence for tradi-
new HIV infections every year in the U.S. and nearly 15,000 tional pharmacist roles and identify new areas of emerging
deaths annually as a result of AIDS. These statistics indi- significance in which pharmacists can establish novel roles
cate that significant challenges remain for public health of- to meet the current and future challenges of the U.S. HIV
ficials and HIV care providers to properly address the HIV epidemic. Specifically, these guidelines address in detail the
epidemic. Furthermore, while long-recognized challenges involvement of pharmacists in the following ten key aspects
to successful HIV care remain relevant (e.g., lack of early of HIV prevention, care, and treatment for patients:
diagnosis, inadequate linkage to and retention in care, poor
adherence to ART, stigma and public perception, and dispar- • HIV testing,
ities in access to care for disenfranchised or socially margin- • treatment of HIV infection,
alized populations), new challenges to successful HIV care • treatment of HIV in key patient populations,
and prevention are emerging (e.g., HIV in an aging popula- • HIV treatment failure,
tion, the application of novel prevention methods such as • management of HIV disease state complications,
pre-exposure prophylaxis, the optimal timing of ART ini- • treatment and prevention of opportunistic infections,
tiation, and management of special patient populations with • prevention of HIV infection,
HIV infection).5-9 • HIV education,
As the HIV epidemic in the U.S. evolves and new • social services and HIV infection, and
challenges to successful care and prevention emerge, health- • professional engagement.
care providers—including pharmacists—are expanding
their roles to ensure optimal patient care.10,11 Pharmacists Pharmacist Involvement in HIV Testing
have long been recognized as essential members of the
HIV patient care team, and their involvement in managing The need for expanded HIV testing in the U.S. is demon-
HIV-infected patients has been associated with improved strated by the fact that one in six individuals with HIV in the
outcomes. Pharmacist activities such as helping the team in United States is unaware of their infection and may there-
selecting individualized HIV treatment regimens, provid- fore present an increased risk of transmission to others.18
ing patient counseling, monitoring for treatment responses Recommendations from both the Centers for Disease Control
and Prevention (CDC) and the U.S. Preventive Services mailed dried blood spot and provides telephone results in as
Task Force (USPTF) stress the importance of routine “opt- little as one day. Community pharmacists should stock over-
out” HIV testing for adults in all healthcare settings, under the-counter HIV test kits and be able to educate individuals
which all patients are informed about and undergo testing about the proper method for administering and interpreting
for HIV unless they specifically decline.19,20 Ubiquity and the tests, as well as taking action on either reactive or non-
flexible hours make pharmacies ideal HIV testing locations. reactive test results.
Pharmacists, as advocates for public health, should be in- In addition to recommending and providing HIV test-
volved with HIV testing initiatives through recommending ing, clinical pharmacists can assist healthcare providers with
HIV testing, providing and/or counseling on HIV tests, and interpreting HIV test results. HIV infection can be diag-
assisting healthcare providers with test interpretation. nosed by serologic assays that detect antibodies against HIV
HIV testing and early HIV diagnoses improve access and by assays that detect HIV antigens or ribonucleic acid
to HIV treatment that prolongs life, preserves health, and (RNA). Reactive screening tests are always confirmed by a
prevents transmission to others. To ensure timely HIV test- supplemental test. Pharmacists’ expertise is useful when cli-
ing, pharmacists should recommend HIV testing according nicians are faced with discordant HIV test results, especially
to recommendations set forth by CDC and USPTF and must during the window period from exposure to seroconversion.
be knowledgeable about the signs and symptoms of early Clinicians may have questions about which additional tests
HIV infection and the behaviors placing an individual at are necessary. New HIV diagnostic algorithms incorporating
risk for HIV infection. The CDC and the U. S. Department the use of fourth generation HIV testing assays are increas-
of Health and Human Services (DHHS) maintain website ingly implemented within US institutions following updated
resources with updated HIV testing recommendations, risk recommendations from CDC.30 Pharmacists should familiar-
behaviors and common symptoms of early HIV infection ize themselves with evolving HIV testing diagnostics and,
(www.cdc.gov/hiv/; www.aids.gov). Pharmacists referring to this end, CDC maintains a website of HIV testing rec-
patients for testing should be knowledgeable about commu- ommendations (www.cdc.gov/hiv/guidelines/testing.html).
nity HIV testing sites. The CDC maintains a list of free HIV At the Clinician Consultation Center, clinical pharmacists
testing sites (hivtest.cdc.gov, or 800-232-4636). The phar- practicing in HIV medicine and physicians are on staff to
macist should support routine HIV testing and help educate assist with healthcare provider telephone inquiries regarding
patients infected with HIV about how to modify their behav- HIV testing.31,32
ior to prevent disease transmission. HIV testing is the first step in linking persons to HIV
HIV testing may not be easily accessible for patients care and prevention. Pharmacists should encourage HIV
with limited access to healthcare. Community pharmacies testing as part of routine care and familiarize themselves
are addressing this issue and improving patient access to with testing methods performed at local medical facilities,
HIV testing by offering onsite rapid HIV testing and coun- pharmacies, or at home. Pharmacist endorsement of HIV
seling services.21,22 Pharmacists in community and out- testing is important for expansion of HIV prevention and
patient settings perform point-of-care HIV tests, provide treatment services.
pre- and post-test counseling, counsel patients with a posi-
tive result about confirmatory testing, and facilitate linkage Pharmacist Involvement
to care.23 CDC is developing a toolkit for HIV testing in
community pharmacies and retail clinics, and the Michigan
in HIV Treatment
Pharmacists Association offers an accredited certificate
Patient Assessment and Laboratory Testing. As ambulatory
course for pharmacists focused on point-of-care testing in
care transitions to the patient-centered medical home model,
community pharmacies.24 These training modules set forth a
it is becoming increasingly important for pharmacists to be
curriculum designed to support pharmacists in the adminis-
able to provide both comprehensive HIV care and primary
tration of point-of-care HIV testing, including competencies
care for HIV-positive patients. A pharmacist should therefore
in pre- and post-test counseling, performing, reading, and
be familiar with both HIV and primary care management
interpreting the HIV test, and identifying sites for linkage
guidelines (see Appendix) and ensure that laboratory test-
to care and confirmatory testing. Where state legislation
ing and monitoring of patients with HIV include parameters
doesn’t permit pharmacists to perform these activities, these
specific to HIV as well as primary care. It is also essential
guidelines can be used to advocate for change and improve
that pharmacists have the ability to interpret laboratory test
and standardize pharmacist care nationally. Expanding HIV
results and provide or recommend appropriate treatment or
testing to pharmacies serves to eliminate barriers and reduce
additional testing when necessary in collaboration with the
stigma by providing convenient, ubiquitous access to test-
patient care team. Pharmacists should understand how cer-
ing. Interest in pharmacy-based HIV testing initiatives has
tain laboratory test results may influence the management
been documented from the perspectives of both pharmacy
of HIV (e.g., the presence of baseline dyslipidemia, renal
staff and patients.25-28 The readiness of pharmacies to pro-
dysfunction, or hepatitis B co-infection among other condi-
vide these services calls attention to their ideal accessibility
tions may influence the selection of antiretroviral agents or
to both urban and rural communities and to hard-to-reach
perhaps the timing of ART initiation). Among the laboratory
populations not integrated into the formal healthcare system.
tests that should be obtained at baseline in a patient with
In 2012, the first point-of-care home HIV test became
HIV are CD4 cell count; viral load; HIV genotype test; hepa-
available for sale in community pharmacies. The OraQuick
titis, tuberculosis, and sexually transmitted infection testing;
In-Home HIV Test provides results in as little as twenty min-
varicella, cytomegalovirus, and toxoplasmosis serologies;
utes using a sample obtained by swabbing the test strip along
complete blood count with differential; chemistry and liver
the gum lines.29 This test joined the already available over-
panels; and fasting lipid profile.33,34 Many of these values
the-counter Home Access HIV-1 Test System, which uses a
will require periodic assessment or ongoing monitoring, par- municated to the healthcare team and used to help determine
ticularly the HIV viral load and CD4 cell count to assess the most appropriate ART regimen for the patient. When
HIV disease progression or treatment response. Following nonprescription medication, food, or nutritional supplement
the initiation of ART, the HIV viral load and CD4 cell count interactions are identified, the pharmacist should educate the
are closely monitored, though over time the frequency of patient and ensure their understanding of any safety and ef-
monitoring may decline once a patient demonstrates a du- ficacy concerns that may be present.
rable virologic and immunologic response. For example, To ensure the accurate assessment of drug interactions,
after receiving ART for two years and consistently achiev- the pharmacist should consult primary resources specific to
ing HIV RNA suppression and a CD4 cell count of greater HIV medications as well as the primary drug interaction lit-
than 500 cells/mm3, viral load monitoring can be extended erature when necessary. Because drug interaction literature
to every six months and CD4 cell count monitoring is con- is constantly expanding and may be difficult to access for
sidered optional.35 Pharmacists should be intimately famil- efficient decision-making, the pharmacist should identify al-
iar with laboratory values that require periodic assessment ternative resources that are current, reliable, easily accessi-
or ongoing monitoring in HIV-positive patients and ensure ble, and that provide an efficient assessment of drug interac-
that appropriate assessment and monitoring occurs. Specific tion information. These sources include (but are not limited
laboratory testing may also be necessary prior to the use of to) the U.S. Department of Health and Human Services HIV
specific antiretroviral agents (e.g., if abacavir is considered Treatment Guidelines for Adults and Adolescents (http://
for therapy, an HLA B5701 test is required to determine a aidsinfo.nih.gov/guidelines), the UCSF HIV InSite Drug
patient’s risk for abacavir hypersensitivity; for maraviroc, Interaction Database (http://arv.ucsf.edu), the University of
HIV tropism must be assessed). Liverpool HIV Drug Interactions website and mobile ap-
plication (www.hiv-druginteractions.org/), and the Toronto
Initiating and Maintaining Antiretroviral Therapy. In ini- General Hospital Immunodeficiency Clinic website (www.
tiating ART, current HIV management guidelines state that hivclinic.ca/main/drugs_interact.html) (see Appendix).
treatment should be offered to all patients regardless of CD4 Since drug interactions are considered a subset of medica-
cell count to reduce the risk of HIV transmission and disease tion errors, preventing drug interactions should lead to better
progression. Treatment is no longer based on the patient’s patient outcomes. Patients with HIV are at high risk of medi-
CD4 cell count but rather on the patient’s willingness and cation errors, and the identification and correction of these
interest in starting and adhering to his or her first ART regi- errors by pharmacists has been instrumental in improving
men.35 The pharmacist, as part of the healthcare team, should the care of HIV-positive patients.36-39
contribute to assessing a patient’s willingness to initiate ART
and provide a readiness assessment. This assessment should Pharmacist Involvement in HIV
include the identification of potential adherence barriers such
as substance abuse, depression, or an unstable social or hous-
Treatment of Key Patient Populations
ing situation. Once identified, the pharmacist should help
The management of HIV infection can pose unique chal-
patients and providers resolve adherence barriers, providing
lenges in key patient populations. These populations include
ongoing adherence assessments and barrier management as
women and children, patients with comorbid conditions or
necessary. This role includes monitoring for side effects fol-
co-infections, patients receiving solid organ transplantation,
lowing ART initiation and implementing side effect manage-
and patients who are immigrants or refugees. These popula-
ment strategies with the patient and provider to improve regi-
tions often have specific medical and/or medication needs
men tolerability and maintain ART adherence.
and regularly require coordinated interdisciplinary care.
In selecting an initial ART regimen, convenience,
Pharmacists are essential members of these interdisciplinary
patient preference, cost, comorbidities, baseline viral load,
teams and can help to ensure optimal patient outcomes.
CD4 cell count, potential for side effects, resistance test-
ing, and concomitant medications need to be considered.35
Women. Women account for 20% of all new HIV infections
Performing a thorough medication history and assessing for
annually in the U.S., and nearly 25% of all persons living
potential drug interactions in particular are essential func-
with HIV in the U.S. are women. The majority of women
tions of the pharmacist.
living with HIV and those that are newly infected in the U.S.
Antiretroviral agents may interact with other antiret-
are between the ages of 13 and 45, or child-bearing age.40,41
rovirals, concomitant medications, food, nutrients, or herbal
The proper use of ART in women of child-bearing age re-
supplements. These interactions may be complex, occurring
quires several important considerations. First, it is important
through multiple mechanisms, and may result in diminished
for pharmacists and other healthcare practitioners to identify
treatment efficacy or an increased risk for toxicity. Drug
patients who should receive preconception counseling, in-
interactions that are not clinically relevant, will not cause
cluding all women of child-bearing age in HIV-concordant
patient harm, or impact treatment outcomes may also occur.
or serodiscordant relationships. To accomplish this, pharma-
The pharmacist is uniquely positioned to evaluate potential
cists should first be familiar with resources related to pre-
drug interactions using appropriate resources and determine
conception counseling in HIV-positive women, including
the clinical significance of each interaction identified. To
the DHHS Guidelines for the Treatment of HIV-Infected
ensure the safety and efficacy of a patient’s initial ART regi-
Pregnant Women and Prevention of Perinatal Transmission
men and other medications, the pharmacist should perform
(see Appendix).42 Additionally, pharmacists should be en-
thorough initial and ongoing assessments of potential drug
gaged in the decision-making process with patients and
interactions, including prescription and nonprescription
providers regarding the use of ART to prevent HIV trans-
medicines, recreational drugs, and all nutritional and herbal
mission. As part of the healthcare team, pharmacists can
supplements. The results of this assessment should be com-
initiate discussions with HIV patients regarding fertility, the first year of life, face a higher risk of disease progression
including a patient’s potential desire to become pregnant than other children and adults.45-48 As a result, pharmacists
or their desire to initiate or maintain contraceptive methods and other specialty care providers must consider the age of
such as hormonal contraception. Multiple complex drug in- the child in addition to HIV-specific laboratory values when
teractions exist between ART agents and commonly used determining the risk of disease progression and the need to
oral hormonal contraceptives. It is therefore essential for initiate ART.
pharmacists to identity potential drug interactions and pro- As with adults, treatment of pediatric HIV infection
vide proper counseling to patients prior to initiating ART.35 is a dynamic field with constant change and progression,
In contrast, for patients who express a desire to become requiring pharmacists to be aware of constantly evolving
pregnant or are inconsistent with contraception, the proper guidelines and treatment recommendations. This is partic-
selection of an ART regimen that is safe during pregnancy ularly true for data regarding the use of specific antiretro-
becomes very important. viral agents in young children. Pharmacists must be aware
The initiation of ART is indicated for all HIV-infected of existing and emerging data describing the efficacy and
pregnant women regardless of CD4 cell count as a means safety of specific antiretroviral agents in this population.
to prevent vertical HIV transmission. Pharmacists should be Pharmacists must also be knowledgeable about the phar-
knowledgeable about current treatment guidelines for the use macokinetic differences that occur in children as a result of
of ART antepartum and intrapartum for the mother as well as developing physiology and maturation of organs involved
postpartum for the infant, including the safety and efficacy in the metabolism and clearance of medications.49 These
of individual antiretroviral agents as well the recommenda- factors, in addition to developmental differences in absorp-
tions for preferred ART combinations.42 When appropriate, tion and body composition, often require that children re-
pharmacists should report outcomes of ART exposures to ceive higher weight-based dosing of antiretroviral agents
The Antiviral Pregnancy Registry (www.apregistry.com/), than adults. In addition to weight, pharmacists must also be
which monitors for the teratogenic effects of antiretrovirals. acutely aware and knowledgeable about antiretroviral agent-
Pharmacists should be acutely aware of the importance specific dosing recommendations that consider body surface
of careful and frequent monitoring for ART efficacy, tolera- area, age, and pubertal development staging.50
bility, and adherence for pregnant patients. They should also When treatment decisions are made, pharmacists must
be aware of physiologic changes that could impact the phar- not only ensure proper regimen selection and dosing, but
macokinetics and dosing of certain ART agents, particularly they must also take active roles in educating children (when
in the third trimester of pregnancy.42 Pharmacists should appropriate) and caregivers about HIV infection and provide
also consider the pregnancy-related safety of concomitant ongoing adherence counseling.50 Adolescents face multiple
agents that are often prescribed to patients with HIV infec- barriers that can affect the initiation and maintenance of
tion, including agents used for the treatment or prevention of ART and other aspects of HIV care, including fear, denial,
opportunistic infections. Postpartum, pharmacists should re- depression, substance abuse, concomitant mental illness,
inforce DHHS recommendations for women to abstain from and lack of social and familial support.51 Healthcare provid-
breastfeeding, even in the presence of a fully suppressive ers, including pharmacists, must work to establish trust and
ART regimen.42 Pharmacists should also continue to pro- build strong relationships with patients and their caregivers
vide adherence support and encouragement for HIV-positive while utilizing patient-care strategies that minimize barri-
women dealing with the challenges associated with being a ers to adherence. For example, regimen fatigue can occur
new mother. in young children who have been receiving ART since early
childhood and can result in poor adherence, virologic resis-
Pediatric Patients. To make meaningful contributions to tance, and the need to implement increasingly complex ART
the management of established HIV infection in infants and regimens.52 Working with pediatric HIV specialty providers,
children, pharmacists must first develop interprofessional pharmacists can help to reduce regimen fatigue through the
partnerships with pediatric HIV specialty care providers. provision of ongoing adherence support as well as the selec-
They must also have a thorough understanding of the dif- tion or simplification of regimens to minimize the number
fering immunologic and virologic patterns associated with of required pills, volumes of prescribed liquids, frequency
HIV infection in children and how they compare to adults of doses, and presence of drug interactions or side effects.
and adolescents. For example, within weeks to months fol- Pharmacists are also uniquely aware of the availability of al-
lowing acute HIV infection, very high HIV RNA levels de- ternative dosage formulations and delivery systems and are
cline rapidly in adults, whereas high RNA levels persist in equipped to recommend methods to improve the palatability
perinatally infected infants for prolonged periods, decreas- of crushed pills or liquid formulations to minimize treatment
ing slowly over years following the first year of life.43,44 aversion due to offending taste.
The different virologic pattern in infants likely reflects an Finally, pharmacists must be sensitive to the many
immature but developing immune system’s relative inabil- psychosocial components of care that may be present in the
ity to contain viral replication compared to that of an adult. pediatric HIV population. These include the housing status
Immunologically, while declines in CD4 cell counts and per- of the child and caregiver; the child’s attendance at school
centages are expected to occur in both adults and children or daycare; the presence of substance abuse, mental health
with advancing HIV infection, absolute CD4 cell counts in or other behavioral issues; and the HIV infection disclosure
children under 5 years old are generally higher than their status of the child.52-54 When contributing to the care of pe-
adult counterparts. However, the risk of disease progression diatric HIV patients, pharmacists may be helpful in identi-
associated with specific CD4 cell counts and/or percentages fying psychosocial issues that require intervention and pos-
varies with the age of the child. For any given CD4 cell sible referral to specialty providers, or to social services and
count or percentage, younger children, particularly those in child protective services when appropriate. These interven-
tions can be essential to the overall health and well-being abuse including illicit drug use as well as mental health
of children as well as their success in managing their HIV conditions including major depression can affect medica-
infection. Pharmacists may also serve as important information adherence and lead to poor patient outcomes.65-67 The
tion resources as children transition into adolescence and management of depression and substance abuse problems in
approach their sexual debut. Counseling on contraceptive patients with HIV is similar to the general population but
methods, safe sex, and preventing HIV transmission should pharmacists must be aware of the potential for drug inter-
occur regularly and should be delivered by members of the actions between ART and antidepressants as well as agents
healthcare team, including the pharmacist. used in the management of substance abuse.
It is often necessary to properly manage mental health
Patients with Comorbid Conditions. Comorbidities are conditions and substance abuse problems before patients are
common among patients with HIV. Compared to the general able to initiate and maintain successful ART.68 As a result,
population, those with HIV infection are more likely to have healthcare providers, including pharmacists, need to be ac-
cardiovascular disease, hypertension, renal failure, osteopo- tive in the screening processes for mental health and sub-
rosis, diabetes, and certain cancers. Not only do these condi- stance abuse problems and provide a means of linking pa-
tions and others appear to occur more commonly in patients tients as necessary to appropriate specialty care and support
with HIV, they also tend to appear earlier in patients with services. Ongoing and close collaboration with specialty ser-
HIV and at times progress more rapidly than in the general vices, particularly in substance abuse treatment settings, is
population, likely due to complex interactions between host therefore necessary, as pharmacists can identify and prevent
risk factors, HIV infection, and ART exposure.55 As a re- possible drug-drug interactions between substance abuse
sult, it is increasingly important to not only provide effective treatment medications and ART.69 For example, methadone
ART to ensure viral suppression and immune reconstitution is a common pharmacologic agent used for the management
but also to provide comprehensive primary care for patients of opioid addiction. Because multiple cytochrome P450
with HIV. Furthermore, due to the success of combination enzymes are involved in methadone metabolism, it is also
ART regimens in reducing AIDS-related mortality over the subject to several interactions with antiretroviral agents.
years, the HIV population is getting older; it is estimated that These interactions can increase methadone concentrations,
more than half of all patients with HIV in the U.S. are over and therefore toxicity, or they can decrease methadone con-
the age of 50.56 centrations, and trigger opioid withdrawal. Pharmacists need
Effective management of the changing HIV popula- to educate providers about these potential interactions, as-
tion will require pharmacists and other healthcare providers sist in ART selection and/or adjustment process, and work
specializing in HIV care to maintain proficient knowledge in collaboration with substance abuse treatment programs
and clinical skills in the screening, prevention, diagno- to ensure successful HIV and substance abuse management.
sis, treatment, and monitoring of a variety of primary care Finally, many recreational drugs, including methylene-
conditions. Conversely, pharmacists practicing in primary dioxymethamphetamine (MDMA), gamma-hydroxybutyric
care settings will likely encounter an increasing number of acid (GHB), ketamine, and methamphetamine, are metabo-
patients with HIV, which will require them to develop the lized in part by cytochrome P450 enzymes and can therefore
knowledge and skills to be increasingly proficient in the interact with certain antiretroviral agents. Overdoses as a
management of this infection. Regardless of practice setting, result of these interactions have been reported, and phar-
pharmacists should be acutely aware of disease management macists can educate providers and identify opportunities to
similarities with the general population and potential differ- counsel patients as a means of prevention.70
ences for patients with HIV. They should also understand the
potential contributions HIV and ART can have in the devel- Patients with Hepatitis B Co-infection. Approximately
opment of certain primary care disease states. For example, 10% of patients with HIV in the U.S. also have chronic hep-
HIV infection and certain antiretroviral agents can contrib- atitis B virus (HBV) infection.71 Compared to patients with
ute to dyslipidemia, insulin resistance, kidney disease, liver HBV infection alone, those with HIV co-infection can have
disease, and lipodystrophy.57-60 They also can contribute to a faster progression to end-stage liver disease, cirrhosis, and
bone loss and an increased risk of osteoporosis and fragility hepatocellular carcinoma.72 Pharmacists involved in HIV
fractures.61-63 Pharmacists can play key roles in understand- care should be familiar with the treatment recommendations
ing the links between HIV, ART, and these disease states; for both infections and be acutely aware that certain medi-
educate patients and other healthcare providers; encourage cations have activity against both infections. More specifi-
disease state screenings; implement prevention programs; cally, tenofovir, lamivudine, and emtricitabine are all active
and ensure proper disease state diagnosis and management against both HIV and HBV, which can be important in deci-
according to available treatment guidelines. They can also sion-making when treatment for either infection is indicated.
assist in the selection or adjustment of HIV treatment regi- For example, tenofovir is a preferred agent for treating HBV
mens that account for a patient’s baseline risk or current di- infection and can be used as a single agent for management
agnosis of primary care conditions that can be exacerbated of infection. However, in a co-infected patient, initiating te-
by certain antiretroviral agents. nofovir alone will lead to HIV resistance. As a result, if HBV
Other comorbidities that commonly present in pa- or HIV treatment is indicated in a co-infected patient, a full
tients with HIV, such as mental health conditions and sub- ART regimen should be initiated, usually with the combi-
stance abuse, may require special attention by pharmacists nation of tenofovir plus emtricitabine or lamivudine as the
and other healthcare professionals. Depression is among nucleoside reverse transcriptase inhibitor backbone.35 If te-
the most common mental health conditions diagnosed in nofovir cannot be used, entecavir is often used for the man-
patients with HIV and is one of the strongest predictors of agement of HBV. Of note, entecavir is not an effective agent
poor patient adherence and treatment outcomes.64 Substance for treating HIV, but it does have some anti-HIV activity and
when used alone in co-infection could result in the selection Although an increasing number of medicines available for
of HIV resistance.73 As a result, if entecavir is initiated for the treatment of HCV will create opportunities to improve
the management of HBV infection in a co-infected patient, it patient outcomes, they may also lead to additional chal-
must be used in addition to a fully suppressive HIV medica- lenges in treating co-infected patients that will require phar-
tion regimen. macist intervention and management.
In addition to concerns regarding the proper selection Additional roles for pharmacists in treating HIV-HCV
of antiviral agents, pharmacists should strongly encourage co-infection include the evaluation of patient immunity to
patients to remain adherent to therapies, as acute HBV treat- hepatitis A virus (HAV) and HBV infection and the recom-
ment discontinuations can cause serious hepatocellular dam- mendation or provision of HAV and HBV immunizations as
age due to spontaneous HBV reactivation. Pharmacists can necessary. As with patients with HBV, pharmacists should
also educate patients about avoiding hepatotoxins, including educate patients with HCV infection about avoiding hepa-
acetaminophen, and encourage patients to abstain from alco- totoxins and encourage patients to abstain from alcohol, or
hol or identify patients with alcohol dependence that require pursue specialized care for the treatment of alcohol abuse.
referrals to specialty care. Finally, pharmacists should rec-
ommend an evaluation of immunity to the hepatitis A virus Patients Undergoing Solid Organ Transplantation.
for all co-infected patients. Those not immune to hepatitis A Increasing numbers of patients with HIV infection are re-
should receive vaccination. ceiving solid organ transplantation, a practice previously
considered controversial or infeasible. The increasing abil-
Patients with Hepatitis C Co-infection. Nearly 25% of pa- ity to provide transplantation for patients with HIV infec-
tients with HIV infection in the U.S. are also infected with tion is largely the result of advances in the management of
hepatitis C virus (HCV).74 Like HBV, HCV progresses more HIV, having a better understanding of the effects of HIV and
rapidly in patients with HIV, resulting in twice the risk of transplant-associated immune suppression, and accumulat-
HCV-related death in patients with co-infection compared to ing clinical trial data demonstrating the viability of trans-
those with HCV infection alone.75 plantation in the HIV population.79,80
The initiation of ART may slow the progression of liver Irrespective of concomitant HIV infection, the process
disease in co-infected patients, so current HIV treatment of solid organ transplantation is complex and requires in-
guidelines recommend considering the initiation of ART in terdisciplinary collaboration. The presence of HIV infection
this population regardless of CD4 cell count.35,75 However, only increases the complexity of the process by introducing
in HIV treatment-naive patients with higher CD4 cell counts additional variables to consider during screening and dur-
(>500 cells/mm3), some clinicians may choose to defer ART ing pre- and post-transplantation management. For example,
until HCV therapy is complete in order to avoid the com- protocols for liver and kidney transplantation often include
plications of combined HIV and HCV treatment (i.e., large thresholds for CD4 cell count levels and usually require
pill burden, drug interactions, and overlapping toxicities).35 patients to have a sustained undetectable HIV viral load.81
In patients with lower CD4 cell counts, combined treatment Pharmacists, in addition to other members of the healthcare
is more likely and pharmacists can play a key role in identi- team, can contribute to the screening process by review-
fying and managing treatment complications. For instance, ing criteria with patients and providing essential adherence
currently available direct-acting antiviral agents for HCV counseling to help patients achieve CD4 cell count and viral
have significant drug interactions with multiple antiretrovi- load goals.
ral agents, including HIV protease inhibitors, elvitegravir/ During pre-transplantation management, pharmacists
cobicistat, and non-nucleoside reverse transcriptase inhibi- should contribute to the selection and/or adjustment of anti-
tors. Pharmacists should contribute to HIV and/or HCV retroviral regimens in anticipation of drug-drug interactions
treatment regimen selection when combined treatment is that can occur following transplantation. For instance, nearly
indicated in order to avoid significant interactions that can all patients will receive proton pump inhibitor medications
lead to treatment failure and drug toxicity. Pharmacists can for stomach acid suppression after transplantation. As a re-
also recommend self-care strategies for side effects and result, ART regimens that contain medications requiring an
port serious adverse effects back to the prescriber. acidic environment for adequate absorption (e.g., atazanavir
Adherence is also essential for optimal HIV and HCV and rilpivirine) may need to be avoided. In addition, phar-
treatment outcomes. As part of an interprofessional team, macists should anticipate antiretroviral drug-drug interac-
pharmacists should provide counseling to ensure patients tions with post-transplantation immunosuppressing agents.
understand what are often complex regimens, including Allograft rejection has been reported to occur at a higher rate
proper administration (e.g., food requirements), the impor- in patients with concurrent HIV infection; one of the causes
tance of adherence, the benefits and goals of therapy, and the may be inadequate exposure to immune-suppressing agents
recognition and management of treatment-related side ef- as a result of interactions with ART agents.82,83 Both HIV
fects. This level of pharmacist involvement has been shown protease inhibitors and non-nucleoside reverse transcriptase
to improve overall adherence and response to therapy in HIV inhibitors can cause complex interactions with commonly
and HCV mono-infected patients and may be particularly used immunosuppressive agents such as calcineurin in-
beneficial in patients with co-infection.76,77 Furthermore, hibitors (e.g., tacrolimus and sirolimus) and cyclosporine.
because the field of HCV medicine is evolving rapidly, it is Pharmacists should provide close monitoring of immuno-
increasingly essential for pharmacists to maintain a height- suppressive drug levels and recommend dosing adjustments
ened awareness of evolving HCV treatment guidelines as necessary to achieve stable therapeutic concentrations.
(available at: www.hcvguidelines.org) and newly available Proper interdisciplinary communication should also occur
HCV medications including those in development and their between HIV specialty pharmacists, transplant pharmacy
potential impact on the management of HIV co-infection.78 specialists, and other members of the HIV and transplan-
tation healthcare teams. Communication will help ensure with HIV to enter the U.S. each year.91,92 At least some of
proper awareness and management of potential drug-drug these immigrants will have missed opportunities for early
interactions. HIV diagnosis and entry into care. Furthermore, although
The primary indications for solid organ transplanta- the CDC recommends HIV screening for all immigrants and
tion in patients with HIV are end-stage kidney disease due refugees, these patients will encounter barriers to healthcare
to HIV-associated nephropathy (HIVAN) and advanced liver as they enter the U.S. (e.g., lack of familiarity with the U.S.
disease due to HBV or HCV co-infection.81 The presence healthcare system) that not only limit their opportunities to
of viral hepatitis adds to the complexity of both pre- and receive HIV testing but also proper primary care services.93
post-transplantation management. Pharmacists should be Pharmacists can assist in overcoming these barriers by being
acutely aware of the differences in managing these infec- knowledgeable of the local medical clinics and organiza-
tions in transplantation patients, including the differing roles tions serving immigrant and refugee populations and help-
of antiviral therapy. For example, patients with HBV infec- ing to link patients into care as necessary.
tion should continue to receive antiviral agents after trans- As patients enter into care, additional barriers may
plantation to prevent a hepatitis flare and will also receive need to be addressed prior to performing HIV testing. These
therapy with HBV immune globulin.84 Patients with HCV include language differences, cultural beliefs regarding HIV
may not require antiviral therapy initially, but recurrent in- and healthcare in general, and mistrust regarding confiden-
fection is common and can adversely impact transplantation tiality and disclosure of HIV status.94 Pharmacists must be
outcomes.81,85,86 As a result, patients should be followed sensitive to these issues and help reduce barriers whenever
closely following transplantation to identify recurrent HCV possible. Language barriers can be addressed through use
infection and the need to initiate therapy. of interpreters. Patients should receive HIV education and
During the post-transplantation stage, pharmacists counseling in their primary spoken language, and interpret-
should ensure that the use of medications toxic to trans- ers should be medically knowledgeable so they can explain
planted organs is limited. They should also work closely with the complexities of HIV infection and the importance of test-
patients to develop strategies to maintain medication adhering. Pharmacists should be sensitive to situations in which
ence to complex drug regimens. At the very least, these post- a patient declines the use of an interpreter for fear of dis-
transplantation regimens will include antiretroviral agents, closure within their community and seek alternative transla-
immunosuppressive agents, and antibiotics for opportunistic tion methods if they are available (family member or close
infection prophylaxis. The inclusion of the pharmacist on the friend). The delivery of information to the patient in their
transplantation team has been shown to improve patient ad- primary language and in a safe environment is paramount
herence to these complex regimens and may be essential to as it not only helps to ensure patient understanding but can
the overall success of the patient following transplantation.87 also be helpful in developing a trusting patient-provider re-
Finally, pharmacists must be aware of the role of lationship.
post-transplantation opportunistic infection prophylaxis. When providing HIV education and prevention coun-
Although patients generally receive prophylaxis against seling, pharmacists should also be particularly sensitive
Pneumocystis jirovecii, opportunistic infections and other to the HIV risk profiles that may be present in immigrant
AIDS-defining conditions are uncommonly reported fol- populations. Specifically, foreign-born persons with HIV are
lowing transplantation.83,88 Importantly, the risk of infection more likely than those in the U.S. to be women who have
may change following the administration of thymoglobulin acquired HIV through heterosexual contact.95 Pharmacists
for the treatment of acute rejection. Thymoglubulin has been should also be aware of conditions heightening HIV risk
associated with prolonged CD4 cell declines, loss of cyto- for refugees, such as sexual abuse, violence, and gender in-
toxic antiviral T-cell responses, and the development of se- equality.93,96 Failure to recognize these issues may limit the
vere bacterial infections.89,90 To address these risks, pharma- patient’s engagement in care as well as the pharmacist’s abil-
cists must have a thorough understanding of anti-rejection ity to provide proper counseling or referral to social services.
medications, their impact on CD4 cells, and the need for in- When testing is performed, it is important for phar-
creased monitoring and/or additional prophylaxis to reduce macists and other healthcare providers to follow CDC rec-
a patient’s risk of severe infection. ommendations specific to the refugee population.93 These
include specific recommendations for screening adults and
Immigrant and Refugee Populations. In January 2010, the adolescents as well as pregnant women and children from
restriction on immigration to the United States for non-U.S. endemic areas. Also included are recommendations for
citizens living with HIV was lifted.91 The restriction had screening patients at risk for HIV-2. Pharmacists should
been in place for more than 20 years and its removal not only have an understanding of the testing for HIV-2 infection as
helped to reduce social barriers, discrimination, and stigma well as groups of HIV-1 infection that are endemic in certain
for immigrants and refugees with HIV, it also aligned the countries and may not be detected with assays commonly
domestic position of the U.S. with its increasing efforts to used in the U.S.
combat HIV and AIDS internationally. Finally, pharmacists, as part of an interprofessional
While there are many positive implications from the team, should be involved in the ART selection process for
removal of the immigration restriction, there are now also HIV-positive refugees and immigrants. They should provide
challenges for U.S. healthcare professionals to ensure that ongoing HIV education and adherence counseling using an
immigrants and refugees living with HIV consistently re- interpreter as well as ongoing evaluations for potential drug-
ceive proper care. For example, the removal of the immi- drug interactions. Patients should be assessed for co-infec-
gration restriction also removed mandatory HIV testing tions endemic to their home countries and receive proper
as a part of the immigration process. The CDC estimates treatment and/or opportunistic infection prophylaxis when
that lifting the ban will allow an additional 4,275 persons necessary. Patients may encounter financial difficulty, and
pharmacists should pursue available services that can assist Once ART adherence and pharmacokinetic compli-
patients in paying for their medications. cations have been assessed, attention should then focus on
ART resistance testing. An HIV genotype and other specific
Pharmacist Involvement in the medication tests (as needed) should be obtained to deter-
mine the presence of viral mutations. Specialized pharma-
Management of HIV Treatment Failure cists involved in HIV care should be fully versed in order-
ing appropriate resistance tests, including the appropriate
Once an ART regimen is initiated it is critical to monitor
timing of particular tests, as well as in interpreting test re-
the success of therapy via routine assessment of the CD4
sults. Pharmacists thus serve an important role in the review
cell count and HIV viral load. Pharmacists can play a key
and interpretation of viral genotypes. This role requires an
role in interpreting test results to detect possible treatment
understanding of primary and secondary mutations, poly-
failure. Treatment failure may be defined immunologically
morphisms, and the accumulation of mutations to a criti-
by identifying a significant CD4 cell count decline or viro-
cal number that will contribute to ART failure. Pharmacists
logically by finding a significant quantity of virus when full
should be familiar with resources available to assist with
viral load suppression is expected. In identifying potential
HIV resistance mutation assessment including the Stanford
treatment failure, monitoring trends in viral load are essen-
University HIV Drug Database and International AIDS
tial as a single detectable viral load is not generally sufficient
Society-USA online repository (see Appendix).99 With
to diagnose treatment failure. These viral “blips” occur when
knowledge of the viral genotype, mutation patterns, and
a previously undetectable viral load becomes detectable but
associated antiretroviral medications, pharmacists can be a
does not exceed 200 copies/mL and generally reduces to un-
resource for the healthcare team in determining treatment
detectable levels again with subsequent testing. Increasing
options. Pharmacists should apply the results of genotype
viral loads over time or a viral load > 200 copies/mL are
testing as well as consider clinical guideline recommenda-
suggestive of treatment failure. Pharmacists can reduce the
tions, ART regimen history, adverse effects, pill burden, and
chances of unnecessary ART regimen changes in response
patient preference to provide a new ART regimen for a pa-
to viral load blips by monitoring the viral load trend and un-
tient. Pharmacists should be involved in any ART regimen
derstanding the definitions of virologic failure. If true fail-
change with the goal of reestablishing viral suppression and
ure is identified, pharmacists should then work with other
improving the CD4 cell count.
members of the healthcare team to identify the cause of the
regimen failure.
Most treatment failures may be attributed to three main Pharmacist Involvement in the
reasons: nonadherence, pharmacokinetic complications, and Management of HIV Disease State
ART resistance. Pharmacists, especially those with special- Complications
ized training in adherence assessment, interventions, and
motivational interviewing, can help determine which of Long-term complications of HIV infection have become an
these reasons may have contributed to valid ART failure. area of focus as patients with HIV live longer. Historically,
Many factors lead to non-adherence, including medication research and treatment efforts have revolved around anti-
intolerance and adverse effects, depression, substance use, retroviral-related medication toxicities and little has been
psychosocial factors, lack of social support, housing inse- known about the long-term consequences of being infected
curity or homelessness and patient beliefs. The pharmacist with HIV. However, recent literature has identified that be-
should work with the patient to assess and resolve any bar- ing chronically infected with HIV can lead to end-organ tox-
riers to ART adherence. Strategies for improving adher- icities, thrombotic complications, non-AIDS-defining can-
ence include utilizing an interprofessional team approach, cers, and metabolic abnormalities.100 Pharmacists can play a
establishing a rapport with the patient, proactively identify- key role in the identification and treatment of these emerging
ing adherence barriers prior to regimen initiation, assessing complications.
for medication intolerance and adverse effects, providing The mechanism by which HIV infection causes organ
mental health and social resources for the patient, assess- toxicity remains unclear. One postulated theory is that the
ing adherence at every pharmacy visit, involving the patient virus causes a prolonged state of immune system activation
in regimen selection, providing adherence aids such as pill that can lead to inflammation, endothelial dysfunction, and
boxes and calendars, and assisting the patient in setting a accelerated atherosclerosis, resulting in organ damage.101
cell phone alert or text message.97 Literature has shown that This prolonged inflammatory state may lead to the genera-
virologic failure has been rescued and the initial ART regi- tion of free radicals and oxidative stress in various organs.102
men preserved with pharmacist involvement and adherence Another possible mechanism is via a hypercoagulable state
interventions.35 that is seen in patients with HIV. Evidence supports a deple-
Pharmacokinetic complications may also contribute tion of proteins C and S, leading to enhanced thrombosis and
to HIV treatment failure. Malabsorption, alterations in drug subsequent disease complications.101,103 The extent of contri-
distribution, and drug-drug and drug-herbal interactions may bution of the virus itself in these conditions is unknown and
all cause subtherapeutic antiretroviral concentrations and the increased disease incidence may be a combination of the
lead to HIV resistance and ART failure. Pharmacists should effects of the virus, ART, and the longevity of HIV-infected
be aware of and monitor for these factors and suggest treat- patients. Organ toxicity, via a variety of mechanisms, may
ment alternatives. Although not routinely recommended, be seen in virtually all organ systems, but most research has
therapeutic drug monitoring may be obtained in specific been in HIV-associated cardiovascular, renal, hepatic, and
clinical situations and pharmacists may assist in the inter- neurological toxicities.
pretation of antiretroviral drug levels. 35,98
HIV and Cardiovascular Disease. In the cardiovascular sys- and recommend lifestyle modifications, including smok-
tem, HIV infection has been linked to coronary artery dis- ing cessation, diet modification, and exercise adherence, as
ease and cardiomyopathy. Cardiovascular disease is now the these have also been shown to decrease cardiovascular risk
third-most common cause of death in HIV-infected patients in patients with HIV.118-120
in the U.S., and literature has shown that patients with HIV In addition to controlling risk factors, pharmacists
have a greater incidence of myocardial infarction than non- should minimize exposure of direct cardiotoxic medications
infected patients.104,105 In addition to myocardial infarction, and to other medications that have adverse effects on the
cardiomyopathy in the form of systolic dysfunction has been lipid profile. Abacavir, a nucleoside reverse transcriptase in-
seen in 10–20% and diastolic dysfunction in 48% of HIV- hibitor, has been linked with possible increased risk of myo-
infected individuals.106,107 The mechanism underlying this cardial infarction.121,122 While literature is conflicting re-
increase in cardiovascular disease is thought to be a combina- garding this adverse effect, pharmacists should be cognizant
tion of HIV infection, treatment with ART, and the increased of this possibility and recommend alternative antiretroviral
lifespan of HIV-infected patients.105 Known inflammatory therapies as appropriate. Additionally, pharmacists involved
markers associated with cardiovascular risk are elevated in in HIV management may recommend an ART regimen that
HIV disease, leading to chronic inflammation, endothelial may have a less detrimental lipid effect.123
dysfunction, and accelerated atherosclerosis and throm-
bosis.108 Additionally, adverse effects of ART, specifically HIV and Renal Disease. HIV infection is associated with
protease inhibitors, include metabolic abnormalities such as nephropathy in the form of both acute kidney injury and
hyperlipidemia and hyperglycemia that heighten the risk of chronic renal failure.124 Acute kidney injury has been found
cardiovascular complications.109 Pharmacists are vitally im- to be more common among HIV-infected patients than the
portant in assisting with control of risk factors and improving general patient population and is associated with poor out-
the cardiovascular risk of patients living with HIV. comes.125 Acute kidney injury presents in many forms, but
Pharmacists should be actively involved in control- pre-renal failure and acute tubular necrosis are most com-
ling the cardiovascular risk factors of patients living with mon. Postulated mechanisms of HIV-induced acute renal
HIV. Pharmacists should recommend annual cardiovascular failure include medication-induced toxicities, specifically
risk assessments that include a lipid profile, fasting glucose, nephrolithiasis with atazanavir and indinavir, Fanconi’s
hemoglobin A1c (HbA1c) and blood pressure assessment. Syndrome with tenofovir, and dehydration from opportu-
Specifically, pharmacists who practice in the ambulatory nistic infections.125 Pharmacists are vital in the management
care setting may advocate for complete care via pharmacist- of HIV-induced renal toxicities and should review the se-
directed outpatient clinics based on physician collaborative rum creatinine and urinary analysis for the development of
practice agreements. Most research on pharmacist impact acute renal toxicity.33 Pharmacists should readily identify
has been conducted in pharmacist-managed outpatient lipid, contributing nephrotoxic medications that may compound
hypertension, diabetes, and heart failure clinics. Pharmacists nephrotoxicity and recommend possible discontinuation and
in these settings may conduct risk assessment screening, therapeutic alternatives. In addition, pharmacists should be
limited physical examinations, laboratory monitoring, medi- familiar with common medications used in the treatment
cation adjustments, and patient education. While not specific of HIV that interfere with the tubular section of creatinine,
to the HIV disease state, incorporation of a pharmacist into such as cobicistat, rilpivirine, dolutegravir, ritonavir, and
outpatient clinics has been shown to have a significant reduc- trimethoprim-sulfamethoxazole.126 These medications, al-
tion in cardiovascular events, low-density lipoprotein (LDL) though not inherently nephrotoxic, may increase the serum
cholesterol, blood pressure, HbA1c, and improved utiliza- creatinine and complicate the renal assessment of patients on
tion of mortality-reducing heart failure medications.110-114 these antiretroviral medications.
Pharmacist patient care may be conducted by facilitating in- Patients with HIV may also present with chronic forms
person clinic visits or via telephone consultations.115 In addi- of nephrotoxicity. Perhaps the most widely recognized form
tion, the benefits of pharmacist management of cardiovascu- of renal failure in HIV disease is HIV-associated nephropa-
lar risk factors in the patient-centered medical home model thy (HIVAN). HIVAN is most common among patients of
have been demonstrated.116,117 Pharmacists practicing in the African descent and is a significant contributor to chronic
community setting should recommend routine blood pres- renal failure. ART has been shown to aid in the reversal of
sure monitoring at all pharmacy visits and assist in appropri- HIV nephropathy by suppressing viral replication in the
ate selection and training of diabetes supplies such as glu- kidney, and pharmacists should advocate for prompt initia-
cose meters and test strips.33 Community pharmacists should tion of ART in these circumstances.127,128 HIV infection may
perform routine medication profile review and recommend also enhance other common risk factors for chronic kidney
selection of safe and effective over-the-counter medica- disease, such as diabetes and hypertension. As with cardio-
tions and herbal products. Pharmacists may also be proac- vascular toxicity, pharmacists should assist in glucose and
tive by recommending and overseeing the use of patient blood pressure control and additionally recommend thera-
self-monitoring treatment journals documenting changes in pies such as angiotensin-converting enzyme (ACE) inhibi-
blood pressure and glucose control. Finally, inpatient phar- tors or angiotensin receptor blockers that are thought to de-
macists may facilitate increased use of medication prescrip- lay the progression of kidney failure.129,130
tions for cardiovascular risk reduction at hospital discharge. For patients with renal failure, pharmacists should
In all practice settings, pharmacists should be familiar with take responsibility for ensuring appropriate dose adjust-
lipid, blood pressure, and blood glucose treatment goals and ments of renally eliminated medications, including antiret-
guidelines and should directly apply those guidelines to as- roviral medications and other medications on a patient’s
sist in decreasing the cardiovascular risk in HIV-infected profile (see Appendix).35 Active pharmacist involvement in
patients. In addition, pharmacists should routinely monitor ensuring proper doses of renally eliminated medications has
been demonstrated to decrease adverse effects and result in of possible cognitive decline. If such symptoms are recog-
cost savings.131 Medication renal dose adjustment is espe- nized, communication and facilitation with the patient’s pro-
cially important in advanced nephropathy requiring dialysis. vider is recommended.
Pharmacists should be familiar with various dialysis modali- Several theories about the mechanism of HAND have
ties and their effects on medication removal. Pharmacists been postulated, with most suggesting that the chronic in-
should then pair this with knowledge of specific medication flammation state caused by HIV infection generates free
renal elimination characteristics to ensure safe and effective radicals that inflict neuronal damage. There is no correla-
medication regimens. tion between the development of HAND and HIV plasma
Finally, pharmacists knowledgeable about HIV may concentration, current CD4 count, or the presence of effec-
recommend ART that minimizes nephrotoxicity, taking into tive ART.134,136 The development of HAND has been asso-
consideration the HIV genotype and laboratory markers of ciated with a low CD4 nadir, however.137 This association
HIV disease. Alteration of a patient’s ART to minimize renal reinforces the need for early initiation of ART to prevent low
involvement can lead to enhanced safety and simplification CD4 levels and protect against the development of neuro-
of the HIV regimen. In addition, pharmacists should aim to toxicity. No other therapy has been shown to prevent or im-
minimize renal toxicity of all medications prescribed, with prove HAND, so pharmacists can contribute to the care of
the goal of providing a safe and effective complete medica- these patients by focusing on early and effective utilization
tion profile. of ART.102, 138
HAND and its complications have serious ramifica-
HIV and Hepatic Disease. As with HIV-associated neph- tions on other aspects of HIV care. Decreased neurologic
rotoxicity, pharmacists should be cognizant of HIV hepato- function has been linked to poor patient adherence to ART
toxicity. Although the majority of literature revolves around and other therapies, unemployment, lack of transportation,
mechanisms such as medication-induced hepatotoxicity, and increased reliance on financial assistance for medica-
co-infection with viral hepatitis, and alcohol injury, there is tions.139 Pharmacists should work closely with their patients
some evidence that HIV infection alone may contribute to to create personalized medication adherence programs and
accelerated liver damage.132 Pharmacists should first rou- provide access to medication assistance programs. Ensuring
tinely monitor liver function tests to detect the presence of safe and effective use of medications is the pharmacists’
hepatic toxicity. If clinically significant elevations in hepatic highest priority in caring for these patients.
function tests are detected, pharmacists should identify and Other HIV-associated neurologic complications in-
limit all medications that may induce hepatic injury. Many clude peripheral neuropathy and ischemic stroke. Peripheral
classes of antiretroviral medications have been linked to neuropathy is the most frequently reported neurologic diag-
hepatotoxicity, including non-nucleoside reverse transcrip- nosis in HIV-positive patients and usually responds to medi-
tase inhibitors and protease inhibitors. Specifically, nevi- cations typically used to treat neuropathic pain.136 Common
rapine, maraviroc, and tipranavir have boxed warnings for causes of peripheral neuropathy in HIV-infected patients
hepatotoxicity, and ART regimens may need to be altered include neurotoxic medications (such as didanosine), diabe-
for patients being treated with those medications. If toxicity tes, alcohol use, and nutritional deficiencies (such as B12).
progresses to advanced liver failure and cirrhosis, pharma- Pharmacists should assess for the development and progres-
cists need to recognize that altered drug metabolism may oc- sion of peripheral neuropathy and recommend appropriate
cur and monitor for medication toxicities and possible treat- therapeutic treatment options.
ment failure.133 Pharmacists should also recommend testing Hospital admissions for ischemic stroke in HIV-
for viral hepatitis, as co-infection has been known to accel- infected patients have increased 43% over the last decade in
erate liver decline.130 Pharmacists may also recognize cur- the U.S. The higher incidence of ischemic stroke is thought
rent alcohol and illicit drug use and facilitate admission into to be caused by a combination of accelerated atheroscle-
treatment programs if necessary.133 In addition, recognizing rosis and thrombosis.101 Pharmacists should play an active
that alcohol and illicit drug consumption may alter medica- role in assisting in the medication selection of acute stroke
tion adherence, pharmacists should reinforce the importance treatment. Because stroke patients often suffer from dyspha-
of medication adherence and adopt adherence strategies that gia, necessitating use of short- and long-term enteral feed-
are acceptable to patients. Finally, pharmacists should rec- ing tubes, pharmacists should be familiar with guidelines for
ommend hepatic dose adjustment of medications for which proper administration of medications via enteral tubes (e.g.,
adjustment has been identified (see Appendix). determining whether a medication may be crushed and the
implications of the site of enteral medication absorption) (see
HIV and Neurologic Disease. Neurotoxicity and central ner- Appendix).140,141 After an acute stroke episode, pharmacists
vous system disorders are recognized complications of HIV should be involved in assisting patients with the selection of
infection. HIV-associated neurocognitive disorders (HAND) secondary prevention medications (e.g., antiplatelet and lipid
classifies certain neurologic HIV complications, including therapies) to minimize drug interactions and maximize the
mental slowing, memory loss, motor disorders, and behav- safety and efficacy of the patient’s entire medication regimen.
ioral abnormalities.134 These progressive symptoms lead to Pharmacists should also be aggressive in helping manage
a decline in cognitive function that may eventually develop modifiable risk factors, such as hypertension, diabetes, and
into HIV dementia. HAND complications occur in approxi- hyperlipidemia. Literature demonstrates that interdisciplin-
mately half of patients diagnosed with HIV and represent a ary teams including active pharmacist intervention improve
substantial cause of morbidity and mortality.134-136 Although management of ischemic stroke risk factors.142 Pharmacists
the known incidence of HAND is high, this estimate may be should encourage intensive management of these risk factors
conservative, as HAND is often unrecognized and may be and other lifestyle modifications, such as smoking cessation,
under-diagnosed. Pharmacists should be alert to symptoms exercise regimens, and weight management programs.
In addition to physiologic causes, medications are an- should also minimize ART agents that have adverse meta-
other important consideration in the neurological state of the bolic effects and recommend appropriate alternatives.147 In
patient with HIV. Pharmacists should review the medication addition, pharmacists should work closely with dietitians to
profile for all medications that may affect cognitive func- ensure appropriate nutrition support for the complete care of
tion, such as opioid narcotics and benzodiazepines. Certain the HIV-infected patient.154 Morphologic complications may
antiretroviral medications, including efavirenz, have also have detrimental physical and psychological effects on pa-
been associated with CNS abnormalities. The pharmacist tients, which may decrease adherence to ART. Pharmacists
should be alert to and aim to minimize the neurological ad- should be cognizant of morphologic complications, recom-
verse effects of medications in patients experiencing HIV- mend medical and lifestyle modifications as appropriate,
associated neurotoxicity and recommend appropriate thera- and work with patients and providers to maximize treatment
peutic alternatives. and adherence to HIV therapies.
In addition to traditional endocrine complications, al-
HIV and Malignancy. AIDS-associated malignancies are a terations in bone metabolism have become a significant en-
well-documented complication of HIV, but HIV-infected pa- docrine complication of HIV. HIV infection leads to earlier
tients also face increased incidence of other cancer types.143 and more frequent loss of bone density than non-infected
Collectively, these cancers are termed “non-AIDS-defin- individuals, leading to increased incidence of osteopenia,
ing cancers” and include cancers such as Hodgkin’s lym- osteoporosis and fractures.155 Like other chronic HIV com-
phoma and malignancies of the lung, kidney, anus, liver, plications, this is due to traditional risk factors, effects of the
and skin.144,145 Guidelines for identification of these cancers virus itself and use of certain antiretroviral therapies, spe-
overall mimic recommendations for the general population; cifically tenofovir.156 Specific screening recommendations
however, some, such as cervical cancer, require more fre- have been developed for patients with HIV, and pharmacists
quent monitoring, and pharmacists should recommend rou- should be informed of these recommendations and take an
tine cancer screening when appropriate. active role in screening patients for this complication.157
Cancer treatment in patients with HIV presents a chal- Pharmacists should also be versed on appropriate osteopo-
lenge to pharmacists and practitioners, as the need to balance rosis treatments and recommend vitamin supplementation
cancer cure must be weighed against the risk of chemother- and pharmacologic therapy when warranted. In addition,
apy-enhanced immunosuppression and resulting opportunis- pharmacists should aid in recommending nonpharmacologic
tic infections. Given their expertise in drug-drug interaction strategies for prevention of bone loss, including reducing al-
and toxicity management, pharmacists are uniquely qualified cohol intake, smoking cessation, and advocating for healthy
to assist in chemotherapy and ART selection. Pharmacists body weight.
should be knowledgeable in drug interactions between ART As patients with HIV live longer, more information
and chemotherapy agents and assist with regimen selections will emerge regarding the role of chronic HIV disease state
for both disease states that minimize toxicity while ensur- complications. What is already evident is that proper rec-
ing efficacy (see Appendix). In addition, pharmacists can ognition and treatment of cardiovascular, renal, hepatic,
aid in the initiation of appropriate opportunistic infection neurological, malignant, and endocrine complications is
prophylaxis. Finally, more research is needed on the interac- desperately needed to fully care for HIV-infected patients.
tion between cancer, chemotherapy, HIV disease, and ART. Pharmacists are integral to the medical team that must care
Pharmacists should be a key component in future research for the whole patient, including HIV infection itself and
teams where research is desperately needed to ensure safe long-term complications of HIV disease.
and appropriate patient care.
Pharmacist Involvement
HIV and Endocrine Disease. Patients living with HIV are
also at risk for the development of traditional endocrine
in Opportunistic Infections
disorders related to HIV disease, including lipodystrophy,
Opportunistic infections contribute significantly to the mor-
hypogonadism, and HIV wasting syndrome. These condi-
bidity and mortality of HIV-infected individuals. Although
tions are thought to be caused by mitochondrial toxicity and
effective ART has reduced the incidence of opportunistic
alterations in levels of growth hormone accelerated by ad-
infections, prevention, recognition, and treatment of those
verse effects of antiretroviral medications, specifically pro-
infections continue to be of utmost importance in this patient
tease inhibitors.146,147 Lipodystrophy consists of an increase
population.158 The complexity of prophylaxis and treatment
in visceral fat and decrease in subcutaneous fat stores, par-
of opportunistic infections in HIV patients requires an inter-
ticularly in the face and extremities.147 Low levels of tes-
disciplinary approach. Pharmacists can be involved in the
tosterone may lead to hypogonadism, sexual dysfunction,
prevention and treatment of HIV-associated opportunistic
and muscle wasting in HIV-infected individuals.148 Some
infections by providing recommendations on the initiation
patients with HIV suffer from HIV wasting syndrome due in
or discontinuation of opportunistic infection prophylaxis,
part to increased energy expenditure that leads to a decrease
the recognition and diagnosis of active opportunistic in-
in lean body mass and total body mass index.149 New agents
fections, treatment and dosing recommendations for active
are being investigated for treatment of these disorders, and
opportunistic infections, and the timing of ART initiation.
pharmacists caring for patients living with HIV should
Through these interventions pharmacists play a key role in
be knowledgeable about available recommended thera-
improving the medication management of individuals with
pies.150,151 Specifically, pharmacists may assist in testos-
HIV disease.
terone formulation selection, contraindication assessment,
Pharmacists may first intervene with recommenda-
laboratory monitoring, and counseling on proper testoster-
tions for when to initiate opportunistic infection prophy-
one administration and adverse effects.152-154 Pharmacists
laxis. Medication prophylaxis for various opportunistic in- the complexity and alteration of medication regimens, the
fections is offered to individuals with advanced HIV disease. necessity of transitions of care, and the need for their care
Primary prophylaxis aims to prevent the first occurrence of to be provided by practitioners that may be unfamiliar with
an opportunistic infection; secondary prophylaxis is geared ART and HIV complications.166 The inpatient setting pro-
toward preventing disease recurrence.159 The decision to ini- vides pharmacists a unique venue for impact in the care of
tiate prophylaxis is therefore dependent on the patient’s CD4 HIV-infected patients, and literature has shown that phar-
cell count and the patient’s history of an active opportunistic macist involvement specifically in this patient population
infection. Pharmacists should be familiar with and recom- decreases medication relation errors.167 Pharmacists should
mend specific prophylactic agents and alternative regimens be involved in admission and discharge medication recon-
for patients with medication allergies. Published guidelines ciliation, provide patient discharge medication education,
that can help pharmacists in making recommendations re- and assist with the transition of the patient to outpatient care.
garding appropriate prophylactic medications and when to
initiate primary and secondary opportunistic infection pro- HIV and Immunization. Immunization, as disease preven-
phylaxis are available (see Appendix).160 tion, is important in the care of patients with HIV, as im-
The recognition of when to discontinue prophylaxis is munodeficiency creates enhanced susceptibility to infection
as important as its initiation. Literature supports the safety of acquisition. Pharmacists should be aware of current immuni-
discontinuation of opportunistic infection prophylaxis when zation recommendations for HIV-infected patients and work
the CD4 cell count rises above a threshold for a defined pe- to assure appropriate and timely routine immunization (see
riod of time while on effective ART.159-161 Pharmacists fa- Appendix). Additionally, pharmacists should also be active
miliar with discontinuation recommendations may intervene immunization advocates by facilitating pharmacist-adminis-
to discourage inappropriate continuation of drug therapy. tered immunization programs.
Discontinuation of opportunistic infection prophylaxis may The Advisory Committee on Immunization Practices
lead to a decrease in side effects and drug-drug interactions, (ACIP) publishes annual immunization recommendations
limit drug resistance, lower pill burden, increase rates of ad- for all patients, including specific recommendations for those
herence, and provide cost savings.159 with HIV infection. It is generally accepted that inactivated
Pharmacists also play a vital role in the recognition vaccines are considered safe for HIV-infected patients; some
and treatment of active opportunistic infections. Pharmacists live vaccines may be administered based on a patient’s CD4
aid in the diagnosis of opportunistic infections via symptom cell count. Patients with HIV should be immunized against
recognition and testing recommendations. Once a patient infections such as influenza, pneumococcus, hepatitis A,
is diagnosed, pharmacists can contribute to the treatment hepatitis B, and tetanus/diphtheria.168 In addition, certain im-
of opportunistic infections by offering evidence-based rec- munizations may require different dosages in HIV-infected
ommendations on anti-infective drug selection and dosing, patients. Pharmacists should be aware of the immunization
monitoring medication efficacy and toxicity, preventing and status of their patients and provide recommendations regard-
recognizing drug-drug and drug-nutrient interactions, and ing safe and effective vaccine administration.
making literature-based recommendations on total treat- Effective seroprotective antibody levels after immuni-
ment duration.160 zation are a concern in patients with HIV. Immunization is
After an opportunistic infection has been diagnosed most effective at high CD4 cell counts and may be delayed
and treatment initiated, pharmacists should be active in de- until the CD4 count is above 200 cells/mm3. There are situ-
termining the optimal timing of ART initiation. The decision ations, however, in which delay is not feasible, as patients
regarding ART initiation is complex and must weigh the ben- with HIV may receive pneumococcal vaccination upon HIV
efits of ART against the possibility of the complication of im- diagnosis and an annual influenza vaccination regardless of
mune reconstitution inflammatory syndrome. Although some CD4 cell count.169 In addition, certain live vaccines are now
literature has shown that early ART initiation is paramount in being safely administered if the CD4 cell count is near nor-
improving survival and decreasing AIDS progression by im- mal levels. Pharmacists should aid HIV care practitioners
proved immune functioning, other studies have demonstrated in the appropriate timing of immunizations to enhance ad-
that ART may not improve or may perhaps be detrimental in equate immune response while balancing the safety of vac-
certain types of opportunistic infections.162-164 Current guide- cine administration.
lines provide recommendations on when to initiate ART in After determination of immunization needs and timing,
specific types of opportunistic infections and can help guide pharmacists in the community and clinic settings may also
patients, pharmacists, and other healthcare providers in this directly administer immunizations. Pharmacist-managed
decision-making process.160,165 Pharmacists can assist other immunization programs improve access to vaccine adminis-
HIV care practitioners by providing evidence-based recom- tration and corresponding immunization rates.170 Pharmacist
mendations regarding the initiation of ART in the setting of immunization administration privileges vary by type of vac-
an active opportunistic infection and contributing to the se- cine, patient age, and immunization training requirements,
lection of an ART treatment regimen that avoids interactions so pharmacists should practice in accordance with state
with the anti-infective medication regimen. and local regulations. Pharmacists certified or licensed in
Patients with opportunistic infections are on com- immunization administration should take an active role in
plex medication regimens and often require hospitalization. immunizing patients with HIV. Documentation of vaccine
Pharmacists practicing in the inpatient setting play a key administration and communication of immunization status
role in the appropriate care of these patients by preventing to prescribers and other practitioners should be completed to
and resolving medication-related errors. Patients with HIV bridge the continuum of HIV patient care.171
specifically have a high rate of medication errors due to
Pharmacist Involvement in HIV regarding PrEP, pharmacists should be familiar with clinical
practice guidelines on the use of PrEP in high-risk popula-
Prevention
tions published by CDC and make informed and appropriate
recommendations about PrEP safety, efficacy, acquisition,
HIV prevention requires an interdisciplinary approach in-
and need for routine follow-up HIV testing.181 Pharmacists
volving pharmacists as active members of the healthcare
practicing in community settings that sell barrier methods,
team. Active pharmacist participation in prevention initia-
or those who fill prescriptions for PrEP or medications used
tives can help prevent transmission and reduce the rate of
to treat sexually transmitted infections, can help identify pa-
HIV infection. Pharmacists play a key role in HIV prevention
tients who may benefit from PrEP and link them to PrEP
through both pharmacological and behavioral interventions.
prescribers in the community. The success of PrEP is largely
High viral load is a risk factor for HIV transmission.35
dependent on high levels of medication adherence. To date,
By reinforcing ART adherence, and subsequently lower-
five clinical trials have demonstrated the efficacy of PrEP
ing a patient’s HIV viral load, the risk of HIV transmission
for HIV prevention in various patient populations, with
can be reduced. The benefits of ART for prevention have
improved efficacy for adherent individuals.182-186 Notably,
been demonstrated in various populations, including preg-
other PrEP studies have been halted early due to futility,
nant women, HIV-serodiscordant partners, and geographic
primarily attributed to lower medication adherence.187,188
communities. Because the risk of mother-to-child transmis-
Pharmacists have the opportunity to assist with developing
sion is strongly associated with a higher HIV viral load, the
PrEP protocols for newer prevention modalities and, with
use of ART in pregnancy has dramatically reduced the inci-
appropriate training and resources, pharmacists can improve
dence of perinatally acquired HIV infections and is recom-
patient understanding, promote medication adherence, and
mended by DHHS guidelines.42 Decreases in HIV viral load
enhance PrEP efficacy.189,190 Pharmacists are well positioned
via ART are also associated with decreased heterosexual
to play a key role in helping patients make choices about
transmission, as demonstrated in both observational studies
PrEP, managing their therapy, and developing policy.
and randomized trials.173-175 Based on these results, DHHS
Post-exposure prophylaxis (PEP) is the short-term
guidelines recommend ART be offered to those at risk of
use of antiretroviral medications by uninfected individuals
transmitting HIV to sexual partners, including heterosexuals
following an HIV exposure. CDC has published guidelines
and other risk groups.35 In addition to the benefits of ART
for the implementation of HIV post-exposure prophylaxis
for preventing HIV transmission in serodiscordant couples,
following both occupational and non-occupational expo-
data have shown that widespread use of ART may benefit
sures.191,192 Effective perinatal ART is also thought of as a
entire communities via reductions in community viral load
form of PEP, and pharmacists are involved in prevention of
and decreased numbers of new infections.176,177
mother-to-child transmission.193 Opportunities for pharma-
Medication adherence is the key to maximizing the full
cist involvement in PEP varies by setting and may include
benefits of ART. Pharmacist involvement in antiretroviral
developing institutional protocols, dispensing initial PEP
medication adherence is perhaps the most well-documented
doses, counseling patients on PEP medications, identify-
prevention intervention in the literature and, as shown in a
ing drug interactions, and coordinating follow-up testing.
systematic review, is associated with statistically significant
An important resource for pharmacists and other healthcare
adherence improvements and positive impact on viral sup-
providers is the Clinician Consultation Center, which pro-
pression.178 Pharmacist involvement in direct patient-care
vides national expert telephone consultation, free of charge,
efforts focused on adherence extend well beyond required
surrounding PrEP, PEP, and perinatal HIV infection (www.
prescription counseling and may include providing practical
nccc.ucsf.edu). The use of antiretroviral chemoprophylaxis
and social support to motivate adherence, educating to en-
for preventing HIV after accidental or occupational expo-
hance patient self-efficacy, regularly monitoring adherence,
sure and in maternal-to-fetal transmission has become a
collaborating with other healthcare professionals, recogniz-
widely accepted method to combat HIV, and pharmacists
ing and managing side effects, making recommendations
can effectively contribute to these initiatives.
regarding self-management, advocating for patients with
HIV testing, in addition to ensuring early entry into
insurance issues, and instructing on the use of adherence-
care for HIV-infected individuals, is also an effective HIV
enhancing tools.178-180 The DHHS adult HIV guidelines
prevention strategy. Pharmacists should be an entry point
provide evidence-based recommendations on assessing and
for early HIV testing; they should recognize HIV risk fac-
monitoring adherence and outline strategies to help patients
tors and signs and symptoms of HIV/AIDS, and recom-
maintain high levels of adherence.35 Identifying patients with
mend testing, whether it is provided on site in community
adherence challenges requiring attention and implement-
pharmacies or as a take-home test. Pharmacists should link
ing methods to enhance adherence are essential roles for all
those who test negative with effective prevention measures,
members of the treatment team, including pharmacists.
including PrEP. For patients who test positive, pharmacists
Although ART adherence is an essential component of
should ensure that patients access medical care.
HIV prevention among HIV-infected individuals, it is also a
Decreasing circulation of contaminated syringes in
necessary factor for prevention among HIV-exposed individ-
and beyond the intravenous drug user (IDU) community is a
uals taking pre- or post-exposure prophylaxis. Pre-exposure
central HIV prevention strategy.194 Pharmacists can play an
prophylaxis (PrEP) is the use of antiretroviral medications by
integral role in providing HIV prevention and health services
higher-risk, uninfected individuals before and during periods
to IDU populations by counseling IDUs regarding syringe
of risk to prevent HIV acquisition. Currently, the fixed-dose
access and disposal and addiction treatment programs. The
combination tablet of tenofovir/emtricitabine taken orally is
literature documents pharmacist participation in providing
the only FDA-approved product for PrEP; however, ongoing
and encouraging use of sterile syringes and injection equip-
studies are examining use of other antiretroviral agents in
ment, providing patient counseling on harm-reduction strat-
various dosage forms. When responding to patient inquiries
egies (e.g., substance abuse treatment, safe injection and dis- ing medication side effects, and providing information on
posal practices, and safe sex practices), and supporting local clinically oriented questions. Because HIV management is
syringe exchange programs.194,195 In some areas, IDUs have complex and involves coordination of multi-drug therapies,
the option of purchasing syringes from a pharmacy without pharmacists should support providers and assist prescrib-
a prescription. Such policies are controversial, however, ers and patients in attaining specific disease state goals.
and ultimately the decision to sell syringes without a pre- Pharmacists have expertise in medication dosing, adverse
scription belongs to the individual pharmacist. Pharmacists effects, drug-drug interactions, and medication adherence,
should be aware of syringe replacement programs in their and they serve as useful drug information sources for pro-
community and provide appropriate information to IDUs vider and patient inquiries.
when requested. Providing HIV-related services to IDUs Pharmacists practicing in HIV medicine should edu-
may not only limit HIV transmission but may also present cate healthcare team members, provide in-service training
an opportunity to expand healthcare services to a population to healthcare staff, and conduct community seminars for pa-
that is historically underserved and may have limited access tients, caregivers, and the public on HIV, ART, drug interac-
to other healthcare services. tions, and adherence. As a leader in HIV medication use, the
Pharmacists should be knowledgeable about behav- pharmacist should train colleagues and the next generation
ioral interventions to reduce HIV transmission, although of providers by teaching pharmacy students and residents.
documentation of pharmacists’ delivery of behavioral inter- Trainee education could expand to other health professions,
ventions is still nascent. Pharmacists should provide educa- including medical students and residents, nursing students,
tional messages and materials, advise patients on prevention especially those in advanced degree programs, mid-level pro-
methods (e.g., condom promotion, safer sex practices, and vider students, and allied health professions students as well
drug-use counseling), and deliver behavioral risk-reduction as those receiving advanced training in the field of infectious
counseling. diseases. Teaching may be clinical in nature (e.g., experiential
Pharmacists’ unique position in society allows them rotations) or didactic training in a classroom setting.
to contribute to HIV prevention efforts. Pharmacist in- Emphasis on the importance of keeping current with
volvement includes both traditional roles (providing ART the rapidly evolving HIV field is vital for both practicing cli-
education and ensuring legal access to sterile needles and nicians and future providers. Whatever the setting, pharma-
syringes) and innovative roles (developing PrEP protocols cists should continue to serve as a liaison between patients
and delivering behavioral interventions). As HIV prevention and providers to remain knowledgeable and credible within
becomes increasingly important, the pharmacist’s role will the field and to interact with colleagues in the HIV field at
continue to expand within the healthcare team. an interprofessional level. It is important to stay active and
to be part of the exchange of information and clinical experi-
Pharmacist Involvement ence with other connected providers and trainees.
in HIV Education
Pharmacist Social Services Involvement
Pharmacists are extensively involved in providing education
to patients and providers about medication-related care, as- Access to healthcare, including prescription medications, is
sessing the patient’s readiness and ability to adhere to ART, a growing problem as the cost of healthcare rises. The cost of
providing initial or follow-up education on HIV-related medications and copayments are major predictors of adher-
disease and complications as well as antiretroviral medica- ence to medication therapy regimens.197,198 Many programs
tions, and evaluating adherence to a therapeutic regimen. are available to assist with healthcare costs, but eligibility
Pharmacists perform these tasks within an interprofessional guidelines and application processes can be complicated.
healthcare environment. As medication experts, pharma- Pharmacists are well poised to assist patients in overcoming
cists play a role in education of patients, communities, and these obstacles, making medications more accessible and re-
healthcare workers. ducing costs to individuals and healthcare entities.
A central pharmacist role is patient education and Pharmacists are in an ideal position to educate patients,
provision of medication counseling to patients and commu- monitor adherence with therapy, and help patients work
nities. A recent systematic review documents the positive through drug-related problems. Pharmacists should monitor
impact of pharmacist-conducted medication adherence edu- refills – both for availability and for timeliness – and no-
cation on clinical patient outcomes.38 Education about medi- tify the prescriber of any concerns. Pharmacists also have
cation indication, dose, route, frequency, potential adverse an important role in being aware when prior authorization
effects, and the importance of adherence should occur at ev- requirements exist for medications and how to facilitate ap-
ery patient encounter. For returning patients, medication un- proval to prevent delays in medication access for patients.199
derstanding and adherence should be reassessed not just for Pharmacists should ensure all antiretroviral medications
antiretroviral medications but for all medications. Through and medications for opportunistic infection treatment and
patient educational initiatives, pharmacists can assure opti- prophylaxis can be ordered for stock quickly and easily to
mal pharmacotherapy, adherence, and successful outcomes. minimize delays in medication access. Pharmacists can also
Pharmacists often act as an educational liaison be- ensure an adequate stock is available for the most common
tween the patient and the medical provider. Pharmacist regimens. Likewise, pharmacists in all settings can play a
tasks can include helping with the selection of the optimal significant role in medication reconciliation during care
ART regimen, assisting patients in overcoming adherence transitions.200 Pharmacists should assist other healthcare
issues, counseling patients, identifying and advising on providers in providing seamless care transitions (from out-
potential drug-drug interactions, recognizing and manag- patient care to institutional care, during hospitalization, and
at the time of discharge) to prevent medication errors.201 Pill
burden, side effects, and demands on time and attention pose ages pharmacist membership and invites pharmacists to
considerable obstacles to adherence; helping patients obtain serve as active members in organizational leadership and
their medications in a timely manner removes one major ob- committees. Several national HIV organizations also have
stacle. pharmacist-specific registration, programming, and con-
Pharmacists should assist patients at risk of nonadher- tinuing education credit opportunities at their educational
ence due to limited financial means. Patients often misun- conventions. Internationally, the Canadian HIV/AIDS
derstand available insurance benefits, and pharmacists can Pharmacist Network (CHAP) strives to connect pharmacists
support patients by reviewing drug formularies, suggesting involved in HIV care and provides educational information
cost-effective options, and relaying this information to the to its members. In addition, the International Association of
prescriber. Pharmacists must know how to access national, Providers of AIDS Care has expanded to recognize phar-
state, and local resources. For patients with prescription macists as part of the HIV treatment team. Pharmacists in-
drug insurance but difficulty affording copayments, or for volved in HIV care should strive to be active members of
patients lacking insurance, the pharmacist should confirm professional organizations, attend organizational meetings,
all medications are necessary and identify less-expensive provide meeting lectures on HIV clinical updates, partici-
alternatives. Many antiretroviral medication manufacturers pate in the sharing of HIV information via pharmacist net-
offer prescription copay cards that reduce a patient’s out- works, and support enhanced pharmacist membership in
of-pocket costs. Pharmaceutical manufacturers also offer these organizations (see Appendix).
patient assistance programs (PAPs) to ease the financial The creation of pharmacist HIV credentialing pro-
burden of medications. Eligibility criteria and enrollment re- grams highlights the importance of having pharmacists
quirements for PAPs vary, but they generally include docu- knowledgeable about and trained in the treatment of HIV
mentation of limited income, lack of prescription drug cov- disease. The American Academy of HIV Medicine HIV
erage, and ineligibility for public assistance. Although PAP Pharmacist credential (AAHIVP) is offered to pharmacists
applications usually require both the prescriber’s and the who have completed certain requirements, such as evidence
patient’s signature, pharmacists can assist in the application of direct HIV patient care, HIV continuing education, and
process.197,198 Pharmacists should also be aware of pharma- successful completion of the AAHIVP credentialing exam.204
cies—local or mail order—that offer special generic retail Other institutions also offer specific pharmacist HIV certifi-
pricing, which is sometimes less than insurance copayments. cate programs. Pharmacists should investigate certification
Pharmacists should have the knowledge to effectively opportunities, seek the knowledge and skills necessary to be
help low-income patients gain access to national and state- certified HIV providers, and lead the pharmacy profession in
level prescription drug programs for which they may be eli- the care of the HIV patient (see Appendix).
gible, including Medicare Part D, Ryan White AIDS Drug Pharmacists should also be aware of local and national
Assistance Programs (ADAPs), and Medicaid. Medicare Part policy issues surrounding HIV care. The world of HIV
D is designed to offer the beneficiary a choice between pre- changes rapidly, and many challenges require legislative or
scription drug plans, and many pharmacists offer Part D plan regulatory action. Pharmacists should be advocates for HIV
selection assistance to help beneficiaries obtain optimal drug patients by being familiar with current HIV legislation and
coverage.202 ADAPs are available in each state, guarantee- national HIV programs such as the Ryan White Program.
ing antiretroviral medication prescription assistance to low- Pharmacists should also contact local and national policy-
income and under- and uninsured HIV-infected patients. The makers to ensure proper education about HIV issues, be
Patient Protection and Affordable Care Act will expand health involved in HIV advisory panels, provide expert testimony,
insurance program eligibility and provide opportunities for and participate in advocacy initiatives to assist in the devel-
pharmacists to assist with care coordination and expand their opment of laws that best serve HIV patients. Through these
scopes of practice.203 Although pharmacists cannot choose opportunities, pharmacists can steer policy development and
prescription drug plans for patients, pharmacists should serve actively advocate for HIV patients.
as a resource to help patients understand their options to en- There are also many opportunities for pharmacists to
sure continued access to antiretroviral medications. volunteer for HIV-related activities. Locally, pharmacists can
volunteer in their communities by participating in fundrais-
Pharmacist Professional Involvement ing events such as AIDS walks, auctions, and other functions
in which proceeds go to fund local HIV programs. Many
Although pharmacists have a role in direct HIV patient care, communities are in need of pharmacists to serve in free medi-
there are other ways pharmacists can assist the HIV patient cal and dental clinics, where underserved patients receive ac-
population. Pharmacists should be active in extracurricular cess to much-needed HIV care. Pharmacists can also choose
professional involvement, which can be achieved via orga- to volunteer outside of their communities, through programs
nizational membership, HIV pharmacist certification, ad- such as Doctors Without Borders that focus on delivering
vocacy initiatives, volunteer positions, and participation in HIV care and medications to developing countries.205 There
clinical research. These areas represent possible opportuni- are numerous volunteer opportunities that benefit HIV pa-
ties for pharmacists to supplement clinical roles. tients outside of medical settings, and pharmacists should
In recent years, HIV-focused professional organiza- dedicate time to serving in these capacities.
tions have expanded to include pharmacist membership. Finally, pharmacists should play an active role in HIV
State and regional AIDS Education and Training Centers clinical research. Pharmacists should be knowledgeable
have embraced pharmacist involvement and many pro- about ongoing clinical research trials on topic areas such as
vide education, networking, and faculty appointments for new antiretroviral medications, disease state complications,
pharmacists involved in HIV care. On a national scale, the and prevention strategies that will shape the future of HIV
American Academy of HIV Medicine (AAHIVM) encour- care. Pharmacists can serve in a variety of capacities as part
of HIV clinical research teams, as principal or co-investi- 3. Rodger AJ, Lodwick R, Schecter M, et al. Mortality
gators, in recruitment and consent of trial participants, and in well controlled HIV in the continuous antiretrovi-
in facilitation of clinical research trials within their prac- ral therapy arms of the SMART and ESPRIT trials
tice settings.206 Permissible scope of pharmacist involve- compared with the general population. AIDS. 2013;
ment in clinical research varies by state, and pharmacists 27(6):973–9.
should be familiar with laws that define pharmacist activity. 4. Centers for Disease Control and Prevention. Estimates
Pharmacists may also be involved in research by publishing of new HIV infections in the United States, 2006-
case reports, serving on institutional review boards, acting as 2009. August 2011. Available at: http://www.cdc.gov/
consultants in HIV clinical research trials, and serving as re- nchhstp/newsroom/docs/HIV-Infections-2006–2009.
search mentors to other practitioners caring for patients with pdf. Accessed October 16, 2012.
HIV. With over 30 antiretroviral medications available, and 5. El-Sadr WM, Mayer KH, Adimora AA. The HIV epi-
more in the investigational pipeline, pharmacists can have demic in the United States: A time for action. JAIDS.
an integral role in facilitating the introduction of safe and 2010; 55:S63.
effective HIV medications and clinical research. 6. Millet GA, Crowley JS, Koh H, et al. A way forward:
Pharmacist involvement in the care of the HIV patient The national HIV/AIDS strategy and reducing HIV
extends beyond the bedside to include other types of pro- incidence in the United States. JAIDS. 2010; 55:S144–
fessional activity. Through organizational membership, HIV S147.
pharmacist certification, advocacy initiatives, volunteer po- 7. El-Sadr WM, Mayer KH, Hodder SL. AIDS in
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should be true advocates in all aspects of HIV patient care. 2010; 362:967–70.
Pharmacists are a tremendous resource that should be mobi- 8. Moore RD. Epidemiology of HIV Infection in the
lized and each pharmacist has a responsibility to be an active United States: Implications for Linkage to Care. Clin
proponent for the advancement of HIV care. Infect Dis. 2011; 52:S208–S213.
9. Centers for Disease Control and Prevention. U.S.
Conclusion Department of Health and Human Services. MMWR.
2011; 60(47):1618–23.
HIV medicine is a dynamic field that has evolved dramati- 10. Smith M, Bates DW, Bodenheimer TS. Pharmacists
cally since its inception. It continues to evolve today, provid- belong in accountable care organizations and inte-
ing both opportunities and challenges to delivering optimal grated care teams. Health Aff. 2013; 11: 1963–70.
patient care. These challenges and opportunities should be 11. Smith M, Bates DW, Bodenhimer TS, et al. Why phar-
met with interprofessional efforts that identify and optimize macists belong in the medical home. Health Aff. 2010;
the roles of all healthcare team members, including pharma- 5: 906–13.
cists, as a means to provide comprehensive care and improve 12. Henderson KC, Hindman J, Johnson SC, et al.
patient outcomes. The pharmacist in particular is uniquely Assessing the effectiveness of pharmacy-based ad-
capable of contributing to all components of HIV care by herence interventions on antiretroviral adherence in
being highly accessible to both patients and providers in persons with HIV. AIDS Patient Care STDs 2011;
a variety of healthcare settings. Their expert drug therapy 25(4):221–8.
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1010–1. • International Association of Providers of AIDS Care
(www.iapac.org)
Appendix • International AIDS Society (www.iasociety.org)
Website Resources Information Exchange
General HIV Care and Treatment Information • The Canadian HIV/AIDS Pharmacists Network (hiv-
clinic.ca/chap/)
• U.S. Department of Health and Human Services • National AIDS Treatment Advocacy Project (natap.
AIDSinfo Web site (www.aidsinfo.nih.gov) org)
• Clinical Care Options HIV–in Practice (www.inprac- • American College of Clinical Pharmacy, HIV Practice
tice.com/Textbooks/HIV.aspx) and Research Network (http://www.accp.com/about/
prns.aspx)
Clinical Practice Guidelines and Recommendations
Clinical Trials
• U.S. Department of Health and Human Services
AIDSinfo Web site (www.aidsinfo.nih.gov) • U.S. Department of Health and Human Services
• International Antiviral Society—USA (www.iasusa. AIDSinfo Web site (www.aidsinfo.nih.gov)
org/guidelines)
• World Health Organization (www.who.int/hiv/pub/ Hotlines and Clinical Consultation
guidelines/en/)
• European AIDS Clinical Society (eacsociety.org/ • Clinicians Consultation Center (nccc.usf.edu)
Guidelines.aspx) • Pre-Exposure Prophylaxis (855) 448-7737
• Post-Exposure Prophylaxis (888) 448-4911
Antiretroviral Information (Drug Interactions, Renal/ • HIV/AIDS Management (800) 933-3413
Hepatic Dose Adjustments and Crushing/Liquid • Perinatal HIV/AIDS (888) 448-8765
Formulations)
HIV Certificate and Credentialing Programs
• U.S. Department of Health and Human Services
AIDSinfo Web site (www.aidsinfo.nih.gov) • American Academy of HIV Medicine, HIV Pharmacist
• University of Liverpool Drug Interaction Database Credentialing (www.aahivm.org/about)
and Mobile Application (www.hiv-druginteractions. • University of Buffalo School of Pharmacy and
org/) Pharmaceutical Sciences (tdm.pharm.buffalo.edu/
• Toronto General Hospital Immunodeficiency Clinic hiv_cert_main/)
website (www.hivclinic.ca/main/drugs_interact.html
and www.hivclinic.ca/main/drugs_extra.html)
Continuing Education for Pharmacists RN-BC, CPHIMS; Shanna Chan, B.Sc.Pharm., ACPR, AAHIVP
(CHAP); Patrick Clay, Pharm.D. FCCP, CCTI (APhA); Natalie
• Clinical Care Options–HIV (www.clinicaloptions. Dayneka, B.Sc.Pharm., ACPR, Pharm.D., FCSHP (CHAP); Heather
com/HIV.aspx) Easterling, Pharm.D., M.B.A. (SCSHP); Devon Flynn, Pharm.D.,
• International Antiviral Society–USA (iasusa.org) BCPS, AAHIVP; Michelle Foisy, B.Sc.Pharm., Pharm.D., FCSHP,
• American Academy of HIV Medicine (aahivm.org) AAHIVP (CHAP); Patricia Pecora Fulco, Pharm.D., BCPS, FASHP,
• AIDS Education and Training Centers (aidsetc.org) AAHIVP; Barbara Giacomelli, Pharm.D., M.B.A., FASHP; Pierre
Giguère, B.Sc.Pharm., M.Sc. (CHAP); Christine Hughes, B.Sc.
Pharm., Pharm.D, AAHIVP (CHAP); Tara K. Jellison, Pharm.D.,
M.B.A., FASHP; Deborah V. Kelly, B.Sc.Pharm., ACPR, Pharm.D,
Approved by the ASHP Board of Directors on September 17, 2015. FCSHP, AAHIVP (CHAP); William Kuykendall, Pharm.D.; Kris-
Developed through the ASHP Section of Clinical Specialists and tina Lantis, Pharmacy Student, Class of 2016; J. Craig Phillips,
Scientists. Ph.D., LLM, RN, ARNP, PMHCNS-BC, ACRN; Carlo Quaia, B.Sc.
Pharm., ACPR (CHAP); James R. Rinehart, R.Ph., M.S., FASHP;
These guidelines supersede the ASHP Statement on the Pharma- Linda Robinson, B.Sc.Pharm., AAHIVE (CHAP); Nancy Sheehan,
cist’s Role in HIV Care dated June 1, 2003. B.Sc.Pharm., M.Sc. (CHAP); Shannon Stone, B.Sc.Pharm., ACPR
(CHAP); Alice Tseng, B.Sc.Pharm., Pharm.D., FCSHP, AAHIVP
Jason J. Schafer, Pharm.D., M.P.H, BCPS, AAHIVP; Taylor K. (CHAP); Andrea Weddle, M.S.W. (HIVMA); Jody Jacobson We-
Gill, Pharm.D., BCPS, AAHIVP; Elizabeth M. Sherman, Pharm.D., dret, FASHP, FCSHP; and Deborah Yoong, B.Sc.Pharm., ACPR,
AAHIVP; and Ian R. McNicholl, Pharm.D., FCCP, BCPS (AQ-ID), Pharm.D. (CHAP).
AAHIVP are gratefully acknowledged for authoring these guide-
lines. The authors have declared no potential conflicts of interest. Copyright © 2015, American Society of Health-System Pharma-
cists, Inc. All rights reserved.
ASHP gratefully acknowledges the following organizations and in-
dividuals for reviewing these guidelines (review does not imply en- Note: These guidelines had not been published in the American
dorsement): American Pharmacists Association (APhA); Canadian Journal of Health-System Pharmacy (AJHP) when ASHP Best
HIV/AIDS Pharmacists Network (CHAP); HIV Medicine Associa- Practices 2015–2016 went to press. Some minor editorial differ-
tion (HIVMA); Society of Infectious Disease Pharmacists; South ences may exist between this document and the official one that
Carolina Society of Health-System Pharmacists (SCSHP); Melissa will eventually appear in AJHP and subsequent editions of this
Badowski, Pharm.D., BCPS, AAHIVP; Carol J. Bickford, Ph.D., publication.
ASHP Guidelines on the Pharmacist’s Role

in Immunization
Purpose of immunization information, hosts of immunization sites,

and immunizers.16 Vaccine administration may occur pur-
Pharmacists can play an important role in disease prevention suant to individual prescription orders or through standing
by advocating and administering immunizations. Such orders or protocols. The Centers for Disease Control and
activities are consistent with the preventive aspects of phar- Prevention (CDC) Advisory Committee on Immunization
maceutical care and have been part of pharmacy practice for Practices recommends the use of standing orders to improve
over a century.1,2 These guidelines address the pharmacist’s adult immunization rates.17 Its recommendations encourage
role in promoting and conducting proper immunization of pharmacists, among other providers, to establish standing-
patients in all organized health care settings. The pharma- order programs in long-term-care facilities, home health
cist’s role in promoting disease prevention through partici- care agencies, hospitals, clinics, workplaces, and managed
pation in community efforts is also discussed. care organizations. The Centers for Medicare and Medicaid
Services (CMS) no longer requires a physician order for
influenza or pneumoccocal immunizations administered in
Background participating hospitals, long-term-care facilities, or home
health care agencies.18 Development of state-specific pro-
Each year, an average of 90,000 Americans die of vaccine- tocols or standing-order programs can be facilitated through
preventable infections such as influenza, pneumococcal dis- partnerships with state pharmacy associations, boards of
ease, and hepatitis B.3,5 Most of these people visited health care pharmacy, and health departments.
providers in the year preceding their deaths but were not vac
cinated.6–11 Influenza and pneumonia, considered together, are Training. Although legal authority to administer vaccines
the fifth leading cause of death for Americans 65 years of age or may be granted through pharmacy practice acts, pharmacists
older.12 Although vaccination rates for U.S. children at the time must achieve competency in all aspects of vaccine adminis-
they enter school exceed 95%, nearly 25% do not complete their tration. A comprehensive training program should address
primary series by the age of two years.13 Most American adults the following:
are inadequately vaccinated, particularly against pneumococcal
disease, influenza, hepatitis B, tetanus, and diphtheria.6 Tens of 1. The epidemiology of and patient populations at risk
millions of Americans remain susceptible to potentially deadly for vaccine-preventable diseases,
infections despite the availability of effective vaccines. 2. Public health goals for immunization (e.g., local,
This long-standing failure to adequately immunize the regional, state, and federal goals),
U.S population helped prompt the inclusion of immuniza- 3. Vaccine safety (e.g., risk–benefit analysis),
tion as a leading health indicator for Healthy People 2010.14 4. Screening for contraindications and precautions of
The renewed focus on immunization and the potential for vaccination in each patient,
increased vaccination needs in response to threats of 5. Vaccine stability and transportation and storage
bioterrorism should stimulate pharmacists, as well as other requirements,
health care providers, to reassess what they and their in- 6. Immunologic drug interactions,
stitutions can do to improve immunization rates in their 7. Vaccine dosing (including interpreting recommended
communities. Pharmacists can contribute to this effort by immunization schedules and patient immunization
administering immunizations where scope of practice allows records and determining proper dosing intervals and
and by promoting immunization in other ways. the feasibility of simultaneous administration of
multiple vaccines),
Immunization Administration 8. Proper dose preparation and injection technique,
9. Signs and symptoms of adverse reactions to vaccines,
As health care providers, pharmacists can administer vaccines adverse reaction reporting, and emergency procedures,
or host other health care professionals who can administer vac- such as basic and advanced cardiac life support (BCLS
cines. Pharmacists must understand the legal and professional and ACLS),
mechanisms by which authorization to administer vaccines is 10. Documentation,
granted, as well as the additional responsibilities and consider- 11. Reporting to the primary care provider or local health
ations that accompany this expanded role. The feasibility of vac- department, and
cine administration by pharmacists within a particular practice 12. Billing.
site or health care system can be determined by analyzing the
issues of legal authority, training, and program structure. Live and videotaped programming is available through
some state and national pharmacy associations and offered in
Legal Authority. The pharmacist’s authority to administer many college of pharmacy curricula. Information regarding im-
vaccines is determined by each state’s laws and regulations munizations can change rapidly. To maintain competency, phar-
governing pharmacy practice. At least 36 states permit vaccine macists must have access to current immunization references
administration by pharmacists as part of the scope of pharmacy (e.g., CDC’s National Immunization Program publications, in-
practice.15 The American College of Physicians–American cluding the “Pink Book”19) and continuing-education programs
Society of Internal Medicine supports pharmacists as sources to stay abreast of evolving guidelines and recommendations.
Program Structure. A vaccine administration program requires Pharmacists should seek out leadership roles in some or all
a solid infrastructure of appropriately trained staff, physical of the following forms of immunization screening.
space, and written policies and procedures to ensure appropriate Occurrence screening. With this type of screening,
vaccine storage and handling, patient screening and education, vaccine needs are identified at the time of particular events,
and documentation. The structure of a vaccine administration such as hospital or nursing home admission or discharge,
program must also provide for storage and disposal of injec- ambulatory care or emergency room visits, mid-decade
tion supplies, disposal of and prevention of exposure to biologi- birthdays (e.g., years 25, 35, and 45),42,43 and any contact
cal hazards as dictated by the Occupational Safety and Health with a health care delivery system for patients under 8 years
Administration (OSHA), and emergency procedures (e.g., or over 50 years of age.
BCLS and ACLS). Pharmacists should be fully immunized to Diagnosis screening. This screening reviews the vaccine
protect their health and the health of their patients.20 needs of patients with conditions that increase their risk of
preventable infections. Diagnoses such as diabetes, asthma,
Reimbursement. Immunization has repeatedly been shown heart disease, acute myocardial infarction, congestive heart
to be cost-effective21–24; it may be the most cost-effective failure, chronic obstructive pulmonary disease, hemophilia,
practice in medicine. However, third-party reimbursement thalassemia, most types of cancer, sickle cell anemia,
policies often do not provide coverage for recommended vaccines chronic alcoholism, cirrhosis, human immunodeficiency
despite this evidence. A major exception is Medicare Part virus infection, and certain other disorders should prompt
B, which not only covers immunization services for its par- specific attention to the patient’s vaccine needs.12,33,42 The
ticipants but also recognizes and compensates pharmacists immunization rate for patients diagnosed with community-
as mass immunization providers. Enrollment as a Medicare acquired pneumonia is considered a marker for quality by
provider is required to bill for covered services. Provider some accrediting bodies. Incorporating assessment of vacci-
status can be obtained through local Medicare offices, which nation status into an institution’s critical pathways has been
also process CMS claims for reimbursement (CMS-1500 shown to improve vaccination rates.44
claims). The CMS Web site (www.cms.hhs.gov) is a useful Procedure screening. Immunization needs are assessed
source for billing information. Pharmacists should continue on the basis of medical or surgical procedures using this type
to closely monitor other immunization reimbursement policies of screening. These procedures include splenectomy, heart
and advocate third-party coverage for immunizations as a or lung surgery, organ transplantation, antineoplastic ther-
cost-effective preventive measure. For patients without apy, radiation therapy, immunosuppression of other types,
insurance coverage, requesting out-of-pocket payments dialysis, and prescription of certain medications used to treat
from the patient remains a viable option for pharmacists to conditions that increase patients’ risk of preventable infec
obtain compensation for their immunization services. tions.45,46 When designing and implementing automated
prescription databases, pharmacy managers should consider
specifications that allow retrieval of lists of patients receiv-
Immunization Promotion ing drugs that suggest the need for immunization.33,37
Periodic mass screening. This type of screening is a
Pharmacists who do not administer vaccines can promote immu- comprehensive assessment of immunization adequacy in
nization through six types of activities: (1) history and screening, selected populations at a given time. Such screening may be
(2) patient counseling, (3) documentation, (4) formulary manage- conducted, for example, during autumn influenza programs
ment, (5) administrative measures, and (6) public education.25,26 or outbreaks of certain vaccine-preventable illnesses (e.g.,
These promotional activities can also be integrated into or measles and meningococcal disease).29,32,33 Schools and other
accompany a pharmacy-based immunization program. institutions can perform mass screening when registering new
students or residents. Mass screening may also be appropriate
History and Screening. Pharmacists can promote proper in areas where no comprehensive immunization program has
immunization by identifying patients in need of immuniza- been conducted recently. This type of screening helps improve
tion. Tasks that support this objective include gathering vaccine coverage rates at a given time, but long-term benefits
immunization histories, encouraging use of vaccine profiles, are much greater when such intermittent programs are com-
issuing vaccination records to patients,27–34 preventing bined with ongoing comprehensive screening efforts. Several
immunologic drug interactions,35,36 and screening patients states, including South Dakota, New Jersey, and Oklahoma,
for immunization needs.28–33,37–39 have enacted laws requiring that influenza and pneumococcal
Immunization screening should be a component of all vaccines be offered annually to residents of nursing homes.
clinical routines, regardless of the practice setting. All health Occupational screening. This screening method focuses
care institutions should implement consistent, systematic on the immunization needs of health care personnel whose
monitoring systems and quality indicators to ensure that responsibilities place them at risk of exposure to certain
all patients are assessed for immunization adequacy before vaccine-preventable diseases or bring them into contact with
they leave the facility. The health care provider designated to high-risk patients (i.e., patients with those conditions listed
identify patient immunization needs should have the authority, in the Diagnosis screening section above). Health care pro-
knowledge, and responsibility to provide or arrange for the viders who have contact with these patients should receive
immunization service.40 Clinics that provide treatment for a an annual influenza vaccination. Health care employers
large number of patients at high risk for contracting vaccine- frequently provide immunization screening and vaccination
preventable diseases (e.g., diabetic, asthmatic, heart disease, of employees as part of employee health programs. OSHA
and geriatric clinics) have a particular obligation to employ requires that health care employers provide hepatitis
immunization screening and ensure appropriate vaccine use. B vaccination at no cost, on a voluntary basis, to all employees
Screening for immunization needs may be organized at risk for occupational exposure to blood borne pathogens.47
in several ways; prototype screening forms are available.39,41 Depending on their risk of exposure, it may be advisable for
members of the pharmacy staff to receive hepatitis B efficient method for maintaining and retrieving immuniza-
vaccination. tion records.39 Efforts to develop electronic vaccination reg-
Screening for contraindications and precautions. After istries, especially for children, are under way by states col-
candidates for immunization have been identified, they should laborating with CDC.61
be screened for contraindications and precautions. A CDC- NCVIA also mandates that selected adverse effects
reviewed contraindication screening questionnaire is available.48 noted after any inoculation be reported to the Vaccine
Adverse Event Reporting System (www.vaers.org).57,59,62
Patient Counseling. Patients in need of immunization should Because pharmacists have experience with adverse-drug-
be advised of their infection risk and encouraged to accept reaction reporting, they can take the lead in developing and
the immunizations they need. Patient concerns about vaccine implementing a program to meet this requirement, even if
safety and efficacy should be discussed and addressed.49,50 they are not responsible for administering the vaccine.
Health care providers can influence patients’ attitudes Patients should maintain personal immunization records
regarding immunization.51,52 Physicians should be informed that document all immunization experiences and function
of their patients’ need for vaccination if standing orders or as a backup if the clinicians’ immunization records are lost.
collaborative practice agreements are not in place. Patients Several personal immunization record forms are available.
who need immunizations should be vaccinated during the Public Health Service Form 731 (International Certificate of
current health care contact unless valid contraindications ex- Vaccination), colloquially called the “yellow shot record,” is
ist. Delaying vaccination until a future appointment increases used to document vaccines indicated for international travel
the risk that the patient will not be vaccinated. but can also serve as a patient’s personal record of vaccinations.
Advising patients of their need for immunization can The Immunization Action Coalition distributes a standard
take several forms. In the ambulatory care setting, individu- adult immunization record card developed in collabora-
alized or form letters can be mailed to patients, patients can tion with CDC.63 In addition, each state and the District of
be called by telephone, or an insert can be included with Columbia prints its own uniform immunization record form
prescriptions informing patients of their infection risk and for pediatric immunizations, which may also be a suitable
the availability and efficacy of vaccines.30,33,53–55 Adhesive personal patient record. It has been recommended that adults
reminder labels can also be affixed to prescription containers carry personal immunization records in their wallets.46
for drugs used to treat conditions that may indicate the need
for vaccination against influenza and pneumococcal disease Formulary Management. Formulary systems in organized
(e.g., digoxin, warfarin, theophylline, and insulin33); these health care settings should include vaccines, toxoids, and
labels would be analogous to labels currently in widespread immune globulins available for use in preventing diseases
use (e.g., “Shake well” and “Take with food or milk”). Such in patients and staff. Decisions by the pharmacy and thera-
labels might read, “You may need flu or pneumonia vaccine: peutics committee (or its equivalent) on immunologic drug
Ask your doctor or pharmacist.” Chart notes, consultations, choices require consideration of relevant immunologic phar-
messages to patients, one-on-one conversations, and similar maceutics, immunopharmacology, and disease epidemiology.
means can be used to communicate with inpatients and Because of their expertise and training, pharmacists are well
institutional patients.28,31,56 equipped to provide information and recommendations on
Federal law requires that health care providers who which these decisions may be based.
administer diphtheria, tetanus, pertussis, measles, mumps, It is the pharmacist’s responsibility to develop and
rubella, varicella, polio, Haemophilus influenzae type B, maintain product specifications to aid in the purchase of
hepatitis B, and pneumococcal conjugate vaccines give drugs under the formulary system.64,65 The pharmacist should
the most recent version of the CDC-developed Vaccine establish and maintain standards to ensure the quality, proper
Information Statement (VIS) to the adult or the parent or storage, and proper use of all pharmaceuticals dispensed.
legal guardian of the child to be vaccinated.57 VISs are Pharmacists must choose between single dose or multidose
available in many languages from state or local health de- containers of vaccines on the basis of efficiency, safety,
partments or the CDC.58 VISs are also available for other economic, and regulatory considerations. Pharmacists in
commonly used vaccines, such as influenza, pneumococ- institutions should develop guidelines on the routine stocking
cal polysaccharide, hepatitis A, meningococcal, and anthrax of immunologic drugs in certain high-use patient care areas.
vaccines. Pharmacists should also ensure that informed con- Proper transportation and storage are an important
sent is obtained in a manner that complies with state laws.20 consideration for immunologic drugs, including vaccines,
because many require storage at refrigerated or frozen tem-
Documentation. The National Childhood Vaccine Injury peratures. Pharmacists have an important responsibility to
Act of 1986 (NCVIA) requires all health care providers who maintain the “cold chain” in the handling of these drugs.
administer vaccines to maintain permanent vaccination re- Detailed references on this topic have been published.66–73
cords and to report occurrences of certain adverse events Storage considerations include the conditions in all areas in
specified in the act.57,59 The recipient’s permanent medical which immunologic drugs are kept, as well as a method for
record (or the equivalent) must state the date the vaccine ensuring that immunologic drugs received by the pharmacy
was administered, the vaccine’s manufacturer and lot number, have been transported under suitable conditions.
and the name, address, and title of the person administer- It is important that methods be established for detecting
ing the vaccine. Pharmacists in organized health care settings and properly disposing of outdated and partially administered
may encourage compliance with this requirement by pro immunologic agents. Live viral (e.g., varicella, yellow fever,
viding reminder notices each time doses of vaccines are and smallpox) and live bacterial (e.g., bacille Calmette-
dispensed.60 Automated databases that allow for long-term Guérin) vaccines should be disposed of in the same manner
storage of patient immunization information may provide an as other infectious biohazardous waste.
Administrative Measures. Pharmacists on key committees 5. Thompson WW, Shay DK, Weintraub E, et al. Mortality
(e.g., infection control and risk management) in organized associated with influenza and respiratory syncytial vi-
health care settings can promote adequate immunization rus in the United States. JAMA. 2003; 289:179–86.
delivery among staff and patients by encouraging the devel- 6. Williams WW, Hickson MA, Kane MA, et al.
opment of sound organizational policies on immunization. Immunization policies and vaccine coverage among
Health care organizations should develop policies and adults. The risk for missed opportunities. Ann Intern
protocols that address the following: Med. 1988; 108:616–25.
7. Fedson DS, Harward MP, Reid RA, et al. Hospital-
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12. Bratzler DW, Houck PM, Jiang H, et al. Failure to vac-
diabetes, asthma, heart disease, and pregnant or immu-
cinate Medicare inpatients: a missed opportunity. Arch
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13. Barker L, Luman E, Zhao Z, et al. National, state,
9. Emergency measures in the event of vaccine-related
and urban area vaccination coverage levels among
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children aged 19–35 months—United States, 2001.
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MMWR. Morb Mortal Wkly Rep. 2002; 51(30):664–6.
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14. Office of Disease Prevention and Health Promotion.
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coalitions, and other groups (e.g., state or local parent— vaccination rates: recommendations of the Advisory
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65. ASHP statement on the pharmacist’s responsibil-
of immunization assessment into critical pathways in
ity for distribution and control of drug products. In:
an acute care setting. Hosp Pharm. 2002; 37:1050–4.
Deffenbaugh JH, ed. Best practices for health-sys- 79. Grabenstein JD. Stop buying tetanus toxoid (with one
tem pharmacy. Positions and guidance documents exception). Hosp Pharm. 1990; 25:361–2.
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Society of Health-System Pharmacists; 2002:91. sis vaccines among infants and young children.
66. Grabenstein JD. ImmunoFacts: vaccines and immunologic Recommendations of the Advisory Committee on
drugs. 28th ed. St Louis: Facts and Comparisons; 2002. Immunization Practices (ACIP). MMWR Recomm
67. Centers for Disease Control and Prevention. Vaccine Rep. 1997; 46(RR-7):1–25.
management: recommendations for handling and storage 81. American Academy of Pediatrics Committee on
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vac_mgt_book.htm (accessed 2003 Mar 27). tussis vaccine and brain damage: reassessment.
68. Casto DT, Brunell PA. Safe handling of vaccines. Pediatrics. 1991; 88:397–400.
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69. Ross MB. Additional stability guidelines for routinely tions of the Advisory Committee on Immunization
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1987; 44:2698, 2701. Letter. in high-risk populations: recommendations of the
71. Miller LG, Loomis JH Jr. Advice of manufacturers Advisory Council for the Elimination of Tuberculosis.
about effects of temperature on biologicals. Am J Hosp MMWR Recomm Rep. 1995; 44(RR-11):19–34.
Pharm. 1985; 42:843–8. 84. Anergy skin testing and tuberculosis [corrected] pre-
72. Vogenberg FR, Souney PF. Stability guidelines ventive therapy for HIV-infected persons: revised rec-
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73. Wolfert RR, Cox RM. Room temperature stability of 85. Health information for international travel, 2001–02.
drug products labeled for refrigerated storage. Am J Washington, DC: Government Printing Office; 2001.
Hosp Pharm. 1975; 32:585–7. 86. American College of Obstetricians and Gynecologists
74. Update: recommendations to prevent hepatitis B virus committee opinion. Immunization during pregnancy.
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75. Update: recommendations to prevent hepatitis B virus
transmission—United States. MMWR Morb Mortal
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76. Prevention of hepatitis A through active or passive Practice and by the Board of Directors and were found to still be ap-
immunization: recommendations of the Advisory propriate.
Committee on Immunization Practices (ACIP).
MMWR Recomm Rep. 1999; 48(RR-12):1–37. Developed through the ASHP Council on Professional Affairs and
77. Human rabies prevention—United States, 1999. approved by the ASHP Board of Directors on May 31, 2003.
Recommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR Recomm Copyright © 2003, American Society of Hospital Pharmacists, Inc.
Rep. 1999; 48(RR-1):1–21. All rights reserved.
78. Diphtheria, tetanus, and pertussis: recommenda-
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Advisory Committee (ACIP). MMWR Recomm Rep. pharmacist’s role in immunization. Am J Health-Syst Pharm. 2003;
1991; 40(RR-10):1–28. 60:1371–7.
ASHP Guidelines on the

Pharmacist’s Role in Providing Drug Information
Background and Rationale pharmacist should have the skills to perform the following
DI activities2,3:
The provision of drug information (DI) is among the fun-
damental professional responsibilities of all pharmacists. 1. Providing DI to patients, caregivers, and health care
Recent practice trends, including increased provision of professionals.
medication therapy management services and efforts to 2. Creating and maintaining currency of a variety of print
obtain provider status, have placed pharmacists in increas- and online educational resources for patients (e.g., tip
ingly complex patient-care roles and necessitated a higher sheets, pamphlets) and health care professionals (e.g.,
level of competence by all pharmacists in meeting DI needs. in-service documents, newsletters) on topics such as
Drug information may be patient specific, academic (for optimal medication use, general health, or select clini-
educational purposes), or population based (to aid in the cal questions.
decision-making process for evaluating medication use for 3. Educating health care professionals on safe and effec-
groups of patients). The goal of providing carefully evalu- tive medication-use policies and processes, including
ated, evidence-based recommendations to support specific development of resources to communicate this infor-
medication-use practices is to enhance the quality of patient mation.
care, improve patient outcomes, and ensure the prudent use 4. Leading or participating in continuing education ser-
of resources. The primary focus of these guidelines is to devices for health care professionals.
scribe contemporary DI activities, including the application 5. Precepting and educating pharmacy students and resi-
of a systematic approach, appropriate documentation meth- dents.
ods, and use of high-quality DI resources. This information 6. Participating in quality improvement research projects
is intended to assist pharmacists in providing optimal DI ser- and drug cost analyses.
vices in a variety of practice settings, including hospitals and 7. Contributing to the biomedical literature and providing
health systems, outpatient care centers, managed care envi- peer review for other contributors.
ronments, medical communication departments, and univer-
sity or academic-based drug information centers. Some of Some activities may be more appropriate for pharmacists
the activities described in these guidelines are the subjects with additional expertise and training in DI, such as those
of other American Society of Health-System Pharmacists who have completed a postgraduate year two (PGY2) drug
(ASHP) policy and guidance documents, which should be information residency. Drug information specialists often
referred to for additional information. Pharmacists providing perform DI activities that overlap with other pharmacists
DI should use professional judgment in assessing ASHP’s and health care professionals. However, as a result of their
policy and guidance documents and in adapting them to advanced training and experience, DI specialists may be
meet their health care organizations’ and patients’ needs and able to more efficiently retrieve, evaluate, and disseminate
circumstances. information in order to develop evidence-based recommen-
dations and assist in patient care decisions.2 Many DI spe-
cialists are also involved in medication-safety activities and
Drug Information Activities
collaborate with experts in informatics. These activities are
highlighted in other ASHP statements.4,5 Specific activities
To be an effective provider of DI, the pharmacist must ex-
of the DI specialist may include some or all of the follow-
ercise excellent oral and written communication skills and
ing2,6-11:
be able to
1. Providing information when there is not sufficient time
1. Anticipate and evaluate the DI needs of patients and
for other health care professionals to appropriately re-
health care professionals;
search the DI question, when there is a knowledge gap,
2. Obtain appropriate and complete background infor-
or when the question requires more thorough research.
mation as described under the section Systematic
2. Establishing and maintaining a formulary based on sci-
Approach for Responding to Drug Information
entific evidence of efficacy and safety, pharmacoeco-
Requests;
nomics, and institution-specific factors.
3. Use a systematic approach to address DI needs by ef-
fectively searching, retrieving, and critically evaluat- 3. Coordinating programs to support population-based
ing the literature (i.e., assessment of study design, sta- medication practices that maximize patient outcomes
tistics, bias, limitations, applicability); and (e.g., development of pharmacotherapeutic guidelines,
4. Appropriately synthesize, communicate, document, medication-use evaluation criteria, and therapeutic in-
and apply pertinent information to the patient care terchange protocols).
situation.1,2 4. Developing and participating in efforts to prevent
medication errors and adverse drug events, includ-
A variety of DI activities may be performed by pharmacists, ing surveillance, ensuring institutional compli-
depending on the particular practice setting and need. Every ance to Risk Evaluation and Mitigation Strategies
(REMS), and leading reporting and analysis programs ing a response.1,13 The importance of gathering pertinent pa-
(e.g., MedWatch). tient data and understanding the context of a question prior
5. Monitoring and assessing the clinical significance of to answering a DI request is described in the literature.14-16
medication safety alerts communicated by the FDA, drug Of note, a full systematic approach may not be practical for
manufacturers, and other sources. all requests, especially for urgent clinical needs in the di-
6. Performing health outcome and comparative effec- rect patient care setting. In addition, consideration should
tiveness analyses. be given to the ethical and legal aspects of responding to DI
7. Coordinating investigational drug services, including requests, including patient privacy concerns.1
participating on institutional review boards (IRBs), A systematic approach may be outlined as follows.1,13
evaluating protocols, and providing DI to patients,
caregivers, and health care professionals. 1. Identify the requestor. In order to obtain complete in-
8. Managing drug shortages, including identify- formation and develop a response with the appropriate
ing alternative treatments, developing proto- perspective, consider the health literacy and profes-
cols for restrictive use, and addressing formulary sional background of the requestor.
concerns. 2. Define the true question and information need.
9. Developing clinical decision support tools such as or- Identify the true question and information needed by
der sets, dosing protocols, and order-entry alerts. asking probing questions of the requestor. For exam-
10. Maintaining DI and medication-use policy-related in- ple, “Why is the question being asked?” and “Does
tranet resources. the question pertain to a specific patient?” may help
11. Precepting or providing advanced DI education and reveal important details of the true question.1 This
training to interprofessional and pharmacy students kind of information helps in optimizing the search
and residents. process and assessing the appropriate time frame of
12. Coordinating selection and purchase of pharmacy and response need.
institution-wide DI resources. 3. Obtain complete background information. Obtain
13. Participating in various fee-for-service projects (e.g., more complete background information, including
formulary support, database development, training examining the medical record for patient data, if ap-
programs) for clients. plicable, to individualize the response to meet the re-
14. Planning and delivering academic detailing programs. questor’s need.
4. Categorize the question. Classify requests as patient-
Although the above activities may be best suited for phar- specific or academic and by type of question (e.g.,
macists with advanced DI training, many institutions lack product availability, adverse drug event, compatibility,
a formal DI specialist. Therefore, other pharmacists may compounding/formulation, dosage/administration, drug
be involved in more in-depth DI activities, depending on interaction [drug-drug, drug-disease, drug-laboratory],
their level of expertise. For example, preparing drug mono- drug product identification, pharmacokinetics, thera-
graphs for pharmacy and therapeutics committees was once peutic use/efficacy [FDA approved vs. unlabeled indi-
considered almost exclusively the responsibility of the DI cations], safety in pregnancy/nursing toxicity/poison-
specialist. As pharmacy practice has evolved, the expertise ing) to aid in tailoring the search strategy and selecting
and knowledge of all pharmacy practitioners have been inte- resources.
grated into this process. 5. Perform a systematic search. Perform a systematic
Today, depending on the institution, pharmacists search of appropriate tertiary, secondary, and primary
without specialized DI training may prepare monographs, resources, including electronic resources, as necessary.
assist in the design of medication-use evaluation criteria, 6. Analyze the information. Evaluate, interpret, and com-
participate in medication monitoring activities, or educate bine information from the resources used. Other infor-
health care professionals on appropriate medication use. If mation needs should be anticipated as a result of the
available, a DI specialist may serve in an oversight role by information gathered.
editing and providing feedback on these projects or provid- 7. Disseminate the information. Provide an oral or writ-
ing general DI support to pharmacists involved in direct ten response, or both, as needed by the requestor that
patient care. Moreover, a DI specialist may be involved in specifically applies the information to the particular
implementation and follow-up of medication-use policies situation. The information, its urgency, and its purpose
and formulary changes as part of a larger medication policy may influence the method of response. Supporting
management program, which may include interpreting the documentation (e.g., primary literature) should be in-
impact of legislation, regulation, and public policy on medi- cluded when possible.
cation utilization. 8. Document. Document the request, information re-
sources used, the information found in each source,
Systematic Approach for Responding time spent on the response, and the response itself as
appropriate for the request and the practice setting.
to Drug Information Requests 9. Follow-up. Perform a follow-up assessment to de-
termine the utility of the information provided and
A systematic approach for responding to DI requests was
whether the information resulted in changes in medi-
first introduced by Watanabe, et al. in 1975.12 This approach
cation-use practices or patient outcomes.
has been modified and expanded over the years to ensure
that all relevant information is considered prior to formulat-
Documentation and Quality Assessment more time can be devoted to analyzing, applying, and com-
municating the information.
Numerous methods of documenting pharmacist interven- The following factors should be considered when pur-
tions, including the provision of DI, have been described in chasing DI resources, including electronic subscriptions, for
the literature. Drug information centers are moving toward the pharmacy department or practice setting:
increased use of electronic documentation systems, which
have helped to increase the depth and quantity of documen- 1. Features of the resource (e.g., frequency of updates,
tation, as well as provide increased efficiency and cost sav- qualifications and affiliations of authors, year of pub-
ings.17-21 In addition, an electronic system can promote a lication, type of information, organization of material,
standardized and systematic approach and provides a readily method of delivery, cost).
retrievable archive that can be used to rapidly search previ- 2. Practice setting (e.g., type of facility and needs of health
ously answered questions.22,23 Documentation of DI services care professionals within that environment, state-
should incorporate elements identified through the sys- specific regulatory requirements).
tematic approach. The ASHP Guidelines on Documenting 3. Accessibility of the resource (e.g., location of print re-
Pharmaceutical Care in Patient Medical Records states that sources, number of users allowed by subscription).
“the professional actions of pharmacists that are intended
to ensure safe and effective use of drugs and that may af- Keeping Current
fect patient outcomes should be documented in the patient
medical record.”24 Therefore, if the DI request is patient- Pharmacists are challenged with keeping up to date with
specific, it is appropriate, but not always necessary, to docu- an increasing number of new drugs and literature.3 Drug
ment the request and response in the patient’s medical re- information and literature evaluation skills are crucial for
cord. Documentation is critical to appropriate patient care, building clinical knowledge and providing evidence-based
highlights the value of pharmacist services, demonstrates recommendations. It is the responsibility of the pharmacist
accountability, provides a basis for quality assessment and to commit to lifelong learning and make an effort to keep
performance improvement, and details an appropriate sys- abreast of advances both in the methods of delivering DI
tematic approach in case a medico-legal dispute arises from and the information itself. In addition to keeping up to date
a DI request. Consequently, even academic or population- with clinical knowledge, it is important for pharmacists to
based DI activities should be appropriately documented. keep current on changes in pharmacy practice as the health
Despite the importance of assessing the quality of drug- care system evolves. Recommendations for staying current
related information provided by pharmacists, there is cur- include the following:
rently no standardized method described in the literature.
However, some DI centers have reported use of double-check 1. Subscribe to table of contents of or full access to rel-
systems prior to providing a response, random retrospective evant journals, as appropriate.
audits by a DI specialist or another individual, obtaining 2. Subscribe to appropriate email listservers (e.g., Food
feedback from the requestor, and conducting an internal re- and Drug Administration Drug Information Updates,
view by a committee as methods of quality assessment.25 National Guideline Clearinghouse, Centers for Disease
Control and Prevention, Medline Plus).
Resources 3. Receive email alerts from relevant health-related web-
sites (e.g., MedWatch, Medline Plus).
It is important for pharmacists to use appropriate and cred- 4. Bookmark important websites and check regularly for
ible resources. The amount of medical knowledge has updates (e.g., Institute for Safe Medication Practices,
grown substantially and access to information has changed ASHP Drug Shortages Resource Center).
dramatically over the last few decades. Traditional print re- 5. Choose pertinent continuing education activities and
sources are rapidly being replaced by electronic databases methods that challenge learning.
(both online and included in health information management 6. Maintain active membership in local, state, and na-
systems), online resources, and mobile applications.26 The tional pharmacy associations/societies.
internet and mobile technology have allowed for convenient 7. Pursue board certification from the Board of Pharmacy
and quick access to medical information. However, pharma- Specialties.
cists should critically evaluate all resources prior to use to
ensure that they are accurate, current, and unbiased. Conclusion
General principles to consider when critically evaluat-
ing medical information available on the internet have been All pharmacists are involved in the provision of DI, which
published.27 Pharmacists should work closely with others includes a broad array of activities. A systematic approach
within the organization to ensure that up-to-date resources, should be considered for all DI requests, and pharmacists
including representative primary (e.g., peer-reviewed origi- should document their services to demonstrate account-
nal studies), secondary (e.g., indexing or abstracting ser- ability and justify the value of pharmacist care. Increased
vices such as MEDLINE and International Pharmaceutical availability of medical information, both due to increased
Abstracts), and tertiary resources (e.g., electronic databases, knowledge and technological advances, has not changed the
textbooks, review articles, clinical practice guidelines) are overall process of DI practice. It is important for pharma-
available to assist in answering a variety of DI requests. cists to select appropriate resources and keep current on new
Pharmacists should be familiar with the features of each re- literature and new tools to address a variety of DI requests.
source; familiarity makes searching more efficient so that
References 18. Simonian AI. Documenting pharmacist interven-

tions on an intranet. Am J Health-Syst Pharm. 2003;
1. Malone PM, Kier KL, Stanovich JE. Drug informa- 60:151–5.
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McGraw-Hill; 2012. Documenting clinical pharmacist intervention before
2. Bernknopf AC, Karpinski JP, McKeever AL, et and after the introduction of a web-based tool. Int J
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3. Wang F, Troutman WG, Seo T, et al. Drug informa- tem for documenting drug information consultation
tion education in doctor of pharmacy programs. Am J requests and responses. Poster presented at: ASHP
Pharm Educ. 2006; 70(3):51. Midyear Clinical Meeting; December 2012; Las
4. American Society of Health-System Pharmacists. Vegas, NV.
ASHP statement on the role of the medication safety 21. Brown JN. Cost savings associated with a dedicated
leader. Am J Health-Syst Pharm. 2013; 70:448–52. drug information service in an academic medical cen-
5. American Society of Health-System Pharmacists. ter. Hosp Pharm. 2011; 46:680–4.
ASHP statement on the pharmacist’s role in informat- 22. Erbele SM, Heck AM, Blankenship CS. Survey of
ics. Am J Health-Syst Pharm. 2007; 64:200–3. computerized documentation system use in drug in-
6. American Society of Health-System Pharmacists. formation centers. Am J Health-Syst Pharm. 2001;
ASHP accreditation standards for postgraduate year 58:695–7.
one (PGY1) pharmacy residency programs. http:// 23. Cheng SC. Computerized tools that standardize the
www.ashp.org/DocLibrary/Accreditation/ASD- systematic approach to researching drug information
PGY1-Standard.aspx (accessed 2013 May 9). requests. Poster presented at: ASHP Midyear Clinical
7. American Society of Health-System Pharmacists. Meeting; December 2006; Anaheim, CA.
ASHP accreditation standards for postgraduate year 24. American Society of Health-System Pharmacists.
two (PGY2) pharmacy residency programs. http:// ASHP guidelines on documenting pharmaceutical care
www.ashp.org/DocLibrary/Accreditation/ASD- in patient medical records. Am J Health-Syst Pharm.
PGY2-Standard.aspx (accessed 2013 May 9). 2003; 60:705–7.
8. Rosenberg JM, Schilit S, Nathan JP, et al. Update on 25. Rosenberg JM, Koumis T, Nathan JP, et al. Current
the status of 89 drug information centers in the United status of pharmacist-operated drug information centers
States. Am J Health-Syst Pharm. 2009; 66:1718–22. in the United States. Am J Health-Syst Pharm. 2004;
9. Powell L, Pepper M. Reviewing the pharmacy depart- 61:2023–32.
ment’s drug information activities. Am J Health-Syst 26. Fass JA, Carvajal M, Polen H, et al. Knowledge, use,
Pharm. 2000; 57:2260–1. and decision-making considerations for drug informa-
10. American Society of Health-System Pharmacists. tion resources in community and hospital pharmacies.
ASHP guidelines on managing drug product short- Poster presented at: ASHP Midyear Clinical Meeting;
ages in hospitals and health systems. Am J Health-Syst December 2012; Las Vegas, NV.
Pharm. 2009; 66:1399–1406. 27. Grossman S, Zerilli T. Health and medication informa-
11. Wisniewski CS, Robert S, Ball S. Collaboration be- tion resources on the World Wide Web. J Pharm Pract.
tween a drug information center and an academic 2013; 26:85–94.
detailing program. Am J Health-Syst Pharm. 2014;
71:128–33.
12. Watanabe AS, McCart G, Shimomura S, et al. Developed through the ASHP Council on Therapeutics and ap-
Systematic approach to drug information requests. Am proved by the ASHP Board of Directors on April 10, 2014. These
J Hosp Pharm. 1975; 32:1282–5. guidelines supersede the ASHP Guidelines on the Provision of
13. Nathan JP. Drug information—the systematic ap- Medication Information by Pharmacists dated April 24, 1996.
proach: continuing education article. J Pharm Pract.
2013; 26:78–84. Shadi Ghaibi, Pharm.D., BCPS, is Pharmacist, Drug Information
14. Calis KA, Anderson DW, Auth DA, et al. Quality of and Medication Safety, Intermountain Medical Center, Murray, UT.
pharmacotherapy consultations provided by drug infor- Heather Ipema, Pharm.D., BCPS, is Clinical Assistant Professor;
mation centers in the United States. Pharmacotherapy. and Michael Gabay, Pharm.D., J.D., BCPS, is Clinical Associate
2000; 20:830–6. Professor, Pharmacy Practice, University of Illinois at Chicago,
15. Beaird SL, Coley RM, Blunt JR. Assessing the accu- Chicago.
racy of drug information responses from drug infor-
mation centers. Ann Pharmacother. 1994; 28:707–11. ASHP gratefully acknowledges contributions made to these guide-
16. Halbert MR, Kelly WN, Miller DE. Drug information lines by the following individuals: Karim Calis, Pharm.D., M.P.H.,
centers: lack of generic equivalence. Drug Intell Clin FASHP, FCCP; Erin Fox, Pharm.D.; Randy Hatton, Pharm.D.,
Pharm. 1977; 11:728–35. BCPS, FCCP; Corinne Johnson, Pharm.D., M.B.A.; Joe Jordan,
17. Wisniewski CS, Pummer TL, Krenzelok EP. Pharm.D.; Mandy Leonard, Pharm.D., BCPS; Michelle W. Mc-
Documenting drug information questions using soft- Carthy, Pharm.D., FASHP; Genevieve Ness, Pharm.D.; Jennifer
ware for poison information documentation. Am J Riggins, Pharm.D.; Ryan Rodriguez, Pharm.D., BCPS; and Sheri
Health-Syst Pharm. 2009; 66:1039–43. VanOsdol, Pharm.D., BCPS.
ASHP also gratefully acknowledges the following organizations Ness, Pharm.D.; James A. Owen, Pharm.D., BCPS (APhA); Frank
and individuals for reviewing these guidelines (review does not P. Paloucek, Pharm.D., DABAT, FASHP; Fred J. Pane, B.S.Pharm.,
imply endorsement): American Pharmacists Association (APhA); FASHP; Lois F. Parker, B.S.; Peter Pascale, M.S.; Stephanie C.
Institute for Safe Medication Practices (ISMP); Joseph Aloi, Peshek, Pharm.D., M.B.A., M.S.Ed., FASHP; James Ponto, M.S.,
Pharm.D., BCPS; Jason Babby, Pharm.D., BCPS; Linda Banares, BCNP, FASHP; William H. Puckett, M.S., M.B.A., FASHP; Curt
Pharm.D., BCACP; Sara J. Beis, M.S., FASHP; John D. Bowman, W. Quap, M.S., FASHP; Dan Rackham, Pharm.D., BCPS; James R.
B.S.Pharm., M.S., BCPS, FASHP; Susan Teil Boyer, M.S., FASHP; Rinehart, M.S., FASHP; Martha M. Rumore, M.S., Pharm.D, J.D.,
Jamie N. Brown, Pharm.D., BCPS; William Budris, B.S.Pharm.; FAPhA; Sam Shimomura, Pharm.D., CGP, FASHP; Sarah J.
Juan Hincapie Castillo, Pharm.D.; Erin S. Christensen, Pharm.D., Steinhardt, Pharm.D., J.D., M.S.; Allen J. Vaida, Pharm.D., FASHP
BCPS; Jason C. Cooper, Pharm.D.; Michelle C. Corrado, Pharm.D., (ISMP); Kristina Ward, Pharm.D., BCPS; Jody Jacobson Wedret,
M.H.A.; Paul Driver, Pharm.D., BCPS, FASHP; Steven Dzierba, FASHP, FCSHP; Tom Westerkamp, M.S.; Phipson Wu, Pharm.D.,
Pharm.D., M.S., FASHP; Lauren Ellison, Pharm.D.; Margo Farber, BCPS; and Kristi Yamasaki, Pharm.D.
Pharm.D.; Leah Frantzen, Pharm.D., BCPS; Kelli Garrison,
Pharm.D., BCPS; Kelly N. Glover, Pharm.D.; Conor Hanrahan, The authors have declared no potential conflicts of interest.
Pharm.D., BCPS; Joe Jordan, Pharm.D., BCPS; Julie P. Karpinski,
Pharm.D., BCPS; Tim Lanese, M.B.A.; Ashley Lewis, Pharm.D.; Copyright © 2015, American Society of Health-System Pharma-
Gregory Light, Pharm.D. (candidate); Jim Lile, Pharm.D., FMPA, cists, Inc. All rights reserved.
FASHP; Patrick M. Malone, Pharm.D., FASHP; Jeannell Mansur,
Pharm.D., FASHP, FSMSO; Shannon Manzi, Pharm.D., NREMT; The bibliographic citation for this document is as follows: Ghaibi
Linda Gore Martin, Pharm.D., M.B.A., BCPS; Theresa Mays, B.S., S., Ipema H., Gabay M. ASHP guidelines on the pharmacist’s role
Pharm.D., BCOP, FASHP; Leslie McCament-Mann, Ph.D.; John F. in providing drug information. Am J Health-Syst Pharm. 2015;
Mitchell, Pharm.D., FASHP; Ruth W. Ndungi, Pharm.D.; Genevieve 72:573–7.
ASHP Guidelines for Providing

Pediatric Pharmaceutical Services in
Organized Health Care Systems
Patient care consists of integrated domains of care, including Inpatient Services
medical care, nursing care, and pharmaceutical care. The
provision of pharmaceutical care involves not only medi- A lack of availability of commercially prepared dosage
cation therapy but decisions about medication selection, forms, combined with the documented risk of calculation
dosages, routes and methods of administration, medication errors, requires the use of comprehensive unit dose drug
therapy monitoring, and the provision of medication-related distribution systems and intravenous (i.v.) admixture services
information and counseling to individual patients.1 The for pediatric patients. Appropriate dosage standardization in
pediatric patient population poses some unique challenges both oral and parenteral drug distribution systems may
to the pharmaceutical care provider in terms of these med- facilitate the provision of these services.
ication-related activities. These challenges include the lack
of published information on the therapeutic uses and moni- Unit Dose System. The pediatric unit dose system must meet
toring of drugs in pediatric patients; the lack of appropriate the original intent of these systems, which is to minimize
commercially available dosage forms and concentrations of errors and provide drugs to the patient care areas in ready-
many drugs for pediatric patients; and the resulting need to to-administer form. Multidose containers and stock medica-
develop innovative ways of ensuring that the patient receives tions should be avoided. An extemporaneous preparation
the drug in a manner that allows the intended therapeutic ef- service should facilitate the preparation and packaging of
fect to be realized.2 These guidelines are intended to assist medications according to sound compounding principles.
pharmacists in meeting the special needs of the pediatric
patient in any organized health care setting. I.V. Admixture Service. The drugs provided by the i.v.
admixture service should include all i.v. push, i.v. minibag,
General Principles intramuscular, and subcutaneous doses; large-volume
injections; antineoplastic agents; parenteral nutrient fluids;
The pharmacy service should be organized in accordance ophthalmic products; peritoneal dialysis solutions; and
with the principles of good management. It should be under irrigation fluids. Knowledge of pediatric fluid requirements
the direction of a pharmacist and be provided with suffi- and limitations, drug administration techniques and devices,
cient physical facilities, personnel, and equipment to meet and acceptable volumes for intramuscular injection is
the pharmaceutical care needs of the pediatric population. critical. Care should be taken when making dilutions to
Resources necessary for compounding and testing alterna- maximize concentrations of drug products (when safe to do
tive doses and dosage forms of commercially available so) for fluid-sensitive patients, as well as to minimize hyper-
products are essential. The pharmacy should comply with all osmolar solutions that might lead to destruction of vascula-
applicable federal, state, and local laws, codes, statutes, and ture or, in the neonate, intraventricular hemorrhage. Quality
regulations.3 The setting should meet applicable accredi- controls for both manually prepared and computer-driven
tation criteria of the Joint Commission on Accreditation preparation should exist to ensure that each product contains
of Healthcare Organizations. Organizations such as the the ingredients ordered and that they are properly labeled.
National Association of Children’s Hospitals and Related Knowledge of products that contain benzyl alcohol and the
Institutions, the American Academy of Pediatrics, and the risks of this substance in neonates is essential in a pediatric
Pediatric Pharmacy Administrative Group are useful sources i.v. admixture service.
of further information on pediatric health care services. The labels of all products should be evaluated for
legibility, clarity of expression, and their potential for lead-
ing to a medication error.5 Labels should include the drug
Orientation and Training Programs name; the drug concentration; the route of administration;
the expiration date or time; appropriate instructions for
Orientation, training, and staff development programs for administration, additional preparation, and storage; and the
pharmacists providing services to pediatric patients should lot number (if a batch-prepared product).6
emphasize dosage calculations, dosage-form selection
appropriate to the patient’s age and condition, and specialized
drug preparation and administration techniques. Pharmacists Ambulatory Care Services
should be familiar with the pharmacokinetic and pharma-
codynamic changes that occur with age (e.g., in volume of Ambulatory care pharmacy services should be attentive to
distribution, protein binding, renal elimination, metabolism, the unique drug needs of the pediatric patient. These include
muscle mass, and fluid requirements) and with disease- the need for special dosage forms (e.g., liquids and chewable
specific conditions that might affect drug choice or admin- tablets), measuring devices, and detailed counseling on drug
istration (e.g., short-gut syndrome, lactose intolerance). A administration. When product stability is a problem, care-
sensitivity to the nature, frequency, and severity of medication- givers may have to be taught how to prepare an appropri-
related errors in the pediatric population is important for all ate dosage form in the home. Consideration must be given
pharmacy personnel.4 to taste and the need for an extra prescription container to
be taken to school or daycare. Children should be included The prevention of accidental ingestion of medications should
whenever possible in discussions concerning their medica- also be emphasized. The benefits of educational programs are
tions. In the ambulatory care setting, the pharmacist is well best realized when a cooperative multidisciplinary approach
positioned to play a role in preventive health care, including is used. Sharing of pertinent information by all participants
poison prevention and immunization.7 is fundamental to the success of patient education services.9
Drug Information Medication Errors
Drug information services should provide the pharmacist Systems for the recognition, documentation, and prevention
practicing in the pediatric setting with information unique of medication errors are essential for the pediatric population.
to the pediatric population. References should include Pharmacist participation in quality-improvement committees
pediatric medical texts and current information on pediatric and the participation of pharmacists, nurses, physicians, and
dosages, extemporaneous formulations, drug compatibilities risk managers are important in minimizing medication errors
and stability, poison control, and drug effects during preg- in pediatric patients. The development and enforcement of
nancy and lactation. Drug information should be available policies and procedures for minimizing medication errors
in areas where decisions are being made about drug therapy. are essential. Pediatric patients are especially vulnerable
Literature supporting the use of drugs for unlabeled uses to errors caused by mistakes in calculations. Pharmacists
in pediatric patients should also be available.8 Pharmacists should recognize that since some commercially available
should provide other health care professionals with informa- products are available in strengths that can be potentially
tion on new and investigational drugs, adverse effects of and toxic to a pediatric patient, special scrutiny of these products
contraindications to drug therapy, compatibility and stability is necessary.5
information, dosage computations, pharmacokinetics, and drug
interactions. This may be accomplished through educational Adverse Drug Reactions
presentations, seeing patients in conjunction with other care-
givers (“rounding”), and printed materials (e.g., newsletters). Pediatric patients frequently have the same kinds of adverse
drug reactions that adults have, but adverse reactions in
Therapeutic Drug Monitoring the pediatric population may be harder to recognize or of
greater or lesser intensity. The lack of literature on newly
Therapeutic drug monitoring enables assessment of thera- introduced therapeutic agents makes it imperative to monitor
peutic outcomes and recognition at the earliest moment of an experience with new drugs initially used in the pediatric popu-
undesirable response to a drug. Both desired and undesired lation. Comprehensive adverse drug reaction monitoring and
effects should be documented. The person performing thera- reporting programs are important in reducing the occurrence
peutic drug monitoring should take into consideration the of these reactions in pediatric patients.10
age-related differences in dosage when recommending or
reviewing drug therapy. Drug-Use Evaluation
Pharmacokinetic Services Drug-use evaluation should be directed at drugs with a low

therapeutic index that require extensive monitoring, those
For both oral and injectable drugs, pharmacokinetic services that are responsible for serious medication errors in the
should ensure that the drug has been administered appropriately institution, and those that are found to be associated with
before samples are taken for the measurement of serum drug high frequency of preventable adverse drug reactions. Cost-
concentrations. The frequency and timing of sampling should related issues may also become important in the evaluations,
also be monitored to avoid excessive and traumatic sampling in since many expensive drugs are not available in package
children. Knowledge of age-related differences in absorption, sizes appropriate for the pediatric patient.
distribution, metabolism, and elimination is essential for the
pharmacist who is involved in pharmacokinetic services for Research
pediatric patients. The collection and publication of accurate
pharmacokinetic data on the pediatric population are encouraged. Pediatric patients have long been recognized as “therapeutic
orphans” because of a relative absence of therapeutic trials
Patient and Caregiver Education in this patient population. The reasons for this are numerous
and include ethical issues, potential adverse publicity, possible
Pharmacists should counsel and educate patients and care- litigation, methodological hurdles, and an inability to justify
givers about their medications, including the purpose of each such studies for economic reasons. Nonetheless, the need for
medication, dosage instructions, potential drug interactions, timely and effective research on medication safety, effi-
potential adverse effects, and any specific age-related issues cacy, and practical application in the pediatric population is
(e.g., compounding and diluting techniques, measuring and compelling. The paucity of pediatric drug information, the
administration instructions). Caregivers should be informed impact of new drug delivery systems, the expansion of adult
of any drug products for which crushing, chewing, dividing, diseases (such as AIDS) into the pediatric population, and
or diluting should be avoided. Suggestions about masking expanded applications of new and established therapeutic
the taste of an unpleasant medication should also be pro- agents are all areas warranting additional research. The
vided. Administration of products, including ophthalmics, pediatric pharmacist can be directly involved in collabora-
otics, inhalers, and injectables, should be demonstrated. tion with other health care providers in conducting pediatric
research. Examples of pediatric research topics include, but 3. American Society of Hospital Pharmacists. ASHP
are not limited to, the following: guidelines: minimum standard for pharmacies in insti-
tutions. Am J Hosp Pharm. 1985; 42:372–5.
• Safety and efficacy of drug products in pediatric patients; 4. Folli HL, Poole RL, Benitz WE, et al. Medication
• Pharmacokinetics and pharmacodynamics of new error prevention by clinical pharmacists in two chil-
medications; dren’s hospitals. Pediatrics. 1987; 79:718–22.
• Stability, safety, and efficacy of extemporaneously 5. American Society of Hospital Pharmacists. ASHP
compounded sterile and nonsterile drug products; guidelines on preventing medication errors in hospi-
• Safety and efficacy of administration techniques; tals. Am J Hosp Pharm. 1993; 50:305–14.
• Comparative evaluations of medications addressing 6. American Society of Hospital Pharmacists. ASHP
treatment regimens, outcomes of therapy, and their technical assistance bulletin on single unit and unit
relative costs; dose packages of drugs. Am J Hosp Pharm. 1985;
• Behavioral and socioeconomic compliance issues in 42:378–9.
pediatric pharmaceutical care; and 7. American Society of Hospital Pharmacists. ASHP
• New and existing pharmacy drug distribution systems technical assistance bulletin on the pharmacist’s role
and services for pediatric patients. in immunization. Am J Hosp Pharm. 1993; 50:501–5.
Examples of direct involvement include statement on the use of medications for unlabeled
uses. Am J Hosp Pharm. 1992; 49:2006–8.
• Serving as a member of an institutional review board; 9. American Society of Hospital Pharmacists. ASHP
• Maintenance, oversight, and dissemination of all guidelines on pharmacist-conducted patient counsel-
information on investigational drug studies and coming. Am J Hosp Pharm. 1993; 50:505–6.
parative trials involving medications in the pediatric 10. American Society of Hospital Pharmacists. ASHP
population; and guidelines on adverse drug reaction monitoring and
• Maintenance, coordination, and oversight of policies reporting. Am J Hosp Pharm. 1989; 46:336–7.
and procedures involving investigational drug studies
and comparative trials involving medications in the
pediatric population. Approved by the ASHP Board of Directors, April 27, 1994.
Developed by the ASHP Council on Professional Affairs.
References
Copyright © 1994, American Society of Hospital Pharmacists, Inc.
1. American Society of Hospital Pharmacists. ASHP All rights reserved.
statement on pharmaceutical care. Am J Hosp Pharm.
1993; 50:1720–3. The bibliographic citation for this document is as follows: American
2. Pediatric Pharmacy Administration Group Committee on Society of Hospital Pharmacists. ASHP guidelines for providing pe-
Pediatric Pharmacy Practice. Pediatric pharmacy prac- diatric pharmaceutical services in organized health care systems.
tice guidelines. Am J Hosp Pharm. 1991; 48:2475–7. Am J Hosp Pharm. 1994; 51:1690–2.
ASHP Guidelines on Surgery and Anesthesiology

Pharmaceutical Services
Purpose 5. Improved revenue generation through accurate patient

billing;
In hospitals, surgery and anesthesiology generally have been 6. Improved documentation of drugs administered to pa-
without direct pharmacist involvement. Drugs have been tients;6
available through a stock-distribution system maintained 7. Clinical activities;
by operating-room (OR) personnel, and documentation of 8. Formulary management;
controlled-substance use has often been handled by person- 9. Drug accountability and control, including adherence
nel other than those administering the drugs. More impor- to organizational drug-use guidelines;
tant, without direct pharmacist involvement, patient-related 10. Quality assurance and continuous quality improve-
issues that are best addressed by a pharmacist usually have ment;
been handled by other health care personnel out of neces- 11. Compliance with standards of the Joint Commission on
sity. ASHP believes that pharmaceutical services (including Accreditation of Healthcare Organizations (JCAHO);
drug-use control) to these areas should be provided by phar- 12. Informational, educational, and research activities;
macists, ideally with their direct presence. In many hospitals 13. Involvement with the use of drug administration
this is accomplished through an onsite satellite pharmacy.1–5 devices; and
The purpose of these guidelines is to help pharmacists 14. Enhanced interdisciplinary decision-making.
identify services they could provide in the areas of surgery
and anesthesiology, decide on the scope of these services, Drug Preparation and Distribution
and develop performance improvement plans. In addition,
the appendix provides guidance for justifying and implement- In most ORs, the drug preparation and distribution functions
ing a satellite pharmacy. Some topics outlined in these can be improved by pharmacy personnel practicing in this
guidelines are the subject of other ASHP practice standards, setting. These activities should not be so labor-intensive as to
which should be referred to for additional information and exclude cognitive services being provided by the phar-
guidance. Pharmacists should use professional judgment macist. Technicians should be assigned most of the drug
in assessing their organization’s needs for pharmaceutical preparation and distribution activities, under the supervision
services in surgery and anesthesiology. The guidance should of a pharmacist. Drug preparation and distribution can be
be adapted, as applicable, to meet those needs. accomplished in various ways. For non-anesthesiology drugs
The term “surgery and anesthesiology pharmaceutical and drugs that are not case specific, a secure general sup-
services” should not be interpreted too literally. Many satellite ply of predetermined medications in limited quantities (e.g.,
pharmacies serving surgery and anesthesiology areas also in cart or cassette) can be provided, with the understanding
serve other areas. These may include cystoscopy and endoscopy that these drugs may be used for any patient. Anesthesiology
suites, cardiac catheterization laboratories or suites, preop- medications could be supplied by case or by daily stock
erative holding areas, postanesthesia care units (PACUs), replenishment (e.g., an “anesthesia cart”). Increasingly, au-
labor and delivery rooms, freestanding surgical centers, and tomated medication storage and distribution devices (e.g.,
critical care areas. In general, these satellite pharmacies are Pyxis Medstation [Cardinal Health]) are being used to sup-
termed “OR satellite pharmacies” and the pharmacist an ply medications to the anesthesiology, nursing, and surgery
“OR pharmacist.” The guidelines do not distinguish among staffs. With these devices, automatic and more accurate
terms, because terms may be applied differently in various patient charging is often realized and pharmacy staff spend
settings. The terms “satellite pharmacy” and “the pharma- less time in distribution activities. The methods chosen may
cist” are used in their broadest senses. depend on the preferences and needs of the anesthesiologists
and surgery staff, available resources, and whether there is a
satellite pharmacy. The choice should be based on the method
that will provide accurate and timely delivery of medications
to meet the needs of patients. The common objectives for all
The successful establishment of pharmaceutical services in
methods, however, are reducing the time spent by nursing
surgery and anesthesiology will depend to a large extent on
and anesthesiology staff in gathering and preparing medi-
the OR pharmacist’s ability to positively affect drug-use man-
cations and maximizing patient safety by limiting the se-
agement, take a leadership role in all aspects of cost contain-
lection of drugs, quantities, and dosage forms.
ment, and contribute to improving patient care and outcomes.
The performance of many activities and services may
be improved in surgery and anesthesiology through the Drug Accountability and Control
establishment of pharmaceutical services. Often these
include the following: The pharmacist should be responsible for all drugs and con-
trolled substances dispensed and distributed in the setting.
1. Drug preparation and distribution; Pharmacy technicians could be assigned most of the respon-
2. Drug inventory control; sibility for these daily activities. If there is a satellite phar-
3. Waste reduction; macy, all drug inventories, to the extent possible, should be
4. Drug cost reduction; centralized there. Minimal drug stock should be kept in each
surgical suite. Ideally, the satellite pharmacy should be staffed drug—drug or drug—disease interactions and for proper
whenever the surgery and anesthesiology areas are normally continuation of maintenance medications and discontinuation
staffed. If the satellite pharmacy is not open 24 hours a day, it of unnecessary medications postoperatively.
may be necessary to establish an after-hours drug supply (e.g.,
a cart). The pharmacist should decide the drugs and quantities Medication-Use Evaluation. The pharmacist should take
required for this supply and the accountability system to be a leadership role in the performance of medication-use
used. The supply levels should be checked and replenished evaluations by establishing criteria, collecting data, analyzing
daily. With an OR pharmacy, trends in drug use or disap- the data, making recommendations, and performing follow-
pearance are more easily identified, noted, and reconciled. up. Data collection is often more easily accomplished pro-
Systems to track drugs used, to adjust par levels as needed, spectively or concurrently by coordination with surgery and
and to monitor drug expiration dates should be devised. anesthesiology staff. High-cost or high-use medications are
good starting places for medication-use evaluations in the OR.
Clinical Services Medication-use evaluations are especially useful for assessing
compliance with established guidelines. In organizations with
Provision of clinical services should be a major focus of automated anesthesia record keepers, collection and manipu-
pharmacists practicing in the surgery and anesthesiology lation of medication-use information is greatly facilitated.11
areas. These services may be similar to those provided to all
other patient care areas. Clinical services can be provided by Drug Information. The pharmacist should provide timely
a pharmacist even without a satellite pharmacy. and accurate drug information in response to known needs
To make effective clinical contributions, the pharma- and random inquiries. Inquiries may originate from any type
cist should be familiar with all drugs used in the setting, of staff, including surgery and recovery-room staff, anesthesia
including drugs for general and regional anesthesia, neuro- staff, residents, nurses, perfusionists, and students. Drug
muscular blockade, analgesia, preoperative management, information may be provided in oral or written form, as
hemodynamic control, diagnosis and manipulation during appropriate. The preparation of responses could require
surgery, prevention of infection, treatment of intraoperative detailed literature searches with accompanying interpreta-
emergencies, control of bleeding, and postoperative nausea tions. The satellite pharmacy should maintain a body of phar-
and vomiting (PONV). Knowledge may be gained by ob- maceutical literature containing current primary, secondary,
servation of surgery and anesthesia procedures, attendance and tertiary literature sources. Scientific and professional
at anesthesia and surgery conferences, assigned topics to be practice journals in pharmacy, anesthesiology, and surgery
presented by each pharmacy team member, review of should be directly available or readily accessible to support
pertinent literature, and direct clinical involvement in patient clinical decision-making for patients in the OR. Online drug
care. Clinical services may include the following7: information and access to the Internet should also be readily
available to OR pharmacists. Reference texts should be
Medication-Use Management. The pharmacist is especially current and should provide detailed information in at least
suited to taking a leadership role in medication-use manage- the following areas: drug action, adverse effects, dosages,
ment in the OR. This could be accomplished through the de- drugs of choice, efficacy, formulations, incompatibilities,
velopment of pharmaceutical practice guidelines and critical indications for use, drug interactions, laws and regulations,
pathways for select surgical procedures, including intraop- pharmacology, pediatric medication administration (if appli-
erative drug use. Guidelines are routinely developed for the cable), nonprescription drugs, drug use during pregnancy
neuromuscular blocking agents, synthetic opioids, propofol, and lactation, pathophysiology, pharmacokinetics, toxicol-
antiemetic agents, volatile inhalation agents, and anti-infectives ogy, surgery, and anesthesia. The pharmacist may also de-
for surgical prophylaxis. Additional guidelines could be velop and distribute a newsletter and make available specific
developed on the basis of organizational needs. It has been articles of interest to others in the setting. The pharmacist
demonstrated that pharmaceutical practice guidelines for should have access to a formal drug information center.
anesthesia-related medications reduce costs without adversely
affecting patient outcomes.8–10 With or without established Formulary System. The pharmacist should continually
guidelines, the presence of an OR satellite pharmacy allows evaluate the organization’s formulary and advise the medical
the pharmacist to reinforce the appropriate use of agents dis- staff and pharmacy and therapeutics (P&T) committee about
pensed from the pharmacy and to monitor patient outcomes. drug efficacy, adverse-effect experiences, cost, and ongoing
need for formulary agents. OR pharmacists can enforce P&T
Medication-Regimen Review. Whenever possible, medica- committee-approved restrictions on anesthesiology and sur-
tion requests from surgery or anesthesiology staff should be gery drugs and educate OR personnel on these restrictions.
evaluated before the drug is dispensed for appropriateness
(e.g., allergies, disease states, adherence to pharmaceutical Drug Research. The pharmacist should strive to initiate and
practice guidelines), dose, route of administration, timing participate in research related to drug use in surgery and
of administration, and cost compared with other therapeutic anesthesia. Pharmacists could be principal investigators or
alternatives. The pharmacist should review the surgery sched- could support the studies of others (e.g., perform randomiza-
ule and routinely screen patient profiles or charts before sur- tion, prepare drugs, assist in study design and data collection).
gery for allergies (e.g., antimicrobials, narcotics, latex) and Because the OR is one of the most medication-intensive
notify appropriate personnel of pertinent findings. In ad- areas of a hospital, it is an excellent setting for pharmaco-
dition, doses, timing, and choices of prophylactic antimi- economic analyses and outcome studies.12–14 These studies
crobials should be monitored. Profiles or charts should also are best accomplished when they are collaborative. Given
be reviewed whenever possible for potential perioperative that newer anesthetic agents are often more expensive than
older ones, studies are useful for learning whether a higher Pharmacokinetic Management and Consultation. The
drug cost will result in a lower total cost for the patient. pharmacist should participate in the pharmacokinetic manage-
ment of patients and should serve as a consultant to surgery
Adverse-Drug-Reaction Monitoring and Reporting. The and anesthesiology staff on pharmacokinetic of medications
pharmacist should monitor, detect, document, report, and dosing.
recommend appropriate management of adverse drug
reactions that occur in the OR. OR health care providers Compliance with JCAHO Standards. The presence of phar-
should be asked to report suspected adverse drug reactions macy personnel in the surgery and anesthesiology areas,
to the OR pharmacist for follow-up. especially with an established satellite pharmacy, could
help to ensure adherence to Joint Commission standards.
Education. Educational presentations on drug-related topics Specifically, pharmacy plays a key role in compliance with
should be made regularly by the pharmacist to surgery and the standards related to the medication-use process. These
anesthesiology residents and staff, nursing staff, pharmacy include reviewing medication orders; considering patient
staff, and other personnel. This could include information information when preparing and dispensing medication(s);
on drugs added to the organization’s formulary, drug pre- ensuring pharmaceutical services are available when the
cautions, periodic reviews of drugs used during cardiac and pharmacy department is closed or pharmacy personnel are
respiratory arrest, pain management, and the management not available; controlling the preparation and dispensing
of malignant hyperthermia and latex allergy. The pharma- of medication(s) (drugs should be secure from tampering,
cist should also educate OR personnel about drugs used in safe from patient-to-patient contamination, and properly
the setting, giving special attention to the synthetic opiods labeled); ensuring that emergency medications are consis-
neuromuscular blocking agents, anesthetic gases, intravenous tently available, controlled, and secure in the pharmacy and
anesthetic agents, local anesthetics, antiemetics, and anti- patient care areas; and monitoring the effects of medications
microbials (surgical prophylaxis). on patients.
Formal educational rotations in the satellite pharmacy
may be conducted for undergraduate and graduate pharmacy Documentation of Clinical Activities. The pharmacist should
document clinical activities and identify activities leading to
students, pharmacy residents, or pharmacy fellows. Specific
improved patient outcomes and cost reductions. This type of
learning and experiential goals and objectives should be devel-
information is critical in order for the pharmacist to prove his
oped. The student should learn about satellite pharmacy services
or her value and the ongoing need for the services provided.
and preoperative, intraoperative, and postoperative medication
The pharmacist is responsible for safeguarding the patient’s
therapy through didactic instruction, observation, project par-
rights to privacy and the confidentiality of the patient’s
ticipation, and selected readings. Rotations should be coordi-
clinical information.
nated with the anesthesiology and nursing departments.
Rounds. When possible, the pharmacist should be an active Controlled Substances

participant with anesthesia, surgery, and PACU staff in
patient care rounds. The pharmacist may limit rounds to All controlled-substance procedures should comply with
specific types of patients (e.g., cardiothoracic surgery, trans- applicable federal and state laws and regulations as well as
plant) for whom the pharmacist’s preoperative or postopera- the organization’s policies and procedures. Procedures for
the satellite pharmacy and the surgery and anesthesiology
tive involvement may be most beneficial. The pharmacist
areas served should address the following:
should participate in anesthesia grand rounds, morbidity and
mortality reviews, and other scheduled educational sessions
1. Controlled substances (and other drugs) to be moni-
as appropriate. Pharmacy grand rounds could be conducted
tored;
by pharmacy staff to provide detailed drug information or to
2. Methods of distribution;
supplement anesthesia grand round topics.
3. Records;
4. Ordering;
Pain Management. The pharmacist should participate
5. Storage, access, and inventory control;
actively in epidural anesthesia, patient-controlled analgesia,
6. Reconciliation and disposal;
and other pain-management programs. Participation could
7. Discrepancy reporting and disciplinary action; and
include the development of such a program, identification 8. Performance of quality control checks.
of appropriate patients, patient education, drug preparation,
educational presentations to other staff, and participation in The goal of the controlled-substance system is to
rounds with acute-pain-management teams as time permits. prevent diversion yet be practical enough that patient care
is not adversely affected. The system should limit exposure
Participation in Emergency Life Support. The pharmacist to controlled substances, be accountable and consistent, and
should be authorized to participate in the medication therapy contain an educational component for health care personnel.15
for cardiac or respiratory arrests that occur in the OR. At a
minimum, the pharmacist should have current certification Controlled Substances (and Other Drugs) to Be Monitored.
in basic cardiac life support (BCLS) procedures and, preferably, The pharmacist should be responsible for monitoring the use
training in advanced cardiac life support (ACLS). The phar- of all controlled substances. As required (e.g., because of
macist should also participate in the treatment of malignant abuse or diversion potential), drugs other than controlled
hyperthermia by preparing and maintaining malignant substances (e.g., ketamine) could also be handled according
hyperthermia emergency kits and preparing and administer- to procedures similar or identical to those used for controlled
ing medications used to treat malignant hyperthermia. substances.
Methods of Distribution Ordering

One of two primary methods could be used for distribution The pharmacist should be responsible for ordering all con-
of controlled substances in the OR: a per-case method or a trolled substances for the satellite pharmacy. Once received,
daily-supply method. the controlled substances should be added to the satellite
A per-case system is advantageous in that it minimizes the pharmacy’s stock and recorded in inventory records. If the
quantity of controlled substances available to the anesthesiologist satellite pharmacy does not provide 24-hour services, the
and the anesthetist at any one time and allows for a good audit pharmacist is responsible for ensuring that adequate supplies
trail. Its major disadvantage is that it is very time intensive for are available in a secure, specially designated after-hours
an organization that performs many surgeries per day. This time location. The pharmacist should maintain controlled-
may be better spent by the pharmacist in clinical activities. substance inventory amounts sufficient only to meet the
Daily distribution of controlled substances is less time needs of the OR for a reasonable time. This time should
intensive and can be accomplished from a central pharmacy depend on the frequency and timeliness with which con-
or an OR satellite pharmacy. Its disadvantages are that trolled substances are available from the central pharmacy.
greater amounts of controlled substances are dispensed at Less inventory is required, for example, if controlled sub-
one time and that these substances need to be kept secure stances are ordered on a daily basis rather than less often.
throughout the day. The inventory system should be perpetual in order to provide
The various advantages and disadvantages of each the most current record of controlled substances on hand.
method must be considered and the appropriate system Shortly after the initial opening of a satellite pharmacy
selected on an organization-specific basis. and after drug use has stabilized, stock levels should
To the extent possible, controlled substances should be be reassessed and adjusted as needed. During order-
distributed only in response to signed orders or oral requests ing, the pharmacist should note developing trends in use.
from prescribers. Given the urgency often present during Nonformulary controlled substances should be dispensed
surgical procedures, the necessity for prescribers to devote only by special request.
undivided attention to anesthesia procedures, and the use of
sterility-safeguard procedures during surgery, it may not
always be possible to comply with such a requirement. When Storage, Access, and Inventory Control
it is possible, the organization’s standard physician-order sheet
or a special controlled-substance request form developed spe- Controlled substances should be stored in a locked space
cifically for use in the surgical suite could be used. A par level (e.g., cabinet, drawer, cart) within the satellite pharmacy.
of controlled substances needed per type of case or for the day These storage spaces should remain locked when controlled
could be devised; requests for controlled substances beyond substances are not being dispensed. Access to the space
this would be treated as special orders. Whatever the methods should be limited to satellite pharmacy personnel. If 24-hour
used, clear documentation that all controlled substances used satellite pharmacy services are not provided, a separate
were administered to the patient should be signed by the locked after-hours storage space will be required. Kits of
responsible prescribers at the end of each surgical procedure. after-hours controlled substances may be useful. No matter
Ideally, unused controlled substances drawn up by the anes- how they are configured or located, all after-hours supplies
thesiologist should be returned to the satellite pharmacy and should be checked and all records reconciled by satellite
wasted by the pharmacist. Alternatively, controlled substances pharmacy staff on the first working day after the after-hours
could be disposed of by the anesthesiologist in the presence supplies are entered.
of a witness, with both parties documenting the disposal. No If possible, one person per shift should be identified
matter the system, disposal of contaminated controlled as being responsible for controlled substances (and related
substances (e.g., with blood or other body fluid) should occur procedures) when the satellite pharmacy is not open. That
in the OR and be properly documented. person should have access (key or code) to locked after-hours
supplies. This approach enables more consistent record
Records keeping, limits the number of people with access to after-
hours supplies, and enables more reliable monitoring of
controlled-substance use. Individuals often assigned this
Records should be kept of the following:
responsibility include an “in-charge” nurse or the “first-call”
anesthesiology resident.
1. Controlled substances dispensed;
Controlled-substance inventories should be verified by
2. Controlled-substance inventories;
physical count at least once daily. If the satellite pharmacy
3. Controlled substances returned (including controlled
is open for two shifts, an end-of-shift count by the morning
substances drawn up but not used), and records rec-
pharmacist is recommended. The use of automated medica-
onciliation;
tion storage and distribution devices for controlled substances
4. Controlled substances disposed; and
may be a timesaving benefit for maintaining a perpetual
5. Controlled-substance use, categorized by prescriber.
inventory. Unscheduled audits of controlled substances in the
satellite pharmacy should be done by staff not normally
If the satellite pharmacy does not provide 24-hour assigned to this setting. The results should be documented.
services, the documentation procedures for after-hours use
should be as similar as possible to those used when the satellite
pharmacy is staffed. This will help ensure staff efficiency Reconciliation and Disposal
and familiarity with the record-keeping requirements after
hours. Forms specific to the setting and to the after-hours A thorough system for reconciling controlled-substance use
circumstance may have to be developed. should be developed and include the following components16–18:
1. Comparison of quantities dispensed with quantities 11. Allergy and patient demographic monitoring.
documented as administered. The quantity of controlled
substances returned to the satellite pharmacy should be Some of these activities should not be difficult to imple-
compared with the quantity dispensed. The amount ment in a satellite pharmacy, because ongoing procedures should
dispensed should equal the amount returned (unopened already be developed for the organization overall. Sometimes,
and partially filled containers and partially used sy- it may be necessary to develop new programs or variations of
ringes) plus the amount documented as administered. existing ones tailored to the surgery and anesthesiology areas.
2. Verification of use through review of the anesthesia
record. The anesthesia record should be reviewed to
ensure that the amount documented as administered (in Other Activities
records returned to the satellite pharmacy) is identical to
the amount documented in the patient’s anesthesia record. Policies and Procedures. If there is a satellite pharmacy, the
This verification is ideally done for all cases but may be pharmacist should develop and maintain policies and pro-
done by periodic audits of randomly selected cases if cedures for the satellite pharmacy and its services. There
anesthesia records are not readily available for every case. should be policies and procedures for the preparation of
3. Qualitative testing of returned controlled substances. drug kits (if applicable), medication distribution systems,
To verify that unadulterated drug is contained in par- controlled-substance handling, hours of operation, prepa-
tially used containers returned to the satellite phar- ration of parenteral products, expiration-date checking and
macy, a refractometer or other device can be used. monthly inspections, recycling of products, monitoring of
It is important to randomly audit controlled-substance drug inventory levels, staff training, quality assurance activi-
returns in order to detect trends in diversion. The or- ties, and after-hours drug distribution.
ganization’s legal department should be consulted to
make sure such testing is permitted. Interdisciplinary Interfaces. The pharmacist should func-
tion as a liaison between the pharmacy department and all
The pharmacist should account for all controlled staff in the setting served, including anesthesiology, nurs-
substances dispensed and should report all discrepancies to ing, and surgery staff; perfusionists; and management staff.
internal and external authorities as required. The pharmacist should represent the pharmacy department
Disposal of controlled substances (e.g., partially used on appropriate interdisciplinary committees charged with
syringes) should be done in the satellite pharmacy by a evaluating or making recommendations about services and
member of the pharmacy staff in the presence of a witness. medication selection and use in the surgery and anesthesiol-
This action should be documented in the satellite pharma- ogy areas. A committee specifically designed to focus on
cy’s controlled-substance records. pharmacy matters may be appropriate.
Financial Analysis. The pharmacist should document drug

Communication and Education costs, service costs, revenues, and savings attributable to the
satellite pharmacy and the activities (clinical and distributive)
It is important that there are open lines of communication of its staff. If there is no OR satellite pharmacy, some of the
among the pharmacist, the chair of anesthesiology (or aforementioned items will not need to be included in the analy-
designee), and the head surgical nurse to allow sharing of sis. Financial reports should be prepared periodically (e.g.,
information indicative of diversion (e.g., behavioral change). quarterly, annually) and provided to the hospital administration
In addition, periodic continuing education for all members and the departments of anesthesiology, surgery, and pharmacy.
of the OR team on the potential for substance abuse may
sensitize staff to this problem.15
The Pharmacy Technician’s Role
Performance Improvement
Pharmacy technicians assigned to the satellite pharmacy
The pursuit of continuous improvement in the quality of should be trained to perform their assigned functions. It is
services provided should be a philosophy of practice of the critical and appropriate for the technician to do most of the
pharmacist and the satellite pharmacy staff.19 In that light, drug distribution-related activities in the satellite pharmacy.
many activities may be seen as pertinent to performance im- Within the total work force of pharmacy technicians in the
provement efforts. Some of these are the following: organization, it is desirable to have some technicians trained as
available back-up staff for the satellite pharmacy. Technicians
1. Adverse-drug-reaction monitoring and reporting, should be trained and certified by the Pharmacy Technician
2. Medication-error monitoring and reporting, Certification Board or equivalent. In general, technician training
3. Medication histories, and experience should include parenteral drug preparation,
4. Periodic inspections of all drug storage sites, drug distribution procedures, physician-order interpretation,
5. Drug therapy monitoring related to improved patient anesthesia and OR record interpretation, computer order entry,
outcome (e.g., decreased time in the PACU, decreased and controlled-substance record keeping. Specific training
frequency of PONV), should include a review of the following:
6. Medication-use evaluations,
7. Drug-interaction monitoring, 1. Procedures unique to surgical suites, including special
8. Controlled-substance monitoring, apparel (e.g., caps, masks, foot covers) and restricted
9. Quality control of compounded parenterals (e.g., movements and areas within surgical suites;
cardioplegic solutions) and batch-prepared syringes, 2. Surgical-suite terms, including abbreviations and
10. Medication-waste monitoring, and acronyms used to name surgical procedures;
3. Drug classes, indications for use, and proper handling Orientation and Training of New Staff. Helping with the
of drugs routinely used in surgical suites (e.g., special orientation and training of new staff (including other techni-
packaging, preservative requirements for spinal and cians and pharmacy students) could also be a responsibility
epidural drugs, infusion concentrations); of the technician. An orientation checklist, workflow sheets,
4. Controlled-substance procedures; and task lists are helpful training tools. An OR pharmacy
5. Emergency drugs typically used in surgical suites; and student module would be a helpful teaching tool for students
6. A review of the role of the pharmacy technician in the on rotation in the satellite pharmacy.
OR pharmacy area.
Quality Assurance. The technician could be involved in
Typical activities performed by pharmacy technicians quality assurance activities of the satellite pharmacy. Such
in the satellite pharmacy under the supervision of the phar- activities may include regular controlled-substance audits or
macist are drug distribution, controlled-substance handling, assays, microbiological monitoring of parenteral drugs pre-
sterile drug preparation, drug ordering and restocking, pared, and inspections of drug supplies (e.g., expiration dates).
orientation and training of new staff, and quality assurance
activities. Each of these will be discussed in greater detail.
Summary
Drug Distribution. The technician could distribute medi-
Pharmaceutical services in surgery and anesthesiology
cations to storage sites in the setting and prepare per-case
should be the standard of practice in health care organiza-
or per-prescriber kits of medications and distribute these af-
tions across the United States. Although not essential, an
ter they have been checked by the pharmacist. If automated
onsite satellite pharmacy would help in the provision of
medication storage and distribution devices are used, the tech-
these services. A majority of distribution-related activities
nician is responsible for all activities associated with restock-
should be done by technicians. The availability of automated
ing these. Given the nature of surgical procedures and the ur-
devices and other technology may lessen, to some extent, the
gency of the need for the requested medications, distribution
time devoted to drug distribution. It is important for the OR
would be required in response to oral requests. The pharma-
pharmacist to concentrate on the provision of clinical ser-
cist should screen such requests to ensure proper choices of
vices, such as medication-use management, drug information
drugs for specific patients. The technician should be trained
services, medication-use evaluations, formulary manage-
to ask about patient allergies and relay this information to the
ment, and pharmacoeconomic analyses of anesthesia- related
pharmacist before preparing a medication. The technician
medications. These activities provide the best opportunity
also should be taught which situations must be handled by the
for the pharmacist to contribute to improving patient care
pharmacist (e.g., drug information, dose calculations).
and outcomes and containing costs. Finally, pharmaceuti-
The technician could return unused drugs to stock and
cal services in surgery and anesthesiology should be periodi-
charge patients or departments for medications used.
cally assessed for patient care and financial effectiveness.
Another technician function could be to check and
replenish after-hours drug supplies and charge medications
used to appropriate patients or departments. References
The technician could be responsible for monthly
inspections of drug storage areas and drug supply areas in 1. Powell PJ, Maland L, Bair JN, et al. Implementing an
the satellite pharmacy. Technicians should be assigned their operating room pharmacy satellite. Am J Hosp Pharm.
own inspection zone when drugs are stored in many places. 1983; 40:1192–8.
2. Opoien D. Establishment of surgery satellite pharmacy
Controlled Substances. Other responsibilities of the techni- services in a large community hospital. Hosp Pharm.
cian could be the distribution of controlled substances and the 1984; 19:485–90.
creation of appropriate records according to the distribution 3. Keicher PA, McAllister JC III. Comprehensive phar-
procedures of the satellite pharmacy and according to federal maceutical services in the surgical suite and recovery
and state laws and regulations. Typical activities could include room. Am J Hosp Pharm. 1985; 42:2454–62.
helping with inventory counts, maintaining perpetual inventory 4. Buchanan EC, Gaither MW. Development of an oper-
records, disposing of controlled substances with the pharmacist, ating room pharmacy substation on a restricted budget.
and participating in audits, assays, and preparation of reports. Am J Hosp Pharm. 1986; 43:1719–22.
5. Vogel DP, Barone J, Penn F, et al. Ideas for action: the
Sterile Drug Preparation. The technician could aseptically operating room pharmacy satellite. Top Hosp Pharm
compound, package, and label sterile drugs—for injection Manag. 1986; 6:63–80.
and for irrigation—and document all products made. Appro 6. Donnelly AJ. Multidisciplinary approach to improving
priate records of drug name, diluent, lot numbers, and expira- documentation of medications used during surgical
tion dates of batch-prepared products should be maintained by procedures. Am J Hosp Pharm. 1989; 46:724–8.
the technician. 7. Shafer AS. Clinical pharmacy practice in the operating
room. J Pharm Pract. 1993; 6:165–70.
Drug Ordering and Restocking of the Pharmacy Satellite. 8. Gora-Harper ML, Hessel E II, Shadick D. Effect of
In addition, technicians could routinely order replenishment prescribing guidelines on the use of neuromuscu-
supplies of drugs for the satellite pharmacy, check supplies lar blocking agents. Am J Health-Syst Pharm. 1995;
delivered in response to the orders, and place the stock in 52:1900–4.
appropriate places. Requests for odd medications or unusual 9. Freund PR, Borolle TA, Posner KL, et al. Cost-
trends in medication demand should be reported to the phar- effective reduction of neuromuscular-block drug ex-
macist for further review. penditures. Anesthesiology. 1997; 87:1044–9.
10. Lubarsky DA, Glass PSA, Ginsberg B, et al. The of medications in the OR and has significant patient care
successful implementation of pharmaceutical practice responsibilities in this setting. Support for pharmaceutical
guidelines. Anesthesiology. 1997; 86:1145–60. services from anesthesiology department administration is
11. Lubarsky DA, Sanderson IC, Gilbert WC, et al. Using important for the success of the project. If the request for
an anesthesia information management system as a cost satellite pharmacy services originates in the anesthesiology
containment tool. Anesthesiology. 1997; 86:1161–9. department, the justification process may be simpler and
12. Lorighlin KA, Weingarten CM, Nagelhout J, et al. A more collaborative. Data gathered during the preliminary
pharmacoeconomic analysis of neuromuscular block- review of the site and information obtained from the litera-
ing agents in the operating room. Pharmacotherapy. ture can be used when the project is discussed with anes-
1996; 16:942–50. thesiology administration. It may be valuable to solicit the
13. DeMonaco HJ, Shah AS. Economic considerations support of any anesthesiologists who have been especially
in the use of neuromuscular blocking drugs. J Clin receptive to pharmacy involvement. Many anesthesiolo-
Anesth. 1994; 6:383–7. gists have had positive experiences with OR pharmaceutical
14. Tang J, Watcha MF, White PF. A comparison of costs services at other organizations. The proposal for a satellite
and efficacy of ondansetron and droperidol as prophy- pharmacy might then be presented jointly by pharmacy per-
lactic antiemetic therapy for elective outpatient gyne- sonnel and anesthesiologists. Once formalized, the proposal
cologic procedures. Anesth Analg. 1996; 83:304–13. should be presented to hospital administration. The admin-
15. Castellano FC. Developing methods for preventing istration’s opinion will provide some guidance on how to
and detecting substance abuse in the operating room: a facilitate the approval process for the satellite pharmacy.
disease approach. J Pharm Pract. 1993; 6:159–64. If conceptual support from these groups is obtained,
16. Satterlee GB. System for verifying use of controlled development of a more formal proposal can begin. If there
substances in anesthesia. Am J Hosp Pharm. 1989; are still concerns about the benefits gained from OR satellite
46:2506–8. pharmacy services, it may be helpful to propose an interim
step to expose more hospital staff to OR pharmaceutical
17. Shovick VA, Mattei TJ, Karnack CM. Audit to verify
services in order to keep the process moving forward. One
use of controlled substances in anesthesia. Am J Hosp
possible approach is to suggest that a pilot project be conducted
Pharm. 1988; 45:1111–3.
involving several ORs or one specific surgical specialty. The
18. Gill DL, Goodwin SR, Knudsen AK, et al. Refractometer
establishment of a permanent satellite pharmacy would
screening of controlled substances in an operating room
depend on favorable results from the pilot project.
satellite pharmacy. Am J Hosp Pharm. 1990; 47:817–8.
19. Hawkins PR. Quality improvement: pharmacy involve
Initial Assessment of Setting. A general review of the surgery
ment in the operating room. J Pharm Pract. 1993; 6:171–6.
and anesthesiology areas to be served by the satellite pharmacy
should be done after staff have become familiar with the proj-
Appendix— ect. At this time, it is not essential that detailed information be
Justifying and Implementing an obtained. Useful information to collect includes the following:
Operating-Room Satellite Pharmacy
1. All locations and quantities of drugs stored in the set-
Justification of the need for a satellite pharmacy is a critical ting,
step in establishing pharmaceutical services in surgery and 2. The location and storage of controlled substances,
anesthesiology.1,2 3. Controlled-substance accountability systems used,
The pharmacist’s ability to positively affect medication- 4. Drug preparation and distribution procedures used in
use management, to take a leadership role in all aspects of the setting,
cost containment, and to contribute to improved patient care 5. Billing systems used for all drugs,
and outcomes must be highlighted. 6. Stock replenishment and rotation systems used, and
7. The role (or potential role) of automation in the in-
Familiarization with Surgery and Anesthesiology Phar volved areas.
maceutical Services. As an initial step, the person in charge of
the project should become familiar with typical surgery and anes- The collection of this information could be speeded by
thesiology satellite pharmacy services. Review of pertinent litera- a tour of the area and by inquiries through nurses, anesthesi-
ture, discussions with pharmacists in other organizations, and site ologists, supply technicians, surgeons, and other OR person-
visits to established satellite pharmacies are methods of accom- nel (e.g., perfusionists).
plishing this step. The site visit is especially useful, because it can
reinforce and further define information gained by other means. Formal Proposal. The development of a formal proposal is
At the conclusion of this step, the pharmacist should have a real- an important part of the justification process. It is essential
istic view of the types and scope of services typically provided. that the proposal be well organized and factual. The writers
of the proposal should expect the proposal to be examined in
Obtaining Support. If justification is to be successful, the sup- great detail by hospital administration and others during the
port of key individuals from the major departments affected decision-making process. The proposal should expand upon
by the service should be obtained.1 In most organizations, the information obtained in the initial review of the surgery
these are hospital administration, anesthesiology (anesthesiol- and anesthesiology areas. Information that should be in the
ogists and certified registered nurse anesthetists), and surgery, proposal includes the following:
operating-room (OR), and postanesthesia care unit nursing.
The support of the anesthesiology department is nec- 1. The dollar value of current drug inventory,
essary because this department represents the major users 2. The dollar value of drugs used per period (e.g., per year),
3. The dollar value of patient charges currently generated, who will be assigned to staff the satellite pharmacy;
4. The estimated dollar value of increased revenue, often, it is valuable for the project leader to be a super-
5. The average cost of drugs used per surgical case, visor or assistant director),
6. An estimated cost of drug waste per period, 3. Identify construction and equipment needs,
7. The general quality and completeness of controlled- 4. Oversee construction work,
substance records, 5. Obtain and install equipment,
8. The number of controlled-substance discrepancies 6. Draft policies and procedures (e.g., controlled-
reported per month, substance accountability, medication distribution
9. The number of reports of drug-related incidents re- system, inventory control),
ceived per month, 7. Develop job descriptions,
10. The time personnel in the setting currently spend 8. Select staff (pharmacists and support personnel),
performing pharmacy-related activities, 9. Design and print forms,
11. The time pharmacy personnel currently spend performing 10. Formalize policies and procedures,
activities for the setting, and 11. Determine satellite pharmacy drug-stock levels,
12. Opportunities for collaborative efforts by pharmacy– 12. Train staff,
anesthesiology, pharmacy–nursing, pharmacy–perfu- 13. Identify back-up and relief staff and orient them to the
sion, and pharmacy–surgery in drug-use management setting,
(e.g., development of pharmaceutical practice guide- 1 4. Educate nursing staff,
lines, performance of medication-use evaluations). 15. Educate anesthesiology department staff,
16. Educate surgeons,
Collection of this information could be helped through 17. Open the satellite pharmacy for operation,
the formation of a multidisciplinary team. Representatives of 18. Determine future goals for service, and
the departments of pharmacy, anesthesiology, nursing, and 19. Determine systems for periodic analyses of the impact
surgery should be included. This approach has several ben- of the program.
efits. Data collection can be expedited, because the expertise
of each individual can be used. The value of a satellite phar- Many of these steps can be expedited by a close
macy will be continually reinforced to these individuals, and working relationship with members of the anesthesiology
all groups will have input into the decision-making process. and nursing departments.
A formal proposal should be prepared once the required The satellite pharmacy’s services should be monitored
information has been collected. Minimally, the proposal and evaluated on an ongoing basis through workload statistics,
should contain the following sections1: data on controlled-substance discrepancies, financial data,
and patient outcomes data. In addition, the satisfaction levels
1. Introduction; of the nursing and anesthesiology staffs should be assessed
2. Statement of problems and anticipated benefits (and before the program is implemented, six months after
beneficiaries); implementation, and yearly after that.
3. Summary of the proposed services;
4. Cost–benefit analysis, including staffing, estimated cost References
savings, revenue projections, and inventory savings; and
5. Implementation plan. 1. Vogel DP, Barone J, Penn F, et al. Ideas for action: the
operating room pharmacy satellite. Top Hosp Pharm
During preparation of these sections, it is important to Manage. 1986; 6:63–80.
be as specific as possible and to assign dollar values when- 2. Ziter CA, Dennis BW, Shoup LK. Justification of an
ever these are available. The proposal should be endorsed operating-room satellite pharmacy. Am J Hosp Pharm.
by the members of the multidisciplinary team and should be 1989; 46:1353–61.
submitted to the administration by the director of pharmacy.
Careful planning, data collection, analysis, and presentation
of the information gathered will make approval more likely.
These guidelines were reviewed in 2003 by the Council on
Implementation. Implementation should begin as soon as Professional Affairs and by the Board of Directors and were found
possible after administrative approval.1 Implementation to still be appropriate.
steps should be planned and executed in a clear, concise
manner. To guide planning, an implementation time line Approved by the ASHP Board of Directors November 14, 1998.
should be developed (e.g., Gantt chart), listing the steps to be Developed through the ASHP Council on Professional Affairs.
taken, the task force member responsible for each step, and Supersedes the ASHP Technical Assistance Bulletin on Surgery
the expected amount of time required for each activity. The and Anesthesiology Pharmaceutical Services dated November
amount of time required for each activity may vary from 14, 1990.
organization to organization, but the order in which the steps
should be performed will be reasonably standard. Copyright © 1998, American Society of Hospital Pharmacists, Inc.
The major implementation steps and an approximate All rights reserved.
order in which they should be completed are as follows1:
1. Obtain a formal commitment of space, Society of Health-System Pharmacists. ASHP guidelines on surgery
2. Assign a project leader (who should be responsible for and anesthesiology pharmaceutical services. Am J Health-Syst
the project’s development and need not be the pharmacist Pharm. 1999; 56:887–95.
Pharmaceutical Industry
396 Pharmaceutical Industry: Drug Products, Labeling, and Packaging–Positions
Drug Products, Labeling, and Packaging
Excipients in Drug Products (1528) Elimination of Surface Contamination on Vials of

Source: Council on Pharmacy Practice Hazardous Drugs (0618)
To advocate that manufacturers remove unnecessary, poten- Source: Council on Professional Affairs
tially allergenic excipients from all drug products; further, To advocate that pharmaceutical manufacturers eliminate
To advocate that manufacturers declare the name and surface contamination on vials of hazardous drugs; further,
derivative source of all excipients in drug products on the To inform pharmacists and other personnel of the po-
official label; further, tential presence of surface contamination on the vials of haz-
To advocate that vendors of medication-related data- ardous drugs; further,
bases incorporate information about excipients; further, To encourage health care organizations to adhere to
To foster education on the allergenicity of excipients published standards and regulations to protect workers from
and documentation in the patient medical record of allergic undue exposure to hazardous drugs.
reactions to excipients. This policy was reviewed in 2010 by the Council on
This policy supersedes ASHP policy 0808. Pharmacy Practice and by the Board of Directors and was
Ensuring Effectiveness, Safety, and Access to Orphan
Drug Products (1413) Mandatory Labeling of the Presence of Latex (0501)
Source: Council on Therapeutics Source: Section of Inpatient Care Practitioners
To encourage continued research on and development of or- To urge the Food and Drug Administration to mandate that
phan drug products; further, manufacturers of medications and medication-device com-
To advocate for the use of innovative strategies and bination products include labeling information on whether
incentives to expand the breadth of rare diseases addressed any component of the product, including its packaging, con-
by this program; further, tains natural rubber latex.
To encourage postmarketing research to support the This policy was reviewed in 2014 by the Council on
safe and effective use of these drug products for approved Pharmacy Practice and by the Board of Directors and was
and off-label indications; further, found to still be appropriate.
To urge health policymakers, payers, and pharmaceuti-
cal manufacturers to develop innovative ways to ensure pa- Ready-to-Use Packaging for All Settings (0402)
tient access to orphan drug products. Source: Council on Professional Affairs
This policy supersedes ASHP policy 0715. To advocate that pharmaceutical manufacturers provide all
medications used in ambulatory care settings in unit-of-use
Standardized Clinical Drug Nomenclature (0920) packages; further,
Source: Council on Pharmacy Management To urge the Food and Drug Administration to support
To encourage federal agencies, the pharmaceutical industry, this goal; further,
pharmacy and medical software providers, and purveyors To encourage pharmacists to adopt unit-of-use pack-
of clinical data repositories and drug databases to explore aging for dispensing prescription medications to ambulatory
the potential benefits of supplementing or modifying the patients; further,
National Drug Code with a coding system that can be used To support continued research on the safety benefits
effectively to support patient care, research, and financial and patient adherence associated with unit-of-use packaging
management; further, and other dispensing technologies.
To encourage that such a coding system encompass (Note: A unit-of-use package is a container–closure
prescription drug products, nonprescription medications, system designed to hold a specific quantity of a drug product
and dietary supplements and include both active and inac- for a specific use and intended to be dispensed to a patient
tive ingredients. without any modification except for the addition of appro-
This policy was reviewed in 2013 by the Council on priate labeling.)
Pharmacy Management and by the Board of Directors and This policy was reviewed in 2013 by the Council on
was found to still be appropriate. Pharmacy Practice and by the Board of Directors and was
Standardizing Prefixes and Suffixes in Drug Product
Names (0720) Unit Dose Packaging Availability (0309)
Source: Council on Public Policy Source: Council on Administrative Affairs
To collaborate with others, including the United States To advocate that pharmaceutical manufacturers provide all
Pharmacopeia and the Food and Drug Administration, in medications used in health systems in unit dose packages;
standardizing and defining the meaning of prefixes and suf- further,
fixes for prescription and nonprescription drugs to prevent To urge the Food and Drug Administration to support
medication errors and ensure patient safety. this goal in the interest of public health and patient safety.
Public Policy and by the Board of Directors and was found Pharmacy Management and by the Board of Directors and
to still be appropriate. was found to still be appropriate.
Pharmaceutical Industry: Drug Products, Labeling, and Packaging–Positions 397
Drug Shortages (0002) Drug Nomenclature (9011)

Source: Council on Administrative Affairs Source: House of Delegates Resolution
To declare that pharmaceutical manufacturers, distributors, To work with the FDA, USP, and pharmaceutical industry to
group purchasing organizations, and regulatory bodies, assure that drug products are named in a manner that clearly
when making decisions that may create drug product short- and without confusion permits identification of ingredients’
ages, should strive to prevent those decisions from compro- strengths and changes.
mising the quality and safety of patient care. This policy was reviewed in 2013 by the Council on
This policy was reviewed in 2014 by the Council on Public Policy and by the Board of Directors and was found
Pharmacy Practice and by the Board of Directors and was to still be appropriate.
Codes on Solid Dosage Forms of Prescription Drug
Pediatric Dosage Forms (9707) Products (8709)
Source: Council on Professional Affairs Source: Council on Legal and Public Affairs
To support efforts that stimulate development of pediatric To support efforts requiring manufacturers of solid dosage
dosage forms of drug products. form prescription drug products to imprint a readily identifi-
This policy was reviewed in 2012 by the Council on able code indicating the manufacturer of the drug product
Pharmacy Practice and by the Board of Directors and was and the product’s ingredients; further,
found to still be appropriate. To make information on transition of the codes readily
available.
Use of Color to Identify Drug Products (9608) This policy was reviewed in 2011 by the Council on
Source: Council on Professional Affairs Public Policy and by the Board of Directors and was found
To support the reading of drug product labels as the most to still be appropriate.
important means of identifying drug products; further,
To oppose reliance on color by health professionals Elimination of Apothecary System (8613)
and others to identify drug products; further, Source: Council on Professional Affairs
To oppose actions by manufacturers of drug products To recommend to all health professions and to the
and others to promulgate reliance on color to identify drug Pharmaceutical Manufacturers Association (PMA) [now
products. the Pharmaceutical Research and Manufacturers of America
This policy was reviewed in 2013 by the Council on (PhRMA)] that the apothecary system be eliminated in
Pharmacy Practice and by the Board of Directors and was referring to dosage quantities and strengths.
Expiration Dating of Pharmaceutical Products (9309) found to still be appropriate.
Source: House of Delegates Resolution
To support and actively promote the maximal extension of ex- Size, Color, and Shape of Drug Products (8310)
piration dates of pharmaceutical products as a means of reduc- Source: Council on Legal and Public Affairs
ing health care costs and to recommend that pharmaceutical To approve the authority of manufacturers to copy the size,
manufacturers review their procedures to accomplish this end. shape, and color of generically equivalent drug products as a
This policy was reviewed in 2011 by the Council on means of promoting better patient compliance (rational drug
Pharmacy Practice and by the Board of Directors and was therapy), but only when the source and identity of the prod-
found to still be appropriate. uct are readily ascertainable from a uniform mark or symbol
on the product.
Tamper-Evident Packaging on Topical Products (9211) This policy was reviewed in 2012 by the Council on
Source: House of Delegates Resolution Public Policy and by the Board of Directors and was found
ASHP should support the standardization and requirement to still be appropriate.
of tamper-evident packaging on all topical products, includ-
ing all dermatologicals and nonprescription products.
398 Pharmaceutical Industry: Marketing–Positions
Marketing
Identification of Prescription Drug Coverage and include mechanisms that direct consumers to a medication
Eligibility for Patient Assistance Programs (1521) adverse event reporting system (AERS); further,
Source: Council on Pharmacy Management To advocate that the Food and Drug Administration
To advocate that pharmacists or pharmacy technicians en- require an AERS reporting link in direct-to-consumer adver-
sure that the use of patient assistance programs is optimized tising material available on the Internet; further,
and documented to promote continuity of care and patient To support the development of legislation or regula-
access to needed medications; further, tion that would require nonprescription drug advertising
To advocate that patient assistance programs should to state prominently the benefits and risks associated with
incorporate the pharmacist–patient relationship, including product use that should be discussed with the consumer’s
evaluation by a pharmacist as part of comprehensive medi- pharmacist or physician.
cation management; further, This policy supersedes ASHP policy 0609.
To support the principle that medications provided
through manufacturer patient assistance programs should Regulation of Off-label Promotion and Marketing (1120)
be stored, packaged, labeled, dispensed, and recorded using Source: Council on Public Policy
systems that ensure the same level of safety as prescription- To advocate for authority for the Food and Drug Admin-
based programs that incorporate a pharmacist–patient rela- istration to regulate the promotion and dissemination of
tionship. information about off-label uses of medications by manu-
This policy supersedes ASHP policy 0603. facturers; further,
To advocate that such promotion and dissemination be
Manufacturer-Sponsored Patient Assistance Programs permitted only if manufacturers submit a supplemental new
(1420) drug application for new use within a reasonable time after
Source: Council on Pharmacy Management initial dissemination of information about off-label uses.
To encourage pharmaceutical manufacturers to extend their
patient assistance programs (PAPs) to serve the needs of Pharmaceutical Distribution Systems (1016)
both uninsured and underinsured patients; further, Source: Council on Pharmacy Management
To advocate that pharmaceutical manufacturers and To support wholesaler/distribution business models that
PAP administrators enhance access to and availability of meet the requirements of hospitals and health systems with
such programs by standardizing application criteria, pro- respect to timely delivery of products, minimizing short-term
cesses, and forms, and by automating PAP application outages and long-term product shortages, managing and re-
processes through computerized programs, including Web- sponding to product recalls, fostering product-handling and
based models; further, transaction efficiency, preserving the integrity of products as
To advocate expansion of PAPs to include high-cost they move through the supply chain, and maintaining afford-
drugs used in inpatient settings; further, able service costs.
To encourage pharmacists and pharmaceutical manu- This policy was reviewed in 2014 by the Council on
facturers to work cooperatively to ensure that essential ele- Pharmacy Management and by the Board of Directors and
ments of pharmacist patient care are included in these pro- was found to still be appropriate.
grams.
This policy supersedes ASHP policies 0404 and 9703. Restricted Drug Distribution (0714)
Direct-to-Consumer Advertising of Prescription and To affirm support for the current system of drug distribution
Nonprescription Medications (1119) in which prescribers and pharmacists exercise their profes-
Source: Council on Public Policy sional responsibilities on behalf of patients; further,
To oppose direct-to-consumer advertising unless it is educa- To acknowledge that there may be limited circum-
tional in nature about prescription drug therapies for certain stances in which constraints on the traditional drug distribu-
medical conditions and appropriately includes pharmacists tion system may be appropriate if the following principles
as a source of information; further, are met: (1) the requirements do not interfere with the con-
To oppose direct-to-consumer advertising of specific tinuity of care for the patient; (2) the requirements preserve
prescription drug products unless the following require- the pharmacist–patient relationship; (3) the requirements are
ments are met: (1) that such advertising is delayed until based on scientific evidence fully disclosed and evaluated
postmarketing surveillance data are collected and assessed, by prescribers, pharmacists, and others; (4) there is scientific
(2) that the benefits and risks of therapy are presented in consensus that the requirements are necessary and represent
an understandable format at an acceptable literacy level for the least restrictive means to achieve safe and effective pa-
the intended population, (3) that such advertising promotes tient care; (5) the costs of the product and any associated
medication safety and allows informed decisions, (4) that a product or services are identified for purposes of reimburse-
clear relationship between the medication and the disease ment, mechanisms are provided to compensate providers for
state is presented, (5) that no such advertising or market- special services, and duplicative costs are avoided; (6) all
ing information for prescription or nonprescription medica- requirements are stated in functional, objective terms so that
tion is directed toward minors, and (6) that such advertising any provider who meets the criteria may participate in the
Pharmaceutical Industry: Marketing–Positions 399
care of patients; and (7) the requirements do not interfere This policy was reviewed in 2011 by the Council on
with the professional practice of pharmacists, prescribers, Public Policy and by the Board of Directors and was found
and others; further, to still be appropriate.
To advocate that the Food and Drug Administration
(FDA) be granted the authority to consult with practicing Drug Samples (9702)
pharmacists and others when the establishment of a re- Source: Council on Legal and Public Affairs
stricted distribution system is contemplated for a drug prod- To oppose drug sampling or similar drug marketing pro-
uct; further, grams that (1) do not provide the elements of pharmaceuti-
To advocate that FDA be granted the authority to re- cal care, (2) result in poor drug control, allowing patients
quire that manufacturers disclose all of the considerations to receive improperly labeled and packaged, deteriorated,
that led to the establishment of a restricted distribution sys- outdated, and unrecorded drugs, (3) provide access to
tem for a specific product; further, prescription drugs by unauthorized, untrained personnel,
To advocate that FDA be granted the authority to re- (4) may encourage inappropriate prescribing habits, or
quire that manufacturers include in each restricted distribu- (5) may increase the cost of treatment for all patients.
tion system a mechanism that will ensure medication recon- This policy was reviewed in 2011 by the Council on
ciliation and continuity of care as patients transition from Public Policy and by the Board of Directors and was found
one level or site of care to another; further, to still be appropriate.
To advocate that FDA be granted the authority to re-
quire manufacturers to conduct a follow-up assessment of
the impact of a restricted drug distribution system.
400 Pharmaceutical Industry: Marketing–Guideline
ASHP Guidelines for Pharmacists on the

Activities of Vendors’ Representatives in
Organized Health Care Systems
For purposes of this document, vendors’ representatives are 4. Availability of vendor-contact information to profes-
defined as agents who promote products and provide infor- sionals in the setting. In some individual settings,
mation and services to health care providers on behalf of the pharmacy department provides the setting’s pro-
manufacturers and suppliers. The narrow focus of this docu- fessional staff with the information in item 3, upon
ment is on those vendors who serve and interact with settings request.
with respect to drug products, drug-related devices, and other 5. Registration while on premises. In some individual
equipment, supplies, and services purchased by pharmacies. settings, vendors’ representatives register with the
Each individual setting should develop its own spe- pharmacy department or other designated depart-
cific policies and procedures relating to the activities of ven- ment upon each visit to the setting. At such time, the
dors’ representatives. Such policies and procedures should vendors’ representatives document the time, purpose,
supplement and complement applicable federal, state, and and location of their appointments. In many settings,
local laws and regulations (for example, statutes that address during the registration process, the representative is
prescription drug-product sampling). The ASHP Guidelines provided with a dated name badge to be prominently
on Pharmacists’ Relationships with Industry, the ASHP worn along with the representative’s current vendor-
Guidelines for Selecting Pharmaceutical Manufacturers and supplied name tag (if any).
Suppliers, and setting-specific conflict-of-interest policies 6. Locations permitted. In some individual settings, re-
may be helpful in the development of policies and proce striction (if any) from patient care and pharmacy stor-
dures.1,2 The policies and procedures should be developed age and work areas in the setting are specified in the
by the setting’s pharmacy and therapeutics committee (or policies and procedures. Meetings with professional
equivalent body) and approved by higher authorities in the staff are conducted in areas convenient to staff and
setting as required. Depending on the individual setting, pol- generally in non-patient-care areas.
icies and procedures may be useful in the following areas. 7. Appointments and purposes. In some individual
settings, representatives are encouraged to schedule
1. A defined scope of applicability. The vendors’ repre- appointments with appropriate pharmacy department
sentatives to which any policies and procedures apply staff to
should be defined by the individual setting. For exam- • Provide information useful for product evalua-
ple, if the policies and procedures are applicable only tion. Representatives might be asked to include
to drug-product vendors’ representatives and not to balanced scientific literature (journal reprints,
those promoting medical–surgical supplies, packaging for example) on drug-product safety and effi-
equipment, or drug administration devices, this should cacy, as well as documentation of likely cost
be clearly stated. benefits.
2. Orientation of representatives. In some individual • Provide timely information on the vendor’s
settings, vendors’ representatives receive an orienta- products and services.
tion packet upon their initial visit to the setting. Such • Facilitate procurement and crediting transactions.
a packet might contain a copy of the setting’s poli- • Obtain and provide information necessary to
cies and procedures, a medical staff directory, and the support the setting’s formulary system.
formulary. Some settings provide a formal orientation • Facilitate informational activities for the phar-
program that includes meeting key individuals and macy staff and other health care professionals
touring the setting. with respect to the vendor’s products.
3. Directory. In some individual settings, a file of current 8. Exhibits. In some individual settings, the pharmacy
vendor-contact information is maintained in the phar- department provides opportunities for vendors’ rep-
macy. A form for recording such information might resentatives to distribute informational material by
include the following: arranging for organized, scheduled exhibits. Policies
• The vendor’s name and address; and procedures about the times, places, content, and
• The name, address, telephone number, and an- conduct of such events are established.
swering service number (if any), and drug-prod- 9. Dissemination of promotional materials. In some indi-
uct assignment (purview) of each representative; vidual settings, there are policies and procedures about
• The name, address, and telephone number of the the dissemination (by vendors’ representatives) of in-
representative’s manager; formation on formulary and nonformulary products,
• The names, telephone numbers, and emergency including the designation of appropriate categories
telephone numbers of the vendor’s directors of recipients of the information (e.g., attending physi-
of distribution, sales, and product information cians, department chairmen, house staff physicians).
(titles may vary); and Representatives may be asked to promptly provide the
• The names and telephone numbers of the pharmacy department with copies of all informational
vendor’s medical director and research director and promotional materials disseminated in the setting.
(titles may vary). The Food and Drug Administration (FDA) prohibits
Pharmaceutical Industry: Marketing–Guideline 401
the advertising and promotion of drug products for 2. American Society of Hospital Pharmacists. ASHP
uses not reflected in FDA-approved product labeling guidelines for selecting pharmaceutical manufacturers
(“unlabeled uses”).3 Pharmacists and other health care and suppliers. Am J Hosp Pharm. 1991; 48:523–4.
professionals should be aware of these laws and regu- 3. American Society of Hospital Pharmacists. ASHP
lations when evaluating the content of promotional statement on the use of medications for unlabeled
materials. uses. Am J Hosp Pharm. 1992; 49:927–8.
10. Samples. In some individual settings, there are poli- 4. American Society of Hospital Pharmacists. ASHP
cies and procedures with respect to product samples. guidelines: minimum standard for pharmacies in insti-
ASHP urges that the use of drug samples within the tutions. Am J Hosp Pharm. 1985; 42:372–5.
institution be eliminated to the extent possible.4,5 5. Greenberg RB. The Prescription Drug Marketing Act
11. Noncompliance. In some individual settings, policies of 1987. Am J Hosp Pharm. 1988; 45:2118–26.
and procedures exist to address noncompliance with 6. American Society of Hospital Pharmacists. ASHP guide-
the policies and procedures by either vendors’ repre- lines for pharmaceutical research in organized health-
sentatives or professional staff. care settings. Am J Hosp Pharm. 1989; 46:129–30.
Each setting should have policies and procedures

concerning research to be conducted on its premises.
This guideline was reviewed in 1998 by the Council on Professional
Pharmacists and vendors’ representatives should clearly
Affairs and by the ASHP Board of Directors and was found to still
differentiate research from sales and promotional ac-
be appropriate.
tivities, applying appropriate policies and procedures ac-
cordingly.6 Generally, scientific research involving drug
Approved by the ASHP Board of Directors, November 17, 1993.
products is coordinated through research departments of
Developed by the Council on Professional Affairs.
product manufacturers rather than through sales and pro-
motional representatives.
Copyright © 1994, American Society of Hospital Pharmacists, Inc.
References
1. American Society of Hospital Pharmacists. ASHP Society of Hospital Pharmacists. ASHP guidelines for pharmacists
guidelines on pharmacists’ relationships with industry. on the activities of vendors’ representatives in organized health care
Am J Hosp Pharm. 1992; 49:154. systems. Am J Hosp Pharm. 1994; 51:520–1.
Pharmacy Management
404 Pharmacy Management–Positions
Pharmacy Management
Disposition of Illicit Substances (1522) Workload Monitoring and Reporting (0901)

Source: Council on Pharmacy Management Source: House of Delegates Resolution
To advocate that healthcare organizations be required to To strongly discourage the use of pharmacy workload and
develop procedures for the disposition of illicit substances productivity measurement systems (“pharmacy benchmark-
brought into a facility that ensure compliance with appli- ing systems”) that are based solely upon dispensing func-
cable laws and accreditation standards; further, tions (e.g., doses dispensed or billed) or a variant of pa-
To advocate that healthcare organizations be required tient days, because such measures do not accurately assess
to include pharmacy leaders in formulating such procedures. pharmacy workload, staffing effectiveness, clinical practice
contributions to patient care, or impacts on costs of care,
Pharmacy Department Business Partnerships (1416) and therefore these measurement systems are not valid and
Source: Council on Pharmacy Management should not be used; further,
To recognize that a key objective of pharmacy departments To advocate the development and implementation of
is to provide comprehensive medication management across pharmacy benchmarking systems that accurately assess the
the continuum of patient care, and that pharmacy leaders impact of pharmacy services on patient outcomes and total
should proactively evaluate potential business partnerships costs of care; further,
against this objective; further, To define pharmacy workload as all activities related
To recognize that hospitals and health-system phar- to providing pharmacy patient care services; further,
macy leaders must ensure that business partners meet all ap- To continue communications with health-system ad-
plicable patient safety and accountability standards; further, ministrators, consulting firms, and professional associations
To provide education and tools for pharmacy leaders regarding the value of pharmacists’ services and the impor-
to aid in the evaluation of and development of business part- tance of using valid, comprehensive, and evidence-based
nerships; further, measures of pharmacy workload and productivity; further,
To educate health-system administrators on the impor- To encourage practitioners and vendors to develop and
tance of pharmacy leadership in evaluating and developing use a standard protocol for collecting and reporting phar-
pharmacy-related business partnerships; further, macy workload data and patient outcomes; further,
To encourage health-system pharmacy leaders to con- To advocate to health-system administrators, con-
sider evolving health care financing systems when evaluat- sulting firms, and vendors of performance-measurement
ing and developing business partnerships. services firms the development and implementation of
pharmacy benchmarking systems that accurately assess the
Integration of Pharmacy Services in Multifacility Health impact of pharmacy services on patient outcomes and total
Systems (1417) costs of care.
Source: Council on Pharmacy Management This policy was reviewed in 2013 by the Council on
To advocate that pharmacists are responsible for organiza- Pharmacy Management and by the Board of Directors and
tional efforts to standardize and integrate pharmacy services was found to still be appropriate.
throughout the entire pharmacy enterprise in multifacility
health systems and integrated delivery networks; further, Pharmacist Leadership of the Pharmacy Department
To educate health-system administrators about the (0918)
importance of pharmacy leadership in setting system-wide Source: Council on Pharmacy Management
policy regarding the safe and effective use of medications; To affirm the importance of an organizational structure in
further, hospitals and health systems that places administrative, clin-
To advocate for the regulations and resources needed ical, and operational responsibility for the pharmacy depart-
to support efforts to achieve optimal patient health outcomes ment under a pharmacist leader; further,
in multifacility organizations. To affirm the role of the pharmacist leader in oversight
This policy supersedes ASHP policy 1210. and supervision of all pharmacy personnel; further,
To recognize the supporting role of nonpharmacists in
Proliferation of Accreditation Organizations (1303) leadership and management roles within pharmacy depart-
Source: Council on Pharmacy Management ments.
To advocate that health care accreditation organizations in- This policy was reviewed in 2013 by the Council on
clude providers and patients in their accreditation and stan- Pharmacy Management and by the Board of Directors and
dards development processes; further, was found to still be appropriate.
To encourage health care accreditation organizations
to adopt consistent standards for the medication-use process,
based on established principles of patient safety and quality
of care; further,
To encourage hospitals and health systems to include
pharmacy practice leaders in decisions about seeking recog-
nition by specific accreditation organizations.
Pharmacy Management–Positions 405
Pharmacy Staff Fatigue and Medication Errors (0504)

To encourage pharmacy managers to consider workload
fatigue, length of shifts, and similar performance-altering
factors when scheduling pharmacy staff, in order to ensure
safe pharmacy practices; further,
To oppose state or federal laws or regulations that
mandate or restrict work hours for pharmacy staff; further,
To support research on the effects of shift length, fa-
tigue, and other factors on the safe practice of pharmacy.
406 Pharmacy Management–Statements
ASHP Statement on the Roles and Responsibilities

of the Pharmacy Executive
Position by creating organizational parity between the pharmacy ex-
ecutive and other chief officers (e.g., chief nursing, medical,
The American Society of Health-System Pharmacists and information officers).2 When the pharmacy executive
(ASHP) believes that complex hospitals and health systems works collaboratively with others at this executive level, the
benefit from having a pharmacy executive responsible for pharmacy department is better positioned to effectively con-
the strategic planning, design, operation, and improvement tribute to the organization’s strategic initiatives and address
of their organization’s medication management system. This system-wide issues regarding medications and medication
individual (sometimes referred to as the “chief pharmacy of- management.
ficer” but hereafter “the pharmacy executive”) must be prop-
erly positioned within the organization to ensure the best Qualifications and Responsibilities
utilization of his or her expertise in all decisions regarding of the Pharmacy Executive
medication management. To promote effective communica-
tion, collaboration, and teamwork with peers, the pharmacy The pharmacy executive is a professionally competent, le-
executive should gally qualified pharmacist. He or she must be thoroughly
knowledgeable about and have experience in hospital phar-
• Have a title internally consistent with others reporting macy practice and management. Additional qualifications
at that organizational level, might include completion of a pharmacy residency program
• Report directly to the organization’s principal execu- accredited by ASHP, an advanced management degree (e.g.,
tive (e.g., chief executive officer [CEO], chief operat- M.B.A., M.H.A.), or an administrative specialty residency.
ing officer [COO]), What distinguishes the pharmacy executive from the
• Be involved in the organization’s strategic planning established director of pharmacy position is a deeper knowl-
regarding all components of the medication manage- edge of the organization’s operations as well as a greater
ment process across the continuum of care, degree of involvement in the organization’s strategic plan-
• Participate in regularly scheduled healthcare execu- ning and decision-making processes. The pharmacy execu-
tive-level meetings (e.g., CEO, COO, chief financial tive provides the organization with pharmacy’s unique clini-
officer [CFO], chief medical officer [CMO], and chief cal and business perspectives in discussions and decisions
nursing officer [CNO]), related to changes in the medication management system.3
• Be a member of the medical executive committee (or He or she has experience leading evidence-based clinical
its equivalent), and decision-making about drug use, controlling pharmaceuti-
• Engage in regular, direct communication with health cal expenses while maximizing patient benefit through the
system leadership and the board of directors about formulary system. The pharmacy executive has in-depth
medication management system performance. knowledge of the pharmaceutical supply chain, clinical
therapeutics, physician prescribing habits, medication man-
Background agement systems, medication-use policy, and the technol-
ogy used to deliver and support patient care and about how
Hospitals and health systems are complex organizations. those issues affect the overall success of the organization.
Executive-level decisions that affect the medication man- The pharmacy executive understands the relationships be-
agement system are made at a rapid pace, often with pro- tween third-party requirements, coding, documentation, bill-
found implications for patient care, patient safety, and the ing equations, pricing updates, and organizational resources
health system’s fiscal well-being. The pharmacy executive and can provide quality assurance for all these functions,
must be properly positioned within an organization to ensure improving financial performance.4
the best utilization of his or her expertise in decision-making The pharmacy executive’s responsibilities include but
that affects the policies, procedures, and systems that support are not limited to the following: strategic planning; design-
safe, effective, and efficient medication management. The ing, managing, measuring and improving the medication
quality and timeliness of information exchange improves management system; ensuring quality outcomes through
significantly when pharmacy leadership reports directly to performance-improvement activities; leading drug-utili-
the principal executive rather than through multiple layers of zation efforts; optimizing use of information systems and
management. Pharmacy leaders can more actively engage in technology; managing the pharmaceutical supply chain,
critical decision-making and will be more effective in help- pharmacy department financial operations, and human re-
ing the health system anticipate and address rapid change. sources; ensuring compliance with regulatory and accredita-
Significant changes in pharmacy practice, healthcare, tion requirements; fulfilling the organization’s research and
and health-system management over the past 20 years have educational missions; and providing institutional representa-
dramatically transformed the traditional role of the phar- tion and leadership.5,8 The pharmacy executive fulfills these
macy director.1 More widespread use of the title “chief phar- responsibilities through his or her own actions, proper del-
macy officer” was first proposed in 2000 in an attempt to egation to competent individuals on his or her staff, and col-
enhance the contribution pharmacy makes to patient care laborative efforts with other healthcare professionals.
Pharmacy Management–Statements 407
Strategic Planning. The pharmacy executive assesses the Medication System Management and Improvement. The
ever-changing healthcare environment for emerging trends pharmacy executive is responsible for overseeing the de-
that will influence the pharmacy enterprise. He or she iden- sign, implementation, and management of a safe and effec-
tifies opportunities to leverage pharmacy expertise to im- tive medication management system. He or she ensures that
prove quality, safety, patient experience, access across the systems are developed and improved based on evidence and
continuum of care and the economic performance of the best practices, operate effectively and efficiently across the
organization. It is also the pharmacy executive’s responsibil- continuum of care, and are continuously evaluated and im-
ity to continually assess healthcare related trends and dis- proved using contemporary quality-improvement methods.
coveries to ensure the value of pharmacy and pharmacists The pharmacy executive provides leadership at the organi-
is advocated for and advanced in overall efforts to improve zational level to ensure that pharmacists are positioned to
patient care.6,7 improve the quality, safety and efficiency of medication
management throughout the health system. The pharmacy
Optimizing Medication Management and Advancing executive (or his or her designee) should be a member of
Pharmacy Practice. The pharmacy executive is responsible all of the institution’s key committees responsible for per-
for ensuring that pharmacists participate as the interdis- formance-improvement activities related to medication
ciplinary team members who are responsible for patients’ management and patient safety. The pharmacy executive
medication-related outcomes. He or she ensures that phar- and his or her staff must be intimately involved in all im-
macy is responsible for developing and ensuring compliance provement initiatives involving medication management.
with evidence-based prescribing criteria that support effec- The pharmacy executive should give particular attention to
tive, safe and fiscally responsible treatment. The pharmacy patients in high-risk areas (as identified by organizations
executive will ensure collaboration outside of the walls of such as the Centers for Medicare and Medicaid Services, the
the institution, fostering pharmacist communication with pa- Joint Commission and other accreditation organizations) to
tients and outpatient providers following discharge to ensure ensure that pharmacy services meet patient care needs and
continuity of medication therapy and monitoring of patient that drug therapy is as safe, effective, and economical as
outcomes. With the expanded role of the pharmacist in drug possible. Safe handling of hazardous medications through-
therapy management, he or she is responsible for the profes- out the medication process (preparation, administration, and
sional development of the pharmacy team in order to support disposal) is assured. The pharmacy executive is responsible
this advanced role. for developing plans for the continued operation of medica-
tion management systems and for the provision of pharma-
Advancing the Application of Information Technology in ceutical services during emergencies and disasters.
the Medication Management System. The pharmacy execu-
tive provides leadership at the organizational level regard- Quality Outcomes. With a greater percentage of reimburse-
ing planning, purchasing, implementing and maintaining ment being tied to quality outcomes, the pharmacy executive
information systems that support patient care. He or she is is responsible for leveraging pharmacy expertise in support
responsible for the adoption of a long-term perspective and of value based purchasing, including leading core measures
commits themselves to achieving the patient-safety innova- initiatives involving medication therapy, playing an active
tions made feasible by Electronic Health Records (EHRs) role in reducing readmissions, and owning the process for
and other clinical applications: Computerized provider order medication related customer satisfaction indicators. He
entry (CPOE), clinical decision support (CDS), automated or she will take steps to ensure that pharmacists in the de-
medication reconciliation, bar-coded medication administra- partment are highly skilled at communicating with patients
tion (BCMA), medication surveillance, telepharmacy, and through assessment of individual pharmacist competency in
smart infusion pumps. The pharmacy executive will leverage this area and implementation of professional development
technology to advance pharmacist clinical practice through plans. The pharmacy executive will identify and implement
implementation of processes that allow pharmacist work specific ways that the pharmacy enterprise can contribute
load to be more heavily devoted to patient-care activities to the patient experience related to the care they receive
and ensuring that the EHR supports drug therapy manage- at admission, during the stay and at discharge. He or she
ment services. He or she will leverage technology capabili- takes a leadership role in program development to reduce
ties to improve the safety of medications, specifically those drug-related hospital readmissions through patient educa-
identified as high-risk. The pharmacy executive will utilize tion about the appropriate management of medications,
technology enabled medication management data to capture embedding pharmacy in the care transitions process and
and report pharmacy metrics and to drive improvements in implementing programs such as medication history techni-
patient care and outcomes. He or she will ensure CDS sys- cians and bedside delivery of discharge prescriptions. The
tems support processes for the enhancement of medication- pharmacy leader also commits to continuously improve the
related decisions and actions with pertinent, organized clini- organizations medication reconciliation process at all care
cal knowledge and patient information to improve health and transitions.
healthcare delivery. The pharmacy executive will ensure that
appropriately trained and qualified pharmacy team mem- Drug-Utilization Management. The pharmacy executive
bers are available to safely develop, implement and main- collaborates with peers to develop drug-utilization and for-
tain medication related technology. Use of technology to mulary initiatives that optimize therapeutic outcomes, reduce
increase the safety and efficiency of medication distribution, the risk of drug-related problems, and ensure the use of cost-
including automated dispensing units (ADU), carousels, and effective pharmacotherapy throughout the health system.
compounding automation should also be leveraged.8 The pharmacy executive ensures there is pharmacist rep-
resentation on the pharmacy and therapeutics committee(s) in the development of student and resident standards to en-
of the health system as an active voting participant. He or sure that education and training reflects the needs of patients
she identifies inappropriate utilization and leads efforts to and health systems, and to further expand the capability of
modify practices to improve medication management. The the pharmacy enterprise. The pharmacy executive ensures
pharmacy executive (or a designee) is a member and active effective and timely staff recruitment, orientation, training,
participant of the antimicrobial stewardship committee, anti- education, mentoring, career development, performance re-
coagulation, pain and other specialized teams to ensure that view, and retention efforts.
stewardship principles are applied to the prescribing, dis-
pensing, and administration of these agents. Regulatory and Accreditation Compliance. The pharmacy
executive ensures continued compliance with all national,
Supply Chain Management. The pharmacy executive is state, and local regulations related to medications and their
responsible for oversight of all pharmaceutical contract- management. He or she is responsible for the implemen-
ing, procurement, receiving, security, inventory control, tation of Board of Pharmacy, Drug Enforcement Agency,
diversion prevention, and distribution policies across the Centers for Medicare and Medicare Services, The Joint
continuum, including outsourced sterile products, alternate Commission and other medication management accredita-
distribution channels utilized during drug shortages, reverse tion standards; for maintaining ASHP accreditation, where
distribution and other methods of pharmaceutical waste dis- applicable (e.g., residency and technician training); and for
posal. He or she ensures that the methods used to contract the implementation of best practices. When applicable, the
and obtain products are safe, cost-effective, and timely. The pharmacy executive is responsible for compliance oversight
pharmacy executive is also responsible for emergency pre- of the 340B program for the covered entity, all covered out-
paredness of the supply chain, including strategies to ensure patient departments and contract pharmacy arrangements.
ongoing safe and effective patient care during drug product
shortages through the collaborative development of alterna- Research and Educational Missions. The pharmacy ex-
tives to treatment and restricted use guidelines. ecutive has an integral role in supporting the organization’s
research and educational missions by overseeing investiga-
Financial Management. The pharmacy executive manages tional drug services, fostering staff and resident research,
the health-system pharmacy’s financial performance within participation in organizational grant funding applications
the context of the broader health system. He or she develops and managing student and residency educational programs.
budgets aligned with organizational and departmental ob-
jectives and monitors financial performance appropriately, Institutional Representation and Leadership. The phar-
performing financial audits and analysis as needed to ensure macy executive demonstrates the personal leadership quali-
accurate, appropriate, and timely recording and classifica- ties and business acumen essential to operate effectively
tion of actual revenue capture and expenses. The pharmacy within the health system and to advance the profession and
executive evaluates medication expenditure patterns and re- practice of pharmacy. He or she serves as the primary phar-
imbursement trends, including the potential development of macy representative on relevant committees of the organi-
value-based approaches to pharmaceutical reimbursement. zation’s leaders to ensure that medication management sys-
He or she seeks opportunities to implement medication re- tems and pharmaceutical services meet the needs of patients
lated services that can improve the financial health of the and health care providers across the continuum of care. The
organization, such as retail pharmacy and ambulatory infu- pharmacy executive assumes a leadership role within the
sion. He or she ensures that the pharmacy department has the profession through active participation in local, state, and
expertise to manage the clinical and financial implications national professional associations.
of specialty pharmaceutical products. The pharmacy execu-
tive may be called upon to provide guidance in areas outside Conclusion
of the traditional pharmacy arena, including management of
drug expenditures in the self-insured employee population Complex hospital and health systems should have a phar-
and in payer shared risk arrangements that include medica- macy executive responsible for the strategic planning, de-
tion management incentives. sign, operation, and improvement of the organization’s
medication management system. This individual must be
Managing the Pharmacy Workforce. The pharmacy execu- properly positioned within the organization to ensure the
tive manages the health-system pharmacy’s workforce ef- best utilization of his or her expertise in all decisions regard-
forts. These efforts include determining the appropriate num- ing medication management.
ber, type and qualification of staff required to meet patient
care needs, satisfy regulatory and accrediting requirements,
achieve the organization’s mission and advance pharmacy References
practice. In order to accomplish this task, he or she imple-
ments standards and development programs to advance the 1. Nold EG, Sander WT. Role of the director of phar-
use of pharmacy technicians within the organization, allow- macy: the first six months. Am J Health-Syst Pharm.
ing the redeployment of pharmacists’ time to drug therapy 2004; 61:2297–310.
management activities. The pharmacy executive works with 2. Godwin HN. Achieving best practices in health-sys-
state and federal regulatory agencies to support this expan- tem pharmacy: eliminating the ‘practice gap.’ Am J
sion in the role of the pharmacy technician. He or she devel- Health-Syst Pharm. 2000; 57:2212–3.
ops programs that fully leverage the use of students and resi-
dents within the organization, which includes participating
3. Anderson RW. Health-system pharmacy: new practice
framework and leadership model. Am J Health-Syst Approved by the ASHP Board of Directors on April 10, 2015,
Pharm. 2002; 59:1163–72. and by the ASHP House of Delegates on June 7, 2015. Developed
4. Mitchell CL, Anderson ER, Braun L. Billing for in- through the ASHP Council on Pharmacy Management. This state-
patient hospital care. Am J Health-Syst Pharm. 2003; ment supersedes a previous version dated June 10, 2008.
60(suppl 6):8–11.
5. Ivey MF. Rationale for having a chief pharmacy of- Karl Kappeler, M.S., FASHP; Michael Nnadi, Pharm.D, MHS; Sam
ficer in a health care organization. Am J Health-Syst Calabrese, M.B.A., FASHP; Debra Cowan, Pharm.D., FASHP;
Pharm. 2005; 62:975–8. Bonnie Kirshenbaum, M.S., FASHP, FCSHP; John Lewin, Pharm.D.,
6. The consensus of the Pharmacy Practice Model M.B.A.; Christine Marchese, Pharm.D.; Tricia Meyer, Pharm.D.,
Summit. Am J Health-Syst Pharm. 2011; 68:1148–52; M.S., FASHP; Brandon Ordway, Pharm.D., M.S.; Roger Woolf,
doi:10.2146/ajhp110060. Pharm.D.; Rusol Karralli, Pharm.D., M.S.; and Kelly Sennett, B.S.,
7. CPO Perspectives Scott Knoer; Stewardship of the are gratefully acknowledged for revising this statement.
pharmacy enterprise Am J Health-Syst Pharm. 2014;
71:1204–9; doi:10.2146/ajhp140170. Copyright © 2015. American Society of Health-System Pharmacists,
8. CPO Perspectives Thomas W. Woller, Scott Knoer, Inc. All rights reserved.
and Rowell Daniels; Strategic considerations for cen-
tralization of services across the pharmacy enterprise. Note: This statement had not been published in the American Journal
Am J Health-Syst Pharm. 2015; 72:74–7; doi:10.2146/ of Health-System Pharmacy (AJHP) when ASHP Best Practices
ajhp140401. 2015–2016 went to press. Some minor editorial differences may ex-
ist between this document and the official one that will eventually
appear in AJHP and subsequent editions of this publication.
ASHP Statement on Standards-Based Pharmacy

Practice in Hospitals and Health Systems
Position ASHP best practices reinforce health-system pharma-
cists’ established roles in health care and encourage develop-
Pharmacy practice leaders in hospitals and health systems ment of responsibilities that answer the growing need and
have a distinguished history of advancing health-system public demand for expanded involvement of pharmacists in
pharmacy practice beyond the minimum required by law, patient care. ASHP best practices are based on professional
regulation, and accreditation. The American Society of and scientific literature and are developed with input from
Health-System Pharmacists (ASHP) supports those efforts ASHP members, the public, regulatory bodies, other profes-
by developing and disseminating a comprehensive body of sional associations, and representatives of other health care
evidence-based, peer-reviewed descriptions of best practices disciplines. Peer groups of ASHP expert members system-
in health-system pharmacy. ASHP believes that pharmacists atically review ASHP best practices and compare them with
who practice in hospitals and health systems (“health-system the existing literature, the changing expectations of society,
pharmacists”) and pharmacy leaders in health systems can and changes in the professional and ethical challenges faced
continuously improve the delivery of patient care by regu- by health-system pharmacists. A compilation of these docu-
larly assessing compliance with ASHP best practices, iden- ments is published annually as Best Practices for Hospital
tifying gaps in practice, establishing practice improvement and Health-System Pharmacy and made available to the
priorities appropriate for their unique circumstances, and public (www.ashp.org/bestpractices).
working to close the targeted gaps. Most ASHP best practices represent the professional
beliefs and aspirations of pharmacists practicing in health
systems, based on evidence and expert opinion. Only three
Purpose ASHP guidelines describe a minimum level of practice that
all hospital pharmacy departments should consistently pro-
The purpose of this statement is to promote understanding of vide; these guidelines are designated as ASHP minimum
how health-system pharmacists use ASHP best practices to standards.3-5 Institutions that offer ASHP-accredited resi-
develop and promote in health systems a standard of practice dencies are required to meet ASHP best practices to ensure
that exceeds what is required by law, regulation, or accredi- the quality of the educational experience.
tation. ASHP best practices represent a commitment by ASHP
members to advancing the standard of pharmacy practice.
Standards-Based Pharmacy Practice ASHP believes that all health-system pharmacists have a
role to play in raising health-system pharmacy practice to
A standard is “a statement that defines the performance ex- a level consistent with the best practices that have been de-
pectations, structures, or processes that must be in place for veloped and have gained acceptance by a peer-reviewed,
an organization to provide safe and high quality care, treat- consensus-based process. Practicing pharmacists and phar-
ment, and service.”1 In health care, practice standards serve macy leaders in health systems should use their professional
as guideposts for a profession and as a way of communicat- judgment to regularly assess compliance with ASHP best
ing to peers, patients, policymakers, other professionals, and practices, identify gaps in practice in their settings, establish
the public the roles and responsibilities of members of the practice improvement priorities appropriate for their unique
profession. Practice standards also provide a benchmark for circumstances, and work to close those practice gaps to en-
evaluating the quality of services and patient care. sure continuous improvement in the delivery of patient care.
Health-system pharmacists, like other health care
professionals, practice under a number of mandated stan- Conclusion
dards. These standards include state board of pharmacy
regulations, public health requirements, Drug Enforcement Health-system pharmacy practice leaders have a long tra-
Administration regulations, Joint Commission accreditation dition of striving to advance practice beyond the minimum
standards, Centers for Medicare and Medicaid Services con- required by law, regulation, and accreditation. ASHP best
ditions of participation, and the standards of other accredit- practices embody those aspirations and provide health-sys-
ing bodies and professional associations. Individual health tem pharmacists with a means to continuously improve the
care organizations also develop their own interdisciplinary delivery of patient care.
practice policies and standards of care related to medication
use, with health-system pharmacists serving as key partici-
pants in their development. References
ASHP members have invested decades of effort in de-
veloping and maintaining an extensive body of policy po- 1. Comprehensive accreditation manual for hospitals.
sitions, statements, and guidelines (hereinafter “ASHP best Oakbrook Terrace, IL: Joint Commission; 2007:GL-
practices”) that serve as a guide for effective, high-quality 22.
pharmacy practice in hospitals and health systems.2 This 2. Zellmer WA. Overview of the history of hospital
comprehensive set of policies is unique in pharmacy. pharmacy in the United States. In: Brown TR, ed.
Handbook of institutional pharmacy practice. 4th ed.
Bethesda, MD: American Society of Health-System Scott Mark, Pharm.D., M.S., M.Ed., CHE, FASHP, FABC, is grate-
Pharmacists; 2006:19–32. fully acknowledged for drafting this statement.
ASHP guidelines: minimum standard for pharmacies Copyright © 2009, American Society of Health-System Pharmacists,
in hospitals. Am J Health-Syst Pharm. 1995; 52:2711– Inc. All rights reserved.
7.
ASHP guidelines: minimum standards for home care The bibliographic citation for this document is as follows: American
pharmacies. Am J Health-Syst Pharm. 1999; 56:629– Society of Health-System Pharmacists. ASHP statement on stan-
38. dards-based pharmacy practice in hospitals and health systems. Am
5. American Society of Health-System Pharmacists. J Health-Syst Pharm. 2009; 66:409–10.
ASHP guidelines: minimum standard for pharmaceu-
tical services in ambulatory care. Am J Health-Syst
Pharm. 1999; 56:1744–53.
Developed through the ASHP Council on Pharmacy Management

and approved by the ASHP Board of Directors on March 7, 2008,
and by the ASHP House of Delegates on June 10, 2008.
412 Pharmacy Management–Guidelines
ASHP Guidelines on Medication Cost Management

Strategies for Hospitals and Health Systems
Because medication costs comprise the majority of health- Trends in Medication Expenditures
system pharmacy budgets and continue to increase faster
than other health care expenditures,1 drug costs are a con- Senior hospital administrators have recognized the impor-
stant target for cost containment initiatives. The purpose of tance of drug costs to the fiscal status of health systems. For
these guidelines is to provide guidance on medication-cost- example, a health care consultancy reported that in 1996,
management strategies. “managing hospital drug utilization and expenditures” was
These guidelines recommend techniques to manage not ranked in the top 20 concerns for hospital CEOs.4 When
drug costs in hospitals and health systems. The guidelines the survey was repeated in 2000; however, hospital CEOs
focus on drug use in inpatient settings and hospital clinics, ranked drug costs as their seventh most important concern.
where health-system pharmacies typically have responsibil- The 2000 survey also reported that among hospitals’ greatest
ity for purchasing and distributing drugs. Strategies for other financial challenges, drug and technology costs were second
settings, such as managed care and ambulatory care settings, only to decreased reimbursement, and hospital CEOs said
and strategies for revenue optimization are beyond the scope that drugs offered the single greatest opportunity for cost
of this document. Although revenue optimization and medi- savings.4 Although somewhat dated, these data illustrate that
cation cost management are complementary approaches to drug-expenditure management presents health systems with
improving the financial performance of pharmacy depart- an important challenge that is recognized by senior hospital
ments, revenue optimization is best addressed through litera- administration.
ture specific to that topic2,3 and is not extensively reviewed Four primary factors drive growth in overall drug ex-
in this document. penditures: price, utilization, mix, and innovation.1
These guidelines examine methods for nonlabor phar- Price inflation is an increase in the unit price of exist-
maceutical cost containment, focusing primarily on vari- ing medications. Utilization is an increase in use of a drug,
able costs (costs dependent on patient volume) and direct such as an increase in number of users, days of therapy, or
drug costs. Fixed and indirect costs, such as labor to pre- dose per day of therapy. Mix changes when newer, more ex-
pare or administer medication, nonpharmaceutical materi- pensive therapies are used in place of older, less expensive
als, and overhead, are also beyond the scope of these guide- but equally effective drugs. Finally, a blend of the utilization
lines. There is also not an attempt to consider the impact of and mix factors increases drug expenditures when expen-
drug costs and drug-cost-management strategies on other sive, new medications become available to treat conditions
hospital departments (e.g., laboratory, respiratory care) or previously untreatable with drug therapy (i.e., innovative
on the total health care costs once the patient leaves the therapy).
acute care setting. Although not discussed here, these shifts The United States spent over $250 billion dollars on
in drug costs are important to consider as drug therapies prescription drugs in 2005, but total drug costs represent a
influence other health care costs, and pharmacists should relatively small portion of total U.S. health care spending
lead efforts to promote the value medications provide (approximately 11%).5 However, double-digit increases in
across the hospital and health care system. prescription drug expenditures have been common (e.g.,
A broad range of drug-cost-management strate- 15% in 2000, 18% in 2001, 12% in 2002, 11% in 2003, and
gies exist throughout hospitals and health systems. Some 9% in 2004).1,4,6 The rate of drug-expenditure growth has
approaches are relatively straightforward and can be frequently been higher than inflation, increases in wages,
implemented within the pharmacy. Other approaches and other health care spending, including spending for hos-
are more complex and require high-level strategic plan- pitals, physician services, and total health care expenditures.
ning and extensive collaboration throughout the hos- However, with the exception of 26% growth in 2001, the re-
pital. Successful drug cost management requires sys- cent rate of growth in hospital drug expenditures has been
tematic attention to and integration of both approaches. less than the growth of total drug expenditures. Hospital drug
Because of the different nature of various drug-cost- expenditures grew 4.9% in 2000, 26% in 2001, 9.7% in 2002,
management activities, these guidelines present information 6.3% in 2003, 7.9% in 2004, and 5.7% in 2005.1,5–7 However,
at different levels of complexity appropriate to the approach the rate of growth in clinic drug expenditures has consistently
being described. exceeded the growth of total drug expenditures. Clinic drug
When selecting and implementing drug-cost-manage- expenditures grew 24.6% in 2000, 23% in 2001, 21.3% in
ment strategies, it is essential that pharmacists remain mind- 2002, 22.2% in 2003, 13.5% in 2004, and 12.4% in 2005.1,5,7
ful of patient safety and the quality of patient care. While the rate of increase in prescription drug expendi-
Drug-cost-containment initiatives must never compro- tures moderated somewhat between 2004 and 2006, drug-
mise the department’s ability to provide the best possible expenditure growth remains substantial. Long-range fore-
care to patients. In many cases, it is prudent and necessary to casts suggest that the rate of increase in total prescription
monitor and evaluate the safety and outcomes of drug-cost- drug expenditures will continue to exceed the rate of increase
management projects. Fortunately, many drug-cost-contain- for total health care expenditures through 2014. Because
ment strategies have little or no potential for detrimental drug expenditures are the largest component of every health-
effects on patient care, and efforts to improve the quality system pharmacy’s operating budget and often a meaningful
of drug use often coincide with cost-containment initiatives. portion of the entire hospital operating budget, drug expenses
Pharmacy Management–Guidelines 413
attract significant attention from hospital leaders. For these Table 1.
reasons, it is apparent that drug-expenditure-management Steps for Developing Annual Drug Budget7
will remain an area of focus and responsibility for health- Collect and review data (e.g., drug purchase data, drug
system pharmacists for the foreseeable future.8 utilization data, workload and productivity data, other
financial statements).
Systematic Approach to Medication- Develop budget for high-priority agents (top 50–60 drugs).
Identify relevant new drugs and build new agent budget.
Cost-Management Measures Budget for nonformulary drugs and lower-priority drugs.
Establish a drug cost containment plan (identify drugs going
A systematic approach to planning and prioritizing specific off patent, opportunities for therapeutic interchange or
drug cost management strategies is essential when imple- protocol development).
menting initiatives that will influence drug expenditures in Finalize and present the total drug budget.
a health system. Annual financial planning (i.e., budgeting) Continue the budgeting process throughout the year
is the most common planning approach, and specific drug- through constant vigilance and monitoring of drug use.
cost-management strategies should be considered a part of
the budgeting process. However, longer-term strategic and
programmatic planning activities also have an important role Pareto Principle, or 80/20 rule, applies to drug budgeting and
in managing drug expenditures. states that in nearly all cases, a few vital factors are important
A systematic approach to drug-cost containment re- and many are trivial. A relatively small number of drugs (50–
quires specific and detailed data on both health-system drug 60) typically account for 80% of most hospital drug budgets.
purchases and actual drug-use patterns. Data must underlie Therefore, budgeting and cost-containment efforts should
all types of planning to manage medication expenditures. focus on those drugs, and the cost-management plan should
Systems should be established to have ready access to the especially concentrate on those top drugs for which it is fea-
data and continually review and monitor these data. sible to influence prescribing patterns. Much of this docu-
It is essential to interact and collaborate consistently ment focuses on the need to develop a cost-containment plan
with physician leaders from various specialties to success- after initial estimates of drug costs are completed (Table 1).
fully plan, prioritize, and implement medication-cost man- Medication-cost-management projects should be care-
agement efforts. Physician involvement must be sought fully selected and prioritized as part of an ongoing financial
during the annual financial planning process and when do- planning process. Because drug-cost containment strategies
ing strategic or programmatic planning related to drug ex- must be customized to each health system’s unique charac-
penditures. Appropriate physician representatives must also teristics, a global assessment of the pharmacy department
be engaged in specific drug-cost-management initiatives. and the hospital must be conducted to identify opportunities
for drug-cost-management. This assessment must go beyond
During the annual financial planning process, physicians can
a qualitative assessment of opportunities and must include
provide important information related to drug costs, such as
retrieval and analysis of both drug purchase and drug-utili-
anticipated use of key drugs in the pipeline, programmatic
zation data. Pharmacy departments may need to obtain and
or new service implementation, anticipated recruitment of
develop resources, such as personnel and software, to ana-
specialists who may require high-cost agents, projections for
lyze these data.
use of high-priority drugs, and insights for drug cost con-
Despite the need to customize the strategy and tactics
tainment. Pharmacy leaders can also use this opportunity to
to fit the needs of different hospitals and health systems, a
update physicians on the pharmacy department’s recent ac-
systematic approach to identifying, prioritizing, and imple-
complishments and goals for the future.
menting medication-cost containment initiatives is neces-
sary and can be applied in any setting. A clearly defined list
Drug Budgeting. Although a complete discussion of the of cost-containment targets should be established during
drug-budgeting process is beyond the scope of this docu- each financial planning cycle. To be successful, the number
ment, several important suggestions are provided below. A of initiatives should be manageable and should focus on the
general approach to systematically developing the annual institution’s top expenditures. In many situations, multiple
drug budget is outlined in Table 1.7 At the beginning of approaches for cost containment will be necessary.
each calendar year, the American Journal of Health-System The foundation for effective cost-management strat-
Pharmacy publishes a projection of drug expenditures for egies, and the first stage of the systematic approach, be-
that year.1,5–7 gins with determining current costs of medications, both
Annual drug budgeting is a challenging exercise. as ongoing expenses and those held as assets in inventory.
Unanticipated situations that result in extreme increases in Understanding and tracking key medication-cost indicators
drug expenditures will likely occur and the pharmacy direc- on an ongoing basis is necessary to determine the oppor-
tor should be prepared to explain those situations. Better data tunities for medication-cost reduction. Examples of these
and more experience will improve a department’s ability to indicators may include:
forecast institutional drug expenditures. Regardless of the
drug budget’s accuracy in forecasting the institution’s drug • Medication inventory per adjusted patient day
expenditures, a well-planned drug budget should help the de- • Medication inventory turnover rate
partment understand drug use patterns and identify opportu- • Contract coverage percentage
nities for drug cost management. Specific reports that can be • Contract compliance percentage
helpful in understanding drug use will be described below. • Intravenous-to-oral dosage ratio
During the annual financial planning process, it is im- • Volume-adjusted total medication costs (e.g., cost per
portant to identify and focus on key drug expenditures. The adjusted patient day, discharge, etc.)
• Volume-adjusted drug category costs (e.g., antibiotics, Because of the relative ease of implementation, cost-
anesthesia-related drugs, etc.) containment opportunities in areas that are primarily under
• Descending-order total purchase histories, tracked the department’s control will usually be pursued first. After
over time these initiatives are underway, more complex techniques
that require collaboration with the medical staff and others
In addition, the use of external benchmarks may pro- should be pursued.
vide assistance in identifying medication-cost-reduction These guidelines are structured so that the cost-man-
opportunities. External benchmarks may be available as agement techniques are presented in the order in which
a component of services provided by consulting organiza- health systems often implement them. Components of a
tions, the pharmacy’s drug wholesaler or group-purchasing cost-management program are listed in Table 2. An appen-
organization (GPO), or from professional published data. dix that lists specific cost management opportunities is also
Benchmark data should be used with care; however, be- provided. It is important to note that although these guide-
cause there may be important limitations to the applicabil- lines are separated into sections on purchasing and inven-
ity of the data to a specific site. For example, difficulties tory management and medication-use management, both
may exist in adjusting the data for the specific pharmacy activities are integral and indivisible to drug-cost manage-
practice, such as models and intensity of services, and in ment planning and the practice of pharmacy in hospitals
finding an appropriate peer group.9 and health systems.
After cost-management opportunities are identified,
they need to be quantified. Dollar values should be as- Purchasing and Inventory Management
signed to each opportunity, including inventory reduction,
improvement in inventory turns, improving contract compli- When selecting drug-cost-containment initiatives, purchas-
ance, therapeutic interchange of various agents, and others. ing and inventory management procedures should be con-
A specific goal and action plan should be set for each drug- sidered first.
cost-management target. For example, one goal might be to
reduce expenditures for a drug class by 8% by establishing a Drug Product Costs and Procurement. At the most fun-
contract for a new, preferred agent and implementing a ther- damental level, drug costs are a function of unit costs and
apeutic interchange program to shift use to the new agent.
Alternatively, the goal might be to slow the rate of increase
in use of a particular drug or drug class (e.g., based on cur- Table 2.
rent patterns, use of this drug class is expected to grow 15% Components of a Cost-Management Programa
in the next fiscal year, but the goal of interventions is to limit Pharmacy-Directed Activities
the rate of increase to 10%). Monitoring is essential, so drug Purchasing
cost containment targets should be consistently measured GPO contracts
and evaluated. Identifying and quantifying the opportunities Facility contracts
Wholesaler contracts
must be completed before prioritization and in-depth evalu-
Inventory management
ation begins.
Wholesaler ordering
programs
Assessment and Prioritization. Once opportunities for cost Storage
management have been identified and quantified, assessment Waste reduction
and prioritization can occur. There are many methods of pri- I.V. product waste
oritization, but most of them contain two key elements: deter- Returns
mining the potential benefit and estimating the relative ease Interdisciplinary Activities
or difficulty of attaining the benefit. Even though potential Medication utilization program
benefit may be clear-cut, the degree of difficulty is often hard Clinical pharmacy services
to establish. Important points to consider when determining Assessment of drug costs
the relative degree of difficulty and likelihood of achieving Medical staff support
Formulary management
benefits from a given drug-cost-management opportunity in-
Therapeutic interchange
clude (1) the amount of time pressure (the time available until
Guideline (protocol)
the cost reductions occur), (2) key stakeholder (e.g., nurse, development
physician) sensitivity and willingness to collaborate, (3) ex- Pharmacist interventions
tent of leadership support for the initiative, (4) resources re- Plan implementation and
quired, and (5) existing level of expertise within the organiza- analysis
tion for the specific cost-management opportunity. Reimbursement & Charging
Drug-cost management strategies that are under the Reimbursement
direct and exclusive purview of the pharmacy department 340B programs
(e.g., purchasing, inventory management, and waste re- CMS (DRG class)
duction approaches) are generally easier to implement and Commercial insurance (payer
provide more immediate benefits. These activities, how- mix)
ever, often provide smaller or one-time financial benefits. Outpatient infusion center
Charging
Utilization management tactics (e.g., clinical practice guide-
Coding and processing
lines and therapeutic interchange) generally provide greater Indigent care programs
financial benefits, but these efforts have correspondingly a
GPO = group purchasing organization, CMS = Centers for Medicare
higher degrees of difficulty and complexity. and Medicaid Services, DRG = diagnosis-related group.
utilization. Drug-unit costs are a function of acquisition Typically, market share agreements are utilized when
costs (contracted or non-contracted), the external (in-bound) two or more products can be used to treat the same disease
distribution fee, inventory management costs, and internal and no generic equivalent exists. The incentive, such as a
distribution costs. rebate, a lock-in of a current discount, or achievement of a
higher discount, is contingent upon attaining a given mar-
Contracting. There are three main avenues for purchasing ket share for a particular product in the institution’s market
pharmaceuticals at discounted rates: GPO contracts, facil- basket. To achieve the greatest financial advantage from the
ity contracts, and wholesaler own-use contracts. All facili- contract (lowest net drug cost), the pharmacy must work
ties should seek to maximize savings available from use of with the medical staff. This process requires a careful evalu-
generic products, and some may have other considerations, ation of comparative efficacy and safety of the product and
such as use of 340B or indigent care programs. its alternatives.
GPO contracts. GPOs utilize the aggregate purchasing Some GPOs have multiple products on contract within
power of many facilities in negotiating pricing agreements categories of pharmaceuticals, allowing the facility to re-
with manufacturers. Most hospitals are members of a GPO. ceive discounted pricing on similar agents when prescribing
While there are GPOs that focus exclusively on drugs, the practices are not standardized to one agent. More aggressive
majority of GPOs offer contracts for medical and surgical GPOs will sometimes contract for a single agent within a
supplies, food, and other support products and services in particular class (e.g., for one fluoroquinolone or one lipo-
addition to pharmaceuticals. Most GPOs make their con- somal amphotericin B product to the exclusion of others) in
tract portfolio available to members via hard copy, and some order to gain the maximum value for its members.
GPOs have contract portfolios available on secure internet Successful use of GPO contracts requires a construc-
sites. Considerations in contracting with a GPO are listed tive and collaborative relationship between the member, the
in Table 3. It is also important to have routine surveillance, GPO, the manufacturer, and the distributor (i.e., wholesaler).
preferably an automated service, that ensures that contract Potential advantages of GPO contracts are listed in Table 4.
prices are applied to all purchases. In addition to the contracting portfolio, GPOs offer
GPOs are funded by one of two means. First, most, services such as lost savings and compliance reports, rebate
if not all, GPOs collect a contract administrative fee (CAF) and contract administrative fee reports, clinical utilization
from the manufacturers or distributors with which they con- management programs, and letters of commitment.
tract. The CAF is rarely greater than 3% of the dollar volume Lost savings and compliance reports. These reports
of product purchased through the contract. Some GPOs re- provide data and analysis of missed savings opportunities
turn a portion or all of the CAF to its members. If any or all in the user’s purchase history (e.g., items purchased off-
of the CAF for a particular drug product is returned to the contract when a generically equivalent alternative item was
facility by the GPO, it should be taken into account when on-contract). These reports may also indicate the compli-
calculating the net cost of the drug. The second method by ance level, or the amount of purchases on-contract versus
which GPOs are funded is direct payment of fees by mem- the amount of purchases that could have been made on-con-
bers to the GPO. In this arrangement, all of the CAF is re- tract (drugs purchased on-contract plus the value of drugs
turned to the facility. purchased off-contract when alternatives were on-contract).
Contracts through GPOs consider not only the unit cost These reports should be reviewed monthly to determine if
of the pharmaceutical but also include the allowable distribu- purchasing practices are effective.
tion methods for the pharmaceutical, payment terms, returns Rebate and contract administration fee report. These
policies, and supplier performance requirements. Many GPO reports tally the amount of rebates and contract administra-
contracts, especially those for multi-source generics, include tion fees generated by the facility’s purchases of specific
simple line-item pricing, which only requires the purchaser to products under contact. When evaluating the costs of two
buy and pay for the product. Other contracts are more compli- or more equivalent products, it is important to include any
cated, with incentive rebates for all purchases or rebates for applicable rebates to arrive at net cost.
achieving volume or market share targets. Clinical utilization management programs. These pro-
grams assist facilities in managing the utilization of vari-
ous drug products and classes, often through evaluation and
Table 3.
Considerations in Group Purchasing Organization Table 4.
(GPO) Contracting Potential Advantages of Group Purchasing
Fees (e.g., contract administrative fee) Organization Contracts10,11
Allowable distribution methods Standardization of products
Payment terms Reduction of contract labor costs for institutions
Return policies Enhancement of member institution’s purchasing program
Supplier performance requirements Enhancement of information sharing
Rebates Enhancement of purchasing expertise
Market-share agreements Protracted periods of price protection
Single-agent contracts Coordination of contracting and budgeting process
GPO services (e.g., lost savings and compliance reports, Reduction of duplication of purchasing efforts among
rebate and contract administration fee reports, clinical institutions
utilization management programs) Assistance identifying alternative or secondary products
Letters of commitment during drug shortage
comparison of product efficacy, safety, and cost, as well as in the wholesaler’s proprietary contract portfolio. This cre-
therapeutic interchange programs. ates margin for the wholesalers that can be used to fund dis-
Letters of commitment. Letters of commitment (LOC) tribution discounts. Wholesalers also take advantage of cash
available through GPOs should be evaluated and taken ad- discounts and quick-payment terms from manufacturers to
vantage of when appropriate. The LOCs usually contain increase their margin and to offer discounts to customers.
requirements for the pharmacy to do one or more of the fol-
lowing in order to gain lower pricing or rebates: Generic Drug Savings Maximization. The expiration of
patents on widely used branded drugs can result in large re-
• Declare that a particular drug is on formulary. ductions in drug expenditures. It is important to be mindful
• Declare that a particular drug will be on formulary and of the opportunities presented by the first-time introduction
will not be restricted. of generics on high-spend branded drugs, both in budget-
• Achieve a target periodic volume. ing and implementing rapid and effective uptake of generics
• Achieve a target market share relative to competitive when they are introduced.
drugs for a given period of time. Budgeting. There are several sources for monitoring
patent expiration dates (off-patent dates) for branded drugs,
The LOC may not require significantly more purchas- including www.drugpatentwatch.com and the GPO. The
ing of the drug. If LOC requirements do not conflict with GPO may also be able to estimate the potential initial sav-
formulary and utilization management strategies, the LOC ings from contracting for generic drugs that are first-time
should be signed if there is a reasonable chance of meeting introductions. It is also important to determine when the
the requirements. first-time generic product will be available from multiple
Facility contracts. The alternative to GPO contract- manufacturers. The initial savings differential between the
ing is individual contracting. This type of contracting may branded and generic versions may be small because a single
be done at the facility or the health-system level. In some generic manufacturer often has a period of exclusivity before
cases, equal or better pricing than GPOs can be obtained by the generic drug becomes available from multiple sources.
individual facilities when contracting, especially large facili- In some cases the savings may be so insignificant that health
ties or integrated delivery networks (IDNs). Opportunities systems will choose to remain with the branded drug for
for better pricing through individual contracting may exist safety reasons and consistency in product supply. Changing
for specialized health systems (e.g., those focused on oncol- products several times within a short period of time could
ogy or transplantation), that purchase a large volume of a confuse caregivers, so pharmacy managers should weigh the
selected drug and are able to commit to maintaining a market benefits and risks of making such changes.
share for the drug. Operational considerations. Swift uptake of the ge-
It is important to carefully evaluate the benefits of neric product is necessary to maximize the savings after a
individual contracting and its influence on the collective branded drug comes off-patent and multiple generic versions
bargaining power of the GPO. Continual use of individual are available. The following steps should be taken during
contracts that are in contravention to GPO contracts, in the- any product conversion, but they are particularly important
ory, will eventually erode the GPO’s ability to consistently when converting from a brand name product to a first-time
contract aggressively for its members. Because of larger generic equivalent product.
GPO volume, manufacturers often will not offer the same
pricing or other terms to individual facilities or IDNs that
• Contracting. Be sure that the health system has access
they offer to GPOs. Another factor to consider with indi- to contract pricing on a generic product on the first
vidual contracting is that a facility may require contracts date that the drug is available as a multisource item.
to be reviewed by attorneys, whereas the GPO acts as the The contract pricing will usually be through the health
contracting agent of the facility, obviating the need for legal system’s GPO, but in some cases, the health system
review of each contract by the facility’s counsel. Finally, the may write its own contract for the generic product.
amount of time required to negotiate, write, and maintain an
• Contract Price Loading. The contract pricing for the
individual contract should be weighed against the incremen- product must be loaded at the wholesaler with enough
tal value gained over what a GPO contract would offer. In notice to become effective. Up to 30 days notice may
many situations, it may be more efficient and productive to be required before the contract pricing becomes effec-
voice contract concerns to GPO representatives and become tive through the wholesaler. Although the manufac-
involved in GPO committees rather than write multiple, in- turer or GPO typically send the contract information
dividual contracts outside the GPO. to the wholesalers, when the hospital or health system
Some drug contracts, especially for sole-source directly contracts for the generic drug, the contract in-
awards to generic manufacturers, call for the manufacturer formation should be sent directly to the wholesaler by
to reimburse the pharmacy for the difference in cost when the hospital or health system.
the pharmacy must purchase a product off-contract because
• Demand Matching. Work with the wholesaler to en-
the manufacturer was not able to supply the contracted prod- sure that there will be a sufficient supply of the generic
uct. The manufacturer-unable-to-supply reimbursement pro- product at the local wholesaler distribution center to
cess is time-consuming and the requirements can be rigid, match current purchases of the branded product, a pro-
but submitting reimbursement to manufacturers under these cess called demand matching. Wholesalers will need
provisions can return additional funds to the pharmacy. at least 30 days notice on demand matching to ensure
Wholesaler own-use contracts. Wholesalers are also sufficient stock of the generic product on the off-patent
able to take advantage of special pricing on certain branded date. Working with the wholesaler on demand match-
and generic drugs and offer those products to their customers ing also improves overall supply chain management
by allowing the wholesaler to draw down inventory of Through automated inventory, stock replacement, and
products that will be in less demand. order fulfillment, wholesalers have streamlined the deliv-
• Autosubstitution. Some wholesalers allow pharmacies ery process and lowered pharmaceutical costs in the sup-
to institute autosubstitution rules in the wholesaler or- ply chain. In the past, wholesalers increased their margins
dering system to substitute a preferred generic product through speculative buying, which is buying pharmaceuti-
for a branded product or non-preferred generic prod- cals in large quantities and holding them past the date of fu-
ucts. This process maximizes savings and contract ture manufacturer price increases. The products would then
compliance. Care must be exercised in creating auto- be sold to customers at the higher price. These practices
substitution rules to ensure correct product-to-product have reportedly decreased since 2004.12 However, at the
substitution in chemical entity, dosage form, package same time that speculative buying decreased, the wholesale
size, package form (unit dose, bulk oral, liquid), and drug industry instituted inventory management agreements
so forth, especially in cases in which a brand-name with manufacturers, who in return for agreements regarding
drug goes off-patent. Autosubstitution rules may also product supply and demand, pay the wholesalers a negoti-
be implemented in the wholesaler ordering system for ated fee based on the percentage of the volume that the
medication safety reasons (e.g., reduction of sound- wholesalers purchase from them. These methods of creating
alike and look-alike drugs) in addition to savings opti- margin through increasing revenue and decreasing expenses
mization or contract compliance. can be translated into a cost-minus fee structure for the hos-
pital that is purchasing from the wholesalers.
Other Considerations. Pharmacy managers should explore Individual hospital factors that influence wholesaler
whether the hospital can obtain pharmaceuticals at advanta- fee structure. Several characteristics of individual hospital-
geous pricing using 340B (disproportionate share) programs. pharmacy purchasing can affect a wholesaler’s revenue and
Because hospitals and health systems must meet specific expenses and result in higher or lower distribution fees. To
criteria to be designated as a 340B facility, pharmacy man- some degree, a higher purchasing volume results in a lower
agers should collaborate with the chief financial officer and distribution fee. However, other factors, including deliveries
financial services department to determine if they can access per week, dollars per drop, dollars per line extension, num-
340B pricing for pharmaceuticals. Detailed descriptions of the bers of delivery sites per location, payment terms, and spe-
qualifications and benefits of 340B programs are also avail- cial services, must also be considered. These factors should
able through the Health Resources and Services be considered collectively and not in isolation. In addition,
Administration Office of Pharmacy Affairs www.hrsa.gov/ most major wholesalers have supply, automation, and other
opa/; the Pharmacy Services Support Center, pssc.aphanet. service and equipment divisions, and an institutional con-
org/; the Safety Net Hospitals for Pharmaceutical Access, tract with multiple divisions can provide additional savings.
safetynetrx.org; and ASHP 340B Information Site www.ashp. Deliveries per week. The fewer deliveries from the
org/s_ashp/cat1c.asp? CID=3813&DID=6225. wholesaler per week, the lower the expenses for the whole-
Pharmaceutical manufacturers also continue to offer saler, which can reduce the wholesaler distribution fee to the
indigent patient care programs for select drugs for qualified pharmacy. Some large hospitals have up to 11 deliveries per
patients on an individual basis. Although substantial sav- week, but other large hospitals are able to manage inven-
ings can be realized through replacement drugs at no charge, tory so that patient care can be well-maintained with only
the process can be arduous and complex. There are inde- 5. Inventory and patient care can be well maintained at less
pendent consulting services that specialize in assisting with than five deliveries per week at small hospitals. Fewer deliv-
coordination of the program for hospitals and typically re- eries may require additional purchasing discipline, but some
quire payment as a percentage of the savings. Patients eli- wholesalers have programs to help pharmacies improve
gible for Medicaid and other regional or local low-income their purchasing practices.
health insurance do not usually qualify for the indigent care Dollars per drop. This factor is important to whole-
programs sponsored by the pharmaceutical industry. salers because the higher the number of delivery locations
(drops), the higher the wholesalers’ cost, and vice versa. For
Wholesalers and Distribution Fees. Most hospital phar- a given dollar value of pharmaceuticals purchased, a whole-
macies purchase 80% or more (by dollar volume) of their saler’s expenses are lower, and margin is higher, for a lower
pharmaceutical needs from a drug distributor (wholesaler). number of delivery points. This margin can be translated
Hospital pharmacies can lower their costs by ensuring that into lower distribution fees for the pharmacies, particularly
the distribution fee mark-up is as low as possible. To under- for IDNs of multiple pharmacies.
stand the cost that wholesalers charge for drugs, and the dis- Dollars per line extension. For each line of products on
tribution fee charged to hospital pharmacies, it is necessary an invoice that a wholesaler fills and delivers to a pharmacy,
to understand wholesalers’ revenue streams and expense there is an associated cost. The dollars per line extension
drivers. is the total dollars purchased by a pharmacy over a given
The adoption of the prime-vendor system, in which a period of time divided by the number of lines of products or-
pharmacy procures a very large portion of its pharmaceu- dered over the same period of time. Pharmacies with higher
tical needs from one supplier, has led to great efficiencies dollars per line extension purchased can sometimes have
in the pharmaceutical supply chain. Through these efficien- lower distribution costs than pharmacies with lower dol-
cies, wholesalers are able to offer low incremental fees to lars per line extension because it costs relatively less for the
their customers for distribution of pharmaceuticals. In many wholesaler to service the pharmacy with the higher dollars
cases, they are able to offer discounts to the contracted price per line extension.
of the drug or “cost-minus” discounts to the wholesale ac- Secondary wholesalers. Secondary wholesaler rela-
quisition cost of the drug if it is not contracted. tionships should be avoided if inventory levels meet patient
care needs. Purchases from secondary wholesalers usually If they are, they should be reviewed monthly for opportuni-
carry a much higher distribution fee. Such purchases also re- ties to improve contract purchasing.
sult in a higher primary wholesaler distribution fee because Some wholesalers have automatic substitution pro-
there are decreases for the pharmacy in its dollars per drop, grams to assist pharmacy buyers in selecting the correct
dollars per line extension, and total volume. Wholesalers product when multiple generic alternatives exist. These
are increasingly requiring pharmacies to meet a minimum programs allow the pharmacy manager to direct purchases
monthly volume to maintain an account, and the costs of of less-preferred products (as determined by the pharmacy
maintaining the minimum volume at a significantly higher management) to more-preferred items. For example, if one
distribution fee can be prohibitive. brand of unit dose acetaminophen 325-mg tablet is on con-
Expanding the use of the wholesaler within the health tract as a sole-source award, the autosubstitution program
system may offer additional opportunities for cost sav- can allow for inadvertent orders for noncontract unit dose
ings. Hospital departments such as radiology, the clinical acetaminophen 325-mg tablets to be substituted with the
laboratory, interventional cardiology, and anesthesiology preferred version. Such programs may not be available from
may procure pharmaceuticals directly from the manufac- all wholesalers, and they should receive careful consider-
turer through the purchasing or materials management ation before being implemented.
departments. Utilizing the pharmaceutical wholesaler for
these products through a separate purchasing account does Inventory Management. Inventory management is a bal-
not change the process of procurement or distribution but ancing act. It involves meeting patient and internal customer
reduces the unit cost through application of the wholesaler needs while committing the least amount of dollars possible
discount. Because some of these products may be relatively to drugs on the shelves or in automated cabinets. The rate of
costly (e.g., contrast agents, blood factors, or anesthetic inventory turnover (defined as total annual drug expenses
gases), there is a potential for additional savings if these pur- divided by the dollar value of the inventory assessed on an
chases push the hospital into a higher tier of the wholesaler annual basis) is dependent on many factors. Typically, the
cost structure. Pharmacy directors should communicate with pharmacies of smaller hospitals will have a lower drug in-
other department managers to determine how pharmaceuti- ventory turnover (8–10 turns per year) than the pharmacies
cals are purchased, and it is usually best if all drug purchases of larger hospitals (12–18 turns per year or higher) and some
are managed by the pharmacy. specialty hospitals.
Payment method and frequency. Payment method and Many wholesalers’ ordering programs provide sys-
frequency can also affect the distribution fee. Many whole- tematic methods for asset management (i.e., inventory value
salers offer a lower distribution fee to hospitals that pay by optimization and increasing turnover). Wholesaler repre-
electronic fund transfer (EFT). Pharmacy managers should sentatives can assist in the initial setup of these programs.
work with their accounts-payable departments to establish Inventory items should be divided into high-, medium-, and
EFT, which is usually a more efficient method of payment low-value products, and the minimum and maximum inven-
for both the hospital and the wholesaler. In addition, the tory levels for at least the high- and medium-value prod-
more frequent the payment, the lower the wholesaler dis- ucts should be established. At the same time, reorder points
tribution fee will generally be. Since 2004, the amount of and reorder quantities should be established for at least the
speculative buying has waned and large discounts for more high- and medium-value products. Systematic use of these
frequent payments have decreased. However, many whole- programs can decrease the time required for the ordering
salers offer terms based on prepayment, or placing funds on process and increase inventory turns. The minimum and
deposit with the wholesaler, and then paying invoices on a maximum levels, as well as the reorder points and reorder
go-forward basis. The advantage in lower distribution fee is quantities, should be reviewed on a routine schedule and re-
clear, but this gain must be balanced against the time value vised when necessary.
of money for having the funds on deposit with the whole- When seeking to increase inventory turns, storage in
saler rather than drawing a return for the health system. the central pharmacy and automated dispensing cabinets
Most GPOs have wholesaler-distribution agreements should also be considered. Configuring pharmacy storage
for use by their members. However, because of higher-than- locations so that each drug product has only one storage lo-
average dollars per drop, dollars per line extension, and cation in the central pharmacy sometimes helps to free capi-
discipline in number of deliveries per week, large hospitals tal by reducing inventory. Automated cabinet inventories
and health systems can often get better pricing and terms by should be regularly reviewed for appropriate turnover. Most
dealing directly with wholesalers rather than through GPO cabinet systems have report capabilities to optimize both
wholesaler agreements. the products and the quantities that should be in a particular
Other wholesaler tools. Most wholesalers provide cabinet based on the dispensing philosophy devised by phar-
pharmacies with access to computer software or Web-based macy and nursing departments. Cabinet manufacturers have
solutions for product ordering, reporting, and inventory product specialists that consult with pharmacy management
management. The programs will allow the buyer to check to optimize use of the cabinets.
for lower-priced alternatives and contract compliance prior I.V. product waste. Many pharmacies waste a signifi-
to placing orders. Pharmacy managers should work with cant quantity of drugs, particularly unused IV solutions, and
their wholesaler representatives to be sure that these features many do not have an accurate valuation of the amount of
are available and utilized. waste because it is only sporadically monitored. Table 5 lists
Some wholesalers produce contract compliance re- strategies for reduction of IV product waste.
ports. These reports can be used to gauge the effectiveness of Returns. Most pharmacies use a third party (reverse
purchasing practices. Pharmacy managers should check with distributors or returns companies) to process wasted and ex-
their wholesalers to determine if these reports are available. pired drugs. However, not all pharmacies completely track
Table 5. system management. The director of pharmacy provides

Strategies for Reducing I.V. Product Waste leadership by facilitating the efforts of the medical staff, set-
Establish policies that are based on the most recent
ting priorities for the clinical pharmacy staff, and cultivating
literature for maximum i.v. bag hang-times and i.v. set the support of senior leadership. Clinical pharmacists with
change frequency. advanced training and education must have dedicated time
Institute an i.v.-to-oral switch program for both cost to develop and implement the cost management initiatives.
reduction and patient care benefits. They must also be empowered to monitor the program and
Periodically audit the amount of i.v. admixtures being wasted educate other staff to participate in therapeutic interchange,
and log the date and time of waste, date and time of medication utilization review, and other interventions while
preparation, the i.v. fluid type and drug admixed, quantity encouraging the infusion of fresh ideas for pharmaceutical
of products, and the cost of the products. Review the log cost management.
and determine the most common occurrences.
Reduce i.v. batch sizes (creating more, smaller batches)
Role of Clinical Pharmacy Services in Drug Cost Manage-
and reduce the amount of time between preparation of
the i.v. dose and the actual administration time.
ment. Clinical pharmacy services, activities in which phar-
Routinely monitor the status of i.v. drips that are adjusted. macists provide direct patient care, are an important foun-
Routinely return all unused i.v. admixtures to the i.v. dation for a successful medication-utilization-management
preparation area as soon as possible. program that is focused on managing drug costs. Clinical
Consider the use of manufacturer premixed products where pharmacy services have demonstrated an overall positive
advantageous, both economically and for patient care. financial impact. In a systematic review of original assess-
Compare the quality, economic, and regulatory (e.g., USP ments of clinical pharmacy services from 1988 to 1995,
chapter 797) differences within your practice site between Schumock et al.13 reported that 89% of 104 studies reviewed
different administration methods such as i.v. syringe reported positive financial results. In the seven studies of
infusion, i.v. intermittent infusion (i.v. piggyback), and
clinical pharmacy services where sufficient information
volumetric drip chambers.
was available to calculate a benefit-to-cost ratio, the median
Establish standard concentrations, dosages, and base
solutions for i.v. admixtures.
benefit-to-cost ratio was 4.09:1. Therefore, in these studies,
Ensure that there is an efficient process for communicating every dollar invested in clinical pharmacy services returned
changes in i.v. admixtures (e.g., rate, fluid, dosage) or four dollars. The systematic review was updated in 2003 to
discontinuation. review published assessments of clinical pharmacy services
Reduce total parenteral nutrition use by employing enteral from 1995 to 2000, and once again, the value of clinical
nutrition when possible, and establish standardized pharmacy services was demonstrated.14 For this five-year
total parenteral nutrient base solutions, hang times, and period, benefit-to-cost ratios could be determined from 16
related policies and procedures. studies, and when these studies were combined, the median
benefit:cost ratio was 4.68:1.
Some specific types of clinical pharmacy services
and trend the drugs that are most commonly wasted, the dollar have also been associated with decreased drug costs. Bond
value of the expired and wasted drugs, or whether credits were et al.15 have used an extensive database of the outcomes of
received. The pharmacy manager and pharmacy buyer should clinical pharmacy services to show that drug information
work together to utilize reports from the reverse distributor services, medication admission histories, and drug protocol
to determine the opportunities for reducing the amount of ex- management are associated with lower drug costs.
pired and wasted drugs and insuring that all credits due to the In addition, clinical pharmacists’ active involvement
pharmacy from the manufacturers are received. is crucial to the success of many drug-cost-management
ini-tiatives. Many of the drug-cost-containment techniques
Medication Utilization Management can only be successful with diligent and often daily sup-
port from clinical pharmacists. For example, successful
implementation of a clinical practice guideline as a drug-
Planning and Developing a Medication Utilization Man-
cost-management technique will require the expertise of
agement Program. An effective plan for medication utiliza-
the department’s clinical pharmacists to develop the guide-
tion management must provide the health system with a road
line, and will also require the pharmacy staff’s consistent
map for continuous improvement in pharmaceutical expense
enforcement of the guideline in their interactions with pre-
management, with specific goals and outcome measures of
scribers. Similarly, it will often be the clinical pharmacist’s
success. It is important to acknowledge that although one
responsibility to routinely carry out the hospital’s thera-
purpose of medication-utilization-management is to add
peutic interchange policies.
economic value, the quality and safety of patient care are
foremost in the mission of pharmacy services and should
never be compromised for cost. Medication-utilization- Assessment of Drug Costs
management must integrate evidence-based science with
the standards of medical practice within the health system. A successful pharmaceutical-cost-management program must
Before embarking on a comprehensive medication- be data driven. GPOs, wholesalers, distributors, pharmaceuti-
utilization-management plan, goals must be established, a cal manufacturers, and supply-chain divisions of multi-hospi-
reporting structure delineated, roles identified, measurement tal systems need to track costs in a variety of ways. Advances
tools developed, and implementation procedures established. in information technology have made drug usage data more
The successful plan is dependent on many levels of commit- accessible and sophisticated, and effort should be spent to
ment, including commitment to administrative and clinical manage and analyze these data. Pharmacy management must
pharmacy management, the medical staff, and senior health- also take advantage of the data available in its own facility
through the materials management department, purchasing influence market share and drug pricing. Several effective
department, and finance department. Internal and external strategies that can harness physician knowledge, cultivate
data sources are the foundation for the decision-making pro- a collaborative relationship, and facilitate ownership of the
cess for medication-utilization-management and must be process by the medical staff are described in Table 7.
examined closely prior to setting goals for cost-management Once the medical staff is engaged and there is a com-
initiatives. mitment from senior management for the medication-utiliza-
Because each health system has a unique mix of pation-management program, a detailed procedure for initiative
tients, services, and centers of excellence, the drug-cost- generation can be established. Key steps include the following:
assessment process must be customized to create a priority
list of initiatives that will provide the greatest value. Key • Designating clinical sub-groups based on categories of
reports that should be considered are listed in Table 6. Once the initiatives,
the formulas for denominator data are established as consis- • Identifying the lead physicians, clinical pharmacists,
tent across many facilities, a multihospital health system can and other key practitioners for each group,
effectively benchmark drug costs. • Using evidence-based studies and the drug assess-
ment data to make decisions,
Medical Staff Support. Any program that involves alter- • Defining the types and categories of the initiatives,
ing prescribing patterns to improve the cost-effectiveness • Creating a dashboard and a clear and concise reporting
of drug therapy requires the support and engagement of the format for communicating progress,
medical staff. Although health systems have the ability to • Facilitating the infusion of ideas through brainstorm-
negotiate discounted unit prices for pharmaceuticals, the ef- ing and other effective meeting and group techniques,
forts of the GPOs and the increased availability of generics and
have leveled the expense of many high-cost drug products • Defining measurable outcomes and benchmarks for
used in hospitals. Cost-management programs have there- evaluation.
fore become increasingly dependent on the hospital’s ability
to manage utilization and prescribing, which will ultimately
Formulary Management. The guid-
ing principles of a sound formulary
Table 6. management system are well de-
Key Reports to Consider in Assessing Drug Costs scribed in two documents,17,18 and
are concisely summarized in the fol-
Report Considerations
lowing statement: a well-managed
Wholesaler purchasing reports For 80/20 analysis, by therapeutic class, formulary system ensures a close
and of top 200 drugs; drugs with multiple relationship between the organiza-
strengths and sizes need to be aggregated;
tion’s medication-use policies, the
wholesalers can also provide monthly
therapies offered by the organiza-
trending reports and benchmarks from their
customers. tion, and the medication routinely
stocked by the pharmacy.18 Although
Direct (nonwholesaler) purchase Available from the purchasing or finance
the primary goal of a formulary sys-
reports departments.
tem is to promote safe and effective
Interdepartmental purchasing reports Available from materials management or other drug therapy, it can be a valuable
departments that have internal transfers. cost management tool and has in-
Cost (total drug costs or specific Drug-utilization data will be needed to produce herent medical staff support through
drugs) per medical service or this report. the actions of the pharmacy and
hospital area therapeutics (P&T) committee. The
Cost per drug-related group reports Available from internal sources (ideally) or fee- medication-utilization-management
based external vendors; distinction must be program is highly dependent on an
made between using cost or charge data. effective formulary system. Key
Cost per occupied bed, adjusted Adjusted patient days are calculated with a aspects of formulary management
patient day, admission, discharge, standard financial formula that modifies in cost-management efforts are de-
or case mix index adjusted patient patient days with a ratio of outpatient to scribed in Table 8. Once again, the
day inpatient revenue to correct for volume efforts of clinical pharmacists are
changes and severity of illness.16 External crucial to successful implementa-
and internal benchmarking is dependent on tion of the formulary system.
these kinds of reports.
Pharmacy-adjusted patient days Calculated using the same ratio of outpatient to Methods of Pharmaceutical Cost
inpatient revenue but for drugs only, and may Management. Pharmaceutical cost-
also add specificity and value to comparative management initiatives are typically
data. categorized by therapeutic class or
Cost per case, procedure, or These are important based on the patient mix group or by method of implementa-
admission (e.g., surgical case, and the drugs that comprise the greatest tion. The latter is usually subdivided
cardiac procedure, dialysis costs within the health system. Physician into three or four different types:
admission) participation in the dissemination of the data therapeutic interchange (therapeutic
is essential.
substitution), guideline (protocol)
Table 7. Table 8.
Strategies to Involve Medical Staff Key Aspects of Formulary Management
in Cost-Management Efforts in Cost-Management Efforts
Enlist the pharmacy and therapeutic (P&T) committee to Policy for formulary drug addition and deletion through
review medication-utilization management issues as a evidence-based product selection, including efficacy,
standing agenda item. safety, and pharmacoeconomic assessments
Identify the centers of excellence and work with individual Policy for the use and monitoring of non-formulary
chiefs of service to gain support. medications
Meet with key medical staff departments and divisions, Policy for medication-use evaluation
including infectious diseases, anesthesiology, cardiology, Limitation on combination, sustained-release, and long-
and oncology, as well as intensivists, hospitalists, and acting products
interventionalists as appropriate. Policy for therapeutic interchange and prescribing
Develop prescriber reports on the targeted high-cost drugs guidelines
and discuss methods for cost reduction. Reduction of drugs in the same therapeutic group or class
Provide continuous feedback to the P&T committee Periodic house cleaning to reduce under-used and
and individual departments and divisions on cost discontinued line items
management successes. Policy for drug restriction
Provide hospitalwide expenditure data on the top 50 items Procedure for consistently monitoring the use of new agents
to the P&T committee. particularly if there are specific guidelines for use
Utilize evidence-based research to propose changes in System to provide the formulary electronically with timely
medication utilization. updated information
Identify physician champions for specific initiatives. Off-label or ad hoc use of medications
Create a consistent procedure for developing prescribing Restricted use (by indication, prescriber, patient care area,
guidelines, protocols, care paths, and preprinted orders. patient)
Dose adjustment or discontinuation based on clinical
triggers or end points
Injectable to oral conversion
development, and pharmacist interventions (clinical and op-
Therapeutic equivalence
erational), such as parenteral-to-oral conversions, renal-dose
adjustments, drug restrictions, repackaging, dosage-form
changes, waste reduction, and others. Although the terms are
sometimes used interchangeably, therapeutic group refers to drugs appropriate for therapeutic interchange may dif-
a broad classification (e.g., anesthetic agents, anti-infectives, fer in chemistry or pharmacokinetic properties, and
or chemotherapeutic agents), whereas therapeutic class is a may possess different mechanism of action, adverse-
narrower designation (e.g., beta-lactam antibiotics, volatile reaction, toxicity, and drug interaction profiles. In
anesthetic gases, serotonin antagonists). If the decision is most cases, the interchanged drugs have close similar-
made to use therapeutic class, then each of the methods of ity in efficacy and safety profiles.
implementation are used as appropriate within the medication
categories. An example would be selecting third-generation The ACCP guidelines also describe a comprehensive
cephalosporins utilizing a therapeutic interchange for cefo- five-part process for health-system TI implementation, with
an emphasis on patient safety; an extensive review of drug
taxime and ceftriaxone (therapeutic interchange method).
classes appropriate for therapeutic interchange, including
Third-generation cephalosporins may also be the preferred
specific evidence-based examples; discussion of legal and
class of antibiotics within a pneumonia protocol (guidelines
regulatory issues; viewpoints of other professional organi-
method). Examples of using the implementation method
zations, including the American Medical Association, the
rather than the therapeutic class would be to select several
American College of Physicians, and the Pharmaceutical
drug classes for therapeutic interchange, some for guideline
Research and Manufacturers of America; and medical and
development, and some for other intervention types.
pharmaceutical literature references.
Therapeutic interchange. ASHP defines therapeutic
The health system, through the action of the P&T
interchange (TI) as “an authorized exchange of therapeutic committee, must decide on the general policy for a TI pro-
alternatives in accordance with previously established and gram, particularly regarding the authority and autonomy
approved written guidelines or protocols within a formulary of the pharmacy staff. The committee may define TI as an
system.”17 This definition stipulates that the interchange is automatic conversion by the pharmacist, may require con-
between two or more drugs that are not generic equivalents. tact with the prescriber before the change can occur, or may
Although FDA defines the term therapeutic equivalent to employ a combination of both. The prescriber may be in-
include generically equivalent products, therapeutic inter- formed orally before the drug is dispensed or through writ-
change or substitution in the hospital setting generally reten communication in the medical record. Most commonly,
fers to drugs that are not generically identical. TI implies pharmacist autonomy once the P&T committee
The American College of Clinical Pharmacy (ACCP) has sanctioned the policy, but there may be exceptions based
Guidelines for Therapeutic Interchange19 contain a more re- on the level of clinical judgment required. A survey of the
cent definition of TI: prevalence of TI conducted in 2002 revealed that the vast
majority (88%) of hospitals use TI programs, and most of
Therapeutic interchange is defined as the dispensing of those did not require the pharmacist to contact the prescriber
a drug that is therapeutically equivalent to but chemi- before making the conversion.20
cally different from the drug originally prescribed. Categories of drugs that offer modest savings with min-
Although usually of the same pharmacological class, imal challenge include various non-prescription groups, such
as antacids, vitamins, nonsteroidal antiinflammatory drugs, • Solicitation of thought leaders and clinical experts
topical products, and cold and cough remedies. To make (e.g., physician specialists, chiefs of service, chief
significant gains in pharmaceutical cost savings, the health medical officers),
system must consider the drug classes that comprise the • Review and approval of the P&T committee,
greatest proportion of drug expenditures, such as colony- • Education of clinical staff,
stimulating factors, antiinfectives, cardiac agents, and drugs • Ongoing support from front line clinical pharmacist
used in critical care settings. An abundance of literature staff,
supports the success of TI programs, both in terms of qual- • Use of quantifiable measures, and
ity patient outcomes and economic benefit. Based on the • Utilization of medication-use evaluation (MUE) to de-
literature, therapeutic classes offering the most opportunity termine compliance.
for success with the medical staff, as well as significant cost
savings, include histamine-2 antagonists, fluoroquinolones, The last step is an important distinction between TI
hydroxymethylglutaryl–coenzyme A reductase inhibitors, se- and guidelines because what is approved by the medical staff
rotonin antagonists, colony-stimulating factors, low molecu- and what is done in practice may differ. Conducting periodic
lar weight heparins, and proton pump inhibitors.20–27 MUEs with the approved criteria can determine the thor-
Although it is not the intent of these guidelines to delineate an oughness and consistency of the guidelines and ultimately
exhaustive list of all potential TI opportunities, the appendix the success of this component of cost management. It should
contains examples of the TIs that have proven successful.
also be emphasized that although guidelines can be used to
Most of the evaluative studies on TI initiatives focus
reduce drug costs, improving quality of care may require
on the economic value and quality improvement related to
more spending rather than less.
standardization and formulary management. As the popu-
When guidelines reduce inappropriate prescribing, drug
larity of TI programs increases in the acute care, managed
costs will also be reduced. Due to the complex uses of some
care, and ambulatory settings, an associated risk may also
drugs and drug classes, such as low-molecular-weight hepa-
increase due to substitutions along the continuum of care
rins, guidelines may be more practical and effective in man-
and patient confusion regarding drug classes and duplica-
aging drug costs than TI and other approaches.37 Drotrecogin
tive therapy.28,29 The Joint Commission standard requir-
alfa was one costly agent for which guidelines became the
ing medication reconciliation can be partially traced to
anecdotal reports of the potential for medication errors as standard of care in most acute care settings.38–40 Other suc-
a result of TI programs in various health care settings.29 cessful guideline efforts have been demonstrated with a
Pharmacists can play a vital role in supporting medication- number of drugs and drug classes, such as third-generation
reconciliation activities through medication history assess- cephalosporins,41 statins,42 antifungals,43, 44 albumin,45 and
ments and discharge counseling.30,31 serotonin-receptor antagonists.46 Drug shortages can also be
Guidelines. A variety of terms are used to describe an impetus for the development and implementation of guide-
these tools, including prescribing guidelines, therapeutic lines, as was the case with the use of parenteral pantoprazole,
position statements, therapeutic guidelines, clinical practice which may be used inappropriately and at a much higher cost
guidelines, protocols, or pathways. There may be subtle dif- in place of histamine-2 antagonists for stress ulcer prophy-
ferences beween these tools, but they all seek to enhance laxis.47 Although volatile anesthetic agents are often a top-20
patient safety, reduce variation in medical practice, and in- item in the pharmaceutical budget and offer a unique chal-
crease standardization. lenge for guidelines or TI implementation, accurate evalua-
Guidelines can focus on a disease state, a thera- tion of cost savings can be accomplished by using the hourly
peutic class, or a specific drug.32 Published guidelines cost to maintain a minimum alveolar concentration.48
are available for many drugs and drug classes.33,34 The
Agency for Health Care Research and Quality maintains Implementation of Medication Utilization Management
an extensive online collection of published guidelines at Initiatives. Careful thought and attention to the implementa-
www.guideline.gov. A 2004 ASHP survey found that 83% tion is required to successfully influence drug expenditures
of U.S. hospitals use guidelines that include medica- through medication utilization initiatives, and multifaceted
tions.35 Successful implementation of such general guide- interventions are often necessary. The active involvement
lines often requires customization to meet the needs of and support of clinical pharmacists and the medical staff
individual health systems, however. For example, local are crucial to effective implementation of these initiatives.
guidelines should be developed that reflect the best avail- It is necessary to seek out ways to integrate or hard-wire
able evidence, incorporate the opinions of local prescriber initiatives such as guidelines and TI into the care provided
experts when necessary, and are applicable within the con- at the bedside. For example, passive guideline dissemination
text of the individual health system. (e.g., simply posting to the hospital’s intranet site) is rarely
Guidelines are also an important step leading to rules- successful. Protocols, order sets, and pathways that reflect
based computerized prescriber order entry (CPOE), which is the evidence in the guideline should be used to integrate the
recommended by NQF in its 2006 Safe Practices.36 CPOE guideline into daily patient care. The growing use of CPOE
facilitates guideline adherence during the ordering process. systems and other technologies can also be leveraged to
Steps to implementing an effective pharmaceutical implement medication-utilization-management endeavors.
cost-containment program using drug-specific or drug class CPOE can be used to guide prescribing in such straightfor-
guidelines mirror those for TI and include: ward ways as leading prescribers to select formulary prod-
ucts or recommended dosing frequencies.49 CPOE can also
• Utilization of evidence-based criteria, promote efficient medication use through more complex
• Adoption of published, evidence-based, and peer- scenarios such as prompting therapeutic interchanges or re-
reviewed guidelines from national organizations, quiring prescribers to follow interactive prescribing guide-
lines. For example, one institution established guidelines or similar body that has overall responsibility for non-labor
for activated protein C use and utilized an interactive com- cost management.
puter order entry algorithm to implement the guideline.50
Conclusion
Data Analysis. To ensure the validity of the medication-
utilization-management program, regardless of the method Medication costs continue to rise and will continue to be a
of implementation, the estimated and actual cost savings target for cost management. Drug costs make up a majority
calculations must be grounded in accurate and consistent of health-system pharmacy budgets, and budgeting for these
data analysis. Unfortunately, there is no standard regarding expenses is an important function, but longer-term program-
a method to determine the pharmaceutical cost savings with matic and policy planning is also essential for successful
programs such as TI. Hospitals have struggled for years to cost management. An effective plan for medication utiliza-
balance practical considerations while striving for accuracy tion management must provide the health system with a road
and completeness.20 Hospitals have to decide early in the map for continuous improvement in pharmaceutical expense
process whether to consider indirect costs such as devices containment with specific goals and outcome measures of
and other non-pharmaceuticals, price changes during the re- success. Gathering the data to understand drug expenditures
view period, general drug price inflation, volume changes, and drug-use patterns is a prerequisite for cost-savings ef-
and labor costs. forts, and constant vigilance and monitoring of these data
Equivalent doses for all drug alternatives for each TI are required.
must be established based on scientific evidence and cur- A relatively small number of drugs usually makes up
rent practice standards, which may not be the same as FDA- the majority of the drug budget. Cost-management efforts
approved manufacturers’ recommendations. Most of the ref- focused on these drugs will generally offer the best return.
erences cited for TI above list the therapeutic equivalence for Cost-management strategies that fall completely under the
the drugs in a specific class. Days of therapy is the common pharmacy department’s control (e.g., purchasing and inven-
method to compare equivalent costs of drug therapy within tory strategies) will be easiest to implement and should be
a therapeutic class, particularly for antibiotics and other pursued first. Strategies that require an interdisciplinary ef-
classes that include scheduled drugs that are dosed multiple fort (e.g., use of protocols or guidelines, therapeutic inter-
times per day. For classes that include drugs with extended change, IV-to-PO switches) can be led by pharmacists with
half-lives and durations of action, weeks of therapy or cost the proper clinical background. Clinical pharmacy services,
per course of therapy may be more appropriate. Examples such as participation in rounds, pharmacokinetic monitoring,
include colony-stimulating factors (e.g., epoetin versus dar- and renal dose adjustment, can also reduce drug expenses.
bopoetin and filgrastim versus pegfilgrastim). Correcting for Cost management efforts should be coordinated. The
equivalent strengths, sizes, and units of packaging is another programs should contain a clearly defined and manage-
important step in cost-savings calculations, particularly for able list of cost containment targets with a goal and specific
liquid and parenteral products. The number of standard targets for each initiative. Results should be measured and
doses available from a container of liquid medication or a evaluated, and this information should be shared with the
large volume parenteral medication varies based on the size interdisciplinary team involved in the effort as well as with
of the container. Medical staff input is important in deter- health-system administration.
mining equivalent doses, particularly if there is a divergence When selecting and implementing drug-cost-manage-
between manufacturer’s recommendations and published ment strategies, pharmacists must keep patient safety and
literature on dosing. the quality of patient care in mind. Cost-management ini-
Once the methodology of data analysis is established, a tiatives must never compromise the pharmacy department’s
drug savings matrix should be developed. This becomes the ability to provide the best possible care. Fortunately, there
primary monitoring document that tracks the progress of each are many drug-cost-management opportunities that have
initiative based on the changes in utilization. Purchase data is little or no potential for detrimental effects on patient care,
the typical source for maintaining the cost savings matrix, and efforts to improve appropriate use of a drug or drug class
but it is essential to adjust and scrub the data before matrix often also offer opportunities for cost containment.
input. It is important to maintain a consistent common de-
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50. Fischer MA, Lilly CM, Churchill WW, et al. An algo- Prescribing Guidelines
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the prescribing of new therapeutic agents: case study diseases for which health-systems have developed prescrib-
of activated protein C at an academic medical centre. ing guidelines, protocols, or pathways in collaboration with
Drug Saf. 2004; 27:1253–61. the medical staff and nursing staff.
Appendix—Therapeutic Interchanges, Albumin

Anesthesia gas, low flow and guidelines for selection
Prescribing Guidelines, and Other Antibiotic surgical prophylaxis
Interventions Antibiogram and antibiotic guidelines
Antifungal (injectable) agents (voriconazole, itracon-
Therapeutic Interchanges azole, caspofungin)
The following are some examples of drugs and drug classes Aprotinin dosing
for which health systems have successfully implemented Carbapenems
therapeutic interchange protocols: Chemotherapy-induced nausea and vomiting
Colony-stimulating factor guidelines/monitoring
Angiotensin-converting-enzyme inhibitors Drotrecogin alfa
Adenosine–dipyridamole for cardiac stress test Fosphenytoin
Amphotericin, lipid-based Heparin-induced thrombocytopenia
Angiotensin-receptor blockers Intensive care unit sedation protocol
Benzodiazepine hypnotics I.V. immune globulin
Beta-lactamase inhibitor antibiotics Levalbuterol
Cephalosporins: first- (oral), second-, and third- Nesiritide
generation Octreotide
Cholesterol-lowering agents Pneumonia protocol
Colony-stimulating factors (filgrastim and sargramos- Postoperative nausea and vomiting
tim, darbopoetin and epoetin alfa) Proton-pump inhibitors (i.v.)
Fluroquinolones Venous thromboembolism, use of anticoagulants in
Glycoprotein IIb/IIIa inhibitors acute coronary syndrome
Hepatitis B vaccine, pediatric strength Ziprasidone injection
Histamine H2-receptor antagonists
Inhaled and intranasal corticosteroids Interventions—Other
I.V. immune globulin Other initiatives or activities that pharmacists can collabo-
Insulins – various, including insulin aspart and insulin rate with the medical staff to reduce drug costs.
lispro
Cost per case in anesthesia ASHP gratefully acknowledges the expert panel that devel-
Antibiotic monitoring, laboratory reporting of sensi- oped these guidelines: Michael Rubino, M.S., FASHP; James M.
tivities Hoffman, Pharm.D., M.S., BCPS; Larry J. Koesterer, M.B.A.; and
Antibiotic restrictions Robert G. Swendrzynski, M.S.
Eptifibatide waste reduction
Epoetin alfa waste reduction, prepare syringes Copyright © 2008, American Society of Health-System Pharmacists,
Pegfilgrastim is used in outpatients only Inc. All rights reserved.
The bibliographic citation for this article is as follows: American

Society of Health-System Pharmacists. ASHP guidelines on medi-
Approved by the ASHP Board of Directors on January 17, 2008.
cation cost management strategies for hospitals and health systems.
These guidelines supersede the ASHP Technical Assistance Bulletin
Am J Health-Syst Pharm. 2008; 65:1368–84.
on Assessing Cost-Containment Strategies dated September 27, 1991.
Developed through the ASHP Council on Pharmacy Management.

Purpose Organizational and Operational
Health-system pharmacy, as an essential component in health • Re-engineering and downsizing initiatives

care organizations, is challenged by changes in the structure • Consolidation and integration of health systems and
and financing of health care to reduce costs and improve per- departments within health systems
formance. One option being used to achieve these goals is • Elimination of or reduction in the size of traditional
outsourcing. Outsourcing is a formal arrangement by which departments
a health care organization contracts with an outside company • Reorganization around patient-focused care
to obtain selected pharmaceutical services or comprehensive • Implementation of automated pharmacy systems and
management of the organization’s pharmacy. Through this ar- the attendant need to reorganize medication distribu-
rangement, the organization negotiates a contract with a com- tion functions
pany to access its expertise, technologies, and resources.
ASHP believes that the organization’s pharmacist- Staffing
in-charge (e.g., a pharmacy director) must take complete re-
sponsibility for patient outcomes from all medication-related • Shortage of nurses and other health care professionals
activities performed at or for the organization’s work sites, • Shortage of pharmacists with specific experience and
whether they are carried out by the organization’s or contrac- capabilities
tor’s onsite staff or by the contractor off site. This responsi-
bility should be explicitly stated in all outsourcing contracts. Financial and Cost-Control
Health care organizations considering outsourcing
pharmaceutical services should have a clear understanding • Restricted budgets
of what they want to accomplish. Consideration should in- • Increased operating costs
clude, at the least, an internal needs assessment, a cost analy- • Increased drug costs
sis, and a careful review of possible contractors. The organi- • Increased emphasis on measuring performance in
zation should examine the potential long-term consequences terms of staffing and costs instead of clinical outcomes
of outsourcing as well as the short-term outcomes expected
during a contract’s performance period. Quality
The purpose of these guidelines is to provide an over-
view of factors and processes for health care organizations to • Increased expectations of and pressures from accredi-
consider when exploring outsourcing. The ideas presented in tation organizations and consumer groups to improve
this document could be used for strategic planning with the the quality of patient care
organization’s decision-makers, for drafting contract provi-
sions, for comparing prospective contractors, for preparing Governmental and Regulatory
for contract negotiations, or for evaluating a contractor’s
performance. These guidelines may be applied, for example, • Increased numbers of individuals dependent on fed-
to independent and networked acute care hospitals, ambula- eral, state, and local governments for health care
tory care clinics, and home care providers. • Reduced ability of federal, state, and local govern-
This document includes ideas about reasons for out- ments to finance health care
sourcing and reasons for not outsourcing, services available • Increased government controls on reimbursement for
from contractors, the outsourcing process and outsourcing ar- health care
rangements, and evaluation of contractor performance. The
appendix provides a topical list of contract provisions, some Competitive
of which relate to specific pharmaceutical services, pharmacy
practices, or administrative functions that may be the subject • Increased competition among health care organizations
of other ASHP practice standards. Organizations should refer • Increased competition among suppliers of pharmaceu-
to pertinent ASHP practice standards for additional informa- tical products and related services
tion on which to base their contract provisions, agreements, and
decisions. This document addresses representative outsourcing Purposes of Outsourcing
options and contract agreements and is not intended to cover all
situations. Managers of pharmacy and health care organizations Health care organizations that conduct in-depth assessments
should use their professional judgment about applicability to may decide that outsourcing either is or is not a good option
their own needs and circumstances. for meeting their needs. Reasons for their decision will vary
according to a variety of factors.
Environment
Reasons Health Care Organizations Outsource Pharmaceu-
Various environmental influences and market forces that tical Services. Organizations tend to outsource pharmaceutical
may contribute to outsourcing being considered as an option services when guided by a careful assessment of their capabili-
include the following. ties of providing services themselves, when unsuccessful in
using their own resources to provide services, or, in some cases, Reasons Health Care Organizations Do Not Outsource
when influenced by a consultant. Contracting with an outsourc- Pharmaceutical Services. An organization’s choice to con-
ing firm may produce one or more of the following results. tinue providing its own pharmaceutical services may be
based on one or more of the following reasons.
Organizational and operational
• Ease the consolidation of pharmaceutical services in Organizational and operational
integrated health systems • A belief that pharmaceutical services are well man-
• Resolve operational inefficiencies (e.g., by improving aged and are provided as effectively as or better than
medication distribution systems, designing new phar- they could be by a contractor
macy workspaces, reducing medication dispensing • Negative experiences with outsourcing contractors
and administration errors, and improving computer (pharmacy or nonpharmacy) or awareness of other or-
and information systems) ganizations’ negative experiences with such contrac-
• Enable the organization to acquire additional re- tors
sources and expertise to carry out other changes • Concern that the decision to outsource pharmaceutical
(e.g., reallocation of existing staff to pharmaceuti- services can be reversed only with great difficulty
cal care roles in patient care areas) • A belief that the organization’s needs are currently
• Provide educational programs for patients and met cost-effectively and that changes are therefore
their families and for health care staff unnecessary
• Concern about losing short-term and long-term control
Staffing over decisions about pharmaceutical services
• Help the organization to staff hard-to-fill pharmacy • Concern about reduced involvement of pharmacy lead-
positions ership in organizationwide initiatives (e.g., develop-
• Allow the organization to reach optimal staffing levels ment and implementation of information systems, clini-
for achieving productivity targets cal care plans or pathways, and disease management)
Financial and cost-control Staffing

• Control or reduce the cost of the organization’s services • Concern that staff will be reduced to unacceptable levels
• Control or reduce labor costs (e.g., by shifting the cost • Concern about potentially alienating relationships be-
of employees, benefits, and liabilities to a contractor) tween pharmacists and other health care staff
• Enable the organization to acquire a contractor who
will share the risks associated with operating the phar- Financial and cost-control
maceutical services • An assessment that outsourcing would increase rather
• Avoid the cost of purchasing and maintaining phar- than decrease costs
macy equipment • Concern that high-cost drugs might be excluded from
• Avoid the cost of physical remodeling (e.g., by using contract agreements
an offsite contractor to provide specific services for • Concern that the organization may not be able to
which remodeling would be required) recapitalize pharmaceutical services if outsourcing is
• Increase the organization’s financial operating margin unsuccessful
(e.g., by allowing the organization to purchase drugs
in bulk quantities, use group purchasing contracts, de- Quality
crease lost charges, improve billing accuracy, decrease • Concern that conflicting values and priorities of the
drug diversion and pilferage, improve drug formular- outsourcing contractor and the organization will re-
ies, and transfer drug inventory, equipment, and sup- duce quality
ply activities to a contractor) • Concern that clinical quality could be reduced as a re-
sult of a loss of continuity of pharmacy staffing and
Quality relationships with medical and nursing staffs
• Enable the organization to maintain or improve the qual-
ity of patient care (e.g., by expanding clinical services Professional responsibility
and pharmaceutical care, establishing new services, and • Concern that outsourcing will confuse or dilute the on-
obtaining specialized expertise in pharmaceutical care) site pharmacists’ ultimate professional authority and
• Provide support for the medical and nursing staffs and responsibility for all medication-related activities and
improve physician–nursing–pharmacy collaboration outcomes at the site
Governmental and regulatory

• Correct regulatory and accreditation problems relating Pharmaceutical Services
to pharmaceutical services Provided by Contractors
• Ensure continuing compliance with accreditation and
certification standards Some contractors manage and provide comprehensive
pharmaceutical services. Other contracors focus more on
Competitive providing specialty services or carrying out specific tasks
• Enhance the organization’s image (e.g., drug information services, offsite preparation of
• Allow the organization to gain an edge on competitors sterile products). The needs of the health care organiza-
through improvements in service, quality, or price tion should guide the identification of potential contractors
with the appropriate expertise and capabilities. Examples • The organization’s financial status (e.g., a current bal-
of services that may be available from contractors follow. ance sheet and audited financial statement, the phar-
(This list is likely to grow over time.) macy’s financial status)
• A description of the process the organization will use
Organizational and Operational to select the contractor
• Development of pharmacy policies, procedures, and • The organization’s standard terms and conditions for
processes contracting for services
• Pharmacy record-keeping systems • The names and telephone numbers of individuals in
• Productivity reviews the organization who are involved in the outsourcing
• Feasibility studies on expanding services (e.g., outpa- decision (the director of pharmacy should be included)
tient dispensing and home infusion) • A description of the specific outsourced services re-
• Unit dose medication distribution quired of the contractor (e.g., pharmacy workspace
• Pharmacy-based or offsite preparation of sterile products design, intravenous admixture preparation, and imple-
• Pharmacokinetic monitoring and dosage determinations mentation of an automated pharmacy system) and per-
• Medication therapy monitoring (e.g., for appropriate formance-measurement criteria or targets
and effective use) • The date(s) on which the contractor can inspect the
• Investigational drug programs facility and the pharmacy
• Patient profile reviews • The number of copies of the proposal to submit
• Medication therapy-related consultation with physi- • The name and address of the individual to whom the
cians, nurses, and other health care professionals proposal is to be delivered
• Assessment of patients’ nutritional needs • Acceptable method(s) for delivery of the proposal
• Guidance in purchasing and implementing automated (e.g., mail, delivery service, courier)
pharmacy equipment • A statement that the organization reserves the right to
• Educational programs for patients, families, and cancel its solicitation for services and reject any and
caregivers all proposals
• Drug information services • A deadline date and time for receipt of the proposal
• Packaging and repackaging of pharmaceuticals • The date on which the contractor would be expected to
initiate services
Staffing • The date by which the selected contractor must pro-
vide a written contract
• Competency assessment and performance review
• Management, operational, and clinical training • Other requirements related to the proposal (e.g., that
it be typewritten, that it include reference to an RFP
• Recruitment and retention assistance
number [if any], that it be signed by an officer of the
Financial and Cost-Control firm who is authorized to contract)
• Billing Contents of Proposals. RFPs often require contractors to

• Inventory control submit the following information with their proposals.
• Formulary management
Quality
• A brief history of the contractor, including its mission,
vision, and values
• Performance improvement (including improvement of • The location of the contractor’s offices and other fa-
medication use and reduction of medication errors) cilities that would provide services to the organization
• Quality assurance • The names, addresses, telephone numbers, and résu-
més or background information on the individual(s)
Outsourcing Process who will provide the services
• Evidence that the contractor can provide qualified staff
After the health care organization has completed an internal who are licensed or eligible for licensure by federal,
assessment of its needs and capabilities and decided to ex- state, and local agencies and a history of turnover in
plore outsourcing, it should identify and contact reputable management, pharmacist, and support staff
and experienced contractors. Some organizations simply • A history of the results of Joint Commission on Accre-
identify prospective contractors and ask them to submit a ditation of Healthcare Organizations (JCAHO), Health
proposal. A more thorough approach is to require prospec- Care Financing Administration, National Committee
tive contractors to respond to a request for proposals (RFP). for Quality Assurance, state, or other accreditation or
Although a formal RFP (and the contractor’s formal pro- regulatory surveys conducted in the contractor’s sites
posal based on the RFP) may not be necessary, the informa- • Proof of professional liability, general liability, and
tion found in typical RFPs and proposals may be helpful for workers’-compensation insurance coverage (includ-
making a decision about outsourcing. ing the name, address, and telephone number of the
insurance company) and a history of claims filed
Contents of RFPs. RFPs often include the following against the contractor
information. • Minimum-experience requirements (e.g., years of
experience in providing outsourced pharmacy-
• A description of the organization (including statistical management services, total number of clients served,
information) current number of clients)
• A list of the requested services that the contractor can • Additional qualities (e.g., high employee morale, con-
provide fidentiality, creativity, sensitivity to minorities and the
• A list of the requested services that the contractor can- community, willingness to share risks and rewards)
not provide and the reasons for the contractor’s inabil- • Cost aspects of services (e.g., cost-effectiveness, abil-
ity to provide them ity to affect economies of scale)
• Evidence of organizational and staff experience and
competence (including nature and extent) in the ser- The organization should assign an evaluation rating
vices the contractor can provide (e.g., pharmaceutical to each proposal. Ratings should be weighted appropriately
care, specialty clinical practice, antineoplastic medica- with respect to professional services, experience, references,
tion preparation, enteral and parenteral nutrition solu- and cost of services. The organization should base its deci-
tion preparation), as pertinent sion to outsource pharmaceutical services on its assessment
• A copy of a standard or proposed contract of the contractor’s ability to meet the organization’s needs
• A list of all fees and charges that would be billed under and fulfill the terms of the contract.
the contract and the detailed methods for their calcula-
tion, as well as a billing schedule Negotiating the Contract. The organization should carefully
• A description of reports that the contractor will be ex- review the proposal and clarify the provisions of the contract.
pected to submit to the organization Assistance from the organization’s risk-management and legal
• Information relating to the contractor’s financial status counsel may be necessary. Negotiations can ensure a contract
and stability (e.g., balance sheets and audited financial that best meets the needs of the organization and the contractor.
statements for the past three years, bank references,
lists of principal equity owners) Signing the Contract. In some organizations the director
• The names, addresses, and telephone numbers of cur- of pharmacy may be authorized to sign contracts for out-
rent clients receiving similar services sourced services. If this is not the case, the director of phar-
• The names, addresses, and telephone numbers of other macy should be fully involved in negotiating the contract
clients served within the past two years and the rea- and advising the authorized signer(s).
sons for all, if any, terminations of services
• Written references and copies of annual performance- Outsourcing Arrangement
improvement reports from clients of a similar size with
similar types of patients The health care organization and the contractor should agree on
the outsourcing arrangement that best meets their needs. Several
Visits to Contractors and Their Clients. Contractors should outsourcing options are available to health care organizations.
allow the organization’s representatives to visit their corporate Variations and combinations of these options are common. The
offices and production facilities and to tour pharmacies in the contract should clearly describe the outsourcing arrangement.
facilities of other clients. The contractor should provide ample Examples of outsourcing arrangements include the following.
opportunity for the organization’s representatives to confer
with the contractor’s corporate and pharmacy staff. Consulting. The contractor acts as a pharmacy consultant to
the organization. Some consulting arrangements are limited
Evaluating Proposals. A decision to outsource pharmaceuti- to an assessment of all pharmaceutical services or to specific
cal services should be collaborative and should involve, as aspects of pharmaceutical services (e.g., clinical pharmacy
appropriate, the governing board, the chief executive officer services, productivity, compliance with JCAHO standards).
(CEO), the chief financial officer (CFO), the chief operating Other consulting arrangements may include advising the
officer (COO), the chief of the medical staff, the chair of the pharmacy and helping it to improve its services.
pharmacy and therapeutics committee, the director of nurs-
ing (DON), the director of pharmacy, and department heads, Onsite Advisor. The contractor provides a full-time onsite ad-
for example. The organization should scrutinize the follow- visor to the organization’s director of pharmacy. The advisor
ing factors when evaluating proposals. works with the director of pharmacy and others, as needed,
to carry out programs that will fulfill the contract provisions.
• Services offered versus services requested (including
the contractor’s ability to enhance current services) Management of Specific Pharmaceutical Services. The
• Professional experience (e.g., years of service; num- contractor provides one or more specific services (e.g., i.v.
ber, size, and types of clients; knowledge of the client’s admixture preparation, drug information, stock replenish-
business) ment, medication distribution). Services may be provided
• Financial stability (e.g., ability to absorb start-up expenses onsite or at an offsite location.
and to commit the resources needed to effect change)
• References and reputation (e.g., client-satisfaction re- Comprehensive Management. The contractor assumes
ports, reputation in the health care industry, commit- complete responsibility for operating the pharmacy and may
ment to improving patient care) provide some or all of the pharmacy staff.
• Technology or automated pharmacy systems (e.g., up-
to-date hardware, proprietary software, the capability to
interface with the organization’s information systems) Contract Provisions
• Education and training (e.g., internal and external con-
tinuing-education programs, educational allowances A contract that meets the needs of the health care organiza-
for professional and technical staff) tion and of the contractor is the foundation for a successful
relationship. Contracts should include provisions of the out- 8. Gates DM, Smolarek RT, Stevenson JG. Outsourcing
sourcing arrangement that describe agreements between the the preparation of parenteral nutrient solutions. Am J
organization and the contractor concerning their respective Health-Syst Pharm. 1996; 53:2176–8.
responsibilities. These provisions will vary depending on the 9. Burruss RA, Carroll NV, Schraa C, et al. Outsourcing in-
kind and scope of services outsourced. For example, contrac- patient IV compounding: expense and medication error
tors who prepare sterile products at an offsite location will not implications. Pharm Pract Manage Q. 1996; 16(3):52–9.
require onsite pharmacy space and utilities. Also, the assign- 10. McAllister JC III. Collaborating with re-engineering
ment of responsibilities may vary. A contract may specify that consultants: maintaining resources for the future. Am J
the organization will purchase all drugs. Conversely, another Health-Syst Pharm. 1995; 52:2676–80.
contract may assign this responsibility to the contractor. See 11. Anderson RJ. Clinical service contracts between hos-
the appendix for examples of contract provisions. pital pharmacy departments and colleges of pharmacy.
Am J Hosp Pharm. 1991; 48:1994–7.
Evaluation of Contractor’s Performance 12. Murphy JE, Ward ES, Job ML. Implementing and
maintaining a private pharmacokinetics practice. Am
Health care organizations should evaluate and document J Hosp Pharm. 1990; 47:591–7.
their contractor’s performance and assess their contrac- 13. Souhrada L. Contract management. Hospitals. 1990;
tor’s compliance with the terms of the contract. Objective 64(8):66–8.
and subjective evaluations should be regular (e.g., quarterly 14. Wagner M. Basic pitfalls can undermine hospital–
or annually). Evaluations should address all measurable service firm relationship. Mod Healthc. 1993; 23(8):32.
standards of performance that are specified in the contract. 15. Wagner M. Contract-managed pharmacy depart-
Evaluations should be multidisciplinary and should involve, ments are just the prescription at some hospitals. Mod
for example, the CEO, CFO, COO, DON, and medical staff Healthc. 1988; 18(8):36–40.
representatives, as appropriate. An evaluation may include
an assessment of how well the contractor performed the fol- Appendix—Contract Provisions
lowing functions.
The following are examples of contract provisions that,
• Improved the quality of patient care among others, the organization and contractor might adapt as
• Responded to the organization’s needs needed and include in a contract, depending on the scope of
• Helped the organization to achieve its financial and services being considered. In addition, a contract would in-
patient-outcome goals clude provisions about the specific pharmaceutical services
• Evaluated the productivity and performance of phar- to be provided by the contractor. The language in contract
macy staff provisions should be adapted to meet the needs of the health
• Provided continuing education for pharmacy staff care organization and to comply with the organization’s con-
• Implemented and improved pharmacy clinical programs tracting policies and applicable laws and regulations.
• Improved pharmacy processes (e.g., medication dis-
pensing and delivery) Accreditation and Certification: A contract may include
• Reduced and controlled pharmacy costs without com- a requirement that services meet or exceed applicable
promising patient care accreditation and certification standards. These in-
• Worked and communicated effectively with the orga- clude, but are not limited to, the standards (or require-
nization’s staff and resolved interdepartmental prob- ments) of the following organizations.
lems • Joint Commission on Accreditation of Health-
• Participated effectively in the organization’s perfor- care Organizations
mance-improvement program • American Osteopathic Association
• Health Care Financing Administration
Suggested Reading • National Committee for Quality Assurance
After-Hours Pharmaceutical Services when 24-Hour
1. Curtis FR, Stai HC. Contract pharmacy services. In: Services Are Not Provided: The contractor may
Brown TR, ed. Handbook of institutional pharmacy agree, for example, to provide an after-hours stock
practice, 3rd ed. Bethesda, MD: American Society of of drug products for authorized staff to use in filling
Hospital Pharmacists; 1992: 299–306. urgent medication orders. In addition, the contractor
2. Talley CR. Outsourcing drug distribution. Am J may agree to ensure that a pharmacist is on call or
Health-Syst Pharm. 1997; 54:37. Editorial. available to return to the facility to provide pharma-
3. Schneider PJ. Outsourcing: a key to professional sur- ceutical services.
vival. Am J Health-Syst Pharm. 1997; 54:41–3. Automation: A contract may outline responsibilities for the
4. Lazarus HL. Outsourcing: a success story. Am J purchase or lease and the use of automated medication
Health-Syst Pharm. 1997; 54:43–4. storage and distribution equipment and software asso-
5. Puckett WH. Outsourcing: taking the first step. Am J ciated with the equipment.
Health-Syst Pharm. 1997; 54:45–8. Choice of Law: There may be a statement that the contract
6. Kolar GR. Outsourcing: route to a new pharmacy prac- is governed by the laws of the state in which patient
tice model. Am J Health-Syst Pharm. 1997; 54:48–52. care is provided.
7. Eckel FM. Outsourcing: at odds with pharmacy’s pro- Compensation for Contractor’s Services: There may be
fessional foundation. Am J Health-Syst Pharm. 1997; compensation arrangements, which vary greatly but are
54:52–5. often based on one or more of the following principles.
• Management fee(s) vide a hazardous-materials handling program, includ-

• Fee per item dispensed or service performed ing staff training, that meets Occupational Safety and
• Fixed fee per patient per patient day, admission, Health Administration (OSHA) requirements.
discharge, adjusted patient day, adjusted admis- Drug Inventory Disposition upon Termination of the
sion, or adjusted discharge Contract: A provision for the disposition of the drug in-
Besides agreeing on a compensation arrangement, the ventory is based on inventory ownership. In cases in which
organization and the contractor may agree on ways for the drug inventory may be purchased by either party, a mu-
the contractor to share the financial risk of contract tually acceptable, independent appraiser could decide the
performance with the organization; these might in- purchase price. Legal advice may be needed to ensure that
clude guarantees or incentives for meeting targets and purchases comply with the Prescription Drug Marketing
penalties for underperformance. Act and other applicable laws and regulations.
Computer Equipment and Information Systems: A con- Drug Inventory Ownership: If the contractor purchases the
tract may outline responsibilities for the purchase, organization’s inventory, a mutually acceptable, indepen-
ownership, and maintenance of computer equipment dent appraiser could decide the purchase price. Expired
and related software. Agreements might extend to per- and other unusable drugs should be excluded from the pur-
sonal computers used by pharmacy staff. There should chase. The contractor could agree to obtain credit for the
be clear agreement about access to and use of data gen- organization for expired and other unusable drugs if credit
erated by the information system. is obtainable. Legal advice may be needed to ensure that
Confidentiality: There may be a requirement that informa- purchases comply with the Prescription Drug Marketing
tion not generally available to the public (e.g., finan- Act and other applicable laws and regulations.
cial statements, medical records, market information) Drug Ordering: A contract may assign responsibilities for
be kept confidential. Both parties must agree to safe- selecting vendors and purchasing drug supplies for the
guard access to computer databases and patient records organization. The contract should specify that all drugs
to ensure that the patient’s rights to privacy and confi- used must be subject to approval by the organization’s
dentiality is protected. Use of the information should pharmacy and therapeutics (P&T) committee or its
be limited solely to purposes specified in the contract. equivalent. The organization should understand how
Contractor Reports: The content and regularity of perfor- purchasing discounts are accounted for, recorded, and
mance reports that the contractor will submit to the distributed. The impact of removing pharmacy items
organization may be specified. from group purchasing programs should be clear also.
Controlled Substances: Responsibilities may be assigned Early Termination: There may be conditions for early ter-
for the procurement and security of controlled sub- mination of the contract.
stances in compliance with Drug Enforcement Admi- Extension of Period of Performance: Conditions for ex-
nistration (DEA) and state regulations. For example, tending the period of performance may be included in
the organization may be required to the contract.
• Register with the DEA and any state equivalent Forms: Responsibilities for the design, approval, purchase,
for each site involved and storage of forms may be assigned.
• Assume complete responsibility for record Formulary System: A contract may assign responsibilities
keeping and security of controlled substances for evaluation of medications, collaboration with the
throughout the facility P&T committee, and provision of formulary-related
• Ask the contractor to maintain proper records and information services.
provide adequate security for controlled substances Hours of Pharmacy Operation: A contract may specify
as required by federal, state, and local laws and reg- hours of operation that meet or exceed legal require-
ulations and ments and that are sufficient to serve patients’ needs.
• Verify that the contractor maintains proper re- Laws, Rules, and Regulations: Requirements for services
cords and provides adequate security for con- to meet or exceed federal, state, and local laws, rules,
trolled substances and regulations may be specified. These include but
It may be necessary for the organization to grant are not limited to those of FDA, DEA, OSHA, and
power of attorney to the contractor to order and pur- the state board of pharmacy. The pharmacy should
chase controlled substances. maintain (e.g., display, file) the appropriate licenses,
Similarly, the contractor may be required to permits, and records of equipment maintenance and
• Ensure that all registrations are current certification. Any contractor required to be licensed as
• Order and maintain an adequate stock of con- a manufacturer must be so licensed. The organization
trolled substances may agree to allow the contractor to act on the organi-
• Ensure compliance with record-keeping and se- zation’s behalf in communicating with the state board
curity requirements of pharmacy and other regulatory agencies.
• Inform the organization of problems with Liability Insurance: Responsibilities for maintaining liabil-
compliance ity insurance coverage for the acts of employees may
Cost Control: A contract may include objectives, methods, be assigned. The contract might specify, for example,
and performance measures for controlling costs. that the contractor must maintain adequate liability in-
Cytotoxic and Hazardous Drug Products: Responsibilities surance coverage for the acts of its employees.
for ensuring the safety of the organization’s staff and Nondiscrimination: There might be a requirement that the
patients during the preparation and distribution of cy- contractor abide by all laws and regulations relating
totoxic and hazardous drug products may be assigned. to discrimination in appointments, promotions, and
Either the organization or the contractor should pro- terminations.
Ownership of Equipment, Fixtures, and Supplies: A con- Record Maintenance: A contract may assign responsibili-
tract may specify ownership of equipment, fixtures, ties for maintaining and storing records. The contract
and supplies and responsibilities for ensuring that should specify that all pertinent records must be kept
equipment is maintained and certified according to ap- for the time required by law and by the organization.
plicable practice standards, laws, and regulations. Space: Responsibilities for space required by the contrac-
Performance Improvement: Responsibilities for establishing tor to provide onsite services might be outlined. The
any performance-improvement programs and integrating organization should agree to provide space for the
them with the organization’s performance-improvement provision of onsite contractor services that is accept-
activities may be included. Performance-improvement able to the contractor and within the guidelines of
programs might be appropriate, for example, for the order- the agencies that regulate the practice of pharmacy.
ing, dispensing, and administering of medications and for Organizations might agree to provide the following fa-
the monitoring of medication effects and misadventures, cilities, depending on the contract’s scope of services.
including adverse drug reactions and adverse drug events. • Adequate square footage
Period of Performance: The contract might specify the pe- • Space for preparing, compounding, packaging,
riod for which the contractor will provide services to and storing drugs under proper conditions
the organization. • Space for receiving and storing intravenous flu-
Pharmacy Staff Education and Training: Responsibilities ids and supplies
for required ongoing staff education and training may • Refrigerators and freezers
be specified. For example, there might be an agreement • Adequate space for maintaining and storing
that the contractor’s staff will participate in the organi- pharmacy records
zation’s education and training programs. In addition, • Laminar-airflow hoods and biological safety
the contractor may agree to provide specific training to cabinets (if needed)
ensure that all pharmacy personnel can perform any du- Sterile Products: A contract might include requirements for the
ties imposed by contractor-implemented functions. quality of sterile products provided by the contractor. The
Pharmacy Staff Employment: There may be a provision for contractor should ensure that sterile products (e.g., large-
the employment of pharmacists and technical and support volume intravenous admixtures, total parenteral nutrient
personnel; this may specify those who will be employed solutions) are prepared and labeled in a suitable environ-
by the organization and those who will be employed by ment by trained and competent employees. The contrac-
the contractor. Whether employed by the organization or tor should provide quality-control information periodi-
by the contractor, all staff should be competent and legally cally and on demand. For services that involve deliveries,
qualified. The organization should retain the right to as- the contract should specify order cutoff and delivery
sess, accept, or reject the performance of any of the con- times, any penalties for late deliveries, and arrangements
tractor’s staff who are used at the organization’s work sites. for after-hours or emergency services and deliveries.
Pharmacy Staff Expenses: Responsibilities for any person- Successors: The rights of each party in the event that the or-
nel expenses may be assigned. A contract might spec- ganization or contractor merges or transfers its business
ify, for example, that the organization will be responsi- or assets to a successor may be included in a contract.
ble for the salary, wages, and benefits of its employees Utilities: A contract may assign responsibility for utilities re-
whereas the contractor will be responsible for such quired by the contractor to provide onsite services. These
expenses for its own employees. The contract might utilities may include the following, as appropriate.
also allocate expenses for parking, meal discounts, and • Electrical service
similar privileges for employees. • Water
Pharmacy Staff Levels: There may be a requirement that • Heating and air conditioning
the staffing levels for the contracted services be suf- • Plumbing
ficient to meet the organization’s needs. • Janitorial services
Pharmacy Staff Orientation: A contract may assign re- • Internal and external telephone services (allow-
sponsibilities for orientation of all new pharmacy staff ance might be made for a private external tele-
members to the organization and to the pharmacy, ac- phone line for the contractor)
cording to the organization’s requirements. • Security
Pharmacy Staff Performance: Responsibilities for phar- • Waste disposal
macy staff competency assessments and performance
evaluations and for ensuring that assessments and
evaluations are based on criteria in the individual’s job These guidelines were reviewed in 2013 by the Council on Pharmacy
description may be assigned. Management and by the Board of Directors and were found to still
Policies and Procedures: Responsibilities may be assigned be appropriate.
for developing policies and procedures covering the
outsourced services, all of which should comply with Approved by the ASHP Board of Directors, April 22, 1998.
applicable laws, regulations, and accreditation or certi- Developed through the Council on Administrative Affairs.
fication standards. The contract should specify that the
policies and procedures must not conflict with those of Copyright © 1998, American Society of Health-System Pharmacists,
the organization. Inc. All rights reserved.
Purchasing and Accounts Payable: Responsibilities for main-
taining the pharmacy’s purchasing and accounts-payable The bibliographic citation for this document is as follows: American
functions, including ordering drugs, monitoring costs, Society of Health-System Pharmacists. ASHP guidelines on outsourcing
and authorizing payment to vendors, might be specified. pharmaceutical services. Am J Health-Syst Pharm. 1998; 55:1611–7.

Sterile Compounding Services
Purpose Compounding Pharmacies. Section 503A clarified the
FD&C Act for activities described as traditional patient-
The purpose of these guidelines is to provide an overview specific compounding (sometimes now called “503A com-
of factors and processes for healthcare organizations to pounding”). Healthcare organization pharmacies fall into
consider when contracting with compounding pharmacies this category, as do other pharmacies that fill prescriptions
or outsourcing facilities to obtain sterile compounding ser- or medication orders within a prescriber–pharmacist–patient
vices. These guidelines describe services available from professional relationship. All 503A compounding pharma-
compounding pharmacies or outsourcing facilities, reasons cies, except those in federal facilities, are regulated by state
for outsourcing and reasons for not outsourcing, the out- boards of pharmacy; however, they may also be subject to
sourcing process and outsourcing arrangements, and recom- Food and Drug Administration (FDA) inspection under the
mendations for evaluating a contractor’s performance. The agency’s authority to enforce section 503A of the FD&C
guidelines also provide a topical list of contract provisions, Act. The agency’s expectations for compliance are specified
some of which relate to practices that are the subject of other in the FDA Compliance Policy Guide (CPG) on Pharmacy
ASHP guidelines. Organizations should refer to pertinent Compounding of Human Drug Products Under Section
ASHP guidelines for additional information on which to 503A of the Federal Food, Drug, and Cosmetic Act.5 In ad-
base their contract provisions, agreements, and decisions.1-3 dition to current regulatory requirements, such as prescrip-
The concepts presented in this document could be used for tions or medication orders for compounded preparations and
strategic planning with the organization’s decision-makers, compliance with applicable United States Pharmacopeia
assisting in assessing the quality of compounded sterile (USP) chapters on compounding (i.e., USP chapters 795
preparations or products, drafting contract provisions, com- and 797),8,9 inspectors may look for implementation of ad-
paring prospective contractors, preparing for contract nego- ditional CPG recommendations. The services provided by
tiations, and evaluating contractor performance. compounding pharmacies are limited by the existing re-
This document addresses representative outsourcing quirement for individual prescriptions or medication orders
options and contract agreements and is not intended to cover and may be further limited by forthcoming regulation of
all situations. Managers of pharmacy and healthcare orga- distribution across state lines,7 state and federal restrictions
nizations should use their professional judgment about ap- on office-use preparations, and other limitations of section
plicability to their own needs and circumstances. 503A.
Outsourcing Facilities. Section 503B outsourcing facilities

Services Provided by are not required by federal regulation to be licensed phar-
Vendors of Outsourced macies or to fill prescriptions or medication orders; how-
Sterile Compounding Services ever, a licensed pharmacist must supervise compounding.
Outsourcing facilities are federally regulated by FDA, which
The Drug Quality and Security Act (DQSA) of 2013 dra- has established guidance documents for the industry that will
matically changed federal regulation of pharmacy com- be updated as necessary. Outsourcing facilities must com-
pounding.4 The DQSA amended the federal Food, Drug, ply with applicable Current Good Manufacturing Practices
and Cosmetic (FD&C) Act, carving out a safe harbor for (CGMPs) established under section 503B by FDA,6 which
traditional, prescription-based compounding pharmacies differ from those for manufacturers. States may establish
(called “503A compounding pharmacies” for the section of additional requirements with which outsourcing facili-
the FD&C Act that regulates them, or, more simply, “com- ties must comply. All outsourcing facilities are inspected
pounding pharmacies”) and creating a new category of drug by FDA. The frequency of reinspections is determined by
establishment, Human Drug Compounding Outsourcing a risk-based schedule. Inspection findings are documented
Facilities. These facilities (frequently referred to as “reg- on form FDA-483, Inspectional Observations. A form FDA-
istered 503B outsourcing facilities” for the section of the 483 is used to notify the entity of any concerns or potential
FD&C Act that regulates them, or, more simply, “outsourc- violations and provide an opportunity for correction before
ing facilities”) are permitted to engage in the manufacture enforcement action.10 The compounding facility may work
and interstate shipment of larger quantities of compounded with inspectors to resolve issues during the inspection or re-
sterile drug products without prescriptions or medication spond in writing with a corrective action plan, usually within
orders. (For the purposes of these guidelines, both types 15 days. The contents of these forms are publicly available.11
of entities are referred to as “vendors of outsourced sterile However, findings in FDA-483 reports do not represent a
compounding services” or, simply, “vendors.”) The regula- final determination of noncompliance, nor is information
tory changes spawned by the DQSA have significant impli- available indicating that the findings have been satisfacto-
cations for compounding pharmacies, outsourcing facilities, rily resolved.
and their customers. Healthcare organizations considering Healthcare organization pharmacy leaders must be
outsourcing sterile compounding services need to have a aware of the quality standards that should be expected
clear understanding of how these two distinct types of enti- from outsourcing facilities.12,13 In a letter sent to hospitals
ties are regulated (Table 1). in January 2014, FDA encouraged healthcare organizations
Table 1.
Differences Between Compounding Pharmacies and Outsourcing Facilitiesa
Section 503B Registered Outsourcing
Variable Section 503A Compounding Pharmacies Facilities
Regulatory authority State boards of pharmacy FDA, according to guidelines established
by federal legislation; states may add
requirements
Applicable standards USP compounding standards; FDA Compliance Applicable section 503B-specific FDA Current
Policy Guide on Pharmacy Compounding of Good Manufacturing Practice6; subject to
Human Drug Products Under Section 503A of additional state requirements
the Federal Food, Drug, and Cosmetic Act5
FDA inspection Subject to FDA inspection under authority to Subject to risk-based FDA inspection and
enforce section 503A enforcement procedures
State inspection Subject to state board of pharmacy inspection May be subject to state inspection if state law
imposes additional requirements
Limitations on services • May only dispense pursuant to an • Not required to be a licensed pharmacy or
individual prescription or medication order obtain prescriptions for specific patients
for an identified patient • May compound and maintain inventory of
• Anticipatory compounding of “limited compounded products in anticipation of
quantities” is permitted, but a prescription customer orders
or medication order is required before • No federal limit on interstate commerce;
dispensing5 some state regulations may apply
• FDA limitations on interstate distribution, • Compounding from bulk APIs only allowed
either 5% or 30%, depending on whether for drugs on approved list
the state has entered into an MOU with • May compound copies of FDA-approved
FDAb products from bulk substances if on FDA
• May not compound shortage list
• Drugs that present demonstrable
difficulties for compounding
• Copies of FDA-approved products
• Drugs using certain prohibited bulk
substances
Office-use compounding Not yet addressed in FDA guidance5 Permitted; resale prohibited but “resale” does
not include administration or dispensing by
the purchaser4
Labeling requirements As mandated by state law and regulation Must include “Office use,” “This is a
compounded drug,” and “Not for resale”
aFDA = Food and Drug Administration, USP = United States Pharmacopeia, MOU = memorandum of understanding, API = active
pharmaceutical ingredient.
bAt the time of writing, FDA had not issued final guidance on interstate distribution by section 503A facilities but had proposed a 30% limit on
interstate distribution of compounded sterile preparations by section 503A compounding pharmacies in states that had entered into an MOU with
FDA and a 5% limit in states that had not entered into an MOU.7
to purchase compounded sterile drugs from FDA-registered Environmental Influences Affecting

outsourcing facilities.14 Although FDA usually inspects an
Outsourcing Decision
outsourcing facility soon after registration (unless the facil-
ity has been inspected previously), pharmacy leaders should
There are various environmental influences and market
be aware that registration does not necessarily mean that a
forces that may contribute to a facility’s decision to consider
particular outsourcing facility has been inspected and found
outsourcing sterile compounding services. A list of some of
to meet FDA standards. FDA’s website listing registered
those considerations follows.
outsourcing (503B) facilities provides dates of the initial
and most recent registration as an outsourcing facility; the
Organizational and Operational
end date of the last FDA inspection related to compounding;
whether an FDA-483 was issued; whether FDA action was
taken, if any, based on the last inspection; and whether the
• Elimination of or reduction in the size of traditional
pharmacy departments, re-engineering, and downsiz-
outsourcing facility intends to compound sterile drugs from
ing initiatives.
nonsterile bulk active pharmaceutical ingredients (APIs).15
Pharmacy leaders should bear in mind that FDA or state in-
• Limited available physical or technological resources
(e.g., sterile compounding area, inventory storage
spections only reflect conditions at one particular time and
area, engineering controls) to provide the specific de-
should consider a facility’s history as well as its most recent
sired services.
results.
• Consolidation and integration of health systems and meeting their needs. Reasons for their decision will vary ac-
departments within health systems, including pres- cording to a variety of factors, some of which are outlined
sure to provide pharmacy services to acquired entities below. As with use of other contracted services, hospital
(e.g., physician practices). leadership must be included in the decision-making process
• Implementation of automated pharmacy systems and for outsourcing. A decision to outsource sterile compound-
the attendant need to reorganize medication prepara- ing services should be collaborative and may involve, as
tion and distribution functions. appropriate, the governing board, chief executive officer
• Inability to cost-effectively perform in-house testing (CEO), chief financial officer (CFO), chief operating officer
to establish extended beyond-use dating for sterile (COO), chief of the medical staff, chair of the pharmacy and
preparations. therapeutics (P&T) committee, director of pharmacy, direc-
• Federal restriction under section 503A of the DQSA tor of nursing, legal counsel, medication safety officer, risk
on the distribution of compounded sterile preparations management director, and department heads.
from a central site in the healthcare organization to
other campuses of the same system.a Reasons Healthcare Organizations Outsource Sterile
Compounding Services. Organizations tend to outsource
Staffing sterile compounding services when guided by a careful as-
• Shortage of pharmacy personnel with specific experi- sessment of their capabilities of providing services them-
ence and capabilities, especially regarding sterile prepa- selves, when unsuccessful in using their own resources to
ration. provide those services, or, in some cases, on the advice from
• Lack of resources, experience, or investment to effec- a qualified consultant. Contracting with a compounding
tively train staff on sterile compounding and aseptic pharmacy or outsourcing facility may produce one or more
technique. of the following results.
Financial and Cost Control Organizational and Operational
• Restricted budgets. • Resolve operational inefficiencies (e.g., batch com-

• Increased operating costs. pounding, staff scheduling, high-demand periods).
• Increased drug costs. • Provide compounded sterile preparations outside the
• Increased emphasis on measuring performance in scope of those routinely provided (e.g., complex or
terms of staffing and costs. rarely compounded sterile preparations).
• Enable the organization to reallocate resources and ex-
Drug Shortages pertise to carry out other priorities (e.g., reassignment
of existing staff to roles in patient care areas).
• Unavailability of medications or specific dosage
forms. Staffing
• Conservation of limited supplies of available medica-
tions. • Allow organizations to acquire quality compounded
sterile preparations or products without hiring for
Quality Assurance hard-to-fill pharmacy positions and to concentrate on
other staffing priorities.
• Increased expectations of and pressures from payers, • Allow the organization to reach optimal staffing levels
regulatory agencies, accreditation organizations, and for achieving quality and productivity targets.
consumer groups to improve the quality of patient
care, reduce the incidence of hospital infections, and Financial and Cost Control
demonstrate compliance with applicable standards and • Control or reduce the cost of the organization’s ser-
regulations. vices (e.g., by shifting costs associated with sterile
compounding services from fixed to variable).
Governmental and Regulatory • Control or reduce labor costs (e.g., by shifting respon-
sibility for employees, benefits, and liabilities to a
• Increased federal and state interest in standards for compounding pharmacy or outsourcing facility).
sterile compounding (i.e., USP chapter 7979). • Enable the organization to acquire a business partner
to share the risks and other associated liability by de-
Competitive lineating and contracting for the responsibilities asso-
ciated with operating sterile compounding services.
• Increased competition among healthcare organiza- • Minimize the cost of facility remodeling or mainte-
tions. nance (e.g., to meet USP chapter 7979 or chapter 80016
• Increased competition among suppliers of pharmaceu- requirements).
tical products and related services.
Quality Assurance
Purposes of Outsourcing
• Provide consistent and high-quality pharmacy and
sterile compounding services, including documented
Healthcare organizations should conduct an in-depth as- or extended beyond-use datingb and batch-level steril-
sessment to decide whether outsourcing is a good option for ity, potency, and endotoxin testing.
• Enable the organization to maintain or improve the Quality Assurance

quality of patient care (e.g., by expanding clinical ser-
vices or establishing new services). • Concern that conflicting values and priorities of the
• Enhance patient safety by providing more medications contractor and the organization will reduce quality.
in a dose-specific, ready-to-administer form. • Loss of direct control over quality-assurance proce-
• Provide support for the medical and nursing staffs and dures for the compounding process.
improve prescriber–nursing–pharmacy collaboration. • Concern about the qualifications or competencies of
• Improve organizational procedures by learning from contractors’ pharmacy staff.
contractors’ experience and knowledge, especially
with technologies used to improve safety (e.g., label- Governmental and Regulatory
ing, barcoding, or tamper-evident technologies).
• Legal, regulatory, certification, and accreditation re-
Governmental and Regulatory quirements may hinder operational efficiencies.
• Assist and ensure compliance with legal, regulatory, Outsourcing Process

certification, and accreditation requirements.
The needs of the healthcare organization should guide the
Reasons Healthcare Organizations Do Not Outsource identification of potential vendors of outsourced sterile
Sterile Compounding Services. An organization’s choice compounding services with the appropriate expertise and
to continue providing its own sterile compounding services capabilities. Among the services that may be available from
may be based on one or more of the following reasons. such vendors are the preparation of implantable and external
pump cartridges; total parenteral nutrition; cardiovascular
Organizational and Operational solutions; anesthesia syringes and solutions; dialysis, irri-
gation, or cardioplegia solutions; continuous renal replace-
• The organization demonstrates that its sterile comment therapy, hydration, and oxytocin solutions; antibiotics;
pounding services meet the requirements and stan- ophthalmic injectables and solutions; chemotherapy prepa-
dards of USP chapter 7979; comply with applicable rations; and analgesic preparations (patient-controlled anal-
local, state, and federal regulations; are cost-effective, gesia, epidural, or regional nerve-block devices).
well managed, and provided as efficiently as or better After the healthcare organization has completed an in-
than services that could be provided by a compound- ternal assessment of its needs and capabilities and decided to
ing pharmacy or an outsourcing facility. explore outsourcing, it should identify and contact vendors
• Negative experiences with outsourcing other clinical of outsourced sterile compounding services.
services, or awareness of other organizations’ negative Organizations that are part of a larger network (e.g.,
experiences with such outsourcing. an integrated delivery network) may explore options that are
• Concern about time delays in receiving compounded available to them through the network or from other orga-
sterile preparations or products, especially ones that nizations in the network. A health system may be exempt
are needed urgently or have poor stability or short from registering as a 503B entity if it compounds medica-
beyond-use dates (BUDs). tions for the health system’s own patients in response to a
• Concern that the contractor may experience inter- prescription or medication order or in a “limited quantity” in
ruptions in service, perhaps with little notice, due to anticipation of such prescriptions or orders, based on a his-
quality-control issues not related to services provided tory of such prescriptions or orders, as long as the pharmacy
to the organization. complies with state laws.5 This exemption is expected to be
• Concern that the decision to outsource sterile com- clarified by FDA in the future.13
pounding services can be reversed only with great dif- Many organizations begin to identify prospective con-
ficulty. tractors through a request for information (RFI). The RFI
• Concern about losing short- and long-term control should provide
over decisions regarding or expertise in sterile com-
pounding services. • A short history of the prospective contractor, includ-
ing number of years in business, number and location
Staffing of facilities, approximate number of customers served,
and approximate volume of compounded sterile prod-
• Concern that staff will be reduced to unacceptable lev- ucts or preparations delivered per month or year.
els. • The prospective contractor’s regulatory status (i.e.,
compounding pharmacy or registered outsourcing fa-
Financial and Cost Control cility) and applicable licensure or registration informa-
tion (e.g., pharmacy license number).
• An assessment that outsourcing would increase rather • Whether the prospective contractor compounds ster-
than decrease costs. ile preparations or products from nonsterile bulk APIs
• Concern that high-cost drugs might be excluded from (for registered outsourcing facilities, this information
contract agreements. is available on FDA Registered Outsourcing Facilities
• Concern that the organization may not be able to re- website).15
capitalize sterile compounding services if outsourcing
is unsuccessful.
• Description of products and services typically avail- • The date by which the selected contractor must pro-
able (e.g., customer support, website), value-added vide a written contract.
services available (e.g., clinical support), and typical • Other requirements related to the proposal (e.g., that it
ordering process and turnaround times. be in a specific file format, include reference to an RFP
• Representative prices for specified compounded ster- number [if any], or be signed by an officer of the firm
ile products or preparations and services at an annual who is authorized to contract or his or her designee).
unit demand.
• Whether the prospective contractor has any contracts Contents of Responses or Proposals. RFPs should require
with group purchasing organizations. prospective contractors to submit the following information
• A description of the prospective contractor’s backup with their responses or proposals:
facility capabilities and business continuity and disas-
ter recovery plans. • A brief history of the contractor, including its mission,
• Whether the prospective contractor has ever been the vision, and values.
subject of an enforcement or accreditation action. • A history of the results of all regulatory or accredi-
tation surveys conducted of the contractor’s sites, in-
After prospective contractors have been identified through cluding copies of significant regulatory actions.
RFIs, many organizations require them to respond to a more
• The location of the contractor’s offices and other fa-
detailed request for proposal (RFP). Although a formal RFP cilities that would provide services to the organization.
(and the contractor’s formal proposal based on the RFP) may
not always be necessary, the information found in typical
• The contractor’s regular business hours or hours of
operation and emergency and after-hours contact in-
RFPs and prospective contractor responses or proposals is formation.
often helpful in making a systematic decision about out-
sourcing.
• The names, addresses, telephone numbers, and resu-
més or background information on individuals who
will provide the services.
Contents of RFPs. RFPs often include the following infor-
mation: • Assurance that all pharmacists employed at the com-
pounding facility are licensed as required and that all
technicians involved in the compounding process are
• A description of the demographics of the organization
registered (if required by the state or by the healthcare
making the RFP (e.g., number of hospitals, bed sizes,
organization’s policy).
typical census).
• A description of the process the organization will use • Evidence of the following documentation regarding
the contractor:
to select the contractor.
• The organization’s standard terms and conditions for • Proof and description of coverage of current li-
ability insurance.
contracting for services or, if available, a sample con-
tract from the organization. • Current accreditation or certification certificates,
if applicable.
• The names and telephone numbers of individuals in
the organization who are involved in the outsourc- • State pharmacy licensure or other appropriate
ing decision (the organization’s director of pharmacy licenses.
should be included). • Registration with FDA as an outsourcing facil-
ity, which can be obtained on FDA’s registered
• A description of the specific services required of the
contractor (e.g., desired drugs, strengths, concentra- outsourcing facilities webpage.15
tions, diluents, container systems, annual demand) and • Proof of FDA registration as a device manufac-
performance-measurement criteria or targets. Special turer, if applicable.
packaging, handling, and delivery procedures for haz- • Current Drug Enforcement Administration
ardous drugs should be included. (DEA) registration, consistent with federal and
• A request for documentation of follow-up and correc- state regulations.
tion of any enforcement or accreditation findings. • Licensure of pharmacists employed and verifica-
• The dates on which the organization’s representatives tion that they are in good standing, are on file,
can inspect the contractor’s facility, with reasonable and available for review.
notice. (Inspections by the organization’s representa- • Registration of pharmacy technicians employed
tives will be more important when contracting with and verification that they are in good standing,
vendors that are not regularly inspected by FDA or are on file, and available for review, if applicable.
state inspectors.) • Pharmacist and pharmacy technician notarized
• The number of copies of the proposal to submit. statements stating that they have never been con-
• The name and address of the individual to whom the victed of a drug-related misdemeanor or felony
proposal is to be delivered. or proof of background check, are on file, and
• Acceptable methods for delivery of the proposal (e.g., available for review.
e-mail, mail, delivery service, courier). • Pharmacist and pharmacy technician training
• A statement that the organization reserves the right to manual are on file and available for review.
cancel its solicitation for services and reject any and • Standard operating procedures manual are on
all proposals for any reason or for no reason. file and available for review.
• A deadline date and time for receipt of the proposal. • Certificates of analysis for nonsterile ingredients
• The date on which the contractor would be expected to used in compounding are on file and available
initiate services. for review, if applicable.
• Policies and procedures for stability testing are Additional information to obtain from the prospective con-
on file and available for review. tractor but not necessarily contained in the proposal may
• Policies and procedures for sterility assurance include
testing are on file and available for review.
• Policies and procedures for pyrogen testing are • Whether the contractor has had product liability law-
on file and available for review, if applicable. suits filed against it for preparations it compounded.
• Examples of batch reports for products being If so, the contractor should be asked to provide a
considered for outsourcing are on file and avail- description of the lawsuits filed, the file date of the
able for review. lawsuits, and the outcome, though such information is
• Examples of the quality-control and quality- sometimes sealed as part of a settlement or decision
assurance reports. and may not be disclosable.
• Stability documents and clinical references, as • A description of the contractor’s formal procedures for
well as any materials that are used to determine conducting recalls and whether there have ever been
BUDs on file and available for review. (Because recalls of any of its compounded preparations. If the
studies used to establish BUDs are sometimes contractor has ever recalled any of its compounded
considered proprietary, compounding service preparations, it should be asked to provide the dates
providers may require a nondisclosure agree- of recall, a description of the preparations recalled,
ment.) and the reasons for the recall. Outsourcing facilities
• Proof of professional liability, general liability, and must comply with the specific requirements of FDA
workers’ compensation insurance coverage (including for 503B entities, which include having procedures for
the name, address, and telephone number of the insur- putting into place corrective and preventive actions.6
ance company). • Information related to the delivery process and backup
• Experience (e.g., years of experience in providing planning when severe or catastrophic events happen
sterile compounding services, total number of clients (e.g., severe weather).
served, current number of clients).
• A list of the requested services that the contractor can Visits to Contractors and Their Clients. Outsourcing fa-
provide and the normal terms of service, including but cilities and compounding pharmacies should allow the or-
not limited to normal delivery cycles, availability and ganization’s representatives to visit their corporate offices
cost of emergency preparation and delivery, remedies and compounding facilities. The contractor should provide
for failure to perform to the contract, specific goods and ample opportunity for the organization’s representatives to
services to be provided, and the infrastructure available confer with the contractor’s corporate, pharmacy, and com-
at the compounding site for electronic ordering. pounding staff. During the evaluation phase, the organiza-
• A list of the requested sterile compounding services tion’s representative should expect to give notice of a visit,
that the contractor cannot provide and the reasons for but after a contract has been signed the contractor should
its inability to provide them. allow unannounced inspections, provided that the visit will
• Expectation statements to assist in meeting the Centers be conducted in a manner that does not interfere with daily
for Medicare and Medicaid Services (CMS) require- activity or compromise the state of microbial control.
ments17 and accreditation organization standards18-23 For outsourcing facilities, the FDA inspection report
related to contracted services, if applicable. and documentation of follow-up and correction of any en-
• A copy of a standard or proposed contract. forcement or accreditation findings should be reviewed
• A list of all fees and charges, including shipping, han- in advance of the visit. For compounding pharmacies, the
dling, and delivery charges, and any fees associated healthcare organization should, in addition to requesting
with order changes that would be billed under the con- any FDA or state inspection reports and any applicable ac-
tract and the billing methodology for their calculation. creditation reports, assess the contractor’s compliance with
• A billing schedule and a copy of a sample bill for each USP chapter 797 using a standard tool, such as the ASHP
of the preparations compounded by the contractor. Research and Education Foundation’s contractor assessment
• A description of a routine delivery schedule (e.g., daily tool for outsourcing sterile products preparation.24
by a specified time) and options for nonroutine deliv-
ery (e.g., later the same day, after-hours, weekends, Evaluating Proposals. A decision to outsource sterile com-
holidays, during emergencies). pounding services should be collaborative and may involve,
• Examples of reports that the contractor will be ex- as appropriate, the organization’s governing board, CEO,
pected to submit to the organization. CFO, COO, chief of the medical staff, chair of the P&T
• The process for requesting new preparations from the committee, director of pharmacy, director of nursing, legal
contractor. counsel, medication safety officer, risk management direc-
• The contractor’s policy on unannounced inspections tor, and department heads, for example. The organization
by its customers. should scrutinize the following factors when evaluating
• The names, addresses, and telephone numbers of proposals:
• Current clients of a similar size or those receiv-
ing similar types of compounded preparations • Services offered versus services requested (including
or products, with written references and copies the contractor’s potential to enhance currently offered
of annual performance-improvement reports, if sterile compounding services or customize to the orga-
possible. nization’s needs).
• Reference accounts currently served.
• Professional experience (e.g., years of service; num- sterility, and endotoxin testing that is available for
ber, size, and types of clients; knowledge of the orga- review.
nization’s operations). • If the contractor is compounding high-risk prepara-
• Quality management program, specifically as it re- tions or products, provide documentation of the end
lates to facility cleaning and validation, environmental product–testing processes used to determine that the
monitoring, staff training, and competency assess- preparations or products are sterile, free of endotox-
ment. ins and unintended particulate matter, and (for prepa-
• Financial stability (e.g., ability to absorb startup ex- rations or products made from bulk APIs) meet the
penses and to commit the resources needed to initiate strength requirements of the drug.
service). • Deliver appropriate preparations or products in tam-
• References and reputation. per-resistant packaging and in containers that will
• Information systems and other technological infra- maintain the sterility and stability of the drugs. All
structure (e.g., the capability to interface with the or- products must be shipped under proper storage tem-
ganization’s information and drug delivery systems, peratures and (when required) protection from light.
such as infusion pumps or barcode-assisted medica-
tion administration systems). The organization should assign an evaluation rating to each
• Demonstrated commitment to continually integrating proposal. Ratings should be weighted appropriately with
technology and knowledge to improve patient safety. respect to services, experience, references, and cost. The
• Education and training of the contractor’s staff (e.g., organization should base its decision to outsource sterile
internal and external continuing-education programs, compounding services on its assessment of the contractor’s
educational allowances for professional and technical ability to meet the organization’s needs and fulfill the terms
staff). of the contract.
• The organization’s and the contractor’s policies on
specific compounding practices (e.g., references with Outsourcing Arrangement. The healthcare organization
real-time stability data supporting beyond-use dating, and the contractor should agree on the outsourcing arrange-
compliance with standards and regulations, use of ment that best meets their needs. The contract should clearly
USP–National Formulary-grade ingredients or FDA- describe all aspects of the outsourcing arrangement. The
approved products in accordance with the organiza- healthcare organization’s pharmacy should
tion’s intended use).
• Risk-assessment program to ensure that medication er- • Ensure that the proper body of the healthcare organi-
rors are not introduced by new or increased outsourced zation (e.g., the organization’s P&T committee) has
compounding activities and that the medications dis- developed a formal process to identify which prepa-
pensed are compatible with the client’s medication rations will (and which preparations will not) be pre-
administration devices (e.g., automated distribution pared by the contractor, based on the organization’s
devices, barcode labeling, smart pumps). assessment of the therapeutic needs of patients and
• Knowledge of the regulatory requirements and accred- logistical considerations associated with outsourcing.
itation standards that the organization must meet and • Establish the components of the medication orders or
willingness to assist the organization in meeting these prescriptions for preparations that will be compounded
standards. by an outside facility.
• Inventory and supply chain issues (e.g., the organiza- • Determine whether patient consent must be obtained
tion’s and contractor’s back-order policies, the con- for use of preparations compounded outside the
tractor’s ability to produce drug products in shortage healthcare organization’s pharmacy, consistent with
through validated compounding procedures). state board of pharmacy regulations and prevailing
• Emergency-preparedness implications (e.g., the abili- law.
ties of the organization and the contractor to deliver • Determine a method for identifying patients receiving
services in the event of a disaster). the contractor’s preparations or products.
• Additional qualities (e.g., high employee morale, con- • Ensure that the contract and the contractor’s facility
fidentiality, creativity, dedication to the community, have been reviewed by all the necessary bodies in the
collaborative spirit). pharmacy’s healthcare organization (e.g., the organi-
• Cost aspects of services (e.g., cost-effectiveness, abil- zation’s risk management team, legal counsel, P&T
ity to achieve economies of scale). and infection control committees, epidemiology de-
partment).
The contractor should, at a minimum, be able to • Determine how to handle situations in which a patient
presents with a compounded medication that is not
• Provide assurance that each compounded sterile prep- available from the healthcare organization’s pharmacy
aration or product meets applicable state and federal or the contractor under the existing contract (e.g.,
labeling requirements and is sterile and free of en- medication in an implantable device, i.v. push medi-
dotoxins (when required) and unintended particulate cation, i.v. infusion) and that has not been previously
matter, according to professionally established and ac- considered by the P&T committee. Considerations in-
cepted quality-monitoring data. clude what the process will be for:
• If the contractor is extending beyond-use dates longer • Having the P&T committee consider outsourc-
than defined in USP chapter 797,9 confirm the validity ing the compounding of such medications to
of those beyond-use dates with stability and strength,25
another contractor with which the healthcare or- • Describe the expectations to be met by the contractor.
ganization has an agreement. These expectations must comply with CMS Hospital
• Acquiring certain compounded medications if Conditions of Participation for Contracted Services re-
the contractor already under contract cannot or quirements,17 which state (in part) that “The governing
will not prepare them and how the associated body must ensure that a contractor of services . . . fur-
liability risks will be addressed (e.g., how the nishes services that permit the hospital to comply with
healthcare organization’s pharmacy will negoti- all applicable conditions of participation and stan-
ate an agreement with another contractor from dards for the contracted services.” Hospital accredi-
which the preparation or product is available) tation organizations (Joint Commission,18 DNV GL
until the P&T committee decision is obtained Healthcare,19 the Healthcare Facilities Accreditation
regarding such medications. Program,20 and the Center for Improvement in
Healthcare Quality21) and other accreditation or-
Negotiating the Contract. The healthcare organization ganizations (e.g., Accreditation Commission for
should carefully review the proposal and clarify the provi-
Health Care’s Pharmacy Compounding Accreditation
sions of the contract. Active participation by the healthcare
Board,22 National Association of Boards of Pharmacy
organization’s risk management team and legal counsel is
Verified Pharmacy Program23) have additional stan-
highly recommended. Negotiations can ensure a contract
dards that must be addressed.
that best meets the needs of the healthcare organization and
the contractor. ASHP believes that the healthcare organiza-
Both operational and quality expectations should be defined
tion’s pharmacist-in-charge (e.g., a pharmacy director) must
by the organization, such as expectations that
take responsibility for patient outcomes from all medication-
related activities performed at or for the organization’s work
sites, whether they are carried out by the organization’s staff • Delineate routine sterile compounding turnaround
or by contractors. This responsibility should be explicitly times (e.g., from receipt of the request, medication
stated in all outsourcing contracts. order, or prescription by the contractor to delivery to
The signed contract between the parties should at a the healthcare organization) and describe acceptable
minimum deviations from the agreed-upon schedules (e.g., raw
product availability problems, unique end-product
testing requirements, compounded preparation stabil-
• Describe the term length of the contract and the pro-
ity characteristics, nonroutine and emergency delivery
cesses for the contractor’s billing to the healthcare
organization, including methods of determining the requests).
charge for the compounded items, payment terms, and • Describe the specific drugs provided, documentation
processes for resolution of disputed invoices. flow, delivery methods, security considerations, and
time frames for the provision of controlled substances
• Contain a confidentiality clause and a Health Insurance
Portability and Accountability Act business associate by the contractor.
agreement, if applicable. • Describe any special processes, documentation flow,
• Establish the pharmacy’s right to unannounced in- delivery methods, security considerations, and time
spections of the premises where compounding occurs, frames for the provision of hazardous drugs by the
including the right to inspect quality-control reports, contractor.
provided that the visit will be conducted in a manner • Describe the frequency of quality statements provided
that does not interfere with daily activity or compro- to the healthcare organization, such as quarterly sum-
mise the microbial state of control. maries of facility, personnel, and environmental moni-
• Describe the method of communicating the medica- toring.
tion order or prescription from the healthcare organi-
zation’s pharmacy to the contractor (e.g., telephone, Signing the Contract. In some organizations, the director
fax, computer transmission, hard copy, controlled- of pharmacy may be authorized to sign contracts for out-
substance ordering system). sourced services. If this is not the case, the director of phar-
• Protect both parties from liabilities created by errors macy must be fully involved in negotiating the contract and
made by the other party and delineate the obligations advising the authorized signers.
of both parties.26
• Establish recall procedures that comply with hospital Contract Provisions
policy mandates and prevailing law should a prepara-
tion or product need to be recalled by the contractor. A contract that meets the needs of the healthcare organiza-
• Address documentation, regulatory and accreditation tion and of the contractor is the foundation for a successful
compliance, sterile compounding process, and com- relationship. Contracts should specifically describe the re-
pounded preparation or product considerations. spective responsibilities of the organization and the contrac-
• Describe the pertinent situations and processes for the tor. See the appendix for examples of contract provisions.
return, credit, or destruction of compounded prepara-
tions or products with the contractor.
• Describe any requirements regarding the submission Evaluation of the
of quality reports by the contractor. Contractor’s Performance
• Describe the procedures for resolving preparation or
delivery issues encountered by the organization or the The healthcare organization must evaluate and document
contractor. the contractor’s performance and assess the contractor’s
b
compliance with the terms of the contract. The contractor Draft CGMP limits on BUDs for 503B outsourcing facilities may pres-
should regularly submit quality reports, and the organization ent challenges to those purchasing them. For sterile preserved drugs, the
must regularly perform objective and subjective evaluations longest permissible BUD is 30 days beyond completion of a sterility test.
(e.g., quarterly, annually). Evaluations should address all If a sterility test is completed before release, the BUD must not exceed
measurable standards of performance specified in the con- 14 days (at USP controlled room temperature or refrigerated) beyond
tract. Evaluations should be led by the director of pharmacy, completion of the test (e.g., for a 14-day sterility test, the BUD could
be multidisciplinary, and should involve, for example, the not exceed 28 days). For terminally sterilized products without a steril-
CEO, CFO, COO, director of nursing, and medical staff rep- ity test, the BUD cannot exceed 14 days. And for aseptically processed
resentatives, as appropriate. An evaluation may include an products without a sterility test, the BUD cannot exceed 24 hours at USP
assessment of how well the contractor has controlled room temperature or 3 days refrigerated. BUDs for frozen
products are considerably longer.6
• Helped improve the quality of patient care.
• Responded to the organization’s needs (e.g., invoicing, References
process adjustment).
• Met its contractual obligations, including timely and 1. American Society of Health-System Pharmacists.
complete deliveries of products. ASHP guidelines on outsourcing pharmaceutical ser-
• Provided clear and concise quality metric data ensur- vices. Am J Health-Syst Pharm. 1998; 55:1611–7.
ing compliance with state and federal regulations and 2. American Society of Health-System Pharmacists.
patient-safety standards. ASHP guidelines on compounding sterile prepara-
• Helped the organization achieve its financial and pa- tions. Am J Health-Syst Pharm. 2014; 71:145–66.
tient-outcome goals. 3. American Society of Hospital Pharmacists. ASHP
• Improved the productivity and performance of phar- guidelines for selecting pharmaceutical manufacturers
macy staff. and suppliers. Am J Hosp Pharm. 1991; 48:523–4.
• Improved medication management processes (e.g., 4. Drug Quality and Security Act (November 27, 2013).
medication dispensing and delivery). www.govtrack.us/congress/bills/113/hr3204/text (ac-
• Reduced and controlled medication costs without cessed 2015 Jan 20).
compromising patient care. 5. Food and Drug Administration. FDA guidance on
• Worked and communicated effectively with the orga- pharmacy compounding of human drug products
nization’s staff and resolved problems. under section 503A of the Federal Food, Drug, and
Cosmetic Act (July 2014). www.fda.gov/downloads/
Handling Performance or Quality Issues Drugs/GuidanceComplianceRegulatoryInformation/
Guidances/UCM377052.pdf (accessed 2015 Jan 20).
The contractor should provide the healthcare organization 6. Food and Drug Administration. FDA guidance for
with information at least quarterly on its compliance with industry: Current Good Manufacturing Practice—
contract requirements and other information needed for the interim guidance for human drug compounding out-
organization’s quality-assurance programs. A mechanism sourcing facilities under section 503B of the FD&C Act
should be in place for resolving preparation or delivery is- (July 2014). www.fda.gov/downloads/drugs/guidance
sues (e.g., delivery to the wrong location, late deliveries). complianceregulatoryinformation/guidances/
ucm403496.pdf (accessed 2015 Jan 20).
7. Food and Drug Administration. FDA draft memo-
Conclusion
randum of understanding addressing certain dis-
tributions of compounded human drug products
These guidelines offer an overview of factors and processes
(February 12, 2015). www.fda.gov/downloads/
for healthcare organizations to consider when exploring the
Drugs/GuidanceComplianceRegulatoryInformation/
outsourcing of pharmacy sterile compounding. Such consid-
PharmacyCompounding/UCM434233.pdf (accessed
erations include an internal needs assessment, a cost analy-
2015 Feb 24).
sis, a careful review of prospective outsourcing facilities
8. General chapter 795: pharmaceutical compound-
and compounding pharmacies, and an examination of the
ing—nonsterile preparations. In: The United States
potential long-term consequences of outsourcing as well as
pharmacopeia, 38th rev., and The national formulary,
the short-term outcomes expected during a contract’s perfor-
33rd ed. Rockville, MD: United States Pharmacopeial
mance period. The ideas presented can be used for strategic
Convention; 2014:560–7.
planning, drafting of initial contract provisions, comparing
9. General chapter 797: pharmaceutical compounding—
prospective contractors, preparing for contract negotiations,
sterile preparations. In: The United States pharma-
or evaluating a contractor’s performance. These guidelines
copeia, 38th rev., and The national formulary, 33rd
are intended to address representative outsourcing options
ed. Rockville, MD: United States Pharmacopeial
and contract agreements and may not be applicable to all sit-
Convention; 2014:567–611.
uations. Managers of pharmacy and healthcare organizations
10. Food and Drug Administration. FDA inspections,
should exercise professional judgment about applicability to
compliance, enforcement, and criminal investigations:
their own needs and circumstances.
FDA Form 483—frequently asked questions. www.
fda.gov/ICECI/Inspections/ucm256377.htm (accessed
a 2015 Feb 24).
At the time of writing, FDA had not issued final guidance on inter-
11. Food and Drug Administration. FDA pharmacy
state distribution by 503A facilities.7
inspections and related records. www.fda.gov/
AboutFDA/CentersOffices/OfficeofGlobal usp.org/sites/default/files/usp_pdf/EN/2014-01-13_
RegulatoryOperationsandPolicy/ORA/ORA strength_versus_stability_testing_for_compounded_
ElectronicReadingRoom/ucm431393.htm (accessed preparations_3.pdf (accessed 2015 Apr 1).
2015 Apr 1).
26. Food and Drug Administration. FDA draft guid-
12. Kastango E, Douglass K. Quality standards for large ance for industry: adverse event reporting for
scale sterile compounding facilities (May 2014). www. outsourcing facilities under section 503B of the
clinicaliq.com/images/stories/clinicaliq_compound- Federal Food, Drug, and Cosmetic Act. www.
ing%20quality%20standards.pdf (accessed 2015 Jan fda.gov/downloads/Drugs/GuidanceCompliance
20). RegulatoryInformation/Guidances/UCM434188.pdf
13. Kastango ES. Impact of the US Drug Quality and (accessed 2015 Apr 1).
Security Act. www.pppmag.com/article_print.
php?articleid=1595 (accessed 2015 Feb 24). Suggested Readings
14. Food and Drug Administration. Letter to hospi-
tal/purchaser from Margaret A. Hamburg, M.D., Allen LV. Quality assurance in pharmaceutical compound-
Commissioner of Food and Drugs (January 8, 2014). ing, part 2: documentation and verification. Int J
www.fda.gov/downloads/drugs/guidancecompliance Pharm Compound. 2012; 16:230–4.
regulatoryinformation/pharmacycompounding/ Donnelly AJ, Kienle PC, Lake RT et al. The Drug Quality
ucm380599.pdf (accessed 2015 Jan 20). and Security Act: a new reality for the practice of
15. Food and Drug Administration. Registered outsourcing outsourcing compounded sterile preparations. Pharm
facilities. www.fda.gov/drugs/guidancecompliance Pract News. 2014; 41(suppl):1–8.
regulatoryinformation/pharmacycompounding/ Douglass K, Kastango ES. Consolidation of pharmacy com-
ucm378645.htm (accessed 2015 Mar 16). pounding services: an alternative to outsourcing. Int J
16. United States Pharmacopeial Convention. General Pharm Compound. 2001; 5:140–4.
chapter 800 hazardous drugs—handling in health- Eberts MW, Cecere DA, Mark S. Ensuring the safety of
care settings. www.usp.org/usp-nf/notices/general- sterile admixtures prepared outside of the institution.
chapter-hazardous-drugs-handling-healthcare-settings Hosp Pharm. 2013; 48:248–52.
(accessed 2015 Feb 24). Fiebert L. Adjusting to the new world of outsourced com-
17. Centers for Medicare and Medicaid Services. pounding. www.pppmag.com/download.php?file=
Conditions of participation for hospitals, §482.12 (e), documents/V11N7/pdfs/ppp_1407_outsourcedcom-
(e)(1), and (e)(2). http://cms.hhs.gov/Regulations- pounding.pdf (accessed 2014 Nov 28).
and-Guidance/Guidance/Manuals/downloads/ Gates DM, Smolarek RT, Stevenson JG. Outsourcing the
som107ap_a_hospitals.pdf (accessed 2015 Jan 20). preparation of parenteral nutrient solutions. Am J
18. Joint Commission. Standard LD.04.03.09. Health-Syst Pharm. 1996; 53:2176–8.
Comprehensive accreditation manual for hospitals Kastango ES. Sterile-product preparations: mix or buy? Int J
(update 2, November 2014). Oakbrook Terrace, IL: Pharm Compound. 2001; 5:59–63.
Joint Commission Resources; 2014. Kastango ES. Impact of the US Drug Quality and
19. National Integrated Accreditation for Healthcare Security Act. www.pppmag.com/article_print.
Organizations (NIAHO) interpretive guidelines and php?articleid=1595 (accessed 2015 Feb 24).
surveyor guidance–version 11. Milford, OH: DNV GL Kastango E, Douglass K. Quality standards for large scale
Healthcare USA; 2014:20–1. sterile compounding facilities (May 2014). www.
20. Accreditation requirements 01.00.29, 01.00.30, clinicaliq.com/images/stories/clinicaliq_compound-
and 01.01.13. 2012 accreditation requirements for ing%20quality%20standards.pdf (accessed 2015 Jan
acute care facilities. Chicago: American Osteopathic 20).
Association, Healthcare Facilities Accreditation Myers CE. History of sterile compounding in U.S. hospi-
Program; 2012. tals: learning from the tragic lessons of the past. Am J
21. Accreditation standards for acute care hospi- Health-Syst Pharm. 2013; 70:1414–27.
tals (October 2014) Round Rock, TX: Center for Ponto JA. Outsourcing radiopharmaceutical services. Am J
Improvement in Healthcare Quality; 2014:3. Health-Syst Pharm. 1998; 55:2537.
22. Pharmacy Compounding Accreditation Board, Souhrada L. Contract management. Hospitals. 1990; 64:66–8.
Accreditation Commission for Health Care. Pharmacy Timko RJ, Crooker PE. Pharmaceutical compounding or
accreditation. www.achc.org/programs/pharmacy (ac- pharmaceutical manufacturing: a regulatory perspec-
cessed 2014 Jul 24). tive. Int J Pharm Compound. 2014; 18:101–11.
23. National Association of Boards of Pharmacy. Verified Wagner M. Basic pitfalls can undermine hospital–service
Pharmacy Program. www.nabp.net/programs/licensure/ firm relationship. Mod Healthcare. 1993; 23:32.
verified-pharmacy-program (accessed 2015 Apr 1).
24. ASHP Research and Education Foundation. Outsourc-
ing sterile products preparation: contractor assess- Appendix—Contract Provisions
ment tool, 2011. www.ashpfoundation.org/MainMenu
Categories/PracticeTools/SterileProductsTool/ The following are examples of contract provisions that,
SterileProductsAssessmentTool.aspx (accessed 2015 among others, the organization and a contractor might adapt
Jan 20). as needed and include in a contract, depending on the scope
25. Allen LV, Bassani GS, Elder EJ, et al. Strength and of services being considered. In addition, a contract would
stability testing for compounded preparations. www. include provisions about the specific compounding services
to be provided by the contractor. The language in contract of the acts or omissions related to the services and/
provisions should always be adapted to meet the specific or products provided pursuant to this contract attached
needs of the healthcare organization and to comply with the hereto, (b) breach of contractor’s representations and
organization’s contracting policies and applicable laws and warranties, (c) injuries to persons, including death,
regulations. or damage to property caused by contractor’s agents,
In reviewing the following list of suggested contract servants, or employees, or in any way attributable to
provisions, attention should be paid to the fact that listed contractor’s performance of this contract, and (d) any
provisions are not intended and should not be considered breach of any laws or regulations in connection with
all-inclusive and do not constitute legal advice but rather contractor’s performance of services or provision of
are provided solely to convey general information related products pursuant to the contract.
to legal issues commonly addressed in contracts for the out-
Contractor Reports. The content and regularity of perfor-
sourcing of sterile compounding services. The purpose of
mance reports that the contractor will submit to the
enumerating the following possible contract provisions is to
organization may be specified.
provide a general understanding of the types of provisions
Contractor’s Performance Responsibilities. The contrac-
that may be included in a contract. Because laws vary from
tor’s responsibilities and commitments associated
jurisdiction to jurisdiction and are subject to varying inter-
with proper federal (if necessary) and state licensure
pretations, healthcare organizations considering outsourcing
and regulatory requirements for all the preparations
sterile compounding services should consult with profes-
or products it compounds are outlined in this section
sional legal counsel in their relevant jurisdictions regarding
(e.g., labeling). It further describes the contractor’s re-
the drafting of contracts.
sponsibilities to operate in accordance with applicable
Current Good Manufacturing Practices, United States
Accreditation and Certification. A contract should include a
Pharmacopeia (USP) compounding standards, Drug
requirement that services meet or exceed applicable accredi-
Enforcement Administration (DEA) requirements (as
tation and certification standards. These include, but are not
applicable), and company standard operating proce-
limited to, the standards (or requirements) of the following
dures.
organizations:
Customer Responsibilities. This section describes the
healthcare organization pharmacy’s responsibilities
• Centers for Medicare and Medicaid Services17
for affirming that it has all required state, local, and
• Joint Commission18
federal licenses associated with the receipt of services
• DNV GL Healthcare19
being provided by the contractor. It may also describe
• American Osteopathic Association20
the healthcare organization’s responsibilities for deter-
• Center for Improvement in Healthcare Quality21
mining clinical appropriateness of any compounded
• Pharmacy Compounding Accreditation Board22
preparation or product it purchases from the contractor
• National Association of Boards of Pharmacy Verified
as well as the procedures to be used to ensure the trace-
Pharmacy Program23
ability of compounded preparations or products.
Extension of Period of Performance. Conditions for ex-
After-Hours Access. This section describes the process and
tending the period of performance should be included
extent of access to off-site contractor resources after
in the contract.
normal business hours.
Force Majeure. This section describes when neither party
Choice of Law. The contract should state by which state law
shall be liable for nonperformance or delays related to
the contract is governed.
causes that are beyond one’s reasonable control.
Confidential Information. This section describes what in-
Forms. Responsibilities for the design, approval, purchase,
formation is considered confidential and actions that
and storage of forms may be assigned.
are required to prevent unauthorized distribution of
General Provisions. This section outlines a myriad of other
such information. Both parties must agree to safeguard
contractual items, such as contract assignment, pro-
access to computer databases and patient records to
cess for adding or changing compounding services,
ensure that the patients’ rights to privacy and confi-
reference to other agreements, and reference to other
dentiality are protected. Use of the information should
applicable terms outside the services agreement.
be limited solely to purposes specified in the contract.
Hazardous Drug Preparations or Products. Responsibilities
Contractor. The outsourcing facility or compounding phar-
for ensuring the safety of the organization’s staff and
macy contracted by the healthcare organization to pro-
patients during delivery and distribution of hazardous
vide sterile compounding services.
drug preparations or products may be assigned. Either
Contractor Indemnification. This section describes in detail
the organization or the contractor must provide a haz-
the indemnities the contractor owes the healthcare or-
ardous materials handling program, including staff
ganization, such as
training, that meets ASHP guidelines, Occupational
Safety and Health Administration (OSHA) require-
Contractor shall indemnify and defend customer and
ments, and USP compounding standards.
its affiliates, and each of their respective officers, di-
Indemnification. This section describes specific conditions
rectors, trustees, employees, agents, and representa-
under which, and responsibilities for which, both par-
tives (collectively, the “customer indemnities”) and
ties will hold each other harmless for, and potentially
hold them harmless from and against any and all losses
defend, the actions of the other.
on account of any claims asserted by a third party in
connection with, arising from, or related to (a) any
Information Transfer. This section describes the mecha- there might be a clause in the contract that the contrac-
nisms by which the organization transfers orders and tor’s staff will participate in some of the organization’s
other information to the contractor. education and training programs. In addition, the con-
Laws, Rules, and Regulations. Requirements for services tractor may agree to provide specific training to ensure
to meet or exceed federal, state, and local laws, rules, that all contractor and healthcare organization person-
and regulations may be specified. These include nel can perform the duties created by the contractor’s
but are not limited to those of the Food and Drug services.
Administration, DEA, OSHA, USP, and the state board Successors. The rights of each party in the event that the
of pharmacy. The contractor should maintain (e.g., healthcare organization or contractor merges or trans-
display, file) the appropriate licenses, permits, and fers its business or assets to a successor are described
records of equipment maintenance and certification. in this section.
Any contractor required to be registered as an out- Term of Agreement. This section communicates the length
sourcing facility must be so registered. of time the agreement is in effect between the health-
Liability Insurance. This section describes the responsi- care organization and the contractor, including renew-
bility for maintaining liability insurance coverage. als.
The contract might specify, for example, the specific Termination. This section describes how and when the con-
level and types of liability insurance coverage that the tract will end or be terminated, including early termi-
healthcare organization and the contractor must main- nation. It should also address any penalties that may be
tain. appropriate or when the contract may be ended with-
Payment Terms. This section describes the agreed-upon out penalty.
number of days from receipt of an invoice by the
healthcare organization’s pharmacy until payment is
due to the contractor. Developed through the ASHP Council on Pharmacy Management
Period of Performance. This section specifies the period and approved by the ASHP Board of Directors on June 6, 2015.
for which the contractor will provide services to the These guidelines supersede the ASHP Guidelines on Outsourcing
organization. Sterile Compounding Services dated January 14, 2010.
Policies and Procedures. This section describes the re-
quired written policies and procedures covering the The revision of this document was led by Patricia C. Kienle, M.P.A.,
outsourced services, all of which should comply with FASHP. The contributions of Bona E. Benjamin, B.S.Pharm., to this
applicable laws, regulations, and accreditation or certi- document are gratefully acknowledged.
fication standards. The contract should specify that the
policies and procedures must not conflict with those of The following individuals are gratefully acknowledged for re-
the organization. viewing draft versions of these guidelines (review does not imply
Pricing. The price of each service the hospital pharmacy endorsement): Darrell Chan, Pharm.D.; Michael Cunningham,
is interested in purchasing from the contractor, along Pharm.D.; Kate Douglass, M.S., RN, APN, CRNI; Bernadette
with conditions and methodology for price increases, Henrichs, Ph.D., CRNA, CCRN; Eric Kastango, M.B.A., FASHP;
is described in this section, which may be an adden- Michael Koch, M.B.A.; Rich Kruzynski, B.S.Pharm., M.B.A.;
dum to the contract. Shipping, handling, and delivery Kathy Parrinello, Ph.D., RN; James R. Rinehardt, M.S., FASHP;
charges for both routine and nonroutine deliveries Douglas Smith, Pharm.D.; Ross W. Thompson, M.S., B.S.Pharm.;
should also be detailed. and Tom Woller, M.S., FASHP.
Purchase Volume Requirements. This section establishes
a mutual understanding of annual purchase volume The drafters have declared no potential conflicts of interest.
commitments between the healthcare organization’s
pharmacy and the contractor. Copyright © 2015, American Society of Health-System Pharmacists,
Record Maintenance. The contract should specify that all Inc. All rights reserved.
pertinent records must be kept for the time required by
law and by the organization and describe how, where, The bibliographic citation for this document is as follows: American
and by whom the records will be maintained. Society of Health-System Pharmacists. ASHP guidelines on out-
Staff Education and Training. Responsibilities for required sourcing sterile compounding services. Am J Health-Syst Pharm.
ongoing staff training may be specified. For example, 2015; In press.
446 Pharmacy Management: Compensation and Reimbursement–Positions
Compensation and Reimbursement

Payer Processes for Payment Authorization and To advocate for the development of consistent billing
Coverage Verification (1301) and reimbursement policies and practices by both govern-
Source: Council on Pharmacy Management ment and private payers; further,
To advocate that public and private payers collaborate with To advocate that information technology (IT) vendors
each other and with health care providers to create standard- enhance the capacity and capability of IT systems to support
ized and efficient processes for authorizing payment or veri- and facilitate medication-related billing and audit functions;
fying coverage for care; further, further,
To advocate that payment authorization and coverage To investigate and publish best practices in medica-
verification processes (1) facilitate communication among tion-related revenue cycle compliance and management.
patients, providers, and payers prior to therapy; (2) provide This policy supersedes ASHP policy 9902.
timely payment or coverage decisions; (3) facilitate access
to information that allows the pharmacist to provide pre- Value-Based Purchasing (1209)
scribed medications and medication therapy management to Source: Council on Pharmacy Management
the patient; and (4) foster continuity in patient care. To support value-based purchasing reimbursement models
This policy supersedes ASHP policy 1206. when they are appropriately structured to improve health
care quality, patient satisfaction, and clinical outcomes, and
Drug Product Reimbursement (1304) encourage medication error reporting and quality improve-
Source: Council on Pharmacy Management ment; further,
To pursue, in collaboration with public and private pay- To encourage pharmacists to actively lead in the de-
ers, the development of improved methods of reimbursing sign and interdisciplinary implementation of medication-
pharmacies for the costs of drug products dispensed, com- related value-based purchasing initiatives.
pounding and dispensing services, and associated overhead; This policy supersedes ASHP policy 0708.
further,
To educate pharmacists about those methods. Reimbursement for Unlabeled Uses of FDA-Approved
This policy supersedes ASHP policy 0207. Drug Products (0206)
Revenue Cycle Compliance and Management (1205) To support third-party reimbursement for FDA-approved
Source: Council on Pharmacy Management drug products appropriately prescribed for unlabeled uses.
To encourage pharmacists to serve as leaders in the devel- This policy was reviewed in 2011 by the Council on
opment and implementation of strategies to optimize med- Pharmacy Management and by the Board of Directors and
ication-related revenue cycle compliance, which includes was found to still be appropriate.
billing, finance, and prior authorization, for the health care
enterprise; further,
Pharmacy Management: Human Resources–Positions 447
Human Resources
Credentialing, Privileging, and Competency Assessment specialists for certification examination and ensure the main-
(1415) tenance of core competencies in their area of specialization.
To support the use of post-licensure credentialing, privileg- Professional Socialization (1113)
ing, and competency assessment to practice pharmacy as a Source: Council on Education and Workforce Development
direct patient-care practitioner; further, To encourage pharmacists to serve as mentors to students,
To advocate that all post-licensure pharmacy creden- residents, and colleagues in a manner that fosters the adop-
tialing programs meet the guiding principles established by tion of: (1) high professional standards of pharmacy practice,
the Council on Credentialing in Pharmacy; further, (2) high personal standards of integrity and competence, (3)
To recognize that pharmacists are responsible for a commitment to serve humanity, (4) analytical thinking and
maintaining competency to practice in direct patient care. ethical reasoning, (5) a commitment to continuing profes-
This policy supersedes ASHP policy 0006. sional development, and (6) personal leadership skills.
Financial Management Skills (1207)
Source: Council on Pharmacy Management Credentialing and Privileging by Regulators, Payers, and
To foster the systematic and ongoing development of man- Providers for Collaborative Drug Therapy Management
agement skills for health-system pharmacists in the areas (0905)
of (1) health-system economics, (2) business plan devel- Source: Council on Public Policy
opment, (3) financial analysis, (4) metrics for clinical and To advocate expansion of collaborative drug therapy man-
distributive services, (5) pharmacoeconomic analysis, (6) agement (CDTM) practices in which the prescriber and the
diversified pharmacy services, (7) compensation for phar- licensed pharmacist agree upon the conditions under which
macists’ patient-care services, and (8) revenue cycle compli- the pharmacist initiates, monitors, and adjusts a patient’s
ance and management; further, drug therapy; further,
To encourage colleges of pharmacy to incorporate To acknowledge that as a step toward the goal of uni-
these management areas in course work and experiential versal recognition of and payment for pharmacist CDTM
education; further, services, public or private third-party payers may require
To encourage financial management skills develop- licensed pharmacists to demonstrate their competence to
ment in pharmacy residency training programs and new provide CDTM, before the payers authorize them to engage
practitioner orientation. in or be paid for such clinical services; further,
This policy supersedes ASHP policy 0508. To support (1) the development (as a professional ini-
tiative by pharmacist associations rather than as a government
Board Certification for Pharmacists (1225) activity) of national standards for determining a pharmacist’s
Source: Section of Clinical Specialists and Scientists competence to provide CDTM and (2) the appropriate use of
To support the principle that pharmacists who practice where these standards by clinical privileging systems, government
a pharmacy specialty has been formally recognized by the authorities, and public or third-party payers; further,
profession should become board certified in the appropriate To support the use of clinical privileging by hospitals
specialty area; further, and health systems to assess a licensed pharmacist’s com-
To recognize the Board of Pharmacy Specialties (BPS) petence to engage in CDTM within the hospital or health
as an appropriate organization through which specialties are system; further,
formally recognized and specialty pharmacy certification To advocate that state boards of pharmacy apply the
should occur; further, principles of continuous quality improvement in assessing
To advocate prioritization for recognition of new spe- the quality, safety, and outcomes of CDTM.
cialties in those areas where sufficient numbers of postgrad- (Note: Privileging is the process by which an over-
uate year two residency training programs are established sight body of a health care organization or other appropri-
and where adequate numbers of pharmacists are completing ate provider body, having reviewed an individual health
accredited training programs to prepare them to practice in care provider’s credentials and performance and found them
the specialty area; further, satisfactory, authorizes that individual to perform a specific
To advocate for standardization of credentialing eligi- scope of patient care services within that setting.)
bility and recertification requirements to include consistent This policy was reviewed in 2013 by the Council on
requirements for advanced postgraduate residency training; Public Policy and by the Board of Directors and was found
further, to still be appropriate.
To promote a future vision encouraging accredited
training as an eventual prerequisite for board certification; Intimidating or Disruptive Behaviors (0919)
further, Source: Council on Pharmacy Management
To encourage BPS to be sensitive to the needs of cur- To affirm the professional responsibility of the pharmacist
rent practitioners as prerequisites evolve; further, to ensure patient safety by communicating with other health
To actively encourage and support the development of care personnel to clarify and improve medication manage-
effective training and recertification programs that prepare ment; further,
448 Pharmacy Management: Human Resources–Positions
To advocate that hospitals and health systems adopt Image of and Career Opportunities for Hospital and
zero-tolerance policies for intimidating or disruptive behav- Health-System Pharmacists (0703)
iors; further, Source: Council on Education and Workforce Development
To encourage hospitals and health systems to develop To sustain and enhance the public information program pro-
and implement education and training programs for all moting the professional image of hospital and health-system
health care personnel to encourage effective communication pharmacists to the general public, public policymakers, pay-
and discourage intimidating or disruptive behaviors; further, ers, other health care professionals, and hospital and health-
To encourage colleges of pharmacy and residency system decision-makers; further,
training programs to incorporate training in communications To provide ASHP informational and recruitment mate-
and managing intimidating or disruptive behaviors; further, rials identifying opportunities for pharmacy careers in hospi-
To collaborate with other organizations to advocate tals and health systems.
codes of conduct that minimize intimidating or disruptive This policy was reviewed in 2012 by the Council on
behavior in hospitals and health systems. Education and Workforce Development and by the Board of
This policy was reviewed in 2013 by the Council on Directors and was found to still be appropriate.
was found to still be appropriate. Influenza Vaccination Requirements to Advance Patient
Safety and Public Health (0615)
Education, Prevention, and Enforcement Concerning Source: Council on Professional Affairs
Workplace Violence (0810) To advocate that hospitals and health systems require health
Source: Council on Public Policy care workers to receive an annual influenza vaccination ex-
To advocate that federal, state, and local governments rec- cept when (1) it is contraindicated, or (2) the worker has
ognize the risks and consequences of workplace violence religious objections, or (3) the worker signs an informed
in the pharmacy community and enact appropriate criminal declination; further,
penalties; further, To encourage all hospital and health-system pharmacy
To collaborate with federal, state, and local law en- personnel to be vaccinated against influenza; further,
forcement and other government authorities on methods for To encourage hospital and health-system pharmacists
early detection and prevention of workplace violence; further, to take a lead role in developing and implementing policies
To encourage all workplace environments to develop and procedures for vaccinating health care workers and in
and implement a policy for pharmacy personnel that (1) edu- providing education on the patient safety benefits of annual
cates about prevention and deterrence of workplace violence, influenza vaccination; further,
(2) identifies escalating situations that can lead to violence To work with the federal government and others to im-
and instructs employees on protection and self-defense, and prove the vaccine development and supply system in order
(3) provides continued support and care to heal personnel to ensure a consistent and adequate supply of influenza virus
who were directly or indirectly involved in an incident of vaccine.
workplace violence; further,
To encourage the health care community to develop
and maintain a communication network to share information
about incidents of potential and real workplace violence.
Staffing for Safe and Effective Patient Care (0201)
To encourage pharmacy managers to work in collaboration
with physicians, nurses, health-system administrators, and
Appropriate Staffing Levels (0812)
others to outline key pharmacist services that are essential to
safe and effective patient care; further,
To advocate that pharmacists at each practice site base the
site’s pharmacist and technician staffing levels on patient To encourage pharmacy managers to be innovative
safety considerations, taking into account factors such as (1) in their approach and to factor into their thinking legal re-
acuity of care, (2) breadth of services, (3) historical safety quirements, accreditation standards, professional standards
data, and (4) results of research on the relationship between of practice, and the resources and technology available in
staffing patterns and patient safety; further, individual settings; further,
To advocate that regulatory bodies not mandate spe- To support the following principles:
cific, uniform pharmacy personnel ratios but rather ensure
that site-specific staffing levels optimize patient safety; fur- • Sufficient qualified staff must exist to ensure safe and
ther, effective patient care;
To encourage additional research on the relationship • During periods of staff shortages, pharmacists must
between pharmacy staffing patterns and patient safety. exert leadership in directing resources to services that
This policy was reviewed in 2012 by the Council on are the most essential to safe and effective patient care;
Public Policy and by the Board of Directors and was found • Within their own organizations, pharmacists should
to still be appropriate. develop contingency plans to be implemented in the
event of insufficient staff—actions that will preserve
services that are the most essential to safe and effec-
tive patient care and will, as necessary, curtail other
services; and
Pharmacy Management: Human Resources–Positions 449
• Among the essential services for safe and effective To recognize that staff development encompasses
patient care is pharmacist review of new medication more than formal inservice or external programs and in-
orders before the administration of first doses; in set- cludes informal learning among colleagues, mentoring, and
tings where patient acuity requires that reviews of other types of learning; further.
new medication orders be conducted at any hour and To strongly encourage pharmacy directors and health-
similar medication-use decisions be made at any hour, system administrators to support staff development pro-
there must be 24-hour access to a pharmacist. grams as an important benefit that aids in recruiting and
retaining qualified practitioners; further,
This policy was reviewed in 2011 by the Council on To assist pharmacy directors with staff development
Pharmacy Management and by the Board of Directors and initiatives by providing a variety of educational programs,
was found to still be appropriate. services, and resource materials.
Image of and Career Opportunities for Pharmacy Education and Workforce Development and by the Board of
Technicians (0211) Directors and was found to still be appropriate.
To promote the image of pharmacy technicians as valuable Drug Testing (9103)
contributors to health care delivery; further, Source: Council on Legal and Public Affairs
To develop and disseminate information about career To recognize the use of pre-employment drug testing or drug
opportunities that enhance the recruitment and retention of testing for cause during employment based on defined crite-
qualified pharmacy technicians. ria and with appropriate validation procedures; further,
This policy was reviewed in 2011 by the Council on To support employer-sponsored drug programs that
Education and Workforce Development and by the Board of include a policy and process that promote the recovery of
Directors and was found to still be appropriate. impaired individuals.
Pharmacist Recruitment and Retention (0218) Public Policy and by the Board of Directors and was found
Source: Council on Legal and Public Affairs to still be appropriate.
To support federal and state incentive programs for new
pharmacy graduates to practice in underserved areas; further, Employee Testing (9108)
To provide information and educational programming Source: Council on Legal and Public Affairs
on strategies used by employers for successful recruitment To oppose the use of truth-verification testing such as
and retention of pharmacists and pharmacy technicians; polygraphs as routine employment practices because of
further, the possible interference with the rights of individuals;
To conduct regular surveys on trends in the health- further,
system pharmacy work force, including retention rates for To recognize the limited use of such testing during
pharmacists and pharmacy technicians. employment where such testing may protect the rights of
This policy was reviewed in 2011 by the Council on individuals against false witness.
Public Policy and by the Board of Directors and was found This policy was reviewed in 2011 by the Council on
to still be appropriate. Public Policy and by the Board of Directors and was found
Professional Development as a Retention Tool (0112)
To recognize that pharmacy department staff development is
an essential component of staff recruitment and retention as
well as quality of work life; further,
450 Pharmacy Management: Human Resources–Guideline
ASHP Guidelines on the Recruitment, Selection,

and Retention of Pharmacy Personnel
Purpose should be developed for each position being filled. This plan
should incorporate strategies that have worked in the past
These guidelines are intended to assist pharmacy manag- while allowing for innovative ideas. Organizations that recruit
ers in the recruitment, selection, and retention of qualified frequently or have very limited candidate pools should con-
employees. The pharmacy manager working in an organized sider a continuous recruitment plan so that a list of prospective
health care system will usually have to work with the sys- candidates is available even before an opening occurs.
tem’s human resources department and within the frame- Recruitment of individuals from within the department
work of the specific recruitment, selection, and hiring poli- or the organization (e.g., from another department) creates
cies of the organization. internal growth opportunities and may result in greater em-
ployee retention and staff loyalty. Internal recruitment may
also be less disruptive and expensive. To facilitate internal
Recruitment recruitment, notice of a vacant position can be posted within
the organization before the information is made available to
Position Descriptions. Well-developed job descriptions are outsiders. Posting can be accomplished by various means,
extremely important in addressing many personnel issues. including memoranda, e-mail, voice mail, newsletters, an-
They are often used to establish salary ranges, define per- nouncements at staff meetings, and bulletin boards.
formance expectations, and write performance evaluations, Recruitment of outside candidates expands the number
but they can also be crucial tools in a successful recruitment of potential candidates and the experience available to the or-
effort.1 The position description should contain detailed in- ganization. It brings in new talent and discourages a reliance
formation on the knowledge, skills, experience, and abilities on seniority as the primary basis for promotion. Budgetary
that an acceptable candidate should possess. The following constraints and the urgency to fill a position may affect the
information may be included in a position description: recruitment method selected for external candidates. When
recruitment of individuals outside the organization becomes
• Position title and position control number (if applicable), necessary, the following methods should be considered:
• Duties, essential job functions, and responsibilities of
the position, • Advertisements in professional journals, newspapers,
• Education, training, experience, and licensure required, state professional society newsletters, and electronic
• Knowledge, skills, and abilities required to perform bulletin boards,
assigned duties, • Personnel placement services provided by national or
• Reporting relationships, state professional societies,
• Pay grade and salary range (optional), • Oral and written recommendations from colleagues.
• Education and training required to maintain compe- Some organizations offer a “finder’s fee” for hires that
tence, and result from an employee referral,
• Other specifications of the position that may be re- • Personal discussion or correspondence with potential
quired to meet legal requirements (e.g., the Americans candidates,
with Disabilities Act) or the objectives of the organiza- • Recruitment visits to colleges of pharmacy or to facili-
tion (e.g., residency or certification requirements). ties that conduct technician-training programs,
• Professional recruiting firms, which typically charge
[Note: A variety of sample job descriptions can be found the organization a percentage of the position’s annual
in Section 7.3 of the Pharmacy Management Toolkit: Tools salary. In addition, recruitment advertising companies
of the Trade for Pharmacy Managers and Directors (CD- offer access to a list of job seekers for a fee,
ROM) and in module 1 of Competence Assessment Tools for • Familiarizing students with the organization by offer-
Health-System Pharmacies (online and print versions), both ing summer jobs or participating in college of phar-
available from ASHP.] macy experiential rotations,
A revised position description should be reviewed • Tuition assistance programs for students in exchange
with staff members currently in that position and with the for future work commitments,
supervisor of that position. In many workplaces, human re- • A “prospect list” of individuals applying for previous
sources departments maintain a file of position descriptions job openings, which can often be supplied by the hu-
and may require approval of all position descriptions in the man resources department,
organization. Procedures specific to the workplace should • Internet-job-site postings,
be followed. Staff with legal expertise should review revised • Community job fairs and local or state welfare-
position descriptions to determine compliance with organi- to-work programs, and
zational and legal requirements. • Organization-sponsored events such as continuing-
education sessions, award presentations, or commu-
Recruitment Sources. Recruitment processes will depend on nity outreach programs.
the type of position being filled. Strategies for filling a sup-
port staff position may not be appropriate when searching for The ability to recruit qualified candidates will depend on
a management candidate and vice versa. A recruitment plan a multitude of factors, including the financial stability and
Pharmacy Management: Human Resources–Guideline 451
location of the organization, the area’s cost of living, the or- The composition of the interview team will depend
ganization’s compensation program (including salary, fringe on the position being filled. The team should include peo-
benefits, and raise structure), the position’s schedule and re- ple with a common interest in the outcome of the selection
porting structure, opportunities for professional growth and process and people who have been in the organization long
advancement, and the reputation and scope of pharmaceuti- enough to share with the applicant some history of the orga-
cal services offered. Only some of these factors are within nization and the department.2
the pharmacy manager’s control. Characteristics of an effective interview process in-
clude the following:
Preinterview Information. The applicant’s correspondence,
resumé or curriculum vitae, letters of recommendation, aca- • Prior to the interview, the manager should provide
demic records, and completed application form (if any) should the following to the candidate: information about the
be carefully evaluated on the basis of the position description health-system institution, department, city, and state
to determine the suitability of the candidate for an interview. (if the applicant is not from the area); an agenda for the
There are certain legal restrictions on the type of informa- interview; the position description; travel directions to
tion that may be requested from candidates on an application the facility; and clarification of expenses that will be
form. In general, an application form may request only infor- incurred or reimbursed.
mation that relates directly to the evaluation of the applicant’s • The interview should be carefully planned. Consider
ability to perform the job for which he or she is applying. If an the availability of those who need to participate in the
application form different from that of the organization is used, process and allow adequate time for each event, in-
it is advisable to have the human resources and legal depart- cluding a tour of the facility (if needed).
ments review it before distribution to potential candidates. • Interviewers should be well prepared. Preinterview infor-
mation submitted by the candidate should be distributed to
and reviewed by participants in advance of an interview.
Selection • Carefully planned, open-ended questions should be
developed in advance. Literature can be consulted to
Initial Screening Interview. An initial screening interview obtain sample questions and questions that are inad-
may be necessary if several qualified candidates have been visable or prohibited by law.2–5 Human resources de-
identified. The screening interview is generally a brief inter- partments can usually assist in developing questions.
view conducted by the human resources department or the (Refer to the appendix for sample questions.)
direct supervisor for the position; it offers a quick assess- • To the extent possible, a core group of questions
ment of the suitability of the candidate for the position. This should be asked of all candidates as a means of com-
interview is often conducted by telephone, especially if the paring them. This does not negate the need to inves-
candidate lives far away. The screening interview should be tigate different areas for each candidate or to pursue
documented and included in the applicant’s file. specific questions that surface during the interview.
• Questions should focus on predetermined criteria for
The Interview Process. A successful interview process is one the position and the qualifications of the candidates.
that matches the best available candidate with a specific posi- The goal is to match the best candidate with the vacant
tion. The process should allow the interviewers to predict the position. Questions should focus on past performance,
future performance of candidates as accurately as possible. which is often a good indicator of future performance.
One style of interview is the individual interview—one in- In addition to questions regarding professional compe-
terviewer and one interviewee. Individual interviews offer tency, the interview should contain questions that will
the advantages of simplicity, ease of scheduling, and consis- help determine whether the applicant’s attitudes and
tency of perspective. Because they are less intimidating to the behaviors will be suitable for the job. Behavior-based
candidate than group interviews, individual interviews may selection criteria should be used when possible.
allow the interviewer to more accurately evaluate the appli- • The interviewer should give the candidate a realistic
cant and provide the applicant with more opportunities to ask view of the position, including both favorable and un-
questions. The disadvantage of an individual interview is that favorable information. If the candidate is “oversold”
it does not allow for multiple viewpoints and therefore in- on the position, dissatisfaction may set in when the
creases the chance that something will be overlooked. truth becomes apparent.
Another style, team interviewing, involves a group of in- • Performance standards and methods used for evalua-
terviewers. Members of the team may interview the candidate tion should be fully explained, and opportunities for
individually and then pool their results or they may interview professional growth should be presented.
the candidate as a group. The well-prepared team approach • A description of employee benefits (e.g., medical in-
offers multiple perspectives within a standardized evaluation surance, vacation, sick leave, retirement benefits, and
scheme. Its disadvantages are extra time consumed to train the holidays) should be provided, either by the manager or
team and conduct interviews and the intimidating effect it may by the human resources department.
have on candidates. Its advantage is that it incorporates more • The initial salary and salary range for the position
individuals into the process of analyzing a candidate’s qualifi- should be discussed with the candidate.
cations.2 Team interviews foster the ideal of teamwork, and the • The employee work schedule should be reviewed with
involved employees share responsibility for the success or fail- the candidate.
ure of the person hired. They also provide an opportunity to ob- • Any additional services or covered expenses the de-
serve the candidate’s ability to interact with groups, which may partment offers should be outlined. Examples of these
be important if the position will require that type of activity. services of covered expenses include serving as a
provider of continuing-education programs, travel • Date on which employment will begin,
expenses and time off for continuing-education pro- • Supervisor’s name and position,
grams, payment of professional membership fees, and • Position description,
any other benefits that would attract the candidate to • Performance standards and evaluation system,
the position. • Next performance review date,
• A tour of the department should be provided. • Next compensation increase date,
• If the candidate is not from the area, a tour of the re- • Expected work schedule and whether it is subject to
gion should be given. Employees of the department or change depending on future needs of the department,
a real estate agency may show a candidate the area and • Employee benefits (e.g., insurance, vacation, tuition
describe the housing market and local schools. assistance, sick leave, holidays, and retirement and
• A follow-up letter is sent to the candidate after the in- pension benefits),
terview to express thanks for interest in the position • Miscellaneous commitments (e.g., employment bonus,
and the organization and to advise the candidate of the relocation expenses, licensure reimbursement, payment
next steps. Timely and well-organized communication for professional association memberships, and payment
between recruiters and candidates is essential to a suc- for attendance at professional education programs), and
cessful recruitment effort. • Potential drug screening (as applicable and in keeping
with the law) or employee physical examination and
Each interview should be documented to keep track of each can- the dates of these activities.
didate’s responses and to avoid confusion later. Documentation
could include interview questions and the candidate’s responses Retention
or simply a rating of the candidate’s responses to specific ques-
tions. One person may be designated to collect and collate Staff turnover is costly. The time required to recruit and
comments from a group interview. Documentation should oc- train new employees has been shown to cause a temporary
cur immediately after the interview.2 When considering a po- loss of productivity in the workplace.6 Staff turnover also
tential employee, the interviewer should examine punctuality, has a negative impact on staff morale, which may further
completeness and accuracy of the resumé or curriculum vitae, reduce productivity and increase turnover. Because indi-
communication skills, compensation expectations, skills and viduals have varied needs and wants that may change over
knowledge pertinent to the position, and optimal fit with co- time, there is no consistent formula for managers to apply
workers. The recruitment team should agree in advance on a to ensure employee retention.7-9 Each organization’s experi-
systematic method for selecting the successful candidate. ence will depend on such factors as the age of employees,
the employees’ stages in life and career, the organizational
Background Verification. The accuracy of information structure, the work environment, and the work itself.
provided by the candidate should be verified by the human Retention may compete with recruitment. For exam-
resources department. Information may be obtained from ple, creating staff positions with exclusively morning shifts
the following sources: may help retention but hurt recruitment, because fewer can-
didates are interested in evening shifts. When competing is-
• Personal reference letters provided by the applicant, sues arise, pharmacy managers must balance them with the
• Letters of reference provided by previous employers short- and long-term departmental goals and the current de-
or preceptors (with the applicant’s permission), mand for employment.
• State board of pharmacy records, Each organization should identify and assess reten-
• Academic records, and tion factors by examining the unique aspects of the respec-
• Legal background searches (when permitted by law tive department and organization. For example, a committee
and/or by the applicant). broadly representing the organization could be established to
determine major retention factors. On the basis of this assess-
Job Offer. The job offer should be made as quickly as possible ment, a retention plan should be developed. The plan should
after the interview process is completed. Offers should be made be reviewed periodically as the needs of employees change;
to candidates with enthusiasm and should include a deadline for employee surveys may help determine these. The following
response. Information about candidate selection should be kept factors may be considered in analyzing staff retention:
confidential until the offer has been accepted. The organization
may have specific policies and procedures regarding job offers.2 • Training period. The department should devote sufficient
The salary offered to a candidate will usually be com- time and attention to training. Prepare for the new em-
petitive with salaries for similar jobs in other organizations in ployee’s first day by providing him or her with key mate-
the same market and compatible with the organization’s exist- rial in advance and by developing an organized training
ing salary structure. The market may vary, depending on the schedule. Introduce the new employee to key people on
position. For example, the market for a pharmacy technician the first day and have everyone in the department intro-
may be local, whereas the market for a pharmacist or phar- duce themselves during the orientation period. Commu-
macy manager may be regional or national. To preserve equity nicate with the new employee regularly during the train-
within the organization, the salary offered to a candidate gen- ing period and throughout the first three months.10
erally should be consistent with salaries of staff currently in Sufficient training time ensures that the new employee is
that position. When exceptions are considered, it may become comfortable in the new work environment and decreases
necessary to reassess the compensation of existing staff. the likelihood that he or she will become frustrated in the
In addition to salary, other commitments made to a new position. Some organizations have developed a struc-
candidate should be expressed in writing as part of the for- tured mentoring program in which a new employee is
mal job offer. These may include the following: paired with a senior employee during the training period.
• Intent to stay. In several studies, this factor was the best • Promotion opportunities. These may be in the form
predictor of staff retention.11 Employees can simply be of formal promotions, career advancement programs,
asked whether they intend to stay. Replies will reflect training opportunities, or special project or commit-
employee perceptions and should be considered in light tee appointments. Flat organizational structures pro-
of behavior (i.e., the actual turnover rate). Replies also vide fewer formal opportunities for staff promotion.
may be influenced by the employees’ fear of reprisal. Employees who have made personal investments in
• Job satisfaction. Job satisfaction is a measure of the de- the organization—through expanded responsibilities
gree to which individuals like their jobs, their work en- associated with promotion—may have stronger feel-
vironment, and relationships with their coworkers. Job ings of loyalty that translate into increased retention.
satisfaction is important to retention, although the re- Succession planning is a key organizational strategy
lationship may be direct or indirect. Employees can be that ensures the availability of future leaders.
asked how satisfied they are with their jobs; there are • Job design. This refers to the general tasks that an em-
many survey instruments to assist pharmacy managers ployee performs—the content of the work. Job design
and directors in performing this task.12 Job dissatisfac- includes autonomy, the complexity of tasks, and the
tion does not necessarily lead to staff turnover if other support and tools provided to the employee. Studies
factors are more important to the individual.13,14 have found that job content is more highly correlated
• Pay and benefits. These refer to the remuneration for work with retention as the level of an employee’s education
performed and the organization’s overall benefit plan. Pay increases.11 Motivational theories suggest that the job
may be hourly (a wage) or salaried and may include over- itself can motivate intrinsically and that success in the
time premiums or bonuses and incentive plans. A benefit job can lead to increased employee satisfaction.
plan may include life, medical, dental, disability, and li- • Peer relations. This refers to working relationships with
ability insurance; tuition payments; retirement packages; peers, nurses, physicians, and technical support staff.
paid organizational membership dues; sick leave; paid Peer relations are often rated highly as a reason for stay-
vacation; child care; and prescription benefits. The value ing with an organization. It is difficult to predict during
of specific benefits to an employee will likely change over the interview process how a candidate’s peer relations
time. Many organizations offer a benefits plan that gives will develop, but past behaviors and discussion of hy-
the employee the option of choosing benefits individually pothetical scenarios can provide some insight.
suited to stages in his or her life and career. • Kinship responsibilities. This refers to family consid-
• Performance management. Performance appraisal is erations, such as child care needs, spouse-employment
a periodic assessment of an employee’s performance transfers, and care for elderly relatives. Child and elder
throughout the year. Performance appraisal is only care needs are important for working parents. These
one step in a performance management process that considerations are also difficult to screen for during
includes appraisal, ongoing feedback, goal setting, and the interview process, and they will change over time.
development. This process is important to the success Legal restrictions prevent recruiters from asking some
of the manager, the employee, and the organization. questions; the organization’s human resources depart-
The goal of performance management is to share infor- ment should be able to offer advice on this issue.
mation that will help the employee grow, both person- • Opportunity. This refers to other options in the job
ally and professionally, and improve the organization. market. Obviously, tight job markets (a relative lack
Periodic discussions with the employee are necessary of alternative positions) increase retention, whereas
to provide and receive feedback and to avoid surprises open job markets (those with many other open posi-
at the time of the scheduled performance appraisal.15 tions) may increase turnover. Managers should always
Direct observation and evaluation by supervisors and be attentive to retaining good employees, but in open
coworkers can contribute to a meaningful appraisal. job markets they need to be especially attentive.
• Recognition and awards. Employees often feel that • Staff-development opportunities. This refers to job
recognition is lacking in the workplace.7–10 New su- training, educational opportunities, and tuition reim-
pervisors or managers should receive training in em- bursement or other educational and personal growth
ployee recognition, which includes both formal and opportunities for staff. Training and educational op-
informal feedback mechanisms, from structured em- portunities can affect recognition and awards, promo-
ployee of the month (or year) programs to a simple tion opportunities, job design, and peer relations, so
thank-you given in private or at a department meeting. they can have a big impact on employee retention.
Managers should identify how employees want to be • Management style. This refers to the organizational
recognized, through employee surveys or informal dis- structure and prevalent management style in the orga-
cussions.10 Methods of employee recognition include nization (e.g., on the spectrum from autocratic to parti
cipatory). The accessibility of management staff may
• Thank-you notes, be a factor as well as the extent to which staff input
• Commendations, is encouraged. Each employee will prefer a particular
• Acknowledgment at department meetings, management style; no one style will work equally well
• Organization-wide events during National Phar- for all employees. Managers must be sensitive to the
macy Week, management styles that are effective for their staff.
• Employee of the month, quarter, or year, • Employee coaching. This refers to the manager’s men-
• Support for attendance at a professional meeting, torship role. Managers should provide feedback to
and employees regarding performance, teach specific job-
• Small awards such as movie tickets or gift cer- related skills, hold formal and informal career discus-
tificates for coffee.16 sions with employees, help employees achieve greater
self-awareness, advise employees on how best to pre- and directors [CD-ROM]. Bethesda, MD: American
pare for career options, and assist employees in prepar- Society of Health-System Pharmacists; 2001.
ing a yearly career-development plan.10 In addition, it 2. Nimmo CM, ed. Human resources management.
is important that managers recognize and acknowledge ACCRUE level II. Bethesda, MD: American Society
the employee’s contributions to the health system. of Hospital Pharmacists; 1991.
• Management survey. This refers to the organization’s 3. Yate M. Hiring the best. 3rd ed. Holbrook, MA:
commitment to identifying opportunities for improv- Adams; 1990.
ing management. Such opportunities can be identified 4. Wilson R. Conducting better job interviews. Haup-
by surveying employees about their manager’s perfor- pauge, NY: Barrons; 1991.
mance. The survey should be conducted by each man- 5. Smart B. The smart interviewer. New York: Wiley; 1989.
ager’s supervisor. Managers should also complete the 6. Donovan L. The shortage. RN. 1980; 8:21–7.
survey to see how their rating compares with that of 7. Smith SN, Stewart JE, Grussing PG. Factors influenc-
their staff. Action plans should be established on the ing the rate of job turnover among hospital pharma-
basis of the survey results.10 Such “360-degree” sur- cists. Am J Hosp Pharm. 1986; 43:1936–41.
veys should be managed with caution, however; they 8. Porter LW, Stears RM. Organizational work and per-
may create animosity and foster unhealthy relation- sonal factors in employee turnover and absenteeism.
ships between management and staff. Psychol Bull. 1973; 80:151–76.
• Physical working conditions. This refers to the physi- 9. Loveridge CE. Contingency theory: explaining staff
cal characteristics and safety of the workplace, such as nurse retention. J Nurs Adm. 1988; 18:22–5.
space, equipment, noise levels, parking accommoda- 10. Branham FL. Keeping the people who keep you in
tions, and cleanliness. business. 1st ed. New York: Amacon; 2001.
• Scheduling. This refers to opportunities for varied 11. Cavanagh SJ. Predictions of nursing staff turnover. J
scheduling, vacation time, shift rotation, job sharing, Adv Nurs. 1990; 15:373–80.
flexible hours, and part-time work. 12. Section 7.5: employee satisfaction. In: Pharmacy
• Motivation. Extrinsic motivators for change (such as management toolkit: tools of the trade for pharmacy
salary, promotion, and recognition) can affect behavior, managers and directors [CD-ROM]. Bethesda, MD:
but they cannot change values and attitudes.17 In the American Society of Health-System Pharmacists; 2001.
workplace, change occurs most readily when people are 13. Johns G. Organizational behavior: understanding life
motivated by the desire to bring their professional activi- at work. Glenview, IL: Scott, Foresman; 1983.
ties in line with their personal and professional values 14. Maslow AH. Motivation and personality. 2nd ed. New
and beliefs. Living vision and value statements offer York: Harper & Rowe; 1970.
employees an opportunity to shape an inspiring organi- 15. Chrymko MM. How to do a performance appraisal.
zational culture. Although each employee’s motivations Am J Hosp Pharm. 1991; 48:2600–1.
will be different, some theories of motivation can help 16. Nelson B. 1001 ways to reward employees. New York:
managers understand what contributes to job satisfaction. Workman Publishing; 1994.
Maslow’s14 hierarchy of needs, for example, states that 17. Nimmo CM, Holland RW. The practice change model:
employees will be happiest when they are working to- an innovative pharmacy-specific approach to motivat-
ward self-actualization, which requires that their more ba- ing staff change. In: Pharmacy management toolkit:
sic needs for security, esteem, belonging, and knowledge tools of the trade for pharmacy managers and direc-
be satisfied first. Herzberg et al.’s18 motivation/hygiene tors [CD-ROM]. Bethesda, MD: American Society of
theory explains that employees cannot be motivated by Health-System Pharmacists; 2001.
the “hygiene” aspects of their work (organization poli- 18. Herzberg F, Mausner B, Snyderman BB. The motiva-
cies, supervision, salary, peer relations, and working con- tion to work. 2nd ed. New York: Wiley; 1959.
ditions), but that dissatisfaction with those aspects can
interfere with motivating factors (the work itself, respon- Appendix—Sample Questions to Ask of
sibility, achievement, recognition, and advancement). Job Candidates2
• Exit interview. An interview should be scheduled with a
director of the department, the human resources depart- Questions for Experienced Pharmacists and Technicians
ment, and the exiting employee. The director should
ask in-depth questions to identify why the employee
• How did you become interested in pharmacy?
is leaving. The exit interview should explore the em-
• What skills or traits do you think a pharmacist needs to
ployee’s opinion of the company, department, his be successful?
or her direct manager as well as any other issues the
• What is the single greatest contribution you have made
employee may have for leaving. Pharmacy managers in your present (or most recent) position?
should validate and share this information with the ap-
• What is something you have recommended or tried
propriate management staff to decrease the likelihood in your present (or most recent) position that did not
that another employee may leave for a similar reason.14 work? Why didn’t it?
• How are you evaluated in your present (most recent)
References job?
• What would your present (most recent) employer say
1. Poremba AC. Determining the department’s staffing: are your strong points? Your weak points?
writing job descriptions. In: Pharmacy management • Why did you (do you want to) leave your last (present)
toolkit: tools of the trade for pharmacy managers job?
• Do you prefer working on a team or alone? Why? • Age,

• What part of the job did you like the best and least? • Marital or family status,
• Child care arrangements or childbearing plans,
Questions for Recent College of Pharmacy Graduates • Arrest records (although convictions related to drug
use would be appropriate),
• What was your most rewarding college experience? • Credit rating and other financial information (unless
• Why did you want to study pharmacy? the position involves financial responsibilities),
• What would you change about your college experi- • Military discharge status, unless resulting from a mili-
ence if you could? tary conviction, and
• Do you think your grades accurately reflect your aca- • General information that would point out handicaps or
demic achievements? health problems unrelated to job performance.
• What subjects did you like most and least? Why?
General Questions
• What qualities are you looking for in your next super-

visor?
• What supervisory style do you think you have? Approved by the ASHP Board of Directors, September 27, 2002.
• What are your long-term career goals? Revised by the ASHP Council on Administrative Affairs. Supersedes
• How does this position fit in with your long-term ca- the ASHP Technical Assistance Bulletin on the Recruitment,
reer goals? Selection, and Retention of Pharmacy Personnel dated April 27, 1994.
• What are you looking for in your next position that has
been lacking in previous positions? Copyright © 2003, American Society of Health-System Pharmacists,
Subjects About Which You May Not Ask
• Race, Society of Health-System Pharmacists. ASHP guidelines on the re-
• National origin, cruitment, selection, and retention of pharmacy personnel. Am J
• Religion, Health-Syst Pharm. 2003; 60:587–93.
456 Pharmacy Management: Human Resources–Report
ASHP Long-Range Vision for the Pharmacy Work

Force in Hospitals and Health Systems
Ensuring the Best Use of Medicines in Hospitals and Health Systems
Executive Summary • Conducting quality reviews of medication utilization

in the hospital’s or health system’s population of pa-
The ASHP Vision for the Pharmacy Workforce in Hospitals tients and seeking improvements where indicated.
and Health Systems expresses a vision for building the • Leading and influencing decisions about medication-
workforce capacity of pharmacy departments in hospitals related informatics, other technology (including drug
and health systems to meet the growing challenges related to administration devices), and automated processes in
optimizing the use of medicines in those settings. medication use.
Challenges The most effective pharmacy departments coordinate

and integrate these functions into a cohesive whole, bringing
The scientific knowledge about drugs and the professional together a team of pharmacists, pharmacy technicians, and
knowledge about pharmacy service delivery expand con- others that have differentiated roles in management, patient
tinuously. Many patients in hospitals and health systems in care, medication-use policy, quality improvement, informat-
the United States have serious, complex, and urgent health ics, and drug product preparation and distribution.
problems that require advanced diagnostic evaluations, in-
tricate medical procedures, and aggressive care. Medication Vision for Teamwork. Overall medication-use processes
use in hospitals and health systems is a prominent therapy (which include prescribing, order review, dispensing, ad-
for virtually all patients, and it is inherently complex and ministration, monitoring, and adjusting therapy based on pa-
dangerous. tient response) will be carried out by interdisciplinary teams,
and pharmacists will continue to be the only health profes-
sionals with the depth and breadth of knowledge about, and
Pharmacy Functions
the interest to focus their full time leadership attention on,
the use of medicines.
The objective of the overall pharmacy function in hospitals
and health systems is to support sound patient care through
Vision for Technology. Hospitals and health systems
the safe, evidence-based, and cost-beneficial use of medi-
will continue to be technology-intensive environments.
cines. Hospitals and health systems—in part because of de-
Shortages of pharmacists and pharmacy technicians quali-
mands by the government and external quality bodies—will
fied for work in hospitals and health systems are expected
require that pharmacists and pharmacy technicians possess
to be chronic. Technology will not eliminate these shortages.
and maintain sound credentials attesting to their competence
The use of technology will remain incomplete and nonstan-
to handle the tasks assigned to them. The overall pharmacy
dardized (an important safety issue in itself) for some time.
function in hospitals and health systems includes:
Vision for Pharmacists’ Responsibilities. Increasingly,

• Reviewing individual patients’ medication orders for
pharmacists will apply their time to direct, interdisciplin-
safety and effectiveness and taking corrective action
as indicated. ary patient care to ensure the best use of medicines by indi-
vidual patients. A growing number of pharmacists will work
• Collaboratively managing medication therapy for indi-
in highly specialized therapeutic areas. The expanded use of
vidual patients.
uniformly educated and certified pharmacy technicians will
• Educating patients and caregivers about medications
permit a larger portion of a pharmacy department’s pharma-
and their use.
cist staff to focus on direct patient care activities.
• Leading continuous improvements in the medication-
use process.
• Leading the interdisciplinary and collaborative devel- Credentials
opment of medication-use policies and procedures.
• Acquiring quality drug products from trusted supply Licensure alone will be insufficient for pharmacy practice in
sources. hospitals and health systems.
• Preparing medications in the doses and dosage forms
needed. Vision for Residencies. Hospital and health-system employ-
• Distribution of medications to inpatients and outpa- ers will expect all entry-level pharmacists to have completed
tients. an ASHP-accredited first-year postgraduate pharmacy resi-
• Ensuring the availability of quality drug information. dency. First-year residency programs in hospitals and health
• Influencing drug administration policies, procedures, systems concentrate on developing pharmacists that un-
and the use of related devices. derstand the organizational environment, can work in that
environment to provide clinical care to individual patients,
are capable of interdisciplinary professional work at both
Pharmacy Management: Human Resources–Report 457
an organizational and clinical level, understand the internal • An expression of ASHP’s continuing aim to support
and external standards of quality that apply, and are adept at the development of competence building, sound cre-
measuring and documenting metrics of success to manage dentials, and credentialing and privileging processes
quality. for pharmacists and pharmacy technicians in hospitals
and health systems,
Vision for Specialty Certification. Second-year ASHP- • A guide for ASHP in its long-term development of
accredited postgraduate residencies will be required for policies, education, publications, and activities to help
pharmacists caring for highly specialized and complex pa- pharmacists and pharmacy technicians develop and
tients. These programs prepare pharmacists to effectively maintain the competence and credentials needed to
interface with specialized physicians and nurses and manage work in hospitals and health systems, and
pharmacy services and informatics. Pharmacists who pro- • An advocacy tool to stimulate public policymak-
vide services in an area in which specialty certification ex- ers, external quality standards groups, hospital and
ists will be expected to be certified in that specialty. health-system trustees and administrators, hospital
and health-system pharmacy directors, and leaders in
Vision for Leadership. All hospital and health-system other collaborative health professions to ensure that
pharmacists will be required to refresh their credentials the pharmacy work force in hospitals and health sys-
continuously and to engage actively in personal continu- tems is appropriately competent, has the appropriate
ing professional development. Strong leadership will be credentials, and is appropriately privileged on the basis
required to provide and sustain comprehensive profes- of credentialing processes.
sional vision for pharmacy departments. Pharmacy manag-
ers will possess credentials appropriate to the scope of ser-
vices and the size and complexity of the setting, including,
Hospitals and Health Systems
in many cases, advanced graduate degrees in pharmacy
Hospitals and health systems include individual hospitals,
or nonpharmacy disciplines. Pharmacy departments will
multiple-hospital systems, health maintenance organization
be headed by pharmacists; nonpharmacist managers will
clinics, hospital-affiliated predischarge and postdischarge
handle many tasks that do not require the expertise or judg-
clinics, hospital-based ambulatory care pharmacies, home
ment of a pharmacist.
care services, rehabilitation facilities, skilled-nursing facili-
ties, and assisted-living facilities. Common to all of these
Vision for Pharmacy Technicians. Pharmacy technicians
settings are the health-system characteristics of (1) an inter-
eventually will be defined in laws and regulations as those
dependent and interdisciplinary work force, (2) collabora-
individuals working under a pharmacist’s responsibility that
tively developed and evidence-based medication-use pro-
(a) have completed an ASHP-accredited pharmacy techni-
cesses, (3) a governance structure that is accountable for
cian training program, (b) are certified by the Pharmacy
safe, effective, and appropriate patient care, (4) multiple
Technician Certification Board, and (c) are registered with
levels of care with continuity of care among these levels, and
state boards of pharmacy.
(5) an ongoing assessment of performance using externally
established quality standards and accreditation require-
Achieving the Vision ments.
ASHP is assessing what it and others need to do to achieve The Overall Pharmacy Function in Hospitals and Health
this vision for the pharmacy workforce in hospitals and Systems. Pharmacists and pharmacy departments bear pro-
health systems. Future programs and advocacy of ASHP will fessional and legal responsibility for all medication-use ac-
be based on this assessment. tivities in hospitals and health systems. That responsibility is
abundantly clear in professional standards, statutes, regula-
Introduction tions, court precedents, and external quality standards. The
overall pharmacy function in hospitals and health systems
Medication use in hospitals and health systems is complex will continue to include
and inherently risky. The American Society of Health-
System Pharmacists (ASHP) believes it is inevitable that • Leading the interdisciplinary and collaborative de-
public policymakers, hospital and health-system administra- velopment of medication-use policies and procedures
tors, and others will seek to modify the roles and required within the setting, including pharmacy and therapeutics
credentials for the pharmacy work force in those settings to committee policies and therapeutic protocols,
ensure that medication use is safe, effective, and appropri- • Reviewing patients’ medication orders for safety and
ate. ASHP believes the decisions will be best guided by a effectiveness,
long-range vision about the pharmacy work force for those • Collaboratively managing medication therapy for indi-
settings. vidual patients,
This vision is consistent with the ASHP Vision • Educating patients and caregivers about medications
Statement for Pharmacy Practice in Hospitals and Health and their use,
Systems,1 the ASHP Health-System Pharmacy 2015 • Leading continuous improvements in the quality of
Initiative,2 and the future vision of pharmacy practice3 de- medication-use processes,
veloped by the Joint Commission of Pharmacy Practitioners. • Acquiring quality drug products from trusted supply
This document serves as sources,
• Preparing medications in the doses and dosage forms at all levels, including clinical practice, to ensure that the
needed, overall pharmacy function successfully influences the care
• Distributing medications to inpatients and outpatients, of patients. In successful pharmacy departments, middle
• Integrating the work of staff in clinical and other func- management positions will exist, and qualified personnel
tions to ensure coordinated attention to safe, effective, at all levels will be mentored for leadership and advanced-
and appropriate care, level positions. Hospitals and health systems in which
• Functioning as a gatekeeper with respect to the quality this does not occur will be vulnerable to lapses in quality
of drug information available to caregivers throughout when inevitable turnover occurs in top management posi-
the setting as a means to support up-to-date, evidence- tions. Therefore, ongoing investment in succession plan-
based care, ning will be essential. In large hospitals and multiple-
• Influencing drug administration policies and proce- facility systems, some pharmacists will be corporate-level
dures and the use of related devices, directors (e.g., vice presidents). Some will have responsibil-
• Conducting quality reviews of medication utilization ity for departments in addition to pharmacy.
in the hospital or health system’s population of pa- Pharmacies and pharmacy departments in hospitals
tients, and and health systems will continue to be headed by pharma-
• Leading and influencing decisions about medication- cists. In most cases, major positions below the department
related informatics, other technology (including drug head level are currently occupied by pharmacists. However,
administration devices), drug administration, and au- it is likely that nonpharmacists will increasingly be em-
tomated medication-use processes. ployed below the department head level to handle various
tasks that do not require the expertise or judgment of a phar-
Differentiation and Teamwork. In hospitals and health sys- macist. These tasks may include secondary management,
tems, the overall pharmacy function will be accomplished finance, personnel administration, quality assurance, infor-
via a differentiated pharmacy work force that includes man- matics and technology, and supply and distribution logistics.
agers, pharmacists practicing in direct inpatient and outpa- Nonpharmacist positions of these types may be more com-
tient clinical roles, pharmacists and pharmacy technicians mon in large, complex hospitals and health systems where
in inpatient and outpatient drug preparation and logistical a differentiated work force is more necessary and possible.
distribution, pharmacists leading informatics and other tech-
nology activities, pharmacy technicians, business and opera- Experiential Learning. Hospital and health-system pharma-
tions managers, and other personnel, including informatics cists and pharmacy technicians will attain their knowledge,
assistants, secretarial and administrative assistants, clerks, skills, and abilities in various ways. All pharmacists and
stock-handling personnel, and couriers. Differentiation in the pharmacy technicians will receive on-the-job orientation,
pharmacy work force will increase with the size and scope training, and experiences that hone their knowledge and
of hospitals and health systems. Differentiation will be most skills necessary for specific workplaces. New pharmacy
pronounced in academic health centers where there are ad- college graduates will continue to be prepared primarily
ditional missions of education and research. Overall medi- to deliver individual patient care. They will have in-depth
cation-use processes will be conducted by interdisciplinary knowledge about medications, their pharmacology, and their
teams. Pharmacists will continue to be the only health profes- therapeutic uses. The Accreditation Council for Pharmacy
sionals with the depth and breadth of knowledge about—and Education’s (ACPE’s) accreditation standards for doctor of
the interest to focus their full-time leadership attention on— pharmacy degree programs require colleges to include ex-
the safe, effective, and appropriate use of medicines. periential education in community pharmacy, ambulatory
care, a hospital or health-system pharmacy, and inpatient or
Technology. Hospitals and health systems will continue acute care general medicine.5 These learning experiences are
to be technology-intensive environments. Many of the tech- expected primarily to involve direct patient care rather than
nologies, including those for automated medication delivery, learning to navigate and fully influence the interdisciplin-
pharmaceutical compounding, pharmaceutical packaging and ary and multidepartmental aspects of medication use within
labeling, automated distribution and vending, bedside verifi- hospitals and health systems. Concerns exist about the ca-
cation, drug administration (e.g., infusion pumps), electronic pacity of hospitals and health systems to accommodate the
drug information, electronic communications, and electronic growing volume of pharmacy students needing this experi-
patient records, will influence medication use. Automation ential education. Most new graduates entering hospital and
and information technology will be increasingly integrated health-system practice will continue to require substantial
into medication-use processes. Pharmacists with technology further education in order to fully function in those settings.
and informatics expertise will influence the choice and use of As a means to achieve that education, they should—at mini-
technologies to ensure patient safety, effectiveness of care, mum—complete an ASHP-accredited pharmacy residency.
and efficiency.4 As new technologies evolve, pharmacists Some hospitals and health systems may create mechanisms
will ensure that these preserve and enhance medication-use for existing staff to enroll in such residencies.
safety, effectiveness, and appropriateness.
Pharmacists’ Responsibilities
Leadership. Ongoing pharmacy leadership and manage-
ment will be required to provide and sustain a comprehen- In hospitals and health systems, all pharmacists will be re-
sive professional vision and evidence-based medication sponsible for error prevention, patient safety, and patient
use via an integrated and interdisciplinary work force and outcomes related to medication therapy. Many will work at
to apply limited resources to activities that will be the most various supervisory and management levels in the acquisi-
effective. Leadership and management will be required tion, preparation, and dispensing of drug products, operating
facilities and equipment for those activities, ensuring the sup- Interpersonal Skills. Pharmacists in hospitals and health
ply and integrity of drug products, providing evidence-based systems will possess exceptional interpersonal skills, work
drug information to other professionals and patients, manag- well in interdisciplinary teams, and lead the development
ing the technology applied to medication use, monitoring the of medication-use policies and procedures to meet patients’
quality of pharmacy services, and conducting medication-use- needs. They will possess competence in caring for and ef-
safety activities. Some pharmacists will be engaged in sterile fectively interacting with patients from a variety of cultures.
compounding. Some will influence the selection and man- They will engage in behavior and activities that promote the
agement of technology and information systems for medica- pharmacy profession and will represent the profession in a
tion use. Depending on the role of the hospital and health positive light and promote its goals.
system in education, some pharmacists will educate and
train pharmacy students, residents, and pharmacy techni- Proliferation of Potent and Complex
cians. All pharmacists will appropriately balance their roles
as employees of the setting and their autonomous public pro-
Medications
fessional obligations on behalf of patients.
The scientific knowledge about drugs and the professional
Increasingly, and dependent partly on the expanded
and managerial knowledge about pharmacy service deliv-
use of uniformly trained and educated pharmacy techni-
ery expand continuously. Further, many patients in hospi-
cians certified by the Pharmacy Technician Certification
tals and health systems in the United States have serious,
Board (PTCB), pharmacists will apply their time to direct,
complex, and urgent health problems that require advanced
interdisciplinary, and collaborative drug therapy to ensure
diagnostic evaluations, intricate medical procedures, and ag-
that the medication therapy of individual patients is ef-
gressive care. Even for nonurgent care, medication use in
fective, evidence based, safe, and cost-effective.6 Some
hospitals and health systems is a prominent (or at least ad-
pharmacists will work in highly specialized clinical areas.
junct) therapy for virtually all patients, and it is inherently
Specialists will train and support generalist pharmacists.
complex and dangerous. The medications used are among
To ensure a high level of coordination by all components of
the most potent, and many require complex administration
the pharmacy function in hospitals and health systems and
procedures. Many of these medications are injectable prod-
appropriate medication use and safety, the work of clini-
ucts that pose both inherent pharmacologic and infection-
cal pharmacists will be integrated with other aspects of the
control challenges and must be handled by individuals in
overall medication-use process. Depending on the volume of
multiple disciplines, some of whom have little education and
clinical work required, most pharmacists will have some on-
training about medications. Even more potent and riskier
going work assignments and responsibilities in medication
medications are anticipated in the future, and medication use
distribution. Hospitals and health systems will require that
in hospitals and health systems is expected to become even
all clinical pharmacists and faculty of colleges of pharmacy
more intense and complex. Medications for patient groups
working in their facilities be credentialed through the routine
with specific genomic characteristics will evolve.
processes used for all other pharmacy staff and be managed
by the department of pharmacy.
Throughout the work setting, the acquisition of patient Public Demand
medication histories and the provision of discharge medica-
tion information to patients and downstream caregivers will Medication-use problems (particularly errors) are well docu-
be managed by pharmacists. This will facilitate continuity of mented,7–25 but the public is not yet sufficiently aware that
care, reconciliation of medication regimens, and avoidance there is available a professional (the pharmacist) with the
of medication-related problems. Pharmacists will ensure that expertise and interest to help prevent those problems and
necessary clinical monitoring of laboratory test values oc- better ensure optimum medication therapy in hospitals and
curs pertinent to medication use for individual patients. They health systems.26–34 However, an increasing public aware-
will engage in disease prevention activities on behalf of pa- ness and debate is evolving about medication-use safety and
tients. Pharmacists will influence the selection of authorita- costs, including the cost of preventable errors.35–44 This will
tive, evidence-based drug information that is made available ultimately function as an important driver of public demand
to all caregivers in the workplace. They will engage in inter- that pharmacists and pharmacy technicians in hospitals and
disciplinary development of systemwide policies, proce- health systems be competent to achieve (and manage the
dures, and therapeutic protocols about medica-tion use. achievement of) desired patient outcomes with respect to
They will engage in medication-related public health activi- medication use.
ties on behalf of their communities.
Sound Credentials Required for
Medication-Use Process. Pharmacists will continuously im- Pharmacy Personnel in Hospitals and
prove and collaboratively redesign medication-use processes Health Systems
to optimize patient safety and improve patients’ health-related
quality of life. They will ensure that medication-use processes ASHP believes that every pharmacist and pharmacy tech-
incorporate system characteristics of interdependency, checks, nician working in hospitals and health systems will be re-
and immediate safety feedback mechanisms. In addition to car- quired to possess and maintain sound credentials attesting to
ing for individual patients, pharmacists will ensure that the out- their competence. Hospitals and health systems will engage
comes of medication therapy are assessed and managed on both in ongoing systematic assessments of the credentials and ex-
a systemwide and patient population basis. perience of all pharmacists and pharmacy technicians.45,46
Some local policies may, with good reason, allow privileges
for some pharmacists and pharmacy technicians who lack ing clinical specialties for which there is available certifica-
specific formal credentials; some of these practitioners may tion by the Board of Pharmaceutical Specialties (BPS) or
have well-documented experience and competence. As an the American Society of Consultant Pharmacists (ASCP)
ongoing investment in the safety and evidence-based effec- Commission for Certification in Geriatric Pharmacy will be
tiveness of medication use, hospitals and health systems will expected to be certified or to be working with appropriate
develop incentives to stimulate pharmacy staff to obtain de- promptness to become certified.52,b They will be expected to
sired credentials. Mechanisms will exist for acquisition of maintain the certification. Other sound certification creden-
necessary credentials by entry-level pharmacists and phar- tials may evolve.
macy technicians and those in practice that aspire to expand
their roles. Continuous Professional Development. Hospital and health-
system administrators, public policymakers, and pharmacists
Residencies. ASHP believes that a variety of sound creden- will insist that up-to-date, evidence-based medication use
tials will exist for pharmacists who practice in hospitals and occurs in hospitals and health systems. Effective, evidence-
health systems. ASHP-accredited postgraduate residency based interdisciplinary care of hospital and health-system
training exists to equip entry-level practitioners with the patients requires currentness in professional knowledge and
knowledge and skills they need to function safely and ef- skills. Therefore, all pharmacists will be required to refresh
fectively and to successfully influence medication-use poli- their credentials continuously and to engage actively in per-
cies and procedures in their workplaces. First-year ASHP- sonal continuing professional development. Professionally
accredited postgraduate residency programs in hospitals motivated pharmacists will seek out some of the updating of
and health systems concentrate on developing pharmacists their knowledge and skills on their own. In order to sustain
who (1) understand that organizational environment, (2) can pharmacy work force competence, hospitals and health sys-
work in that environment to provide clinical care to indi- tems will financially support staff development and will allow
vidual patients, (3) understand the academic health center paid work time for it. The extent to which pharmacists and
environment (if the residency is conducted there), (4) are ca- pharmacy technicians engage in activities to sustain and ex-
pable of interdisciplinary professional work at both an orga- pand their competence will be a factor in ongoing local assess-
nizational and clinical level, (5) understand both the internal ments of their credentials and their continued employment.
and external standards of quality that apply, and (6) are adept
at measuring and documenting the metrics of success that Evolving Credentials. Additional competence-building
are necessary for the management of quality in hospitals and mechanisms will evolve to educate and train pharmacists
health systems.47–49 for specific tasks in hospitals and health systems, including
Second-year ASHP-accredited postgraduate residen- those involving complex and high-risk services for which
cies are of several types. Some develop pharmacists capable in-depth knowledge is necessary. Sound credentials will
of the care of highly specialized and complex patients, ca- evolve for those tasks, and pharmacists will be expected to
pable of effectively interacting with specialized physicians obtain those credentials to do that work. Examples of spe-
and nurses and conducting collaborative research. Others cial certification roles include diabetes education, advanced
focus on hospital and health-system pharmacy management cardiac life support, emergency department care, handling
or informatics.50,51,a of biological products and products hazardous to workers,
Individuals enrolled in ASHP-accredited residency sterile compounding, distribution logistics, informatics, and
programs are licensed pharmacists. Similar to residencies clinical research.
in medicine, pharmacy residencies are intense, structured, Current sound credentials specific for pharmacists in-
“learn-by-doing” experiences that involve close work with clude the following:
preceptors and mentors. Pharmacy residents are fully ac-
countable for the outcomes of their clinical and operational • Doctor of pharmacy degrees awarded by colleges of
actions. Residencies are not “learn-by-observing” experi- pharmacy accredited by ACPE. The current entry-
ences, and they differ from internships, which are intended level degree awarded by all colleges of pharmacy is the
only to bring learners to a minimal competency for academic Doctor of Pharmacy degree. Until recently, colleges of
graduation or licensure. Among the benefits of residency pharmacy awarded bachelor of science degrees as the
training is the development of clinical skills and competency entry-level degree, which also are sound credentials,
for work and leadership in hospitals and health systems. It • Graduate degrees in pharmacy,
is conceivable that future medication-use residencies may • National Association of Boards of Pharmacy License
evolve that enroll pharmacists, physicians, and nurses and Examination for state board of pharmacy licensure,
are conducted in an interdisciplinary fashion. • Certification by BPS,b
Hospital and health-system employers will expect new • Certification by the ASCP Commission for
entry-level pharmacists in hospitals and health systems to Certification in Geriatric Pharmacy,b and
have completed an ASHP-accredited first-year postgraduate • Graduation from an ASHP-accredited pharmacy resi-
pharmacy residency. ASHP believes that licensure alone will dency program.
be insufficient for practice in hospitals and health systems.
Parallel with these sound credentials there likely will
Specialty Credentials. For some roles, pharmacists will be be purported “credentials” that are based on unsound ap-
required to have completed ASHP-accredited second-year proaches lacking ensured validity and depth. ASHP supports
postgraduate pharmacy residencies for specialized clini- only sound credentials. In their own quality and liability in-
cal activities, informatics, and top management positions. terests, hospitals and health systems will come to understand
Pharmacists who spend the majority of their time practic- that there is a quality spectrum of pharmacy credentials and
will insist on sound credentials for their pharmacy staff. The and distribution under the physical supervision of pharma-
multiorganizational Council on Credentialing in Pharmacy cists. Some pharmacy technicians will manage aspects of
(CCP) has created guiding principles for sound certification product acquisition and supply logistics. Some will manage
programs in pharmacy.53 the use of technology and quality assurance activities. Some
Additional sound credentials in pharmacy may be rec- will supervise other pharmacy technicians. Some will as-
ognized in the future, particularly for clinical specialties. sist pharmacists in collecting and screening routine patient-
BPS now certifies pharmacists in five specialties: pharma- specific clinical laboratory data and routine screening of
cotherapy (plus two “added qualifications” in infectious clinical monitoring data to identify out-of-range findings
diseases and cardiology), nuclear pharmacy, nutrition sup- that warrant pharmacist attention. Some will manage aspects
port pharmacy, psychiatric pharmacy practice, and oncology of informatics.
pharmacy practice.c More BPS added qualifications may
evolve. Hospitals and health systems will require pharma- Technician Credentials. Additional competence-building
cists working in those areas to attain them. The Department mechanisms will evolve to educate and train pharmacy tech-
of Veterans Affairs has established a mechanism for creden- nicians for specific tasks in hospitals and health systems, in-
tialing and privileging pharmacists to perform some tasks, including those involving complex and high-risk services for
cluding medication prescribing.54–57 Privileging is defined as which in-depth knowledge is necessary. Hospitals and health
the process by which an oversight body of a health systems will require pharmacy technicians to obtain those
care organization or other appropriate provider credentials to do that work. Pharmacy technicians will con-
body, having reviewed an individual health care tinue to work under the supervision of pharmacists and will
provider’s credentials and performance and found not be sanctioned to work independently. Although legisla-
them satisfactory, authorizes that individual to tures and regulatory bodies may establish licenses for phar-
perform a specific scope of patient care services macy technicians, these will not be licenses for independent,
within that setting.45 unsupervised practice. Telepharmacy arrangements may
evolve in which a supervising pharmacist may be physically
It is conceivable that legislatures and regulatory bodies may
remote from a pharmacy technician.
establish additional required pharmacist licenses for specific
Sound credentials for pharmacy technicians currently
activities.
include graduation from an ASHP-accredited pharmacy
technician training program and certification by PTCB.
Leadership Credentials. All pharmacy managers (whether For pharmacy technicians, there also exists a spectrum
pharmacists or nonpharmacists) will possess credentials ap- in the quality of education and training available (some of
propriate to the scope of services and the size and complex- which is unsound). Hospitals and health systems will be dili-
ity of the setting. Some pharmacists, particularly in large and gent in insisting on sound credentials. All pharmacy techni-
complex settings and multiple-facility organizations, will cians will be registered with state boards of pharmacy.
have corporate-level administrative appointments higher
than the department head level. Individuals with that author-
ity will have sufficient management experience to have de- Entry-Level Staff
veloped the skills and talents for that role and will possess
appropriate advanced credentials, which may include gradu- Some entry-level staff will lack all the competencies and
ation from an ASHP-accredited second-year postgraduate credentials needed to work fully in hospitals and health sys-
residency in management or advanced graduate degrees in tems. Employers will require them to build competence and
pharmacy or nonpharmacy disciplines. The ASHP Research acquire appropriate credentials promptly. The initial work
and Education Foundation has created a Center on Health- assignments of entry-level staff may be somewhat restricted
System Pharmacy Leadership. It is possible that this may until completion of the necessary competence building and
lead to an available certification for pharmacy leaders in acquisition of credentials.
hospitals and health systems.
Assumptions and Expectations
Pharmacy Technicians
This vision is based on the following assumptions and ex-
In the pharmacy profession and in laws and regulations, pectations:
pharmacy technicians eventually will be defined as those
individuals working under a pharmacist who (1) have com- 1. As scientific pharmacologic advances increase, mor-
pleted an ASHP-accredited pharmacy technician training tality from various diseases will decrease. People
program,58–60 (2) are certified by PTCB, and (3) are reg- will live longer and will have chronic conditions and
istered with state boards of pharmacy. Other support staff more temporary acute conditions for which they will
will be employed in pharmacies in hospitals and health sys- increasingly use hospital and health-system services.
tems, but they will not be defined in laws and regulations They will use more medications, necessitating greater
as pharmacy technicians. All pharmacy technicians will be numbers of qualified pharmacists and pharmacy tech-
required to participate in continuing education offered by nicians.
accredited providers of such continuing education. ACPE 2. For reasons of quality assurance and compliance with
conducts a process to accredit such providers. accreditation requirements (such as Joint Commission
standards61), hospitals and health systems will insist
Role of Technicians. Most pharmacy technicians will be en- that pharmacists and pharmacy technicians demon-
gaged in drug-product acquisition, preparation, dispensing,
strate that they are competent to perform the tasks set system work, this avenue for recruitment will not
forth in their job descriptions. likely be very effective for those settings.
3. Hospitals and health systems will establish systematic 15. Graduation from an ASHP-accredited pharmacy resi-
and ongoing processes to assess the competence and dency will become a minimum requirement by em-
credentials of pharmacists and pharmacy technicians. ployers for pharmacists to work in hospitals and health
Many hospitals and health systems will develop their systems.d
own tools for assessing employee competence and 16. Graduation from an ASHP-accredited pharmacy techni-
credentials. Some will use external validation meth- cian training program, certification by PTCB, and reg-
ods, such as BPS certification and graduation from an istration with a state board of pharmacy will become
ASHP-accredited residency. minimum requirements for pharmacy technicians to
4. The quality of patient care in hospitals and health sys- practice in hospitals and health systems.d
tems will be enhanced by pharmacists and pharmacy 17. Greater quality and consistency in the education and
technicians with appropriate credentials. training of pharmacy technicians will allow for ex-
5. To ensure safe, effective, and coordinated patient care, panded roles for pharmacy technicians, similar to
clinical and other pharmacy activities in hospitals and those seen in U.S. military facilities and to the legal
health systems will be staffed, conducted, and man- allowances for the work of pharmacy technicians in
aged in an integrated fashion. several European and Nordic countries.
6. The public will increasingly wish to be able to distin- 18. The demand for qualified pharmacy technicians with
guish pharmacists who are qualified to provide medi- appropriate credentials will increase in the United
cation therapy management services from those who States. State requirements for the credentials of phar-
are not. macy technicians are advancing rapidly.
7. Governments and quality-standards organizations, 19. Hospital and health-system pharmacy departments
such as the Joint Commission, will eventually insist on will continue to employ supportive personnel who are
appropriate credentials for pharmacists and pharmacy not legally defined as pharmacy technicians and are
technicians in hospitals and health systems. not legally authorized to perform the same functions
8. Medicare provider status will evolve for pharma- as pharmacy technicians.
cists with appropriate credentials, enabling payment 20. Technology will not eliminate pharmacy work-force
to hospitals and health systems for their medication shortages in hospitals and health systems. Moreover,
therapy management. Medicare payments to hospitals the use of technology will remain incomplete and non-
and health system will be contingent on active local standardized (an important safety issue in itself) for
credentialing and privileging processes for all major some time.
health care workers in hospitals and health systems, 21. As health care becomes increasingly collaborative and
including pharmacists. multidisciplinary, pharmacists’ knowledge about med-
9. Specialization will increase, and hospitals and health ications will continue to be different from and more
systems will look to sound credentials as indications of complete than that of other health care professionals.
pharmacists’ specialized competencies.
10. BPS will be urged to develop additional clinical cre-
dentialing processes in cooperation with professional
Some Implications
associations.
Embedded in the following implications are numerous pri-
11. In the face of shortages of qualified pharmacists and
orities that will influence ASHP’s ongoing and long-term
pharmacy technicians for hospital and health-system
actions with respect to the pharmacy work force in hospitals
work, and in the face of the increasing need for quali-
and health systems. Other actions will evolve as well.
fied workers, accreditation bodies for hospitals and
health systems will become increasingly insistent that
the pharmacists and pharmacy technicians in those set- • Hospital and health-system trustees, administrators,
and human resource, risk-management, and legal
tings have appropriate credentials.
departments must be helped to understand that only
12. Compared with the chronic shortage of pharmacists
qualified pharmacists and pharmacy technicians with
across the entire pharmacy profession, the shortage of
pharmacists competent to work in hospitals and health appropriate credentials must comprise the pharmacy
systems will continue to be more severe.62–68 work force in hospitals and health systems.
13. The demographics of the pharmacy work force in hos- • Mechanisms must be developed to help hospital and
pitals and health systems are changing, and hospital health-system employers readily discern sound phar-
and health-system employers will need to respond re- macy credentials from unsound ones.53,71
sourcefully and creatively to adjust to those changes.69 • Model local credentialing and privileging processes
14. State laws and regulations will continue to require must be developed and implemented to assist hospitals
that pharmacists be graduates of colleges accredited and health systems in assessing whether pharmacists
by ACPE. However, some hospital and health-system and pharmacy technicians possess the necessary cre-
employers in the United States will consider hiring dentials for the functions assigned to them.
graduates of foreign pharmacy schools. A process ex- • Colleges of pharmacy and pharmacies in hospitals
ists for foreign graduates to achieve a foreign phar- and health systems must better articulate and inte-
macy graduate equivalency certification.70 Given that grate their respective roles in preparing graduates for
licensure alone will not be sufficient for successful ASHP-accredited pharmacy practice residencies.
work in hospitals and health systems, and given the • Since patient care in hospitals and health systems is
advanced credentials needed for hospital and health- inherently interdisciplinary, the education of pharma-
cists must be conducted in a more interdisciplinary cist’s qualifications to provide patient care services.
manner. [Similarly, credentialing can be applied to pharmacy
• Sound credentials are needed for various subdepart- technicians.]
ment-level activities within hospitals and health sys-
tems (e.g., sterile compounding). ASHP and CCP
should lead a prompt identification of the primary a
Federal funding is available to help support ASHP-accredited
activities and develop a time-certain call for the pro- first-year residencies in hospitals caring for Medicare pa-
fession to develop corresponding training and cre- tients. To address the growing need in hospitals and health
dentials for those activities. systems for pharmacists with advanced credentials, ASHP is
• Public policymakers must be helped to understand the seeking similar funding (which previously existed) for ASHP-
need for qualified pharmacists and pharmacy techni- accredited second-year residencies. ASHP is the accrediting body
cians within hospitals and health systems and to sup- for pharmacy residencies. In early 2007, there were 714 ASHP-
port mechanisms to educate and train practitioners for accredited postgraduate residency programs (481 first-year pro-
those roles. grams and 233 second-year programs). These programs graduate
• In cooperation with professional associations, BPS approximately 1400 residents per year. More ASHP-accredited resi-
should expand the credentials for pharmacy practice dencies and residency graduates are needed to fulfill the work-force
and the number of pharmacists certified. needs in hospitals and health systems.
• Pharmacy technicians must receive uniform education b
The processes used by BPS and ASCP for designating specialties
and training before becoming PTCB certified. and assessing the knowledge of individuals applying for certifica-
• Pharmacy technicians must be registered with state tion are different.
boards of pharmacy. c
As of early 2007, BPS is engaged in a practice analysis in am-
• The National Association of Boards of Pharmacy bulatory care, which could lead to a sixth designation or “added
should establish model laws and regulations to support qualifications.”
state requirements for uniform education and training d
While this evolves to become a requirement by employers, a natu-
for pharmacy technicians and for PTCB certification ral transition period will exist when pharmacists and pharmacy tech-
of all pharmacy technicians. nicians who have achieved competence and successful experience
in hospitals and health systems will continue to be employed.
Definitions
References
In this document, the following definitions apply, as pub-
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Practice Settings
468 Practice Settings–Positions
Practice Settings
Use of Two Patient Identifiers in the Outpatient Setting Home Intravenous Therapy Benefit (0414)
(1024) Source: Council on Legal and Public Affairs
Source: Council on Pharmacy Practice To support the continuation of a home intravenous therapy ben-
To encourage the use of two identifiers to confirm patient efit under federal and private health insurance plans, and
identity when transferring filled prescriptions to the posses- expand the home infusion benefit under Medicare Part B at
sion of the patient or patient’s agent in outpatient settings. an appropriate level of reimbursement for pharmacists’ patient
This policy was reviewed in 2014 by the Council on care services provided, medications, supplies, and equipment.
Pharmacy Practice and by the Board of Directors and was This policy was reviewed in 2008 by the Council on
found to still be appropriate. Public Policy and by the Board of Directors and was found
Practice Settings–Guidelines 469
ASHP Guidelines on
Home Infusion Pharmacy Services
Background and Purpose Many of the activities included in these guidelines are
the subjects of other American Society of Health-System
Background. Home infusion services are provided by a va- Pharmacists (ASHP) policy and guidance documents, which
riety of organizations, including hospitals, community phar- should be referred to for additional information. Pharmacists
macies, home health agencies, hospices, and specialized practicing in home infusion should use professional judg-
infusion companies. Patients receive care in non-inpatient ment in assessing ASHP’s policy and guidance documents
settings, such as their homes and ambulatory infusion cen- and in adapting them to meet their health care organizations’
ters, or in alternative-site settings, such as skilled-nursing and patients’ needs and circumstances.
facilities. Home infusion pharmacies may provide one or To ensure the safe, appropriate, and effective use of
more of several service lines: medications in the home, home infusion pharmacies should
develop comprehensive services to address factors unique
• Infusion therapies (e.g., intravenous, subcutaneous, to home infusion. Caregivers such as family members, who
intrathecal, epidural); often have no health care experience, should be trained if
• Specialty pharmacy services; deemed safe and appropriate to properly administer, store,
• Ambulatory infusion center services; and dispose of medications supplies and biohazard waste;
• Home health nursing; operate medication administration devices; and monitor pa-
• Private duty nursing; tients as necessary. Many medications must be aseptically
• Respiratory equipment and clinical respiratory services; compounded, often in quantities sufficient for a week’s use,
• Hospice services; and delivered under conditions that will ensure that prod-
• Home medical equipment and supplies (with or with- uct potency and purity are maintained. Vascular access for
out oxygen service); or infused therapies should be maintained for the intended du-
• Enteral products and supplies. ration of treatment, which may range from days to years.
Medication administration devices should be selected and
It should be noted that different aspects of home infusion maintained to accurately and safely administer a variety of
can be provided by different organizations. When services therapeutic regimens. Potential complications should be an-
are shared among providers, pharmacists have a professional ticipated, and a proactive individualized plan of care should
responsibility to ensure that all patient care responsibilities be established for monitoring, detecting, and managing com-
are defined, understood, agreed upon, coordinated, and doc- plications, including those related to equipment, enteral and
umented in advance by all providers. These guidelines apply parenteral access, compliance, response to therapy, and pa-
to the provision of home infusion services by pharmacists tient and family education. Economic considerations should
practicing in all health care settings. be taken into account so that care is provided in the most
cost-effective manner. Home infusion pharmacies should
Purpose. The purposes of these guidelines are to define the have an effective organizational structure with the flexibility
role of the pharmacist in providing home infusion care to to meet the changing needs of patients, as well as to keep
patients and to outline minimum requirements (indicated by pace with the rapid growth of the industry and changes in
use of the word “shall”) and best practices for the operation health systems. As health care providers in the home setting,
and management of services provided by pharmacies in the pharmacists must be concerned with the outcomes of ther-
home or alternative-site setting. In broad terms, home in- apy and not just the provision of services. Effective manage-
fusion includes the provision of specialized, complex phar- ment is necessary to ensure that quality outcomes of therapy
maceutical products; development and execution of plans are achieved. While the scope of pharmacy services is likely
to manage the medication therapy of patients; and clinical to vary from site to site, depending upon the needs of the
assessment and monitoring of patients in their homes. These patients served, these criteria are strongly linked to patient
services generally include home infusion therapy; other outcomes; neglect of any one area may compromise quality.
injectable drug therapy; parenteral and enteral nutrition
therapy; and occasionally preparation of other sterile prepa- Practice Management
rations, compounds, or products. As the number and types
of therapies administered in the home and alternative sites Mission and Goals of the Home Infusion Organization.
expand, the resources and support required to provide these The pharmacy or its affiliated organization shall have a
therapies will expand as well. Specific and unique pharma- written mission statement that reflects patient safety, qual-
cist education and training in drug product admixtures and ity of care, and operational responsibilities. The statement
administration techniques, equipment operation and mainte- should be consistent with the mission of the parent home
nance, patient monitoring, and patient and family education infusion organization and/or health system, if applicable.
are required to ensure successful outcomes. These guidelines The development and prioritization of goals, objectives, and
outline the pharmacist’s role in providing these services and work plans shall be consistent with the pharmacy’s mission
products. They are not intended to apply to home health or statement. The mission should be understood by employees,
previously mentioned services that do not involve the provi- contract staff, and other participants (e.g., students and resi-
sion of home infusion pharmacy services. dents) in the pharmacy’s activities.
470 Practice Settings–Guidelines
Laws and Regulations. The home infusion pharmacy shall tion, its scope of services, and the population served. Such
comply with all applicable local, state, and federal laws and practice standards and guidelines should be adapted into the
regulations. Laws and regulations change frequently, so it is organization’s policies and procedures when appropriate.
imperative to remain up to date on these changes so that the
pharmacy remains in compliance. The pharmacy shall main- Policies and Procedures Manual. A policies and procedures
tain written or computerized documentation of compliance manual governing the scope of the home infusion pharmacy
regarding procurement, storage, and distribution of drug prod- services (e.g., administrative, operational, clinical, quality
ucts, patient information, and related safety regulations from performance and/or improvement, infection control, drug
applicable state boards of pharmacy, the federal Food and Drug preparation and dispensing, equipment maintenance) shall
Administration (FDA), the United States Pharmacopeia (USP), be properly maintained and available. The manual should
the Drug Enforcement Administration (DEA), the Centers be reviewed and revised annually or whenever necessary
for Medicare & Medicaid Services (CMS), the Occupational to reflect changes in procedures specific to the sites where
Safety and Health Administration (OSHA), the National the pharmacy’s products and services are provided. All per-
Institute for Occupational Safety and Health (NIOSH), and sonnel should be familiar with the contents of the manual.
the Environmental Protection Agency (EPA), among others. Appropriate mechanisms should be established to ensure
Pharmacy management of patient information shall conform compliance with the policies and procedures.
to the Health Insurance Portability and Accountability Act of
19961 (HIPAA) and to the parent organization’s policies and Human Resources
procedures. Pharmacies that participate in Medicare Part D
plans shall comply with government regulations for Medicare The responsibilities and related competencies for home infu-
Part D, which may include annual compliance training regard- sion pharmacy employees should be clearly defined in writ-
ing Medicare fraud and abuse. Appropriate business licenses, ten position descriptions for all job categories.
permits, and tax stamps should also be available.
Director of Home Infusion Pharmacy Services. Effective
Licensure. Professional staff shall maintain pharmacist li- leadership and practice management skills are necessary for
censure applicable to their practice. Policies and procedures pharmacists’ delivery of care that meets the needs of patients
should be available to ensure that health care providers meet and the health system and results in continuous improvement
applicable state licensure and home infusion organization in patient outcomes. These guidelines use the term director
authorization, if required, for prescribing medications. of home infusion pharmacy services (or, more simply, direc-
Many states require pharmacies with out-of-state phar- tor) to indicate the person responsible for managing those
macy licenses to also have a pharmacist licensed in the state services. Depending on the health system’s organizational
of the prescription recipient. Pharmacies dispensing drugs structure and other factors, designations such as manager or
across state lines shall comply with out-of-state licensure pharmacist-in-charge may also be used.
requirements, as well as other state and federal interstate The director of the home infusion pharmacy services
laws and regulations. The pharmacy director shall have a must work in collaboration with appropriate health-system
process in place for validating current licensure of all pro- leaders to create a long-term vision for the home infusion
fessional staff, and the source(s) of this validation shall also pharmacy department that is consistent with that of the
be verified. In locations in which pharmacy technicians are health system. Depending on the size and scope of the set-
required to be registered and/or certified, such registration ting, these functional responsibilities may be assigned to a
and/or certification shall be validated annually or as required single person or a team. It is the responsibility of the director
by law or regulation. to monitor the status of the goals set forth in the department’s
vision, provide feedback to the pharmacy team as necessary,
Accreditation. Accreditation provides patients, referral and support the team’s implementation of the core functions
sources, and payers the assurance that the pharmacy meets of the pharmacy practice.
a basic level of quality in patient care. Accreditation may be Home infusion pharmacy services should be managed
required by some payers and is recommended for the home by a professionally competent, legally qualified pharmacist.
infusion pharmacy. Accrediting bodies may include the Joint In addition to the requirements for a staff pharmacist, the
Commission, Community Health Accreditation Program director shall be thoroughly knowledgeable about home in-
(CHAP), Pharmacy Compounding Accreditation Board fusion pharmacy practice and management. Completion of a
(PCAB), Healthcare Quality Association on Accreditation pharmacy residency program and/or home infusion experi-
(HQAA), Accreditation Commission for Healthcare ence is desirable.
(ACHC), and Medicare. The director shall be responsible for
Practice Standards and Guidelines. Appropriate practice • Establishing the mission, vision, goals, and scope of
standards and guidelines of professional pharmacy orga- services of the pharmacy on the basis of the needs of
nizations such as ASHP should be assessed and utilized as the patients served, the needs of the health system, and
appropriate to the scope of pharmacy services provided. developments and trends in health care;
The standards of other professional clinical organizations, • Developing, implementing, evaluating, and updating
such as the American Society for Parenteral and Enteral plans and activities to fulfill the mission, vision, goals,
Nutrition (A.S.P.E.N.), the Infusion Nurses Society (INS), and scope of services of the pharmacy;
the Infectious Diseases Society of America (IDSA), and the • Ensuring the development and implementation of
Oncology Nursing Society (ONS), should also be assessed policies and procedures that provide safe and effective
and used when applicable to the home infusion organiza- medication use for the patients served by the institution;
• Mobilizing and managing the resources, both human ulations. In states in which registration of pharmacy tech-
and financial, necessary for the optimal provision of nicians and/or special licensure or training is required for
pharmacy services; specific responsibilities (e.g., preparing sterile preparations),
• Overseeing contracts (for example vendors, home the pharmacy shall ensure that such requirements are met.
health agencies, payers, etc.); Pharmacy technicians are responsible for compound-
• Ensuring that pharmacy services are delivered in coming sterile and nonsterile preparations in a manner to en-
pliance with applicable state and federal laws and reg- sure patient safety, managing drug inventory, contacting
ulations, as well as national practice standards; and patients about scheduled deliveries, and other duties as as-
• Ensuring all technology and automation used through- signed. Customer service staff may be tasked with contact-
out the medication use process is implemented, main- ing patients about scheduled deliveries, communication with
tained, and utilized to promote patient safety. customers (e.g., other suppliers, patients, families, referral
sources), and other duties as assigned. Drivers and/or ware-
A part-time or contract director shall have the same obliga- house managers may be responsible for delivery of medi-
tions and responsibilities as a full-time director. The direc- cation to the patient, processing of initial paperwork to be
tor, in carrying out these responsibilities, should supervise signed, storage of medication in the home, observation of
an adequate number of competent, qualified personnel. quantities of medications and supplies left in the home, and/
or communication with the pharmacist if there are any ques-
Home Infusion Pharmacists. Pharmacists who provide tions or concerns. Intake personnel, insurance verification
home infusion services shall have an active license to practice staff, and/or billers take referrals, determine insurance cov-
pharmacy issued by the applicable state board of pharmacy erage, obtain authorizations or precertifications and renew
and other credentials as required by local, state, or federal them as needed, bill payers for services provided, and follow
laws and regulations. Some states require special licensure up on rejected claims.
or training for preparing sterile preparations. Pharmacists
dispensing medications to patients who reside in other states Staffing, Work Schedules, and Assignments. The director
may also be subject to laws and regulations in those states; should ensure that work schedules, procedures, and assign-
additional licensure may be required. The pharmacist should ments make the best use of pharmacy personnel and other
be knowledgeable about all applicable federal and state laws resources. Resources should be sufficient to ensure patient
and regulations. The pharmacist is responsible for: safety. Flex time, weekend options, exempt and nonexempt
status, shift differentials, and on-call pay and responsibilities
• Day-to-day supervision of dispensing sterile prepara- should all be considered when creating a staffing plan.
tions and delivery activities;
• Drug information provided to nurses, physicians, pa- Recruitment and Selection of Personnel. Personnel should
tients, and caregivers; be recruited and selected on the basis of the requirements
• Clinical monitoring, care planning, and assessment of stated in the established job description, the candidates’
home infusion patients; job-related qualifications, and their prior performance. The
• Maintaining a professional image and demeanor in pharmacy director should assist in identifying the relevant
both appearance and actions; professional and technical qualifications for each job de-
• Maximizing work efficiency and patient safety through scription and should participate in candidate interviews
the use of technology; and final selection. The organization should have a human
• Maintaining confidentiality of patient and proprietary resources manual stating the requirements for reference
information; and checks, criminal background checks, and primary source
• Utilizing support personnel effectively. verification of professional licenses. In addition, it should be
organization policy that the Office of the Inspector General
Technicians and Other Support or Clinical Staff. Sufficient (OIG) List of Excluded Individuals/Entitites2 is checked
support personnel (pharmacy technicians, clinical staff [e.g., to ensure that potential candidates for employment have
nurses, dietitians, respiratory therapists], and customer ser- not been excluded from federally funded health care pro-
vice, procurement, delivery, clerical, and administrative grams. Employees’ professional licenses and the OIG List
personnel) should be available to facilitate the delivery of of Excluded Individuals/Entities should be verified at least
home infusion pharmacist care and services. Pharmacy tech- annually.
nicians should have completed an accredited pharmacy tech- Recruitment for home infusion pharmacy positions
nician training program and be certified by the Pharmacy can be a challenge, especially when the pharmacist la-
Technician Certification Board (PTCB). The pharmacy bor market is tight. Home infusion pharmacy practice is a
should hire pharmacy technician trainees without those unique practice setting with which many pharmacists are
qualifications only if those individuals (1) are required to not familiar, especially new graduates. Infusion pharmacy
both successfully complete an accredited pharmacy techni- practice training in college of pharmacy curricula varies,
cian training program and successfully complete PTCB cer- so recruiting staff with home infusion experience may not
tification within 12 months of employment or as required by be possible. Creative recruitment techniques, such as hiring
law or regulation, and (2) are limited to positions with lesser part-time pharmacists to cover open positions and offering
responsibilities until they successfully complete such train- on-site training, may help recruitment.
ing and certification. The pharmacy should require ongoing
PTCB certification as a condition of continued employment. Orientation and Training. All employees shall be oriented
Appropriate supervisory controls should be maintained and to the type(s) of care and services provided by the organiza-
documented, consistent with federal and state laws and reg- tion. There should be an established procedure for orienting
new personnel to the pharmacy, the parent organization, the Financial Management
health system(s) that the home infusion pharmacy serves, re-
spective staff positions, and the patient populations served. Budget Management. The home infusion pharmacy should
All employees should understand the roles and responsibili- have a budget that is consistent with the health system’s fi-
ties of others in the organization and should be oriented and nancial management process and supports the scope of and
demonstrate proficiency on equipment they are expected to demand for pharmacy services. Oversight of workload and
operate or support as part of their duties. Employees should financial performance should be managed in accordance
be knowledgeable about the supplies and equipment that are with the health system’s requirements. Management should
delivered to the patient. All personnel should possess the provide for the determination and analysis of pharmacy ser-
education and training needed to fulfill their responsibilities, vice costs, the determination and analysis of capital equip-
including specific knowledge related to home infusion. All ment costs, and the determination and analysis of new proj-
personnel should participate in continuing education pro- ect growth.
grams and activities relevant to home infusion practice as The pharmacy budget processes should enable the
necessary to maintain or enhance their competence.3 analysis of pharmacy services by unit of service and other
A home infusion organization is responsible for help- parameters appropriate to the organization (e.g., organiza-
ing teach employees, patients, family members, and care- tion-wide costs by medication therapy, clinical service, spe-
givers about standard safety precautions. The pharmacist cific disease management categories, and patient third-party
should ensure that the home infusion organization provides enrollment). The director should have an integral part in the
appropriate education for its employees and patients, in- organization’s financial management process.
cluding education about appropriate disposal and handling
of medical waste, procedures for preventing and manag- Health-System Integration. Other functional units within
ing needle and sharps stick injuries,4 handling of cytotoxic the health system should factor the cost of pharmacy ser-
and hazardous medications,5 and material safety data sheets vices being provided by the home infusion pharmacy into
(MSDSes).6 The pharmacist should be a key resource in the their departmental budget when appropriate.
development of such educational programs. The pharmacist
should assume an active role in the home infusion organiza- Third-Party Contract Review. In conjunction with the or-
tion’s infection-control activities. ganization’s legal department, the pharmacy director’s team
Pharmacists should receive training as necessary to should review third-party payer contracts to ensure that re-
ensure that they possess the knowledge and skills required imbursement is appropriate for services being rendered and
for the provision of home infusion services. They should that terms of the contracts are in the best interests of the
participate in ongoing continuing education activities to up- patient and the health system. The pharmacy should contract
date and enhance their knowledge and skills related to home with third-party payers that are relevant to the pharmacy’s
infusion. Pharmacists should also participate in an ongoing patient population.
competence assessment program as part of an overall staff
development program. A valid assessment of competence Drug and Supply Expenditures. Specific policies and pro-
should consider the pharmacist’s responsibilities and the cedures for managing drug expenditures should address
types and ages of patients served. The assessment should such methods as competitive bidding, group purchasing, uti-
be conducted and documented on an ongoing basis for all lization review programs, inventory management, and cost-
pharmacists. When appropriate, pharmacists should assist effective patient services.
in training and in continuing education programs for other
home infusion providers. Manufacturers and Suppliers. Criteria for selecting drug
product manufacturers and suppliers should be established
Performance Evaluation, Contribution Management, and by the pharmacy to ensure the quality of drug products and
Competency Assessment. Policies and procedures should the best prices, and that vendors are able to supply products
define the ongoing performance evaluations, contribution in the volume required.
management, and competency assessments of home infusion
pharmacy personnel. All home infusion pharmacy personnel Reimbursement. The director of the pharmacy or home infu-
should receive regular and timely evaluations. Performance sion organization should be knowledgeable about reimburse-
should be evaluated on the basis of position description re- ments for home infusion pharmaceutical services, medica-
quirements and expected competencies. ASHP guidelines7 tions, supplies, durable medical equipment, and, if applicable,
and USP Chapter 7978 describe requirements for initial and nursing services. Processes should exist for routine verifica-
ongoing assessment of compounding knowledge and skills. tion of patient reimbursement benefits and for counseling
Competency assessments should include practical skills (e.g., patients about their anticipated financial responsibility for
aseptic technique challenge), clinical competencies (e.g., as- planned therapies. A process should also exist for responding
sessing patients, developing a plan to manage patient care, to service requests from medically indigent patients.
and executing the plan), equipment competencies, and patient The director of the pharmacy or home infusion organi-
teaching competencies, if appropriate (i.e., if the employee zation should also be responsible for policies regarding drug
will be instructing patients). Monitoring clinical outcomes is procurement, drug expenditures, inventory management,
a critical part of the home infusion pharmacist’s roles. determination and analysis of pharmacy service costs, capi-
tal equipment acquisition, budgeting (including analysis of
budgetary variances, patient revenue projections, and justifi-
cation of personnel commensurate with workload productiv-
ity), and payer audits.
Medication Use and requirements, should be supplied before the medication is

administered. Information about the stability of drugs for
Drug Information Services
home infusion should address administration via a variety
Medication-Use Policy Development. Medication-use of alternative delivery devices, such as portable infusion
policy decisions should be founded on the evidence-based pumps, syringe pumps, implantable infusion devices, elasto-
clinical, ethical, legal, social, philosophical, quality-of-life, meric infusion pumps, and common peripheral and central-
safety, and economic factors that result in optimal patient line administration devices.
care. Committees within the organization (e.g., pharmacy Adequate space, resources, and information handling
and therapeutics, infection control) that make decisions con- and communication technology shall be available to facili-
cerning medication use should include the active and direct tate the provision of drug and related information to patients,
involvement of physicians, pharmacists, and other appropri- caregivers, health care providers, multidisciplinary team
ate health care professionals. The pharmacy should actively members, and referring physicians. The director shall iden-
participate on committees whose decisions could affect the tify a core library (hard copy or electronic) appropriate for
quality, safety, effectiveness, or cost of pharmacy services or a home infusion pharmacy practice setting and ensure that
the medication-use process. those resources are readily available to users. Drug informa-
tion sources should include current professional and scien-
Medication Therapy Decisions. The pharmacist’s preroga- tific periodicals, Web-based research tools (e.g., AHFS-DI,
tives to initiate, monitor, and modify medication therapy for MicroMedex, Lexi-Comp Online), the latest editions of drug
individual patients, consistent with laws, regulations, home compendia and textbooks in appropriate pharmaceutical and
infusion organization policy, and clinical protocols, should biomedical subject areas, and any references required by
be clearly delineated and approved by the home infusion or- state boards of pharmacy. Availability of drug information
ganization’s authorized leadership. on electronic media is desirable. Information may be ac-
cessed and provided in conjunction with medical libraries
Formulary. An independent home infusion provider does and other resources.
not have to abide by a formulary; drugs are dispensed ac- Available information sources should support research
cording to the orders of the physicians in its service area. on patient care issues, facilitate provision of patient care,
A hospital- or health-system-based infusion pharmacy may and promote safety in the medication-use process. When
have to abide by the same formulary restrictions as the rest possible, a pharmacist should have a role within the health
of the hospital or health system. The home infusion phar- system for addressing complex drug information questions
macist should have a mechanism for providing input to the presented by professional staff (e.g., pharmacists, nurses,
formulary committee.9 The pharmacy should have access to physicians).
specialty medications distributed through closed network If applicable, pharmacists should have access to in-
systems when needed to support consistent delivery of pa- formation on all investigational studies and similar research
tient care and medication reconciliation. projects involving medications and medication-related
devices used by the organization. Pharmacists should, fol-
Selection of Medications. Policies and procedures address- lowing the organization’s procedures, provide pertinent
ing the selection of medications should be available. These written information (to the extent known) about the safe
policies should be based on clinical appropriateness and and proper use of investigational drugs, including possible
USP standards. For bulk powders, USP or chemical stan- adverse effects, to family members, nurses, pharmacists,
dards for purity should be applied. Selection criteria should physicians, and other health care providers involved in the
also include safety (including clinical and labeling safety care of patients admitted to the investigational drug proto-
such as manufacturer use of “tall man” lettering), efficacy, cols. Pharmacist representation on the health system’s insti-
and ability to detect counterfeit medications. tutional review board is preferred.10,11
Drug Information. The home infusion pharmacist should Education and Mentoring of Staff, Students, and Providers.
provide accurate, comprehensive, and patient-specific drug The home infusion pharmacy staff should provide in-service
information to patients, caregivers, other pharmacists, physi- education to physicians, nurses, pharmacy technicians,
cians, nurses, and other health care providers as appropriate, and other practitioners on home infusion pharmacy-related
both proactively and in response to requests associated with issues. They should also provide, to the extent possible in
the delivery of pharmacy patient care, educational programs, their organizations, student experiential education, extern-
and publications. Pharmacists should provide concise, ap- ship, and internship training, as well as postgraduate resi-
plicable, and timely responses to requests for drug informa- dency training. Home infusion pharmacy staff also have a
tion from health care providers and home infusion patients. responsibility to keep the home infusion organization’s staff
Responses to general and patient-specific drug information informed about the use of medications on an ongoing basis
requests should be accurate and prompt. Drug information through appropriate consultations, publications, and presen-
requests and responses should be documented and monitored tations. Pharmacists should ensure the timely dissemination
for accuracy and timeliness as part of performance improve- of drug product recall notices, safety alerts, market with-
ment activities. Policies and procedures should be in place drawals, and labeling changes.
for reviewing responses to requests for drug information for
the purpose of performance improvement and education. Administration Devices, Delivery Systems, and Automated
Adequate information about a medication’s thera- Dispensing Devices. Home infusion pharmacists should
peutic use, dosage, potential adverse effects, and safe ad- provide leadership and advice in organizational and clini-
ministration in the home, including storage and stability cal decisions about the selection of drug delivery systems,
administration devices, and automated compounding and governing medication procurement and management should
dispensing devices, and should participate in the evaluation, be developed by the pharmacy in collaboration with other
use, and monitoring of these systems and devices.12 The po- appropriate organization staff and committees.
tential for medication errors associated with such systems
and devices should be thoroughly evaluated. Policies and Selection of Medications and Management of Supplies
procedures should be available for the certification (calibra- and Inventory. Policies and procedures governing selection
tion) and maintenance of equipment and devices. Equipment of medications and management of supplies and inventory
should be adequately maintained and certified in compliance should be developed by the pharmacy director in collabora-
with applicable standards, laws, and regulations. Equipment tion with other appropriate home infusion organization staff
maintenance and certification should be documented. members.
Preventive and Postexposure Immunization Programs. Procurement through Wholesalers, Manufacturers, or

The pharmacy should participate in the development of poli- Group Purchasing Organizations. Each pharmacy should
cies and procedures concerning preventive and postexposure have a primary drug wholesaler for routine stock orders and
programs for infectious diseases (including, but not limited a local source (e.g., a local hospital) for obtaining medica-
to, human immunodeficiency virus infection, tuberculosis, tions it does not have in stock. Group purchasing organiza-
and hepatitis) for patients and employees. tions (GPOs) may be used to control purchasing costs for
drugs and supplies. Policies and procedures should address
Substance Abuse Programs. The pharmacy should assist procurement and management of medications that must be
in the development of, and participate in, substance abuse obtained directly from the manufacturer or a limited set of
prevention, education, and employee and patient assistance distributors to ensure safe and proper pedigree of pharma-
programs.13 ceutical products.15,16
Development of Patient Care Services. The home infusion Storage and Stock Levels. Each pharmacy should determine
pharmacy services team should be involved in the develop- the appropriate level of stock required to serve the local pa-
ment, implementation, and evaluation of new or changing tient population and manage its physical inventory for maxi-
patient care services within the organization, such as the de- mum cost control and operational efficiency.
velopment of new clinic sites or new service areas or lines.
In reviewing the potential for new services, both the value Returns, Recalls, and Backorders. Procedures should be in
added to patient care by the new service and the financial place for responding to drug and device product returns, re-
and logistical implications of the new service should be con- calls, and backorders; for identifying patients who received
sidered. These efforts should promote the continuity of phar- or used a recalled product; and for removing the drug or de-
macist patient care across the continuum of care, practice vice product from the pharmacy or home when the recall is
settings, and geographically dispersed facilities. at the user level. All stocks of medications stored in the home
infusion pharmacy or in the organization’s facilities should
Committee Involvement. The director and other pharmacy be inspected routinely to ensure the absence of recalled, out-
staff should contribute to the organization’s goals through dated, unusable, or mislabeled products. Inspections should
effectively participating in or leading committees and infor- include identification of storage conditions that could com-
mal work groups. The pharmacist should be involved in the promise medication integrity, storage arrangements that
home infusion organization’s initiatives to develop model might contribute to medication errors, and storage locations
clinical protocols and assessments that develop pharmacist that might be vulnerable to drug diversion efforts.
care plans, pathways, or disease management guidelines to
ensure that pharmacist care elements are included.14 Clinical Drug Shortages. There shall be policies and procedures
protocols should be used whenever appropriate to maximize for managing drug product shortages. The pharmacy’s in-
the safety of medication use in the home. ventory management system should be designed to detect
A pharmacist should be a member of and actively par- subminimum inventory levels and alert the pharmacy to po-
ticipate on committees responsible for establishing policies tential shortages, and pharmacy staff should monitor reliable
and procedures for medication use, patient care, and per- sources of information regarding drug product shortages
formance improvement, among other things.9 Pharmacists (e.g., the ASHP17 and FDA18 drug shortages web resource
should also participate in the activities of similar committees centers). The pharmacy should develop strategies for identi-
of a parent home infusion organization or health system, as fying alternative therapies, working with suppliers, collabo-
applicable. rating with physicians and other health care providers, and
The director or a designee should be a member of the conducting an awareness campaign in the event of a drug
home infusion organization’s or health system’s institutional product shortage.19
review board, if applicable.
Compounding. The home infusion pharmacist is responsible
Drug Procurement and Management for assuring appropriate techniques are used for preparing and
dispensing medications, following the home infusion phar-
The home infusion pharmacy should be responsible for the macy’s policies and procedures and accepted standards of
proper acquisition, compounding, dispensing, storage, deliv- practice. Double checks are a good practice in many steps of
ery, and administration of all drug products used in the treat- the pharmacy dispensing process. The pharmacy should have
ment of the organization’s patients, as well as the proper use a process by which all high-risk calculations are checked for
of related equipment and supplies. Policies and procedures accuracy by a second clinician. Pediatric medications (e.g.,
doses), parenteral nutrition (PN), chemotherapy, pain man- nipulation of medications is required before administration,
agement, and inotropes are examples of high-risk therapies. labeling should clearly state current contents and the steps
It is also good practice that the pharmacist who processed for measuring, reconstituting, or adding other ingredients.
a new order should not be the same person who checks the Labels for compounded medications should state the total
order for accuracy and completeness. In addition to double content of the medication or nutrient per container so that it
checks on calculations, there should be visual double checks can be clearly known in case the patient is transferred to an-
on all medications listed as high-alert medications by the other treatment setting. If medications are to be administered
Institute for Safe Medication Practices (ISMP) (e.g., heparin, with an infusion device, pump settings should be included
insulin, chemotherapy agents, PN additives).20 on the label. All labels shall conform to the requirements
of the law. Home infusion pharmacies should adopt the list
Compounding Sterile Preparations. Compounding of ster- of prohibited abbreviations as another safety precaution to
ile preparations should comply with applicable practice ensure that patients and caregivers receive clear instructions
standards, accreditation standards, and pertinent state and for drug use.
federal laws and regulations. If these services are being pro-
vided by another pharmacy, the pharmacist should have rea- Packaging and Delivery. Policies and procedures should
sonable assurance that these standards are being met by the be available to ensure product integrity and temperature
pharmacy providing the service.21 control during home delivery or patient pickup of supplies
Home infusion pharmacists are responsible for ensur- and drugs. The pharmacist should ensure that the delivery
ing the quality of sterile preparations intended for use in the of medications and supplies to the patient occurs in a timely
home. Guidance is available from various sources for devel- manner to avoid interruptions in drug therapy. Furthermore,
oping an adequately designed and equipped facility, training the pharmacist should ensure that storage conditions dur-
and validating employees, validating and documenting coming delivery and while in the patient’s home are consistent
pounding procedures, practicing aseptic technique, moni- with the recommendations for storing the product and be-
toring the work environment, maintaining the facility and yond-use dating. The temperature of home refrigerators or
equipment, ensuring the quality of prepared preparations, freezers in which medications are stored should be within
and developing policies and procedures.7,8 acceptable limits and should be monitored by the patient or
caregiver. The pharmacist should ensure that an adequate
Stability and Compatibility Issues. Home infusion pharma- inventory of medications and ancillary supplies is available
cies are often required to assign extended beyond-use dates in the patient’s home. It may be appropriate to provide addi-
to sterile preparations so that a multiple-day supply of medi- tional inventory for unforeseen circumstances in which extra
cations can be dispensed and delivered. However, pharma- doses or supplies may be required (e.g., waste, breakage, and
cists should take into account circumstances that may affect emergencies). The pharmacist is responsible for providing
the medication’s potency and stability, including: sufficient quantities of medications and supplies to the pa-
tient, so that the ordered dosing regimen is maintained in the
• Delivery of sterile preparations to the home, either by home setting without missed doses due to lack of drugs or
the pharmacy’s own vehicles or by a common carrier; supplies. Delivery to the patient should also include inven-
• Storage of sterile preparations in the home before use; tory management to avoid excessive accumulation of sup-
• Manipulation of sterile preparations in the home envi- plies and drugs. Excesses may indicate poor compliance,
ronment to add ingredients (such as vitamins) and to inadequate patient training, failure to assess patient needs,
set up tubing and filters for administration; and or ineffective inventory management by the patient. When
• Administration of preparations at temperatures that common carriers are used, the pharmacy is responsible for
are warmer than controlled room temperature because ensuring that the carrier can provide timely delivery, proper
of administration in outdoor or non-air-conditioned handling, and external temperature control. Delivery person-
environments or the use of ambulatory infusion pumps nel should know the shipping requirements for each package.
worn close to the body. If products are packaged so that product labels containing
storage instructions are concealed, an exterior label specify-
The home infusion pharmacist should consult USP Chapter ing the storage conditions shall be used. To protect patient
7978 and other appropriate resources to establish an appro- confidentiality, prescription labels with medication names
priate beyond-use date. Applying published stability data and directions should not be used to label boxes. Box la-
can introduce inaccuracies if the intended conditions of use bels should include only the patient’s name and address, the
differ greatly from the reported conditions. Pharmacists storage requirements, and delivery instructions. Additional
should maintain a record of the resources used for establish- precautions (i.e., double bagging, using at least one leak-
ing beyond-use dates. A table or chart of accepted beyond- proof container, and cushioning) should be used to safeguard
use dates, formulations, and conditions of use for commonly hazardous products from breaking and leaking. The delivery
prepared preparations may be helpful in ensuring that as- person, patient, and caregiver shall be trained to recognize
signed dates are consistent and appropriate. Patients should and manage accidental spills. Packages containing hazard-
be trained to check preparations for current beyond-use ous products should have appropriate precautionary labels.
dates prior to their use. Products should be delivered in appropriate packaging
to ensure that labeled storage requirements are met during
Labeling. Medications for home use should be labeled so transit under the expected environmental conditions. The
that patients and caregivers can easily understand instruc- pharmacy should develop and follow written procedures
tions for drug storage, preparation, and administration. for packaging; these procedures should include privacy-
Auxiliary labels should be used as necessary. When ma- protection considerations. Product confirmation after deliv-
ery should be used to ensure that the packaging procedures definite outcomes; these outcomes are intended to improve
and materials used were effective in maintaining product the patient’s quality of life; and the provider accepts personal
integrity and temperature control during transit. The stabil- responsibility for the outcomes.23
ity of refrigerated products at room temperature should be The mission of the pharmacist is to help people make
taken into account in the development of packaging proce- the best use of medications. At a minimum, pharmacists are
dures. A few refrigerated products have extended stability responsible for assessing the legal and clinical appropriate-
at room temperature and may be safely delivered without ness of medication orders (or prescriptions), educating and
refrigerated packaging. Products that are stable for 24 hours counseling patients on the use of their medications, monitor-
or less at room temperature should always be delivered in ing the effects of medication therapy, and maintaining pa-
temperature-controlled packaging (coolers, ice packs, etc.). tient profiles and other records. In the home infusion care
setting, these responsibilities are best accomplished through
Hazardous Drugs. Policies and procedures for the defini- the provision of pharmacist-provided patient care in which
tion, storing, handling, and disposing of hazardous drug pharmacists are responsible for establishing relationships
products should be available to ensure patient and employee with patients and providers that will facilitate coordination
safety in compliance with applicable local, state, and federal and continuity of care, improve access to care, and improve
laws and regulations. Receipt, storage, and disposal of haz- patient outcomes.
ardous substances shall comply with all applicable federal,
state, and local laws and regulations, including the Resource Preadmission Assessment. The pharmacist, alone or in col-
Conservation and Recovery Act (RCRA), as well as applica- laboration with other home infusion health care providers
ble guidance (e.g., ASHP guidelines,22 USP Chapter 7978). (e.g., nurses), should ensure that each patient referred for
Hazardous drug products should be stored in a negative home infusion is assessed for appropriateness on the basis of
pressure compounding room whenever possible. Additional admission criteria, including the following:
storage precautions may include placement on a lower
shelf or containment in a resealable plastic bag. Employees • The patient, family, and caregiver agree with provision
of infusion services in the home;
should be specially trained, and their handling and disposal
of these products should be monitored. Spill kits should be • The patient or caregiver is willing and able to be edu-
cated about the correct administration of medications;
available in locations where hazardous drugs are handled,
and all personnel who handle these agents should be trained • The pharmacy can provide this education in a manner
that the patient, family and caregiver can understand;
on using the kits.4,22
• The home environment is conducive to the provision
of home infusion services (e.g., electricity and running
Controlled Substances. Policies and procedures for the stor-
water are present, and the home is clean and safe);
age, distribution, use, and accountability of controlled sub-
stances should be available to ensure appropriate use and to
• The home infusion provider has reasonable geographic
access to the patient;
prevent diversion in compliance with applicable local, state,
and federal laws and regulations. Controlled substances
• There is psychosocial and family support (e.g., care-
giver requirements and financial concerns are manage-
shall be kept in a secure and locked storage area that meets
able, and the family environment is suitable);
the requirements of state law. Pharmacists should be aware
of the ways drugs can be diverted. Employees should be
• There is ongoing prescriber involvement in the assess-
ment and treatment of the patient;
carefully screened before hire. Processes should be in place
to minimize the risk of drug diversion and allow detection
• The medical condition and prescribed medication ther-
apy are suitable for home infusion services, and there
should diversion occur. Policies or procedures for activities is a prognosis with clearly defined outcome goals;
such as ordering, receiving product, and conducting invento-
ries should assure proper supervision and limit opportunities
• The indication, dosage, and route and method of ad-
ministration of medications are appropriate; and
for a single individual to control the entire process.
• Appropriate laboratory tests are ordered for monitor-
ing the patient’s response to medications.
Drug Samples. The use of drug samples should be elimi-
nated to the fullest extent possible. If samples are permitted, Using the information collected during the preadmission
the pharmacy should control these products to ensure proper assessment, the pharmacist, in conjunction with the other
storage, records, labeling, and product integrity. health care providers involved in the patient’s care and the
patient or caregiver, will determine the patient’s appropri-
Patient Care ateness for home infusion services. The conclusions of the
assessment should be communicated to all parties and ap-
Pharmaceutical care, defined as the responsible provision of propriately documented.
drug therapy for the purpose of achieving definite outcomes
that improve a patient’s quality of life, has been adopted by Initial Patient Database and Assessment. The complete pa-
much of the pharmacy profession.23 The concept of pharma- tient database should be documented in the patient’s home
ceutical care is evolving into a more comprehensive, patient- infusion record in a timely manner. This database should in-
focused model of pharmacist-provided care, sometimes clude, at a minimum, the following:
termed pharmacist patient care. The principal elements of
such care are the same: it is medication related; it is care that • The patient’s name, address, telephone number, and
is directly provided to the patient; it is provided to produce date of birth;
• The person to contact in the event of an emergency, • A description of desired outcomes of the drug therapy
including the legal guardian or representative, if ap- provided;
plicable; • A proposal for patient education and counseling; and
• Information on the existence, content, and intent of an • A plan specifying proactive objective and subjective
advance directive, if applicable; monitoring (e.g., vital signs, laboratory tests, physical
• The patient’s height, weight, and gender; findings, patient response, toxicity, adverse reactions,
• All diagnoses; and noncompliance) and the frequency with which
• The location and type of termination site of the vas- monitoring is to occur.
cular access device and internal and external catheter
lengths, if applicable; The care plan should be developed at the start of therapy
• Pertinent laboratory test results; and regularly reviewed and updated; the degree of detail of
• Pertinent medical history and physical findings; the plan should be based on the complexity of drug therapy
• Nutrition screening test results; and the patient’s condition. Updates or changes to the plan,
• An accurate history of allergies; as they occur, should be communicated to other health care
• Initial and ongoing pharmaceutical assessments; providers involved in the patient’s care, to the patient, and to
• A detailed medication profile, including all medica- caregivers. The care plan and updates should be a part of the
tions (prescription and nonprescription), immuniza- patient’s record.
tions, home remedies, and investigational and nontra-
ditional therapies; Clinical Monitoring. The pharmacist is responsible, in col-
• The prescriber’s name, address, and telephone num- laboration with other health care providers, for ongoing
ber and any other pertinent information (e.g., Drug clinical monitoring of the patient’s drug therapy according
Enforcement Administration number, National to the care plan and for appropriately documenting and com-
Provider Identifier [NPI]); municating the results of all pertinent monitoring activities
• Other agencies and individuals involved in the to other health care providers involved in the patient’s care.
patient’s care and directions for contacting them; The pharmacist is also responsible for ensuring that relevant
• A history of medication use; and information is obtained from the patient, the caregiver, and
• A care plan and a list of drug-related problems, if any. other health care providers and for documenting this infor-
mation in the patient’s home infusion record.
To obtain this information, the pharmacist could use the Pharmacists may, in collaboration with prescribers
medical record; laboratory test results; direct communica- and others, wish to develop clinical monitoring protocols
tion with the patient, caregiver, nurse, and prescriber; and for various therapies that could be individualized in specific
direct observation. When the pharmacist cannot directly ob- care plans. Pharmacists may receive laboratory test results
serve the patient, the patient’s home infusion nurse or other before other health care providers. In such cases, the phar-
appropriate health care provider could provide the results macist is responsible for communicating the test results to
of direct observation and physical assessment. If a shared- the prescriber and other health care providers. The pharma-
service agreement exists among multiple providers, the cist should provide an interpretive analysis of the informa-
pharmacist should ensure that this agreement specifies the tion and recommendations for dosage adjustments and for
responsibilities of each provider for obtaining and sharing continuation or discontinuation of drug therapy. The phar-
pertinent patient information. macist should ensure that sufficient laboratory test results
are readily available for monitoring the patient’s therapy. In
Medication Reconciliation. Pharmacists should prepare or shared-service arrangements, clinical monitoring responsi-
have access to comprehensive medication histories for each bilities should be delineated.
patient, including prescription drugs, nonprescription drugs, The patient, the family, the caregiver, and all health
and alternative therapies. A pharmacist-conducted medica- care providers involved in the patient’s care should have
tion history for each patient is desirable; however, another access to a pharmacist 24 hours a day. The pharmacist is
appropriate health care provider (e.g., home infusion nurse, responsible for providing a summary of all relevant clinical
pharmacy technician) may obtain and maintain current med- information to another pharmacist providing coverage for
ication histories, provided this information is accessible to that patient (e.g., an on-call pharmacist) before transferring
the pharmacist and other health care providers. patient care responsibilities.
Development of Care Plans. The pharmacist, in collabo- Patient Consultation and Education. Home infusion phar-
ration with the patient or caregiver and other health care macists will primarily consult patients or caregivers over
providers, is responsible for developing an appropriate and the telephone. Home visits should be considered for en-
individualized care plan for each patient. The pharmacist’s hancing compliance or simplifying complex drug-related
contribution to the care plan should be based on informa- patient issues.
tion obtained from the initial pharmacy assessment and other The home infusion pharmacist, or the home infusion
relevant information obtained from the nurse, prescriber, pa- nurse as the agent, should ensure that the patient, caregiver,
tient, and caregivers. At a minimum, the pharmacist’s contri- and other health care providers understand the proper use
bution to the care plan should include the following: and administration of medications provided, including vas-
cular access and infusion devices, as required. The home in-
• A description of actual or potential drug therapy prob- fusion pharmacist, or the nurse as the agent, should explain
lems and their proposed solutions; to the patient or the patient’s agent the directions for use and
any additional information.
The pharmacist is responsible for ensuring that the pa- caregivers. The pharmacist should contact the patient or the
tient or caregiver receives appropriate education and coun- caregiver, as appropriate, to
seling about the patient’s medication therapy.24 The pharma-
cist should verify that the patient or caregiver understands • Obtain information needed for the initial pharmacy as-
the therapy. Other health care providers may be involved in sessment;
the education and counseling. A home infusion pharmacist • Provide supplemental patient education and counsel-
should be readily accessible if questions or problems arise. ing as needed;
Supplementary written information should be provided to • Assess compliance with drug therapy;
reinforce oral communications. Contingencies should be • Assess progress toward the goal of therapy;
available to provide education, counseling, and written ma- • Inform the patient how to contact the pharmacist when
terials to patients whose understanding of English may be needed; and
compromised. Depending on the need, this might require ac- • Assess drug therapy problems (e.g., failure to respond
cess to interpreters or bilingual pharmacists. Patients who to therapy and adverse drug events).
have hearing and sight impairments will potentially need
other support or communication resources. All contacts with the patient should be documented in the
Professional judgment is required to determine what patient’s home infusion record.
information should be included in patient education and
counseling. The following should be considered: Communication with Physicians, Prescribers, Nurses, and
Other Health Care Providers. Effective communication
• A description of medication therapy, including drug, among pharmacists and other health care providers is essen-
dose, route of administration, dosage interval, and du- tial to ensuring continuous, coordinated care. The pharma-
ration of therapy; cist should ensure that effective channels of communication
• The goals of medication therapy and indicators of about care are in place, including shared-service arrange-
progress toward those goals; ments (e.g., regarding pain assessments and laboratory test
• Self-assessment techniques for monitoring the effec- data). Oral and written communication methods can be used
tiveness of therapy; for communicating patient information. All relevant clinical
• The importance of following the therapeutic plan; communication should be documented in the patient’s home
• Proper aseptic technique; infusion record. The pharmacist is responsible for protecting
• Hand hygiene; the patient’s privacy and confidentiality while communicat-
• Proper care of the vascular-access device and site, if ing this information to other health care providers. Personnel
applicable; involved in the care of the patient should meet regularly to
• Precautions and directions for administering medica- discuss the clinical status of the patient and any operational
tions; issues related to the patient’s care.
• Inspection of medications, containers, and supplies
prior to use; Medication Administration. Policies and procedures on the
• Equipment use, maintenance, and troubleshooting; administration of medications should be available. Only per-
• Home inventory management and procedures for sonnel who are authorized by the home infusion organization
securing additional supplies and medications when and are appropriately trained and licensed should be per-
needed; mitted to administer medications to a patient. Pharmacists,
• Potential adverse effects, drug–drug interactions, where legally permitted, may be authorized to administer
drug–nutrient interactions, contraindications, adverse medications after receiving appropriate training.
reactions, and the management of those events;
• Special precautions and directions for the preparation, Emergency Medical Care. The home infusion pharmacist
storage, handling, and disposal of drugs, supplies, and should participate in decisions about the emergency care of
biomedical waste; patients at home, including the development of protocols
• Information on contacting health care providers infor using emergency drugs in the home. Policies and proce-
volved in the patient’s care; dures should exist within the organization for providing ap-
• Examples of situations that should be brought to the at- propriate levels of patient care during emergency situations
tention of the pharmacist or other health care providers 24 hours a day, including access to the pharmacist respon-
involved in the patient’s care (e.g., missed doses, doses sible for the care, when appropriate. Appropriately trained
not given at the proper time, and low supplies); and pharmacists should have an authorized role in responding
• Emergency procedures. to medical emergencies. The pharmacy should participate in
the development of policies and procedures to ensure avail-
Patient counseling and education should be performed in ac- ability of, access to, and security of emergency medications.
cordance with applicable state regulations and documented
in the patient’s home infusion record. Discharge from Home Infusion. When patients have com-
pleted therapy as ordered, they should be discharged from
Communication with Patients and Caregivers. Effective service. Items that should be documented in the medical
communication among pharmacists, patients, and caregiv- record upon discharge include the patient’s response to
ers is also essential to ensuring high-quality care. The phar- therapy and status at discharge.
macist providing home infusion services should establish
free and open channels of communication with patients and
Transfer to Another Care Setting. The pharmacist should en- • The ability of an infusion device to accommodate the
sure continuity of pharmacist care to and from the home and appropriate volume of medication and diluent, and to
other patient-care settings. The pharmacist should routinely deliver the prescribed dose at the appropriate rate;
contribute to processes ensuring that each patient receives • The ability of the patient or caregiver to learn to oper-
pharmacist care regardless of transitions that occur across ate an infusion device;
different health care settings (for example, among different • The potential for patient complications and noncom-
components of a health system and different types of home pliance;
infusion services). When home infusion patients are admit- • Patient preference;
ted to a hospital, the home infusion pharmacy should inform
• Nursing or caregiver experience with therapies and
the hospital about (1) the medications the patient is currently selected devices;
receiving from the home infusion pharmacy and (2) known
• Prescriber preferences;
allergies. The home infusion pharmacy should recognize hos-
pital policy when considering whether properly stored medi-
• Cost considerations; and
cations and medical equipment from the home can be used

• The safety features of infusion devices.
during the home infusion patient’s hospitalization. Patient’s Own Medications. Drug products and related de-
vices not dispensed by the home infusion pharmacy that are
Documentation in the Home Infusion Medical Record. to be used during the patient’s course of therapy should be
Clinical actions and recommendations by pharmacists that documented in the patient’s home infusion medical record.
are intended to ensure safe and effective use of medications When home infusion patients are known to be admitted to a
and that have a potential effect on patient outcomes should hospital or other extended care facility, the home infusion
be documented in patients’ home infusion medical records. pharmacy should inform the hospital about the medications
Pharmacists should provide oral or written consultations the patient is currently receiving from the home infusion
to other health professionals regarding medication therapy
pharmacy and about any known allergies. The home infu-
selection and management. Consultations should be docu-
sion pharmacy should recognize hospital policy when con-
mented in the patient’s home infusion medical record. The
sidering whether properly stored medications and medical
pharmacy should have an ongoing process for consistent
equipment from the home can be used during the home infu-
documentation (and reporting to physicians, administrators,
sion patient’s hospitalization.
and others) of pharmacist care and patient outcomes resulting
from medication therapy and other pharmacy actions. Patient
Emergency Medications. The home infusion pharmacist,
privacy and confidentiality should be protected at all times.
in consultation with the prescriber, should determine when
A home infusion record should be developed and
emergency medications and supplies (e.g., anaphylaxis
used for documenting the home infusion services provided
“kits”) should be dispensed to home infusion patients. When
to each patient. Written organizational policies and proce-
standing orders for ancillary drugs or supplies or standardized
dures should address the security of home infusion records
treatment protocols are used, the pharmacist should review
and specify personnel authorized to review patient records
each protocol to determine its appropriateness for the patient.
and to make entries. The need to maintain confidentiality
of patient information should be stressed to all personnel.
The pharmacist is responsible for documenting all pharmacy Performance Improvement Activities
clinical activities in the patient’s record in a timely manner.
General clinician-oriented forms are preferred over specific The home infusion pharmacy should have an ongoing, sys-
nursing, pharmacy, and other health care professional forms tematic program for assessing pharmacist patient care, and
to minimize duplication of information. It may be advis- pharmacists should be active participants in performance
able for organizations that provide multiple home infusion improvement activities. A performance improvement pro-
services (e.g., pharmacy, nursing, respiratory therapy, dieti- gram for home infusion should monitor patient satisfaction
cians) to use a single home infusion record for documenting and outcomes, and the program should also include appro-
all clinical information regarding each patient. The patient’s priate quality control measures for compounding sterile
record should be accessible at all times to authorized person- preparations and other activities. Performance improvement
nel involved in the care of the patient, but confidentiality activities based on assessments should be integrated with the
should be maintained. health system’s overall performance improvement activities,
as applicable. The performance improvement team should
Selection of Products, Devices, and Ancillary Supplies. The work with frontline staff to implement systems that include
pharmacist, in collaboration with other health care provid- proper checks and balances focused on protecting against
ers and the patient, is responsible for selecting infusion de- human error. Performance improvement initiatives should
vices, ancillary drugs (e.g., heparin lock flush solution, 0.9% be focused on error reporting trends and high-risk functions
sodium chloride flush), and ancillary supplies (e.g., dressing such as dispensing high-alert medications.
kits, syringes, and administration sets). Pharmacists should
be thoroughly trained and knowledgeable in the selection, Benchmarking. As part of the performance improvement
proper use, and maintenance of these devices, drugs, and program, operational and outcomes data should be bench-
supplies. Factors involved in the selection of devices and marked with those of other home infusion pharmacy ser-
ancillary supplies may include the following: vices of similar size and scope. The results, including fol-
low-up actions for improvement, should be documented and
• The stability and compatibility of prescribed medica- provided to the organization’s managers, the frontline staff
tions in infusion device reservoirs; using the system, and others as appropriate.
Clinical Outcomes. Most accrediting bodies and some regu- programs for pharmacists and nurses to improve the quality
latory agencies require the home infusion pharmacy to mon- of care and patient outcomes. Serious adverse drug reactions
itor clinical patient outcomes. Common measures that are and device-related problems should be reported promptly to
tracked routinely by home infusion companies include the the manufacturer and to the Food and Drug Administration’s
rate of catheter-related infections, adverse drug reactions, MedWatch program.25
medication errors, warehouse/delivery errors, equipment
malfunctions, and unplanned hospitalizations. In addition, Operations
the organization should have an infection control program
in which both staff and patient infection (communicable dis- Hours of Operation. Home infusion pharmacy services shall
eases) rates are monitored. The organization may also select be available 24 hours a day, seven days a week. A pharma-
outcomes that are monitored over a short time as a specific cist should be available for consultation or dispensing after
process is improved. hours. Home infusion pharmacy staff may be supplemented
by knowledgeable and experienced part-time or on-call per-
Medication Error Reporting. Medication error monitoring sonnel to extend pharmacy services coverage.
and prevention should be part of every pharmacy’s perfor-
mance improvement program. Information about strate- Pharmacy Security and After-Hours Access. Only autho-
gies to prevent medication errors is available from several rized pharmacy personnel should have access to the phar-
sources, including ISMP, which produces regular newslet- macy area. Other home infusion organization personnel may
ters on this topic. be in the pharmacy area only when an authorized pharmacist
All pharmacies should have processes in place that is present, in accordance with the home infusion organiza-
are designed to prevent and detect medication errors before tion’s policies or as required by laws and regulations. In an
they leave the pharmacy. If an error does occur, the phar- emergency situation in which a pharmacist is not present,
macy director and staff should determine how and why the such as a fire or security alarm, policies and procedures
error happened, and what can be done to prevent similar er- should guide safe access to the pharmacy area and provide
rors from occurring. Medication errors should be reported for notification of the pharmacist in charge or a designee.
to voluntary national reporting systems and, as required, to
accrediting organizations or regulatory agencies. Reports Emergency Preparedness and Business Continuity
should be documented, analyzed, trended and reviewed con- Planning. Policies and procedures should be available that
sistent with National Coordinating Council for Medication include a plan for providing pharmacy services in case of
Error Reporting and Prevention (NCCMERP) standards. an area-wide disaster affecting the home infusion pharmacy
or patients’ home infusion settings. Appropriately trained
Patient Satisfaction. Most accrediting bodies require the pharmacists and representatives from the pharmacy team
home infusion pharmacy to measure patient satisfaction should be members of emergency preparedness teams and
with treatment and services. This function can be performed participate in drills. Patients should be informed about what
in-house by mailing questionnaires to the patient, or it can be to do to safely continue needed home therapies in the event
outsourced to a contractor. Patient satisfaction surveys that of a disaster. The health system’s business continuity plan
are returned should be reviewed for both positive and nega- should address the provision of pharmacy services in non-
tive comments so that corrective action can be targeted to emergency situations, such as information system failures or
service issues. disruptions of the drug procurement process.19,26
Medication-Use Evaluation. An ongoing program of moni- Communications. Staff meetings should be conducted on a
toring drug utilization and costs should be in place to ensure regular basis for various purposes, which may include:
that medications are used appropriately, safely, and effec-
tively, and to increase the probability of desired outcomes
within defined populations of patients. The medication-use
• Brief daily meeting to review on-call issues, upcoming
referrals, and current daily plan;
policy committee should define specific parameters for eval-
uation (e.g., disease state, pharmacologic category, high-use/
• Hand-off communications to and from evening staff or
on-call personnel;
high-cost drug products, high-alert medications) as appro-
priate for the organization. Through this ongoing evaluation,
• In-services regarding updates to policies or proce-
dures, law, regulation, or services;
areas in need of improvement in medication prescribing and
management can be identified and targeted for intervention.
• Review of new medications;
• Analysis of sales and marketing efforts;
Adverse Drug Event Reporting. The home infusion phar-
• Performance improvement functions;
macist should take a leadership role in the development of
• Team building among the staff; or
a program for reporting and monitoring all adverse drug
• Interdisciplinary meetings or case conferences to com-
municate the pharmacist’s care plan for a patient (with
events and device-related events, including adverse drug patients, caregivers, physicians, prescribers, or other
reactions and medication errors. The pharmacist should en- health professionals).
sure that the prescriber is notified promptly of any suspected
adverse drug events. Adverse drug events should serve as Equipment Management. Equipment may be owned, leased,
outcome indicators of quality, and the monitoring of adverse or rented by the infusion pharmacy. It is usually most cost-ef-
drug events should be a part of the organization’s ongoing fective to lease-purchase infusion pumps that are used in high
performance improvement program. Relevant trends should volume. Pumps with specialized uses (e.g., micro-infusers)
be integrated into staff development and in-service education may be used less frequently and may be rented as needed.
Equipment may be purchased or rented from a properly quali- requirements. Since much of the waste eventually is sent
fied vendor. Routine maintenance (i.e., basic safety checks, to dump sites, waste that needs to be incinerated should be
alarm testing, and accuracy validation) is performed between discarded separately. The companies that provide mail-back
patient use, and preventive maintenance for medical equip- service also incinerate all the waste they receive, so it is
ment is defined by the manufacturer for each specific device. not necessary to separate the waste. It is also important that
The manufacturer’s preventive maintenance recommenda- the pharmacist understand the OSHA and RCRA require-
tions should be followed, and all equipment should be main- ments regarding management and disposal of hazardous
tained so that the preventive maintenance is not overdue dur- substances. There should be a designated area for hazardous
ing patient use. Technical repair of medical equipment should waste, including sharps. Spill kits should be readily avail-
be done by a properly qualified service technician. Home able in locations where hazardous substances are handled,
infusion pharmacies typically do not have the capacity to and all personnel who handle these agents should be trained
employ staff on site with the technical certification required on using these kits.4,22
for equipment preventive maintenance or repair. Outsourcing
these functions is usually the most efficient and cost-effective Facilities
way to maintain equipment in good working order.
To ensure optimal operational performance and quality pa-
Records Storage and Maintenance. Adequate space should tient care, adequate space, equipment, and supplies should
be available for maintaining and storing records, including be available for all professional and administrative func-
medication profiles and other patient information, man- tions related to medication use. These resources should be
agement information, equipment maintenance sheets, con- located in areas that facilitate the provision of services to
trolled-substances inventory sheets, and MSDSes, among patients, nurses, prescribers, and other health care providers
others, to ensure compliance with laws, regulations, ac- and should be integrated with the home infusion organiza-
creditation requirements, and sound management practices. tion’s communications, delivery, or transportation systems.
Patient records shall be secure. Records shall be retained ac- Facilities should be constructed, arranged, and equipped to
cording to applicable laws and regulations, which may vary promote safe and efficient work and to avoid damage to or
by state and by Centers for Medicare & Medicaid Services deterioration of drug products.
(CMS) participation guidelines. There may be additional re-
cord retention requirements for specific patient population Ambulatory Infusion Center or Infusion Suite. Pharmacies
(e.g., pediatric patients) medical records in some states and that have an on-site (ambulatory) infusion suite must in-
according to accreditation standards. clude appropriate access to the facility (e.g., handicapped
parking, sidewalk ramp) and other internal design features
Information Technology. Computer resources should be (e.g., restroom grab bar) according to the Americans with
used to maintain patient medication profiles, perform nec- Disabilities Act. Local building code regulations may also
essary patient billing procedures, manage drug product in- apply. Accreditation standards for home care organizations
ventories, and interface with other available computerized typically include a section on infusion suites and cover such
systems to obtain patient-specific clinical information for items as patient access, facility safety checks, nursing pro-
drug therapy monitoring and other clinical functions and to cedures, and room sanitation. State and local authorities
facilitate the continuity of care after patients transfer to and may have additional regulations for ambulatory treatment
from other care settings. centers; these should be researched before planning to offer
ambulatory treatment services.
Home Infusion Medical Record Systems. A patient medi-
cation profile should be maintained by all home infusion Home Infusion Pharmacies. Designated space and equip-
pharmacies regardless of where the dispensing of medica- ment for compounding and packaging sterile preparations
tions takes place. The home infusion medical record should should be available.7,8 The compounding environment
include assessment and care planning documents, progress should be monitored and maintained on an ongoing basis.
notes, laboratory test results, and other patient information Appropriate facility space, equipment, and supplies for com-
related to determining the appropriateness of medications pounding hazardous preparations should be available.7,8,22
and monitoring their effects. The system should provide Adequate facilities and equipment should be established
safeguards against the improper manipulation or alteration for decontaminating, cleaning, and maintaining infusion de-
of records and provide an audit trail. vices, including durable medical equipment.
An automated information system is preferred, but
the system may be manual, automated, or a combination General Work Area. The pharmacy work area should allow
of the two. If an automated information system is used, an pharmacists to observe work being done by support staff
auxiliary record-keeping procedure should be available for (telephone calls to patients, computer data entry, compound-
documenting medication information in case the automated ing, etc.). Pharmacies should consider having an area dedi-
system is inoperative, and a daily data backup system should cated to the function of checking compounded preparations
be in place. and other prescriptions that is out of the main traffic pat-
tern and where the checking pharmacist is not distracted by
Hazardous Waste Management and Disposal. There are noise, telephones, or conversation.
many ways to dispose of hazardous waste generated by the
pharmacy. In addition to the established waste management Stockroom and Storage Areas. Facilities should be avail-
companies, there are also mail-back services. For the tra- able for storing and preparing medications in the home
ditional services, it is important to follow the company’s infusion pharmacy under proper conditions of sanitation,
temperature, light, moisture, ventilation, segregation, and 7. American Society of Health-System Pharmacists.
security to ensure medication integrity and personnel safety ASHP guidelines on quality assurance for pharmacy-
and to prevent drug diversion.27 Adequate refrigeration and prepared sterile products. Am J Health-Syst Pharm.
freezer capacity should be provided within the secure phar- 2000; 57:1150–69.
macy area. 8. Pharmaceutical compounding—sterile preparations
(general information chapter 797). In: The United
Office and Meeting Space. Office and meeting areas should States pharmacopeia, 34th rev., and The national for-
be available for administrative, clinical, technical, and re- mulary, 29th ed. Rockville, MD: The United States
imbursement staff. Ideally, interdisciplinary team members Pharmacopeial Convention; 2011: 336–73.
from pharmacy, nursing, and reimbursement are located 9. American Society of Health-System Pharmacists.
within a proximate space. ASHP guidelines on the pharmacy and therapeutics
committee and the formulary system. Am J Health-
Cleanroom and Anteroom (Compounding Area). The home Syst Pharm. 2008; 65:1272–83.
infusion pharmacy should follow all applicable federal, 10. American Society of Health-System Pharmacists.
state, and local requirements, including USP Chapter 797,8 ASHP guidelines on clinical drug research. Am J
for building and maintaining the pharmacy’s compound- Health-Syst Pharm. 1998; 55:369–76.
ing facilities. Options for building out a cleanroom include 11. American Society of Hospital Pharmacists. ASHP
purchase of a modular prefabricated unit or building out an guidelines for pharmaceutical research in organized
existing space with only those materials needed to bring the health-care settings. Am J Hosp Pharm. 1989; 46:129–
facility into compliance with laws, regulation, and guidance. 30.
Design and organization of the cleanroom should allow for 12. American Society of Health-System Pharmacists.
the pharmacist’s view of compounding activities through a ASHP guidelines on the safe use of automated dis-
large window or clear wall and efficient flow of materials and pensing devices. Am J Health-Syst Pharm. 2010;
compounding documents into the cleanroom for processing 67:483–90.
and out of the cleanroom for the checking/verification step. 13. American Society of Health-System Pharmacists.
Sterile medications shall be compounded within a pri- ASHP statement on the pharmacist’s role in substance
mary engineering control such as a laminar flow hood or abuse prevention, education, and assistance. Am J
a compounding aseptic containment isolator. Compounding Health-Syst Pharm. 2014; 71:243–6.
facilities shall be cleaned and maintained following fed- 14. American Society of Health-System Pharmacists.
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cable guidance (e.g., ASHP guidelines, USP Chapter 797).7,8 velopment, implementation, and assessment of critical
Environmental monitoring of the compounding facilities pathways. Am J Health-Syst Pharm. 2004; 61:939–45.
shall be ongoing and should include all elements required 15. American Society of Hospital Pharmacists. ASHP
by federal, state, and local laws or regulations as well as guidelines for selecting pharmaceutical manufacturers
applicable guidance (e.g., ASHP guidelines, USP 797).7,8 and suppliers. Am J Hosp Pharm. 1991; 48:523–4.
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Barbara J. Petroff, M.S., FASHP; Donald Filibeck, Pharm.D., Copyright © 2014, American Society of Health-System Pharmacists,
M.B.A.; Anna Nowobilski-Vasilios, Pharm.D., M.B.A., CNSC, Inc. All rights reserved.
BCNSP, FASHP; R. Stephen Olsen, Pharm.D.; Carol J. Rollins,
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Infusion Pharmacy Services. Am J Health-Syst Pharm. 2014;
ASHP gratefully acknowledges the contributions of the following 71:325–41.
individuals to these guidelines: Mitra Gavgani, Pharm.D.; Brian
G. Swift, Pharm.D., M.B.A.; Lisa Linn Siefert, B.S.Pharm., ASQ-
CQM, FASHP; Kelly Rogers, B.S.Pharm.; and Caryn M. Bing,
M.S., FASHP.
ASHP Guidelines: Minimum Standard

for Ambulatory Care Pharmacy Practice
In recent years, there has been an increasing emphasis in dress many of the outlined topics for additional information
health systems on the provision of ambulatory care services. and guidance. Aspects of these guidelines may not be ap-
Payers have created incentives to decrease hospitalization plicable in some settings due to differences in settings and
rates and length of stay, making way for a new shift toward organizational arrangements and complexity. Pharmacists
pay-for-performance, outcomes-based reimbursement, and practicing in ambulatory care settings should use their pro-
accountable care. There is also an increasing focus in medi- fessional judgment in assessing and adapting these guide-
cine on preventive health, patient education, and care tran- lines to meet the needs of their own practice settings.
sitions. Yet, the number of patients with multiple chronic These guidelines are intended to be a comprehensive
medical conditions that require longitudinal and integrated overview of current minimum requirements for the opera-
care management across a continuum of care settings is tion and management of services for patients in the am-
growing. Appropriate medication therapy in the ambulatory bulatory care setting. These guidelines are complemented
care setting is often the most common and most cost-effec- by the ASHP/ASHP Foundation Ambulatory Conference
tive form of treatment, yet the consequences of adverse drug and Summit consensus recommendations,5 which provide
events (ADEs) and the inappropriate use of medications in a long-term vision for aspirational and forward-thinking
this setting can be catastrophic.1 Ambulatory care pharmacy pharmacy practice models that will ensure that pharmacists
services are therefore an essential component of any com- participate as members of the ambulatory healthcare team
prehensive healthcare delivery system. who are responsible and accountable for patient and popula-
Pharmacists have become integral members of health- tion outcomes.
care teams in a variety of settings, such as patient-centered
medical homes, community health centers, long-term care Standard I. Practice Management
facilities, hospital outpatient departments, and freestanding
pharmacies, among others; the care they provide has enabled Effective leadership and practice management skills are nec-
patients, other providers, and payers to achieve their clinical, essary for the delivery of pharmacy services in a manner con-
humanistic, and economic goals.2,3 There is growing recog- sistent with the health system’s and the patient’s needs. Such
nition and understanding that ambulatory care pharmacy ser- leadership should foster continuous improvement in patient
vices extend far beyond the dispensing of medications and care outcomes. The management of ambulatory care phar-
include direct patient care and the design and management macy services should focus on the pharmacist’s value and
of complex medication regimens and care delivery systems. responsibilities as a patient care provider and leader of the
Current evidence demonstrates that the inclusion of pharma- pharmacy enterprise through the development of organiza-
cists practicing in ambulatory care settings on the healthcare tional structures that support this mission. Development of
team improves quality of care, enhances patient outcomes, such structures will require communication and collaboration
and contributes to cost avoidance.4 Most states now allow with other departments and services throughout the health
pharmacists to provide direct patient care services under a system that support ambulatory care, which every member
physician–pharmacist collaborative agreement, further sup- of the pharmacy team should cultivate at every opportunity.
porting the expansion of ambulatory care pharmacy services.
The primary purpose of these guidelines is to outline A. Pharmacy and Pharmacist Services
the minimum requirements for the operation and manage- Pharmacy Mission, Goals, and Scope of Services. Ambula-
ment of services for patients in this rapidly evolving ambulatory care pharmacy services should have a written mission
tory care setting. The elements of service that are critical to statement that, at a minimum, reflects both pharmacy patient
optimal, safe, and effective medication use in the ambulatory care and service responsibilities. The mission should be con-
setting include (1) leadership and practice management, (2) sistent with the mission of the health system. The develop-
patient care, (3) drug distribution and control, and (4) facili- ment and prioritization of goals, objectives, and work should
ties, equipment, and other resources. Although the scope of be consistent with the mission statement. The mission state-
pharmacy services will vary from site to site, depending ment may also incorporate consensus-based national goals,
on the needs of the patients served and the resources avail- such as those expressed in the recommendations from the
able, these elements are directly linked to improved patient, ASHP Pharmacy Practice Model Initiative.6
population, and health-system outcomes. Specific attention Ambulatory care pharmacy services should also main-
to each element is essential to delivering patient care of the tain a written document describing the scope of pharmacy
highest quality. As providers of care to patients in ambulatory services. These services should be consistent with the health
care settings, pharmacists should be concerned with and take system’s scope of services and should be applied in all prac-
responsibility for the outcomes of their services in addition tice sites. The mission, goals, and scope of services should
to the provision of these services. Care should also extend be clearly communicated to everyone involved in the provi-
into and be coordinated with care providers in other settings; sion of pharmacy services.
therefore, these guidelines should be used, as applicable, in
conjunction with minimum standards for other practice set- Practice Standards and Guidelines. The standards and reg-
tings. Rather than including detailed advice in this document, ulations of all relevant government bodies (e.g., state boards
readers should refer to other referenced documents that ad- of pharmacy, departments of health) shall be met. The
practice standards and guidelines of the American Society informed about what to do to safely continue medication
of Health-System Pharmacists, the Joint Commission, the therapy in the event of a disaster.7
National Committee for Quality Assurance, and other appro- The health system’s business continuity plan should
priate accrediting bodies should be assessed and adapted, as consider the provision of pharmacist patient care services
applicable. Guidelines set forth by other independent orga- in emergency situations. Factors to consider should include
nizations such as the Institute for Safe Medication Practices system failures and breakdowns in the drug procurement
(ISMP) should be assessed and adapted as applicable. The process.
health system and the pharmacy should strive to meet these
standards, regardless of the particular financial and orga- Medical Emergencies. Policies and procedures should ex-
nizational arrangements by which pharmacy services are ist within the organization for providing appropriate levels
provided to the health system and its patients. Pharmacists of patient care during emergency situations 24 hours a day,
practicing in ambulatory care settings should play a critical including access to the pharmacist responsible for patient
role in ensuring that the health system adheres to medica- care, when appropriate. Pharmacists in the ambulatory care
tion-related national quality indicators and evidence-based setting are an essential part of both rapid-response teams
practice guidelines. and resuscitation teams. Appropriately trained pharmacists
should have an authorized role in responding to medical
B. Laws and Regulations emergencies. The pharmacy should participate in the devel-
Compliance with local, state, and federal laws and regula- opment of policies and procedures to ensure the availability
tions applicable to the ambulatory care pharmacy shall be of, access to, and security of emergency medications, includ-
required. The pharmacy shall maintain relevant documenta- ing antidotes.
tion of compliance with requirements concerning procure-
ment, distribution, and disposal of drug products; secu- Preventive and Postexposure Immunization Programs. If
rity of patient information; and workplace safety from the appropriate, the pharmacy team should participate in the
state board of pharmacy, Food and Drug Administration development of policies and procedures concerning preven-
(FDA), Drug Enforcement Administration (DEA), Centers tive and wellness programs and postexposure programs for
for Medicare and Medicaid Services (CMS), Occupational infectious diseases (e.g., human immunodeficiency virus,
Safety and Health Administration, and others. Ambulatory tuberculosis, hepatitis) for patients and employees. As ap-
care pharmacies dispensing medications across state bound- propriate, pharmacists should promote the use of immu-
aries shall comply with out-of-state licensure requirements nizations and, when legally allowed, participate as active
as well as other state and federal interstate laws and regu- immunizers.8
lations. Pharmacists practicing in ambulatory care settings
may enter into prescriptive authority and collaborative Substance Abuse Programs. If appropriate, the pharmacy
practice agreements that are state specific in scope. Finally, team should assist in the development of and participate in
pharmacists practicing in ambulatory care settings should be the health system’s substance abuse education, prevention,
knowledgeable about reimbursement rules and compliance identification, and organization-sponsored programs for
and billing requirements. staff and patients.9
C. Policies and Procedures D. Human Resources

Policies and Procedures Manual. A policy and procedures Position Descriptions. Areas of responsibility within the
manual governing the scope of the ambulatory care phar- scope of pharmacy services shall be clearly defined. The
macy services being provided (e.g., administrative, op- responsibilities and related competencies of pharmacy per-
erational, and clinical) should be available and consistent sonnel shall be clearly defined in written position descrip-
with current department processes. The manual should be tions. Pharmacists should be responsible for the provision
reviewed and revised on a regular basis to reflect changes of patient care and for the supervision and management of
in policies and procedures, the scope of services, organiza- support staff. Sufficient support staff (pharmacy technicians,
tional arrangements, objectives, or practices. All personnel clerical) should be employed to facilitate the provision of
should be familiar with and adhere to the contents of the care. Technicians should be responsible for aspects of drug
manual. Appropriate mechanisms should be established to procurement, dialogue with third-party payers, support of
ensure compliance with all policies and procedures. pharmacists’ patient care activities, and preparation of pre-
scription orders for a pharmacist’s clinical review.
Personnel Safety. Ambulatory care pharmacy personnel
should be involved in the health system’s plans for emer- Director of Ambulatory Care Pharmacy Services. These
gency response, infection prevention and control, manage- guidelines use the term director of ambulatory care phar-
ment of hazardous substances and waste, and incident re- macy services (or, more simply, director) to indicate the
porting. All pharmacy staff shall be familiar with these plans. person responsible for managing these services. Depending
on the health system’s organizational structure and other fac-
Emergency Preparedness. Policies and procedures should tors, designations such as manager or pharmacist-in-charge
exist for providing pharmacy services during facility, local, may also be used. Ambulatory care pharmacy services shall
or areawide disasters affecting the organization’s patients. be managed by a professionally competent, legally quali-
Appropriately trained pharmacists and representatives from fied pharmacist. The director should be knowledgeable
the pharmacy team should be members of emergency pre- about and have experience in all aspects of pharmacy care
paredness teams and participate in drills. Patients should be for ambulatory care patients. Completion of an advanced
management degree (e.g., M.B.A., M.H.A., M.S., M.P.H.),
a residency, or both is desirable. Completion of an ASHP- tient and employee safety, and pharmacy technician duties
accredited postgraduate year 1 (PGY1) residency should be and responsibilities as defined by the board of pharmacy
considered a minimum competency, while completion of for that state. Pharmacy technicians should have completed
an ASHP-accredited postgraduate year 2 (PGY2) residency an ASHP-accredited pharmacy technician training program
would be optimal. and be certified by the Pharmacy Technician Certification
The director of ambulatory care pharmacy services Board (PTCB). The pharmacy should hire pharmacy tech-
shall be responsible for nician trainees without those qualifications only if those
individuals (1) are required to both successfully complete
• Establishing the mission, vision, goals, and scope of an ASHP-accredited pharmacy technician training pro-
services of the ambulatory care pharmacy practice gram and successfully complete PTCB certification within
setting on the basis of the needs of the patients served, 24 months of employment and (2) are limited to positions
the needs of the health system, and developments and with lesser responsibilities until they successfully complete
trends in healthcare and pharmacy practice, such training and certification. The pharmacy should require
• Developing, implementing, evaluating, and updating ongoing PTCB certification as a condition of continued
plans and activities to fulfill the mission, vision, goals, employment.
and scope of services,
• Actively working with health-system leadership to de- Education and Training. All personnel should possess the
velop and implement policies and procedures that pro- education and training needed to fulfill their job responsibil-
vide safe and effective medication use for all patients ities. All personnel should participate in relevant continuing-
served by the organization, education programs, staff development programs, and other
• Ensuring the development and implementation of activities as necessary to maintain or enhance their compe-
policies and procedures that provide safe and effective tence. Both the ambulatory care pharmacy department and
medication use for the patients served by the organiza- the health system should make available to personnel, as
tion, appropriate, training and education on new processes, pro-
• Mobilizing and managing the resources, both human cedures, and methods of patient care.12 For pharmacists,
and financial, necessary for the optimal provision of ASHP-accredited PGY1 residency should be considered
pharmacy services, and a minimum competency, while completion of an ASHP-
• Ensuring that patient care services provided by phar- accredited PGY2 residency would be optimal.
macists and other pharmacy personnel are delivered in
compliance with applicable state and federal laws and Recruitment, Selection, and Retention of Personnel.
regulations as well as national practice standards. Qualities to consider in recruitment include completion of one
or two years of postgraduate residency training, board certifi-
A part-time director shall have the same obligations and re- cation, previous participation in a collaborative practice envi-
sponsibilities as a full-time director.10,11 ronment, and other credentials and privileges as appropriate.
The ambulatory care pharmacy team should be a An ASHP-accredited PGY1 residency should be considered
cross-functional group whose skills set includes operations a minimum competency, while completion of an ASHP-
management, clinical care, financial management, process accredited PGY2 residency would be optimal. Personnel
improvement, and informatics. Depending on the size and should be recruited and selected on the basis of requirements
scope of the setting, these functional responsibilities may be in established position descriptions. Criteria used in the se-
assigned to a single person or a team. It is the responsibility lection process should include the candidate’s performance
of the director to monitor the status of the goals set forth in of similar job-specific duties, education history relevant to
the vision, provide feedback to the pharmacy team as nec- job-specific duties, and willingness to contribute to achiev-
essary, and support the team’s implementation of the core ing the mission of the department and the health system.
functions of the pharmacy practice. The director should assist in identifying the professional and
technical requirements that a candidate must meet to qualify
Pharmacist Licensure and Certification. All pharmacists for the position. Clinical specialist positions are a necessary
must possess a current state license to practice pharmacy. part of any health system in order to advance practice, edu-
Functional responsibilities may mandate additional degrees cation, and research activities. An employee retention plan
(M.S., M.B.A., M.H.A., M.P.H.), certificates, or creden- is desirable.13
tials (e.g., Board of Pharmacy Specialties certification).
Pharmacists who provide direct patient care and drug ther- Orientation of Personnel. Personnel who are new to either
apy management should be certified through the most appro- a specific position or the organization should be oriented to
priate Board of Pharmacy Specialties certification process. their position through an established and structured proce-
As appropriate, these pharmacists should also be privileged dure. During the orientation process, personnel should be
and credentialed by the health system. trained in their new job functions by an employee knowl-
edgeable in the work assigned. During the orientation pe-
Technician Requirements. The ambulatory care setting riod, the trainer’s normal workload should be reduced in or-
shall adhere to all state guidelines regarding pharmacy der to provide dedicated instruction time to the person being
technician registration, certification, and licensure, as ap- oriented, particularly in distributive settings. The orientation
plicable. All pharmacy technicians should successfully com- period of new personnel should be tailored to both the new
plete a training course approved by the ambulatory care site employee’s needs and the functions of the employee’s posi-
that includes education on at least the following topics: the tion. Evaluation of the effectiveness of orientation programs
prescription-dispensing process, patient service skills, pa- should be done in conjunction with the competency assess-
ment required before a new hire can assume full responsibil- Patient Care and Counseling Areas. A designated area
ity for the new position. should be available for private patient care and counseling
by pharmacists to enhance patients’ knowledge and under-
Work Schedules and Assignments. Assignments of phar- standing of and adherence to prescribed medication therapy
macists and pharmacy technicians should be clearly defined regimens and monitoring plans, to provide disease state
to allow the optimal use of personnel and resources. Work management and patient care services, and to foster continu-
schedules should take into account peak demand times ity of care. Space should accommodate the pharmacist and
for pharmacist-provided patient care. Sufficient personnel patient and, as appropriate, parents, caregivers, or chaper-
should be available to ensure the safe and timely delivery of ones. These areas should be stocked with relevant supplies
pharmacy services. Hours of operation should be designed and equipment, including computers, drug references, moni-
to meet the needs of the patient population given the avail- toring equipment, and other necessary tools.20
able resources of the health system.
Office and Meeting Areas. Adequate office and meeting
Performance Evaluation and Job-Specific Competencies. areas should be available for administrative, educational,
Scheduled periodic evaluations of performance should occur and training activities. These areas should be stocked with
for all pharmacy personnel. Performance should be evalu- relevant supplies and equipment, including computers, drug
ated on the basis of position description requirements and references, and other necessary tools.
expected competencies, and the evaluation format should be
consistent with that used by the health system. Evaluations Automated Systems. Automated mechanical systems and
should include comments from professional and techni- software can promote safe, accurate, and efficient medica-
cal staff as well as other members of the healthcare team. tion ordering and preparation, drug distribution, and clinical
Pharmacy staff should meet the expectations defined in their monitoring. Barcode technology that is associated with any
position descriptions for adequate performance of their du- of these systems provides an additional level of safety. The
ties. The director should ensure that an ongoing competency potential for medication errors with any of these systems
assessment program is in place for all staff, and each staff should be thoroughly understood, evaluated, and eliminated
member should have a continuous professional development to the greatest extent possible. Organizations should have
plan. policies and procedures for the evaluation, selection, use,
calibration, monitoring, and maintenance of all automated
E. Facilities, Equipment, and Other Resources pharmacy systems.21,22 The greatest benefits to safety and
Pharmacy. To ensure optimal performance and quality pa- productivity are seen with robust functionality, proper sys-
tient care, adequate space, equipment, and other resources tem maintenance, and the prevention of workarounds.
should be available for all professional, administrative, dis- Automated systems and devices should interface with
tributive, and direct patient care functions. Patient care ar- pharmacy-based systems and support and augment the med-
eas, which include the pharmacy counter, counseling rooms, ication-use process. The replenishment of dispensing equip-
and clinic offices or examination rooms where direct patient ment should be overseen by pharmacists or by technicians
care is provided, should ensure proper patient confidential- who have been certified as part of a technician-checking
ity, promote safe and efficient patient care, and contain all program, depending on specific state board requirements.
tools and supplies necessary for the provision of such care. Calibration, maintenance, and certification as required by
Pharmacy services operations shall be located in areas that applicable standards, laws, and regulations should be con-
facilitate the provision of services to patients and health- tinual and documented. All automated systems shall include
care providers. Distributive areas should be constructed, adequate safeguards to maintain the confidentiality and se-
arranged, and equipped to promote safe and efficient work- curity of patient records, and there shall be procedures to
flow for staff and patients and to ensure medication integrity. provide essential patient care services in case of equipment
All facilities shall be designed to comply with applicable failure or downtime.
state and federal guidelines.
Health Information Technology. A comprehensive phar-
Medication Storage and Preparation Areas. Facilities macy computer system shall be employed and should be in-
should exist for the preparation and storage of drug products tegrated to the fullest extent possible with other health-sys-
and medications under proper conditions of sanitation, tem- tem information systems and software. Computer resources
perature, light, moisture, ventilation, segregation, and secu- should be used to support clerical functions, maintain patient
rity throughout the pharmacy and other patient care areas. medication profile records, provide clinical decision support,
Monitored, adequate refrigerator and freezer capacity should perform necessary patient-billing procedures, manage drug
be available within the secure pharmacy area and, as neces- product inventories, provide drug information, access the
sary, in nonpharmacy areas. patient medical record, manage electronic prescribing, and
interface with other computerized systems to obtain patient-
Compounding and Packaging Areas. There shall be suit- specific clinical information for medication therapy moni-
able facilities to enable the compounding, preparation, pack- toring and other clinical functions and to facilitate the conti-
aging, and labeling of sterile and nonsterile drug products, nuity and transitions of care to and from other care settings.
including hazardous drug products, in accordance with es- Pharmacy-based systems experts who act as resources
tablished quality-assurance procedures. The work environ- and consultants in maintaining current systems, planning for
ment should promote orderliness and efficiency and mini- implementations and upgrades, and assisting in performance
mize the potential for medication errors and contamination improvement and evaluation are critical to the success of in-
of products.14-19 formatics implementation and use.
Record and Equipment Maintenance. Adequate space G. Committee Involvement

should exist for maintaining and storing records (e.g., pre- A pharmacist representative from the ambulatory care phar-
scription records, equipment maintenance, controlled sub- macy team shall be a member of and actively participate on
stances inventory) to ensure compliance with laws, regula- committees responsible for establishing and implementing
tions, accreditation requirements, and sound management medication-related policies and procedures, ambulatory
practices. Appropriate licenses, permits, tax stamps, and care leadership, the provision of patient care, informatics,
other documents shall be on display or on file as required by and performance improvement, as appropriate. Members
law or regulation. All equipment shall be adequately main- of the pharmacy team should take part in staff recognition,
tained and certified in accordance with applicable standards, patient service programs, and other programs as identified
laws, and regulations. Equipment maintenance and certifica- in the ambulatory care pharmacy service. Members of the
tion shall be documented. pharmacy team should participate in the activities of similar
committees of the health system, as applicable
F. Managing Financial Resources
Budget Management. The pharmacy shall have a budget Standard II. Managing the
that is consistent with the health system’s financial man-
agement process and supports the scope of and demand for
Medication-Use Process
pharmacy services. Oversight of workload and financial per-
formance should be managed in accordance with the health
A. Medication-Use Policy Development
system’s requirements. Management should provide for the
Medication-use policy decisions should be founded on the
determination and analysis of pharmacy service costs, capi-
evidence-based clinical, ethical, legal, social, philosophical,
tal equipment costs, and new project growth.
quality-of-life, safety, and economic factors that result in op-
The ambulatory care pharmacy budget processes
timal patient care. Committees within the organization that
should enable the analysis of pharmacy services by unit of
make decisions concerning medication use (e.g., pharmacy
service and other parameters appropriate to the organization
and therapeutics, infection control) should include the active
(e.g., organizationwide costs by medication therapy, clinical
and direct involvement of physicians, pharmacists, other ap-
service, specific disease management categories, and patient
propriate healthcare professionals, and patients, where ap-
third-party enrollment). The director should have an integral
propriate. Pharmacists practicing in ambulatory care settings
part in the organization’s financial management process.
should actively participate on committees whose decisions
could affect the quality, safety, effectiveness, or cost of phar-
Health-System Integration. Other functional units within
macy services or the medication-use process. Institutional
the health system should factor the cost of pharmacy ser-
and health-system pharmacists and pharmacy technicians
vices being provided by the ambulatory care pharmacy into
shall be members of an interprofessional team accountable
the departmental budget when appropriate.
and responsible for medication reconciliation, patient coun-
seling, and medication-related outcomes by establishing a
Third-Party Contract Review. In conjunction with the or-
medication-related continuity-of-care process for all patients.
ganization’s legal or contracting department, the pharmacy
Pharmacists practicing in ambulatory care settings should
director’s team should review third-party payer contracts to
be actively involved in the development, maintenance, and
ensure that reimbursement is appropriate for services being
updating of medication-use policies, including tracking and
rendered (including dispensing, patient care, and disease
trending of health-system antibiotic resistance patterns.
state management services) and the terms of the contract are
in the best interest of the patient and the health system. The
B. Formulary Management and Integration
organization, pharmacy, or pharmacist should contract with
Both the patients’ diseases and the medications authorized
third-party payers that are relevant to the ambulatory care
for use by patients’ third-party prescription drug programs
pharmacy’s patient population.
should be taken into account when determining the ambula-
tory care pharmacy’s inventory. The pharmacy should have
Revenue, Reimbursement, and Compensation. The director
access to specialty medications distributed through closed-
should be knowledgeable about revenues for pharmacy ser-
network systems when needed to support consistent delivery
vices, including reimbursement for medication dispensing,
of patient care and medication reconciliation.
patient care, and disease state and drug therapy management
Health systems should maintain a formulary that is ef-
services. Processes should exist for the routine verification
ficacious and cost-effective. This formulary should be devel-
of payment from third-party payers.
oped with feedback from professional healthcare providers
(pharmacists, physicians, social workers, case managers).
Drug Expenditures. Specific policies and procedures for
When possible, charity programs (patient assistance pro-
managing drug expenditures should address such methods
grams, copayment foundations) should be accessed to help
as utilization review programs, inventory management, and
patients with limited income and resources to procure their
cost-effective care for patients with limited income and re-
medications.
sources. The pharmacy department should use practices such
as competitive bidding, group purchasing, and specialized
C. Clinical Care Plans and Disease State Management
pricing (e.g., 340B Drug Pricing Program) when applicable
Pharmacists in their scope of practice should be involved
to develop a responsible drug purchasing model.
as part of an interprofessional team in the development and
implementation of clinical care plans with prescriptive au- Standard III. Drug Product Procurement
thority in the healthcare setting (clinical practice guidelines,
and Inventory Management
critical pathways) and disease state management programs
involving collaborative drug therapy management (CDTM)
The pharmacy or contracted network pharmacies should be
agreements and treatment protocols. In addition, medica-
responsible for the procurement, distribution, and control of
tion therapy management (MTM) services should be de-
all drug products used in the treatment of the organization’s
veloped to assist with collaborative patient care. Emphasis
patients. The pharmacy is responsible for the development
should be placed on clinical care plans, primary care, and
of policies and procedures governing medication distribu-
medication treatment protocols that cover dosage calcula-
tion and control. Policies and procedures should be devel-
tions and limits and medications frequently associated with
oped in collaboration with other appropriate professionals,
adverse (potential and actual) events, including medication
departments, and interprofessional committees of the orga-
errors.23,24 Primary care protocols should consider whole-
nization.26
patient needs for health promotion and disease prevention
measures as well as appropriate patient assessments, com-
A. Purchasing and Maintaining the Availability of Drug
prehensive management of chronic disease states, manage-
Products
ment of medication-related care problems, and referrals for
Drug Product Acquisition and Availability. Drug products
acute medical care. The targeting of diseases should con-
approved for routine use should be purchased, stored, and
sider the prevalence of the disease in the population served
available in sufficient quantities to meet the needs of ambu-
by the organization and the potential impact on clinical and
latory care patients. Drug products not approved for routine
economic outcomes.25
use but necessary to meet the needs of specific patients or
categories of patients should be obtained in response to or-
D. Drug Information
ders, according to established policies and procedures.
Policies and procedures should be in place for review-
ing responses to requests for drug information for the pur-
Pharmaceutical Manufacturers and Suppliers. Criteria for
pose of performance improvement, safety, and education.
selecting pharmaceutical manufacturers and suppliers shall
Pharmacists should provide accurate, comprehensive, and
be established to ensure that patients receive pharmaceuti-
patient-specific drug information to patients, caregivers,
cals and related supplies of the highest quality and at the
other pharmacists, physicians, nurses, and other healthcare
lowest cost.27 Although these duties may be delegated in part
providers as appropriate, both proactively and in response
to a group purchasing organization, the pharmacy maintains
to requests associated with the delivery of pharmacist-pro-
sole responsibility for ensuring the quality of drug products
vided patient care, educational programs, and publications.
used in the hospital.27,28
Expertise in evaluating literature on drugs should be consid-
ered essential to the provision of drug therapy management.
Pharmaceutical Manufacturers’ Representatives. Policies
Drug information sources should include current pro-
and procedures should be developed governing the activi-
fessional and scientific periodicals, Web-based research
ties of manufacturers’ representatives or vendors of drug
tools (e.g., AHFS-DI, MicroMedex, Lexicomp Online), and
products (including related supplies and devices) within
the latest editions of reference books in appropriate pharma-
the pharmacy, ambulatory care setting, and organization.29
ceutical and biomedical subject areas that can be easily ac-
Representatives should not be permitted access to patient
cessed. Available sources should support research on patient
care areas and should be provided with written guidance on
care issues, facilitate the provision of patient care, and pro-
permissible activities. All promotional materials and activi-
mote safety in the medication-use process. When possible,
ties shall be reviewed and approved by the pharmacy.29-31
a pharmacist should play a role in addressing complex drug
information questions presented by professional staff within
B. Managing Inventory
the health system (e.g., pharmacists, nurses, physicians).
Medication Storage. Medication storage areas must have
proper environmental controls (i.e., proper temperature,
E. Development of Patient Care Services
light, humidity, conditions of sanitation, ventilation, and
Pharmacists who practice in ambulatory care settings
segregation), be secure, and be constructed so that drugs are
should be involved in the development, implementation,
accessible only to authorized personnel.32 Adequate inven-
and evaluation of new or changing patient care services and
tory controls must be maintained to allow proper inventory
drug therapy management services within the organization,
levels of medications based on utilization.
such as the development of new clinic or office sites, medi-
cal homes, or accountable care organizations. In reviewing
Drug Shortages. There should be policies and procedures
the potential for new services, both the value added to pa-
for managing drug shortages, and pharmacy staff should
tient care by the new service and the financial and logisti-
monitor reliable sources of information regarding drug
cal implications of the new service should be considered.
product shortages (e.g., drug shortages Web resource cen-
These efforts should promote the continuity of pharmacist-
ters of ASHP33 and FDA34). The pharmacy should develop
provided patient care across the continuum of care, practice
strategies for identifying alternative therapies, working with
settings, and geographically dispersed facilities, particularly
suppliers, collaborating with physicians and other health-
for newly discharged patients. New services should be de-
care providers, and conducting an awareness campaign in
veloped when opportunities arise for earlier involvement in
the event of a drug shortage.35
medication therapy decisions (e.g., clinic rounds) and for
continuity between patient encounters for the purpose of as-
Samples. The use of drug product samples should be pro-
sessing therapy success, tolerance, toxicity, and adherence.
hibited to the extent possible.32 However, if samples are
permitted under certain circumstances, policies and proce- age arrangements that might contribute to medication errors,
dures for their storage, control, and distribution should be in and other safety issues shall be assessed, documented, and
place. The pharmacy should oversee procurement, storage, corrected.33
and distribution of these products to ensure proper storage,
record-keeping maintenance, product integrity, and com- D. Drug Recall and New Prescribing Information
pliance with all applicable packaging and labeling laws, Written procedures should exist for the timely intervention
regulations, standards, and patient education requirements. and dissemination of information regarding drug recalls.
Pharmacists should be involved in the organization’s efforts Procedures should include an established process for re-
to secure safe and effective low-cost medications for low- moving from use any drugs or devices subjected to a recall,
income patients.32,36 notifying appropriate healthcare professionals, identifying
any patients who may have been exposed to the recalled
Patient Care Area Stock. Inventory of drug products held medication, and, if necessary, communicating available al-
in nonpharmacy areas (e.g., nursing station, clinic, physi- ternative therapies to prescribers. The pharmacy shall be
cians’ offices) for direct administration to ambulatory care notified of any defective drug products or related supplies
patients should be minimal. To the extent possible, medica- and equipment encountered by nursing or medical staff. All
tions administered to patients in nonpharmacy areas should drug product defects should be reported to FDA’s MedWatch
be prepared by the pharmacy. If this is not possible, auto- program.33
mated medication dispensing machines should be used to
dispense medications to patients. The list of medications to Standard IV. Patient Care
be accessible and the policies and procedures regarding their
use shall be developed by an interprofessional committee Pharmacists play an integral role in the provision of phar-
of physicians, pharmacists, and nurses.36 Access to medi- maceutical care, which is defined as the responsible pro-
cations should be limited to cases in which the committee vision of drug therapy for the purpose of achieving defi-
determines that an urgent clinical need for the medication nite outcomes that improve a patient’s quality of life.37
outweighs the potential patient safety risks of making the The concept of pharmaceutical care has evolved into a
medication accessible. A separate assessment should occur comprehensive, patient-focused model of pharmacist-pro-
for every location where a medication may be stocked. vided care. The principal elements of pharmaceutical care
are that it is medication related, is directly provided to the
Controlled Substances. Policies and procedures should en- patient, and is provided to produce definite outcomes; these
sure the distribution of controlled substances and other med- outcomes are intended to improve the patient’s quality of
ications with the potential for abuse. Policies and procedures life, and the provider must accept personal responsibility for
should be consistent with applicable laws and regulations the outcomes.37 In 2008, a joint working group consisting
of members and leadership from the American College of
and should include methods for preventing and detecting
Clinical Pharmacy, the American Pharmacists Association,
diversion.33
and the American Society of Health-System Pharmacists
created a definition of ambulatory care practice as part of
Emergency Medications and Devices. The pharmacy should
a petition to the Board of Pharmacy Specialties requesting
ensure the availability, access, and security of emergency
recognition of ambulatory care pharmacy practice as a spe-
medications, including antidotes. The telephone number of
cialty. The definition described ambulatory care pharmacy
the local poison information center should be posted at or
practice as a specialty in medication use for preventive and
near all telephones for staff access. Pharmacists should have
chronic care:
an authorized role in responding to medical emergencies.
All emergency medications should be stored in sealed Ambulatory care pharmacy practice is the provi-
containers that enable the staff to readily determine that the sion of integrated, accessible healthcare services
contents are complete and have not expired. All emergency by pharmacists who are accountable for addressing
medications should be available, controlled, and secured in medication needs, developing sustained partner-
the patient procedure areas. ships with patients, and practicing in the context
of family and community. This is accomplished
Patient’s Own Medications. Drug products and related through direct patient care and medication manage-
devices brought into the organization by patients shall be ment for ambulatory patients, long-term relation-
identified by the pharmacy and documented on the patient’s ships, coordination of care, patient advocacy, well-
medical record if the medications are to be used. These med- ness and health promotion, triage and referral, and
ications shall be administered only pursuant to a prescrib- patient education and self-management.38-40
er’s order and according to policies and procedures, which
should ensure the pharmacist’s identification and validation The mission of the pharmacist is to help people make
of the integrity as well as the secure and appropriate storage the best use of medications. At a minimum, pharmacists are
and management of such medications. responsible for assessing the legal and clinical appropriate-
ness of medication orders (or prescriptions), educating and
C. Drug Product Storage Area Inspections counseling patients on the use of their medications, moni-
All stocks of drug products, whether located within or outside toring the effects of medication therapy, and maintaining
the pharmacy area, should be inspected routinely and man- patient profiles and other records. In the ambulatory care
aged by pharmacy and location staff to ensure the absence of setting, these responsibilities are best accomplished through
outdated, unusable, recalled, or mislabeled products. Storage the provision of pharmacist-provided patient care, whether
conditions that would foster medication deterioration, stor- in the context of collaborative agreements with physicians or
independent of such agreements. Pharmacists are responsi- ing a comprehensive medication review (comprehensive or
ble for establishing relationships with patients and providers targeted) to identify, resolve, and prevent medication-related
who will facilitate the coordination and continuity of care, problems (including ADEs); performing patient health sta-
improve access to care, and improve patient outcomes. tus assessments; formulating medication treatment plans;
selecting, initiating, modifying, discontinuing, or adminis-
Providing Comprehensive Patient Care. The addition of tering medication therapy; managing high-cost and specialty
clinical pharmacy services to healthcare teams has produced medications; administering antibiotic stewardship pro-
significant cost savings to the healthcare system and im- grams; evaluating and monitoring patient response to drug
proved patient satisfaction, medication safety, and therapy therapy; documenting the care delivered for and communi-
outcomes.4 Clinical pharmacy services are designed to im- cating essential information to the patient’s other primary
prove patients’ access to care, provide disease management, care providers; providing education and training designed
and focus on quality-related outcomes. to enhance patient understanding and appropriate use of his
Recommendation B9 from the ASHP Pharmacy or her medications; providing information, support services,
Practice Model Initiative specifically states that “for hos- and resources designed to enhance patient adherence with
pitals and health systems that provide ambulatory care ser- his or her therapeutic regimens; coordinating and integrating
vices, drug-therapy management should be available from a MTM services within the broader healthcare management
pharmacist for each outpatient.”6 Furthermore, many of the services being provided to the patient; and selecting, initiat-
PPMI recommendations support the comprehensive care of ing, modifying, discontinuing, or administering medication
patients by pharmacists practicing in ambulatory care set- therapy under state-approved CDTM agreements.
tings through transitions of care; quality, safety, and finan-
cial outcomes; and facilitating continuity of care and medi- Relationships with Patients. Successful disease state and
cation reconciliation. medication management begins with the relationship be-
Interprofessional care models are accepted and pro- tween the patient and the pharmacist. Pharmacists practicing
moted by the medical community. The American College of in ambulatory care settings who provide direct patient care
Physicians and the American Society of Internal Medicine should develop and maintain a rapport with and the trust of
have stated that “collaborative drug therapy is one of the the patient and the caregiver. The pharmacist should coordi-
best examples of how pharmacists work with physicians. nate all aspects of the individual’s pharmacist-provided pa-
It is designed to maximize the patient’s health-related tient care, serve as a patient advocate, and encourage patients
quality of life, reduce the frequency of avoidable drug- to take responsibility for their health. The pharmacist should
related problems, and improve the societal benefits of phar- be flexible and adapt to patient-specific variables such as the
maceuticals.”41 In addition, governmental agencies support patient’s perception of how an illness or symptoms affect his
the work of pharmacists in the provision of direct patient or her life and the patient’s readiness for change.
care. The Medicare Modernization Act of 200342 mandated
that MTM services be offered by prescription drug plans to Relationships with Providers: CDTM Agreements. Almost
Medicare beneficiaries at high risk for ADEs.43 While nei- every state has amended its pharmacy practice act to allow for
ther the legislation nor the final CMS regulation provided the expansion of pharmacists’ scope of practice. Pharmacists
guidance on the design or reimbursement structure for MTM should actively participate in medication therapy decision-
services, CMS stated that these programs should be “patient- making and management through collaboration with pa-
focused services aimed at improving therapeutic outcomes tients, caregivers, physicians, and other healthcare provid-
that are developed in conjunction with practicing pharma- ers. By participating in CDTM, the pharmacist takes an
cists.”42 The Centers for Disease Control and Prevention active role in the initiation, management, and monitoring of
endorsed pharmacists as integral members of the interpro- medication therapy based on pharmacokinetic parameters,
fessional healthcare team and supports the pharmacist’s role genetic characteristics of the patient, serum concentrations
in providing MTM services to improve patient outcomes.44 of medications, laboratory values, and other patient-related
The strongest statement about pharmacist-delivered direct health and social factors in order to take responsibility and
patient care to date was presented in a report to the U.S. have authority for achieving desired therapeutic outcomes.
Surgeon General.4 This report described how innovative PPMI recommendation B14 states that, when possible
models of care that include pharmacists as members of the through credentialing and privileging processes, pharma-
healthcare team can help to improve safety, access, quality, cists should include in their scope of practice prescribing as
and cost while improving outcomes. Lastly, as the Patient part of the collaborative practice team.6 A collaborative care
Protection and Affordable Care Act is fully implemented, agreement between the pharmacist and physician or other
the involvement of pharmacists practicing in ambulatory healthcare provider must comply with applicable laws and
care settings will be critical in the establishment of account- regulations and the organization’s policies and procedures.
able care organizations. These integrated systems of care
will heavily rely on the expertise of pharmacists to support Patient History and Medication Reconciliation. Upon
safe and appropriate medication use. patient presentation for ambulatory care services, a phar-
macist should obtain a patient and medication history and
Patient Care and Disease State Management Services. The update and validate the patient’s current medication list.
purpose of a direct patient care or disease state management Pharmacists should be integral in identifying, developing,
service is to optimize therapeutic outcomes for patients. reviewing, and approving new medications by conducting
Such services may include elements designed to promote a patient-specific medication review before first-dose ad-
enhanced patient understanding, increase patient adherence, ministration and evaluating patient response to therapy. The
and detect ADEs. Possible services may include perform- history should include pertinent demographic information;
known health problems and diseases; applicable measure- may be established for specific responsibilities or positions.
ments and laboratory values; known drug allergies and Pharmacists in frontline practice should not be limited to
ADEs; behavioral, lifestyle, and socioeconomic influences competency in drug distribution and reactive order process-
on healthcare; and a comprehensive list of prescription and ing, and pharmacists engaged specifically in drug therapy
nonprescription medications and related medical devices management must have an understanding of and responsibil-
currently being used. The current medication list should ity for the medication-use and delivery systems. Individual
be maintained and updated during subsequent patient en- pharmacists must maintain competence in and accept re-
counters in both the inpatient and ambulatory care settings. sponsibility for both the clinical and distributive activities of
Pharmacists should routinely contribute to processes that the pharmacy department. A model for ongoing evaluation,
ensure that each patient’s care is maintained, regardless of which may include peer review, should be developed to en-
transitions across the continuum of care and practice settings sure that pharmacists remain competent.
(e.g., between inpatient and community pharmacies or home
care services). Moreover, pharmacists are uniquely posi- Outcomes. Outcome measurements used to quantify the im-
tioned to aid in establishing a patient medication complexity pact of the interventions of pharmacists practicing in am-
index, which includes severity of illness, number of medica- bulatory care settings can be divided into three categories:
tions, and comorbidities. clinical, economic, and humanistic. Clinical outcomes may
include rates of medication adherence, ADEs, and achieve-
Medication Therapy Assessment. Pharmacists practicing in ment and maintenance of evidence-based therapeutic goals.
ambulatory care settings must ensure safe and effective medi- Examples of economic outcomes include hospitalization
cation therapy. The assessment should include the appropri- rates, emergency room visits, census growth, and revenue
ateness of the prescribed medication for the patient’s diagno- generation. Humanistic outcomes may include provider sat-
sis and history, identification of medication-related problems, isfaction, patient satisfaction, and measurements of impact
and interventions for resolution. In addition, the assessment on patient quality of life and personal productivity.
should produce a plan for monitoring patient adherence, ther-
apeutic and adverse effects, and patient outcomes. Patient Confidentiality. Policies and procedures for access
to and dissemination of confidential patient information
Medication Therapy Monitoring. The pharmacist should must meet all applicable legal and regulatory requirements,
monitor patients’ understanding of and adherence to the including those of the Health Insurance Portability and
medication therapy plan as well as its effects and outcomes. Accountability Act,45 and be made readily available.
During subsequent encounters, pharmacists should obtain
appropriate information from patients, assess their progress, Standard V. Preparing, Packaging,
and identify and resolve problems. All interventions and as-
sessments of the care plan should be documented and made
and Labeling Medications
available to all providers participating in the patient’s care.
A. Preparing Medications
Documentation of Care Plan and Coordination of Care.
Preparation. The pharmacist should prepare or supervise the
Pharmacists should maintain a comprehensive care plan,
preparation of, in a timely and accurate manner, drug formu-
preferably as a component of an interprofessional CDTM
lations, strengths, dosage forms, and packages prescribed.
agreement. The care plan should be documented in the pa-
tient’s medical record and be accessible to other healthcare
Extemporaneous Compounding. Drug formulations, dos-
professionals involved in patient care. The pharmacist is
age forms, strengths, and packaging that are not available
responsible for communicating the plan to the patient and
commercially but are deemed necessary for patient care
other healthcare providers. The care plan should document
should be prepared by appropriately trained personnel
the patient’s medical and medication history, medication
in accordance with applicable standards and regulations
therapy assessment, and medication therapy regimen, in-
(e.g., FDA, United States Pharmacopeia [USP], state boards
cluding drug name, strength, and route of administration, in-
of pharmacy). Adequate quality-control and quality-assur-
dication for therapy, goal of therapy, monitoring parameters,
ance procedures should exist for these operations. Written
and proposed length of therapy.
master formulas and batch records (including product test
results, as appropriate) shall be maintained, and a lot num-
Pharmacist Skills and Competency. Pharmacists partici-
ber or other method to identify each finished product with
pating in direct patient care activities should demonstrate
its production and control history shall be assigned to each
competency in the areas of care provided. Postdoctoral
batch. Commercially available products should be used to
residency training, board certification, and continuing-
the maximum extent possible.14,15,17,18,46-48
education certification programs should be completed by all
pharmacists and documented in a retrievable format. PPMI
Compounded Sterile Preparations. Sterile compound-
recommendation B10 states that pharmacists who provide
ing is regulated by various state and federal agencies and
drug therapy management should be certified through the
shall meet all applicable laws and regulations. When pos-
most appropriate Board of Pharmacy Specialties certifica-
sible, manufactured sterile preparations should be preferred
tion process.6 Examples of minimum requirements include
to compounding in the pharmacy. Whenever compounded
demonstration of proficient communication skills, basic
sterile preparations are prepared, properly-trained staff shall
physical assessment, laboratory interpretation, and disease-
use appropriate techniques to avoid contamination and as-
and age-specific competencies. Minimum requirements
sure quality; this includes but is not limited to the following:
for level of education, experience, or postgraduate training
(1) using aseptic technique; (2) maintaining clean, unclut- Standard VI. Medication Delivery
tered, and functionally separate areas for product prepara-
tion to minimize the possibility of contamination; (3) using A. Dispensing Medications
a primary engineering control that provides an International Prescribing. Policies and procedures should be available to
Organization for Standardization class 5 environment while ensure that healthcare providers have applicable state and
preparing any intravenous admixture, any sterile preparation federal licensure and, if required, organizational authoriza-
made from nonsterile ingredients, or any sterile preparation tion for prescribing medications. Medications should be ad-
that will not be used within 1 hour; and (4) visually inspect- ministered and dispensed to ambulatory care patients only
ing the integrity of the medications. USP Chapter 79718 and after receiving the spoken, written, faxed, or electronic pre-
the ASHP Guidelines on Quality Assurance for Pharmacy- scription of an authorized prescriber. Spoken orders should
Prepared Sterile Products14 further define the compounding be limited to nonroutine and emergency situations and should
of sterile preparations and should be consulted by those re- be strongly discouraged for drug products and regimens
sponsible for this area of practice. prone to medication errors and other ADEs. A pharmacist
All sterile medications for use in the ambulatory care should, as soon as possible, reduce spoken orders to writ-
facility or for use by patients in the home should be prepared ing and verify them using the Joint Commission read-back
in a suitable environment by appropriately trained person- procedure.
nel and labeled appropriately for the user. Quality-control Pharmacists practicing in ambulatory care settings
and quality-assurance procedures for the preparation of ster- should advocate and foster healthcare provider conformance
ile products should exist, including annual competency as- with the formulary, clinical care plans, disease state man-
sessment of the preparer’s aseptic technique. For additional agement programs, and standardized Joint Commission–
guidance regarding therapy in the patient home, refer to approved terminology and abbreviations. Pharmacists
ASHP Guidelines on Home Infusion Pharmacy Services.49 practicing in ambulatory care settings should advocate the
development and use of electronic prescribing systems (di-
Hazardous Drug Products. All hazardous drug products for rect order entry by the prescriber).
use in the ambulatory care facility or for use by patients in
the home should be prepared in a suitable environment by Therapeutic Purpose. Before dispensing any medication,
appropriately trained personnel and labeled appropriately for the pharmacist should substantiate the indication for which
the user.16 Special precautions, equipment, supplies (spill and the medication was prescribed. Prescribers should be en-
eyewash kits), and training for storage, handling, and discouraged to routinely communicate the condition being
posal of hazardous drug products should be in place to ensure treated or the therapeutic purpose with all medication orders.
the safety of personnel, patients, visitors, the community, and
the environment. Quality-control and quality-assurance pro- Medication Orders. Medication orders (or prescriptions)
cedures for the preparation of hazardous products should be shall contain at a minimum the following information: pa-
in place. Institutional policy should address the risk to per- tient name and address; medication name, dose, frequency,
sonnel handling hazardous drug products, including periodic route, and quantity or duration; prescriber name, address,
monitoring of personnel for adverse effects.16 and telephone number; and prescriber DEA number for con-
trolled substances. All medication orders shall be reviewed
B. Packaging and Labeling Medications for legality and clinical appropriateness by a pharmacist be-
Packaging. Medications dispensed to ambulatory care pa- fore being dispensed. Any questions should be resolved with
tients should be packaged and labeled in compliance with ap- the prescriber, and any approved changes to the prescrip-
plicable federal and state laws and regulations and with USP tion shall be documented in a written notation on the face
and other standards. When feasible, dispensing in unopened of the prescription. Information concerning changes should
manufacturers’ containers and in tamper-evident packaging be appropriately communicated to the patient, caregiver, and
is desirable. Packaging materials should be selected that pre- other involved healthcare providers.
serve the integrity, cleanliness, and potency of compounded
and commercially available drug products. Containers, in- Drug Delivery Systems and Administration Devices.
cluding unit dose packages, for patients’ home use shall com- Pharmacists should provide leadership and advice in organi-
ply with the Poison Prevention Packaging Act.50 zational and clinical decision-making regarding drug deliv-
ery systems and administration devices and should partici-
Labeling. At a minimum, labels for patient home use of pate in the evaluation, use, and monitoring of these systems
medications shall comply with applicable federal and state and devices. The potential for medication errors associated
laws and regulations. Generally, labels contain the name, with such systems and devices should be thoroughly evalu-
address, and telephone number of the pharmacy; date of ated. Follow-up and education of staff should occur after sys-
dispensing; serial number of the prescription; patient’s full tems errors are discovered to prevent future systems errors.
name; name, strength, and dosage form of the medication;
directions to the patient for use of the medication; name of Mail Distribution. The pharmacy may mail medications to
the prescriber; precautionary information; authorized re- patients, preferably as part of a comprehensive pharmaceuti-
fills; and initials (or name) of the responsible pharmacist. cal care program that gives patients access to a pharmacist.
Other information may be required by individual state laws Mailed medications shall conform to all federal and state
and regulations. laws and regulations. Outer mailing packages and medica-
tion containers should protect the medication from heat, used appropriately, safely, and effectively and to increase the
humidity, and other environmental conditions that can af- probability of desired outcomes within defined populations
fect stability.51 A toll-free telephone service that is answered of patients. Proactive and continuous quality-improvement
during normal business hours should be provided to enable strategies aid in risk mitigation of medication-use systems.
communication between a patient or the patient’s physician Pharmacists practicing in ambulatory care settings should
and a pharmacist with access to the patient’s records. The play an integral role in this program. The medication-use
pharmacy should have procedures for investigating, replac- policy committee should define specific variables for evalu-
ing, and reporting, as required, medications lost during ation (disease state, pharmacologic category, high-use/
delivery. Special requirements for mailing controlled sub- high-cost drug products, high-alert medications, high-risk
stances vary according to state laws and regulations. therapies, problem-prone regimens) as appropriate for the
organization. Through this ongoing evaluation, areas in need
Standard VII. Evaluating the Effectiveness of improvement in medication prescribing and management
can be identified and targeted for intervention.
of the Medication-Use System
Medication Safety. Ambulatory care pharmacy services
A. Assessing Pharmacy Services and Practices
should be part of the health system’s program for preventing
Documentation and Measurement of Patient Care,
medication errors and ADEs. The health system’s medication
Interventions, and Outcomes. An ongoing process should
safety team should be a cross-functional group of employees
be in place for consistent documentation and measurement
(e.g., pharmacists, physicians, nurses) and patients, when
(and reporting to medical staff, administrators, and others)
applicable. Pharmacists who practice in ambulatory care
of pharmacist interventions, patient outcomes from MTM
settings are an essential part of this medication safety team.
(including patient satisfaction with the care provided and
The medication safety program should foster a just culture
quality of life), and pharmacists’ contributions to patient
for error reporting. The medication safety team should
care.52 Documenting pharmacy plans and recommendations
in the patient’s medical record is important for providing
continuity of care between healthcare providers, commu- • Use a systems-based approach to review errors,
nicating care plans, and underscoring the professional and • Review near-miss medication errors (i.e., errors that
did not cause patient harm but, if repeated, could cause
legal responsibility a pharmacist assumes when making pa-
patient harm),
tient-specific recommendations and modifications in medi-
cation regimens. Participating in this program is an essential • Analyze the root cause of medication errors, and
part of the role of every pharmacist practicing in ambulatory • Work with frontline staff to implement systems that
include proper checks and balances focused on pro-
care settings. An electronic medical record should be used
tecting against human error and mitigating risk.
for documentation and measurement whenever possible, and
the record should be designed to align pharmacists’ docu-
The occurrence of medication errors should be reported to
mentation outlining care provided as well as a method to
voluntary national reporting systems (e.g., USP Medication
trace and ensure the quality of care provided with signed
Errors Reporting Program, ISMP, and FDA MedWatch) to
recommendations and follow-up notes in the patient’s medi-
help prevent similar errors from occurring in other practice
cal record.
settings. Serious medication errors that result in temporary
or permanent harm, disability, or death should be reported to
Performance Improvement. The ambulatory care pharmacy
the appropriate regulatory agency or accrediting body.
service should have an ongoing, systematic program for as-
sessing pharmacist-provided patient care.53 Performance
Patient Safety. Ambulatory care pharmacy services should
improvement activities based on assessments should be
be part of a health system’s program to encourage patients’
integrated with the health system’s overall performance
participation in and accountability for their care. Patient ed-
improvement activities, as applicable. The performance
ucation should be sensitive to the individual patient’s health
improvement team should work with frontline staff to im-
literacy. To maximize the benefits of medication therapy
plement systems that include proper checks and balances
and reduce the potential for errors, the program should en-
focused on protecting against human error. Performance im-
courage patients to ask questions about their medications
provement initiatives should be focused on error reporting
and should emphasize adherence to their therapy plan.
trends and high-risk functions such as dispensing high-alert
Pharmacist–patient dialogue, pamphlets, and videos should
medications.
be used to teach patients how to ask questions about their
As part of the performance improvement program, op-
medications. This process is particularly important for re-
erational and outcomes data should be benchmarked with
cently discharged patients.
those of other ambulatory care pharmacy services of similar
size and scope. The results, including follow-up actions for
Antimicrobial Stewardship and Infection Prevention and
improvement, should be documented and provided to the or-
Control. There shall be policies and procedures to promote
ganization’s managers, the frontline staff using the system,
the optimal use of antimicrobial agents, reduce the transmis-
and others as appropriate.
sion of infections, and educate health professionals, patients,
and the public about these topics. Pharmacists should par-
B. Improving the Medication-Use Process
ticipate in antimicrobial stewardship and infection preven-
Medication-Use Evaluation. An ongoing program of both
tion and control efforts through clinical endeavors focused
prospective and retrospective monitoring of drug utilization
on proper antimicrobial utilization and membership on rel-
and costs should be in place to ensure that medications are
evant interprofessional work groups and committees within healthcare professionals called on to prescribe, dispense,
the health system. and administer these medications.56,57
Pharmacists should monitor patients’ laboratory re-
ports of microbial sensitivities or applicable diagnostic References
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17. American Society of Hospital Pharmacists. ASHP 33. American Society of Health-System Pharmacists.
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20. American Society of Health-System Pharmacists. statement on pharmaceutical care. Am J Hosp Pharm.
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23. Kernodle SJ. Improving health care with clinical prac- recognition of ambulatory care pharmacy practice as
tice guidelines and critical pathways: implications a specialty (November 2008). www.accp.com/docs/
for pharmacists in ambulatory practice. Pharm Pract positions/petitions/BPS_Ambulatory_Care_Petition.
Manag Q. 1997; 17:76–89. pdf (accessed 2015 Mar 19).
24. LaCalamita S. Role of the pharmacist in develop- 41. Keely JL, for the American College of Physicians–
ing critical pathways with warfarin therapy. J Pharm American Society of Internal Medicine. Pharmacist
Pract. 1997; 10:398–410. scope of practice. Ann Intern Med. 2002; 136:79–85.
25. Curtiss FR. Lessons learned from projects in disease 42. Medicare Prescription Drug, Modernization, and
management in ambulatory care. Am J Health-Syst Improvement Act of 2003, Pub. L. No. 108–173
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26. American Society of Health-System Pharmacists. 43. Academy of Managed Care Pharmacy. Sound medica-
ASHP statement on the pharmacist’s responsibility for tion therapy management programs: 2006 consensus
distribution and control of drug products. In: Hawkins document. www.pharmacist.com/sites/default/files/
BH, ed. Best practices for hospital and health-sys- files/mtm_sound_programs_2006.pdf (accessed 2013
tem pharmacy, 2013–2014 edition. Bethesda, MD: Jul 17).
American Society of Health-System Pharmacists; 44. Centers for Disease Control and Prevention. A pro-
2013:125. gram guide for public health: partnering with pharma-
27. American Society of Hospital Pharmacists. ASHP cists in the prevention and control of chronic diseases.
guidelines for selecting pharmaceutical manufacturers www.cdc.gov/dhdsp/programs/spha/docs/pharmacist_
and suppliers. Am J Hosp Pharm. 1991; 48:523–4. guide.pdf (accessed 2015 Mar 19).
28. American Society of Health-System Pharmacists. 45. Health Insurance Portability and Accountability Act
ASHP guidelines on medication cost management of 1996. Pub. L. No. 104-191. www.cms.hhs.gov/
strategies for hospitals and health systems. Am J HIPAAGenInfo/Downloads/HIPAALaw.pdf (ac-
Health-Syst Pharm. 2008; 65:1368–84. cessed 2013 Jul 17).
29. American Society of Hospital Pharmacists. ASHP 46. American Society of Health-System Pharmacists.
guidelines for pharmacists on the activities of vendors’ ASHP guidelines: minimum standard for pharma-
representatives in organized health care systems. Am J cies in hospitals (2012). www.ashp.org/DocLibrary/
Hosp Pharm. 1994; 51:520–1. BestPractices/SettingsGdlMinHosp.aspx (accessed
30. American Society of Hospital Pharmacists. ASHP 2013 Jul 17).
guidelines on pharmacists’ relationships with industry. 47. American Society of Hospital Pharmacists. ASHP
Am J Hosp Pharm. 1992; 49:154. technical assistance bulletin on single unit and unit
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and Manufacturers of America; 2004 Jan. 48. Pharmaceutical compounding—nonsterile prepa-
rations (general information chapter 795). In: The
United States pharmacopeia, 35th rev., and The na-
tional formulary, 30th ed. Rockville, MD: United Professor, University of Illinois at Chicago (UIC), Chicago. Kelly
States Pharmacopeial Convention; 2011:344–50. T. Epplen, Pharm.D., BCACP, FASHP, is Associate Professor of
49. American Society of Health-System Pharmacists. Clinical Pharmacy Practice, James L. Winkle College of Pharmacy,
ASHP guidelines on home infusion pharmacy ser- University of Cincinnati, Cincinnati, OH; at the time of writing she
vices. Am J Health-Syst Pharm. 2014; 71:325–41. was Clinical Coordinator, Ambulatory Pharmacy Services, Health
50. Poison Prevention Packaging Act, 15 U.S.C. 1471−6. Alliance, Greater Cincinnati, Florence, KY. Laurel M. Marsden,
51. General notices and requirements—preservation, B.S.Pharm., M.S.H.A., is Assistant Director of Pharmacy, Virginia
packaging, storage, and labeling. In: The United States Commonwealth University Health System, Richmond. Bridgette
pharmacopeia, 30th rev., and The national formulary, A. Thomas, Pharm.D., is Clinical Applications Manager, Johns
25th ed. Rockville, MD: United States Pharmacopeial Hopkins Outpatient Pharmacy, Baltimore, MD. Nathan S.
Convention; 2007:9–12. Thompson, B.S.Pharm., M.B.A., is Director, Outpatient Pharmacy,
52. Borgsdorf LR, Mian JS, Knapp KK. Pharmacist- Johns Hopkins Home Care Group, Baltimore.
managed medication review in a managed care sys-
tem. Am J Hosp Pharm. 1994; 51:772–7. The contributions of the Section of Ambulatory Care Practitioners
53. MacKinnon N. Performance measures in ambulatory Executive Committee (Seena L. Haines, Pharm.D., FASHP, FAPhA,
pharmacy. Pharm Pract Manage Q. 1997; 17:52–62. BCACP, BC-ADM, CDE; Gloria P. Sachdev, Pharm.D.; Jennifer
54. American Society of Health-System Pharmacists. Askew Buxton, Pharm.D., CPP; Melanie A. Dodd, Pharm.D., Ph.C.,
ASHP statement on the pharmacist’s role in antimicro- BCPS; Sandra Leal, Pharm.D., FAPhA, CDE; Steven M. Riddle,
bial stewardship and infection prevention and control. Pharm.D., BCPS, FASHP; and Justine Coffey, J.D., LL.M.) to this
Am J Health-Syst Pharm. 2010; 67:575–7. document are gratefully acknowledged.
55. Mutnick AH, Sterba KJ, Szymusiak-Mutnick BA.
Integration of quality assessment and a patient- The following organizations and individuals are acknowledged for
specific intervention/outcomes program. Pharm Pract reviewing draft versions of these Guidelines (review does not im-
Manage Q. 1998; 17:25–36. ply endorsement): Academy of Managed Care Pharmacy (AMCP);
56. American Society of Health-System Pharmacists. American Association of Critical-Care Nurses (AACN); American
ASHP guidelines on clinical drug research. Am J College of Clinical Pharmacy (ACCP); American Geriatric Society;
Health-Syst Pharm. 1998; 55:369–75. Joint Commission; Cindi Brennan, Pharm.D., M.H.A.; Mark
57. American Society of Hospital Pharmacists. ASHP N. Brueckl, M.B.A. (AMCP); Anne Burns, Pharm.D.; Frank P.
guidelines for pharmaceutical research in organized Castronovo, Jr., Ph.D.; Sharon Connor, Pharm.D.; Paul F. Davis,
health-care settings. Am J Hosp Pharm. 1989; 46:129– B.S.Pharm.; Ernest Dole, Pharm.D., FASHP; Melanie A. Dodd,
30. Pharm.D., Ph.C., BCPS; Scott R. Drab, Pharm.D., CDE, BC-
ADM; Sarah K. Ford, Pharm.D., BCPS, CPP; Seena L. Haines,
Pharm.D., FASHP, FAPhA, BCACP, BC-ADM, CDE; Deanne
Developed through the ASHP Section of Ambulatory Care L. Hall, Pharm.D., CDE; Philip E. Johnson, M.S., FASHP;
Practitioners and approved by the ASHP Board of Directors Tom Kaye, M.B.A., FASHP; Sandra Leal, Pharm.D., FAPhA,
on September 19, 2014. These guidelines supersede the ASHP CDE; Jeff Little, Pharm.D., M.P.H., BCPS; Jimmy R. Mitchell,
Guidelines: Minimum Standard for Pharmaceutical Services in M.S., M.P.H.; Bruce A. Nelson, M.S.; Colleen O’Malley, M.S.,
Ambulatory Care dated April 21, 1999. B.S.Pharm.; James A. Ponto, M.S., BCNP; Matt Ransom,
Pharm.D., BCACP; Steven M. Riddle, Pharm.D., BCPS,
Jennifer Askew Buxton, Pharm.D., CPP, is Deputy Director, FASHP; Christine Ruby, Pharm.D., BCPS; Gloria P. Sachdev,
Pharmacy Services, Cape Fear Clinic, Wilmington, NC; at the time Pharm.D.; Paul M. Schyve, M.D. (Joint Commission); Pamela
of writing she was Manager of Outpatient/Employee Pharmacy Shellner, B.S.N., M.A., RN (AACN); Melissa Somma-McGivney,
Services, New Hanover Regional Medical Center, Wilmington. Pharm.D., CDE; Richard L. Stambaugh, M.S., Pharm.D., BCPS;
RoseMarie Babbitt, B.S.Pharm., M.A., is Vice President, Marc H. Stranz, Pharm.D.; Megan Wagner, Pharm.D.; C. Edwin
Federal Contracts and Grants, American Pharmacists Association, Webb, Pharm.D., M.P.H. (ACCP); and Jody Jacobson Wedret,
Washington, DC; at the time of writing she was Associate Director, B.S.Pharm., FASHP, FCSHP.
Pharmacy Services, Parkland Health and Hospital System, Dallas,
TX. Cyndy A. Clegg, B.S.Pharm., M.H.A., is Director, Retail and Copyright © 2015, American Society of Health-System Pharmacists,
Home Care Pharmacy, Swedish Medical Center, Edmonds, WA; at Inc. All rights reserved.
the time of writing she was Assistant Director, Ambulatory Pharmacy
Services, Harborview Medical Center, Seattle, WA, and Clinical The bibliographic citation for this document is as follows: American
Associate Professor, University of Washington School of Pharmacy, Society of Health-System Pharmacists. ASHP Guidelines: minimum
Seattle. Sandra F. Durley, Pharm.D., is Associate Director, standard for ambulatory care pharmacy practice. Am J Health-Syst
Ambulatory Care Pharmacy Department, and Clinical Assistant Pharm. 2015; 72:1221–36.
ASHP Guidelines: Minimum Standard

for Pharmacies in Hospitals
Purpose services throughout the hospital, which every member of the
pharmacy team should cultivate at every opportunity.
The following minimum standard guidelines are intended to
serve as a basic guide for the provision of pharmacy services A. Pharmacy and Pharmacist Services
in hospitals. These guidelines outline a minimum level of Pharmacy Mission, Goals, and Scope of Services. The
services that most hospital pharmacy departments should pharmacy shall have a written mission statement that reflects
consistently provide. The reader is strongly encouraged to both patient care and operational responsibilities. Other as-
review the American Society of Health-System Pharmacy pects of the pharmacy’s mission may require definition as
(ASHP) guidance documents referenced throughout these well (e.g., educational and research responsibilities). The
guidelines for more detailed descriptions. Certain elements mission statement shall be consistent with the mission of the
of these guidelines may be applicable to other health care hospital and, if applicable, aligned with the health system of
settings or may be useful in evaluating the scope and quality which the hospital is a component. The development, priori-
of pharmacy services. tization, and implementation of the pharmacy’s goals should
be consistent with the mission statement. Determination of
short- and long-term goals and the undertaking of imple-
Elements of Care mentation activities should be performed in collaboration
with institutional leadership and other hospital staff (e.g.,
The mission of pharmacists is to help people make the
pharmacy, nursing, and medical staff), and these should be
best use of medications.1 Therefore, pharmacists shall be
integrated with the goals of the hospital. The mission state-
concerned with not only the provision but the outcomes of
ment may also incorporate consensus-based national goals,
pharmacy services. The elements of pharmacy services that
such as those expressed in the recommendations from the
are critical to safe, effective, and cost-conscious medica-
ASHP Pharmacy Practice Model Initiative.2
tion use in a hospital include (1) practice management, (2)
The pharmacy shall also maintain a written document
medication-use policy development, (3) optimizing medica-
describing the scope of pharmacy services. These services
tion therapy, (4) drug product procurement and inventory
should be consistent with the hospital’s scope of services and
management, (5) preparing, packaging, and labeling medi-
should be applied throughout the hospital in all practice sites.
cations, (6) medication delivery, (7) monitoring medication
The mission, goals, and scope of services shall be
use, (8) evaluating the effectiveness of the medication-use
clearly communicated to everyone involved in the provision
system, and (9) research. Although the scope of pharmacy
of pharmacy services, including pharmacists, residents, stu-
services will vary from site to site, depending upon the needs
dents, technicians, and support staff.
of patients and the hospital as well as the resources avail-
able, these core elements are inextricably linked to success-
24-Hour Pharmacy Services. Adequate hours of opera-
ful outcomes. Failure to provide any of these services may
tion for the provision of needed pharmacy services shall be
compromise the quality of patient care.
maintained; 24-hour pharmacy services should be provided
when possible. Twenty-four hour pharmacy services should
Terminology be employed in all hospitals with clinical programs that
require intensive medication therapy (e.g., transplant pro-
In these guidelines, the term “shall” is used to indicate a grams, open-heart surgery programs, neonatal intensive care
minimum standard of practice set forth in this document, in units, and trauma centers). When 24-hour pharmacy ser-
other ASHP policies, or in requirements established by laws, vices are not feasible, a pharmacist shall be available on an
regulations, accrediting bodies, or other binding authorities. on-call basis. Remote medication order processing may be
The term “should” is used to indicate a best practice that is employed (to the extent permitted by law and regulation) to
strongly encouraged by ASHP but which may not be appli- help provide pharmacy services but is not a substitute for an
cable to all institutions or in all circumstances. on-call pharmacist.3 Automated drug dispensing equipment
and computer databases are also not a substitute for the skills
Standard I. Practice Management and knowledge of a pharmacist and should not be considered
alternatives to 24-hour pharmacy services.4
Effective leadership and practice management skills are
necessary for the delivery of pharmacy services in a manner After-Hours Pharmacy Access. In the absence of 24-hour
consistent with the hospital’s and patients’ needs. Such lead- pharmacy services, access to a limited supply of medica-
ership should foster continuous improvement in patient care tions shall only be available to authorized, licensed health
outcomes. The management of pharmacy services should care professionals for use in carrying out urgent medica-
focus on the pharmacist’s responsibilities as a patient care tion orders. Access to such medications shall be carefully
provider and leader of the pharmacy enterprise through the monitored and documented, and after-hours access shall
development of organizational structures that support that be reviewed regularly to ensure appropriate use. The list of
mission. Development of such structures will require com- medications to be accessible and the policies and procedures
munication and collaboration with other departments and to be used (including subsequent review of all activity by a
pharmacist) shall be developed by a multidisciplinary com- response (including evacuation), and the facility’s business
mittee of physicians, pharmacists, and nurses (e.g., by the continuity plan shall include procedures for providing safe
pharmacy and therapeutics [P&T] committee or its equiva- and efficient pharmacy services in case of emergencies.
lent).5 Access to medications should be limited to cases in Appropriately trained pharmacists should be members of
which the P&T committee (or its equivalent) determines emergency preparedness teams and participate in applicable
that the urgent clinical need for the medication outweighs preparations and drills.7 The pharmacy shall establish, in
the potential risks of making the medication accessible. The conjunction with the hospitalwide emergency plan, policies
potential safety risks of medications should be considered and procedures for the safe and orderly evacuation of phar-
in the decision to make them accessible, and medications, macy personnel in the event of an emergency in the hospital.
quantities, dosage forms, and container sizes that might en-
danger patients should be limited whenever possible. Medical Emergencies. The pharmacy shall participate in
Routine after-hours access to the pharmacy by non- hospital decisions about the contents of code carts, emer-
pharmacists for access to medications shall not be permit- gency medication kits and trays, and the role of pharma-
ted. The use of well-designed night cabinets, after-hours cists in medical emergencies. Pharmacists should serve on
medication carts, automated dispensing devices,6 and other cardiopulmonary resuscitation teams, and such pharma-
methods precludes the need for nonpharmacists to enter the cists should receive appropriate training and maintain ap-
pharmacy.4 propriate certifications (e.g., Basic Life Support, Advanced
Cardiopulmonary Life Support, Pediatric Acute Life
Practice Standards and Guidelines. The standards and Support).
regulations of all relevant government bodies (e.g., state
boards of pharmacy, departments of health) shall be met. Immunization Programs. The pharmacy shall participate
The practice standards and guidelines of ASHP, appropri- in the development of hospital policies and procedures
ate accrediting bodies (e.g., Joint Commission, American concerning preventive and postexposure immunization pro-
Osteopathic Association Healthcare Facilities Accreditation grams for patients and hospital employees.8 When practi-
Program, Det Norske Veritas), and the Centers for Medicare cal, pharmacists should participate as active immunizers for
and Medicaid Services shall be viewed as applicable, and the hospital and health-system-based preventive immunization
hospital should strive to meet all applicable standards. programs (e.g., influenza).
B. Laws and Regulations Substance Abuse Programs. The pharmacy shall assist in
Applicable local, state, and federal laws and regulations the development of and participate in hospital substance
shall be met, and relevant documentation of compliance abuse education, prevention, identification, treatment, and
shall be maintained. employee assistance programs.9
C. Policies and Procedures D. Human Resources

Policy and Procedures Manual. There shall be a policy and Position Descriptions. Areas of responsibility within the
procedures manual governing pharmacy functions (e.g., ad- scope of pharmacy services shall be clearly defined. The
ministrative, operational, and clinical), and all pharmacy responsibilities and related competencies of professional
personnel shall follow those policies and procedures. The and supportive personnel shall be clearly defined in written
manual may include a statement of the pharmacy’s mission, position descriptions. These position descriptions shall be
philosophy, or values (e.g., the pharmacy’s mission or vision reviewed and revised as required by the hospital’s policies.
statement), but it should concentrate on operational policies Position descriptions should reflect more general aspects of
and procedures to guide and direct all pharmacy services. The performance (e.g., communication, motivation, teamwork)
pharmacy’s policies and procedures should be consistent with in addition to specific responsibilities and competencies.
the hospital’s policies and procedures, and the manual should
be reviewed by a designated medical staff committee for po- Director of Pharmacy. The pharmacy shall be managed by a
tential conflicts and other medical issues. The manual shall be professionally competent, legally qualified pharmacist. The
reviewed by pharmacy staff on a regular basis and revised as director of pharmacy should be thoroughly knowledgeable
necessary to reflect changes in procedures, organization, ob- about and have experience in hospital pharmacy practice
jectives, or practices. The manual shall be accessible to phar- and management. An advanced management degree (e.g.,
macy department personnel as well as other hospital employ- M.B.A., M.H.A., or M.S.) or an administrative specialty
ees (e.g., through the hospital’s intranet), and all pharmacy residency10 is desirable.
personnel should be familiar with its contents. Appropriate The director of pharmacy shall be responsible for
mechanisms to ensure compliance with the policies and pro-
cedures should be established. • Establishing the mission, vision, goals, and scope of
services of the pharmacy based on the needs of the pa-
Personnel Safety. Pharmacy employees should be involved tients served, the needs of the hospital (and any health
in the development of the hospital’s plans for emergency system of which the hospital may be a component),
response, infection prevention and control, management of and developments and trends in health care and hospi-
hazardous substances and waste, and incident reporting, and tal pharmacy practice,
all pharmacy staff shall receive education about those plans. • Developing, implementing, evaluating, and updating
plans and activities to fulfill the mission, vision, goals,
Emergency Preparedness. Facility emergency preparedness and scope of services of the pharmacy,
plans shall describe the role of pharmacy staff in emergency
• Actively working with or as a part of hospital or shortages and fluctuation in workload and/or patient acuity.
health-system leadership to develop and implement Remote medication order processing may be employed to
policies and procedures that provide safe and effective help address staff shortages or workload fluctuations.3
medication use for the patients served by the institu-
tion, Performance Evaluation. There shall be procedures for regu-
• Mobilizing and managing the resources, both human larly scheduled evaluation of the performance of pharmacy
and financial, necessary for the optimal provision of personnel. The evaluation format should be consistent with that
pharmacy services, and used by the hospital. The competencies of the position shall
• Ensuring that patient care services provided by phar- be well defined in the position description, short- and long-
macists and other pharmacy personnel are delivered term goals should be established for each employee, and the
in adherence to applicable state and federal laws and employee’s competency shall be assessed regularly. The phar-
regulations, hospital privileging requirements, and na- macy director shall ensure that an ongoing competency assess-
tional practice standards. ment program is in place for all staff, and each staff member
should have a continuous professional development plan.
A part-time director of pharmacy shall have the same ob-
ligations and responsibilities as a full-time director. Effective Communication. There should be established
methods for communicating important information to staff
Pharmacists. The pharmacy shall employ an adequate num- in a timely manner (e.g., electronic communications, staff
ber of competent, legally qualified pharmacists to meet the meetings, newsletters, bulletin boards). The pharmacy
specific medication-use needs of the hospital’s patients. should establish appropriate mechanisms to regularly assess
Pharmacists hired on a temporary or contract basis shall meet the effectiveness of such communications.
the same requirements as those employed by the hospital.
Ethical Conduct. Standards of ethical conduct shall be es-
Support Personnel. Sufficient support personnel (e.g., tablished, and there shall be procedures for educating all
pharmacy technicians and clerical or secretarial personnel) pharmacy staff regarding these standards. The institution’s
shall be employed to facilitate pharmacy services. Support conflict-of-interest and ethical conduct policies shall be
positions shall have a written job description that includes clearly communicated to all staff, with appropriate staff ac-
a statement of the competencies required for that position. knowledgement of conformance with these policies.13
Support staff shall be properly trained and supervised, and
professional development programs for them are desirable. E. Facilities
Pharmacy technicians should have completed an ASHP- Pharmacy. Adequate space, equipment, and supplies shall
accredited pharmacy technician training program, should be be available for all professional and administrative functions
certified by the Pharmacy Technician Certification Board, relating to pharmacy services. These resources shall meet
and shall meet the requirements of applicable laws and regu- all applicable laws and regulations; shall be located in areas
lations. Pharmacy technicians working in advanced roles that facilitate the provision of services to patients, nurses,
should have additional training and demonstrate competen- prescribers, and other health care providers; and shall be in-
cies specific to the tasks to be performed. tegrated with the hospital’s communication and delivery or
transportation systems.
Education and Training. All personnel shall possess the ed-
ucation and training required to fulfill their responsibilities Medication Storage and Preparation Areas. There shall be
and shall participate in relevant continuing-education pro- suitable facilities to enable the receipt, storage, and prepara-
grams and activities as necessary to maintain or enhance their tion of medications under proper conditions of sanitation,
competence.11 temperature, light, moisture, ventilation, segregation, and
security to ensure medication integrity and personnel safety
Recruitment, Selection, and Retention of Personnel. throughout the hospital.4
Personnel should be recruited and selected by the pharmacy
director on the basis of job-related qualifications and prior Compounding Areas. There shall be suitable facilities to en-
performance. An employee retention plan is desirable.12 able the compounding, preparation, and labeling of sterile
and nonsterile products, including hazardous drug products,
Orientation of Personnel. There shall be an established, in accordance with established quality-assurance proce-
structured procedure for orienting new personnel to the dures. The work environment should promote orderliness
pharmacy, the hospital, and their respective positions.9 and efficiency and minimize the potential for medication er-
Evaluation of the effectiveness of orientation programs rors and contamination of products.14–20
should be done in conjunction with the competency assess-
ment required before a new hire can assume full responsibil- Patient Assessment and Consultation Area. In outpatient
ity for the new position. settings, a private area for pharmacist–patient consultations
shall be available to confidentially enhance patients’ knowl-
Work Schedules and Assignments. The director of phar- edge of and adherence to prescribed medication regimens.21
macy shall ensure that work schedules, procedures, and as-
signments optimize the use of personnel and resources. There Office and Meeting Space. Adequate office and meeting
shall be a written departmental staffing plan that addresses areas shall be available for administrative, educational, and
how patients’ needs will be met during periods of staff training activities.
Automated Systems. There shall be policies and procedures Electronic databases and convenient methods of data
for the evaluation, selection, use, calibration, monitor- dissemination (e.g., e-mail and handheld devices) are desir-
ing, and maintenance of all automated pharmacy systems. able. If such tools are employed, they should be made avail-
Automated mechanical systems and software can promote able to all health care practitioners who require access to
safe, accurate, and efficient medication ordering and prepa- the data.
ration, drug distribution, and clinical monitoring. Use of
such systems and software shall be structured so as to not Record Maintenance. All records shall be maintained in
hinder the pharmacist’s review of (and opportunity to in- accordance with applicable laws, regulations, and institu-
tervene in) medication orders before the administration of tional policies. Adequate space shall exist for maintaining
first doses. The maintenance, calibration, and certification of and storing records (e.g., equipment maintenance, controlled
all automated systems shall be performed and documented substances inventory, and material safety data sheets) to en-
as required by all applicable laws, regulations, and stan- sure compliance with laws, regulations, accreditation re-
dards.6,22,23 All automated systems shall include adequate quirements, and sound management practices. Appropriate
safeguards to maintain the confidentiality and security of licenses and permits shall be on display or on file as required
patient records, and there shall be procedures to provide es- by law or regulation. Equipment shall be adequately main-
sential patient care services in case of equipment failure or tained and certified in accordance with applicable practice
downtime. standards, laws, and regulations. There shall be documenta-
tion of equipment maintenance and certification.
Information Technology. A comprehensive pharmacy com-
puter system shall be employed and should be integrated to F. Committee Involvement
the fullest extent possible with other hospital information A pharmacist shall be a member of and actively participate
systems and software, including computerized provider- in hospital and health-system committees responsible for
order-entry, medication administration, electronic health establishing and implementing medication-related policies
record, and patient billing systems. Computer resources and procedures as well as those committees responsible for
should be used to support clerical functions, maintain patient the provision of patient care, including the P&T, infection-
medication profile records, provide clinical decision support, prevention and control, patient care, medication-use evalu-
perform necessary patient billing procedures, manage drug ation, medication safety, nutrition, and pain management
product inventories, provide drug information, access the committees (or their equivalents), as well as the institutional
patient medical record, manage electronic prescribing, and review board, quality-improvement, and information tech-
interface with other computerized systems to obtain patient- nology committees (or their equivalents).5,24–26
specific clinical information for medication therapy moni-
toring and other clinical functions and to facilitate the con- Standard II. Medication-Use
tinuity of care to and from other care settings. Pharmacists
should be involved in the development and maintenance of
Policy Development
order sets, templates, and dose ranges used in computerized
provider-order-entry and clinical decision-support systems.
A. Policy Development
Pharmacy computer systems should be integrated with the
All committees that make decisions concerning medication
hospital’s clinical, financial, and administrative information
management and use shall have at least one pharmacist as
systems. All computer systems shall include adequate safe-
a member. This includes the P&T, infection-control, patient
guards to maintain the confidentiality and security of patient
care, medication-use evaluation, medication safety, nutri-
records, and a backup system should be available to continue
tion, pain management, and information technology com-
essential computerized functions (e.g., those that support pa-
mittees, as well as the institutional review board (or their
tient care) during equipment failure.
equivalents).5,24–26 Pharmacists shall be involved in the de-
velopment, implementation, and assessment of care plans
Drug Information. Adequate space, current resources, and
(protocols, critical pathways, disease statement management
information-handling and communication technology shall
programs, or clinical practice guidelines), standing orders,
be available to facilitate the provision of drug information.
and order sets that involve medication therapy.27
The department of pharmacy shall select its drug information
resources, and pharmacists shall play a leadership role in the
B. Formulary Management
selection of drug information resources used by other health
Formulary. A well-controlled formulary of approved medi-
care providers in the hospital. Up-to-date, objective drug in-
cations shall be maintained and regularly updated by the
formation shall be available, including current print or elec-
P&T committee (or its equivalent). The impact of and com-
tronic periodicals, newsletters, best-practices guidelines, and
pliance with the formulary should be periodically reviewed
recent editions of reference books in appropriate pharmaceuti-
(e.g., through drug-utilization reviews), and the P&T com-
cal and biomedical subject areas. Electronic drug information
mittee should regularly review the formulary for safety
databases are preferred because they are frequently updated
information. The P&T committee shall be responsible for
and can be made available to all health care professionals,
developing and maintaining written criteria for drug prod-
but sufficient access to print information shall be available in
uct selection, which shall address formulary requests for
case of equipment failure or downtime. Electronic and print
medications intended for use in special populations (e.g.,
drug information may be supplemented with medical libraries
pediatric or geriatric populations). The P&T committee shall
and other available resources. Appropriate drug information
be responsible for developing and maintaining adequate
resources shall be readily accessible to pharmacists located in
product specifications to aid in the purchase of medications
patient care areas.
and related supplies. The pharmacy shall disseminate the ity of medication therapy. Clinical imperatives should be the
formulary by electronic (preferred) or other means to meet primary determinants of medication-use decisions.
the needs of all health care professionals.
There shall be policies and procedures that address the A. Creating a Relationship with the Patient
use of dietary supplements and other alternative therapies. Pharmacist Role in Direct Patient Care. Hospital and phar-
There shall be policies and procedures for the procure- macy department policies should encourage pharmacists to
ment, control, and use of nonformulary medications required provide direct patient care to the greatest extent possible in
for patient care.5 both inpatient and outpatient settings. Hospital and phar-
macy department policies should encourage pharmacists to
Medication Therapy Monographs. Medication therapy engage in medication therapy management,29 collaborative
monographs for medications under consideration for for- drug therapy management, immunization, medication order-
mulary addition or deletion shall be made available to the ing and administration, and other patient care activities to
P&T committee for use in the decision-making process. the extent permitted by law, regulation, and hospital require-
These monographs should be based on evidence gathered ments.
through review and evaluation of the pertinent literature.
Each monograph shall include a comparative therapeu- Continuity of Care. Pharmacists should assume responsibil-
tic, economic, and risk assessment (inclusive of black-box ity for continuity of care for patients’ medication therapy.
warnings) of each medication. The risk assessment should Pharmacists and pharmacy departments should take a lead-
address the likelihood of an error occurring and the risk of ership role in developing and implementing policies and
injury should that error occur.5 procedures for admissions, discharges, and transfers so that
patients’ medication therapy is well managed regardless of
Nondrug Substances. There shall be policies and proce- patient transitions across care settings (e.g., among differ-
dures that describe how the pharmacy shall seek and obtain ent components of a health system or between inpatient and
documented authorization from appropriate medical staff community pharmacies or home care services).
and hospital committees prior to the medical use of any
chemical substance that has not received Food and Drug Patient Confidentiality. Systems shall be in place to ensure
Administration (FDA) approval for use as a drug or medi- that patient confidentiality is maintained in accordance with
cal nutrition therapy. All chemical or biological substances applicable laws and regulations. All pharmacy personnel
whose administration is intended for pharmacological or shall respect and protect patient confidentiality by safe-
medical effect or as a substitute for or complement to ap- guarding access to all patient information. Patient informa-
proved drugs shall be under the control of the pharmacy. tion shall be shared only with authorized health professionals
Documentation shall exist to ensure that appropriate risk and others authorized within the hospital or health system as
management measures (e.g., obtaining informed consent) needed for the care of patients.30 Pharmacy personnel should
have been taken. periodically receive training in how to comply with patient
confidentiality laws and regulations.
C. Drug Information
Drug Information Requests. The pharmacist shall provide B. Acquiring Essential Patient Data
patient-specific drug information and accurate and compre- Pharmacists should obtain, prepare, or have immediate ac-
hensive information about drugs and drug therapy to health cess to comprehensive medication histories for each patient,
professionals, patients, and patients’ caregivers as appropri- from the patient’s medical record or other databases (e.g.,
ate. Responses to general and patient-specific drug informa- a medication profile), or both. A pharmacist-conducted
tion requests shall be provided in an accurate and timely medication history for each patient is desirable. Electronic
manner by a pharmacist, and there should be a process for medical records should be constructed so that medication
assessing and ensuring the quality of responses.28 histories and other data required for medication manage-
ment, including medication reconciliation, are available to
Dissemination of Drug Information. Pharmacists shall all health professionals caring for a patient.
keep the hospital’s staff and health care providers informed
about the use of medications on an ongoing basis through C. Consulting With Other Health Professionals About
appropriate publications, presentations, and programs. Medication Therapy
Pharmacists shall ensure timely dissemination of drug prod- Pharmacist’s Consultations. Pharmacists should provide
uct information (e.g., recall notices, labeling changes, and oral and written consultations to other health professionals
changes in product availability). Electronic communications regarding medication therapy selection and management.30
(e.g., websites, email newsletters, intranet postings) are pre-
ferred because of their timeliness and accessibility.28 Medical Record Documentation. There shall be policies
and procedures for pharmacist review of and documentation
Standard III. Optimizing Medication in patients’ medical records. Recommendations made by the
pharmacist and actions taken in response to those recom-
Therapy mendations should be documented in the patient’s medical
record so that other health care providers have access to that
An important responsibility of the pharmacist is optimizing
information.30
medication use. Pharmacists, in collaboration with medi-
cal and nursing staff, shall develop policies and procedures
Medication Therapy Decisions. The pharmacist’s preroga-
based on demonstrated best practices for ensuring the qual-
tives to initiate, monitor, and modify medication therapy for
individual patients, and to order laboratory tests to exercise rating with physicians and other health care providers, and
those responsibilities, consistent with laws, regulations, and conducting an awareness campaign in the event of a drug
hospital policy, shall be clearly delineated and approved by product shortage.36
the appropriate committee (e.g., P&T, patient care, or medi-
cal executive committee). Samples. The use of medication samples shall be eliminated
to the extent possible. Medication samples shall never be used
Standard IV. Drug Product Procurement for inpatient treatment. If use of samples is otherwise permit-
ted, there shall be policies and procedures to ensure their safe
and Inventory Management use. The pharmacy shall oversee the procurement, storage,
and distribution of these products to ensure proper storage,
The pharmacy shall be responsible for the procurement, dis-
maintenance of records, product integrity, and compliance
tribution, and control of all drug products used in the hospi-
with all applicable packaging and labeling laws, regulations,
tal for inpatient and ambulatory patients. Policies and pro-
standards, and patient education requirements. Pharmacists
cedures governing these functions shall be developed by the
should be involved in hospital efforts to secure safe and ef-
pharmacy with input from other appropriate hospital staff
fective low-cost medications for low-income patients (e.g.,
and committees.4
through manufacturer patient assistance programs).4,5,33
A. Selecting Sources of Pharmaceutical Products
Patient Care Area Stock. The proper use of automated dis-
Medication Acquisition. There shall be policies and proce-
pensing devices reduces the need for medications to be stored
dures for managing medication acquisition. These policies
in nonpharmacy areas.6 Storage of medications in nonphar-
and procedures should address such issues as formulary
macy areas (e.g., patient care and procedural areas) shall to
development (including initial evaluation for formulary
the extent possible be limited to medications for emergency
consideration, medication-utilization review programs,
use and routinely used personal care items (e.g., mouthwash
and therapeutic interchange), competitive bidding, group
and antiseptic solutions). The list of medications to be ac-
purchasing, best practices, medication shortages, outsourc-
cessible and the policies and procedures regarding their use
ing, and cost-effective patient services. Benchmarking of
shall be developed by a multidisciplinary committee of phy-
medication costs should be performed to determine whether
sicians, pharmacists, and nurses (e.g., the P&T committee).5
medication expenses and the change in medication expenses
Access to medications should be limited to cases in which
over time are consistent with industry standards.4,31,32
the committee determines that the urgent clinical need for
the medication outweighs the potential patient-safety risks
Pharmaceutical Manufacturers And Suppliers. Criteria for
of making the medication accessible. A separate assessment
selecting drug product manufacturers and suppliers shall be
should occur for every location where a medication may be
established by the pharmacy to ensure the highest quality of
stocked.
and the best price for drug products. Although these duties
may be delegated in part to a group purchasing organization,
Controlled Substances. There shall be policies and proce-
the pharmacy maintains the sole responsibility for ensuring
dures to ensure control of the distribution and use of con-
the quality of drug products used in the hospital.31,32
trolled substances and other medications with a potential
for abuse. These policies and procedures shall be consistent
Pharmaceutical Manufacturers’ Representatives. There
with applicable laws and regulations and shall include meth-
shall be written policies governing the activities of manu-
ods for preventing and detecting diversion.4
facturers’ representatives or vendors of drug products (in-
cluding related supplies and devices) within the hospital.
Patient’s Own Medications. Drug products and related de-
Representatives should not be permitted access to patient
vices brought into the hospital by patients shall be identified
care areas and should be provided with written guidance on
by pharmacy and documented in the patient’s medical record
permissible activities within the hospital. All promotional
if the medications are to be used during hospitalization. They
materials and activities shall be reviewed and approved by
shall be administered only pursuant to a prescriber’s order
the pharmacy.33
and according to hospital policies and procedures, which
should ensure the pharmacist’s identification and validation
B. Managing Inventory
of medication integrity as well as the secure and appropriate
Medication Storage. Medications shall be received, stored,
storage and management of such medications.
and prepared under proper conditions of sanitation, tempera-
ture, light, moisture, ventilation, segregation, and security to
C. Inspecting Storage Areas and Inventory Items
ensure medication integrity and personnel safety.4
All stocks of medications shall be inspected routinely to
ensure the absence of outdated, unusable, recalled, or mis-
Drug Shortages. There shall be policies and procedures
labeled products. Storage conditions that would foster medi-
for managing drug product shortages. The pharmacy’s in-
cation deterioration, storage arrangements that might con-
ventory management system should be designed to detect
tribute to medication errors, and other safety issues shall be
subminimum inventory levels and alert the pharmacy to po-
assessed, documented, and corrected.4
tential shortages, and pharmacy staff should monitor reliable
sources of information regarding drug product shortages
D. Returning Recalled, Expired, and Other Unusable
(e.g., the ASHP34 and FDA35 drug shortages web resource
Items
centers). The pharmacy should develop strategies for identi-
There shall be a written procedure for the timely handling
fying alternative therapies, working with suppliers, collabo-
and documentation of a drug product recall. These proce-
dures should include an established process for removing code and that code should be used in inventory management,
from use any drugs or devices subjected to a recall, noti- dose preparation and packaging, dispensing, and administra-
fying appropriate health care professionals, identifying pation. It is the responsibility of the pharmacy department to
tients who may have been exposed to the recalled medica- ensure the quality of all aspects of bar-code medication ad-
tion, and, if necessary, communicating available alternative ministration, including scanability of bar codes and database
therapies to prescribers. The pharmacy shall be notified of management.38,39
any defective drug products or related supplies and equip-
ment encountered by the nursing or medical staffs. All drug Standard VI. Medication Dispensing
product defects should be reported to the FDA’s MedWatch
reporting program.4
and Delivery
Standard V. Preparing, Packaging, and A. Medication Dispensing

Labeling Medications Prescribing. Medications shall be prescribed by individu-
als who have been granted appropriate clinical privileges in
the hospital and are legally permitted to order medications.
A. Preparing Medications The pharmacy shall advocate and foster practitioners’ con-
Compounding. Drug formulations, dosage forms, strengths, formance with standardized, approved, and safe terminology
and packaging that are not available commercially but are and abbreviations to be used throughout the hospital when
needed for patient care shall be prepared by appropriately prescribing medications and discourage use of nonstandard
trained personnel in accordance with applicable practice and unapproved terminology and abbreviations.4
standards and regulations. The pharmacy shall provide ad-
equate quality-assurance procedures for these operations. Diagnostic or Therapeutic Purpose. Pharmacists should
Written master formulas and batch records (including prod- have immediate access to the patient’s diagnosis or the in-
uct test results, as appropriate) shall be maintained, and a lot tended therapeutic or medical purpose of medications.
number or other method to identify each finished product
with its production and control history shall be assigned to Medication Orders. All patient medication orders shall be
each batch.14–20 contained in the patient’s medical record. A direct copy
of the prescriber’s order, either hard copy (including fac-
Sterile Preparations. When possible, manufactured sterile simile) or prescriber-entered electronic transmission (pre-
preparations should be preferred to compounding in the ferred method), shall be received by the pharmacist. Oral
pharmacy. All sterile medications shall be prepared and la- orders should be avoided to the extent possible. When
beled in a suitable environment by appropriately trained per- oral orders are necessary, they shall follow the organiza-
sonnel in accordance with established quality-assurance and tion’s established procedures for their use and documen-
expiration dating procedures.14,19 The use of sterile medica- tation. Order transmittal safeguards should be used to en-
tions compounded outside the pharmacy should be avoided sure the security of the prescriber’s order. Appropriate
to the extent possible; when they are used, there shall be pro- records of each medication order and its processing in the
cedures for aseptic preparation, quality assurance, expiration pharmacy shall be maintained in accordance with applicable
dating, and ongoing competency evaluations for compound- laws and regulations.
ing personnel.14,19,37 Sterile compounding outside the phar- A system shall exist to ensure that medication orders
macy or satellite pharmacies (e.g., on nursing units) should are not inappropriately continued.4
be minimized and occur only in emergency situations.14,19
Review of Medication Orders. All medication orders shall
Hazardous Drug Products. There shall be policies and pro- be prospectively reviewed by a pharmacist and assessed in
cedures that describe special precautions, equipment, and relation to pertinent patient and clinical information before
training for preparation, handling, storage, and disposal of the first dose is administered or made available in an auto-
hazardous drug products and products used in their prepara- mated dispensing device, except in emergent situations in
tion. These policies and procedures shall be consistent with which the treatment of the patient would be significantly
applicable laws and regulations and should be adequate to compromised by the delay that would result from pharmacist
ensure the safety of staff, patients, visitors, the community, review of the order. There shall be a procedure for retrospec-
and the environment.17 tive review of these orders.
Any questions regarding an order shall be resolved
B. Packaging Medications with the prescriber prior to administration, and any action
Unit Dose Packaging. Whenever possible, medications taken as a result of this intervention should be documented
shall be available for inpatient use in single-unit packages in the patient’s medical record. Information concerning
and in a ready-to-administer form. Manipulation of medica- changes shall be communicated to the appropriate health
tions before administration (e.g., withdrawal of doses from professionals caring for the patient.4
containers, reconstitution of powdered drug products, la-
beling of containers, and splitting of tablets) by final users B. Medication Delivery and Administration
should be minimized.15 Drug Delivery Systems, Administration Devices, and
Automated Distribution Devices. The pharmacy shall have
Bar-Coding of Unit Dose Packaging and Point of Care responsibility for developing policies, procedures, and qual-
Administration. Unit dose packages should contain a bar ity-assurance programs regarding drug delivery systems,
administration devices, and automated distribution devices vices and departments as well as commercial sources should
that ensure safety, accuracy, security, and patient confiden- be reviewed by the pharmacy staff for accuracy, currency,
tiality. The potential for medication errors associated with literacy appropriateness, and completeness. If necessary,
such systems and devices should be thoroughly evaluated.4,6 interpretative language services (written or oral) should be
Pharmacy personnel shall supervise the stocking and docu- made available to patients.21
mentation of medications in automated dispensing devices.6
Whenever possible, automated dispensing cabinets should Standard VIII. Evaluating
employ profile-based technology integrated with remote
medication order-entry capabilities.
the Effectiveness of the
Medication-Use System
Medication Administration. Only personnel who are au-
thorized by the hospital in accordance with applicable laws There shall be an ongoing, systematic program for quality
and regulations and appropriately trained shall be permit- assessment and improvement of pharmacy services and the
ted to administer medications to a patient. All administered, medication-use system. The program should include rou-
refused, or omitted medication doses should be recorded in tinely evaluating the literature for new technologies or suc-
the patient’s medical record according to an established pro- cessful practices that have been demonstrated to enhance
cedure, and all medications that have not been administered safety in other organizations to determine if such technolo-
should be returned to the pharmacy. No medication should gies or practices can improve the hospital’s medication-use
be administered to a patient unless medical and nursing per- system. This program should be integrated with the hospi-
sonnel have been provided with adequate information about, tal’s or health system’s quality assessment and quality im-
and are familiar with, its therapeutic use, method of admin- provement activities. Quality-improvement activities related
istration, potential adverse effects, and dosage. to the selection, prescription, procurement, storage, prepa-
ration, dispensing, distribution, administration, documenta-
tion, monitoring, and use of medications shall be routinely
Standard VII. Monitoring Medication Use performed in cooperation with other health care providers.
Feedback to appropriate individuals or entities about the
quality achieved shall be provided.
A. Reviewing Patient Responses to Medication Therapy
Medication therapy monitoring shall be conducted by phar- A. Assessing Pharmacy Services and Practices
macists. Medication therapy monitoring includes a proactive Documentation of Pharmacist-Provided Patient Care
assessment of patient problems and an assessment of Services and Medication Therapy Outcomes. The phar-
macy shall have an ongoing process for consistent documen-
a. The therapeutic appropriateness of the patient’s medica- tation of the patient care services provided by pharmacists
tion regimen. and patient outcomes from medication therapy.30
b. Therapeutic duplication or omissions in the patient’s
medication regimen. Workload and Financial Performance. A process shall ex-
c. The appropriateness of the dose of the medication, as ist to routinely monitor and document workload and finan-
well as the route, method, and frequency of adminis- cial performance. Metrics should encompass the full scope
tration of the medication. of patient care services provided by pharmacists and the
d. Patient adherence to the prescribed medication regi- pharmacy enterprise. This process should provide for the
men. determination and analysis of hospital and systemwide costs
e. Medication–medication, medication–food, medica- of medication therapy. A pharmacist should be an integral
tion–dietary supplement, medication–laboratory test, part of the hospital’s leadership teams (e.g., administrative,
and medication–disease interactions. financial).
f. Adverse drug reactions and other undesired effects.40
g. Patient medication allergies and sensitivities. B. Improving the Medication-Use Process
h. Clinical and pharmacokinetic laboratory data to evalu- Medication-Use Evaluation. There shall be an ongoing pro-
ate the efficacy and safety of medication therapy and gram for monitoring drug utilization and costs to ensure that
to anticipate toxicity and adverse effects. medications are used appropriately, safely, and effectively
i. Physical signs and clinical symptoms relevant to the and to increase the probability of desired patient outcomes.
patient’s medication therapy. The P&T committee (or its equivalent) should define spe-
j. Assessment of the effectiveness of the patient’s medi- cific parameters for evaluation (e.g., disease state, pharma-
cation therapy. cological category, or high-use/high-cost drug products) as
appropriate for the organization. Through the ongoing evalu-
ation of medication use, areas in need of improvement in
B. Educating and Counseling Patients and Family medication prescribing and management can be identified
Pharmacists shall be available to participate in patient edu- and targeted for intervention.32,41
cation. Pharmacists should help to ensure that all patients
are given adequate information about the medications they Medication Safety. Pharmacists should provide leadership to
receive in order to help patients participate in their own and participate in collaborative, multidisciplinary efforts to
health care decisions and encourage adherence to medica- prevent, detect, and resolve drug-related problems that can
tion regimens. Patient education activities shall be coordi- result in patient harm. Pharmacists and other appropriate hos-
nated with the nursing, medical, and other clinical staff as pital personnel shall establish and regularly revise policies
needed. Medication-related material developed by other ser-
and procedures regarding medication error and adverse event tional drugs, including possible adverse effects and adverse
prevention and reporting. Monitoring, detecting, review, and drug reactions, to nurses, pharmacists, physicians, and other
analysis of the hospital and health system’s medication er- health care professionals called upon to prescribe, dispense,
rors and near-misses should be an ongoing process in a just and administer these medications.44,45
culture environment,42 and corresponding corrective actions
should be documented. An ongoing program for preventing, References
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ASHP guidelines on the pharmacist’s role in the de- Health-Syst Pharm. 1998; 55:369–76.
velopment, implementation, and assessment of critical 45. American Society of Hospital Pharmacists. ASHP
pathways. Am J Health-Syst Pharm. 2004; 61:939–45. guidelines for pharmaceutical research in orga-
28. American Society of Health-System Pharmacists. nized health-care settings. Am J Hosp Pharm. 1989;
ASHP guidelines on the provision of medication in- 46:129–30.
formation by pharmacists. Am J Health-Syst Pharm.
1996; 53:1843–5.
29. Office of the Law Revision Counsel, United States Developed through the ASHP Council on Pharmacy Practice and
House of Representatives. USCprelim. 42 U.S.C. approved by the ASHP Board of Directors on April 13, 2012.
Sec. 299b-35(c), MTM services to eligible individu-
als. http://uscode.house.gov/lawrevisioncounsel.shtml This document supersedes a previous version approved by the
(accessed 2012 Apr 24). ASHP Board of Directors on September 22, 1995.
ASHP gratefully acknowledges the contributions made by the fol- Kathleen M. Gura, Pharm.D., BCNSP, FASHP, FPPAG; Reginald
lowing individuals to various drafts of these guidelines: Thomas S. L. Hain, B.S.Pharm.; Thomas G. Hall, Pharm.D.; George Hatfield,
Brenner, B.S.Pharm., FASHP; Harold N. Godwin, M.S., FASHP, Pharm.D.; Jesse Hogue, Pharm.D.; Andrew Jarrell, Pharm.D.; Jack
FAPhA; William A. Gouveia, M.S., FASHP; Brian D. Hodgkins, G. Kitrenos, Pharm.D., FASHP; Jamie Kuo, Pharm.D.; Jim Lile,
Pharm.D., FCSHP, FASHP; Stanley S. Kent, M.S., FASHP; Patricia Pharm.D.; Charles “Kurt” Mahan, Pharm.D., Ph.C.; Linda Gore
C. Kienle, M.P.A., FASHP; Harold J. Kornfuhrer, B.S.Pharm., Martin, Pharm.D., M.B.A., BCPS (WSHP); Justine Medina, M.S.,
FASHP; Emory S. Martin III, Pharm.D., BCPS; J. Russell May, RN; Dayna Mitchell, Pharm.D., BCPS; Holly Monatt, Pharm.D.,
Pharm.D., FASHP; Gerald E. Meyer, Pharm.D., M.B.A., FASHP; BCPS; Selma Morrison; Robert J. Moura, M.S.; Jonathan M.
Thomas E. O’Brien, Pharm.D., M.S., FASHP; Sherri L. Ramsey, Mundy, M.B.A. (RISHP); Bruce A. Nelson, M.S.; Beth Norman,
D.Ph., BCPS; Frank G. Saya, Pharm.D., FCSHP, FASHP; Donna M.S., RN, CNS, ACNS-BC; Robert S. Oakley, M.S.; Fred J. Pane,
L. Soflin, B.S.Pharm., FASHP; David K. Solomon, Pharm.D., B.S.Pharm., FASHP; Shreya Parekh, Pharm.D.; Jennifer Phillips,
FASHP; Kasey K. Thompson, Pharm.D., M.S.; and Billy W. Pharm.D.; James Ponto, BCNP, FASHP; Curt W. Quap, M.S.,
Woodward, B.S.Pharm. FASHP; Todd Rowland, Pharm.D.; Renee B. Sager, Pharm.D.;
Joseph Sceppa, M.S., M.B.A.; Nicole Shumiloff, Pharm.D.; Nancy
ASHP also gratefully acknowledges the following organizations and R. Smestad, M.S.; Carolyn M. Smith, Pharm.D., M.B.A., BCPS
individuals for reviewing drafts of these guidelines (review does not (SCSHP); William E. Smith, Pharm.D., M.P.H., Ph.D., FASHP;
imply endorsement): American Nurses Association (ANA); Institute Richard L. Stambaugh, Pharm.D., M.S., BCPS; Therese Staublin,
for Safe Medication Practices (ISMP); Rhode Island Society of Pharm.D.; Marc Stranz, Pharm.D.; Timothy P. Stratton, Ph.D.;
Health-System Pharmacists (RISHP); South Carolina Society of Pamela Swarny, Pharm.D., J.D.; Jane Tennis, B.S.Pharm., M.B.A.;
Health-System Pharmacists (SCSHP); Wyoming Society of Health- Sherry Umhoefer, M.B.A.; Allen J. Vaida, Pharm.D., FASHP
System Pharmacy (WSHP); Tuesday Adams, RN-C, WCC; John A. (ISMP); Jody Jacobson Wedret, FASHP, FCSHP; Roger Woolf,
Armitstead, M.S., FASHP; Phil Ayers, Pharm.D., BCNSP; Ronald Pharm.D.; and Kevin Zak, Pharm.D.
Barnes, M.S.; Paul J. Barrett, Pharm.D., BCPS; Carol J. Bickford,
Ph.D., RN-BC, CPHIMS (ANA); P. Justin Boyd, Pharm.D., BCPS, Copyright © 2013, American Society of Health-System Pharmacists,
CDM; Tim Brown, Pharm.D., BCACP; Margaret Chrymko, Inc. All rights reserved.
Pharm.D.; Toby Clark, M.Sc., FASHP; Wayne F. Conrad, Pharm.D.,
FASHP; Gayle A. Cotchen, Pharm.D., M.B.A.; Debra Lynn The bibliographic citation for this document is as follows: American
Painter Cowan, Pharm.D., FASHP; Arash Dabestani, Pharm.D., Society of Health-System Pharmacists. ASHP guidelines: minimum
M.H.A., FASHP, FABC; Denise F. Daly, Pharm.D., BCPS; Tina standard for pharmacies in hospitals. Am J Health-Syst Pharm.
H. Denetclaw, Pharm.D., BCPS; Deanna Dossey, Pharm.D.; 2013; 70:1619–30.
William L. Fritz, M.S., FASHP; Daphne Hsu Galang, RPhT, CPhT,
B.S., M.H.A.; Michael A. Gillette, Pharm.D., BCPS, BCACP;
ASHP Guidelines on Pharmaceutical Services

in Correctional Facilities
Introduction Correctional Association should be followed, and re-

quirements set by federal, state, and local laws and
Pharmaceutical services in correctional facilities encompass regulations with respect to personnel should be met.
many aspects of community, hospital, and consultant pharmacy
practice. These guidelines are intended to address some of the Fiscal Resources
unique aspects of pharmacy practice and services in correc-
tional facilities. Some correctional facilities may not require, or Pharmacists serving correctional institutions should strive
be able to obtain, the services of a pharmacist. However, the to manage expenses while providing optimal care to the
concepts, principles, and recommendations contained in this inmate-patients. The pharmacist should
standard are applicable to all correctional facilities, regardless
of size or type. Thus, the part-time pharmacy director or con- • Work with the administrators of the correctional in-
sultant pharmacist has the same basic obligations and responsi- stitution to establish a budget for the operation of the
bilities as his or her fulltime counterpart in larger settings. This pharmacy.
document should serve as a guide for the provision of pharma- • Consider factors unique to each institution for the de-
ceutical services in correctional institutions. velopment of the budget (e.g., total inmate capacity,
average daily inmate population, demographics of the
inmate population).
Administration
• Make allowances for the disproportionate amount of
chronic communicable disease in the prison popula-
Pharmaceutical services are an integral part of health care tion and the regional variability of diseases.
provided in correctional institutions. The pharmacist is usu-
ally responsible for multiple tasks ranging from the manage-
• Apply the ASHP Technical Assistance Bulletin on
Assessing Cost-Containment Strategies for Pharmacies
ment of the pharmacy to the direct provision of services to in Organized Health-Care Settings, as appropriate.2
inmate-patients. Two primary management responsibilities
pertain to human and fiscal resources.
Policies and Procedures
Personnel1
• Sufficient support personnel should be available to A policies and procedures manual specifically written to
maximize the use of pharmacists in tasks requiring address aspects of pharmacy practice in the correctional
professional judgment. Appropriate supervisory facility should exist.
controls for support personnel should be maintained.
The use of pharmacy technicians graduated from • All policies and procedures should conform to federal,
ASHP-accredited pharmacy technician training state, and local laws and regulations.
programs is recommended. Pharmacy technicians • The pharmacy director should be familiar with the
should be certified by the Pharmacy Technician Standards for Health Services promulgated by the
Certification Board. National Commission on Correctional Health Care and
• All personnel should possess the education and train- the standards of the American Correctional Association.
ing needed to carry out their responsibilities. The com- • The pharmacy director should be familiar with the
petence of all staff may be enhanced through relevant constitutional rights of inmate-patients, current litera-
continuing education. Credentialing of eligible staff as ture about inmates’ rights, and court rulings affecting
Certified Correctional Health Professionals through the practice of correctional health care in general and
the National Commission on Correctional Health Care correctional pharmacy in particular. Attention to these
is recommended. concepts should be reflected in the manual.
• A pharmacist should be available, at a minimum, on a • The pharmacy director should be familiar with current
consulting basis; the pharmacist should visit each fa- literature, laws, and regulations governing confiden-
cility no less than monthly. If the only pharmaceutical tiality, consent, and other areas of correctional health
services provided are those of a consultant pharmacist, care that diverge from more traditional standards of
the consultant pharmacist should assume the role of pharmacy practice. Attention to these should be re-
pharmacy director. flected in the manual.
• If the pharmacist is an employee of a contract vendor, he • Transportation of inmate-patients’ medications within
or she should be designated as the pharmacy director and and among facilities should be addressed.
assume the associated obligations and responsibilities. • Security of drug products, entry into the pharmacy
• Health care services should be available to inmate- during the absence of a pharmacist, use of night cabi-
patients 24 hours a day. Pharmacist services should nets, emergency supplies of medications, and disaster
also be available, at least on an “on call” basis. services should be addressed.
• Other pertinent guidelines of the American Society of • Policies and procedures on the pharmacy’s role in
Health-System Pharmacists, the National Commission preparing lethal injections for capital punishment
on Correctional Health Care, and the American should exist.
Administrative Reports • The system employed should focus on patient safety and
result in a minimal incidence of medication errors and
Administrative reports generated by the pharmacy department adverse drug reactions. Ongoing processes for the moni-
will vary from facility to facility depending on the level of toring and reporting of adverse drug reactions and the de-
pharmaceutical services provided. Reports should include tection and prevention of medication errors should exist.
• The system employed should be cost-effective.
• The amounts and cost of drugs and services furnished • The system employed should foster drug-control and
• Destruction of unusable or outdated medications drug-use monitoring.
• Inventory value and quantities • The system employed should foster patient compliance,
• Records of formal meetings with administrators, phy- recovery of drugs because of expired orders, and ultimate
sicians, nurses, and other staff and any changes imple- destruction of all unusable and outdated medications.
mented as a result of those meetings • Inmates should not be used in the distribution process.
• Minutes of pharmacy and therapeutics committee • Patient confidentiality should be ensured in the distri-
meetings bution process (e.g., patients receiving medications for
• Medication administration records the treatment of AIDS).
• Reports of quality-control and quality-improvement
Drug Storage
activities
• Reports generated as required by applicable state laws
regulating the practice of pharmacy. (While often not • The pharmacy director should ensure the proper secu-
specifically written for the practice of correctional rity of medications stored in each location.
pharmacy, these laws are nonetheless usually pertinent • The pharmacy director should ensure that drug prod-
to pharmacy practice within the correctional setting.) ucts are stored in accordance with manufacturer or
USP requirements.
Facilities • The pharmacy director should ensure that stored drug
products are not expired.
The pharmacy should be located within or in an area con- Control
tiguous to the space provided for other health care services.
Facilities should be adequate to accommodate appropriate se- • A process for the recovery of medications dispensed to
curity of all drug products, especially controlled substances.3 inmate-patients after the discontinuance of orders or in
compliance with automatic stop orders should exist.
Purchasing, Distribution, and • A process for minimizing and eliminating unauthor-
Control of Medications ized use of medications by anyone other than the in-
tended patient (e.g., exchange of medications between
Purchasing, distribution, and control of medications are es- inmates) should exist.
sential elements of any pharmacy operation. Adequate meth- • A process for minimizing and eliminating pilferage
ods to ensure that these responsibilities are met should exist. should exist.
• A process for monitoring and preventing the dispensing
Purchasing of unusually large quantities of medications should exist.
• A process for preventing the dispensing of sufficient
• The pharmacy director should be responsible for choos- doses of any medication to enable potential suicide
ing the sources from which to obtain drug products.4 should exist. Individuals who are evaluated as high
• The pharmacy director should ensure that all medica- risks for suicide should be identified.
tions meet applicable legal requirements. Guidance • A process for the security and dispensing of controlled
on the obligations of drug product suppliers and pur- substances should exist.
chasers appears in the ASHP Guidelines for Selecting • The pharmacy director, in conjunction with the facil-
Pharmaceutical Manufacturers and Suppliers.5 ity’s medical staff and other responsible health author-
• The pharmacy director should ensure that medications ities, should maintain policies and procedures for the
purchased from sources other than manufacturers or routine review and renewal of medication orders and
wholesalers (e.g., other pharmacies, contract provid- for any automatic discontinuance of orders.
ers) meet all applicable legal requirements. All sup- • Access to patients’ medication records should be lim-
pliers should be able, at the request of the pharmacy ited to authorized personnel only. Complete access by
director, to provide data on the quality of products. the pharmacist should be ensured.
• To the extent possible, all drug products should be • A process for pharmacist review of medication or-
contained in single-unit or unit dose packages. ders to ensure patient safety and appropriateness of
medication should exist. Medication orders (except in
Distribution emergency situations) should be reviewed by the phar-
macist before the first dose is dispensed.
The pharmacist is responsible for the distribution and con-
trol of all drug products (including diagnostics and drug- Medication Administration
related devices).
While medication administration is traditionally the respon-
• A unit dose drug distribution and control system is sibility of nurses, in the correctional setting some or all of
recommended. this responsibility may be assigned to other personnel.
• The pharmacy director should be familiar with stan- • The pharmacy director should maintain policies and
dards of the National Commission on Correctional procedures for accessibility of medications in case of
Health Care with respect to medication administration riots or other emergency situations.
by non-health-care personnel, and policies and pro- • The pharmacy director, in conjunction with the medi-
cedures specifically addressing such administration cal director or other responsible health authority and
should exist. the correctional institution’s administrator, should de-
• The pharmacy director should participate in development velop policies and the procedures that complement the
of medication administration forms and ensure that all standards of the National Commission on Correctional
relevant information is incorporated into the forms. Health Care regarding emergency services.
• The pharmacy director should regularly educate all
personnel involved in medication administration. Therapeutic Policies
These educational programs should include informa-
tion on proper administration, indications, monitoring • The pharmacy director should be a member of the phar-
for adverse effects and allergic reactions, documenta- macy and therapeutics committee or its equivalent.
tion, accountability, confidentiality, and the impor- • A formulary should exist in accordance with the
tance of compliance. Inmates who repeatedly refuse to ASHP Statement on the Formulary System, the ASHP
take medications should be counseled by a pharmacist. Guidelines on Formulary System Management, the
• Policies should be developed regarding the adminis- ASHP Technical Assistance Bulletin on Drug Formu-
tration of medication to inmate-patients assigned to laries, and the ASHP Technical Assistance Bulletin on
jobs or on work-release programs. the Evaluation of Drugs for Formularies.6–9
• Policies and procedures should be developed to ensure • Drug products selected for formulary inclusion should
continuity of therapy upon release. Released inmates serve the needs of the inmate-patient population and
should have access to a limited supply of medications; at the same time be as cost-effective as possible. The
either the drugs should be provided upon release or re- pharmacy director should ensure that cost is not the
leased inmates should have a prescription order trans- only determinant for drug product selection.
mitted to the pharmacy of their choice. • Procedures should exist for the provision of nonfor-
mulary medications when necessary.
Documentation • The pharmacy director should, in conjunction with the
facility’s medical staff, maintain policies and proce-
dures for the use of investigational medications that
• Medication administration records should be reviewed
ensure adherence to the rights of inmate-patients.
by the pharmacist at least monthly for proper docu-
mentation of medication administration. • The pharmacy director should, in conjunction with the fa-
cility’s psychiatrist or medical director, maintain policies
• Review of the medication administration record should
and procedures for the use of psychotropic medications.
include assessments of documentation of medications
administered, doses, frequency of administration, com- • The pharmacy director should be familiar with laws
and regulations governing the treatment of patients
pliance, start and stop dates, and medication allergies.
with AIDS and make appropriate procedural allow-
• Pharmacist interventions should be documented in pa-
ances for the treatment of these patients.
tients’ medical records.
• The pharmacist should have input into decisions about
• The pharmacist should document refills in accordance
infection control policies and procedures pertinent to
with state laws and regulations.
medication use.
• Policies and procedures should exist for documenting
the transportation of medication among separate sites
in correctional facilities, including accountability from Quality Improvement
pickup to drop off.
• A consistent pattern of refusal by an inmate-patient to • The pharmacy director should encourage the develop-
take medication should be documented in the patient’s ment of and participate in an ongoing quality improve-
medical record. ment process that includes drug-use evaluation and
drug-regimen review.
• Policies and procedures should exist for the proper
documentation of the receipt, placement in inventory,
dispensing, administration, and destruction of con- Drug Information
trolled substances.
• A program should exist for regular education of health
care and pertinent non-health-care personnel with re-
Emergency Services spect to medication use.
• An up-to-date resource library that includes current
• A pharmacist should educate medical and correctional publications and those required by law and regulation
personnel on the proper use of medications stocked for should be maintained by the pharmacy.
emergency use.
• The pharmacist should provide drug consultations as
• A pharmacist should be available on an on-call basis in required to nurses, physician assistants, physicians,
case of emergencies. and any others involved in initiating, executing, and
• Policies and procedures for the use of emergency kits monitoring medication therapy.
of medications in life-threatening situations should ex-
• The pharmacist should educate and counsel inmate-
ist. These kits should be maintained by a pharmacist. patients on the proper use of medications.
Research 5. American Society of Hospital Pharmacists. ASHP

guidelines for selecting pharmaceutical manufacturers
• Policies and procedures for the use of investiga- and suppliers. Am J Hosp Pharm. 1991; 48:523–4.
tional drugs within the correctional facility should 6. American Society of Hospital Pharmacists. ASHP
exist. (Additional guidance on pertinent policies and guidelines on formulary system management. Am J
procedures can be found in the ASHP Guidelines Hosp Pharm. 1992; 49:648–52.
for the Use of Investigational Drugs in Organized 7. American Society of Hospital Pharmacists. ASHP
Health-Care Settings.10) technical assistance bulletin on drug formularies. Am J
• The pharmacy director should adhere to the Federal Hosp Pharm. 1991; 48:791–3.
Regulations on Medical Research in Correctional 8. American Society of Hospital Pharmacists. ASHP
Facilities (45 C.F.R. 46, revised March 6, 1983) when technical assistance bulletin on the evaluation of drugs
devising policies and procedures for use of investiga- for formularies. Am J Hosp Pharm. 1988; 45:386–7.
tional drugs. 9. American Society of Hospital Pharmacists. ASHP
• Information on issues that affect pharmacy practice statement on the formulary system. Am J Hosp Pharm.
within the correctional environment (e.g., criminol- 1983; 1384–5.
ogy, medical-legal issues, endemic patient population)
should be maintained. guidelines for the use of investigational drugs in or-
ganized health-care settings. Am J Hosp Pharm. 1991;
48:315–9.
References
1. American Society of Hospital Pharmacists. ASHP These guidelines were reviewed in 2008 by the Council on Phar-
guidelines: minimum standard for pharmacies in insti- macy Practice and by the Board of Directors and were found to still
tutions. Am J Hosp Pharm. 1985; 42:372–5. be appropriate.
technical assistance bulletin on assessing cost- Approved by the ASHP Board of Directors, April 26, 1995.
containment strategies for pharmacies in organized Developed by the Council on Professional Affairs. Drafted for coun-
health-care settings. Am J Hosp Pharm. 1992; 49:155– cil review by Ronald L. Rideman.
60.
3. American Society of Hospital Pharmacists. ASHP Copyright © 1995, American Society of Health-System Pharmacists,
technical assistance bulletin on use of controlled sub- Inc. All rights reserved.
stances in organized health-care settings. Am J Hosp
Pharm. 1993; 50:155–501. The bibliographic citation for this document is as follows: American
4. American Society of Hospital Pharmacists. ASHP Society of Health-System Pharmacists. ASHP guidelines on phar-
technical assistance bulletin on drug distribution and maceutical services in correctional facilities. Am J Health-Syst
control. Am J Hosp Pharm. 1980; 37:1097–103. Pharm. 1995; 52:1810–3.
Research
514 Research–Positions
Research
Research on Drug Use in Obese Patients (1515) pharmacy department before submitting a proposal to the
Source: Council on Therapeutics IRB; further,
To encourage drug product manufacturers to conduct phar- To advocate that IRBs include pharmacists as voting
macokinetic and pharmacodynamic research in obese pa- members; further,
tients to facilitate safe and effective dosing of medications To advocate that IRBs inform pharmacy of all ap-
in this patient population, especially for medications most proved clinical research involving drugs within the hospital
likely to be affected by obesity; further, or health system; further,
To encourage manufacturers to include in the Food To advocate that pharmacists act as liaisons between
and Drug Administration (FDA) – approved labeling de- IRBs and pharmacy and therapeutics committees in the
tailed information on characteristics of individuals enrolled management and conduct of clinical drug research studies;
in drug dosing studies; further, further,
To advocate that the FDA develop guidance for the To strongly support pharmacists’ management of the
design and reporting of studies that support dosing recom- control and distribution of drug products used in clinical re-
mendations in obese patients; further, search.
To advocate for increased enrollment and outcomes This policy was reviewed in 2011 by the Council on
reporting of obese patients in clinical trials of medications; Therapeutics and by the Board of Directors and was found
further, to still be appropriate.
To encourage independent research on the clinical sig-
nificance of obesity on drug use, as well as the reporting and Clinical Investigations of Drugs Used in Elderly and
dissemination of this information via published literature, Pediatric Patients (0229)
patient registries, and other mechanisms. Source: Council on Professional Affairs
This policy supersedes ASHP policy 1013. To advocate increased enrollment of pediatric and geriatric
patients in clinical trials of new medications; further,
Institutional Review Boards and Investigational Use of To encourage pharmacodynamic and pharmacoki-
Drugs (0711) netic research in geriatric and pediatric patients to facilitate
Source: Council on Pharmacy Practice the safe and effective use of medications in these patient
To support mandatory education and training on human sub- populations.
ject protections and research bioethics for members of insti- This policy was reviewed in 2011 by the Council on
tutional review boards (IRBs), principal investigators, and Therapeutics and by the Board of Directors and was found
all others involved in clinical research; further, to still be appropriate.
To advocate that principal investigators discuss their
proposed clinical drug research with representatives of the
Research–Statement 515
ASHP Statement on Pharmaceutical Research

in Organized Health-Care Settings
Pharmacy practice is grounded in the physicochemical, bio- • Clinical research, such as the therapeutic characteriza-
logical, and socioeconomic sciences. Hence, the continued tion, evaluation, comparison, and outcomes of drug
and future success and self-esteem of the profession are de- therapy and drug treatment regimens.
pendent on the expanded knowledge base that can be pro- • Health services research and development, including
duced through dynamic and rigorous scientific research and behavioral and socioeconomic research such as re-
development. This research, to be meaningful and produc- search on cost–benefit issues in pharmaceutical care.
tive in terms of pharmacy’s needs and goals in organized • Operations research, such as time and motion studies
health-care settings, must include the participation of phar- and evaluation of new and existing pharmacy pro-
macists practicing in those settings. grams and services.
Pharmacists in organized health-care settings function
in cooperation with other health-care professionals. They This research will be a critical contribution of phar-
contribute a unique expertise to the drug-related aspects of macy to health care and must be fostered by all facets of the
patient care and take personal professional responsibility profession.
for the outcomes from the pharmaceutical care they provide
to patients. Improvements in drug therapy depend on new
knowledge generated by scientific research. Thus, pharma-
References
cists in organized health-care settings have a professional
1. American Society of Hospital Pharmacists. ASHP guide-
obligation to participate actively in and increase pharmacy-
lines for pharmaceutical research in organized healthcare
related and drug-related research efforts.1,2
settings. Am J Hosp Pharm. 1989; 46:129–30.
Reflecting the collaborative nature of contemporary health
care, this research should be multidisciplinary to be most ben-
guidelines for the use of investigational drugs in or-
eficial. Thus, ASHP encourages pharmacists with a researchable
ganized healthcare settings. Am J Hosp Pharm. 1991;
idea or problem to seek the advice and active participation of
48:315–9.
people and organizations with scientific expertise such as
• College faculty (especially college of pharmacy faculty). Approved by the ASHP Board of Directors, November 14, 1990,
• Other staff and departments within the setting. and the ASHP House of Delegates, June 3, 1991. Revised by the
• Staff and departments in other health-care organizations. ASHP Council on Professional Affairs. Supersedes a previous state-
• Industrial research personnel and laboratories. ment, “ASHP Statement on Institutional Pharmacy Research,” ap-
proved by the ASHP House of Delegates on June 3, 1985, and the
It also is appropriate for pharmacists to function as ASHP Board of Directors on November 14–15, 1984.
principal investigators in research projects.
ASHP encourages pharmacists to increase their in- Copyright © 1991, American Society of Hospital Pharmacists, Inc.
volvement in the following kinds of scientific research and All rights reserved.
development:
• Pharmaceutical research, including the development Society of Hospital Pharmacists. ASHP statement on pharmaceuti-
and testing of new drug dosage forms and drug prepa- cal research in organized health-care settings. Am J Hosp Pharm.
ration and administration methods and systems. 1991; 48:1781.
516 Research–Guidelines
ASHP Guidelines on Clinical Drug Research

Purpose for Human Use. The guideline offers a unified standard for
designing, conducting, recording, and reporting trials that
The use of drug products to manage diseases and improve involve the participation of human subjects in the United
patients’ quality of life is increasing as more effective States, Japan, and the European Union. In particular, the
and safer agents become available. Research to develop guideline provides a clearer understanding of behavioral and
these agents is occurring in health system practice settings compliance standards for regulated drug research.
throughout the world. The credibility of this research and the
protection of human subjects is a major responsibility of all Basic Principles
health professionals involved.
ASHP believes pharmacists should play a pivotal role The institutional components and practice settings of health
in the management of drugs used in the conduct of clinical systems participating in clinical drug research shall develop
research.1–3 Pharmacists have become essential components mechanisms, generally in the form of policies and proce-
of health system infrastructures supporting clinical research dures, for the approval, planning, and implementation of
with both approved drugs and investigational drugs.a,b protocols. Good clinical practices, consistent with national
Pharmacists’ roles in clinical research generally fall into one and international standards, are the cornerstone of drug re-
of two categories: (1) drug storage, preparation, and record search in humans. Principles consistent with good clinical
keeping, frequently through an investigational drug service, practices include the following:
and (2) serving as a principal investigator or a subinvestiga-
tor, manager, or coordinator within a research team that may 1. An organization participating in human drug research
include other health care professionals, research sponsors, studies shall ensure that such studies contain adequate
monitors, contract research organizations, institutional re- safeguards for human subjects, its staff, and the scien-
view boards (IRBs), and institutional administrators. tific integrity of the study. There shall be written poli-
The purposes of this document are to (1) outline the prin- cies and procedures for the approval, management,
ciples of clinical research, (2) describe the roles of participants in and control of research involving investigational (not
clinical research, (3) define pharmacists’ roles in the use of drugs FDA-approved) drugs and post-marketing studies of
in clinical research, and (4) provide guidance to pharmacists and FDA-approved drugs used in a research protocol. All
others responsible for the medication management component of research team members shall be fully informed about
clinical research. ASHP believes these guidelines are applicable and comply with these policies and procedures.
to clinical research conducted in any health-system practice set- 2. The clinical trial shall have adequate prior informa-
ting. These guidelines are an interpretation of federal laws, regu- tion to justify use of human subjects, have a clearly
lations, and standards for pharmacy practice in health systems. defined protocol, and have received IRB approval be-
They should be used in conjunction with the applicable federal fore implementation.
and state laws and regulations, not as a substitute for them. This 3. All drug studies shall meet accepted ethical, legal, and
document uses the term shall when the content is based on law or scientific standards and be conducted by appropriately
regulation and the term should for advice based on other guide- qualified investigators. Investigator qualifications, such
lines, professional judgment, or expert opinion. as prior training and experience in research and with cer-
tain disease states, are required to be reviewed by IRBs,
Background study sponsors, and FDA if the research will be submitted
under an investigational new drug application (IND).
The United States has benefited from a system for researching 4. Every member of the research team shall be qualified by
and marketing drug products that is codified in federal and state experience or training to perform his or her respective role.
laws and regulations. The federal Food, Drug, and Cosmetic 5. All subjects must freely provide informed consent
Act and its amendments4 regulate drug product quality, safety, (documented in writing) before treatment with study
and effectiveness. The Food and Drug Administration (FDA) drugs is begun. Accurate and complete information
is the federal agency charged with enforcing the act and pro- about the study’s objectives, risks, and benefits must
mulgating regulations for its implementation. FDA regulations be provided before consent is obtained from the sub-
concerning the conduct of clinical research with drug products ject or his or her legally authorized representative. No
of particular relevance for health-system pharmacists include unreasonable inducements (i.e., coercion or undue in-
Title 21 Code of Federal Regulations (CFR) Part 50, Protection fluence) shall be offered to subjects to encourage their
of Human Subjects; Title 21 CFR Part 56, Institutional Review participation in the study.
Boards; and Title 21 CFR Part 312, Investigational New Drug 6. All clinical trial data shall be recorded and the records
Application. Also applicable are the Department of Health and stored in such a way that the subject’s rights of privacy
Human Services regulations in Title 45 CFR Part 46, Protection and confidentiality are protected. All records shall be
of Human Subjects. Requirements for and guidance on compli- managed in a way that permits accurate reporting, ver-
ance with regulations are provided in FDA Information Sheets. ification, and retrieval after archiving.
FDA has also published the Good Clinical Practice 7. Qualified pharmacists and other nonphysicians may
Consolidated Guideline5 that was prepared under the aus- serve as principal investigators as long as medical de-
pices of the International Conference on Harmonisation of cisions made for the subjects are always the responsi-
Technical Requirements for Registration of Pharmaceuticals bility of a qualified physician or dentist.
Research–Guidelines 517
Health-System Organization 4. Investigational drugs shall be used only under the

supervision of the principal investigator or authorized
and Oversight
subinvestigators, all of whom shall be members of the
professional staff. The determination of qualifications
The health system should have processes for the adminis-
for investigators is the responsibility of the sponsor,
tration of research that ensure that the aforementioned prin-
IRB, and FDA when appropriate. Properly qualified
ciples are upheld and the following responsibilities are met.
pharmacists with experience and training in research
may serve as principal investigators or subinvestigators.
1. The health system shall be able to review and approve
5. The principal investigator or designee is responsible
a protocol in the context of federal, state, and local laws
for obtaining informed consent from each subject who
and regulations. The health system should consider
is eligible for participation in the study (i.e., meets
whether its own sponsored research or intellectual prop-
inclusion and exclusion criteria).c The informed con-
erty development of drugs requires an IND for drugs
sent process shall conform to current federal and state
not commercially available and approved drugs for
regulations. IRB approval of the consent form (and
unlabeled uses. An IND may be required if proposed
assent form for minors) is required. Review by legal
research on the use of a marketed drug is intended to
counsel may be desirable. The following points shall
support the sponsor’s change in drug labeling, advertis-
be included in the consent document and in an accom-
ing, or indications for use; a significant increase in risk;
panying oral explanation by the investigator:
or a change in dosage level or route of administration.
a. That the trial involves research.
The health system should consult FDA for guidance.
b. The nature and purpose of the study and its ex-
2. The health system should have a mechanism for review
pected benefits and foreseeable risks or discom-
and approval of the financial aspects of drug research,
forts. The name and telephone number of the
whether the study is sponsored by government agen-
principal investigator and persons to contact for
cies, foundations, or the pharmaceutical industry or is not
questions about the study or drug.
sponsored.6 Financial aspects may include contractual
c. A balanced description of the alternative treat-
agreements stipulating cost recovery for resources, in-
ments available, including their respective risks
tellectual property agreements, insurance provisions, in-
and benefits.
demnification terms, and conflict-of-interest statements.
d. A general description of the study procedures,
Cost identification, allocation, and recovery mechanisms
identification of any procedures that are experi-
are imperative items for review and approval.
mental, expected length of therapy with the drug,
3. As required by federal regulation, clinical research
and the subject’s responsibilities. The name(s) of
shall be reviewed and approved by an IRB or equiva-
the investigational drug(s), including brand and
lent committee (21 CFR 56.109). This committee shall
generic names of commercial products.
evaluate each proposed clinical research study in terms
e. A statement that (1) participation is voluntary, (2) the
of human subject protections and compliance with rec-
subject may withdraw from the study at any time,
ognized ethical, legal, and scientific standards. No clini-
(3) refusal to participate in or withdrawal from the
cal study may be initiated unless approved in writing by
study will involve no penalty or loss of benefits to
the committee. Spoken IRB approval may be granted
which the subject is otherwise entitled, and (4) the
in emergency situations for a single subject’s access to
principal investigator may remove the subject from the
an investigational drug, but emergency use shall be re-
study if circumstances warrant. The investigator shall
ported to the IRB within five days; subsequent use re-
supply any new information that may affect a subject’s
quires full IRB review. Studies on the use of drugs in
desire to continue in a study.
emergency or critical care settings do not in themselves
f. The name and signature of the subject (or his or
qualify for single-subject approval and emergency ex-
her legally authorized representative), the name
emption. Specific regulations govern research in the
and signature of the principal investigator or sub-
emergency setting and should be consulted in preparing
investigator, and the name and signature of the
protocols, IRB submissions, and consent procedures.c,7
person presenting the consent form, with lines for
Treatment IND protocols are also subject to
each to personally date the signature.
IRB review and approval. These protocols permit pa-
g. A statement of who will have access to any study
tient access to investigational drugs through a special
records that contain subject identifiers, including
program established by a sponsor. The physician and
monitoring personnel from the study sponsor or
patient must agree that use of the agent may be in the
FDA who may inspect the records to assess compli-
patient’s best interest and must document this agree-
ance with the study protocol and all regulations, or
ment on a consent form.
institutional personnel auditing the quality of clini-
The IRB shall monitor approved studies to ensure
cal research or financial transactions.
that they are carried out appropriately and that the pro-
h. Compensation or treatment available for a re-
tocols are reassessed at least annually. Health system
search-related injury.
policies and procedures shall provide guidance on the
i. Anticipated payments to subjects, pro rata terms,
conversion of human subjects to other therapies in the
or expenses subjects may incur. Any costs for
event that approval of an existing protocol is withdrawn
which the subject will be responsible.
by the IRB. The investigational-drug pharmacist, phar-
The consent form shall be as detailed as is prac-
macy director, or pharmacy director’s designee should
tical, with the goal of minimizing the amount of in-
be a member of the IRB and should be consulted by the
formation that must be presented orally yet enabling
committee whenever drug studies are reviewed.
comprehension by most persons reading the form. f. Bulk supplies of the investigational drug shall be
For non-English-speaking subjects the consent form properly stored and adequately secured. When
shall be in the subject’s own language when feasible, practical, all bulk supplies shall be stored in the
or adequate interpretation shall be provided. For pharmacy to ensure that storage, dispensing, ac-
children able to read, an assent form shall be used to countability, and security are in compliance with
document their participation in the research process. federal and state laws and regulations and with
The subject (or his or her representative) must have standards used by the pharmacy department.
adequate time to read the consent form before sign- g. There shall be a method for ensuring that only an
ing it and shall receive a copy of the signed and dated authorized practitioner or designee prescribes the
form, along with any amendments to it. The subject investigational drug.
shall retain a copy of the consent form. Additional h. Records of the amount of investigational drug re-
copies of the consent form shall be kept on file as received from the sponsor and of its disposition (e.g.,
quired by the sponsor, the IRB, the individual health amounts dispensed to subjects or returned to spon-
system, and the medical records department. sor) shall be maintained. These records shall be re-
Under certain protocols, patient drug or tained as required by regulation. Generally, records
medical information may be collected from exist- shall be maintained for at least two years after the
ing medical or pharmacy records. Pharmacists and date of an approved new-drug application (NDA)
investigators should consult the IRB to determine for the indication that is being investigated or, if
protocol-review and informed-consent require- the application is not approved or no application is
ments for any proposed studies. filed, for at least two years after the investigation
6. The principal investigator is responsible for the proper is discontinued and FDA is notified. Institutions
maintenance of case report forms and all other study should consider retaining records indefinitely. For
records required by the health system, the sponsor, and studies involving international sites, records shall
FDA. be maintained for 15 years after study closure. The
7. The health system’s medication-use system shall con- sponsor may also request that records be stored
tain the following elements concerning drugs used in longer than the minimum required time.
clinical research: i. If the subject is to receive the investigational drug
a. Drugs shall be properly packaged in accordance at another facility, suitable arrangements shall be
with all applicable federal and state laws, regula- made for transfer of the drug. Sufficient informa-
tions, and standards (e.g., FDA, The United States tion for safe use of the investigational drug, includ-
Pharmacopeia and The National Formulary ing copies of the subject’s signed consent form, the
[USP–NF], and the Poison Prevention Packaging study protocol, and the IRB approval letter, shall
Act). accompany the drug. The responsibilities of the
b. Drugs shall be labeled properly to ensure their safe facility to which the drug is transferred are based
use by the research and institutional staff and the on whether that facility is providing care incidental
subject. to or as a participant in the research protocol.8
c. There shall be a mechanism to ensure that j. The institution’s records on investigational-drug
sufficient supplies of the drugs will be always studies should be designed so that various descriptive
available for the duration of the study. reports (e.g., names of all drugs under study, names
d. A mechanism shall be in place to allow the phar- of subjects who have received a given drug) can
macist or other designated health care provider, be generated conveniently and expeditiously. Once
in a medical emergency during a randomized and a study is closed, a copy of all pharmacy-related
blinded trial, to break the blinding code and reveal records should be provided to the principal investi-
the identity of the study drug to other health care gator for storage. For its own records, the phar-
professionals. A reason to break the blind might be macy should have a mechanism for long-term stor-
the need for a treatment decision that can be made age. The drug control responsibilities previously
only with knowledge of drug assignment. described shall be assigned to a pharmacist. If a
e. Nurses, pharmacists, physicians, and other health pharmacist is not available, the investigator shall
care practitioners (e.g., respiratory therapists, physi- make arrangements to comply with these standards.
cian assistants) called on to administer or dispense
investigational drugs should have adequate written Pharmaceutical Services
information about (1) pharmacology (particularly ad-
verse effects), (2) storage requirements, (3) method A pharmacist should be responsible for ensuring that procedures
of dose preparation and administration, (4) disposal for the control of drugs used in clinical research are developed
of unused drug, (5) precautions to be taken, including and implemented. Each health system should develop a struc-
handling recommendations, (6) authorized prescrib- ture and procedures specific to its own needs and organization.
ers, (7) human subject safety monitoring guidelines,
and (8) any other material pertinent to safe and proper 1. A copy of the IRB-approved research protocol and in-
use of investigational drugs. These health care pro- vestigator’s brochure or drug data sheet (see item 2
viders should be informed about the overall study below), or both, and all amendments should be kept by
objectives and procedures and shall have available a pharmacist.
a complete copy of the protocol for reference. Under 2. Using the protocol and additional information (if needed)
all circumstances, investigational drugs shall be supplied by the principal investigator and sponsor, the
safely controlled, administered, and destroyed. pharmacist should prepare an investigational-drug data
sheet that concisely summarizes for the medical, nurs- possible hazards. There shall be a method for verify-
ing, and pharmacy staffs information pertinent to use ing that a valid, signed consent has been obtained. The
of the drug. This communication should contain, at a investigational drug shall be dispensed only on the
minimum order of an authorized investigator or designee.
a. Drug designation and common synonyms. 6. Educating patients and monitoring therapy (includ-
b. Dosage forms and strengths. ing adverse drug reaction monitoring) are two clinical
c. Usual dosage range, including dosage schedule functions that are particularly important and applica-
and route of administration. ble to investigational drugs. The protocol should spec-
d. Indications pursued in this study. ify the provision of these functions by the pharmacists,
e. Expected therapeutic effect to be studied. the authorized investigator(s), and other members of
f. Expected and potential adverse effects, including the research team.
symptoms of toxicity and their treatment. 7. At the conclusion of the study, the pharmacist shall
g. Drug–drug and drug–food interactions. return, transfer, or dispose of all unused investigational
h. Contraindications. drugs according to the specific instructions provided
i. Storage requirements. by the sponsor and in accordance with applicable
j. Instructions for dosage preparation and administra- regulations.
tion, including stability and handling guidelines. 8. The pharmacist should prepare an annual or semiannual
k. Instructions for disposition of unused doses. descriptive summary of investigational-drug use for the
l. Names and telephone numbers of principal and au- pharmacy director and pharmacy and therapeutics com-
thorized subinvestigators and study coordinators. mittee. This summary should include the number of
Confidential copies should be distributed to the studies in progress, a list of all drugs studied during the
appropriate pharmacy staff and all areas within previous period, and a financial statement.
the health system where the investigational drug 9. Drug costs and other expenses associated with drug
will be administered and the subjects monitored. studies (e.g., costs of record keeping and drug admin-
Through the pharmacy or health-system computer istration) should be properly allocated and reimbursed.
system, this information can be made available to Policies and procedures should address the role phar-
all staff members who need it. It is staff members’ macists play in billing sponsors, subjects, and third-
responsibility to become familiar with the infor- party payers for services and goods related to research.
mation in these data sheets and to not share the In general, sponsors and health systems cannot charge
information with persons who do not need it. subjects for an investigational drug. Sponsors may
3. When it is practical, investigational-drug supplies petition FDA for an exception. Health systems may
should be stored in a pharmacy. When the drug is charge subjects for drug preparation and other services
stored outside a pharmacy (e.g., small quantities in necessary to deliver a final product, as is customary
the investigator’s office or in clinics where the drug for delivery of services within the practice setting and
is administered), methods used by the investigator re- when sponsors do not reimburse for this service. The
sponsible for the drug shall be audited by a pharmacist anticipated costs of research should be described in
to ensure that storage, dispensing, accountability, and the consent form. Subjects must be advised that they
security comply with federal and state laws and regu- or their third-party payers are responsible for these
lations and with institutional policy. charges and that a third-party payer may refuse to pay
4. The pharmacist shall maintain a perpetual inventory for charges related to research.
record for investigational drugs stored in the pharmacy. 10. The investigational drugs shall be stored under appro-
This record shall contain the drug’s name, dosage priate environmental control in a limited-access area
form and strength, lot number, and expiration date; the separate from routine drug stocks and shall be inven-
name, address, and telephone number of the sponsor; toried on a regular basis.
the protocol number; and any other information 11. Pharmacists may be confronted with circumstances
needed for ordering the drug. Space shall be provided related to a patient who is receiving an investigational
for recording data on the disposition of the drug drug provided by an investigator at a nonaffiliated
(amounts received, transferred, wasted, or dispensed, practice setting and is admitted to their own practice
with dates; the names of or codes for persons receiving setting for care incidental to the research protocol.
the drug; and the names of prescribers), the amount Pharmacists should have a policy for managing inves-
currently on hand, the minimum reorder level, and the tigational drugs under those circumstances that meets
recorder’s initials. The inventory record shall reflect FDA guidelines.8
drug doses that were dispensed but not administered 12. Pharmacists must ensure the scientific integrity of drug
and were returned to the pharmacist. These records studies by managing access to treatment-assignment
are commonly audited by the sponsor, the sponsor’s records in blinded studies and by ensuring that the cor-
representatives, or FDA.9,10 rect drug was dispensed. The pharmacist, investigator,
5. The dispensing of investigational drugs should be in- and sponsor must agree on a procedure for unblinding
tegrated with the rest of the medication-use system, treatment assignment in emergencies.
including, but not limited to, order review, profile 13. Pharmacists who are assigned to manage investigational
maintenance, packaging, labeling, delivery, and qual- drugs may at times have to delegate certain dispensing
ity-assurance procedures. However, prescription la- activities to other pharmacists within the health system.
bels for investigational drugs shall be marked “inves- To ensure continuity of quality dispensing services, the
tigational drug” or otherwise distinguished from other responsible pharmacist should design and implement
labels. The label should also include an alert to any procedures for educating other members of the pharmacy
staff about the protocol and dispensing requirements. e. How the order is to be shipped (e.g., specific pack-
Often this can be accomplished by personal instruction age-shipping firms).
and by preparing written directives and references for f. Disposition of invoice or drug receipt form once
use by other pharmacists when they are called upon to the drug is received.
dispense an investigational drug. 6. The following information should be supplied by a
14. Pharmacists managing investigational drugs are in a sponsor or investigator to the pharmacist, preferably
unique position to monitor patient adherence to med- in an investigator’s brochure, as applicable:
ication regimens. Because of the requirement that a. Storage conditions required before and after prep-
medication dispensed and returned be accounted for, aration.
pharmacists can readily surmise whether study pa- b. Amounts and types of diluents for reconstitution
tients are consuming the medication in the prescribed and administration and the resulting final concen-
manner. At a minimum, pharmacists should counsel tration of active drug.
the investigator’s research staff with regard to patient c. Stability of the prepared (i.e., ready-to-administer,
adherence. Pharmacists’ skills in patient counseling reconstituted, or diluted) product and compatibil-
should be used to support the investigators’ efforts to ity with drug delivery systems, diluents or i.v. flu-
encourage patients to adhere to their protocols. ids, containers, i.v. tubing, and filters.
d. Known compatibility or incompatibility with other
Pharmaceutical Research products.
e. Light sensitivity.
Sponsors, Monitors, and f. Filtration needs.
Contract Research Organizations g. Expiration dates or retest dates.
h. Special instructions for preparation and admin-
The pharmaceutical company, or any study sponsor, that istration.
supports the use of investigational drugs in health systems i. Acceptable and recommended routes and methods
should receive reliable and valid data. The following rec- of administration, including rates of infusion for
ommendations will serve as a guide to the pharmaceutical injectable products.
industry or other study sponsors to ensure that investiga- j. Known adverse effects during or after administra-
tional drug use is managed appropriately and that studies are tion (e.g., pain, phlebitis, and nausea) and how to
conducted effectively, efficiently, and safely. avoid and treat them.
k. Usual dosage regimens and highest dose tested for
1. Drugs shall be properly packaged in accordance with specific disease states, including dosage expres-
all applicable federal and state laws, regulations, sions for prescribing and labeling that could mini-
and standards (e.g., FDA, USP–NF, and the Poison mize misreading and misinterpretation.
Prevention Packaging Act). l. Contraindications.
2. Drugs shall be properly labeled in accordance with ap- m. Drug interactions.
plicable laws, regulations, and standards. If possible, n. Special precautions for storage, handling, and dis-
ample space shall be left on the drug product container posal of the drugs, including cytotoxic and hazard-
for further labeling by the pharmacist. Expiration dates ous drugs. For all hazardous drugs, the pharmacy
and lot numbers should also be noted on the label. department must be supplied with material safety
3. A 24-hour telephone number should be available to study data sheets.
personnel, including the principal investigator and the o. Pharmacology, including mechanism of action.
pharmacy department. In the event of an emergency, in- p. Pharmacokinetic characteristics.
formation should be available pertaining to (1) adverse 7. If all unused drugs are to be returned to the sponsor,
effects and their treatment, (2) emergency protocol man- information regarding storage and return procedures
agement and dosing and administration guidelines, (3) should be provided to the pharmacist. Drugs that are
the ability to break a “blinded code” to determine the contaminated, outdated, or otherwise unsuitable should
treatment regimen, and (4) the mechanism for procuring be returned to the sponsor or destroyed according to
a supply of medication under an emergency-use protocol. the institution’s policies and procedures and applicable
4. Company representatives should be designated to han- laws and regulations. These options should be agreed
dle routine requests, such as those for additional forms on beforehand by the sponsor and the pharmacist.
and resupply of investigational drugs. If possible, 8. A complete current copy of the research protocol and in-
direct telephone or fax access should be available to vestigator’s brochure should be supplied to the pharmacist.
expedite requests. Additional educational materials for use in informing phar-
5. Investigational drugs should be shipped to the princi- macists, physicians, and nurses about the investigational
pal investigator in care of a pharmacist. The following drug and research protocol should also be provided.
information about procurement should also be sup- 9. An appropriate allotment of research funds should be
plied to the pharmacist: designated as reimbursement for
a. Name and telephone number of the sponsor’s a. Personnel.
study monitor or field representative responsible b. Storage facilities.
for drug ordering. c. Equipment.
b. Estimated time for fulfillment of orders. d. Ancillary products, such as diluents, syringes, and
c. Limits on quantities that can be ordered. needles.
d. Special ordering instructions. e. Forms and miscellaneous clerical materials.
f. Computer and other data-processing costs. Suggested Internet Source
g. Other expenses attributable to the pharmacist’s in-
volvement in the study. Food and Drug Administration information for clinical
h. Apportioned pharmacy overhead costs. investigators. http://www.fda.gov/cder/about/smallbiz/
1 0. Sponsors should respond to requests for information from clinical_investigator.htm.
pharmacists involved in treating patients without formal
research approval at that institution. This may occur, for
Glossaryd
example, when a patient is hospitalized (e.g., in an emer-
gency) at a facility other than his or her usual care site.
Adverse Drug Reaction (ADR): In preapproval clinical expe-
11. When seeking marketing approval for an investigational
rience with a new medicinal product or its new usages,
drug, sponsors should consult pharmacists, physicians,
particularly since the therapeutic dose(s) may not be es-
and others involved in their investigational-drug stud-
tablished, all noxious and unintended responses to a me-
ies for information. Because of their experience with the
dicinal product related to any dose should be considered
drug, these practitioners can supply valuable suggestions
adverse drug reactions. “Responses to a medicinal prod-
for labeling, packaging, palatability, routes of adminis-
uct” means that a causal relationship between a medici-
tration, and other dosage form characteristics, as well as
nal product and an adverse event is at least a reasonable
information regarding patient monitoring and education.
possibility (i.e., that the relationship cannot be ruled out).
12. The sponsor of an investigational drug study should
An ADR to a marketed medicinal product is a re-
provide final closure details within six months of trial
sponse to a drug that is noxious and unintended and
completion. This includes prompt notification of clo-
that occurs at doses normally used in humans for pro-
sure, directions for drug disposition, and final audits of
phylaxis, diagnosis, or therapy of diseases or for modi-
all study records.
fication of physiological function.
13. These recommendations should also apply to the
Adverse Event (AE): An AE is any untoward medical event
postmarketing approval of drugs under study for new
that occurs in a patient or clinical investigation subject
indications or diseases.
administered a pharmaceutical product and that does not
necessarily have a causal relationship to this treatment.
References An AE can therefore be any unfavorable and unintended
sign (including an abnormal laboratory finding), symp-
1. Stolar MH, ed. Pharmacy-coordinated investigational tom, or disease temporally associated with the use of a
drug services. Revised ed. Bethesda, MD: American medicinal (investigational) product, whether or not re-
Society of Hospital Pharmacists; 1986. lated to the medicinal (investigational) product.
2. American Society of Health-System Pharmacists. Audit: A systematic and independent examination of trial-
ASHP guidelines: minimum standard for pharmacies related activities and documents to determine whether
in hospitals. Am J Health-Syst Pharm. 1995; 52:2711– the evaluated trial-related activities were conducted
7. and the data were recorded, analyzed, and accurately
3. American Society of Hospital Pharmacists. ASHP reported according to the protocol, sponsor’s standard
statement on the use of medications for unlabeled operating procedures, good clinical practice, and the
uses. Am J Hosp Pharm. 1992; 49:2006–8. applicable regulatory requirements.
4. Federal Food, Drug, and Cosmetic Act (21 U.S.C. 301 Audit Report: A written evaluation by the sponsor’s auditor
et seq.) 1938, as amended. of the results of the audit.
5. Food and Drug Administration, Department of Health Case Report Form: A printed, optical, or electronic document
and Human Services. International conference on designed to record all of the protocol-required informa-
harmonisation; good clinical practice consolidated tion to be reported to the sponsor on each trial subject.
guideline. Fed Regist. 1997; 62:25692–709. Clinical Trial or Study: Any investigation in human sub-
6. Wermeling DP, Piecoro LT, Foster TS. Financial im- jects that is intended to discover or verify the clini-
pact of clinical research on a health system. Am J cal, pharmacologic, or other pharmacodynamic effects
Health-Syst Pharm. 1997; 54:1742–51. of an investigational product, to identify any adverse
7. Bailey EM, Habowski SR. How to apply for emer- reactions to an investigational product, or to study ab-
gency use of an investigational agent. Am J Health- sorption, distribution, metabolism, and excretion of an
Syst Pharm. 1996; 53:208–10. investigational product with the object of ascertaining
8. Food and Drug Administration. Use of investigational its safety, efficacy, or both. (The terms clinical trial
products when subjects enter a second institution. and clinical study are synonymous.)
IRB operations and clinical investigation information Clinical Trial/Study Report: A written description of a trial
sheet. http://www.fda.gov/oc/oha/useofinv.html (ac- or study of any therapeutic, prophylactic, or diagnostic
cessed August 25, 1997). agent conducted in humans, in which the clinical and
9. Food and Drug Administration. Institutional review statistical description, presentations, and analyses are
board inspections. IRB operations and clinical inves- fully integrated into a single report.
tigation information sheet. http://ww.fda.gov/oc/oha/ Contract Research Organization: A person or organiza-
institut.html (accessed August 25, 1997). tion (commercial, academic, or other) contracted by
10. Food and Drug Administration. Inspections of clini- the sponsor to perform one or more of a sponsor’s
cal investigators. IRB operations and clinical inves- trial-related duties and functions.
tigation information sheet. http://ww.fda.gov/oc/oha/ Direct Access: Permission to examine, analyze, verify, and
inspect.html (accessed August 25, 1997). reproduce any records and reports that are important
in the evaluation of a clinical trial. Any party (e.g., death, is life-threatening, requires inpatient hospital-
domestic and foreign regulatory authorities, spon- ization or prolongation of existing hospitalization, re-
sors, monitors, and auditors) with direct access should sults in persistent or significant disability or incapac-
take all reasonable precautions within the constraints ity, or is a congenital anomaly or birth defect.
of the applicable regulatory requirements to maintain Source Data: All information in original records and certi-
the confidentiality of subjects’ identities and sponsors’ fied copies of original records of clinical findings, ob-
proprietary information. servations, or other activities in a clinical trial that is
Documentation: All records, in any form (including but not necessary for the reconstruction and evaluation of the
limited to written, electronic, magnetic, and optical trial. Source data are contained in source documents
records and scans, roentgenograms, and electrocardio- (original records or certified copies).
grams) that describe or record the methods, conduct, Source Documents: Original documents, data, and records
or results of a trial, the factors affecting a trial, and the (e.g., hospital records, clinical and office charts, labo-
actions taken. ratory notes, memoranda, subjects’ diaries or evalua-
Essential Documents: Documents that individually and tion checklists, pharmacy dispensing records, recorded
collectively permit evaluation of the conduct of a data from automated instruments, copies or transcrip-
study and the quality of the data produced. tions certified after verification as being accurate and
Good Clinical Practice: A standard for the design, conduct, complete, microfiches, photographic negatives, micro-
performance, monitoring, auditing, recording, analy- film or magnetic media, roentgenograms, and subject
sis, and reporting of clinical trials that provides assur- files and records kept at the pharmacy, the laborato-
ance that the data and reported results are credible and ries, and the medicotechnical departments involved in
accurate and that the rights, integrity, and confidential- the clinical trial).
ity of trial subjects are protected. Sponsor: An individual, a company, an institution, or an or-
Independent Ethics Committee: An independent body ganization that takes responsibility for the initiation,
(institutional, regional, national, or supranational re- management, or financing of a clinical trial.
view board or committee), constituted of medical or Sponsor–Investigator: An individual who both initiates
scientific professionals and nonmedical or nonscien- and conducts, alone or with others, a clinical trial, and
tific members, whose responsibility it is to ensure the under whose immediate direction the investigational
protection of the rights, safety, and well-being of human product is administered to, dispensed to, or used by
subjects involved in a trial and to provide public assur- a subject. The term does not include any person other
ance of that protection by, among other things, review- than an individual (e.g., it does not include a corpora-
ing and approving or providing favorable opinion on tion or an agency). The obligations of a sponsor-inves-
the trial protocol and the suitability of the investigators, tigator include both those of a sponsor and those of an
the facilities, and the methods and material to be used investigator.
in obtaining and documenting informed consent of the
trial subjects.
a
Informed Consent: A process by which a subject volun- In this document investigational drugs are defined as those that are
tarily confirms his or her willingness to participate being considered for but have not yet received marketing approval
in a particular trial, after having been informed of all by FDA for human use and those that have FDA approval for at least
aspects of the trial that are relevant to the decision to one indication but are being studied for new indications, new routes
participate. Informed consent is documented by means of administration, or new dosage forms.
b
of a written, signed, and dated form. The principles and procedures described here are applicable to all
Investigator’s Brochure: A compilation of clinical and clinical drug studies, not just those involving investigational drugs.
c
nonclinical data on an investigational product that are In certain emergency situations, prior consent may be waived
relevant to the study of the product in human subjects. (21 CFR 50.24).
d
Monitoring: Overseeing the progress of a clinical trial and Definitions selected from reference 5.
ensuring that it is conducted, recorded, and reported
in accordance with the protocol, standard operating These guidelines were reviewed in 2003 by the Council on
procedures, good clinical practice, and the applicable Professional Affairs and by the Board of Directors and were found
regulatory requirements. to still be appropriate.
Monitoring Report: A written report from the monitor to
the sponsor after each site visit or other trial-related Approved by the ASHP Board of Directors, November 15,
communication, according to the sponsor’s standard 1997. Developed by the ASHP Council on Professional Affairs.
operating procedures. Supersedes the ASHP Guidelines for the Use of Investigational
Protocol: A document that describes the objectives, design, Drugs in Organized Health-Care Settings, dated November 14,
methods, statistical considerations, and organization of 1990.
a trial. The protocol usually also gives the background
and rationale for the trial, but these could be provided Copyright © 1998, American Society of Health-System Pharmacists,
in other protocol-referenced documents. (Throughout Inc. All rights reserved.
the ICH GCP Guideline, the term protocol refers to
protocol and protocol amendments.) The bibliographic citation for this document is as follows:
Serious Adverse Event or Serious Adverse Drug Reaction: American Society of Health-System Pharmacists. ASHP guide-
Any untoward medical event that occurs in a patient lines on clinical drug research. Am J Health-Syst Pharm. 1998;
or subject receiving a drug at any dose and results in 55:369–76.
ASHP Guidelines for Pharmaceutical Research

in Organized Health-Care Settings
The promotion of research in the health and pharmaceuti- 3. Reasoning—Deduction. The scientist deduces the
cal sciences and in pharmaceutical services is a purpose of consequences of the formulated hypothesis. The sci-
the American Society of Hospital Pharmacists, as stated in its entist may find that the deductions reveal a new prob-
Charter.1 In keeping with this purpose, pharmacists in orga- lem that is quite different from the original one. On
nized health-care settings should understand the (1) basic need the other hand, deductions may lead to the conclusion
for research and systematic problem solving in pharmacy prac- that the problem cannot be solved with existing techni-
tice; (2) fundamental scientific approach; (3) basic components cal tools. Such reasoning can help lead to wider, more
of a research plan; (4) process of documenting and reporting basic, and more significant problems as well as to
findings; and (5) responsibilities of investigators with respect to more narrow (testable) implications of the original
patients, employers, grantors, and science in general. hypothesis.
In its purest form, scientific research is the systematic, 4. Observation—Test—Experiment. If the problem has
controlled, empirical, and critical investigation of hypothetical been well stated, the hypotheses have been adequately
propositions (theories) about presumed relationships among nat- formulated, and the implications of the hypotheses
ural phenomena.2 Aspects of the research process (e.g., problem have been carefully deduced, the next step is to test
definition, systematic data gathering, interpretation, and report- the relationships expressed by the hypotheses, that is,
ing), however, are also applicable to resolving specific practice the relationships among the variables. All testing is
problems. Independent, intraprofessional, and interdisciplinary for one purpose: putting the relationships among the
collaborative research and problem solving are encouraged. variables to an empirical test. It is not the hypotheses
that are tested but the deduced implications of the hy-
Need potheses. On the basis of the research evidence, each
hypothesis is either accepted or rejected.
Since pharmacy is based on the theories of the pharmaceu-
tical, medical, and social sciences, pharmacy’s advance- Components of a Research Plan
ment is linked to advancement in those sciences. Scientific
inquiry, through formal research and systematic problem Formal research frequently requires the development of a written
solving, leads to an expansion of knowledge and thus to ad- plan (protocol or proposal). In funded research, the plan may take
vancement. Both research and systematic problem solving the form of a grant application. A typical plan might include
in organized health-care settings are needed for developing
knowledge in pharmaceutics and drug therapy and for eval- 1. A problem statement.
uation, modification, and justification of specific practices. 2. A review of available literature on the subject.
Therefore, an understanding of the research process is im- 3. The objectives for the project, including the hypothe-
portant to pharmacists in such settings. ses and the to-be-tested relationships among variables.
Primary areas for research by pharmacists in organized 4. A description of the methodology to be used.
health-care settings are those in which pharmacists possess 5. A description of statistical analyses to be applied to the
special expertise or unique knowledge. These areas include data collected.
drug therapy, pharmaceutics, bioavailability, pharmacy prac- 6. A budget and time frame for the project (where
tice administration, sociobehavioral aspects of pharmaceuti- applicable).
cal service systems, and application of information handling 7. The expected applicability of the research findings.
and computer technology to pharmacy practice.
Documentation and Reporting
The Scientific Approach
The structure of a research report is similar to the structure
Aspects of the scientific approach may be applied to formal of a research plan. A typical outline is as follows:
research and systematic problem solving. The scientific ap-
proach consists of four basic steps: 1. Problem.
a. Theories, hypotheses, and definitions.
1. Problem—Obstacle—Idea.3 The scientist experiences b. Previous research: the literature.
an obstacle to understanding or curiosity as to why 2. Methodology.
something is as it is. The scientist’s first step is to ex- a. Sample and sampling method.
press the idea in some reasonably manageable form, b. Experimental procedures and instrumentation.
even if it is ill defined and tentative. c. Measurement of variables.
2. Hypothesis. The scientist looks back on experience for d. Statistical methods of analysis.
possible solutions—personal experience, the literature, e. Pretesting and pilot studies.
and contacts with other scientists. A tentative proposition 3. Results, interpretation, and conclusions.
(hypothesis) is formulated about the relationship between
two or more variables in the problem; for example, “If The statement of the problem sets the general stage
such and such occurs, then so and so results.” for the reader and may be in question form. A common
practice is to state the broader, general problem and then Employee investigators bear responsibility for helping
to state the hypotheses, both general and specific. All im- their organizations differentiate true, objective research from
portant variables should be defined, both in general and in product marketing trials and promotions that may purport to
operational terms, giving a justification for the definitions be research projects. Grants for bona fide research typically
used, if needed. bear a direct cost-recovery relationship to projects and typi-
The general and research literature related to the prob- cally involve the direct transfer of grant funds from grant-
lem is discussed to explain the theoretical rationale of the ors to the employee investigator’s employer organization.
problem, to tell the reader what research has and has not Specific institutional policies vary widely, but employee
been carried out on the problem, and to show that this par- investigators can generally better fulfill their fiduciary re-
ticular investigation has not been conducted before (except sponsibilities when funds are not distributed directly from
in the case of validating research). grantors to investigators. In keeping with their fiduciary
The methodology section should meticulously de- responsibilities and their responsibility to be scientifically
scribe what was done so as to enable another investigator objective, investigators should be wary of arrangements
to reproduce the research, reanalyze the data, and arrive at in which prospective grantors offer inducements of value
unambiguous conclusions about the adequacy of the meth- (gifts, trips, experiences, publicity, publications, etc.) to in-
ods. This section should tell what samples were used, how vestigators, institutions, or patients before, during, or after
they were selected, and why they were selected. The means the completion of proposed projects.
of measurement of the variables should be described. The Investigators should make legitimate efforts to docu-
data analysis methods should be outlined and justified. ment publicly the findings of research in scientific, objec-
Where pilot studies and pretesting were used, they should tively refereed publications.
be described.
Results and data should be condensed and expressed References
in concise form. Limitations and weaknesses of the study
should be discussed. The question of whether the data sup- 1. American Society of Hospital Pharmacists. Governing
port the hypotheses must be foremost in the mind of the re- documents of the American Society of Hospital
port writer. Everything written should relate the results and Pharmacists. Bethesda, MD: American Society of
data to the problem and the hypotheses. Hospital Pharmacists; 1984.
2. Kerlinger F. Foundations of behavioral research. New
Investigators’ Responsibilities York: Holt, Rinehart and Winston; 1964:13.
3. Dewey J. How we think. Boston: Heath; 1933:106–18,
Investigators bear a general responsibility to be scientifically as adapted to the scientific framework by Kerlinger, op
objective in their research inquiries, conclusions, and reports. cit., p 13–5.
They bear a responsibility for being methodical and meticu- 4. American Society of Hospital Pharmacists. ASHP
lous in the gathering of research data. They also bear both guidelines for the use of investigational drugs in insti-
a fiduciary and a reporting responsibility to employers and tutions. Am J Hosp Pharm. 1983; 40:449–51.
grantors. In general, employee investigators are at least par-
tially responsible to their employer organizations in the choice
of research topics. Research funded from sources outside an Approved by the ASHP Board of Directors, September 30, 1988.
investigator’s organization may impose additional contractual Developed by the Council on Professional Affairs. Supersedes
obligations on the investigator and the organization. the “ASHP Guidelines for Scientific Research in Institutional
In research involving patients, investigators are re- Pharmacy” approved on November 15, 1977.
sponsible for protecting patients from harm while the
patients are participating in the research. All research Copyright © 1989, American Society of Hospital Pharmacists, Inc.
involving patients should be reviewed and approved, be- All rights reserved.
fore initiation, by an institutional review board. Written,
informed consent should be obtained from every patient The bibliographic citation for this document is as follows: American
participating in each research project.4 Meticulous record- Society of Hospital Pharmacists. ASHP guidelines for pharmaceuti-
keeping is required regarding the clinical experience of pa- cal research in organized health-care settings. Am J Hosp Pharm.
tients participating in research projects. 1989; 46:129–30.
ASHP
Therapeutic Position Statements
526 ASHP Therapeutic Position Statements
ASHP Therapeutic Position Statement

on the Cessation of Tobacco Use
Position addressed by clinicians. Despite the proven negative health
consequences of tobacco use and the fact that approximately
The American Society of Health-System Pharmacists 70% of smokers want to quit,5 20.8% of the U.S. adult
(ASHP) discourages all use of tobacco products and sup- population continues to smoke either every day (16.7%) or
ports evidence-based tobacco-control policies and activities some days (4.1%).6 In 2006, more men (23.9%) than women
that reduce the prevalence of tobacco use. ASHP strongly (18.0%) were smokers.6 The prevalence of smoking also
encourages health care providers to take an active role in varied by race or ethnicity (non-Hispanic American Indian/
promoting the health of their patients by systematically Alaska Native, 32.4%; non-Hispanic white, 21.9%; non-
integrating into routine patient care (a) the identification Hispanic black, 23.0%; Hispanic, 15.2%; non-Hispanic
of tobacco users and (b) the delivery of evidence-based Asian, 10.4%), education level (higher education is asso-
tobacco-cessation interventions. ASHP recommends behav- ciated with a lower prevalence), and poverty level (20.4%
ioral and pharmacologic therapies for cessation, advocates of individuals living at or above the federal poverty level;
their use for all patients attempting to quit smoking (except 30.6% of individuals living below the poverty level).6 An
when medically contraindicated or in specific populations estimated 44.3% of cigarettes smoked in the United States
for which there is insufficient evidence of effectiveness), and are by persons with mental illness.7
advises that these therapeutic interventions be reimbursed Smoking prevalence varies across the nation. In 2006,
under health insurance plans. the highest median prevalence of smoking was evident in
To enable more effective and consistent identification Kentucky (28.6%) and the lowest was in Utah (9.8%).8
of tobacco use and drug interactions with smoking, ASHP Because most teens who smoke at least monthly continue
urges that all patient records, including those in electronic to smoke in adulthood,9 tobacco-use trends among youth are
medical records and pharmacy information technology viewed as a key indicator of future national health trends.10
systems, include a designated field for the collection of In 2007, an estimated 21.6% of 12th graders (23.1% of
tobacco-use data and that this field be integrated within the males and 19.6% of females) had smoked one or more ciga-
system such that clinically significant drug interactions with rettes in the past 30 days.11 The prevalence of smoking has
tobacco products are identified. Schools that offer health declined among adolescents over the past decade; however,
professional degree programs are encouraged to integrate the downward trend has largely diminished among 12th
comprehensive tobacco-cessation training as part of their graders in recent years.
core curricula, and licensed clinicians are advised to par- In the past decade, the prevalence of cigarette smoking
ticipate in continuing-education programs as necessary to has decreased while the per-capita consumption of cigars has
acquire and maintain tobacco-cessation counseling skills. increased.12 However, beginning in 2005, there has been a
Given the established dangers of secondhand smoke expo- slight trend toward decreased cigar use. In 2007, the preva-
sure, ASHP supports legislation promoting smoke-free en- lence of cigar smoking (one or more cigars in the past month)
vironments for the employees and patrons of all workplaces among persons 12 years or older was 5.4%.13 Cigar weight
and public venues. Furthermore, because the sale of tobacco and nicotine content vary widely, with most cigars ranging
products contradicts the clinician’s role in promoting health, in weight from 1 to 22 g. In comparison, a typical U.S. ciga-
ASHP strongly opposes the sale or distribution of tobacco rette weighs <1 g. The nicotine content in 10 commercially
products in all establishments where health care services are available cigars studied in 1996 ranged from 10 to 444 mg.14
rendered. Cigarette brands sold by major manufacturers in the United
States have a lower and less-variable total nicotine content,
ranging from 11.9 to 14.5 mg of nicotine per cigarette.15 As
Epidemiology of Tobacco Use such, it is possible for one large cigar to contain as much
tobacco as an entire pack of cigarettes and to deliver enough
As the former U.S. Surgeon General C. Everett Koop stated nicotine to establish and maintain dependence.14
in 1982, “Cigarette smoking is the chief single, avoidable In 2007, an estimated 8.1 million Americans 12 years
cause of death in our society and the most important pub- of age or older (3.2%) had used smokeless tobacco in the
lic health issue of our time.”1 This statement remains true past month; men (6.3%) were more likely than were women
today, nearly three decades later. The Centers for Disease (0.4%) to be users.13 The prevalence of smokeless tobacco
Control and Prevention (CDC) estimates that nearly 438,000 use is highest among individuals ages 18–25 years and is
Americans die each year from smoking,2 and approximately substantially higher among American Indians, Alaskan
50,000 persons die annually due to involuntary exposure to Natives, and residents of the southern United States and
tobacco smoke.3 Cigarettes are the only marketed consum- rural areas.13,16 While sales of most forms of smokeless to-
able product that, when used as intended, will contribute to bacco (e.g., looseleaf, plug, twist) have declined since the
the death of half or more of its users.4 mid-1980s, moist snuff sales have increased steadily since
While cigarettes are, by far, the most frequently used the late 1980s.12
form of tobacco in the United States, other forms of smoked An enormous economic burden accompanies tobacco
tobacco (e.g., cigars, clove cigarettes [kreteks], pipe to- use. Each pack of cigarettes smoked costs society $7.18
bacco, bidis, hookah) and smokeless tobacco (e.g., chewing ($3.45 for associated medical care and $3.73 for productiv-
tobacco, snuff) can also lead to dependence and should be
ASHP Therapeutic Position Statements 527
ity losses), for a total of $157 billion in annual health-related Table 1.

economic losses.17 The lifelong smoker (e.g., one pack per Diseases and Other Adverse Health Effects
day for 50 years) spends more than $100,000 on his or her Caused by Smoking27
smoking habit in addition to the associated medical care
Cancers
costs of tobacco use. Acute myeloid leukemia
Extensive evidence implicates tobacco as the primary Bladder
known preventable cause of death in the United States. As Cervical
such, ASHP strongly supports evidence-based tobacco- Esophageal
control initiatives that aim to reduce the prevalence of to- Gastric
bacco use by (a) preventing the initiation of tobacco use and Kidney
(b) promoting and maintaining cessation. Tobacco-control Laryngeal
initiatives (e.g., those described in each state’s comprehen- Lung
sive cancer control plan) should comply with recommenda- Oral cavity and pharyngeal
Pancreatic
tions set forth by CDC as delineated in the “Best Practices
Cardiovascular diseases
for Comprehensive Tobacco Control Programs”18 and the Abdominal aortic aneurysm
“Guide to Community Preventive Services: Tobacco Use Coronary heart disease (angina pectoris, ischemic heart
Prevention and Control.”19 disease, myocardial infarction)
Cerebrovascular disease (transient ischemic attacks,
Nicotine Pharmacology stroke)
Peripheral arterial disease
Pulmonary diseases
Tobacco products are carefully engineered formulations Acute respiratory illnesses
that optimize the delivery of nicotine, a chemical that meets Upper respiratory tract (rhinitis, sinusitis, laryngitis,
established criteria for an addictive substance.20 Once ab- pharyngitis)
sorbed, nicotine induces a variety of central nervous sys- Lower respiratory tract (bronchitis, pneumonia)
tem, cardiovascular, and metabolic effects. Within seconds Chronic respiratory illnesses
after inhalation, nicotine reaches the brain and stimulates Chronic obstructive pulmonary disease
the release of various neurotransmitters including dopa- Respiratory symptoms: cough, phlegm, wheezing,
mine, which induces nearly immediate feelings of pleasure dyspnea
and relieves nicotine-withdrawal symptoms. This rapid dose Poor asthma control
Reduced lung function in infants exposed in utero to
response reinforces the need to repeat the administration
maternal smoking
of nicotine, thereby perpetuating smoking behavior. 21 Reproductive effects
The short half-life (t ½ = 2 hours) of nicotine generally Reduced fertility in women
necessitates frequent dosing throughout the day, and Pregnancy and pregnancy outcomes
tobacco users become adept at titrating nicotine intake Preterm or premature rupture of membranes
to maintain pleasure and arousal, modulate mood, and Placenta previa
avoid withdrawal symptoms.21 Placental abruption
When nicotine is discontinued, the following with- Preterm delivery
drawal symptoms may develop: irritability, impatience, Low infant birth weight
anxiety, difficulty concentrating, restlessness, hunger, de- Infant mortality (sudden infant death syndrome)
Other effects
pression, insomnia, and cravings.22-24 Most physical with-
Cataract
drawal symptoms generally manifest within 24–48 hours af- Osteoporosis (reduced bone density in postmenopausal
ter quitting and gradually dissipate over two to four weeks23; women, increased risk of hip fracture)
however, strong cravings for tobacco can persist for months Periodontitis
or even years.25 The nicotine levels generated by smokeless Peptic ulcer disease (in patients who are infected with
tobacco are similar to those of smoking, although their on- Helicobacter pylori)
set of action is less rapid. Upon quitting, smokeless tobacco Adverse surgical outcomes
users experience withdrawal symptoms similar to those of Poor wound healing
smokers.26 Although nicotine is the dependence-causing Respiratory complications
component of tobacco, it is not directly responsible for the
myriad of negative health consequences of tobacco use.
women lose 13.2 and 14.5 years of life because of smok-
Health Consequences of Tobacco Use ing, respectively.17 Between 1997 and 2001, an estimated
and Exposure to Secondhand Smoke 437,902 annual U.S. deaths were attributable to smoking. Of
these deaths, 158,529 (36.2%) were due to cancer, 137,979
Smoking. According to the 2004 Surgeon General’s report (31.5%) to cardiovascular disease, and 101,454 (23.2%) to
on the health consequences of smoking,27 smoking harms respiratory disease.2
nearly every organ of the body, is causally associated with
numerous diseases (Table 1), and reduces the health of Smokeless Tobacco. Users of smokeless forms of tobacco
smokers in general. In addition to contributing to the devel- are often under the mistaken impression that these formula-
opment of disease, smoking also can lead to exacerbation tions are a “safe” alternative to smoking cigarettes. In ad-
or reduced control of existing conditions such as hyperten- dition to cosmetic effects such as halitosis and staining of
sion, diabetes mellitus, and asthma. On average, men and the teeth, smokeless tobacco use is associated with serious
health effects, including cancer, soft tissue alterations (e.g., ciably large quantities in tobacco smoke and are potent in-
leukoplakia), and periodontal effects.16 Smokeless tobacco ducers of hepatic microsomal (cytochrome P-450) enzymes
contains high concentrations of carcinogens, which have di- CYP1A1, CYP1A2, and possibly CYP2E1. Although other
rect contact with mucosal tissues over prolonged periods of substances in tobacco smoke such as acetone, pyridines,
time. The most serious consequence of smokeless tobacco benzene, nicotine, carbon monoxide, and heavy metals (e.g.,
use is an increased risk of developing oral and pharyngeal cadmium) might also interact with hepatic enzymes, their
cancers, and the risk appears to be dose related, in that effects appear to be less significant.34 To enable more ef-
heavy, longtime users are more likely to develop oral cancer fective screening for tobacco use and drug interactions with
than are nonusers. The health effects of smokeless tobacco smoking, all patient records, including those stored and ac-
with regard to cardiovascular disease are not well under- cessed via medical records and pharmacy information tech-
stood, and published data are conflicting.28-30 Although nology systems, should include a designated field for collec-
smokeless tobacco products do not confer many of the tion of tobacco-use data. This field should be integrated into
risks associated with the inhalation of combusted tobacco the system so that relevant drug interactions with tobacco
(e.g., pulmonary disease, lung cancer), these products do smoke can be identified.
impose harm and should not be recommended as aids for
smoking cessation, because safer, effective products (i.e., Health Benefits of Smoking Cessation
medications with FDA-approved labeling for use in smok-
ing cessation) are available.31 Quitting smoking produces immediate as well as long-term
benefits, reducing the risk of developing diseases caused
Secondhand Smoke Exposure. Exposure to secondhand by smoking and improving health in general.35 Some ben-
smoke results in an estimated 50,000 deaths annually, in efits are incurred almost immediately—within the first 24
addition to contributing to numerous diseases among non- hours—after quitting. Within two weeks to three months
smoking children and adults.3 Major conclusions of the after quitting, circulation improves, walking becomes eas-
Surgeon General’s report “The Health Effects of Involuntary ier, and lung function increases up to 30%. Within 1 year,
Exposure to Tobacco Smoke” included the following: the excess risk of coronary heart disease is decreased to half
that of a smoker, and after 5–15 years, stroke risk is reduced
1. Many millions of Americans, both children and adults, to a rate similar to that of people who have never smoked.
are still exposed to secondhand smoke in their homes Ten years after quitting, an individual’s chance of dying of
and workplaces despite substantial progress in tobacco lung cancer is approximately half that of continuing smok-
control, ers. In addition, the risk for mouth, throat, esophagus, blad-
2. Secondhand smoke exposure causes disease and der, kidney, or pancreatic cancer is decreased. Fifteen years
premature death in children and adults who do not after quitting, an individual’s risk of coronary heart disease
smoke, is reduced to a rate similar to that of people who have never
3. Children exposed to secondhand smoke are at an in- smoked. Quitting at ages 30, 40, 50, and 60 has been shown
creased risk for sudden infant death syndrome (SIDS), to be associated with 10, 9, 6, and 3 years of life gained, re-
acute respiratory infections, ear problems, and more spectively.4 Thus, the benefits of quitting the use of tobacco
severe asthma; smoking by parents causes respiratory are significant. It is never too late to quit to incur health
symptoms and slows lung growth in their children, benefits, but there are clear advantages to quitting earlier.
4. Exposure of adults to secondhand smoke has immedi-
ate adverse effects on the cardiovascular system and Strategies for Promoting
causes coronary heart disease and lung cancer, Tobacco Cessation
5. The scientific evidence indicates that there is no risk-
free level of exposure to secondhand smoke, and Because of the immense societal burden that smoking im-
6. Eliminating smoking in indoor spaces fully protects poses, tobacco use and dependence should be addressed
nonsmokers from exposure to secondhand smoke; during each clinical encounter. Routine screening for
separating smokers from nonsmokers, cleaning the air, tobacco-use status enables clinicians to prevent the initiation
and ventilating buildings cannot eliminate exposures of tobacco use among nonusers, facilitate cessation among
of nonsmokers to secondhand smoke. current users, and promote continued abstinence among for-
mer users.
Supplementing the evidence presented in the Surgeon For most smokers, the quitting process is character-
General’s report,3 the California Environmental Protection ized by a series of quit attempts and subsequent relapses.
Agency in January 2006 designated secondhand smoke as On average, former smokers report 10.8 quit attempts over a
a “toxic air contaminant” and, in addition to noting the to- period of 18.6 years before achieving long-term cessation.36
bacco-related diseases described in the Surgeon General’s Most quit attempts are undertaken without assistance, and
report, specified that exposure to smoke is associated with approximately 95% of attempts end in relapse.37
breast cancer in younger, primarily premenopausal women.32 Given the decades of strong, consistent findings in sup-
port of the efficacy and cost-effectiveness of both behavioral
Drug Interactions with Tobacco Smoke. Various substances and pharmacologic interventions to facilitate tobacco cessa-
in tobacco interact with several commonly prescribed tion, ASHP recommends the use of evidenced-based behav-
drugs.33,34 It is widely recognized that polycyclic aromatic ioral and pharmacologic strategies for all patients attempting
hydrocarbons (PAHs), the products of the incomplete com- to quit smoking (except when medically contraindicated or in
bustion of tobacco, are largely responsible for the majority specific populations for which there is insufficient evidence
of drug interactions with smoking. PAHs are found in appre- of effectiveness [e.g., pregnant women, smokeless tobacco
users, light smokers, adolescents]). Treatment for tobacco or time constraints do not afford an opportunity to provide
dependence is highly cost-effective relative to other medi- comprehensive tobacco-cessation counseling, clinicians
cal interventions (e.g., periodic mammography screening, should apply a truncated 5 A’s model whereby they ask about
treatment for hypertension and hyperlipidemia) and should tobacco use, advise tobacco users to quit, and then refer pa-
be made available to all tobacco users.37 In accordance with tients to appropriate cessation providers or programs. With
recommendations set forth in the 2008 clinical practice the October 2004 introduction of a national toll-free quit
guideline, Treating Tobacco Use and Dependence,37 ASHP line number (1-800-QUIT-NOW), all residents of the United
recommends that (1) all insurance plans include counseling States can receive tobacco-cessation counseling at no cost.
and evidence-based pharmacotherapy treatments as a reim- In clinical trials, telephone counseling services for smoking
bursable benefit and (2) clinicians be reimbursed for provid- cessation have been shown to be effective among the patients
ing treatment for tobacco depen-
dence, just as they are reimbursed
for treatment of other chronic con-
ditions. Table 2.
Data consistently reveal that Efficacy of Treatment Methods for Tobacco Use and Dependencea,b
behavioral interventions (e.g., coun- Estimated Estimated
seling from a health care provider) Odds Ratioc Abstinenced Rate
and pharmacotherapy, used either Treatment Method (95% CI) (95% CI)
alone or in combination, increase Behavioral interventions
patients’ odds for quitting their use Advice to quit
of tobacco.37 In a meta-analysis of
No advice to quit 1.0 7.9
29 studies, it was determined that
patients who receive a tobacco- Physician advice to quit 1.3 (1.1–1.6) 10.2 (8.5–12.0)
cessation intervention from a non- Clinician intervention
physician clinician or a physician cli- No counseling by a clinician 1.0 10.2
nician are 1.7 and 2.2 times as likely
Counseling by a nonphysician 1.7 (1.3–2.1) 15.8 (12.8–18.8)
to quit (for at least five months),
Counseling by a physician 2.2 (1.5–3.2) 19.9 (13.7–26.2)
respectively, compared with patients
who do not receive an intervention Format of smoking cessation counseling
from a clinician.37 Estimates of the No format 1.0 10.8
efficacy of various behavioral and Self-help 1.2 (1.0–1.3) 12.3 (10.9–13.6)
pharmacotherapy treatment strate-
Proactive telephone counselinge 1.2 (1.1–1.4) 13.1 (11.4–14.8)
gies are shown in Table 2.
As delineated in the clini- Group counseling 1.3 (1.1–1.6) 13.9 (11.6–16.1)
cal practice guideline, clinicians Individual counseling 1.7 (1.4–2.0) 16.8 (14.7–19.1)
should routinely screen for tobacco Pharmacotherapy
use and apply appropriate inter- Placebo 1.0 13.8
ventions (Figure 1), addressing
First-line agents
five key components for compre-
hensive tobacco-cessation counsel- Bupropion SR 2.0 (1.8–2.2) 24.2 (22.2–26.4)
ing (the 5 A’s): (1) asking patients Nicotine gum (6–14 wk) 1.5 (1.2–1.7) 19.0 (16.5–21.9)
about tobacco use, (2) advising Nicotine inhaler 2.1 (1.5–2.9) 24.8 (19.1–31.6)
tobacco users to quit, (3) assess-
Nicotine lozenge (2 mg) 2.0 (1.4–2.8) 24.2f
ing their willingness to make a quit
Nicotine patch (6–14 wk) 1.9 (1.7–2.2) 23.4 (21.3–25.8)
attempt, (4) assisting patients with
quitting, and (5) arranging follow- Nicotine nasal spray 2.3 (1.7–3.0) 26.7 (21.5–32.7)
up care (Appendix A). To increase Varenicline (2 mg/day) 3.1 (2.5–3.8) 33.2 (28.9–37.8)
the odds for success, patients who Second-line agents
are not ready to quit should receive
Clonidine 2.1 (1.2–3.7) 25.0 (15.7–37.3)
tailored motivational interventions
that address the 5 R’s37 (Appendix Nortriptyline 1.8 (1.3–2.6) 22.5 (16.8–29.4)
B). Patients who are ready to quit Combination therapy
should be provided with a treat- Patch (>14 weeks) + ad lib nicotine 3.6 (2.5–5.2) 36.5 (28.6–45.3)
ment plan that includes behavioral Nicotine patch + bupropion SR 2.5 (1.9–3.4) 28.9 (23.5–35.1)
counseling plus pharmacotherapy
Nicotine patch + nortriptyline 2.3 (1.3–4.2) 27.3 (17.2–40.4)
(as appropriate) and follow-up
counseling. Nicotine patch + nicotine inhaler 2.2 (1.2–3.6) 25.8 (17.4–36.5)
Clinicians should become a
b
Reprinted from reference 43, with permission.
Data from reference 37.
familiar with local community- c
Estimated relative to referent group. CI = confidence interval.
based resources for tobacco ces- d
Abstinence percentages for specified treatment method.
e
sation, including group programs A quitline that responds to incoming calls and makes outbound follow-up calls. After an initial
request by the smoker or via a fax-to-quit program, the clinician initiates telephone contact to
and telephone counseling.37 When counsel the patient.
expertise, practice site logistics, f
One qualifying randomized trial; 95% CI not reported.
Figure 1. Assessing readiness to quit.38 Algorithm for treating tobacco use. cidence of cardiovascular events
or mortality among patients with
cardiovascular disease receiving
Does the patient currently use tobacco?
NRT when compared with that
Yes No of patients receiving placebo.45-47
However, because these stud-
ies specifically excluded patients
Is the patient Did the patient previously
willing to quit? use tobacco? with severe, underlying cardiac
diseases, the clinical practice
Yes No Yes No
guideline37 recommends that be-
cause of a lack of safety data in
Provide appropriate Promote motivation Prevent Encourage these higher-risk populations,
tobacco-dependence to quit relapsea continued NRT should be used with caution
treatments abstinence among patients who have expe-
a
rienced a myocardial infarction
Relapse-prevention interventions are not necessary for adults who have not used tobacco for
many years. within the past two weeks and
among those with serious arrhyth-
mias or unstable angina.37 A large
observational study of more than
who use them.37-39 These positive results have been shown
40 33,000 patients found that NRT use was not associated with
to translate into real-world effectiveness, as evidenced in
an increased risk of myocardial infarction, stroke, or death.48
several meta-analytic reviews.37,38,41,42
Because the serum concentrations of nicotine achieved with
Even the busiest of clinicians can serve an important
the recommended dosages of NRT are generally much lower
role by spending approximately one minute per patient to
than those attained with smoking, most experts have con-
identify tobacco users and to provide referrals to the quit line
cluded that the risks associated with NRT use in patients
for more comprehensive counseling. When patients indicate
with cardiovascular disease are minimal relative to the risks
a willingness to set a quit date in the next month, clinicians
of continued tobacco use.44,49-52
should consider a proactive approach whereby they obtain
Other conditions for which NRT should be used with
the patient’s permission to contact the quit line directly on
caution include active temporomandibular joint disease,
the patient’s behalf as opposed to their providing a passive
pregnancy, and lactation. Patients with active temporoman-
referral (by simply offering the patient contact information
38 dibular joint disease should not use nicotine gum because
for the quit line).
doing so might exacerbate their condition. FDA classifies
prescription formulations of nicotine as pregnancy category
Pharmacotherapy for Cessation. All patients attempting D, indicating that there is evidence of risk to the human fetus.
to quit using tobacco should be encouraged to use effec- Accordingly, none of the NRT formulations have received
tive pharmacotherapies (Table 3) for smoking cessation,43 FDA approval for use during pregnancy. Although NRT may
except when medically contraindicated or in specific popu- pose a risk to the developing fetus, it is arguably less than
lations in which there is insufficient evidence of effective- the risks associated with continued smoking.53 However, be-
ness (e.g., pregnant women, smokeless tobacco users, light cause NRT has the potential to cause fetal harm and because
smokers, adolescents).37 Currently, the agents with approved of insufficient evidence supporting its efficacy in pregnant
FDA labeling for smoking cessation include five nicotine- women, the 2008 clinical practice guideline does not recom-
replacement therapy (NRT) dosage forms, sustained-release mend use during pregnancy.37 Nicotine is secreted in breast
bupropion, and varenicline. Pharmacologic agents that have milk53 and, while the risk is slight, clinicians should be aware
not received FDA approval for use in smoking cessation but that the nursing infant is at risk for nicotine toxicity, espe-
have demonstrated efficacy are clonidine and nortriptyline.37 cially if the mother concomitantly smokes and uses NRT.
NRT. Formulations of NRT products currently available in Sustained-Release Bupropion. The first nonnicotine medi-
the United States include nicotine gum, lozenge, transdermal cation FDA approved for smoking cessation was sustained-
patch, nasal spray, and oral inhaler (Table 3). These agents release bupropion (Zyban, GlaxoSmithKline, Philadelphia).
improve quit rates by reducing the symptoms of nicotine This agent, which was originally marketed as an antide-
withdrawal, enabling the patient to focus on behavior modi- pressant, is hypothesized to promote smoking cessation
fication and coping with the psychological aspects of quit- by inhibiting the reuptake of dopamine and norepineph-
ting. In addition, because the onset of action with NRT is not rine in the central nervous system54 and may function
as rapid as that of nicotine obtained through tobacco (Figure as a nicotinic acetylcholine-receptor antagonist.55 The
2), patients become less accustomed to the nearly immedi- neurochemical effects are believed to modulate the dopa-
ate, reinforcing effects of tobacco. Patients using NRT are mine reward pathway and reduce the cravings for nicotine
approximately two times as likely to quit smoking than are and symptoms of withdrawal.37 Bupropion is effective in
those receiving placebo.37 smokers with or without a history of major depression,56
For selected patients with cardiovascular disease,37 suggesting that the mechanism of action is independent of
NRT should be used with caution, because nicotine can in- the agent’s antidepressant effects. Clinical trials involving
crease the heart rate and blood pressure and also act as a cor- almost 10,000 participants have confirmed the effectiveness
onary vasoconstrictor.44 Despite these effects, randomized, of sustained-release bupropion as an aid to tobacco cessa-
controlled trials have found no significant increase in the in- tion; a recent meta-analysis of 31 trials concluded that the
odds of tobacco abstinence at six or more months was 1.9 drug’s prescribing information have been updated, and FDA
(sustained-release bupropion relative to placebo, 95% CI, recommends that (1) patients tell their health care providers
1.7–2.2).57 Patients receiving sustained-release bupropion about any history of psychiatric illness before starting var-
are approximately two times more likely to quit smoking enicline and (2) clinicians and patients monitor for changes
than are patients receiving placebo.44 in mood and behavior during treatment with varenicline.63
Bupropion is contraindicated in patients (1) with a
seizure disorder, (2) with a history of anorexia or bulimia Second-Line Agents. Second-line agents that have not re-
nervosa, (3) who are using another formulation of bupropion ceived an FDA indication for smoking cessation include
(Wellbutrin, Wellbutrin SR, Wellbutrin XL), (4) who have the prescription medications clonidine and nortriptyline.37
used a monoamine oxidase inhibitor within the past 14 days, Controlled trials suggest that these agents are effective
and (5) who are undergoing abrupt discontinuation of alco- in treating tobacco dependence (Table 2), but they have a
hol or sedatives (including benzodiazepines).58 ln clinical greater incidence of adverse effects and should be reserved
trials for smoking cessation, the frequency of seizures with for patients unable to quit with medications approved for
bupropion was <0.1% (seven seizures among 8000 bupro- smoking cessation.37
pion-treated patients).57 This frequency is comparable to the
report rate of seizures (0.1%) when sustained-release bupro- Combination Therapy. Certain combinations of medications
pion was used in the treatment of depression.59 For this rea- have been shown to be effective smoking-cessation treat-
son, bupropion should be used with extreme caution in pa- ments. In the previous guideline, combination therapy was
tients with a history of seizures, those who have experienced recommended only for patients unable to quit after mono-
cranial trauma, and those receiving medications known to therapy with a first-line agent. Based on data from eight clin-
lower the seizure threshold or those with underlying severe ical trials, the 2008 clinical practice guideline recommends
hepatic cirrhosis. In addition, caution should be exercised that clinicians consider using combinations of first-line
in patients with certain depressive or psychiatric disorders. agents for patients who are willing to quit.37 Combination
FDA has recently reclassified bupropion as a pregnancy NRT involves the use of a long-acting formulation (e.g., nico-
category C drug, meaning that either (1) animal studies tine patch) along with a short-acting formulation (i.e., gum,
have demonstrated that the drug exerts animal-teratogenic lozenge, inhaler, or nasal spray). The long-acting formulation,
or embryocidal effects, but there are no controlled studies which delivers nicotine at relatively constant levels, is used to
in women, or (2) no studies are available in either animals prevent the onset of severe withdrawal symptoms; the short-
or women. The pregnancy category reclassification resulted acting formulation, which delivers nicotine at a more rapid
after the reanalysis of preclinical animal data demonstrated rate, is used as needed to control the withdrawal symptoms
an increased incidence of fetal malformations and skeletal that may occur during potential relapse situations (e.g., after
variations in rabbits receiving dosages approximately twofold meals, during times of stress, when around other smokers).
higher than the maximum recommended human dose (on a Controlled trials suggest that the nicotine patch in com-
milligram per square meter basis) of bupropion. The manufac- bination with short-acting NRT formulations (i.e., gum, nasal
turer continues to recommend that bupropion be used during spray, or inhaler) significantly increases quit rates relative to
pregnancy only if clearly needed.58 placebo.37 Similar results have been observed in trials using
combination therapy with sustained-release bupropion and
Varenicline. A partial agonist selective for the a4b2 nicotinic the nicotine patch. Results from an open-label trial suggest
acetylcholine receptor, varenicline (Chantix, Pfizer, Inc., that a more-aggressive approach consisting of triple agent
New York, NY) was approved in May 2006 for use as an aid NRT (e.g., inhaler, patch, and nasal spray) with or without
to smoking cessation. The drug’s efficacy in smoking cessa- sustained-release bupropion is safe and effective among
tion is believed to be the result of low-level agonist activity highly dependent smokers.64 Clinicians should be aware that
at the receptor site combined with the competitive inhibi- while the combination of the nicotine patch and sustained-
tion of nicotine binding. The partial agonist activity induces release bupropion has been approved by FDA, the concurrent
modest receptor stimulation that attenuates the symptoms of use of two NRT products is not FDA-approved for tobacco
nicotine withdrawal. In addition, by blocking the ability of cessation. Furthermore, the optimal combinations, dosages,
nicotine to activate a4b2 nicotinic acetylcholine receptors, and duration of dual NRTs are currently unknown. The safety
varenicline inhibits the surges of dopamine release that are and effectiveness of varenicline used with sustained-release
believed to be responsible for the reinforcement and reward bupropion or NRT have not been established. Pilot data sug-
associated with smoking.60 gest that patients receiving both varenicline and the nicotine
Data from meta-analyses suggest that the use of va- patch are more likely to experience adverse effects (nausea,
renicline significantly increases long-term smoking-absti- headache, vomiting, dizziness, dyspepsia, and fatigue) than
nence rates relative to placebo and sustained-release bu- are those receiving the patch alone.62
propion.37,61 FDA has classified varenicline as a pregnancy
category C drug. The manufacturer recommends varenicline Smoke-Free Environments
use during pregnancy only if the potential benefit justifies
the potential risk to the fetus.62 Smoking initiation and cessation result from the interplay
In February 2008, FDA issued a public health advi- of numerous factors, including but not limited to environ-
sory to alert health care providers about reports of serious mental influences.21 Smokers in one’s environment can both
neuropsychiatric symptoms in patients attempting to quit promote initiation and inhibit cessation.
smoking while using varenicline, including changes in be- Data on state-specific trends in smoke-free working
havior, depressed mood, agitation, and suicidal ideation environments indicate that 73.4% of employees who work
and behavior. The warnings and precautions sections of the indoors were covered by a smoke-free workplace policy,
Table 3.
Medications with FDA-Approved Indications for Smoking Cessation43,a
Product Name and
Availability Precautions Dosing Administration and Pt Information
c
Nicorette gum, generic, Pregnancy (Category D), ≥25 cigarettes/day: 4 mg, Chew each piece slowly, park between
nonprescription, 2 or breastfeeding, recent (≤2 <25 cigarettes/day: cheek and gum when peppery or
4 mg wk) MI, serious underlying 2 mg tingling sensation appears (~15–30
arrhythmia, serious or Wk 1–6: 1 piece every chews), resume chewing when taste
worsening angina pectoris, 1–2 hr, or tingle fades, repeat chew/park steps
TMJ disease wk 7–9: 1 piece every until most of the nicotine is gone (taste
2–4 hr, or tingle does not return; generally 30
wk 10–12: 1 piece min), park in different areas of mouth,
every 4–8 hr no food or beverages 15 min before or
Maximum, 24 pieces/ during use
day
Duration, up to 12 wk
Commit lozenges, generic Pregnancyc (Category D), First cigarette ≤30 min Allow to dissolve slowly (20-30 min),
nonprescription, 2 or breastfeeding, recent (≤2 after waking: 4 mg, nicotine release may cause a warm,
4 mg wk) MI, serious underlying first cigarette >30 min tingling sensation, do not chew or
arrhythmia, serious or after waking: 2 mg swallow, occasionally rotate to different
worsening angina pectoris Wk 1–6: 1 lozenge areas of the mouth, no food or
every 1–2 hr, beverages 15 min before or during use
wk 7–9: 1 lozenge
every 2–4 hr,
wk 10–12: 1 lozenge
every 4–8 hr
Maximum, 20
lozenges/day
Duration, up to 12 wk
Nicoderm CQ transdermal Pregnancyc (Category D), >10 cigarettes/day: May wear patch for 16 hr if pt has sleep
patch, nonprescription, breastfeeding, recent (≤2 21 mg/day × 6 wk, disturbances (remove at bedtime)
24-hr release; 7,14, or wk) MI, serious underlying 14 mg/day × 2 wk,
21 mg arrhythmia, serious or 7 mg/day × 2 wk
worsening angina pectoris
≤10 cigarettes/day:
14 mg/day × 6 wk,
7 mg/day × 2 wk
Duration: 8–10 wk
Generic patch (formerly Pregnancyc (Category D), >10 cigarettes/day: May wear patch for 16 hr if pt has sleep
Habitrol), prescription breastfeeding, recent (≤2 21 mg/day × 4 wk, disturbances (remove at bedtime)
or nonprescription, wk) MI, serious underlying 14 mg/day × 2 wk,
24-hour release; 7,14, arrhythmia, serious or 7 mg/day × 2 wk
or 21 mg worsening angina pectoris
≤10 cigarettes/day:
14 mg/day x 6 wk,
7 mg/day × 2 wk
Duration: 8–10 wk
c
Nicotrol NS, metered Pregnancy (Category D), 1–2 doses/hr (8–40 For best results, initially use at least
spray, prescription, breastfeeding, recent (≤2 doses/day) 8 doses/day; pts should not sniff,
0.5 mg nicotine in 50 wk) MI, serious underlying swallow, or inhale through nose as
mL aqueous nicotine arrhythmia, serious or 1 dose = 2 sprays (1 spray is administered
solution worsening angina pectoris, in each nostril); each
underlying chronic nasal spray delivers 0.5 mg
disorders (rhinitis, nasal of nicotine
polyps, sinusitis), severe Maximum of 5 doses/
reactive airway disease hr or 40 doses/day
Duration, 3–6 mo
Adverse Effects Advantages Disadvantages Cost/Dayb

Mouth/jaw soreness, hiccups, Might satisfy oral cravings, may Gum chewing may not be socially 2 mg: $3.28–$6.58 (9
dyspepsia, hypersalivation, delay weight gain; pts can acceptable, might be problematic pieces),
effects associated adjust therapy to manage for patients with significant 4 mg: $4.31–$6.58 (9
with incorrect chewing withdrawal symptoms; dental work; pts must use proper pieces)
technique available in a variety of flavors chewing technique to minimize
(lightheadedness, nausea/ adverse effects
vomiting, throat and mouth
irritation)
Nausea, hiccups, cough, Might satisfy oral cravings, might Adverse gastrointestinal effects 2 mg or 4 mg: $3.66–
heartburn, headache, delay weight gain, easy to use (nausea, hiccups, heartburn) $5.26
flatulence, insomnia and conceal; pts can adjust might be bothersome; need for (9 pieces)
therapy to manage withdrawal frequent dosing can compromise
symptoms; available in a adherence
variety of flavors
Local skin reactions Provides consistent nicotine Pts cannot adjust dosage; allergic $1.90–$3.89 (1 patch)
(erythema, pruritus, levels over 24 hr; easy to reactions to adhesive might
burning), headache, sleep use and conceal; once-daily occur, pts with dermatological
disturbances (insomnia), administration associated with conditions should not use patch
abnormal or vivid dreams fewer adherence problems
(associated with nocturnal
nicotine absorption)
Local skin reactions Provides consistent nicotine Pts cannot adjust dosage; allergic $1.90–$3.89 (1 patch)
(erythema, pruritus, levels over 24 hr; easy to reactions to adhesive might
burning), headache, sleep use and conceal; once-daily occur, pts with dermatological
disturbances (insomnia), administration associated with conditions should not use patch
abnormal or vivid dreams fewer adherence problems
(associated with nocturnal
nicotine absorption)
Nasal or throat irritation Pts can adjust therapy to manage Nasal or throat irritation may be $3.72 (8 doses)
(hot, peppery, or burning withdrawal symptoms bothersome; dependence can
sensation), rhinitis, tearing, result; pts must wait 5 min
sneezing, cough, headache before driving or operating heavy
machinery; pts with chronic nasal
disorders or severe reactive
airway disease should not use
spray; need for frequent dosing
can compromise adherence

Table 3. (continued)
Medications with FDA-Approved Indications for Smoking Cessation43,a
Product Name and
Availability Precautions Dosing Administration and Pt Information
c
Nicotrol inhaler, Pregnancy (Category D), 6–16 cartridges/day Initially, use at least 6 cartridges/day;
prescription, 10-mg breastfeeding, recent (≤2 for up to 6 mo, best effects with continuous puffing for
cartridge delivers 4 mg wk) MI, serious underlying individualized dosing 20 min; nicotine in cartridge depleted
inhaled nicotine vapor arrhythmia, serious or after 20 min of active puffing; pt should
worsening angina pectoris, Duration, 3–6 mo inhale into back of throat or puff in
bronchospastic disease short breaths; do not inhale into lungs
(like a cigarette) but “puff” as if lighting
a pipe; open cartridge retains potency
for 24 hr
Zyban (bupropion Pregnancyc (Category C), 150 mg p.o. every Treatment should be initiated while pt
SR), generic and breastfeeding, concomitant morning x 3 days, is still smoking; set quit date 1–2 wk
prescription, 150-mg therapy with medications or then increase to 150 after initiation of therapy; allow at least
sustained-release medical conditions known to mg p.o. twice daily; 8 hr between doses; avoid bedtime
tablets lower the seizure threshold, not to exceed 300 administration to minimize insomnia;
severe hepatic cirrhosis mg/day dose tapering not necessary; can be
Contraindications: used safely with NRT
Seizure disorder, concomitant Duration: 7–12 wk,
bupropion (e.g., Wellbutrin) with maintenance up
therapy, current or prior to 6 mo in selected
diagnosis of bulimia patients
or anorexia nervosa,
simultaneous abrupt
discontinuation of alcohol
or sedatives (including
benzodiazepines), MAOI
therapy in previous 14 days
Chantix (varenicline), Pregnancyc (Category C), Days 1–3: 0.5 mg p.o. Pts should begin therapy 1 wk before
prescription, 0.5- and breastfeeding, severe every morning, quit date; take dose after eating with
1-mg tablets renal impairment (dosage days 4–7: 0.5 mg p.o. full glass of water; dose tapering is not
adjustment is necessary), twice daily, necessary; nausea and insomnia are
safety and efficacy have not wk 2–12:1 mg p.o. side effects that are usually temporary
been established in patients twice daily
with serious psychiatric illness Duration: 12 wks;
an additional 12-wk
course may be used in
selected patients
a
Reprinted from reference 43, with permission. Copyright © 1999-2007 The Regents of the University of California, University of Southern
California, and Western University of Health Sciences. All rights reserved. For complete prescribing information, please refer to the manufacturers’
package inserts. FDA = Food and Drug Administration, MI = myocardial infarction, TMJ = temporomandibular joint, NRT = nicotine-replacement
therapy, MAOI = monoamine oxidase inhibitor.
according to a survey of 14 states conducted in 2005.65 employees and patrons of all workplaces and public ven-
Smoke-free workplaces have been shown to not only protect ues, including but not limited to offices, restaurants, bars,
individuals from secondhand smoke but also to reduce the bowling alleys, and casinos, and for establishments where
prevalence of smoking.66 In a simulation study, smoke-free health care services are rendered. ASHP also strongly sup-
workplace policies were estimated to be approximately nine ports smoke-free campuses for all health care institutions
times more cost-effective per patient than are programs that and facilities. In practice, clinicians should educate patients
provide NRT at no cost.67 about the dangers of secondhand smoke and encourage pa-
Over the past few years, numerous cities and states tients who continue to smoke to do so outdoors.
have adopted clean indoor air laws in workplaces.68
Nationally, the effects of transitioning all workplaces to The Clinician’s Role
smoke-free environments would yield an estimated 4.5%
decrease in the overall prevalence of smoking.66 In its first
To ensure that all future clinicians have received adequate
year of implementation, a nationwide smoke-free workplace
training for treating tobacco use and dependence, schools of-
policy would produce an estimated 1.3 million new quit-
fering health-profession courses or degrees are advised to in-
ters, 1500 fewer myocardial infarctions, 350 fewer strokes,
corporate comprehensive tobacco-cessation training as part of
and a direct saving of nearly $60 million in medical costs.69
the required curriculum for all students.37 Licensed clinicians
Given this substantial impact on public health, ASHP sup-
who have not received the formal training necessary to provide
ports the implementation of smoke-free policies for the
comprehensive tobacco-cessation counseling are encouraged
Adverse Effects Advantages Disadvantages Cost/Dayb

Mouth or throat irritation, Pts can adjust therapy to manage Initial throat or mouth irritation $5.29 (6 cartridges)
unpleasant taste, cough, withdrawal symptoms; mimics can be bothersome; cartridges
headache, rhinitis, hand-to-mouth ritual of should not be stored in very
dyspepsia, hiccups smoking warm conditions or used in
very cold conditions; pts with
underlying bronchospastic
disease must use inhaler with
caution; need for frequent dosing
can compromise adherence
Insomnia, dry mouth, Easy to use; oral formulation Seizure risk is increased; $3.62–$7.40 (2 tablets)
nervousness/difficulty might be associated with several contraindications and
concentrating, rash, fewer compliance problems; precautions can preclude use
constipation, seizures (risk can be used with NRT; might
is 1/1,000 [0.1%]) be beneficial in patients with
depression
Nausea, sleep disturbances Easy to use; oral formulation May induce nausea in up to one $4.49–$4.75 (2 tablets)
(insomnia, abnormal might be associated with fewer third of pts; postmarketing
dreams), constipation, compliance problems; offers surveillance data indicate
flatulence, vomiting, new mechanism of action for potential for neuropsychiatric
neuropsychiatric symptoms pts who have not succeeded symptoms
(behavior changes, with other agents
agitation, depressed
mood, suicidal ideation or
behavior)
b
Average wholesale price from Medi-Span Electronic Drug File. Indianapolis, IN; Wolters Kluwer Health, September 2008.
c
The U.S. clinical practice guideline states that pregnant smokers should be encouraged to quit without medication based on insufficient
evidence and hypothetical concerns with safety. Pregnant smokers should be offered cessation counseling interventions that exceed minimal
advice to quit.37
to complete continuing-education programs. Furthermore, of tobacco products in all establishments where health care
clinicians should systematically integrate the identification of services are rendered (e.g., hospitals, clinics, retail chain
tobacco users and the delivery of evidence-based tobacco- and community pharmacies).71 For more than three decades,
use cessation interventions into routine patient care. In the ab- the pharmacy profession has repeatedly voiced opposition
sence of time or expertise to provide comprehensive cessation to the sale of tobacco products in pharmacies,72 including
counseling, clinicians should—at a minimum—ask patients formal resolutions from state and national organizations.
about tobacco use, advise patients to quit, and refer these Notably, few licensed pharmacists (estimated at <2%)73 and
patients to external resources such as the toll-free quit line pharmacy students (3.5%)74 are in favor of tobacco sales in
(1-800-QUIT-NOW) or a group program.37 Because higher pharmacies. Given this overwhelming lack of support, mem-
quit rates result when patients receive assistance from multi- bers of the profession are advised to insist that tobacco sales
ple health care providers,37 clinicians are encouraged to work no longer occur in the environments where pharmaceutical
in tandem with other providers as part of a team approach to care is rendered. Furthermore, in accordance with a 2003
helping patients quit smoking. Table 4 provides useful online resolution set forth by the American Association of Colleges
links to assist clinicians in tobacco-control initiatives. of Pharmacy, ASHP encourages colleges and schools of
Given that the sale of tobacco contradicts both the cli- pharmacy to give preference as clerkship sites to those phar-
nician’s role in promoting health and the pharmacist’s code macies that choose not to sell tobacco products.74
of ethics,70 ASHP strongly opposes the sale or distribution
Figure 2. Plasma nicotine concentrations for nicotine-containing products. Reprinted with permission from reference 43.
25 ✦ Cigarette
✦
✸ Moist snuff
20
✸
✦
Plasma Nicotine (µg/L)
✸ ✖ Nasal spray
15 ✦
✦ ✸
✸
✸ Inhaler
10 ✦
✦
✖ ✖ ✦ Lozenge (2 mg)
✖ ✖
5
✸ ✖
✖ ✖
✦
✖ Gum (2 mg)
✸
0
0 10 20 30 40 50 60
Patch
Time (min)
Conclusion 5. Centers for Disease Control and Prevention. Cigarette

smoking among adults—United States, 2000. MMWR.
Given the extensive body of data implicating tobacco as the 2002; 51:642–5.
primary known preventable cause of death in the United 6. Centers for Disease Control and Prevention. Cigarette
States, ASHP strongly supports evidence-based tobacco- smoking among adults—United States, 2006. MMWR.
control initiatives that aim to reduce the prevalence of to- 2007; 56:1157–61.
bacco use. These efforts should address a continuum of ser- 7. Lasser K, Boyd JW, Woolhandler S, et al. Smoking and
vices, activities, and policies ranging from the integration mental illness: a population-based prevalence study.
of tobacco-cessation counseling as a routine component of JAMA. 2000; 284:2606–10.
patient care to the adoption of clean indoor air laws. ASHP 8. Centers for Disease Control and Prevention. State-
believes that the active involvement of health care provid- specific prevalence of cigarette smoking among adults
ers is crucial to effective tobacco control at the population and quitting among persons aged 18-35 years—United
level and that the pharmacy profession—as a primary and States, 2006. MMWR. 2007; 56:993–6.
accessible point of contact between the health care system 9. U.S. Department of Health and Human Services. 1994
and the public (including the medically underserved)—has a Surgeon General’s report—preventing tobacco use
unique opportunity to serve as a cornerstone for the nation’s among young people. www.cdc.gov/tobacco/data_statis-
tobacco-control efforts. tics/sgr/sgr_1994/index.htm (accessed 2008 Aug 13).
10. U.S. Department of Health and Human Services.
Healthy People 2010. Vol. I and II. www.healthypeople.
References gov/publications/ (accessed 2008 Jul 16).
11. Johnston LD, O’Malley PM, Bachman JG, et al. Teen
1. The health consequences of smoking: cancer. A report smoking resumes decline. www.monitoringthefuture.
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NN/B/C/D/W/_/nnbcdw.pdf (accessed 2008 Jul 16). May 21).
2. Centers for Disease Control and Prevention. Annual 12. U.S. Department of Agriculture. Tobacco outlook.
smoking-attributable mortality, years of potential life Report TBS-263. http://usda.mannlib.cornell.edu/usda/
lost, and productivity losses—United States, 1997- ers/TBS//2000s/2007/TBS-10-24-2007.pdf (accessed
2001. MMWR. 2005; 54:625–8. 2008 Aug 13).
3. U.S. Department of Health and Human Services. 2006 13. Substance Abuse and Mental Health Services
Surgeon General’s report: the health consequences of Administration Offices of Applied Studies (2008).
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gov/tobacco/data_statistics/sgr/sgr_2006/index.htm (ac- and Health: National findings (DHHS publication no.
cessed 2008 Jul 16). SMA 08-4343). Rockville, MD.
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to smoking: 50 years’ observations on male British doc- concentration, smoke pH and whole tobacco aqueous
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Table 4.
Tobacco-Cessation Resources
Resource Contact Information
Governmental agencies
Centers for Disease Control and Prevention www.cdc.gov
Environmental Protection Agency www.epa.gov
Federal Trade Commission www.ftc.gov
Office of the Surgeon General www.surgeongeneral.gov
National Institutes of Health www.nih.gov
National Cancer Institute www.cancer.gov
National Heart, Lung, and Blood Institute www.nhlbi.nih.gov
National Institute on Drug Abuse www.nida.nih.gov
Organizations
American Cancer Society www.cancer.org
American Heart Association www.americanheart.org
American Legacy Foundation www.americanlegacy.org
American Lung Association www.lungusa.org
American Society of Health-System Pharmacists www.ashp.org/s_ashp/tobacco
Campaign for Tobacco-Free Kids www.tobaccofreekids.org
Global Network of Pharmacists Against Tobacco www.fip.org/pharmacistsagainsttobacco
North American Quitline Consortium www.naquitline.org
Society for Research on Nicotine & Tobacco www.srnt.org
University of California Smoking Cessation Leadership Center smokingcessationleadership.ucsf.edu
University of California Tobacco-Related Disease Research Program www.trdrp.org
World Health Organization www.who.int
Documents
Clinical Practice Guideline for Treating Tobacco Use and Dependence www.surgeongeneral.gov/tobacco
Legacy Tobacco Industry Documents Archive www.legacy.library.ucsf.edu
Pharmacologic aids for cessation—online support
Committed Quitters Program
Nicorette gum www.nicorette.com
Nicoderm patch www.nicodermcq.com
Commit lozenge www.commitlozenge.com
GETQUIT Support Plan
Chantix www.chantix.com
Helping Hand Program
Nicotrol nasal spray and inhaler www.nicotrol.com
Smoke-Free Program
Generic patch (formerly Habitrol) www.habitrol.com
Nonpharmaceutical cessation support and programs
QuitKey (handheld computer for scheduled gradual reduction of smoking) www.quitkey.com
QuitNet (comprehensive online tobacco-cessation support program) www.quitnet.com
Rx for Change: Clinician-Assisted Tobacco Cessation (evidence-based tobacco- rxforchange.ucsf.edu
cessation training materials for educating health professional students and licensed
clinicians)
Tobacco-Free Nurses (national program focused on helping nurses and student www.tobaccofreenurses.org
nurses to stop smoking)
Toll-free quit lines (telephone counseling for cessation, available at no cost to all callers) 1-800-QUIT-NOW
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Appendix A—The 5 A’s of Tobacco Cessation Counseling37

Step Action Strategies for Implementation
Ask—Systematically Implement a system that Expand the vital signs to include tobacco use, or use an alternative universal
identify all tobacco ensures that, for every identification system.b
users at every visit patient at every clinic VITAL SIGNS
visit, tobacco use Blood Pressure: ________
status is queried and Pulse: ___ Weight: ______
documented.a Temperature: _______
Respiratory Rate: ________
Tobacco Use (circle one): Current Former Never
Advise—Strongly urge In a clear, strong, and Advice should be:
all tobacco users personalized manner, • Clear—“It is important that you quit smoking (or using chewing tobacco)
to quit urge every tobacco now, and I can help you.” “Cutting down while you are ill is not enough.”
user to quit. “Occasional or light smoking is still dangerous.”
• Strong—“As your clinician, I need you to know that quitting smoking is the
most important thing you can do to protect your health now and in the
future. The clinic staff and I will help you.”
• Personalized—Tie tobacco use to current symptoms and health concerns,
and/or its social and economic costs, and/or the impact of tobacco use
on children and others in the household. “Continuing to smoke makes
your asthma worse, and quitting may dramatically improve your health.”
“Quitting smoking may reduce the number of ear infections your child has.”

Appendix A—The 5 A’s of Tobacco Cessation Counseling37 (continued)

Step Action Strategies for Implementation
Assess—Determine Assess every tobacco Assess patient’s willingness to quit: “Are you willing to give quitting a try?”
willingness to make user’s willingness to • If the patient is willing to make a quit attempt at the time, provide
a quit attempt make a quit attempt assistance.
at the time. —If the patient will participate in an intensive treatment, deliver such a
treatment or link/refer to an intensive intervention.
—If the patient is a member of a special population (e.g., adolescent,
pregnant smoker, racial/ethnic minority), consider providing additional
information.
• If the patient clearly states that he or she is unwilling to make a quit attempt
at the time, provide an intervention shown to increase future quit attempts.
Assist—Aid the Help the patient with a STAR: A patient’s preparations for quitting:
patient in quitting quit plan. • Set a quit date. Ideally, the quit date should be within 2 weeks.
(provide counseling • Tell family, friends, and coworkers about quitting, and request
and medication) understanding and support.
• Anticipate challenges to the upcoming quit attempt, particularly during the
critical first few weeks. These include nicotine withdrawal symptoms.
• Remove tobacco products from your environment. Prior to quitting, avoid
smoking in places where you spend a lot of time (e.g., work, home, car).
Make your home smoke-free.
Recommend the Recommend the use of medications found to be effective. Explain how these
use of approved medications increase quitting success and reduce withdrawal symptoms.
medication, except The first-line medications include: bupropion SR, nicotine gum, nicotine
when contraindicated inhaler, nicotine lozenge, nicotine nasal spray, nicotine patch, and varenicline;
or with specific second-line medications include: clonidine and nortriptyline. There is
populations for insufficient evidence to recommend medications for certain populations (e.g.,
which there is pregnant women, smokeless tobacco users, light smokers, adolescents).
insufficient evidence
of effectiveness.
Provide practical • Abstinence: Striving for total abstinence is essential. Not even a single puff
counseling (problem after the quit date.
solving/skills training). • Past quit experience: Identify what helped and what hurt in previous quit
attempts. Build on past success.
• Anticipate triggers or challenges in the upcoming attempt. Discuss
challenges/triggers and how the patient will successfully overcome them
(e.g., avoid triggers, alter routines).
• Alcohol: Because alcohol is associated with relapse, the patient should
consider limiting/abstaining from alcohol while quitting. (Note that reducing
alcohol intake could precipitate withdrawal in alcohol-dependent persons.)
• Other smokers in the household: Quitting is more difficult when there is
another smoker in the household. Patients should encourage housemates
to quit with them or to not smoke in their presence.
Provide intratreatment Provide a supportive clinical environment while encouraging the patient in his
social support. or her quit attempt. “My office staff and I are available to assist you.” “I’m
recommending treatment that can provide ongoing support.”
Provide supplementary • Sources: Federal agencies, nonprofit agencies, national quitline network
materials, including (1-800-QUIT-NOW), or local/state/tribal health departments/quitlines.
information on • Type: Culturally/racially/educationally/age-appropriate for the patient.
quitlines. • Location: Readily available at every clinician’s workstation.
Arrange—Ensure Arrange for follow-up • Timing: Follow-up contact should begin soon after the quit date, preferably
follow-up contact contacts, either during the first week. A second follow-up contact is recommended within
in person or via the first month. Schedule further follow-up contacts as indicated.
telephone. • Actions during followup contact: For all patients, identify problems already
encountered and anticipate challenges in the immediate future. Assess
medication use and problems. Remind patients of quitline support
(1-800-QUIT-NOW). Address tobacco use at next clinical visit (treat
tobacco use as a chronic disease).
• For patients who are abstinent, congratulate them on their success. If
tobacco use has occurred, review circumstances and elicit recommitment
to total abstinence. Consider use of or link to more intensive treatment.
a
Repeated assessment is not necessary in the case of the adult who has never used tobacco or has not used tobacco for
many years and for whom this information is clearly documented in the medical record.
b
Alternatives to expanding the vital signs include using tobacco use status stickers on all patient charts or indicating tobacco
use status via electronic medical records or computerized reminder systems.
Appendix B—Enhancing Motivation to • Feeling better physically

Quit: The 5 R’s of Tobacco-Cessation • Performing better in physical activities
Counseling37 • Improved appearance, including reduced wrinkling/
aging of skin and whiter teeth
Roadblocks
Relevance
The clinician should ask the patient to identify barriers or
Encourage the patient to indicate why quitting is personally
impediments to quitting and provide treatment (problem
relevant, being as specific as possible. Motivational infor-
solving counseling, medication) that could address barriers.
mation has the greatest impact if it is relevant to a patient’s
Typical barriers might include:
disease status or risk, family or social situation (e.g., hav-
ing children in the home), health concerns, age, gender, and
other important patient characteristics (e.g., prior quitting • Withdrawal symptoms
experience, personal barriers to cessation). • Fear of failure
• Weight gain
Risks • Lack of support
The clinician should ask the patient to identify potential neg- • Depression
ative consequences of tobacco use. The clinician may sug- • Enjoyment of tobacco
gest and highlight those that seem most relevant to the pa- • Being around other tobacco users
tient. The clinician should emphasize that smoking low-tar/ • Limited knowledge of effective treatment options
low-nicotine cigarettes or use of other forms of tobacco
(e.g., smokeless tobacco, cigars, and pipes) will not elimi- Repetition
nate these risks. Examples of risks are: The motivational intervention should be repeated every time
an unmotivated patient visits the clinic setting. Tobacco us-
ers who have failed in previous quit attempts should be told
• Acute risks: Shortness of breath, exacerbation of
that most people make repeated quit attempts before they
asthma, increased risk of respiratory infections, harm
are successful.
to pregnancy, impotence, infertility.
• Long-term risks: Heart attacks and strokes, lung and
other cancers (e.g., larynx, oral cavity, pharynx, esoph-
agus, pancreas, stomach, kidney, bladder, cervix, and Developed by the ASHP Council on Therapeutics and approved by
acute myelocytic leukemia), chronic obstructive pul- the ASHP Board of Directors on June 30, 2008.
monary diseases (chronic bronchitis and emphysema),
osteoporosis, long-term disability, and need for ex- Karen Suchanek Hudmon, Dr.P.H., M.S., and Robin L. Corelli,
tended care. Pharm.D., are gratefully acknowledged for authoring this therapeu-
• Environmental risks: Increased risk of lung cancer and tic position statement. Dr. Suchanek Hudmon is Associate Professor,
heart disease in spouses; increased risk for low birth- Department of Pharmacy Practice, Purdue University School of
weight, sudden infant death syndrome (SIDS), asthma, Pharmacy and Pharmaceutical Sciencs, West Lafayette, IN. Dr.
middle ear disease, and respiratory infections in chil- Corelli is Professor of Clinical Pharmacy, Department of Clinical
dren of smokers. Pharmacy, University of California San Francisco, San Francisco.
Rewards The following individuals are acknowledged for reviewing draft

The clinician should ask the patient to identify potential versions of this statement: John R. Hughes, M.D., Connie C. Revell,
benefits of stopping tobacco use. The clinician may suggest M.A., Mary H. Zimmerman, BCPS, CACP, Thomas P. Houston,
and highlight those that seem most relevant to the patient. M.D., FAAFP, FACPM, Candice Garwood, Pharm.D., BCPS, Karen
Examples of rewards include: Gunning, Pharm.D., BCPS, Carol Southard, R.N., M.S.N., Frank
Vitale, M.A., Alan J. Zillich, Pharm.D., Laura B. Hanson, Pharm.D.,
• Improved health Daniel A. Hussar, Ph.D., and the American Nurses Association.
• Food will taste better
• Improved sense of smell Copyright © 2009, American Society of Health-System Pharmacists,
• Saving money Inc. All rights reserved.
• Feeling better about oneself
• Home, car, clothing, breath will smell better The bibliographic citation for this document is as follows: American
• Setting a good example for children and decreasing the Society of Health-System Pharmacists. ASHP therapeutic position
likelihood that they will smoke statement on the cessation of tobacco use. Am J Health-Syst Pharm.
• Having healthier babies and children 2008; 65:2055–72.
ASHP Therapeutic Position Statement on the

Institutional Use of 0.9% Sodium Chloride Injection
to Maintain Patency of Peripheral Indwelling
Intermittent Infusion Devices
Statement of Position dium chloride for flushes even before evidence was avail-
able that supported the use of sodium chloride instead of
0.9% Sodium chloride injection is a safe and effective in- heparin.
dwelling solution for maintaining catheter patency of pe-
ripheral indwelling intermittent infusion devices (PIIIDs) in Efficacy
adults and children age one year or older. ASHP supports
the use of 0.9% sodium chloride injection in preference to Studies have indicated that 0.9% sodium chloride injec-
heparin-containing flush solutions (heparin flush) in the in- tion alone is as effective as heparin-containing solutions in
stitutional setting, on the basis of clinical evidence indicat- maintaining PIIID patency.7–16 In several randomized, dou-
ing that 0.9% sodium chloride injection (1) is as effective ble-blind studies in which PIIIDs composed principally of
as heparin flush in maintaining the patency of PIIIDs when fluoroethylene propylene (Teflon) were used, 0.9% sodium
blood is not aspirated into the device, (2) is safer to use than chloride injection for flushing was associated with patency
heparin flush because of a lower potential for adverse ef- rates similar to those achieved with flush solutions contain-
fects, (3) avoids drug incompatibilities associated with hepa- ing heparin sodium 10 or 100 units/mL.10–12 The frequency
rin flush, and (4) is a cost-effective alternative to heparin of phlebitis associated with the use of these solutions was
flush. Because of limited and conflicting available scientific also similar.7,8,17–19 The type of solution used to maintain
evidence to date, this recommendation is not applicable to PIIID patency may not be as important as the positive pres-
children under the age of one year or patients in the home or sure maintained in the i.v. line by the capped (sealed) in-
other outpatient settings. This document is not applicable to jection device, which appears to prevent blood reflux and
catheters used for central venous or arterial access (including clot formation in the devices.8,19 Several studies provide a
peripherally inserted central catheters and midline catheters) scientific basis for using heparin flush,6,20,21 but most pub-
and the maintenance of patency in indwelling venipuncture lished research supports 0.9% sodium chloride injection
devices used to obtain blood samples. Further research on as an effective alternative to heparin flush in maintaining
PIIID patency in the aforementioned patient populations and the patency of PIIIDs. However, 0.9% sodium chloride or
settings is warranted. heparin flush may not be the appropriate flush solution when
flushing drugs that may not be compatible with 0.9% so-
Background dium chloride or heparin. Specific examples of such drugs
include liposomal amphotericin B, doxorubicin, and i.v. im-
PIIIDs, often referred to as “saline locks” and frequently and mune globulin.22 These drugs may need to be “preflushed”
inappropriately called “heparin locks,” are used to provide with another compatible solution such as 5% dextrose injec-
convenient i.v. access in patients who require intermittent tion before and after administering the incompatible drug.
i.v. administration of medications without a continuous infu- In addition, the size of the i.v. catheter in pediatric patients
sion of i.v. fluids. The advantages of PIIIDs include patient appears to be a contributing factor in determining success
mobility and comfort and reduced fluid load.1–4 PIIIDs most with 0.9% sodium chloride for maintaining the patency of
commonly consist of an intravenously inserted catheter at- PIIIDs. Evidence supports the use of 0.9% sodium chloride
tached to a short external cannula with a resealable injec- flushes over heparin in pediatric patients,23–27 and 0.9% so-
tion port that is designed to facilitate multiple needle entries; dium chloride injection is the preferred solution mentioned
thus, these devices eliminate the unnecessary trauma of in the available nursing guidelines on infusion standards.28
multiple venipunctures.4 A problem frequently encountered One survey found that in neonates, it was common
with PIIIDs is the loss of patency because of clot formation practice to flush catheter devices with heparin 1–2 units/
within the catheter. To prevent clot formation, catheters are mL,29 and the literature supports the use of heparin 0.5 unit/
commonly flushed after each administration of i.v. medica- mL added to continuous infusions through peripheral lines.30
tion and every 8–12 hours when the device is not in use.5 Concentrations of heparinized 0.9% sodium chloride injec-
Because of heparin’s anticoagulant effects, diluted solutions tion 1–10 units/mL for flushing have been studied in neona-
of heparin in 0.9% sodium chloride injection (e.g., 10 or 100 tal patients, with no significant difference in catheter life or
units/mL) have traditionally been used to periodically flush patency between 0.9% sodium chloride injection and hepa-
and fill these devices and prevent the formation of clots. rinized 0.9% sodium chloride injection.31–33 A limitation of
Diluted heparin solutions are used to maintain patency while these studies is small sample size, indicating low statistical
avoiding the systemic effects associated with therapeutic power. Despite the lack of evidence-based literature support-
doses of heparin.6 ing the superiority of heparin over 0.9% sodium chloride
However, due to the aforementioned concerns regard- injection or vice versa for neonatal peripheral i.v. flushes,
ing heparin administration and the potential for medication current guidelines published by the National Association of
dose error, many clinicians preferentially began using so- Neonatal Nurses state that heparinized 0.9% sodium chlo-
ride 0.5 unit/mL should be used to flush peripheral i.v. cath- References
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0.9% sodium chloride injection in pediatric patients, avoid 1. Millam DA. Intermittent devices. NITA. 1981; 4:142–
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One trial of pregnant women demonstrated signifi- 2. Larkin M. Heparin locks. NITA. 1979; 2:18–9.
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reactions in some patients. The potential for bleeding com- 9. Fry B. Intermittent heparin flushing protocols. A stan-
plications increases when patients receive multiple unmoni- dardization issue. J Intraven Nurs. 1992; 15:160–3.
tored heparin flushes.37 Repeated injections of heparin, even 10. Epperson EL. Efficacy of 0.9% sodium chloride injec-
in small doses, can alter activated partial thromboplastin tion with and without heparin for maintaining indwell-
time.38 Allergic reactions are an inherent risk of using hepa- ing intermittent injection sites. Clin Pharm. 1984;
rin. Although rare, heparin-flush-associated thrombocyto- 3:626–9.
penia and hemorrhage have been reported.37,39–41 The risks 11. Garrelts JC, LaRocca J, Ast D, et al. Comparison of
of these adverse effects may be avoided by using 0.9% so- heparin and 0.9% sodium chloride injection in the
dium chloride injection instead of heparin flush. Heparin is maintenance of indwelling intermittent i.v. devices.
incompatible with many anthracyclines, including daunoru- Clin Pharm. 1989; 8:34–9.
bicin and doxorubicin, as well as benzodiazepines such as 12. Hamilton RA, Plis JM, Clay C, et al. Heparin sodium
diazepam and midazolam.22 versus 0.9% sodium chloride injection for maintaining
patency of in-dwelling intermittent infusion devices.
Clin Pharm. 1988; 7:439–43.
Cost Implications
13. Shearer J. Normal saline versus dilute heparin flush:
a study of peripheral intermittent i.v. devices. NITA.
Enhanced quality of patient care should be the primary rea-
1987; 10:425–7.
son for deciding to use 0.9% sodium chloride injection for
14. Miracle V, Fangman B, Kayrouz P, et al. Normal saline
flushing. Secondarily, the choice of 0.9% sodium chloride
vs. heparin lock flush solution: one institution’s find-
injection may avoid substantial costs associated with drugs,
ings. Ky Nurse. 1989; 37(Jul–Aug):1, 6–7.
related supplies, and staff time.9
15. Ashton J, Gibson V, Summers S. Effects of heparin
versus saline solution on intermittent infusion device
Summary irrigation. Heart Lung. 1990; 19:608–12.
16. Hook ML, Ose P. Heparin vs. normal saline. J Intraven
Because current therapeutic evidence supports the efficacy Nurs. 1990; 13:150–1. Letter.
of 0.9% sodium chloride injection in maintaining PIIID pa- 17. Garrelts JC. White clot syndrome and thrombocyto-
tency and due to the inherent risks associated with heparin, penia: reasons to abandon heparin i.v. lock flush solu-
ASHP believes that the use of 0.9% sodium chloride injection. Clin Pharm. 1992; 11:797–9.
tion is appropriate for maintaining the patency of PIIIDs in 18. Weber DR. Is heparin really necessary in the lock and,
adults and children age one year or older in institutional set- if so, how much? DICP. 1991; 25:399–407.
tings. Because of limited and conflicting scientific evidence 19. Goode CJ, Titler M, Rakel B, et al. A meta-analysis of
available to date, this recommendation is not applicable to effects of heparin flush and saline flush: quality and
neonates, patients in the home or other outpatient settings, cost implications. Nurs 2Res. 1991; 40:324–30.
catheters used for central venous or arterial access (includ- 20. Cyganski JM, Donahue JM, Heaton JS. The case for
ing peripherally inserted central catheters and midline cath- the heparin flush. Am J Nurs. 1987; 87:796–7.
eters), which was beyond the scope of this therapeutic posi- 21. Holford NH, Vozeh S, Coates P, et al. More on heparin
tion statement, and the maintenance of patency in indwelling lock. N Engl J Med. 1977; 296:1300–1. Letter.
venipuncture devices used to obtain blood samples. 22. Trissel LA. Handbook on injectable drugs. 16th ed.
Bethesda, MD: American Society of Health-System
Pharmacists; 2011.
23. Mok E, Kwong TK, Chan MF. A randomized con- 36. Niesen KM, Harris DY, Parkin LS, et al. The effects
trolled trial for maintaining peripheral intravenous of heparin versus normal saline for maintenance of
lock in children. Int J Nurs Pract. 2007; 13:33–45. peripheral intravenous locks in pregnant women. J
24. Hanrahan KS, Kleiber C, Fagan CL. Evaluation of Obstet Gynecol Neonatal Nurs. 2003; 32:503–8.
saline for iv locks in children. Pediatr Nurs. 1994; 37. Passannante A, Macik BG. The heparin flush syn-
20:549–52. drome: a cause of iatrogenic hemorrhage. Am J Med
25. Kleiber C, Hanrahan K, Fagan CL, et al. Heparin vs Sci. 1988; 296:71–3.
saline for peripheral i.v. locks in children. Pediatr 38. Heparin sodium monograph. In: McEvoy GK, ed.
Nurs. 1993; 19:405–9. AHFS Drug Information. Bethesda, MD: American
26. Danek G, Noris EM. Pediatric iv catheters: efficacy of Society of Health-System Pharmacists; 2006:2616.
saline flush. Pediatr Nurs. 1992; 18:111–3. 39. Heeger PS, Backstrom JT. Heparin flushes and throm-
27. LeDuc K. Efficacy of normal saline solution versus bocytopenia. Ann Intern Med. 1986; 105:143. Letter.
heparin solution for maintaining patency of peripheral 40. Doty JR, Alving BM, McDonnell DE, et al. Heparin-
intravenous catheters in children. J Emerg Nurs. 1997; associated thrombocytopenia in the neurosurgical pa-
23:306–9. tient. Neurosurgery. 1986; 19:69–72.
28. Intravenous Nurses Society. Infusion nursing stan- 41. Cines DB, Tomaski A, Tannenbaum S. Immune endo-
dards of practice. J Infus Nurs. 2011; 34:37–72. thelial-cell injury in heparin-associated thrombocyto-
29. Romanowski GL, Zenk KE. Intravenous flush solu- penia. N Engl J Med. 1987; 316:581–9.
tions for neonates. Paper presented at ASHP Midyear
Clinical Meeting. New Orleans, LA; 1991 Dec 10.
30. Klenner AF, Fusch C, Rakow A, et al. Benefit and risk
of heparin for maintaining peripheral venous catheters
in neonates: a placebo-controlled trial. J Pediatr. 2003; Approved by the ASHP Board of Directors on April 13, 2012.
143:741–5. Developed through the Council on Therapeutics.
31. Shah PS, Ng E, Sinha AK. Heparin for prolong-
ing peripheral intravenous catheter use in neonates. This document supersedes the ASHP therapeutic position statement
Cochrane Database Syst Rev. 2005; 4:CD002774. on the institutional use of 0.9% sodium chloride injection to main-
32. Goldberg M, Sankaran R, Givelichan L, et al. tain patency of peripheral indwelling intermittent infusion devices
Maintaining patency of peripheral intermittent in- approved by the ASHP Board of Directors on January 12, 2006.
fusion devices with heparinized saline and saline.
Neonatal Intensive Care. 1999; 12:18–22. Kim W. Benner, Pharm.D., BCPS, FASHP, and Amber J. Lucas,
33. Heilskov J. A randomized trial of heparin and saline Pharm.D., BCPS, FASHP, are gratefully acknowledged for author-
for maintaining intravenous locks in neonates. J Soc ing this document.
Pediatr Nurs. 1998; 3:111–6.
34. Altimier L, Brown B, Tedeschi L. NANN guidelines Copyright © 2012, American Society of Health-System Pharmacists,
for neonatal nursing policies, procedures, competen- Inc. All rights reserved.
cies, and clinical pathways. 4th ed. Glenview, IL:
National Association of Neonatal Nurses; 2006. The bibliographic citation for this document is as follows: American
35. Meyer BA, Little CJ, Thorp JA, et al. Heparin versus Society of Health-System Pharmacists. ASHP therapeutic position
normal saline as a peripheral line flush in maintenance statement on the institutional use of 0.9% sodium chloride injection
of intermittent intravenous lines in obstetric patients. to maintain patency of peripheral indwelling intermittent infusion
Obstet Gynecol. 1995; 85:433–6. devices. Am J Health-Syst Pharm. 2012; 69:1252–4.
ASHP Therapeutic Position Statement on the

Role of Pharmacotherapy in Preventing Venous
Thromboembolism in Hospitalized Patients
Position patients despite treatment for the initial VTE. The risk of
developing VTE rises sharply when the number of risk fac-
Hospitals should develop formal policies, guidelines, prac- tors increases.13 At 1 year after the initial VTE, the mortality
tices, and procedures to address the appropriate prevention rates associated with PE and DVT are particularly high in
of venous thromboembolism (VTE). In addition, all hos- patients older than 65 years (39% and 21%, respectively).14
pitalized patients should be assessed for risk for both VTE The risk of recurrent VTE continues for up to 90 days after
and bleeding to determine if pharmacologic, mechanical, or hospitalization.15,16
combination VTE prophylaxis should be initiated. Patients Approximately 60% of VTE events17 and 75% of
should also be reassessed following any pertinent clinical autopsy-confirmed fatal PE18–21 occur in nonsurgical pa-
changes. In at-risk patients without contraindications (i.e., tients. More importantly, PE and proximal DVT are occur-
risk for bleeding, active bleeding, or allergy), pharmaco- ring more frequently in medical patients than in surgical
logic thromboprophylaxis should be initiated as soon as pos- patients.22 This increase may be partially attributable to medi-
sible and within the first 24 hours of arrival at the hospital. cal patients having historically lower rates of thrombopro-
Mechanical methods should be used when pharmacologic phylaxis compared with surgical patients. In addition, VTE
prophylaxis is contraindicated. Active interdisciplinary, prophylaxis for surgical patients has been studied for approxi-
multifaceted VTE prevention programs, in contrast to pas- mately 50 years, whereas well-designed studies for medical
sive strategies, should be used to improve appropriate VTE patients began surfacing in the mid-1990s. In placebo-
prophylaxis within hospitals. These programs should in- controlled studies, VTE events have been reduced by 50–
corporate provider, staff, and patient education; audits and 65% in acutely ill patients when prophylaxis was used.23–25
feedback; hospital guidelines and policies; clinical decision- Examples of avoided morbidity associated with VTE are
support software; monitoring for appropriate anticoagulant recurrent VTE, postthrombotic syndrome (PTS), congestive
use; and provider reminders. Guidelines and policies need to heart failure, and pulmonary hypertension. PTS is the term
be individualized at the hospital level, depending on the de- used to describe signs and symptoms that may occur as a
gree to which pharmacy, providers, nursing, and other staff long-term complication of DVT and includes swelling, pain,
are involved. The National Quality Forum (NQF) and the edema, venous ectasia, and skin induration of the affected
Joint Commission recommend creating policies and guide- limb.26 In severe PTS, patients may have painful, intractable
lines regarding anticoagulation. This is also a key recom- leg ulcers, which decrease mobility and require additional
mendation of the American College of Chest Physicians medical care.26 PTS is associated with an annualized cost as
(ACCP). Pharmacy professionals should actively participate high as $11,66727 and can lead to loss of quality of life and
in the development, implementation, and monitoring of an- functional status. After a symptomatic DVT, the overall in-
ticoagulation and VTE prophylaxis programs. In addition, cidence of PTS is 20–50%, and severe PTS occurs in 5–10%
because pharmacologic prophylaxis is the primary method of patients.28 Within 2 years after the development of PE,
to prevent VTE, pharmacy professionals should take a lead- chronic thromboembolic pulmonary hypertension occurs
ership role in these hospital programs. in approximately 3.8% of patients.29 Results from clinical
trials have shown that when pharmacologic prophylaxis is
administered at appropriate doses and durations in medical
Background patients, the breakthrough occurrence of VTE is clinically
uncommon (2.8–5.6%).23–25 The use of thromboprophylaxis
Burden of Disease and Pharmacologic Prophylaxis. VTE has been shown to reduce mortality in both primary studies
comprises pulmonary embolism (PE) and deep vein throm- and meta-analyses.25,30,31 This position statement focuses on
bosis (DVT). Despite a wealth of information regarding key issues and guideline recommendations for the preven-
the mortality and morbidity associated with VTE, hospi- tion of VTE in hospitalized patients augmented by health-
tals worldwide continue to do poorly at preventing VTE system pharmacists.
events for at-risk patients. Between 60,0001 and 300,0002
deaths occur annually in the United States from PE, and as Current Hospital Performance and Barriers. Globally,
many as 200,000 of those deaths occur in U.S. hospitals.3 41.5% of surgical patients and 60.5% of medical patients
Approximately 70% of fatal PEs are first detected postmor- at risk for VTE do not receive appropriate prophylaxis
tem.4,5 Furthermore, up to 2,000,000 new DVTs occur annu- therapy.6 The concept of “appropriate VTE prophylaxis” has
ally within the United States.1 VTE occurs in approximately recently emerged and denotes appropriate drug, dose, and
64.4% of surgical patients and 41.5% of medical patients.6 duration of therapy. Recent studies have demonstrated ap-
PE is the most preventable cause of death among all causes propriate prophylaxis rates of only 13–33% in hundreds of
for patients; therefore, VTE prevention is the best strategy U.S. hospitals.32–35
for improving patient safety in U.S. hospitals.7,8 In the ab- Barriers to VTE prophylaxis include concerns about
sence of thromboprophylaxis, 1 in 10 hospital deaths is at- bleeding complications; underestimation of the VTE risk;
tributed to PE.9 Recurrent VTE occurs in 7% of patients at gaps in provider knowledge of VTE prevention; lack of
six months,10 increasing to up to 30% at 8–10 years11,12 for
knowledge regarding recommendations and standards; het- surgical patients.49 CMS also added DVT and PE after total
erogeneous patient populations; perceived difficulties in risk knee replacement (TKR) or total hip replacement (THR) pro-
assessment; lack of familiarity, agreement, or confidence cedures to a list of conditions whose associated costs will not
with guidelines; belief that implementing guidelines is inef- be reimbursed if acquired during a hospital stay.50 The Joint
fective in improving outcomes; resistance to changing es- Commission collaborated with NQF on the development of
tablished practice patterns; need for approval and funding to these measures to promote VTE prophylaxis, which were pi-
implement guidelines; and lack of clarity and ease of use of loted in U.S. hospitals and then endorsed by NQF in 2008.51
guidelines.36–38 In October 2009, the Joint Commission made available a
core measure set for VTE (Table 1), focusing on prophy-
National Impact and Readmissions. Currently, VTE has laxis, treatment, and one outcome measure of “preventable”
an estimated financial burden of $13.5 billion–$69.3 bil- VTE.52 Hospitals may choose this VTE core measure set as
lion per year in the United States, with $4.5 billion–$39.3 one of four required core measure sets on which to report.52
billion of this being preventable with pharmacist-driven or However, because these measures alone do not give detailed
other VTE prevention programs.39,40 Because of the grav- recommendations on VTE prophylaxis, hospitals should
ity of the problem and poor performance of U.S. hospitals, base their guidelines, policies, practices, and recommenda-
many of the leading U.S. organizations began to prioritize tions on the most recent edition of the ACCP guidelines. At
VTE as a top initiative for improvement within the last de- this time, only 60 of approximately 5000 acute care hospitals
cade. Some of these organizations include NQF, the Agency are reporting on the VTE core measure set. Therefore, hospi-
for Healthcare Research and Quality, the Institute for tals should also adopt the Joint Commission’s VTE measure
Healthcare Improvement, the Joint Commission, the Centers set for core measure reporting to aid in improving patient
for Disease Control and Prevention (CDC), and the Centers care and reduce health care costs.
for Medicaid and Medicare Services (CMS).41
Interestingly, a 2007 study found that approximately Mechanical Methods of Prophylaxis in Hospitalized
5.3% of patients previously hospitalized for a DVT or PE Patients. While the focus of this manuscript is pharmaco-
are readmitted within one year for VTE.42 A clear trend of logic prophylaxis, pharmacists should familiarize them-
hospital readmission occurred within the first 30 days of the selves with mechanical methods of prophylaxis to make
initial event for these patients, with 27.1% readmitted for a appropriate recommendations for patients when a phar-
DVT and 44.3% readmitted for a PE.42 macologic contraindication exists. Mechanical methods of
prophylaxis may be dynamic, static, or a combination of
Guidelines and Quality Measures the two. Dynamic methods include intermittent pneumatic
compression (IPC) devices, sequential compression devices,
and venous foot pumps. Static methods include graduated
Many national and international guidelines exist for ap-
compression stockings, elastic stockings, and thromboem-
propriate, evidence-based treatment of VTE prophylaxis.
bolic deterrent hose. Mechanical methods of prophylaxis
These include the ACCP guidelines, which were last up-
have been shown to only reduce the rates of DVT, not PE or
dated in 2012,43–45 and the International Union of Angiology
death, in contrast with pharmacologic prophylaxis.8 A 2005
guidelines from June 2006.46 Oncology-specific guidelines,
meta-analysis of IPC device use in surgical patients found a
such as those created by the American Society of Clinical
60% risk reduction in DVT with no substantial reduction in
Oncology (ASCO)47 and the National Comprehensive
PE risk, compared with no prophylaxis (p < 0.001).53,54
Cancer Network (NCCN),48 are also available and are very
Inferior vena cava filters (IVCFs) are an alternative
specific about contraindications for prophylaxis, which is
static method of mechanical prophylaxis. To date, IVCFs
helpful to the practicing clinician. ASCO and NCCN guide-
have been shown to reduce recurrent PE at the expense of an
lines were updated in 2007 and 2011, respectively.
increased risk of DVT in the absence of anticoagulation.55
Both the Joint Commission and CMS have initiated
Hospitals should use IVCFs for patients with confirmed
quality measures to promote VTE prophylaxis in hospital-
proximal DVT who have an absolute contraindication to
ized patients. In 2008, the Joint Commission implemented
full-dose anticoagulation (e.g., patients with active bleeding)
a National Patient Safety Goal that focuses on anticoagula-
or who have not responded to standard anticoagulant regi-
tion management in the hospital setting for both medical and
Table 1.
The Joint Commission Venous Thromboembolism (VTE) National Hospital Inpatient Quality Measuresa
Set Measure ID # Measure Short Name
VTE-1 Venous thromboembolism prophylaxis
VTE-2 Intensive care unit venous thromboembolism prophylaxis
VTE-3 Venous thromboembolism patients with anticoagulant overlap therapy
VTE-4 Venous thromboembolism patients receiving unfractionated heparin therapy with dosages/platelet count
monitoring by protocol
VTE-5 Venous thromboembolism discharge instructions
VTE-6 Incidence of potentially preventable venous thromboembolism
a
Reprinted from the Specifications Manual for National Hospital Inpatient Quality Measures, version 4.1, March 2012, a collaborative work of
the Centers for Medicare and Medicaid Services and the Joint Commission. This manual is periodically updated, and users of the manual must
update their software and associated documentation based on the published manual production timelines.
mens (e.g., patients who developed recurrent thromboembo- Risk Stratification and Identification
lism despite full-dose anticoagulant therapy) or in high-risk
patients who have major surgery planned in the very near Most hospitalized patients have at least one risk factor for
future. Once the absolute contraindication to anticoagulation VTE, and approximately 40% have multiple risk factors.8
subsides or the major surgery is completed, treatment with Common risk factors for VTE are listed in Table 2, and
an appropriate anticoagulant should be initiated or resumed, DVT rates among various patient groups are presented in
depending on the clinical scenario.8 Table 3.57 Most critically ill patients have multiple risk fac-
The health care team should ensure patients’ com- tors for VTE. Risk factors that may precede admission to a
pliance with mechanical methods of VTE prophylaxis critical care unit may include trauma, active infection (e.g.,
throughout their hospitalization, as compliance is the most sepsis), recent surgery, active malignancy, stroke, advanced
important determinant of efficacy.56 Most devices used for age, congestive heart failure, respiratory failure, history of
mechanical VTE prophylaxis should be used for a minimum VTE, and pregnancy. In addition, patients admitted to criti-
of 20 hours per day to be effective. Because of these compli- cal care units have an increased risk of developing VTE due
ance issues, hospitals and physicians should attempt to use to immobilization, placement of central venous lines, sepsis,
mobile, battery-powered IPC devices that have the ability pharmacologic paralysis, mechanical ventilation, vasopres-
to record and report the hours the devices are used.8,43–45 sor use, and the need for surgical procedures and dialysis.8,58
Mechanical methods of prophylaxis should be reserved for PE is the second most common cause of death in pa-
patients who are actively bleeding or at high risk for bleed- tients with cancer.8 Patients with hematologic malignancies,
ing, with inclusion of such documentation in the patient re- lung cancer, and gastrointestinal cancer have the highest
cord, or possibly as an adjunct to pharmacologic methods of rates of VTE. Within the first three months after being di-
prophylaxis.8 Studies have demonstrated greater reductions agnosed with cancer, patients have an approximate 50-fold
in VTE rates among certain groups of patients (i.e., trauma increased risk of developing a VTE compared with patients
patients, patients with spinal cord injury, and high-risk pa- with no cancer.59 Even during therapeutic anticoagulation
tients undergoing TKR, THR, hip fracture surgery, neuro- after a VTE, fatal PE outnumbers fatal bleeding events in an
surgery, and elective spine surgery) receiving combination approximate 3:1 ratio.60 Certain cancer treatments, including
pharmacologic and mechanical VTE prophylaxis compared chemotherapy, hormonal manipulation, erythropoiesis, and
with pharmacologic prophylaxis alone.8 the presence of a central venous catheter, are also risk factors
Health-system pharmacists should evaluate patients for for VTE.8 Chemotherapy is associated with an approximate
potential contraindications to anticoagulation therapies. They sixfold increased risk of VTE,61–63 with specific drugs con-
should also familiarize themselves with the specific mechani- tributing to higher VTE rates, including tamoxifen, anastro-
cal methods available at their institution, which could be used zole, letrozole, exemestane, bevacizumab, thalidomide, and
in patients with such contraindications. lenalidomide.64–73 Tamoxifen is associated with a higher rate
Table 2.
Venous Thromboembolism (VTE) Risk Factors8,57
Risk Factor Category Risk Factors
Common general risk factors Previous VTE; surgery; trauma; thrombophilia; obesity (body mass index of >25 kg/m2); acute
hospitalization for medical illness; immobility or lower-extremity paresis; active or occult
malignancy; cancer therapy, such as radiotherapy, hormonal therapy, chemotherapy, or
angiogenesis inhibitors; venous compression from sources such as tumor, hematoma,
or arterial abnormality; increasing age; pregnancy and the postpartum period; estrogen-
containing oral contraceptives or hormone- replacement therapy; selective estrogen-receptor
modulators; erythropoiesis-stimulating agents; inflammatory bowel disease; nephrotic
syndrome; myeloproliferative disorders; paroxysmal nocturnal hemoglobinuria; central venous
catheterization
Specific medical risk factors
High risk History of deep venous thrombosis or pulmonary embolism, family history of thrombosis, acute
infection, active malignancy, age >75 yr, stroke, myocardial infarction, congestive heart failure,
prolonged immobility (≥4 days), pregnancy or postpartum period, acute or chronic lung
disease, acute inflammatory disease, inflammatory bowel disease, shock
Probable risk High-dose estrogen therapy, obesity (body mass index of >25 kg/m2), varicose veins, heparin-
induced thrombocytopenia, congenital or acquired thrombophilia, antithrombin deficiency,
positive lupus anticoagulant, antiphospholipid antibodies, protein S or C deficiency, positive
factor V Leiden, elevated anticardiolipin antibodies, positive prothrombin gene mutation
20210A
Possible risk Paraproteinemia, Behçet’s disease, disorders of plasminogen and plasminogen activation,
nephrotic syndrome, polycythemia, elevated serum homocysteine levels, dysfibrinogenemia,
myeloproliferative disorders, age ≥ 41 yr, sepsis (<1 mo)
Another recent, predictive, evidence-based, weighted-risk

Table 3.
scoring system was developed from the large International
Frequency of DVT Associated with Various Medical Prevention Registry on Venous Thromboembolism
Patients Groups and Conditions in the Absence (IMPROVE) database for medical patients.92 The risk scores
of Prophylaxis8,57,a were derived from the hazard ratios of seven independent
Patient Group or Condition Frequency of DVT, % clinical risk factors for VTE. The Padua prediction score
General medical patients 10–26 is another RAM that uses 11 risk factors to determine VTE
risk in the medical patient and categorizes a patient’s VTE
Myocardial infarction 17–34 risk as low or high.93 For all patients, the risk of bleeding
Stroke 11–75 should be determined using a group-appropriate RAM or
Congestive heart failure 20–40 guideline-delineated risk factors. A clear advantage of the
IMPROVE RAM is that its derivation is evidence based,
Medical intensive care 25–42
whereas the Padua prediction score is not.91 Collectively,
Critical care patients 10–80 these RAMs further validate the concept of weighted scor-
General surgical patients 15–40 ing, demonstrating that all VTE risk factors are not equally
associated with VTE risk.
Major gynecological surgery 15–40
Because risk factors are not weighted equally, clini-
Major urologic surgery 15–40 cians should carefully examine risk factors to determine the
Neurosurgery 15–40 individual care needed for each patient. Furthermore, efforts
Major orthopedic surgery of the 40–60
should be made to maximize the number of risk factors as-
hip or kneeb sessed with the RAM, as this will capture a greater number
of patients at risk for VTE and maximize the sensitivity of
Trauma 40–80
the model.94
Spinal cord injury 60–80 Although a review of all risk-assessment programs to
a
DVT = deep venous thrombosis. reduce VTE is beyond the scope of this position statement,
b
Total knee or hip replacement or hip fracture surgery. several reviews reiterate key characteristics that are essential
to such programs.94–97 Risk-assessment programs should be
multifaceted, and those involved in such programs should
of VTE than the aromatase inhibitors anastrozole, letrozole, provide active interventions instead of merely handing out
and exemestane.74–77 guidelines or placing incomplete risk-assessment forms
Furthermore, surgical patients with cancer have at in patient charts. These programs should also educate and
least twice the risk of developing a postoperative DVT and remind health care providers about the need for VTE pro-
three times the risk of developing a fatal PE as compared phylaxis, educate patients, use audit and feedback for the
with patients with no cancer undergoing the same surger- program itself and for individuals ignoring alerts (i.e., alert
ies.8 VTE recurrence rates are high both during anticoagu- fatigue), monitor for inappropriate use of thromboprophy-
lation and after anticoagulation has been discontinued.78–81 laxis, and use clinical decision-support software, either elec-
Patients with cancer who develop a VTE have a substantial tronically or manually.
reduction in survival compared with cancer patients who do Pharmacist-driven VTE programs have helped improve
not develop a VTE.82-84 the care received by hospitalized patients.39,98–102 The imple-
Research into other risk factors for VTE continues,85–87 mentation of one such program led to a significant increase
though validation of these risk factors will be needed. Risk- in appropriate type, dose, and duration of prophylaxis while
assessment models (RAMs) have been developed for the also significantly reducing “preventable” VTE events (rela-
hospitalized patient and have proved useful in identifying tive risk reduction = 74%, p = 0.0006).39 Another pharmacist-
patients at risk for VTE and bleeding.8 The health-system driven program significantly increased optimal VTE prophy-
pharmacist should take initiative and lead the collaborative laxis among hospitalized nonsurgical patients from 11% to
implementation of RAMs within the hospital. 44% (p < 0.001). The program consisted of presentations, news-
Several methods of risk assessment to reduce hospital- letters, and VTE prophylaxis recommendations made during
acquired VTE exist. Some methods may use one process or clinical pharmacy rounds.98 In addition, a multidisciplinary
form for all patients being evaluated, while others may use program that included pharmacists in the surgical intensive
specific processes or forms for specific patient groups. Both care unit achieved substantial reductions in both hospital-
methods can be computerized (i.e., using electronic alerts) acquired and preventable VTE.103 Lastly, the use of a sim-
or completed manually. RAMs could also be based on a ple, nonscoring, three-tiered (low, moderate, or high) VTE
scoring system (i.e., positive points for specific risk factors RAM led to an 86% reduction in preventable hospital-ac-
and negative points for contraindications) or they could as- quired VTE over three years.104 This RAM was modular and
sess risk factors by patient groups based on guideline recom- embedded into computerized provider-order-entry (CPOE)
mendations.8 order sets but was not a pharmacist-driven program.
Several RAMs have been proposed for hospitalized
patients, incorporating both predisposing and exposing risk Efficacy of Antithrombotic Prophylaxis
factors (e.g., major surgery, acute medical illness).88–92 and Recommendations
For example, Caprini et al.88 developed a RAM for both
hospitalized surgical and medical patients, with the surgi- Heparins and Fondaparinux. Three prospective, randomized,
cal RAM being validated in 2009,90 and Cohen et al.90 de- placebo-controlled studies have been conducted to evaluate
veloped an algorithm-based RAM for medical patients. the efficacy of low-molecular-weight heparins (LMWHs)
and fondaparinux for VTE prophylaxis in medical patients. Optimal Duration for
These include the MEDENOX23 (enoxaparin), PREVENT24
Thromboprophylaxis
(dalteparin), and ARTEMIS25 (fondaparinux) trials. The
number needed to treat to avoid a VTE ranged from 11 to With the average length of stay in U.S. hospitals being ap-
45 in these studies. Major bleeding rates were 1.7%, 0.49%, proximately 5 days,109 the recommended duration of pro-
and 0.2% in the MEDENOX, PREVENT, and ARTEMIS phylaxis in studies and within drug labeling is often not
trials, respectively. The three studies demonstrated signifi- reached. Studies have suggested that the inappropriate dura-
cant relative risk reductions of 63%, 55%, and 49.5% for tion of therapy is a major cause for failure to receive appro-
VTE, respectively, with no significant differences in major priate thromboprophylaxis among hospitalized patients.15,33
bleeding rates. In the United States, enoxaparin and dalte- ACCP guidelines advocate extended thromboprophylaxis of
parin have Food and Drug Administration (FDA)-approved up to 35 days with an LMWH in patients undergoing major
indications for VTE prophylaxis in acutely ill medical pa- orthopedic surgery (especially hip fracture repair and hip re-
tients; fondaparinux does not. Fondaparinux does carry this placement) and up to 28 days in patients with active cancer
indication in certain European Union countries. In the re- undergoing surgery for their cancer.8 Recent results from the
cent PROTECT trial, investigators randomized critical care EXCLAIM study suggest that there is a high-risk subgroup
patients to dalteparin 5000 units daily or unfractionated of hospitalized medical patients (namely, women, patients
heparin (UFH) 5000 units twice daily and found no signifi- with advanced age, or patients with complete immobility)
cant difference in the rate of proximal DVT, major bleeding, who may benefit from extended outpatient thromboprophy-
or inhospital death. However, there was a significant reduc- laxis.110 Results from two recent trials evaluating the use of
tion in the occurrence of PE with dalteparin as compared rivaroxaban and apixaban in VTE prophylaxis did not dem-
with UFH.105 onstrate additional benefits with either drug when used for
According to a recent systematic review conducted by approximately one month.111,112 Further studies are needed
the American College of Physicians (ACP), the use of hepa- to determine whether the use of thromboprophylaxis for the
rin in medical patients to prevent VTE decreases the rate of duration recommended in the drug labeling is safe and im-
pulmonary embolism but does not decrease mortality and proves outcomes in medical patients. The VTE Discharge
leads to more bleeding complications.106,107 No differences Alert Trial is currently assessing if a human alert to physi-
in risks or benefits were found between the types of heparin cians within 48 hours of planned patient discharge has any
used, though there was a nonsignificant difference favoring effect on increasing postdischarge prophylaxis or reducing
LMWH over UFH for PE (odds ratio, 0.67; confidence inter-
VTE within 90 days of hospital admission in the medical
val [CI], 0.45–1.00; p = 0.053; I2 = 0%). The use of mechani-
patient. Major bleeding events within 30 days of hospital ad-
cal devices led to adverse outcomes and did not demonstrate
mission are also being monitored.113 At a minimum, for the
any benefit. Therefore, in medical and stroke patients, ACP
majority of at-risk patients, the optimal duration of prophy-
currently recommends assessing the risks of VTE and bleed-
laxis is the length of the hospital stay if exposing risk factors
ing before starting VTE prevention and only using pharma-
are still present while considering the primary diagnosis and
cologic prophylaxis if the risk of VTE is greater than the
predisposing risk factors. Importantly, no studies evaluating
risk of bleeding. In addition, ACP recommends against using
the impact of ambulation on VTE have been conducted. A
mechanical devices to prevent VTE.106–108 These recommen-
recent study found that despite timely ambulation, medical
dations are similar to those of ACCP, which recommends an
patients were still at risk of VTE, and this risk was substan-
LMWH, a UFH two or three times daily, or fondaparinux for
tially reduced with enoxaparin prophylaxis.114 Therefore,
patients not at risk of bleeding but at risk of VTE. However,
patient ambulation or mobility should not be used as a rea-
ACCP does recommend mechanical means of prophylaxis,
son to discontinue, or restrict, prophylaxis during hospi-
such as IPC devices and graduated compression stockings
talization. Currently, ACCP guidelines recommend against
for patients at risk of bleeding and VTE. ACCP analyses did
extending the duration of thromboprophylaxis beyond the
not note any substantial difference in bleeding, VTE, or hep-
hospital stay or period of patient immobilization in the medi-
arin-induced thrombocytopenia between UFH two and three
cal patient.43
times daily.43 Because ACCP guidelines are in their ninth
edition and ACP guidelines are newly released, we recom-
mend using ACCP guidelines. Key guideline recommenda- Safety of Antithrombotic Prophylaxis
tions for the medical patient are listed in Table 4.
One of the major adverse events that can occur with the
Warfarin versus LMWHs and Fondaparinux. Because of use of heparin is heparin-induced thrombocytopenia (HIT).
its slow onset of action, variable responses among patients, HIT is an antibody-mediated adverse effect of heparin that
drug–drug and drug–food interactions, lower efficacy com- is strongly associated with venous and arterial thrombosis.
pared with LMWHs, need for frequent monitoring, and com- HIT is diagnosed when any of the following events occurs
plexity of both inhospital and postdischarge supervision, in association with the presence of HIT antibodies: an oth-
warfarin has largely been abandoned as thromboprophylaxis erwise unexplained decrease in platelet count, venous or
in Europe. Similarly, the ACCP guidelines concluded that arterial thrombosis, skin lesions at heparin injection sites,
LMWHs, and likely fondaparinux by indirect comparison, and acute systemic reactions (fever or chills, tachycardia,
are more effective than warfarin in preventing inhospital hypertension, dyspnea, cardiopulmonary arrest) that occur
VTE and should be preferred.8 Health-system pharmacists after i.v. heparin bolus administration.115 Although HIT can
should continue to educate themselves on emerging evidence occur with a prophylactic dose of both LMWH and UFH,
on the use of thromboprophylactic agents. They should also it happens about threefold more frequently with UFH than
familiarize themselves with the risks, benefits, and duration with LMWH and incurs approximately $41,133 of addi-
of use in relation to transitions among levels of care. tional costs per case.116,117 Because the occurrence of HIT
Table 4.
Existing Guideline Recommendations for Thromboprophylaxis of Hospitalized Medical and Critical Care
Patientsa
Group and Recommendations Modality and Grade of Recommendation(s)
American College of Chest Physicians (2012)
Acutely ill hospitalized medical patients at low risk of thrombosis: Do not use No thromboprophylaxis
pharmacologic prophylaxis or mechanical prophylaxis.
Acutely ill hospitalized medical patients at increased risk of thrombosis: Grade 1Bb
Provide anticoagulant thromboprophylaxis with LMWH, low-dose UFH twice
or three times daily, or fondaparinux and suggests against extending the
duration of thromboprophylaxis beyond the period of patient immobilization
or acute hospital stay.
Acutely ill hospitalized medical patients at increased risk of thrombosis Grade 2C
who are bleeding or are at high risk for major bleeding: Use mechanical
thromboprophylaxis using GCSs or IPC.
Critically ill patients: Use LMWH or low-dose UFH for thromboprophylaxis. Grade 2C
Critically ill patients who are bleeding or are at high risk for major bleeding: Grade 2C
Use mechanical thromboprophylaxis with GCSs and/or IPC at least until the
bleeding risk decreases.
American College of Physicians (2011)
Recommends assessment of the risk for thromboembolism and bleeding in Grade: strong recommendation; moderate-
medical (including stroke) patients before initiation of prophylaxis of VTE quality evidence
Recommends pharmacologic prophylaxis with heparin or a related drug for Grade: strong recommendation; moderate-
VTE in medical (including stroke) patients unless the assessed risk for quality evidence
bleeding outweighs the likely benefits
Recommends against the use of mechanical prophylaxis with GCSs for Grade: strong recommendation; moderate-
prevention of VTE quality evidence
Policy implication: The American College of Physicians does not support the
application of performance measures in medical (including stroke) patients
that promote universal VTE prophylaxis regardless of risk.
International Union of Angiology (2006)
Acutely ill medical patients (patients older than 40 years with acute medical UFH 5000 units three times daily (grade A),
illness and/or reduced mobility with one of the following morbidities: acute enoxaparin 40 mg once daily (grade A),
heart failure NYHA class III/IV, respiratory disease [respiratory failure with dalteparin 5000 units once daily (grade A),
or without ventilation or exacerbation of respiratory disease], active cancer fondaparinux 2.5 mg once daily (grade B)
requiring therapy, acute infective disease including severe infection and
sepsis, rheumatic disease, ischemic stroke, or acute myocardial infarction)
should be considered for prophylaxis. Patients with acute medical illness
with reduced mobility and one of the following risk factors—history of VTE,
malignant disease, or older than 75 years—should also be considered for
prophylaxis.
National Comprehensive Cancer Network (2011) LMWH, UFH 5000 units three times daily
Cancer patients
American Society of Clinical Oncology (2007) LMWH, UFH 5000 units three times daily
Hospitalized medical patients
a
LMWH = low-molecular-weight heparin, UFH = unfractionated heparin, GCSs = graduated compression stockings, IPC = intermittent
pneumatic compression, NYHA = New York Heart Association, VTE = venous thromboembolism.
b
Fondaparinux is not approved by the Food and Drug Administration for medical prophylaxis in the United States.
is more frequent with UFH, overall costs are likely reduced Major and minor bleeding can also occur with the
by using LMWH over UFH. Taking into consideration that use of prophylactic LMWH, warfarin, fondaparinux,
HIT may be a serious, limb-threatening and life-threatening and UFH. Overall, pharmacologic means of VTE pro-
complication, LMWH may be favored over UFH. Only a phylaxis carry a slightly higher risk of bleeding than
limited number of case reports of fondaparinux-induced placebo or mechanical means, but major bleeding
thrombocytopenia have been reported, and this may be an rates are negligible with prophylactic doses in well-
advantage of fondaparinux over LMWH and UFH. The new controlled clinical trials.23–25,118–121 In studies evaluating the
oral agents will likely also have an advantage over UFH and safety and efficacy of VTE prophylaxis in medical and surgi-
LMWH with regard to HIT and may be a useful alternative cal patients, the rate of major bleeding was between 0.2%
in patients with a history of HIT. and 2.7% among patients given pharmacologic prophylaxis.
One recent meta-analysis in medical patients demonstrated patients, patients with renal impairment, or pregnant pa-
no difference in major bleeding between pharmacologic tients are discussed below.
prophylaxis and placebo and also showed a reduction in fa-
tal PE with pharmacologic prophylaxis versus placebo.122 Major Trauma Patients. Trauma patients, including those
Another meta-analysis concluded that the use of UFH was with acute spinal cord injury, are among those with the
associated with substantially higher rates of major bleed- highest risk of developing VTE. Recommendations are to
ing than LMWH.123 A meta-analysis and two primary administer thromboprophylaxis to all trauma patients.55 One
studies have also demonstrated lower rates of injection- meta-analysis concluded that UFH alone as thrombopro-
site hematoma with LMWH than UFH.124,125 Bleeding rates phylaxis in trauma patients was not any more effective than
with fondaparinux appear comparable to those with LMWHs not using thromboprophylaxis.129 Therefore, according to
for both the medical and surgical patient.40,116 ACCP guidelines, LMWH is preferred over UFH in trauma
Patient groups at high risk for bleeding include those patients. One trial demonstrated that UFH combined with
with serious comorbid diseases, especially active malig- mechanical ankle flexion devices was superior to UFH alone
nancy or cerebrovascular, kidney, heart, and liver disease; in orthopedic trauma patients.130 Therefore, if used in this
older patients; those receiving concurrent antithrombotic patient population, UFH should be combined with mechani-
medications, including antiplatelets and fibrinolytics; pa- cal methods and not used alone. For patients undergoing re-
tients with thrombocytopenia (<100,000 mm3), a hemoglo- habilitation, prophylaxis is recommended to continue with
bin concentration of <13 g/dL (in surgical patients), severe LMWH or warfarin (target International Normalized Ratio
renal insufficiency (creatinine clearance [CLcr] of <30 mL/ [INR] of 2.5 [range, 2–3]) until the risk of VTE subsides,
min), active or recent peptic ulcer disease, recent gastroin- until full ambulation, or for up to three months in trauma
testinal or major bleeding, uncontrolled arterial hypertension patients with spinal cord injury.8,46
(systolic blood pressure of >200 mm Hg, diastolic blood
pressure of >120 mm Hg, or both), or bacterial endocarditis; Patients with Cancer. VTE prevention in this group is par-
and those who have undergone spinal tap or epidural anes- ticularly important, not only because patients with cancer
thesia within 12 hours.43–45,126 have a higher risk of VTE but because VTE is often more
A bleeding RAM from the IMPROVE registry was difficult to diagnose and treat in this population.8 Patients
developed and can be accessed at http://omnifik.com/dev/ who are confined to a bed and with an active malignancy
improve/bleeding/.127 Risk factors for bleeding continue should receive prophylaxis with an LMWH, a UFH, or
to be discovered and are individualized by patient group. fondaparinux.8,46 If there is a contraindication to pharma-
Contraindications to VTE prophylaxis should be agreed on cologic prophylaxis, graduated compression stockings or
at the institution and pharmacy levels. an IPC device should be used, with strong attention paid
The overall avoidance of a substantial number of VTE to compliance.8 Although patients with cancer have a par-
events and their subsequent morbidity is what makes VTE ticularly increased risk of developing VTE, they continue to
prophylaxis so persuasive and important. A recent review have the lowest rates of appropriate VTE prophylaxis.32–35,131
concluded that mortality rates associated with PE were sub- VTE prophylaxis should be initiated in cancer patients
stantially higher than those associated with major bleeding with solid tumors and additional VTE risk factors, including
from the use of anticoagulants, further supporting the focus previous venous thrombosis, immobilization, and the use of
on the prevention of the initial PE.128 The initial cost of pro- hormonal therapy, angiogenesis inhibitors, thalidomide, and
phylaxis reduces overall costs by avoiding VTE and its as- lenalidomide.43 Agents of choice include UFH and LMWH.
sociated morbidity. By and large, there is strong evidence Additional studies are needed to evaluate anticoagulants in
that appropriately dosed thromboprophylaxis has an advan- patients with cancer who do not have a traditional indication
tageous and favorable risk:benefit ratio.8,46 for thromboprophylaxis, such as those with recent cancer
now in remission or undergoing outpatient chemotherapy.8,46
Agreement on contraindications differs between key orga-
Recommendations
nizations and international experts, with some suggesting
that pharmacologic prophylaxis be used with platelet counts
Most hospitalized patients have multiple risk factors for
as low as 5,000 per microliter and others suggesting a low
VTE. Patients at high risk include those in critical care,
of 50,000.47 For more information on when to administer
as well as burn, trauma, surgical, and cancer patients. All
prophylaxis to cancer patients, refer to ACCP, NCCN, and
hospitalized patients, including patients in critical care or
ASCO guidelines.
with burns, should be assessed for the risk of VTE using
a RAM. Importantly, patients should be reassessed every
Surgical Patients. An abundance of trials involving surgi-
24–48 hours, or with pertinent clinical changes, for new or
cal patients have demonstrated substantial reductions in
resolved VTE, bleeding risk factors, and contraindications
VTE with UFH, LMWH, fondaparinux, and warfarin over
to prophylaxis. According to these risks, patients should be
placebo or equivalence or noninferiority to other effective
given an LMWH, a UFH, or fondaparinux prophylactically.
anticoagulants.8,44–46 Because the number of surgical studies
However, if there is a contraindication to pharmacologic
is so expansive and recommendations vary by patient group,
prophylaxis (e.g., active bleeding, high risk of bleeding,
readers are referred to the 2012 ACCP guidelines for spe-
allergy [including HIT within 100 days]), with inclusion
cific details. ACCP guidelines include recommendations and
of such documentation in the patient records, mechani-
background on
cal methods should be used for prophylaxis. Providers
should refer to current ACCP guidelines and NCCN/ASCO • General, vascular, laparoscopic, gynecological, uro-
guidelines for detailed recommendations for VTE prophy- logic, bariatric, thoracic, and coronary bypass surgery;
laxis for hospitalized patients. Special considerations for abdominal–pelvic surgery (including gastrointestinal);
trauma, surgical, and cancer patients as well as for obese major trauma,
• THR, TKR, knee arthroscopy, hip fracture surgery, Patients with Renal Impairment. Several studies have as-
timing of thromboprophylaxis initiation, screening for sessed the effects of LMWHs in patients with renal impair-
DVT before hospital discharge, and duration of throm- ment. Tinzaparin and dalteparin offer the most convincing
boprophylaxis for the aforementioned major orthope- data that these drugs may not accumulate in patients with
dic surgeries, severe renal impairment in both prophylactic and treatment
• Isolated lower-extremity injuries distal to the knee, doses.147–154 However, one recent study comparing tinzapa-
and rin with UFH for the treatment of VTE in elderly patients
• Craniotomy and spinal surgery. with renal insufficiency found increased mortality in the
tinzaparin group.155 The trial was stopped early because of
The following key points should be considered when initiat- these interim results, though the increased mortality was not
ing thromboprophylaxis for surgical patients: related to increased bleeding or VTE. There were nonsig-
nificant trends for tinzaparin-treated patients having higher
rates of VTE than those receiving UFH155; thus, more data
1. Aspirin and warfarin, with a target INR of 2.5, may be are needed. Of note, tinzaparin production was recently dis-
used for the orthopedic population. continued in the United States.156
2. Select mechanical methods may be used alone for The recent Dalteparin’s Influence on Renally
THR; TKR; hip fracture surgery; gynecologic, uro- Compromised anti-Ten-A (DIRECT) trial was a prospective
logic, laparoscopic, or coronary artery bypass surgical study of 120 critically ill patients with a CLcr of <30 mL/
groups; elective spine surgery; and neurosurgery.8 min, who had at least one trough anti-Xa level measured.150
3. LMWH, fondaparinux, and three times daily UFH are The investigators analyzed the safety of prophylactic dos-
typically options for surgical patients with multiple ages of dalteparin and found no bioaccumulation of the drug
VTE risk factors (i.e., high risk), with LMWH and in the patients. Interestingly, 62% of patients had acute re-
fondaparinux being preferred over three times daily nal failure at some point during their prophylactic regimen.
UFH in many high-risk surgical groups.8 These data suggest that in critically ill patients with severe
4. LMWH, fondaparinux, and twice-daily UFH are op- renal insufficiency, VTE prophylaxis with dalteparin is un-
tions in most moderate-risk surgical groups.8 likely to contribute to bleeding and is not associated with
5. The combination of IPC with pharmacologic prophy- an excessive anticoagulant effect due to bioaccumulation.150
laxis typically conveys a 60% further risk reduction in Enoxaparin, however, has shown accumulation when used at
VTE events.8 treatment dosages.157–161
6. LMWH is the preferred agent in THR, TKR, and hip Because there is conflicting evidence regarding the ac-
fracture surgery if patients do not have an increased cumulation of LMWHs in renally impaired patients, further
risk of bleeding. studies are needed. At this time, ACCP recommends using
an alternative agent or dosage-adjusted LMWH in patients
Obese Patients. Although more studies are needed, evi- who are renally impaired (CLcr of <30 mL/min). Because
dence supports the use of weight-based prophylactic dosing laboratory results are not immediately available on admis-
of LMWHs in obese patients (i.e., body mass index of >30 sion, it is important for pharmacists to review patients’ his-
kg/m2). Studies assessing anti-Xa levels at both treatment tory to determine if their LMWH dose needs to be adjusted
and prophylactic dosages demonstrated appropriate anti-Xa or if they should be switched to another agent. Twice-daily
levels and no accumulation of drug. Appropriate anti-Xa UFH 5000 units is an appropriate option in both hemodialy-
levels have been reported in obese patients receiving enoxa- sis patients and patients with severe renal impairment in the
parin, tinzaparin, and dalteparin dosed based on total body absence of contraindications. A recent review with recom-
weights of up to 144, 165, and 190 kg, respectively.132–136 mendations by Nutescu and colleagues146 addressed LMWH
One meta-analysis verified that major bleeding rates were use in both renal impairment and obesity across a wide array
not increased in obese patients who received weight-based of patients.
LMWH when compared with nonobese individuals.137
Nadroparin and enoxaparin have been studied in pro- Pregnant Patients. Pregnancy itself is a risk factor for the
spective studies of obese patients undergoing bariatric sur- development of VTE. VTE in this patient population is com-
gery and orthopedic surgery.138–142 Of note, nadroparin is plicated, and a thorough clinical history and risk assessment
not available in the United States. The usual recommended should be sought to determine antepartum and postpartum
prophylactic doses of these agents may be inadequate for prophylaxis needs. In general, an LMWH is preferred over
VTE prophylaxis in obese patients. For LMWHs, ACCP a UFH for the prevention and treatment of VTE because
guidelines recommend using weight-based dosing for obese of UFH’s increased risks of HIT and osteoporosis. At-risk
patients.8 For enoxaparin, the specific dosing that appeared pregnant patients should receive appropriate VTE prophy-
to be more favorable in bariatric surgery was 40 mg twice laxis per ACCP guidelines. For women undergoing cesarean
daily, though this may still be inadequate in some patients, delivery with at least one major or two minor risk factors,
and higher dosing may be more beneficial.142 Although dos- LMWH should be used or mechanical prophylaxis for pa-
ing suggestions are not yet well-defined in the literature, tients with contraindications to LMWH. For women under-
enoxaparin 0.5 mg/kg every 12–24 hours (e.g., depending on going cesarean delivery with multiple additional risk factors,
the level of obesity, with every-12-hour administration used LMWH should be combined with mechanical methods until
for patients with higher body mass indexes) has been used discharge. For selected high-risk patients, extended prophy-
successfully for prophylaxis at some centers.143–145 Dosage laxis should be considered. Readers are referred to the ACCP
increases of up to 30% have also been suggested.145 guidelines for recommendations regarding the prevention of
VTE in pregnant patients.162
Emerging Anticoagulant Options warfarin (hazard ratio, 0.88; 95% CI, 0.74–1.03; p < 0.001)
(p = 0.12 for superiority). Rivaroxaban received FDA ap-
At present, dabigatran, rivaroxaban, and warfarin are the proval for VTE prevention in TKR, THR, and atrial fibrilla-
only oral anticoagulants available, though dabigatran tion in 2011. However, because of the safety data and higher
and rivaroxaban have only recently gained approval for rates of clinically relevant bleeding, its use in medical pa-
stroke prevention in nonvalvular atrial fibrillation.163–166 tients cannot be recommended at this time.
Dabigatran does not have other indications at this time, and
its efficacy is based on the recently published RELY trial, Apixaban. Apixaban is a new, reversible, direct-acting
which demonstrated that dabigatran was superior to warfarin oral pyrazole-based factor Xa inhibitor that is 25% renally
with a similar rate of bleeding at a dosage of 150 mg twice cleared, is 60% bioavailable, and has a half-life of 9–14
daily.165 Although warfarin has been the only oral antico- hours. The drug is also cleared via the CYP3A4 isoenzyme
agulant available for more than five decades, it has several system; therefore, strong inducers and inhibitors will need
disadvantages when used for VTE prophylaxis in hospital- to be avoided. Apixaban is currently in advanced stages of
ized patients, as discussed above. The development of new testing for the prevention and treatment of thrombotic disor-
anticoagulants has focused on finding new oral formula- ders. It binds to the active site of factor Xa without requiring
tions, specifically targeting single procoagulant complexes antithrombin.167,168
critical to the coagulation process, including blocking the Currently, there are several multinational Phase III
initiation of coagulation, preventing the propagation of co- studies of apixaban being conducted for the prevention of
agulation, and inhibiting thrombin.167,168 There are several thrombotic events, including DVT and PE, in patients un-
types of monotargeted oral anticoagulants: direct inhibitors dergoing knee or hip replacement surgery. The results for
of activated factors IXa and Xa, which are involved in the one of these trials (ADVANCE-1) showed that the primary
propagation of coagulation, and direct inhibitors of thrombin endpoint (symptomatic or asymptomatic DVT, PE, or death
activity, which target factor IIa. Rivaroxaban and dabigatran from any cause) occurred in 9.0% of apixaban recipients (2.5
have recently been approved by FDA. The approval of apix- mg twice daily), compared with 8.9% of those treated with
aban, however, has been delayed due to FDA’s request for enoxaparin (30 mg twice daily) in TKR.173,174 Despite being
additional information. numerically similar, these figures did not meet the statisti-
cal criteria for apixaban noninferiority. The ADVANCE-2
Rivaroxaban. Rivaroxaban is an oral, reversible, once-daily trial was conducted in patients undergoing TKR. The results
factor Xa inhibitor that has an oral bioavailability of 80% demonstrated that apixaban (2.5 mg twice daily) was supe-
and a half-life of 7–11 hours; it is 67% renally cleared.164 rior to enoxaparin 40 mg subcutaneously once daily for VTE
Rivaroxaban is a substrate for P-glycoprotein 1 transporter, prevention without increased bleeding. The ADVANCE-3
located in the gut and kidneys, and is also metabolized via trial was conducted in patients undergoing THR, and its
cytochrome P-450 isoenzyme 3A4 (CYP3A4), so the use results demonstrated that apixaban was superior to enoxa-
of strong inducers or inhibitors of this isoenzyme should parin for VTE prevention at 35 days postsurgery with a
be avoided in patients receiving rivaroxaban. The safety similar rate of bleeding. In the ADOPT study of apixaban
and efficacy of rivaroxaban for VTE prevention after TKR for VTE prevention in medical patients, apixaban showed
and THR have been evaluated in four Phase III studies substantially increased major bleeding at 30 days without
(RECORD trials) in Europe and the United States.169–172 The demonstrating superiority on the primary composite VTE ef-
RECORD 1 and 2 trials were conducted in patients under- ficacy endpoint.168 These results are similar to those of the
going TKR; the RECORD 3 and 4 trials were conducted in MAGELLAN trial mentioned above. The agent is also in
those undergoing THR. Rivaroxaban was found to be supe- Phase II clinical testing in patients with metastatic cancer.174
rior to enoxaparin for preventing VTE and all-cause mortal-
ity with similar bleeding rates. In two of the four RECORD Dabigatran. Dabigatran is a potent, competitive, reversible
trials, rivaroxaban was superior to enoxaparin in the preven- direct thrombin (factor IIa) inhibitor with 80% renal excre-
tion of symptomatic VTE. The agent is approved for these tion, a 14 to 17-hour half-life, and 6% oral bioavailability.163
indications in Europe and Canada and has recently gained Dabigatran inhibits free thrombin, fibrin-bound thrombin,
FDA approval for the same indications within the United and thrombin-induced platelet aggregation. It is also a sub-
States.164 In the Phase III MAGELLAN study, the safety strate of Pgp1; therefore, strong inducers and inhibitors
and efficacy of extended prophylaxis with oral rivaroxaban should be avoided.167,168 Dabigatran has completed Phase III
(10 mg daily for 31–39 days) were compared to short-term clinical trials in Europe and the United States to evaluate its
prophylaxis with subcutaneous enoxaparin (40 mg daily for potential in thromboembolic disorders. It was approved for
6–14 days) for the prevention of VTE in medical patients. marketing by FDA in October 2010 for the prevention of
The results of this study indicate the superiority of rivaroxa- stroke and systemic embolism in patients with nonvalvular
ban over enoxaparin at day 35 for the composite endpoint of atrial fibrillation. It has also been approved by the European
asymptomatic proximal DVT, symptomatic DVT, symptom- Medicines Agency for primary prevention of VTE in adult
atic nonfatal PE, and VTE-related death. However, this came patients who have undergone elective hip or knee replace-
at the cost of substantially more major bleeding events.109 ment and has been subsequently launched in the United
The relative risk of bleeding compared with enoxaparin at Kingdom and Germany.168
10 and 35 days was 2.3 (p < 0.001) and 2.5 (p < 0.001), Three Phase III trials (RE-MODEL, RE-NOVATE,
respectively. Because of these safety results, the risk:benefit RE-MOBILIZE) have been undertaken to study dabigatran
ratio of rivaroxaban in medical patients is questionable. In versus enoxaparin in the prevention of major VTE and VTE-
the ROCKET-AF study, based on the primary endpoint of related mortality after both knee and hip replacement sur-
stroke or systemic embolism in patients with nonvalvular gery. The RE-MODEL (TKR) and RE-NOVATE (THR) met
atrial fibrillation, rivaroxaban was found to be noninferior to noninferiority criteria versus enoxaparin 40 mg daily, but the
RE-MOBILIZE (TKR) failed to meet noninferiority criteria Postoperative orthopedic, cardiac, and vascular surgery pa-
against enoxaparin 30 mg twice daily. Rates of major bleed- tients receiving UFH for one to two weeks for thrombopro-
ing were comparable between the treatment groups.173,174 phylaxis have the highest risk of HIT, ranging from 1% to
5%.115 In this patient group, platelet count should be moni-
Potential Benefits and Limitations of Emerging Agents. tored at least every other day between postoperative days 4
The new oral anticoagulants are considered to be more con- and 14 or until UFH is stopped (if before day 14), whichever
venient and simpler to use than vitamin K antagonists, be- occurs first.115 The risk of HIT is lower (0.1–1%) among
cause routine measuring of anticoagulant effects and dose postoperative patients receiving an LMWH or intravascular
adjustment are not required. Their oral route of adminis- catheter UFH flushes and medical or obstetric patients re-
tration as compared with injectables is favorable and may ceiving LMWH after previously receiving UFH. For these
improve adherence and simplify postdischarge prophylaxis. patients, platelet monitoring should occur at least every two
Ecarin clotting time, thrombin time, activated partial throm- or three days from day 4 to 14, or until the UFH or LMWH
boplastin time, and activated clotting time have theoretical is stopped (if before day 14), whichever comes first.115
potential to be used for measures of anticoagulant effect of When the estimated risk of HIT is less than 0.1%, the risk
dabigatran, whereas factor Xa levels and prothrombin time is described as “rare.” Patients in this group include medi-
have the potential to measure the anticoagulant effect of cal and obstetric patients receiving only LMWH or medical
apixaban and rivaroxaban. In addition, direct thrombin inpatients receiving only intravascular catheter UFH flushes,
hibitor measurement assays and reversal agents are under and platelet monitoring is not recommended.
development for dabigatran. Most of these agents undergo Because LMWH and fondaparinux are cleared renally,
renal clearance, which could lead to drug accumulation in pharmacists play an integral role in monitoring the safety
patients with renal impairment. and efficacy of therapy. They should pay close attention
Currently, there are no antidotes for rivaroxaban, apix- to patients’ renal function and make appropriate dosage
aban, or dabigatran to rapidly reverse drug effects if required. changes or modify prophylaxis to other appropriate regi-
This is also a current limitation shared by fondaparinux. mens in collaborative environments. This may be accom-
LMWH can be partially reversed by protamine, whereas plished by measuring anti-Xa levels.
UFH can be fully reversed with protamine. Because these
novel oral anticoagulants have longer half-lives than UFH Summary
and LMWH, any adverse effects caused by direct inhibition
of thrombin or factor Xa will continue for several hours or Despite decades of evidence showing that pharmacologic
days after the cessation of therapy. and mechanical means can help prevent VTE in hospital-
ized at-risk patients, current national and international pre-
Cost-Effectiveness of vention strategies remain suboptimal. National organization
Antithrombotic Prophylaxis positions are shifting to include omission of appropriate care
as an adverse event or adverse drug event. Therefore, omis-
For the initial hospital admission, the costs of DVT and PE sion of VTE prophylaxis in a patient who develops a VTE
are $9,805 and $14,146, respectively, and readmission costs is considered an adverse drug event if pharmacologic pro-
for the same events are $11,862 (DVT cost significantly phylaxis was indicated or as an adverse event if mechanical
higher, p = 0.006) and $14,722, respectively.42 With the cost prophylaxis was indicated. To date, no adverse-drug-event
of prophylaxis for approximately 10 days being $20–$250 studies are including “omission” of VTE prophylaxis as an
for most pharmacologic agents, cost efficacy for pharmaco- adverse drug event. Inclusion of this adverse drug event will
logic prophylaxis is well established. A median of 10 days is substantially increase the financial implications of adverse
a common duration of therapy for prophylaxis used in many drug events nationally.
medical and surgical trials not requiring an extended dura- Future studies are needed in VTE prevention, includ-
tion of therapy. A minimum duration of 10 days is also rec- ing elicitation of the optimal duration of thromboprophy-
ommended for THR, TKR, and hip fracture surgery patients. laxis (especially after hospital discharge because of the short
Length of hospitalization and hospital costs have also been lengths of stay in U.S. hospitals), the optimal use of cur-
found to be substantially increased for patients who develop rently approved agents for prophylaxis, the impact of pre-
VTE.175,176 One retrospective analysis demonstrated that to- ventable VTE as an adverse event or adverse drug event,
tal costs were not different for patients who were given pro- and validation of individual scoring methods, especially in
phylaxis with LMWH versus UFH, though VTE rates were hospitalized settings. Hospital pharmacy leadership and pro-
substantially lower with LMWH versus UFH.177 Two other active engagement are driving forces to ensure appropriate
studies found lower total costs of LMWH versus UFH178,179 prophylactic management of VTE in hospitalized patients.
and cost-effectiveness of primary prophylaxis to prevent Recent data revealed that inhospital, pharmacy-driven
VTE over no prophylaxis.111 With the introduction of ge- VTE prevention programs can increase the use of appro-
neric enoxaparin and future agents—including a generic priate thromboprophylaxis and reduce VTE events. VTE
fondaparinux, dabigatran, apixaban, and rivaroxaban—the prophylaxis programs and anticoagulation management,
cost of VTE prophylaxis will likely continue to decrease. especially in hospitalized settings, are opportunities that
pharmacists can take advantage of in their respective health
Monitoring Antithrombotic Prophylaxis care settings to reduce unnecessary morbidity and mortality
from this disease. Because of their expertise in pharmaco-
Although the incidence of HIT with LMWH and UFH var- therapy, pharmacists are poised to take a leadership role in
ies by patient group, HIT occurs much more frequently (i.e., VTE prevention programs to positively affect patient care
threefold) with the use of UFH compared with LMWH. within hospitals and beyond.
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Tinzaparin sodium injection. www.ashp.org/ Rivaroxaban versus enoxaparin for thromboprophy-
DrugShortages/NotAvailable/bulletin.aspx?id=749 laxis after total knee arthroplasty (RECORD 4): a ran-
(accessed 2012 Oct 12). domised trial. Lancet. 2009; 373:1673–80.
157. Brophy D, Wazny L, Behr T, et al. The pharmacoki- 173. Merli G, Spyropoulos A, Caprini J. Use of emerg-
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evation acute coronary syndromes. Am Heart J. 2002; nous thromboembolism following major orthopedic
143:753–9. surgery in hospitalized patients. Am J Health-Syst
159. Chow S, Zammit K, West K, et al. Correlation of anti- Pharm. 2002; 59:1750–4.
factor Xa concentrations with renal function in patients 176. Mcgarry LJ, Stokes ME, Thompson D. Outcomes of
on enoxaparin. J Clin Pharmacol. 2003; 43:586–90. thromboprophylaxis with enoxaparin vs. unfraction-
160. Sanderink G, Guimart C, Ozoux ML, et al. Pharmaco- ated heparin in medical inpatients: a retrospective da-
kinetics and pharmacodynamics of the prophylactic tabase analysis. Thromb J. 2006; 4:17.
dose of enoxaparin once daily over 4 days in patients 177. Weinberg R, Lichtig LK, Caprini JA, et al. Cost impli-
with renal impairment. Thromb Res. 2002; 105:225– cations of using unfractionated heparin or enoxaparin
31. in medical patients at risk for venous thromboembolic
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bleeding complications: a review in patients with and 178. Deitelzweig SB, Becker R, Lin J, et al. Comparison
without renal insufficiency. Pharmacotherapy. 2000; of the two-year outcomes and costs of prophylaxis in
20:771–5. medical patients at risk of venous thromboembolism.
162. Bates SM, Greer IA, Pabinger I, et al. Venous throm- Thromb Haemost. 2008; 100:810–20.
boembolism, thrombophilia, antithrombotic therapy,
and pregnancy: American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines (8th edi- Approved by the ASHP Board of Directors on April 13, 2012.
tion). Chest. 2008; 133(suppl):844S–886S. Developed through the ASHP Council on Therapeutics.
163. Boehringer Ingelheim. Pradaxa (dabigatran etexilate)
prescribing information. www.pradaxa.com (accessed The following individuals are acknowledged for reviewing draft ver-
2012 Oct 2). sions of this statement: Kathleen Achor, Jill Bates, Pharm.D., M.S.,
164. Janssen Pharmaceuticals. Xarelto (rivaroxaban) pre- BCOP; Tim Brown, Pharm.D.; Debra Cowan, Pharm.D.; Michele
scribing information. www.xarelto-us.com (accessed Danish, Pharm.D., FASHP; Jean B. Douglas Pharm.D., FASHP;
2012 Oct 2). Stuart T. Haines, Pharm.D., BCPS, FASHP; Jody Jacobson Wedret,
165. Connelly S, Ezekowitz MD, Yusuf S, et al. Dabigatran B.S.Pharm., FASHP, FCSHP; Patrick McDonnell, Pharm.D.;
versus warfarin in patients with atrial fibrillation. N Nicole L. McMaster-Baxter, Pharm.D., M.S., BCPS; Fred Meister,
Engl J Med. 2009; 361:1139–51. Pharm.D.; Charles D. Ponte, Pharm.D., DPNAP, FCCP, FAPhA,
166. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban FASHP; James A. Ponto, M.S., B.S.Pharm., FASHP; and Kay Ryan,
versus warfarin in nonvalvular atrial fibrillation. N M.S., M.B.A.
Engl J Med. 2011; 365:883–91.
167. Mahan CE, Fanikos J. New antithrombotics: the Charles E. Mahan, Pharm.D., Ph.C., is Director of Outcomes
impact on global health care. Thromb Res. 2011; Research, New Mexico Heart Institute, Albuquerque, NM. Alex C.
127:518–24. Spyropoulos, M.D., FACP, FCCP, FRCPC, is Associate Professor
168. Weitz JI, Eikelboom JW, Samama MM. New an- of Medicine, Division of Hematology/Oncology, James P. Wilmot
tithrombotic drugs: Antithrombotic Therapy and Cancer Center, University of Rochester Medical Center, Rochester,
Prevention of Thrombosis, 9th edition: American NY.
Dr. Mahan is a participant in the Traveling Fellowship Program for The bibliographic citation for this document is as follows: American
the North American Thrombosis Forum. Dr. Spyropoulos serves Society of Health-System Pharmacists. ASHP therapeutic posi-
on the advisory board of Johnson and Johnson, Pfizer, and Bristol- tion statement on the role of pharmacotherapy in preventing ve-
Myers Squibb and on the steering committee of Bayer and Eisai. He nous thromboembolism in hospitalized patients. Am J Health-Syst
also serves on the data safety monitoring board of Portola. Pharm. 2012; 69:2174–90.

ASHP Therapeutic Position Statement

on Strategies for Identifying and Preventing
Pneumococcal Resistance
Position come, primarily mortality, when pneumonia or other non-

meningeal infections due to PNSP are treated with penicillin
The American Society of Health-System Pharmacists or cephalosporins. On the contrary, macrolides and fluoro-
(ASHP) supports the establishment of state and national sur- quinolones with poor in vitro activity against S. pneumoniae
veillance systems to track the prevalence of drug-resistant have been associated with poor clinical outcomes and even
Streptococcus pneumoniae so that appropriate antimicrobial treatment failures. It is likely that clinical outcomes are de-
regimens can be used to treat infections caused by this com- pendent on the mechanism and degree of resistance, the site
mon community-acquired pathogen. of infection, and the pharmacokinetic and pharmacodynamic
ASHP supports continued educational efforts to pro- characteristics of the antimicrobial agents used in treatment.
mote the rational use of antimicrobials as a strategy for pre-
venting the development of drug-resistant bacteria. Definitions. The Clinical and Laboratory Standards Institute
ASHP supports pharmacist leadership and involve- (CLSI), previously known as the National Committee for
ment on antimicrobial stewardship teams and the addition of Clinical Laboratory Standards, revised the definitions of S.
antimicrobial stewardship as a core component of pharmacy pneumoniae susceptibility to several antimicrobials in its
services. 2002 standards. Since that time, there have been two sets of
ASHP supports the pharmacist in administration of interpretive criteria for S. pneumoniae isolates for i.v. peni-
vaccines for all persons at risk for acquiring pneumococcal cillin and i.v. cephalosporins, depending on whether menin-
disease. ASHP encourages the development of pharmacy- geal disease is present. S. pneumoniae resistant to penicillin
based programs to increase pneumonia vaccination rates of is defined in terms of the minimum inhibitory concentration
at-risk patients. Use of pneumococcal vaccines is a reliable (MIC) of penicillin. Strains in a patient with meningeal dis-
strategy to decrease the morbidity and mortality associated ease may be distinguished as susceptible (MIC < 0.06 mg/
with invasive infections due to S. pneumoniae. mL) or resistant (MIC ≥ 0.12 mg/mL). Strains in a patient
with nonmeningeal disease may be characterized as sus-
Background ceptible (MIC ≤ 2 mg/mL), intermediately resistant (MIC
= 4 mg/mL), or highly resistant (MIC ≥ 8 mg/mL).2 CLSI ac-
S. pneumoniae, also known as pneumococcus, is the most counted for the pharmacokinetic and pharmacodynamic fac-
common cause of community-acquired, bacterial, respirators of a drug in redefining susceptibility breakpoints. The
tory-tract infections. It is a frequent cause of meningitis, oti- definition of MDRSP is a strain resistant to three or more
tis media, and community-acquired pneumonia. Infections classes of antibacterials (where those antibacterials may
caused by S. pneumoniae have been associated with in- have activity).
creased morbidity and mortality, especially in children under
two years of age and elderly adults. Infections caused by S. Epidemiology. Numerous national and international sur-
pneumoniae have historically been successfully treated with veillance studies have been conducted to determine the
a variety of antimicrobials, including penicillin, cephalospo- prevalence of S. pneumoniae resistance.3–7 Although many
rins, and erythromycin. In the early 1990s, the first reports of these surveillance studies have discontinued the annual
of penicillin-nonsusceptible S. pneumoniae (PNSP) began to collection of data, the Active Bacterial Core Surveillance,
appear in the United States; these strains include both inter- known as the ABCs, remains active in the United States.8
mediately resistant and resistant strains of S. pneumoniae. These networks used similar methodologies and specimens:
To date, reports of increasing resistance of S. pneumoniae clinical isolates of S. pneumoniae from sterile body sites
to penicillin and cephalosporins continue. In the late 1990s, or the respiratory tract, with susceptibility testing in accor-
reports of increasing resistance to trimethoprim–sulfa- dance with CLSI standards. Although these studies showed
methoxazole, macrolides, and fluoroquinolones began to ap- differing resistance rates to the antimicrobials tested, some
pear. Many isolates developed resistance to multiple classes common trends emerged. The incidence of strains highly
of drugs and became known as multidrug-resistant S. pneu- resistant to penicillin has surpassed that of intermediately
moniae (MDRSP). The increasing prevalence of MDRSP resistant strains. The rates of resistance to non-b-lactams
has created a challenge for health care providers in treating have also increased: the prevalence of macrolide resistance
this common community-acquired pathogen. is 20–30%, and trimethoprim–sulfamethoxazole resistance
The clinical significance of drug-resistant S. pneu- ranges between 24% and 38%. S. pneumoniae resistance to
moniae on treatment outcomes is unclear. Most of the levofloxacin is hovering around less than 1%. ABCs per-
available data on clinical outcomes are from retrospective sonnel evaluate the incidence and susceptibility of invasive
reviews, case–control studies, and case reports. There is S. pneumoniae infections in the United States.8 This surveil-
evidence that meningitis due to PNSP does not respond to lance group does not distinguish resistance based on loca-
treatment with either penicillin or standard doses of cephalo- tion of disease (i.e., meningeal versus nonmeningeal). For
sporins, leading to poor clinical outcomes.1 In contrast, there the 2010 isolates, the rates of strains intermediately resistant
does not appear to be a significant difference in clinical out- and highly resistant to penicillin were similar (5.5% and
5.1%, respectively).8 Resistance to macrolides was 25.7%, ing and tracking global outbreaks, identifying new strains
which greatly surpassed the intermediately resistant strains and resistance profiles, setting public health policy, height-
(0.5%), leaving 73.8% of strains susceptible. Trimethoprim– ening awareness of health care providers to local resistance
sulfamethoxazole susceptibility was slightly higher than patterns that may affect the routine care of patients, and de-
the macrolides, at 77.6%, and tetracycline susceptibility termining appropriate treatment for infections.
was higher at 84.9%. Fluoroquinolone (levofloxacin spe- Health systems should develop a mechanism for the
cifically) resistance remained low at 0.3%, and vancomy- local surveillance of bacterial resistance and participate in
cin remained universally susceptible (100%). Previously, state and national surveillance programs when available.
there were reports from Canada9 and the Centers for Disease Ideally, the surveillance system should identify trends in
Control and Prevention (CDC)10 of increasing resistance bacterial susceptibility patterns and correlate them with an-
of S. pneumoniae to fluoroquinolones. Most fluoroquino- timicrobial use in both health systems and communities.15
lone-resistant isolates are resistant to other antimicrobials. The clinical microbiology laboratory, pharmacy, infection
Fluoroquinolone-resistant organisms are more likely to be prevention, and information technology departments play
found in persons over age 65 years, as this population has important roles in maintaining an active surveillance system.
the highest usage rate of fluoroquinolones. At a national level, data acquired through surveillance
systems such as those used by CDC and the World Health
Persons at Risk. The greatest risk factor for becoming in- Organization (WHO) can aid in the research and develop-
fected with a drug-resistant strain of S. pneumoniae is prior ment of policies and treatment guidelines for pneumococcal
antimicrobial use. Other risk factors include carriage of S. disease. State and local surveillance is also essential, as na-
pneumoniae, daycare attendance, exposure to children who tional trends may not reflect trends within specific regions.
attend daycare, severe medical comorbidities, immunosup- On a local level, surveillance programs can help raise pro-
pression, and high alcohol intake.1 Smoking has been identi- vider and public awareness of drug-resistant S. pneumoniae
fied as a risk factor for developing invasive S. pneumoniae and direct patient care on an institutional level and poten-
infections.11 The risk of invasive S. pneumoniae infections is tially on the unit level. Institutional antibiograms should
4-fold if the patient is a smoker and 2.5-fold if the patient is be updated annually, and microbiological data used for di-
exposed to secondhand smoke.11 The risk of invasive disease agnosis should be stored in a way that will facilitate resis-
declines over time for persons who have stopped smoking. tance surveillance.16,17 Surveillance data may also be useful
for tracking the impact of interventions, such as formulary
Mechanisms of Resistance. Resistance of S. pneumoniae to changes and antimicrobial stewardship interventions, target-
b-lactams is due to genetic mutations leading to alterations ing the inappropriate or unnecessary use of antibiotics.
in three or four of the five high-molecular-weight penicillin-
binding proteins (PBPs).12 The degree of S. pneumoniae re- Rational Use of Antimicrobials
sistance is dependent on which PBPs are involved and the
affinity of the b-lactam agent to the PBP. The differences in There is an abundance of literature showing the relationship
expression of these PBPs explain the differences in suscepti- between antimicrobial-use patterns and the development of
bility to a variety of b-lactams. bacterial resistance.18–21 However, the bulk of this literature
S. pneumoniae resistance to macrolides occurs pri- thus far has been generated from hospital or institutional
marily through two mechanisms: active drug efflux (M studies and has little bearing on PNSP. Since S. pneumoniae
phenotype) or ribosomal modification (MLSb phenotype).13 is primarily a community-acquired pathogen, antimicrobial
Active drug efflux confers resistance to all macrolide agents, use in the outpatient setting has the greatest influence on its
whereas ribosomal modification confers resistance not only susceptibility profile. Few studies have shown a relationship
to the macrolides but also to lincosamides (e.g., clindamy- between outpatient prescription use or antimicrobial stew-
cin) and streptogramins. Almost 100% of macrolide-resis- ardship interventions and S. pneumoniae susceptibility pat-
tant S. pneumoniae found in the United States is attributable terns. In the United States, Diekema and colleagues22 found
to ribosomal modification via methylation.13 a positive correlation between high usage rates of outpatient
Resistance of S. pneumoniae to fluoroquinolones is pri- b-lactam agents and the decreased penicillin susceptibility of
marily a result of the mutations of the parC and gyrA genes, S. pneumoniae. No correlation was found between the use of
though efflux pumps may also play a role.14 Alterations in other antimicrobial classes (e.g., macrolides, tetracyclines,
the parC subunit of topoisomerase IV result in the reduced fluoroquinolones) and the decreased penicillin susceptibil-
susceptibility of S. pneumoniae to gatifloxacin, levofloxa- ity of S. pneumoniae. More recently, Hicks et al.23 reviewed
cin, and moxifloxacin. This single-step mutation is difficult outpatient antimicrobial prescription data (penicillins, ceph-
to detect clinically because isolates with a parC mutation alosporins, macrolides, and trimethoprim–sulfamethoxa-
are reported as susceptible using standard laboratory testing. zole) and found a consistent relationship between higher
This is concerning because isolates with single-step muta- prescription rates and increased rates of S. pneumoniae
tions are the progenitors for fully drug-resistant strains of nonsusceptibility to the respective antimicrobial class. This
S. pneumoniae, which have additional mutations in the gyrA study also found that when comparing sites with high ver-
subunit of DNA gyrase. sus low antimicrobial prescription rates for the same class
of antimicrobials, macrolide and cephalosporin prescrip-
Establishment of Surveillance Systems tions were both associated with serotype 19A, despite yearly
decreases in outpatient antimicrobial prescribing rates. Both
Surveillance systems are an integral component of combat- of these studies were large, retrospective database studies
ing bacterial resistance. The data gathered from surveillance and did not account for patient adherence to antimicrobial
systems can be used for many purposes, including identify- regimens. However, these studies demonstrated that antimi-
crobial use in the community is substantial and plays a role 2003, was renamed Get Smart: Know When Antibiotics
in the development of microbial resistance. Work campaign.28 This campaign was launched in response
Approximately 50% of prescriptions for antimicro- to growing antimicrobial resistance with respiratory patho-
bials are unnecessary or inappropriate.24 These agents are gens and aims to reduce the rise of antimicrobial resistance
usually prescribed for treatment of the common cold, upper- through the promotion of appropriate prescribing, decrease
respiratory-tract infections, acute rhinosinusitis, and bron- the demand for antimicrobials to treat viral respiratory in-
chitis, ailments often caused by viruses that do not respond fections, and increase patient adherence with antimicrobials
to antibacterials. Recent clinical practice guidelines from prescribed for upper-respiratory-tract infections. This pro-
the Infectious Diseases Society of America for acute bac- gram provides a wealth of information for the antimicrobial
terial rhinosinusitis in children and adults acknowledged stewards and the public to help increase awareness at their
the difficulty in distinguishing between viral and bacterial facilities and includes promotional material for inpatient,
etiologies. To decrease inappropriate antibacterial use, the outpatient, and long-term-care settings.
guidelines recommend initiating antibacterials only if the
patient has symptoms that are persistent and not improving Vaccination
(duration of ≥10 days), severe (≥3–4 days), or worsening or
“double sickening” (subsequent worsening of symptoms or Pneumococcal infection has been associated with 2.4 mil-
additional symptoms after earlier improvement). Prescribers lion days of hospitalization and approximately 5000 deaths
for patients who do not yet meet the criteria for antibacterial annually in the United States.29 As vaccination may contrib-
treatment of rhinosinusitis will occasionally give a prescrip- ute to a reduction in these numbers and because hospital-
tion for antibacterials with the instructions to fill and take ization is an underutilized opportunity for vaccination, the
the medication if symptoms are persistent. Pharmacists can Joint Commission (in collaboration with the Centers for
assist patients in making appropriate decisions on antimi- Medicare and Medicaid Services) in January 2012 expanded
crobial use by counseling patients on the appropriate tim- the pneumococcal vaccination process measure to include
ing of initiating antibacterials as well as the importance of all patients regardless of diagnosis. This measure evaluates
completing the prescribed treatment course. In addition, em- if, before hospital discharge, patients age 6 years or older
pirical antibacterial selection should not include amoxicillin, were screened for pneumococcal vaccine status and received
macrolides, trimethoprim–sulfamethoxazole, or monother- the pneumococcal vaccine if appropriate. Infections caused
apy with second- or third-generation cephalosporins due to by S. pneumoniae continue to cause significant morbidity
high rates of resistance in S. pneumoniae. Finally, a shorter and mortality despite the availability of effective vaccines.
course of antibacterial treatment (5–7 days) is recommended The 23-valent pneumococcal polysaccharide vaccine
for adults, compared with the 10–14 days recommended (PPSV23), the 13-valent pneumococcal conjugate vaccine
for children. Several national organizations,15,24 CDC, and (PCV13), and the 7-valent pneumococcal conjugate vaccine
WHO have advocated antimicrobial stewardship as a mech- (PCV7) have been shown to be highly effective in providing
anism to limit the development of bacterial resistance.25,26 protection against the most commonly isolated pneumococ-
One of the cornerstones of antimicrobial stewardship is the cal serotypes that cause human disease, including those se-
appropriate use of antimicrobials. Pharmacists should take rotypes known to be antimicrobial resistant. While the use
active roles in antimicrobial stewardship programs, and the of these vaccines will not prevent the development of drug-
infectious diseases pharmacist is considered a core member resistant S. pneumoniae, they will likely prevent invasive
of the antimicrobial stewardship team.24,27 infection caused by a drug-resistant organism. PPSV23 is
In 1995, CDC launched the National Campaign for recommended for all adults age 65 years or older and other
Appropriate Antibiotic Use in the Community, which, in adults with certain comorbid conditions.30 It may also be
Table 1.
Patients Who Should Receive the 13-Valent Pneumococcal Conjugate Vaccine (PCV13)
Risk Group Underlying Medical Condition
Immunocompetent persons Cerebrospinal fluid leak
Cochlear implant
Immunocompromised persons Congenital or acquired immune deficiency
Human immunodeficiency virus infection
Chronic renal failure
Nephrotic syndrome
Leukemia
Lymphoma
Hodgkin disease
Generalized malignancy
Iatrogenic immunosuppression (diseases requiring treatment with
immunosuppressive drugs, including long-term systemic corticosteroids
and radiation therapy)
Solid organ transplant
Multiple myeloma
Persons with functional or anatomical asplenia Sickle cell disease or other hemaglobinopathy
Congenital or acquired asplenia
given to select groups of high-risk patients over 2 years of recommended for all children age 14–59 months and for
age (such as those with cochlear implants) as long as it is children age 60–71 months with certain underlying medi-
administered at least eight weeks after administration of the cal conditions who have already received an age-appropriate
last dose of PCV7 or PCV13. This PPSV23 vaccine does PCV7 series.32 The CDC National Immunization Program
not produce an adequate immunologic response in children has established recommendations for pneumococcal vaccine
under 2 years old and should not be used in that popula- administration.30,32
tion. PCV7 was added to the standard recommended pediat- PPSV23 was licensed in the early 1980s and has dem-
ric vaccines in October 2000.31 PCV13 was added in 2010. onstrated good immunogenicity in both young and older
The PCV series should be given to all children beginning adults; however, an individual will not develop an immune
at age 2 months. A single supplemental dose of PCV13 is response to all 23 pneumococcal serotypes.33 The reason for
Table 2.
Medical Conditions or Other Indications for Administration of 13-Valent Pneumococcal Conjugate Vaccine
(PCV13), and Indications for 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23) Administration and
Revaccination for Adults Age 19 Years or Older24,a
PCV13 PPSV23
Risk Group and Underlying Recommended Recommended Revaccination
Medical Condition 5 Years After First Dose
Immunocompetent persons
Chronic heart diseaseb X
Chronic lung diseasec X
Diabetes mellitus X
Cerebrospinal fluid leak X X
Cochlear implant X X
Alcoholism X
Chronic liver disease, X
cirrhosis
Cigarette smoking X
Persons with functional or
anatomic asplenia
Sickle cell disease or other X X X
hemaglobinopathy
Congenital or acquired X X X
asplenia
Immunocompromised
persons
Congenital or acquired X X X
immunodeficiencyd
Human immunodeficiency X X X
virus infection
Chronic renal failure X X X
Nephrotic syndrome X X X
Leukemia X X X
Lymphoma X X X
Hodgkin disease X X X
Generalized malignancy X X X
Iatrogenic X X X
immunosuppressione
Solid organ transplant X X X
Multiple myeloma X X X
a
All adults age ≥65 years should receive a dose of PPSV23, regardless of previous history of vaccination with pneumococcal vaccine.
b
Including congestive heart failure and cardiomyopathies, excluding hypertension.
c
Including chronic obstructive pulmonary disease, emphysema, and asthma.
d
Includes B- (humoral) or T-lymphocyte deficiency, complement deficiencies (particularly C1, C2, C3, and C4 deficiencies), and phagocytic
disorders (excluding chronic granulomatous disease).
e
Diseases requiring treatment with immunosuppressive drugs, including long-term systemic corticosteroids and radiation therapy.
this is unclear. Despite the vaccine’s long-standing avail- vaccines, with 13 states authorizing pharmacists to vaccinate
ability and documented effectiveness, approximately 64% patients of any age.46 Although vaccinations are typically
of eligible persons actually receive it.34 One of the Healthy administered in the ambulatory care setting, clinicians must
People 2020 goals is for 90% of eligible adults to receive the also seize opportunities to vaccinate hospitalized patients
pneumococcal vaccine.35 This is an excellent opportunity for (Figure 1). Pharmacists have demonstrated that they can in-
pharmacists to improve the vaccination rate of older adult crease the number of persons receiving needed vaccines in
patients and help promote national health care goals. both inpatient and ambulatory care settings.47
Revaccination with PPSV23 is recommended for adults
over age 65 years if the first dose was administered when they Summary
were under 65 years old at the time of vaccination and at least
5 years has elapsed since the first dose.30 In addition, persons The incidence of MDRSP continues to increase, causing
younger than 65 years with immunocompromising conditions significant morbidity and mortality. Health care providers
may receive a one-time revaccination if 5 years has elapsed should seize the opportunity to promote the judicious use
since the first dose of PPSV23. Revaccination with PPSV23 of antimicrobials and vaccinate patients with the pneumo-
results in a somewhat blunted immune response and is associ- coccal vaccines as a means to lessen this significant health
ated with increased injection-site reactions.33 problem. Pharmacists are poised to play a key role in patient
PCV7 for children has been available since February care by assessing for the need and administering vaccines in
2000. Use of this vaccine has been shown to decrease the compliance with the current guidelines. A pharmacist should
carriage rate of S. pneumoniae and the incidence of invasive have a key role on the antimicrobial stewardship team.
pneumococcal disease, acute otitis media, and pneumonia in
vaccinated populations.36,37 The rate of vaccine-specific sero-
References
type S. pneumoniae carriage in vaccinated children remains
below the rate for nonvaccinated children over prolonged pe-
1. Pallares R, Fenoll A, Liňares J, for the Spanish
riods of time. Widespread vaccination of children with PCV7
Pneumococcal Infection Study Network. The epi-
has shown a “herd effect” in decreasing the carriage rate of S.
demiology of antibiotic resistance in Streptococcus
pneumoniae in children, who are an important vector for the
pneumoniae and the clinical relevance of resistance to
transmission of S. pneumoniae to other children and adults.36
cephalosporins, macrolides and fluoroquinolones. Int
This is similar to what was seen with widespread use of the
J Antimicrob Agents. 2003; 22(suppl 1):S15–24.
Haemophilus influenzae type B vaccine and the marked de-
2. Performance standards for antimicrobial susceptibility
crease in H. influenzae-related infections.
testing; 23rd informational supplement. Wayne, PA:
PCV13 for children and adults has been available since
Clinical and Laboratory Standards Institute; 2013.
February 2010 and has taken the place of the discontinued
3. Centers for Disease Control and Prevention. ABCs re-
PCV7. All children age 2–59 months should have routine im-
port: Streptococcus pneumoniae, 2001. www.cdc.gov/
munization with PCV13.32 CDC has established routine and
abcs/reports-findings/survreports/spneu01.html (ac-
catch-up schedules for vaccination. Recommendations by the
cessed 2013 Nov 20).
CDC Advisory Committee on Immunization Practices for the
4. Jacobs MR, Felmingham D, Appelbaum PC, et al. The
use of PCV13 in adults were established in 2012.30 Patients
Alexander Project 1998–2000: susceptibility of patho-
who have immunocompromising conditions should receive
gens isolated from community-acquired respiratory
PCV13 in addition to PPSV23 (Tables 1 and 2). Screening
tract infection to commonly used antimicrobial agents.
and vaccination should occur in all appropriate adult patients.
J Antimicrob Chemother. 2003; 52:229–46.
Timing of PCV13 and PPSV23 administration is important to
5. Doern G, Rybak MJ. Activity of telithromycin against
ensure maximal immune response. If the person has never re-
Streptococcus pneumoniae resistant to penicillin, mac-
ceived a dose of PCV13 or PPSV23, he or she should receive
rolides and fluoroquinolones isolated from respiratory
a dose of PCV13 followed by a dose of PPSV23 at least eight
tract infections: PROTEK US year 2 (2001–2002).
weeks later. If the patient has received one or more doses of
Presented at 43rd Annual Interscience Conference on
PPSV23, the patient should receive one dose of PCV13 at
Antimicrobial Agents and Chemotherapy. Chicago,
least one year after the last dose of PPSV23.
IL; 2003 Sep.
Health care institutions should develop robust pro-
grams to increase pneumococcal vaccination rates as pneu- 6. Doern GV, Heilmann KP, Huynh HK, et al. Antimi-
mococcal disease continues to contribute to a significant crobial resistance among clinical isolates of Strepto-
amount of morbidity and mortaility in the United States. coccus pneumoniae in the United Stated during 1999–
More than 65% of patients with severe pneumococcal dis- 2000, including a comparison of resistance rates since
ease have been hospitalized in the preceding—three to five 1994–1995. Antimicrob Agents Chemother. 2001;
years, but few have received vaccine.34 Most people who 45:1721–9.
succumb to preventable infections have visited a health care 7. Karlowsky JA, Thornsberry C, Jones ME, et al. Factors
provider in the preceding year but were not vaccinated.38–42 associated with relative rates of antimicrobial resis-
Clinicians should ensure that patients receive proper immu- tance among Streptococcus pneumoniae in the United
nizations,43,44 and pharmacists can promote vaccination ef- States: results from the TRUST surveillance program
forts by serving as educators, facilitators, and vaccinators. (1998–2002). Clin Infect Dis. 2003; 36:963–70.
Currently, all 50 states allow pharmacists to administer vac- 8. Centers for Disease Control and Prevention. ABCs re-
cines, and 49 states allow pharmacists to administer pneu- port: Streptococcus pneumoniae, 2010. www.cdc.gov/
mococcal vaccines.45 Variability exists among the states re- abcs/reports-findings/survreports/spneu10.html (ac-
garding patient age limitations and pharmacist-administered cessed 2013 Nov 20).
Figure 1. Example pneumococcal vaccine administration pathway with notification for adult patients. PCV13 = 13-valent pneumococcal
conjugate vaccine, PPSV23 = 23-valent pneumococcal polysaccharide vaccine, CDC = Centers for Disease Control and Prevention.
Does the patient meet Do not vaccinate; send

criteria for pneumococcal NO reminder for future vaccine
vaccination? administration
YES
Administer PCV13
Has the patient received AND
pneumococcal vaccine in the NO Send reminder card for
past? PPSV23 for administration
≥8 weeks later
YES
PCV13 PPSV23
<8 weeks elapsed ≥8 weeks elapsed <1 year elapsed ≥1 year elapsed
Do not vaccinate; send Administer PPSV23 Do not vaccinate; send Administer PCV13
reminder card for AND reminder card for PCV13 for AND
PPSV23 vaccination Send reminder for PPSV23 administration ≥1 year after Send reminder for PPSV23
when ≥8 weeks has when 5 years has elapsed from PPSV23 vaccination when 5 years has elapsed from
elapsed last PPSV23 vaccination for the AND last PPSV23 vaccination for
following patients: Send reminder for PPSV23 the following patients:
1. ≥65 years of age when 5 years has elapsed from 1. ≥65 years of age
2. 19–64 years of age who last PPSV23 vaccination for the 2. 19–64 years of age who
meet CDC criteria for following patients: meet CDC criteria for
revaccination 1. ≥65 years of age revaccination
2. 19–64 years of age who
meet CDC criteria for
revaccination
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Infect Dis. 2011; 53:631–9. based pneumococcal immunization. Epidemiologic
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25. Centers for Disease Control and Prevention. Public cination program directed at hospitalized and ambula-
health action plan to combat antimicrobial resistance. tory patients. Arch Intern Med. 1984; 144:1755–7.
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26. Leung E, Weil DE, Raviglione M, et al. The WHO cal vaccination. Arch Intern Med. 1998; 158:1543–7.
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Am J Health-Syst Pharm. 2010; 67:575–7. cists’ role in immunizing adults against pneumococcal
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Nov 20). pharmacists to vaccinate. www.immunize.org/laws/
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31. Centers for Disease Control and Prevention. Preventing
pneumococcal disease among infants and young chil-
dren: recommendations of the Advisory Committee
Kimberly A. Couch, Pharm.D., M.A., FIDSA, FASHP, is President,
on Immunization Practices (ACIP). MMWR. 2000;
Infectious Diseases Pharmacy Associates, Stevensville, MD, and
49(RR-9):1–35.
Clinical Pharmacist, Complete Rx, Seaford, DE. Teresa Geide,
32. Centers for Disease Control and Prevention. Birth—18
Pharm.D., BCPS, CGP, is Clinical Pharmacy Specialist, Infectious
years and “catch-up” immunization schedules; Uniteed
Diseases, Orlando Veterans Affairs Medical Center, Orlando, FL.
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child-adolescent.html (accessed 2013 Nov 21).
Developed through the ASHP Council on Therapeutics and ap-
33. Artz AS, Ershler WB, Longo DL. Pneumococcal
proved by the ASHP Board of Directors on August 2, 2013.
vaccination and revaccination of older adults. Clin
Microbiol Rev. 2003; 16:308–18.
The following individuals are acknowledged for reviewing draft ver-
34. Centers for Disease Control and Prevention.
sions of this statement: Arthur Chaput; Steven Dzierba, Pharm.D.,
Epidemiology and prevention of vaccine-preventable
M.S., FASHP; Kathleen M. Gura, Pharm.D., BCNSP, FASHP,
diseases. The pink book: course textbook. www.cdc. FPPAG; Mojdeh Heavner, Pharm.D., BCPS; Jody Jacobson Wedret,
gov/vaccines/pubs/pinkbook/pneumo.html#vaccines B.S.Pharm., FASHP, FCSHP; Kristi Kuper, Pharm.D., BCPS; Fred
(accessed 2013 Nov 20). Meister, Pharm.D., FASHP; Robert J. Moura, B.S.Pharm., M.S.;
35. Department of Health and Human Services. Healthy Michael Postelnick, B.S.Pharm, BCPS-AQ Infectious Diseases; and
People 2020. www.healthypeople.gov (accessed 2012 Michael Powell, B.S.P., M.S.P., FASHP.
Sep 27).
36. Dagan R, Fraser D. Conjugate pneumococcal vaccine The authors have declared no potential conflicts of interest.
and antibiotic-resistant Streptococcus pneumoniae:
herd immunity and reduction of otitis morbidity. This document supersedes the ASHP therapeutic position statement
Pediatr Infect Dis J. 2000; 19(suppl):S79–88. for identifying and preventing pneumococcal resistance approved
37. Whitney CG, Farley MM, Hadler J, et al. Decline in by the ASHP Board of Directors on April 15, 2004.
invasive pneumococcal disease after the introduction
of protein-polysaccharide conjugate vaccine. N Engl J Copyright © 2014, American Society of Health-System Pharmacists,
Med. 2003; 348:1737–46. Inc. All rights reserved.
38. Williams WW, Hickson MA, Kane MA, et al.
Immunization policies and vaccine coverage among The bibliographic citation for this document is as follows: American
adults. The risk for missed opportunites. Ann Intern Society of Health-System Pharmacists. ASHP therapeutic position
Med. 1988; 108:616–25. statement on strategies for identifying and preventing pneumococ-
cal resistance. Am J Health-Syst Pharm. 2014; 71:417–24.
Therapeutic Monitoring of Vancomycin in Adult

Patients: A Consensus Review of the American
Society of Health-System Pharmacists, the Infectious
Diseases Society of America, and the Society of
Infectious Diseases Pharmacists
Vancomycin is a glycopeptide antibiotic that has been in and consideration of these suggestions, the document was
clinical use for nearly 50 years as a penicillin alternative revised and circulated among the committee and supporting
to treat penicillinase-producing strains of Staphylococcus organizations for final comment. This consensus review rep-
aureus. It is one of the most widely used antibiotics in the resents the opinion of the majority of committee members.
United States for the treatment of serious gram-positive in- A search of PubMed was conducted using the follow-
fections involving methicillin-resistant S. aureus (MRSA).1 ing search terms: vancomycin pharmacokinetics, pharmaco-
Early use of vancomycin was associated with a number of dynamics, efficacy, resistance, and toxicity. All relevant
adverse effects, including infusion-related toxicities, neph- and available peer-reviewed studies in the English language
rotoxicity, and possible ototoxicity. Upon further investi- published between 1958 and 2008 were considered. Studies
gation, it appears that the impurities in early formulations were rated by their quality of evidence, and the subsequent
of vancomycin caused many of these adverse events.1-4 Its recommendations were graded using the classification sche-
overall use was curtailed significantly with the development mata of the Canadian Medical Association (Table 1).13
of semisynthetic penicillins (e.g., methicillin, oxacillin, naf- Recommendations of the expert panel are presented in Table 2.
cillin) that were considered less toxic.1-4 However, the steady Potential limitations of this review include the facts
rise in the number of MRSA infections since the early 1980s that few prospective or randomized trials of vancomycin moni-
has once again brought vancomycin into the forefront as the toring were available and that most of the published literature
primary treatment for infections caused by this organism. regarding vancomycin monitoring described observational
Over the years, vancomycin has been one of the most studies in patients with S. aureus infection. Vancomycin moni-
studied antibiotics. Extensive pharmacokinetic studies in a toring in pediatric patients is beyond the scope of this review.
variety of patient populations and the availability of com-
mercial drug assays have allowed clinicians to target serum
vancomycin concentrations precisely in a relatively nar-
row range. This approach has been advocated to lessen the
potential for nephrotoxicity and ototoxicity and to achieve Table 1.
therapeutic concentrations. However, it should be noted that Definitions of Levels and Grades for
the practice of routine monitoring and adjusting of serum Recommendations13
vancomycin drug concentrations has been the subject of in-
tense debate for many years.5-9 The controversy has resulted Quality Indicator Type of Evidence
from conflicting evidence regarding the use of serum van- Level of evidence
comycin concentrations to predict and prevent drug-induced I Evidence from at least one properly
toxicity and as a measure of effectiveness in treating infec- randomized, controlled trial
tions. Further, data derived from more recent studies appear
II Evidence from at least one well-
to suggest that vancomycin has little potential for nephro-
designed clinical trial, without
toxicity or ototoxicity when used at conventional dosages randomization; from cohort or
(e.g., 1 g every 12 hours [15 mg/kg every 12 hours]), unless case-controlled analytic studies
it is used concomitantly with known nephrotoxic drugs or at (preferably from more than one
very high dosages.10-12 This consensus review evaluates the center); from multiple time series;
scientific data and controversies associated with serum van- or from dramatic results from
comycin monitoring and provides recommendations based uncontrolled experiments
on the available evidence. III Evidence from opinions of respected
This is a consensus statement of the American Society authorities, based on clinical
of Health-System Pharmacists (ASHP), the Infectious experience, descriptive studies, or
Diseases Society of America (IDSA), and the Society of reports of expert committees
Infectious Diseases Pharmacists (SIDP). Consensus com- Grade of recommendation
mittee members were assigned key topics regarding van-
A Good evidence to support a
comycin that contribute to current knowledge about patient recommendation for use
monitoring. A draft document addressing these areas that in-
cluded specific recommendations was reviewed by all com- B Moderate evidence to support a
recommendation for use
mittee members. After peer review by members of ASHP,
IDSA, and SIDP, the committee met to review the submitted C Poor evidence to support a
comments and recommendations. After careful discussion recommendation for use
Overview of Vancomycin free vancomycin AUC/MIC [AUC × 50% protein binding/

MIC] have been interchangeably reported for vancomycin.
Pharmacokinetic and
Unless designated fAUC/MIC, this consensus review refers
Pharmacodynamic Properties to total AUC/MIC.)
Craig and Andes32 recently evaluated the use of free
Sophisticated pharmacokinetic techniques such as Bayesian vancomycin AUC0–24hr/MIC (fAUC/MIC) as the primary
and noncompartmental modeling have been used to derive parameter for predicting vancomycin activity against VISA,
pharmacokinetic parameters for vancomycin. The serum heteroresistant VISA (hVISA), and MSSA in the murine neu-
vancomycin concentration–time profile is complex and has tropenic mouse model. They found that the fAUC/MIC re-
been characterized as one-, two-, and three-compartment quirement varied depending on the vancomycin MIC and was
pharmacokinetic models. In patients with normal renal func- a function of bacterial density at the site of infection, with a
tion, the a-distribution phase ranges from 30 minutes to 1 lower fAUC/MIC needed for a lower bacterial inoculum. Of
hour, and the b-elimination half-life ranges from 6 to 12 interest, the dose required for a 2 log colony-forming unit/g
hours. The volume of distribution is 0.4–1 L/kg.14-18 kill was 2.5 times higher for hVISA strains than for VISA
While reports of the degree of vancomycin pro- and vancomycin-susceptible S. aureus strains. The research-
tein binding have varied, a level of 50–55% is most often ers concluded that vancomycin dosages of 500 mg every 6
stated.19,20 Penetration of vancomycin into tissues is variable hours or 1 g every 12 hours provide fAUC/MIC values of
and can be affected by inflammation and disease state. For 100–250 and suggested that values around 500 may enhance
example, with uninflamed meninges, cerebral spinal fluid the therapeutic effectiveness of vancomycin in humans.
vancomycin concentrations ranging from 0 to approximately Moise-Broder et al.33 explored the use of AUC/MIC
4 mg/L have been reported, whereas concentrations of 6.4– in predicting clinical and microbiological success in treating
11.1 mg/L have been reported in the presence of inflamma- ventilator-associated S. aureus pneumonia. These investiga-
tion.21 Penetration into skin tissue is significantly lower for tors suggested an average AUC/MIC of 345 for a successful
patients with diabetes (median, 0.1 mg/L; range, 0.01–0.45 clinical outcome and a ratio of 850 for a successful micro-
mg/L) compared with nondiabetic patients based on the me- biological outcome. For pathogens with an MIC of 1 mg/L,
dian ratio of tissue vancomycin to plasma vancomycin con- an AUC/MIC of approximately 250 can be achieved in most
centrations (median, 0.3 mg/L; range, 0.46–0.94 mg/L).21 patients with 1 g every 12 hours based on a patient with an
Vancomycin concentrations in lung tissue ranging from 5% actual body weight (ABW) of 80 kg and normal renal func-
to 41% of serum vancomycin concentrations have been re- tion (i.e., creatinine clearance [CLcr] = 100 mL/min), but ob-
ported in studies of healthy volunteers and patients.5,6,22,23 taining a target AUC/MIC of 850 would require much higher
Epithelial lining fluid (ELF) penetration in critically injured dosages for most patients.
patients is highly variable, with an overall blood:ELF pen-
etration ratio of 6:1.23,24 Summary: Based on these study results, an AUC/MIC ratio
of ≥400 has been advocated as a target to achieve clinical
Selection of Pharmacokinetic and effectiveness with vancomycin. Animal studies and limited
Pharmacodynamic Monitoring human data appear to demonstrate that vancomycin is not
Parameters concentration dependent and that the AUC/MIC is a predic-
tive pharmacokinetic parameter for vancomycin.
A variety of pharmacokinetic and pharmacodynamic moni-
toring parameters have been proposed for vancomycin, in- Impact of Dosing Strategies
cluding time (t) the concentration of vancomycin remains on Pharmacokinetic and
above the minimum inhibitory concentration (MIC), the ratio Pharmacodynamic Parameters
of the area under the serum drug concentration-versus-time
curve and the MIC, and the ratio of the maximum serum drug The initial clinical dosing strategies for vancomycin were
concentration (Cmax) and the MIC. These parameters are ab- developed in the late 1950s before the emergence of anti-
breviated t>MIC, AUC/MIC, and Cmax/MIC, respectively. biotic pharmacodynamics.34 Published data on the phar-
Reviews of pharmacokinetics and pharmacodynamics have macodynamics of vancomycin against specific bacterial
recommended the AUC/MIC as the preferred parameter pathogens or infections are very limited, with much of the
based in part on data from animal models, in vitro studies, available data generated from in vitro or animal models.
and limited human studies.6,25-28 Studies by Ackerman et This is partly due to the drug’s generic status, which dis-
al.,29 Löwdin et al.,30 and Larsson et al.31 demonstrated that courages manufacturers from conducting well-controlled
vancomycin kills S. aureus and Staphylococcus epidermidis scientific investigations that would provide additional and
in a concentration-independent fashion. By simulating free clarifying pharmacodynamic data. It is recommended that
vancomycin peak concentrations of 40, 20, 10, and 5 mg/L in dosages be calculated based on ABW. There are limited data
an in vitro chemostat model with a normal vancomycin ter- on dosing in obese patients; however, initial dosages should
minal half-life of six hours, Larsson et al.31 found no differ- be based on ABW and adjusted based on serum vancomycin
ence in the corresponding bacterial kill curves for S. aureus. concentrations to achieve therapeutic levels.17
Using neutropenic mouse models, investigators have Vancomycin is ideally suited from a pharmacokinetic
concluded that the AUC/MIC is the pharmacodynamically and pharmacodynamic perspective for intermittent adminis-
linked parameter for measuring vancomycin’s effectiveness tration based on the usual susceptibility of staphylococci and
in treating S. aureus, including methicillin-susceptible S. au- streptococci (MIC values of ≤1 mg/L), the most commonly
reus (MSSA), MRSA, and vancomycin-intermediate S. au- used dosage regimen for vancomycin (1 g every 12 hours),
reus (VISA) strains.6,25 (Note: The total AUC/MIC and the and the concentration-independent nature of the drug. As a
Table 2.
Summary of Expert Panel Recommendations for Vancomycin Therapeutic Drug Monitoring (TDM)a
Level of Evidence
and Grade of Section of Consensus
Variable Recommendation Recommendation Review
Recommended TDM Parameters
Optimal monitoring parameter Trough serum vancomycin concentrations are IIB Therapeutic vancomycin
the most accurate and practical method for drug monitoring,
monitoring efficacy. Peak versus trough
concentrations
Timing of monitoring Troughs should be obtained just prior to the IIB Therapeutic vancomycin
next dose at steady-state conditions (just drug monitoring,
before the fourth dose). Peak versus trough
concentrations
Optimal trough concentration Minimum serum vancomycin trough IIIB Therapeutic vancomycin
(see also Optimal concentrations should always be drug monitoring,
trough concentration— maintained above 10 mg/L to avoid Optimal trough
complicated infections) development of resistance. For a pathogen concentrations
with an MIC of 1 mg/L, the minimum trough
concentration would have to be at least 15
mg/L to generate the target AUC:MIC of
400.
Optimal trough Vancomycin serum trough concentrations IIIB Therapeutic vancomycin
concentration— of 15–20 mg/L are recommended to drug monitoring,
complicated infections improve penetration, increase the Optimal trough
(bacteremia, endocarditis, probability of obtaining optimal target concentrations
osteo-myelitis, meningitis, serum concentrations, and improve clinical
and hospital-acquired outcomes.
pneumonia caused by
Staphylococcus aureus)
Dosing Regimen
Dosing to achieve optimal Doses of 15–20 mg/kg (as actual body IIIB Therapeutic vancomycin
trough concentrations weight) given every 8–12 hr are drug monitoring,
recommended for most patients with Optimal trough
normal renal function to achieve the concentrations
suggested serum concentrations when the
MIC is ≤1 mg/L. In patients with normal
renal function, the targeted AUC:MIC of
>400 is not achievable with conventional
dosing methods if the MIC is ≥2 mg/L in a
patient with normal renal function.
Loading doses—complicated In seriously ill patients, a loading dose of 25– IIIB Therapeutic vancomycin
infections 30 mg/kg (based on actual body weight) drug monitoring,
can be used to facilitate rapid attainment Optimal trough
of target trough serum vancomycin concentrations
concentration.
Continuous vs. intermittent Continuous infusion regimens are unlikely to IIA Impact of dosing
dosing substantially improve patient outcome when strategies on
compared to intermittent dosing. pharmacokinetic and
pharmacodynamic
parameters
TDM for Vancomycin-Induced Nephrotoxicity
Definition A minimum of two or three consecutive IIB Vancomycin toxicity;
documented increases in serum creatinine Incidence, mechanism,
concentrations (defined as an increase and definition of
of 0.5 mg/dL or a ≥50% increase from nephrotoxicity
baseline, whichever is greater) after several
days of vancomycin therapy. Continued on next page
Summary of Expert Panel Recommendations for Vancomycin Therapeutic Drug Monitoring (TDM)a
Level of Evidence
and Grade of Section of Consensus
Variable Recommendation Recommendation Review
Criteria for monitoring Data do not support using peak serum IIB Vancomycin toxicity,
vancomycin concentrations to monitor for Role of therapeutic
nephrotoxicity. drug monitoring
in preventing
nephrotoxicity
Trough monitoring is recommended for IIIB Vancomycin toxicity,
patients receiving aggressive dosing Role of therapeutic
(i.e., to achieve sustained trough levels of drug monitoring
15–20 mg/L) and all patients at high risk in preventing
of nephrotoxicity (e.g., patients receiving nephrotoxicity
concurrent nephrotoxins).
Monitoring is also recommended for IIB Vancomycin toxicity,
patients with unstable (i.e., deteriorating Role of therapeutic
or significantly improving) renal function drug monitoring
and those receiving prolonged courses of in preventing
therapy (more than three to five days). nephrotoxicity
Frequency of monitoring Frequent monitoring (more than one trough IIB Vancomycin toxicity,
before the fourth dose) for short course Role of therapeutic
or lower intensity dosing (to attain target drug monitoring
trough concentrations below 15 mg/L) is in preventing
not recommended. nephrotoxicity
All patients on prolonged courses of IIB Vancomycin toxicity,
vancomycin (exceeding three to five days) Role of therapeutic
should have at least one steady-state drug monitoring
trough concentration obtained no earlier in preventing
than at steady state (just before the fourth nephrotoxicity
dose) and then repeated as deemed
clinically appropriate.
There are limited data supporting the safety IIIB Vancomycin toxicity,
of sustained trough concentrations of Role of therapeutic
15–20 mg/L. Clinical judgment should drug monitoring
guide the frequency of trough monitoring in preventing
when the target trough is in this range. nephrotoxicity
Once-weekly monitoring is recommended
for hemodynamically stable patients.
More frequent or daily trough monitoring
is advisable in patients who are
hemodynamically unstable.
TDM for Vancomycin-Induced Ototoxicity
Criteria for monitoring Monitoring for ototoxicity is not recommended IIIB Vancomycin toxicity,
for patients receiving vancomycin Incidence of ototoxicity
monotherapy. and role of therapeutic
drug monitoring
for prevention of
vancomycin-induced
hearing loss
Monitoring should be considered for patients IIIB Vancomycin toxicity,
receiving additional ototoxic agents, such Incidence of ototoxicity
as aminoglycosides. and role of therapeutic
drug monitoring
for prevention of
vancomycin-induced
hearing loss
a
MIC = minimum inhibitory concentration, AUC = area under the concentration-versus-time curve.
result, the likelihood of maintaining free or unbound serum Summary and recommendation: Trough serum vancomycin
vancomycin concentrations in excess of the bacterial MIC concentrations are the most accurate and practical method
for the entire dosing interval is usually 100% with stan- for monitoring vancomycin effectiveness. Trough concentra-
dard intermittent i.v. infusions for typical staphylococci and tions should be obtained just before the next dose at steady-
streptococci. state conditions. (Level of evidence = II, grade of recom-
Despite the absence of clinical data supporting t>MIC mendation = B.) (Note: Steady-state achievement is variable
as a predictive parameter for clinical effectiveness, contin- and dependent on multiple factors. Trough samples should
uous-infusion strategies have been suggested as a possible be obtained just before the fourth dose in patients with nor-
means to optimize the serum vancomycin concentration and mal renal function to ensure that target concentrations are
improve effectiveness. Using a randomized crossover study attained.)
design in intensive care unit (ICU) patients, James et al.35
found no significant difference between intermittent and Optimal Trough Concentrations. While Geraci’s39 recom-
continuous administrations when measuring killing activ- mendation for trough concentration was not based on pro-
ity in vitro, although the ability to maintain serum bacteri- spective clinical trial data, the benchmark total drug con-
cidal titers above 1:8 was better with a continuous infusion. centration of 5–10 mg/L is likely to fall short of achieving
In a similarly designed study in healthy subjects, Lacy et the desired overall vancomycin exposure in many types of
al.36 found virtually no difference in activity as measured infection and isolates with higher (but susceptible) MICs.
by bactericidal titers between continuous and intermit- Therefore, targeting higher trough serum vancomycin con-
tent infusions. Further, in a randomized study, Wysocki et centrations should increase the likelihood of achieving more
al.37,38 evaluated 160 patients with severe staphylococcal effective overall antibiotic exposures (i.e., AUC/MIC) and
infections. No difference in patient outcome was observed assist in addressing the trend of higher vancomycin MIC
between those receiving intermittent or continuous infusion values in these organisms.
vancomycin. Vancomycin differs from b-lactam antibiot- In recently published guidelines for hospital-acquired,
ics, which typically have short half-lives and often require ventilator-associated, and health-care-associated pneumo-
shorter dosage intervals or continuous infusion to optimize nia, the American Thoracic Society (ATS) suggested an
therapy. Therefore, based on the available evidence, there initial vancomycin dosage of 15 mg/kg every 12 hours in
does not appear to be any difference in patient outcomes be- adults with normal renal function.41 ATS acknowledged that
tween vancomycin administered by continuous infusion or vancomycin was a concentration-independent (time-depen-
by intermittent administration. dent) killer of gram-positive pathogens but had lower pen-
etration into the ELF and respiratory secretions. ATS further
Summary and recommendations: Vancomycin dosages recommended that trough serum vancomycin concentrations
should be calculated on ABW. For obese patients, initial dos- be maintained at 15–20 mg/L. However, based on pharma-
ing can be based on ABW and then adjusted based on serum cokinetic dosing principles for patients with a normal body
vancomycin concentrations to achieve therapeutic levels. weight and normal renal function, it is unlikely that vanco-
Continuous infusion regimens are unlikely to substantially im- mycin 15 mg/kg every 12 hours will produce trough con-
prove patient outcome when compared with intermittent dos- centrations of 15–20 mg/L. Furthermore, there are no data
ing. (Level of evidence = II, grade of recommendation = A.) indicating that achieving these trough concentrations over
time is well tolerated and safe.
Therapeutic Vancomycin Drug In an attempt to evaluate the use of targeted trough
Monitoring concentrations of 15–20 mg/L, Jeffres et al.42 retrospectively
evaluated 102 patients with health-care-associated MRSA
Peak versus Trough Concentrations. Over the years, serum pneumonia. Overall mortality was 31% (32 patients). There
vancomycin concentration monitoring practices have varied. were no significant differences in mean ± S.D. calculated
Early suggestions, such as those of Geraci,39 who recom- trough serum vancomycin concentrations (13.6 ± 5.9 mg/L
mended peak serum vancomycin concentrations of 30–40 versus 13.9 ± 6.7 mg/L) or mean ± S.D. calculated AUC
mg/L and trough concentrations of 5–10 mg/L, likely did not (351 ± 143 mg · hr/L versus 354 ± 109 mg · hr/L) between
appreciate the multiexponential decline in the serum vanco- survivors and nonsurvivors. In addition, no relationship was
mycin concentration-versus-time curve. found between trough serum vancomycin concentrations or
How Geraci defined peak concentration is unclear. In AUC and hospital mortality. Although no significant dif-
addition, the pharmacodynamic properties of vancomycin ferences were found between survivors and nonsurvivors
had not been evaluated at the time these recommendations in terms of trough serum vancomycin concentrations and
were made. Because the AUC/MIC has been found to cor- AUCs, several factors should be noted. For instance, a sam-
relate with efficacy in experiments conducted with in vitro ple size calculation was not predetermined; therefore, the
or animal models, this evidence has led some clinicians to potential for a Type II error is possible. There was also large
question the relevance of monitoring peak serum vancomy- variability in both vancomycin trough concentrations (range,
cin concentrations.6 Consequently, some clinicians have de- 4.2–29.8 mg/L) and AUCs (range, 119–897 mg · hr/L),
creased the extent of pharmacokinetic monitoring for this an- which may account for the lack of significant findings. Time
tibiotic.40 However, because it can be difficult in the clinical to achieve targeted serum vancomycin concentrations was
setting to obtain multiple serum vancomycin concentrations not measured and may be a critical factor in determining pa-
to determine the AUC and subsequently calculate the AUC/ tient outcome. In addition, because a disk-diffusion method
MIC, trough serum concentration monitoring, which can be was used for susceptibility testing, organism MIC could not
used as a surrogate marker for AUC, is recommended as the be determined. Therefore, only the AUC, not the AUC/MIC,
most accurate and practical method to monitor vancomycin. was evaluated as a potential predictor of success or failure.
Although the results of this study are of interest, additional cess rate of 55.6%, while treatment of patients infected with
prospective studies are needed to confirm these data. MRSA strains having a vancomycin MIC of 1–2 mg/L had a
Relationship between trough vancomycin concentra- success rate of only 9.5% (p = 0.03). (Treatment failure was
tions, resistance, and therapeutic failure. While vancomy- defined as persistent signs or symptoms of infection [e.g.,
cin is considered a bactericidal antibiotic, the rate of bacte- fever, leukocytosis], new signs or symptoms of infection,
rial kill is slow when compared with that of b-lactams, and or worsening of signs or symptoms of infection in patients
vancomycin’s activity is affected by the bacterial inoculum. receiving at least five days of therapy with targeted trough se-
Large bacterial burdens in the stationary growth phase or in rum vancomycin concentrations of 10–15 mg/L). However,
an anaerobic environment pose a significant challenge to the this was a relatively small study (n = 30) of MRSA bacte-
speed and extent of vancomycin’s bactericidal activity.43-46 remic patients who were refractory to vancomycin therapy
In recent years, VISA or glycopeptide-intermediate and were enrolled in compassionate-use drug trials. In a
susceptible S. aureus (GISA) and vancomycin-resistant S. more recent study of patients with MRSA bacteremia (n =
aureus (VRSA) have appeared and raised questions about 34), Moise et al.58 demonstrated that patients with MRSA
the overall utility of this antibiotic. (Note: The terms VISA isolates with a vancomycin MIC of 2 mg/L had significantly
and GISA are often used interchangeably. For the purpose higher median days to organism eradication, longer treat-
of this consensus review, VISA will be used throughout.) ment with vancomycin, and a significantly lower overall
Although infection with these organisms is infrequent, there likelihood of organism eradication. Hidayat et al.53 evaluated
is fear that the organisms could become more prevalent if the the use of high-dosage vancomycin intended to achieve un-
high rate of use and exposure pressure of vancomycin con- bound trough serum vancomycin concentrations of at least
tinues.47 The discovery of inducible hVISA (i.e., strains with four times the MIC in patients with MRSA infections. Of the
MIC values in the susceptible range of 0.5–2 mg/L in pa- 95 patients evaluated with MRSA pneumonia or bacteremia,
tients whose therapy with standard dosages of vancomycin or both, 51 (54%) had vancomycin MIC values of 1.5 or 2
has failed) raises further questions regarding current dosing mg/L. Although an initial response of 74% was demonstrated
in patients achieving the desired target MIC, a high percent-
guidelines and the overall use of this antibiotic. Concerns are
age of patients infected with strains having an MIC of 1.5 or
related to treatment failures and the inability to easily detect
2 mg/L had a poorer response (62% versus 85%) and signifi-
hVISA isolates in clinical settings.48-50
cantly higher infection-related mortality (24% versus 10%)
In 2006, the Clinical and Laboratory Standards
compared with patients infected with low-MIC strains (0.5,
Institute (CLSI) lowered the susceptibility and resistance
0.75, or 1 mg/L), despite achieving target trough serum van-
breakpoints for the MIC of vancomycin from ≤4 to ≤2 mg/L
comycin concentrations of 15–20 mg/L. The data from these
for “susceptible,” from 8–16 to 4–8 mg/L for “intermedi-
two studies suggest that S. aureus isolates with MICs of 1–2
ate,” and from ≥32 to ≥16 mg/L for “resistant.”51 The deci-
mg/L that are still within the susceptible range may be less
sion to move the breakpoints was primarily based on clinical
responsive to vancomycin therapy. Soriano et al.59 evaluated
data indicating that patients were less likely to be success- the influence of vancomycin MIC on outcome in a total of
fully treated with vancomycin if the S. aureus MIC was ≤4 414 episodes of MRSA bacteremic patients. MIC evalua-
mg/L.51 Despite the change in susceptibility and resistance tions were determined by Etest methodology. Among several
breakpoints, two reports have suggested that patients with S. factors that predicted poor outcome, S. aureus isolates with
aureus isolates having vancomycin MICs of 1–2 mg/L are an MIC of 2 mg/L were significantly associated with in-
less likely to be successfully treated with vancomycin com- creased mortality. Based on the low probability of achieving
pared with patients with S. aureus isolates that demonstrate an appropriate targeted vancomycin concentration exposure
greater susceptibility.52,53 However, this information alone (AUC/MIC), the authors suggested that vancomycin should
does not address whether the use of higher concentrations of not be considered an optimal treatment approach for infec-
vancomycin would improve overall effectiveness. Low se- tion due to strains with a vancomycin MIC of >1 mg/L when
rum vancomycin concentrations may also create problems, using trough serum vancomycin concentrations of >10 mg/L
as there appears to be a direct correlation between low serum as a target.
vancomycin levels and the emergence of hVISA, VISA, or Lodise et al.60 evaluated the relationship between van-
both, at least with certain genotypes of MRSA.54 In addi- comycin MIC and treatment failure among 92 adult non-
tion, studies have suggested that trough serum vancomycin neutropenic patients with MRSA bloodstream infections.
concentrations of <10 mg/L may predict therapeutic failure Vancomycin failure was defined as 30-day mortality, 10 or
and the potential for the emergence of VISA or VRSA.54,55 more days of bacteremia on vancomycin therapy, or recur-
Studies of MRSA and hVISA bacteremia have re- rence of MRSA bacteremia within 60 days of vancomycin
vealed significantly higher rates of morbidity in patients in- discontinuation. Classification and regression tree analysis
fected with hVISA.50,55,56 These patients were more likely to found that a vancomycin MIC breakpoint of ≥1.5 mg/L was
have high bacterial load infections, low initial trough serum associated with an increased probability of treatment failure.
vancomycin concentrations, and treatment failure.56 Jones57 The 66 patients with a vancomycin MIC of ≥1.5 mg/L had a
recently reported that approximately 74% of hVISA strains 2.4-fold higher rate of treatment failure compared with pa-
and 15% of wild-type S. aureus strains were tolerant (mini- tients with a vancomycin MIC of ≤1 mg/L (36.4% versus
mum bactericidal concentration of ≥32 mg/L) to the effects 15.4%, respectively; p = 0.049). Poisson regression analysis
of vancomycin, which contributes to a low probability of determined that a vancomycin MIC of ≥1.5 mg/L was inde-
success in patients harboring these organisms. pendently associated with treatment failure (p = 0.01). Based
Sakoulas et al.52 reported a significant correlation be- on these findings, the investigators suggested that an alterna-
tween vancomycin susceptibilities and patient outcome. tive therapy should be considered.
Treatment of bloodstream infections caused by MRSA strains An analysis of a large surveillance database of 35,458
having a vancomycin MIC of ≤0.5 mg/L had an overall suc- S. aureus strains by Jones57 found that the MIC required to
inhibit the growth of 50% of organisms or the MIC required tional agr locus, making this finding potentially clinically
to inhibit the growth of 90% of organisms (MIC90) for van- relevant and warranting further evaluation.70
comycin is 1 mg/L.57 The Centers for Disease Control and
Prevention 2005 U.S. Surveillance Network data of vanco- Summary and recommendation: Based on evidence sug-
mycin susceptibility reported that 16.2% of 241,605 S. au- gesting that S. aureus exposure to trough serum vancomycin
reus isolates had an MIC of 2 mg/L.51 Regional variability concentrations of <10 mg/L can produce strains with VISA-
exists, and an MIC90 of 2 mg/L has recently been reported like characteristics, it is recommended that trough serum
by several institutions. For example, Mohr and Murray61 vancomycin concentrations always be maintained above 10
reported that as many as 30% of 116 MRSA blood culture mg/L to avoid development of resistance. (Level of evidence
isolates collected from the Texas Medical Center over a = III, grade of recommendation = B.)
one-year period had a vancomycin MIC of 2 mg/L. There
have been recent reports of significant shifts in bacterial Correlating dosing with optimal AUC/MIC and trough
susceptibility to vancomycin over a five-year surveillance concentrations. As mentioned previously, an isolate’s van-
period.62-64 Increasing S. aureus MIC values, coupled with comycin MIC is an important parameter for determining the
reports of failure rates associated with a vancomycin MIC of potential success of a given dosage regimen. Therefore, an
2 mg/L, have raised the question of whether the breakpoint actual vancomycin MIC value should ideally be obtained
for vancomycin resistance should be lowered even further.65 from the clinical microbiology laboratory. Currently, some
New information is emerging regarding the importance clinical microbiology laboratories may be limited in their
of the accessory gene regulator (agr), a global quorum-sens- ability to report vancomycin MIC values, depending on the
ing regulator in S. aureus that is responsible for orchestrating methodology (disk diffusion or automated microdilution)
the expression of adherence factors, biofilm production, tol- used to determine antimicrobial susceptibility. In some in-
erance to vancomycin, and virulence factors.66 The agr locus stances, supplemental Etest methods may be used to obtain
has been a subject of intense study because there appears to this information.
be a relationship between polymorphism in this gene cluster As previously stated, an AUC/MIC of ≥400 has been
and patient response to vancomycin therapy. Several studies promoted as the target predictive of successful therapy (i.e.,
have determined that all VISA strains reported to date from organism eradication). Based on this information, a simple
the United States belong to agr group II. The agr group II evaluation of standard dosing practices (e.g., 1 g every 12
includes the USA 100 MRSA clones that are predominately hours) for an individual with normal renal function (CLcr of
associated with nosocomial infections, and these strains ≥100 mL/min) and average weight (80 kg) would only yield
have been associated with vancomycin treatment failure.33,67 a 24-hour drug AUC of approximately 250 mg · hr/L. Unless
Sakoulas et al.67,68 have determined in in vitro studies that the pathogen had a vancomycin MIC of ≤0.5 mg/L, this
the emergence of hVISA or VISA may occur when S. au- dosage regimen would not generate the targeted AUC/MIC
reus isolates with a down-regulated or defective agr locus of ≥400. For a pathogen with an MIC of 1 mg/L, the mini-
are exposed to suboptimal vancomycin concentrations. In mum trough serum vancomycin concentration would have
a series of in vitro experiments, MRSA belonging to agr to be at least 15 mg/L to obtain the target AUC/MIC. Using
group II with a defective agr locus exposed to vancomycin the vancomycin pharmacokinetic data generated by Jeffres
concentrations of <10 mg/L produced heteroresistant-like et al.42 in patients receiving vancomycin for the treatment
characteristics similar to VISA strains with subsequent MIC of MRSA pneumonia, Mohr and Murray61 determined by
increases from 1 to 8 mg/L.67 This phenomenon was recently Monte Carlo simulation that the probability of achieving an
demonstrated in a patient with chronic renal failure under- AUC/MIC of ≥400 would be 100% if the S. aureus MIC for
going hemodialysis who experienced recurrent MRSA bac- vancomycin was 0.5 mg/L but 0% if the MIC was 2 mg/L.
teremia over a 30-month period.54 The patient was treated Using a similar one-compartment model of vancomycin and
repeatedly with vancomycin at trough serum concentrations a Monte Carlo simulation integrating S. aureus MIC values,
that always exceeded 10 mg/L. Despite frequent recurrences del Mar Fernández de Gatta Garcia et al.71 reported that a
of bacteremia with the same isolate, the isolate remained daily dosage of 3–4 g of vancomycin would be required to
susceptible to vancomycin. The genetic background of this provide 90% probability of attaining a target AUC/MIC of
organism was found to be similar to other VISA strains be- 400 with an MIC of 1 mg/L. For VISA strains, a vancomy-
longing to agr group II. When the isolate was subjected to cin daily dose of ≥5 g would be required to provide a high
vancomycin concentrations of <10 mg/L under laboratory probability of target AUC/MIC attainment for this pathogen.
conditions, it quickly demonstrated characteristics similar to For susceptible S. aureus, total daily doses of ≥40 mg/kg
VISA strains with a subsequent increased MIC. would likely be required for typical patients. Use of these
Tsuji et al.69 used an in vitro pharmacodynamic model larger dosages of vancomycin should be carefully monitored
to evaluate S. aureus agr groups I–IV exposed to optimal for the desired clinical outcome and the absence of drug-
and suboptimal vancomycin doses over a three-day period. induced toxicity. The use of a nomogram is an alternative
In this study, low vancomycin exposures equivalent to total method for dosage adjustments; however, the majority of
trough serum vancomycin concentrations of 1.5–10 mg/L published nomograms in clinical use have been proven to
and an AUC/MIC of 31–264 produced increases in the MIC be inaccurate, and most have not been clinically validated.72
to the range considered to be VISA by the current CLSI van- In addition, no published nomogram to date has been con-
comycin breakpoints. Although resistance was produced in structed to achieve trough serum vancomycin concentrations
both agr functional and defective strains, the likelihood of of 15–20 mg/L.
resistance was fourfold to fivefold higher in agr-defective Loading doses have also been suggested for critically
isolates. Subsequently, the investigators determined that as ill patients to attain target trough serum vancomycin levels
many as 48% of hospital-associated MRSA had a dysfunc- earlier. In a small study of critically ill patients with seri-
ous S. aureus infections, a vancomycin loading dose of 25 have been implicated, and it was assumed that monitoring
mg/kg infused at a rate of 500 mg/hr was found to be safe of serum concentrations would allow interventions that de-
without producing toxic peak serum drug levels.73 While this crease toxicity.
approach is not currently supported by evidence from large
randomized clinical trials, vancomycin loading doses can be Incidence, Mechanism, and Definition of Nephrotoxicity.
considered in the treatment of serious MRSA infections.63,74 A review of the literature published from 1956 through 1986
identified 57 cases of vancomycin-associated nephrotoxic-
Summary and recommendations: Based on the potential to ity, with over 50% of those cases identified within the first
improve penetration, increase the probability of optimal tar- six years of vancomycin use when the product was relatively
get serum vancomycin concentrations, and improve clinical impure.75 The rate of nephrotoxicity attributable to vanco-
outcomes for complicated infections such as bacteremia, en- mycin monotherapy varied from 0% to 17% and from 7% to
docarditis, osteomyelitis, meningitis, and hospital-acquired 35% with concurrent administration of aminoglycosides.81-85
pneumonia caused by S. aureus, total trough serum van- A review of the literature available through 1993, conducted
comycin concentrations of 15–20 mg/L are recommended. by Cantu et al.,8 identified 167 cases of vancomycin-related
Trough serum vancomycin concentrations in that range nephrotoxicity. However, the lack of clear-cut examples of
should achieve an AUC/MIC of ≥400 in most patients if the vancomycin-induced nephrotoxicity (when the drug was
MIC is ≤1 mg/L. (Level of evidence = III, grade of recom- used alone) was striking. The researchers determined that
mendation = B.) the frequency of nephrotoxicity due to vancomycin mono-
therapy was 5–7%. No evidence supported maintaining
In order to achieve rapid attainment of this target concentra- serum vancomycin concentrations within a given range to
tion for seriously ill patients, a loading dose of 25–30 mg/kg prevent nephrotoxicity. However, another study identified
(based on ABW) can be considered. (Level of evidence = III, older age, longer treatment courses, and higher trough serum
grade of recommendation = B.) vancomycin concentrations (30–65 mg/L) as risk factors for
vancomycin-induced nephrotoxicity.81 Although the defini-
A targeted AUC/MIC of ≥400 is not achievable with convention of vancomycin-induced nephrotoxicity has varied, a
tional dosing methods if the vancomycin MIC is ≥2 mg/L in a reasonable composite from the literature defines this adverse
patient with normal renal function (i.e., CLcr of 70–100 mL/ effect as an increase of >0.5 mg/dL (or a ≥50% increase)
min). Therefore, alternative therapies should be considered. in serum creatinine over baseline in consecutively obtained
daily serum creatinine values or a drop in calculated CLcr of
Vancomycin dosages of 15–20 mg/kg (based on ABW) given 50% from baseline on two consecutive days in the absence
every 8–12 hours are required for most patients with normal of an alternative explanation.10,12,53,86-88
renal function to achieve the suggested serum concentrations The exact mechanism and incidence of vancomy-
when the MIC is ≤1 mg/L. It should be noted that currently cin nephrotoxicity have been investigated in animals and
available nomograms were not developed to achieve these humans. The filtration and energy-dependent transport
targeted endpoints. Individual pharmacokinetic adjustments mechanisms found in the proximal tubular epithelium ren-
and verification of serum target achievement are recom- der the kidneys susceptible to toxicant-induced injury.89
mended. When individual doses exceed 1 g (i.e., 1.5 and 2 g), Vancomycin exposure in renal proximal tubule epithelial
the infusion period should be extended to 1.5–2 hours. (Level cells results in increased cell proliferation. The stimulation
of evidence = III, grade of recommendation = B.) of oxygen consumption and the increase in ATP concentra-
tions support the role of vancomycin as a stimulant of oxida-
Vancomycin Toxicity tive phosphorylation.89 In rats, antioxidants protect kidneys
against vancomycin-induced injury, in theory, by inhibiting
Vancomycin was initially dubbed “Mississippi mud” be- free oxygen radical production.90 Human data suggest toxic-
cause of the brown color of early formulations, which were ity from vancomycin (or aminoglycosides) is not confined
about 70% pure. The impurities are thought to have con- to the proximal tubule but may also involve the medullary
tributed to the incidence of adverse reactions.7,75,76 In the region (loop of Henle and collecting duct) of the nephron.91
1960s, purity increased to 75% and in 1985 to 92–95% for Vancomycin destruction of glomeruli and necrosis of the
Eli Lilly’s vancomycin product.74 Concurrently, a decrease proximal tubule are thought to be due to oxidative stress.92
in the reporting of serious adverse events occurred. In humans, nephrotoxicity due to vancomycin mono-
The most common vancomycin adverse effects are un- therapy with typical dosage regimens is uncommon, is usu-
related to serum drug concentration and include fever, chills, ally reversible, and occurs with an incidence only slightly
and phlebitis.7 Red man syndrome may be associated with above what is reported with other antimicrobials not con-
histamine release and manifests as tingling and flushing of sidered to be nephrotoxic.11,83,93-96 Investigators have admin-
the face, neck, and upper torso. It is most likely to occur istered a wide dosing range of vancomycin monotherapy to
when larger dosages are infused too rapidly (>500 mg over rats without appreciable renal injury.97,98 Renal impairment
≤30 minutes).7,77,78 Vancomycin should be administered in- in rats was observed when concurrent aminoglycosides were
travenously over an infusion period of at least 1 hour to min- administered97-99 or if very high dosages of vancomycin were
imize infusion-related adverse effects. For higher dosages used (350 mg/kg twice daily for four days).98 Wood et al.100
(e.g., 2 g), the infusion time should be extended to 1.5–2 investigated the influence of vancomycin on tobramycin-
hours. Less frequent adverse events, such as neutropenia, induced nephrotoxicity in rats and found that toxicity oc-
also appear unrelated to serum drug concentrations.79,80 curred earlier and was more severe with concurrent amino-
Vancomycin has long been considered a nephrotoxic glycoside and vancomycin therapy. Histological evidence
and ototoxic agent. Excessive serum drug concentrations of tubular necrosis occurred earlier and the percentage of
necrotic cells was higher in rats receiving combination recommended target trough serum vancomycin concentra-
therapy compared with animals administered tobramycin tions of 15–20 mg/L.41 However, the safety of higher trough
alone. Indeed, animals receiving vancomycin alone lacked vancomycin concentrations over a prolonged period has not
evidence of nephrotoxicity. Enhanced renal accumulation been sufficiently studied.
of tobramycin was not evident in animals receiving both Lee-Such et al.115 conducted a retrospective chart review
vancomycin and tobramycin. In fact, animals receiving the of patients over age 18 years who received vancomycin for
combination had lower renal tobramycin concentrations at least 14 days and had an available baseline serum creati-
than did animals receiving tobramycin alone. Increased en- nine concentration and a CLcr of >30 mL/min (calculated by
zymuria and crystalluria were seen in rats and may suggest Cockroft-Gault equation). Patients were categorized by trough
toxicity after vancomycin administration.101-104 However, serum vancomycin concentrations (≤15 mg/L [n = 19] or ≥15.1
these markers are very sensitive and could reflect transient mg/L [n = 40]). Nephrotoxicity was defined as a rise in serum
hypotension due to rapid administration rather than toxicity.8 creatinine of ≥0.5 mg/dL above baseline. The median maxi-
Enzymuria in humans was minimally affected during five mum serum creatinine percentage increase was 0.0% (range,
days of vancomycin therapy.105 –31.3 to 30.0) in the low-trough-concentration group and
Data regarding concurrent vancomycin and ami- 17.2% (range, –36.4 to 133) in the high-concentration group (p
noglycoside administration in humans provide conflict- = 0.0045). There were no significant correlations between per-
ing information, with some reports indicating that the cent change in serum creatinine and duration of vancomycin
combination augments aminoglycoside-induced neph- therapy, highest trough concentration, or average daily dose.
rotoxicity,11,76,81,83,91,94,106,107 and others indicating no ef- The frequency of nephrotoxicity was 0% in the low-trough-
fect.81,83,85,86,96,108-111 Rybak et al.10 found that patients given concentration group and 15% in the high-trough-concentration
vancomycin and an aminoglycoside were 6.7-fold more group. The investigators could not discern if higher vancomy-
likely to develop nephrotoxicity than those receiving vanco- cin levels were a cause or an indicator of worsening renal func-
mycin alone. Vancomycin administration for more than 21 tion. In addition, a single trough vancomycin concentration of
days was an additional risk factor (p = 0.007). Bertino et >15 mg/L placed a patient in the high-concentration group, but
al.107 found vancomycin to be an independent risk factor for such a level could be due to a variety of clinical or operational
aminoglycoside nephrotoxicity in a review of 1489 patients factors not related to vancomycin-induced toxicity. Finally, the
who prospectively received individualized pharmacokinetic use of pressors and concurrent nephrotoxins was poorly de-
monitoring. However, vancomycin use was not associated scribed but could provide additional concurrent risk for renal
with increased risk when assessed in a multivariate model in dysfunction. Further details are lacking, as the data are cur-
this study. Most of the available data suggest a 3- to 4-fold rently available only in abstract form.
increase in nephrotoxicity when aminoglycosides are com- Jeffres et al.87 conducted a similar but prospective in-
bined with vancomycin.81,83,93,94 Synergistic toxicity may vestigation of 94 patients with health-care-associated pneu-
also occur when vancomycin is used with other nephrotoxic monia. Nephrotoxicity was defined as a 0.5-mg/dL increase
agents (e.g., amphotericin B, certain chemotherapy agents) from baseline in serum creatinine or an increase of ≥50% in
or used to treat certain diseases (e.g., sepsis, liver disease, serum creatinine from baseline during vancomycin therapy.
obstructive uropathy, pancreatitis).40,86,93 Patients were stratified based on vancomycin trough concen-
Vancomycin administered either as a single, large, 30- trations of <15 mg/L (n = 43) or ≥15 mg/L (n = 51). Overall,
mg/kg once-daily dose or in two divided doses did not in- 40 patients (42.6%) met the criteria for nephrotoxicity. The
fluence nephrotoxicity significantly (p = 0.71).112 However, maximal serum creatinine concentration observed occurred
“high-dose” (defined as a total daily dose of 40 mg/kg, either after the maximum serum vancomycin concentration by at
as a continuous infusion or divided every 12 hours, resulting least 24 hours in 34 patients (85.0%). Patients who devel-
in a mean ± S.D. concentration of 24.4 ± 7.8 mg/L) was found oped nephrotoxicity were more likely to have higher steady-
to be less nephrotoxic than “standard-dose” intermittent ther- state mean trough serum vancomycin concentrations (20.8
apy (defined as 10 mg/kg every 12 hours, resulting in a mean mg/L versus 14.3 mg/L, respectively; p < 0.001), trough se-
± S.D. trough serum vancomycin concentration of 10.0 ± 5.3 rum vancomycin concentrations of >15 mg/L (67.5% versus
mg/L) (p = 0.007) by other investigators.113 It should be noted 40.7%, p = 0.01), and a longer duration (≥14 days) of van-
that the average age of patients in this later investigation was comycin therapy (45.0% versus 20.4%, p = 0.011) than those
60 years; their average weight was not provided. who did not develop nephrotoxicity.
Human trials have suggested that trough serum van- Hidayat et al.53 prospectively investigated the efficacy
comycin concentrations of >10 mg/L are associated with an and toxicity of adjusting vancomycin troughs to achieve an
increased risk of nephrotoxicity.10,76,83,85,86 No correlation has unbound concentration of at least four times the MIC. Patients
been observed between peak vancomycin concentrations and received vancomycin for 72 hours or more. Nephrotoxicity
nephrotoxicity.10 Zimmermann et al.114 found no correlation was defined as a 0.5-mg/dL or ≥50% increase from the base-
between nephrotoxicity and initial serum creatinine concen- line serum creatinine concentration in two consecutive labo-
tration, length of hospital stay, or duration of vancomycin ratory analyses. For nephrotoxicity analysis, groups were
therapy. However, the researchers did find that serum van- divided based on trough serum vancomycin concentrations
comycin concentrations were significantly higher in those (<15 or ≥15 mg/L). Nephrotoxicity occurred only in the ≥15-
patients who eventually developed nephrotoxicity. In that mg/L group (11 of 63 patients [12%] versus 0 of 24 patients
study, no patient who maintained trough serum vancomycin in the <15-mg/L group [p = 0.01]) and was predicted by the
concentrations of <20 mg/L developed nephrotoxicity. It is use of concurrent nephrotoxic agents (p < 0.001). By con-
noteworthy that 21 (57%) of 37 patients consistently had trolling for age, admission to ICUs, Acute Physiology and
trough serum vancomycin concentrations of >20 mg/L and Chronic Evaluation II score, trough serum vancomycin level,
yet did not develop nephrotoxicity. Recent guidelines have and duration of therapy, multivariate analysis demonstrated
concurrent nephrotoxins to be the strongest predictor of van- A patient should be identified as having experienced van-
comycin nephrotoxicity. Without concurrent nephrotoxins, comycin-induced nephrotoxicity if multiple (at least two or
nephrotoxicity occurred in only 1 (2%) of 44 patients with a three consecutive) high serum creatinine concentrations (in-
trough concentration of ≥15 mg/L versus 0 of 24 patients in crease of 0.5 mg/dL or ≥50% increase from baseline, which-
the <15-mg/L group. ever is greater) are documented after several days of vanco-
Lodise et al.12 retrospectively examined the relation- mycin therapy in the absence of an alternative explanation.
ship between vancomycin dosage and rate of nephrotoxic- (Level of evidence = II, grade of recommendation = B.)
ity at a single institution. Nephrotoxicity was defined as an
increase in serum creatinine of 0.5 mg/dL or an increase of Role of Therapeutic Drug Monitoring in Preventing
50%, whichever was greater, on at least two consecutive Nephrotoxicity. Because vancomycin is eliminated via glo-
days during the period from initiation of vancomycin or merular filtration, a decrease in the glomerular filtration rate
linezolid therapy to 72 hours after completion of therapy. from any cause will increase the serum vancomycin concen-
Linezolid usage was also included as a nonvancomycin tration and make the association between renal dysfunction
comparator group. A significant difference in nephrotoxic- and trough concentrations difficult to assess.8
ity was noted among patients receiving vancomycin ≥4 g/ Some investigators have found vancomycin therapeu-
day (34.6%), vancomycin <4 g/day (10.9%), and linezolid tic drug monitoring to be associated with decreased neph-
(6.7%) (p = 0.001). The relationship between high-dosage rotoxicity. Other factors associated with decreased toxicity
vancomycin and nephrotoxicity persisted in the multivariate include shorter courses of therapy, less total dosage in grams
analyses that controlled for potential confounding covari- of the drug, and a decreased length of hospital stay.7,12,116,117
ates. The multivariate analyses also demonstrated that pa- However, Darko et al.7 found therapeutic drug monitoring
tient total weight of ≥101.4 kg, estimated CLcr of ≤86.6 mL/ to be cost-effective only in patients in ICUs, those receiving
min, and ICU residence at the start of therapy each indepen- other nephrotoxins, and, possibly, oncology patients.
dently influenced the time to nephrotoxicity. In a secondary
Summary and recommendations: Available evidence does
analysis, a significant relationship was found between the
not support monitoring peak serum vancomycin concentra-
vancomycin AUC and nephrotoxicity. Specifically, a vanco-
tions to decrease the frequency of nephrotoxicity. (Level of
mycin AUC of ≥952 mg · L/hr was associated with a higher
evidence = I, grade of recommendation = A.)
probability of vancomycin-related nephrotoxicity.
Nguyen et al.88 retrospectively investigated patients
Monitoring of trough serum vancomycin concentrations to
receiving vancomycin between January and December 2006
reduce nephrotoxicity is best suited to patients receiving ag-
at a single institution. Patients included were age ≥18 years,
gressive dosing targeted to produce sustained trough drug
receiving vancomycin for at least 72 hours, and had at least
concentrations of 15–20 mg/L or who are at high risk of
one serum vancomycin value obtained. Hemodialysis pa-
toxicity, such as patients receiving concurrent nephrotoxins.
tients were excluded. Nephrotoxicity was defined as an in- (Level of evidence = III, grade of recommendation = B.)
crease of >0.5 mg/dL over baseline in serum creatinine for
two consecutive assays. Creatinine levels were followed un- Monitoring is also recommended for patients with unstable
til patient discharge. Patients were divided based on trough renal function (either deteriorating or significantly improv-
serum vancomycin concentration attainment of 5–15 mg/L ing) and those receiving prolonged courses of therapy (over
(n = 130) or >15 mg/L (n = 88). The rate of nephrotoxic- three to five days). (Level of evidence = II, grade of recom-
ity was 6.2% in the lower-trough group and 18.2% in the mendation = B.)
higher-trough group (p < 0.01). Multivariate analysis in-
dicated that the main predictors of nephrotoxicity were an All patients receiving prolonged courses of vancomycin
elevated overall average trough concentration and duration should have at least one steady-state trough concentration
of therapy. obtained (just before the fourth dose). Frequent monitoring
Investigations, such as those described herein, are in- (more than a single trough concentration before the fourth
triguing but often limited by small sample size, retrospec- dose) for short-course therapy (less than five days) or for
tive design, and questionable methodology. Additional data lower-intensity dosing (targeted to attain trough serum
are needed, including the timing of the relationship between vancomycin concentrations below 15 mg/L) is not recom-
high vancomycin levels and nephrotoxicity (i.e., which one mended. (Level of evidence = II, grade of recommendation
precedes the other). In addition, while statistically relevant, = B.)
the clinical significance of minor and transient changes in
creatinine or CLcr can be debated. The effect of a 0.5-mg/dL There are limited data to support the safety of sustained
increase in serum creatinine concentration would be greater trough serum vancomycin concentrations of 15–20 mg/L.
in a patient with a lower initial CLcr value than in one with a When this target range is desired, obtaining once-weekly
higher baseline CLcr value. trough concentrations in hemodynamically stable patients
is recommended. Frequent (in some instances daily) trough
Summary and recommendation: There are limited data concentration monitoring is advisable to prevent toxicity in
suggesting a direct causal relationship between toxicity and hemodynamically unstable patients. The exact frequency of
specific serum vancomycin concentrations. In addition, data monitoring is often a matter of clinical judgment. (Level of
are conflicting and characterized by the presence of con- evidence = III, grade of recommendation = B.)
founding nephrotoxic agents, inconsistent and highly vari-
able definitions of toxicity, and the inability to examine the Data on comparative vancomycin toxicity using continuous
time sequence of events surrounding changes in renal func- versus intermittent administration are conflicting and no
tion secondary to vancomycin exposure. recommendation can be made.
Incidence of Ototoxicity and Role of Therapeutic Drug because this toxicity is rarely associated with monotherapy
Monitoring for Prevention of Vancomycin-Induced Hearing and does not correlate with serum vancomycin concentra-
Loss. Vancomycin-induced hearing loss is controversial. tions. Monitoring may be more important when other oto-
Vancomycin has not been found to be ototoxic in animal mod- toxic agents, such as aminoglycosides, are administered.
els.97,98,100,118,119 Early literature attributed ototoxic events to (Level of evidence = III, grade of recommendation = B.)
impurities or to concurrent ototoxic agents.119 Early studies in-
dicated that other ototoxic agents, such as the aminoglycosides Summary
kanamycin and streptomycin, may have additive or synergistic
toxicity when used in combination with vancomycin.120 The In general, pharmacodynamic dosing of antibiotics may sig-
frequency of ototoxicity in humans has been reported to range nificantly augment antibiotic performance. There seems to be
from 1% to 9%3,8,48,121-124 and to be associated with serum van- little difference in the pharmacodynamics of intermittently
comycin concentrations above 40 mg/L.7,125 This most likely or continuously dosed vancomycin. This consensus panel
represents an inflated occurrence rate due to impurities asso- review supports that vancomycin is a concentration-inde-
ciated with the older formulation or poor documentation of pendent killer of gram-positive pathogens and that the AUC/
cause and effect as they relate to serum concentrations. The MIC is likely the most useful pharmacodynamic parameter to
true risk of ototoxicity from vancomycin monotherapy is low predict effectiveness. In many clinical settings where it may
without concurrent therapy with ototoxic agents.77 be difficult to obtain multiple serum vancomycin concentra-
Severe ototoxicity induced by vancomycin is rare and tions to determine the AUC and subsequently the AUC/MIC,
characterized as damage to the auditory nerve that initially trough serum vancomycin concentration monitoring can be
affects high-frequency sensory hairs in the cochlea, then the recommended as the most accurate and practical method to
middle- and low-frequency hairs, and eventually can lead to monitor serum vancomycin levels. Increasing trough serum
total hearing loss.75 High-tone deafness occurs before low- vancomycin concentrations to 15–20 mg/L to obtain an in-
tone deafness at all frequencies and is permanent. Inability creased AUC/MIC of ≥400 may be desirable but is currently
to hear high-frequency sounds and tinnitus are ominous signs not supported by clinical trial data. Target attainment of an
that should result in discontinuation of vancomycin.126,127 Also AUC/MIC of ≥400 is not likely in patients with S. aureus
rare is reversible ototoxicity such as tinnitus, which can occur infections who have an MIC of ≥2 mg/L; therefore, treatment
with or without high-tone deafness.33,120,127 Investigation of with alternative agents should be considered. Higher trough
pediatric pneumococcal meningitis noted that early vancomy- serum vancomycin levels may also increase the potential for
cin administration (relative to ceftriaxone administration) was toxicity, but additional clinical experience will be required to
associated with a substantially increased risk of hearing loss determine the extent of this potential.
due to the effects of rapid bacterial killing by both antimicrobi-
als and the resultant host inflammatory response.128 However,
toxicity did not correlate with vancomycin concentrations.
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111. Goetz MB, Sayers J. Nephrotoxicity of vancomycin
and aminoglycoside therapy separately and in combi- Developed through the ASHP Council on Therapeutics and ap-
nation. J Antimicrob Chemother. 1993; 32:325–34. proved by the ASHP Board of Directors on June 26, 2008, the
112. Cohen E, Dadashev A, Drucker M, et al. Once-daily Infectious Diseases Society of America’s Board of Directors on
versus twice-daily intravenous administration of June 16, 2008, and the Society of Infectious Diseases Pharmacists’
vancomycin for infections in hospitalized patients. J Board of Directors on June 25, 2008.
Antimicrob Chemother. 2002; 49:155–60.
113. Boffi El Amari E, Vuagnat A, Stern R, et al. High Michael Rybak, Pharm.D., M.P.H. is Professor of Pharmacy and
versus standard dose vancomycin for osteomyelitis. Medicine, and Director, Anti-Infective Research Laboratory, Eugene
Scand J Infect Dis. 2004; 36:712–7. Applebaum College of Pharmacy and Health Science, Wayne State
114. Zimmermann AE, Katona BG, Plaisance KI. Associ- University (WSU), Detroit, MI. Ben Lomaestro, Pharm.D., is
ation of vancomycin serum concentrations with out- Senior Clinical Pharmacy Specialist in Infectious Diseases, Albany
comes in patients with gram-positive bacteremia. Medical Center, Albany, NY. John C. Rotschafer, Pharm.D., is
Pharmacotherapy. 1995; 15:85–91. Professor, Department of Experimental and Clinical Pharmacology,
115. Lee-Such SC, Overholser BR, Munoz-Price LS.
College of Pharmacy, University of Minnesota, Minneapolis. Robert
Nephrotoxicity associated with aggressive vanco- Moellering Jr., M.D., is Shields Warren-Mallinckrodt Professor
mycin therapy. Paper presented at 46th Interscience of Medical Research, Harvard Medical School, and Physician,
Conference on Antimicrobial Agents and Chemo- Department of Medicine, Beth Israel Deaconess Medical Center,
therapy. San Francisco, CA; 2006 Sep. Boston, MA. William Craig, M.D., is Professor Emeritus, University
116. Welty TE, Copa AK. Impact of vancomycin therapeu- of Wisconsin School of Medicine and Public Health, School of
tic drug monitoring on patient care. Ann Pharmacother. Medicine and Public Health, University of Wisconsin, Madison.
1994; 28:1335–9. Marianne Billeter, Pharm.D., BCPS, is Manager of Clinical
117. Iwamoto T, Kagawa Y, Kojima M. Clinical efficacy of Pharmacy Services at Ochsner Medical Center, New Orleans, LA.
therapeutic drug monitoring in patients receiving van- Joseph R. Dalovisio, M.D., is Chairman, Department of Infectious
comycin. Biol Pharm Bull. 2003; 26:876–9. Diseases, Ochsner Health System, New Orleans. Donald P. Levine,
118. Davis RR, Brummett RE, Bendrick TW, et al. The M.D., is Professor of Medicine and Chief, Division of General
ototoxic interaction of viomycin, capreomycin and Internal Medicine, WSU.
polymyxin B with ethacrynic acid. Acta Otolaryngol.
1982; 93:211–7. The following individuals are acknowledged for reviewing draft
119. Tange RA, Kieviet HL, von Marle J, et al. An experi- versions of this statement: Diane M. Cappelletty, Pharm.D.; Douglas
mental study of vancomycin-induced cochlear dam- N. Fish, Pharm.D., FCCP, FCCM, BCPS; William L. Greene, B.S.,
age. Arch Otorhinolaryngol. 1989; 246:67–70. Pharm.D., BCPS, FASHP; David J. Ritchie, Pharm.D., FCCP,
BCPS; Annette M. Rowden, Pharm.D., BCPS; and Lynda J. The bibliographic citation for this document is as follows: American
Thompson, Pharm.D. Society of Health-System Pharmacists. Therapeutic monitor-
ing of vancomycin in adult patients: A consensus review of the
The authors have declared no potential conflicts of interest. American Society of Health-System Pharmacists, the Infectious
Diseases Society of America, and the Society of Infectious Diseases
Copyright © 2009, American Society of Health-System Pharmacists, Pharmacists. Am J Health-Syst Pharm. 2009; 66:82–98.
ASHP Therapeutic Position Statement on the Use of

Second-Generation Antipsychotic Medications in the
Treatment of Adults with Psychotic Disorders
Position Individuals with schizophrenia generally exhibit a mixture

of positive, negative, and cognitive symptoms with vary-
The American Society of Health-System Pharmacists ing intensity throughout the course of their illness (Table 1).
(ASHP) recognizes that schizophrenia, schizoaffective dis- Schizoaffective disorder differs from schizophrenia in that
order, and other psychotic disorders are serious mental ill- recurrent mood episodes (mania or depression) occur over a
nesses that can significantly affect an individual’s percep- substantial period of time over the course of the illness in ad-
tual, behavioral, affective, and cognitive functions. These dition to chronic psychotic symptoms. These two disorders
conditions are usually chronic and recurrent, necessitating have been studied together in many clinical trials and will be
continuous treatment over the patient’s lifetime. Individuals considered together for the purpose of this document.
with these disorders frequently require lengthy and expen- It has been estimated that the worldwide lifetime fre-
sive hospitalizations, as well as a variety of ongoing reha- quency of psychotic disorders is about 1%.2,3 Onset of the
bilitative and supportive services that can impose a signifi- first severe psychotic symptoms in a patient with schizo-
cant burden on society. In addition, high rates of suicidal phrenia usually occurs between the late teens and mid-30s,
behavior and completed suicides have been observed in pa- with onset in males peaking between ages 15 and 30 and
tients with psychotic disorders. The management of these females exhibiting a later onset, between ages 20 and 35.4,5
disorders typically requires long-term treatment with anti- Late-onset schizophrenia, occurring after 40 years of age,
psychotic medications, the use of adjunctive pharmacologic may have an otherwise similar course to typical adult-onset
treatments, and ongoing psychosocial and supportive inter- schizophrenia. Prodromal symptoms of psychosis occurring
ventions to reduce morbidity and mortality. in children and adolescents (e.g., apathy, social withdrawal)
ASHP encourages health professionals to consider may be present before the first psychotic break, but the full
the use of second-generation (“atypical” or “novel”) anti symptoms of these disorders are rare in this population.
psychotics as first-line drug treatments for individuals with Because these illnesses frequently have their symptom onset
psychotic disorders. Second-generation antipsychotics share in early adulthood and are characterized by a wide range of
the common pharmacologic action of dual serotonin–dopa symptoms, they usually cause significant, progressive im-
mine antagonism. While the acquisition costs of these agents pairment in the social, occupational, and academic function-
are greater than those of older drugs, randomized controlled ing of affected individuals.
trials and naturalistic studies have demonstrated that second-
generation antipsychotics effectively treat the symptoms of Pharmacologic Characteristics of
psychotic disorders while providing a tolerability profile that Antipsychotic Drugs
improves treatment adherence and reduces the severity of
short- and long-term adverse motor effects. Second-genera The effectiveness of first-generation antipsychotic agents,
tion antipsychotics have also been found to have improved whose primary mechanism of action was blockade of post
profiles for cognitive impairments in schizophrenia, relative synaptic dopamine type 2 (D2) receptors in the brain, led to
to older agents, allowing for opportunities toward psycho- the initial hypothesis regarding dopamine’s role in schizo-
social rehabilitation. There is also evidence that the use of phrenia. While it is apparent that increased dopamine in the
these agents improves outcomes in patients with chronic mesolimbic pathway is responsible for the positive symp-
psychotic disorders compared with older antipsychotics, toms of schizophrenia, it is now understood that psychotic
specifically reducing the rates of symptom relapse and in- disorders frequently involve numerous neurochemical ab
patient rehospitalization. However, it should be noted that normalities. Psychosis has been observed in individuals with
second-generation antipsychotics are associated with sig- idiopathic6 and drug-induced7 hypofunction of the glutamate
nificant treatment risks, such as adverse cardiovascular
and metabolic effects, that should be
carefully considered during treatment
initiation and throughout the course of Table 1.
therapy. Positive, Negative, and Cognitive Symptoms of Schizophrenia
Positive Negative Cognitive
Background Symptoms Symptoms Symptoms
Hostility Emotional withdrawal Impaired attention
Schizophrenia and schizoaffective Excitement Uncooperativeness Impaired short-term
disorder are serious, chronic mental Hallucinations Blunted affect memory
illnesses that affect perceptual, be- Delusions Inappropriate affect Impaired executive
havioral, and cognitive functioning. Suspiciousness Poverty of thought functioning
The DSM-IV-TR established criteria Grandiosity Social withdrawal Impaired verbal fluency
for five main subtypes of schizophre- Conceptual Lack of spontaneity
disorganization Poor abstract thinking
nia and for schizoaffective disorder.1
system. In addition, the high rate of nicotine dependence in Clozapine, the first second-generation antipsychotic
individuals with psychotic disorders–up to 88% in one introduced in the United States, has an established level of
study8—has led to the identification and study of acetyl- efficacy for use in individuals with psychotic disorders re-
choline-receptor abnormalities in the pathophysiology of sistant to treatment with other antipsychotics. Kane et al.13
schizophrenia.9 conducted the landmark trial that demonstrated the superior
The ideal drug for the treatment of psychotic disorders efficacy of clozapine in individuals with treatment-resistant
would have several important characteristics. It would pro- psychosis. This trial enrolled only patients whose psychosis
vide effective relief and prevention of acute positive symp- was treatment resistant, defined as not responding to at least
toms of schizophrenia. Other ideal characteristics would three periods of treatment in the preceding five years with
include effective relief of affective, cognitive, and negative antipsychotic agents from two different chemical classes at
symptoms; minimal short- and long-term adverse effects; dosages equivalent to 1000 mg/day of chlorpromazine for
few drug interactions; and low acquisition cost. Although six weeks. The previous antipsychotic trials must have failed
no antipsychotic agent currently available completely fits all to provide periods of good functioning or significant symp-
these criteria, second-generation antipsychotics offer many tomatic relief. A six-week trial of haloperidol (mean dosage,
benefits not achieved with traditional antipsychotics. 61 mg/day) and benztropine followed to confirm lack of
First-generation antipsychotic agents primarily exert drug response. Participants whose psychosis did not respond
their therapeutic effects through the blockade of postsynap to haloperidol were randomized to receive clozapine (up to
tic D2 receptors in the mesolimbic pathway, thereby reduc- 900 mg/day) or chlorpromazine (up to 1800 mg/day) with
ing positive symptoms over time. However, these drugs are benztropine. Using a priori criteria, response rates were 30%
not selective in their activity. Blockade of dopamine in other for patients treated with clozapine versus 4% for the chlor
areas of the brain often leads to acute extrapyramidal motor promazine group. The authors found that improvements in
effects (e.g., dystonias, parkinsonism), tardive dyskinesia, the Brief Psychiatric Rating Scale total scores and clinical
increased levels of serum prolactin, and exacerbation of neg- global impression (CGI) were three times greater in patients
ative symptoms. Although occurring infrequently at stan- treated with clozapine.
dard doses, an array of adverse neurologic, cardiovascular, The landmark clinical studies used in the evaluation of
and dermatologic effects are associated with these agents. second-generation antipsychotics are summarized in Table
Second-generation antipsychotic drugs share the com- 3. In general, these trials lasted four to six weeks and as-
mon pharmacologic action of dual serotonin–dopamine sessed the efficacy of these agents in the treatment of acute
antagonism (Table 2). Aripiprazole differs slightly in that psychotic disorders. Because of the study designs employed,
it functions as a partial agonist at dopamine receptors, reno assumptions can be made regarding the efficacy of these
ducing dopamine activity in the mesolimbic pathway.10,11 agents for long-term prevention of psychotic relapse, for
Antagonism of serotonin type 2 (5-HT2) receptors increases comorbid substance abuse or mood disorders, or in other
the release of endogenous dopamine.12 This increase in do- complex clinical situations. The medical literature suggests
pamine decreases the likelihood of extrapyramidal motor that all currently available second-generation antipsychotic
symptoms and elevated prolactin levels without signifi- agents are superior to placebo and at least as effective as the
cantly reducing the beneficial effects against positive symp- traditional antipsychotics in the reduction of positive symp-
toms of psychosis. Theoretically, this property of the newer toms of schizophrenia. With long-term therapy, second-gen-
drugs may also help to improve the negative symptoms of eration antipsychotics may also have beneficial effects on
schizophrenia. negative symptoms; however, these benefits have not been
consistently demonstrated in the four- to six-week clinical
Efficacy for Psychotic Symptoms trials.
The Clinical Antipsychotic Trials of Intervention
Second-generation antipsychotic agents have been dem Effectiveness (CATIE) was a multicenter clinical study
onstrated to be at least as effective as the traditional anti sponsored by the National Institute of Mental Health.25 The
psychotic agents in the treatment of positive symptoms of first phase of this study, conducted between January 2001
schizophrenia when used in appropriate therapeutic doses. and December 2004, involved 1460 patients with chronic
The newer antipsychotics also demonstrate benefits for af- schizophrenia age 18–65 years. Patients were randomized
fective symptoms, cognition, and psychosocial functioning to treatment for up to 18 months with one of four available
not seen with the older agents. second-generation antipsychotics (olanzapine, quetiapine,
risperidone, or ziprasidone) or per-
phenazine, a traditional antipsy-
chotic. The primary outcome mea-
Table 2. sured was time to discontinuation of
Second-Generation Antipsychotics Currently Available in the United treatment for any cause, including
States lack of efficacy, intolerable adverse
Drug (Trade Name) Manufacturer Year Approved effects, or patient’s decision to end
treatment. Treatment with olanzap-
Clozapine (Clozaril) Novartis 1989
ine at a mean modal dosage (MMD)
Risperidone (Risperdal) Janssen Pharmaceutica 1993
Olanzapine (Zyprexa) Eli Lilly 1996 of 20.1 mg/day was associated with
Quetiapine (Seroquel) AstraZeneca 1997 a significantly longer median dura-
Ziprasidone (Geodon) Pfizer 2001 tion of treatment (9.2 months) com-
Aripiprazole (Abilify) Bristol-Myers Squibb 2002 pared with quetiapine (4.6 months;
Paliperidone (Invega) Janssen Pharmaceutica 2006 MMD, 543.4 mg/day), risperidone
Table 3.
Major Efficacy Trials of Second-Generation Antipsychotics13–24
Duration
Ref. Patient Population Treatment (wk) Resultsa
13 268 inpatients with schizophrenia refractory Clozapine 500–900 mg/day vs. 6 BPRS total, CGI: Improvement with clozapine 3 times greater
to treatment with adequate trials with chlorpromazine 1000–1800 than with chlorpromazine (p < 0.001).
at least three agents from two different mg/day + benztropine (up to 6 Patient improvement (20% reduction in BPRS and either CGI
chemical classes, after nonresponse to mg/day) of ≤3 or BPRS total of ≤35: Clozapine, 30%; chlorpromazine,
6-wk trial of haloperidol 4% (p < 0.001).
14 39 outpatients with schizophrenia with Clozapine 200–600 mg/day vs. 10 BPRS positive symptoms: Improvement with clozapine greater
history of residual symptoms after at haloperidol 10–30 mg/day + than with haloperidol (p = 0.05).
least two 6-wk trials of neuroleptics from benztropine (up to 4 mg/day) SANS: Improvement with clozapine, worsening with
different classes, after nonresponse to haloperidol (p = 0.04).
6-wk trial of fluphenazine Clinical response rate: Clozapine, 44.4%; haloperidol, 5.5%
(p = 0.017).
15 388 inpatients with schizophrenia Risperidone 2, 6, 10, and 16 mg/day; 8 Clinical improvement (20% reduction in PANSS): Greater
haloperidol 20 mg/day; placebo improvement in patients receiving risperidone 6 and 16 mg
vs. haloperidol.
Clinical improvement (Kane et al. criteria): Risperidone 6, 10,
and 16 mg superior to placebo (p < 0.05).
16 135 patients with schizophrenia Risperidone 2, 6, 10, and 16 mg/day; 8 Clinical improvement (20% reduction in PANSS): Greater
haloperidol 20 mg/day; placebo improvement in patients receiving risperidone 2, 6, 10, and
16 mg and haloperidol recipients vs. placebo.
PANSS—negative subscale: Only risperidone 6 mg superior to
placebo.
17 400 patients with schizophrenia Risperidone long-acting injection 12 Improvement in PANSS and CGI (LOCF) significant for all
25, 50, and 75 mg every 2 wk vs. groups vs. placebo.
placebo
18 335 patients with schizophrenia Olanzapine-L (2.5–7.5 mg/day), 6 CGI, BPRS: Olanzapine-M, olanzapine-H, and haloperidol
olanzapine-M (7.5–12.5 mg/day), groups significantly improved vs. placebo. SANS:
olanzapine-H (12.5–17.5 mg/ Olanzapine-H group demonstrated significant improvement
day), haloperidol 10–20 mg/day, vs. haloperidol.
placebo
19 152 inpatients with schizophrenia Olanzapine 1 and 10 mg/day vs. 6 BPRS total, PANSS-negative score: Olanzapine 10-mg group
placebo superior to placebo. Olanzapine 1-mg group showed no
improvement over placebo for any efficacy measure.
20 361 hospitalized patients with schizophrenia Quetiapine 75, 150, 300, 600, and 6 BPRS total: Significant improvement from baseline vs. placebo
750 mg/day; haloperidol 12 mg/ noted in all treatment groups except quetiapine 75 mg.
day; placebo SANS: Significant improvement vs. placebo noted in
quetiapine 300 mg and haloperidol groups.
(Continued on next page)

(4.8 months; MMD, 3.9 mg/day), perphenazine (5.6 months;

MMD, 20.8 mg/day), and ziprasidone (3.5 months; MMD,
BPRS total, CGI, SANS: Quetiapine-H demonstrated significant
CGI: Scores in LOCF analysis superior to placebo for all active

MADRS: Subset of ziprasidone 160-mg group with depressive
PANSS total: Significant improvement with all active treatment

112.8 mg/day). For patients remaining on the assigned treat-
symptomatology demonstrated improvement vs. placebo.
BPRS = Brief Psychiatric Rating Scale, CGI = clinical global impression, SANS = Schedule for the Assessment of Negative Symptoms, PANSS = Positive and Negative Syndrome Scale, MADRS =
BPRS total, CGI: Ziprasidone 120-mg group demonstrated
ment over the course of the study, overall psychopathology
improvement over placebo. Quetiapine-L group did not
show superiority to placebo for any efficacy measure.
demonstrated significant improvement over placebo.

as assessed by the Positive and Negative Syndrome Scale
and the CGI showed improvement over time. Notably, the
BPRS, PANSS, CGI: Both active treatment groups
traditional antipsychotic perphenazine demonstrated compa-
rable efficacy to the second-generation comparators across
all measures.
There are several concerns that need to be considered
regarding CATIE. First, within the 18-month study period,
Resultsa
74% of the patients discontinued their initial assigned drug

therapy. Second, patients with preexisting tardive dyskine-
sia were not assigned to perphenazine and may have been
significant improvement.
less likely to exhibit adverse motor effects during the study.

treatment groups. Finally, 30% of the patients receiving olanzapine experi-
enced weight gain and adverse metabolic effects, including
groups at 2 wk.
elevated blood glucose, cholesterol, triglyceride, and glyco-

sylated hemoglobin levels. CATIE compared a single tradi
tional antipsychotic, perphenazine, given at a low dosage to
several second-generation antipsychotics. While the data
generated from this study are helpful for determining dif
ferences in effectiveness between the assigned regimens and
comparing important adverse effect issues, they support the
Duration
widely held notion that the selection of antipsychotic drugs

(wk)
should be an individualized process.

6
Neurocognitive Effects
Ziprasidone 80 mg/day(40 mg b.i.d.)
quetiapine-L (up to 250 mg/day),
haloperidol 10 mg/day, placebo

and 160 mg/day (80 mg b.i.d.),
Quetiapine-H (up to 750 mg/day),
Ziprasidone 40 and 120 mg/day,
Impaired cognitive functioning has long been observed as

Aripiprazole 15 and 30 mg/day,
a core feature of psychotic disorders. These impairments

are relatively stable over the natural course of the illness,
Treatment
regardless of the frequency of acute exacerbations of psy-

chotic symptoms.26 Furthermore, cognitive impairment may
Montgomery–Asberg Depression Rating Scale, LOCF = last observation carried forward.
have a greater impact on psychosocial functioning than any

other feature of schizophrenia.27,28
placebo
placebo
placebo
Many domains of cognition, including attention,

short-term memory, and executive function, are affected by
schizophrenia.26 Treatment with traditional antipsychotic
drugs, while relieving positive symptoms of psychosis, do
little to improve cognitive functioning. The concomitant use
of anticholinergic drugs intended to prevent or treat extra
286 hospitalized patients with schizophrenia
pyramidal symptoms that accompany antipsychotic therapy

may actually worsen some cognitive functions.29
Second-generation antipsychotics can play an impor-
302 patients with schizophrenia or
tant role in facilitating the psychosocial rehabilitation of in-

Patient Population
dividuals with psychotic disorders by improving cognition.

schizoaffective disorder
These agents have been shown to improve scores on assess-

ments representing a broad range of cognitive functions. A
lower degree of binding to dopamine-D2 receptors, as well
as 5-HT2 antagonism, in the mesocortical pathway may
contribute to the beneficial effects on cognition. The indi-
vidualized receptor-binding properties of second-generation
Table 3 (continued)
antipsychotics may contribute to differential improvements

in various cognitive domains in individuals with psychotic
disorders.
In a 14-week study of individuals with treatment-
Ref.
resistant schizophrenia, risperidone and olanzapine im-

21
22
23
24
proved executive function, declarative memory, and atten-

tion.30 Clozapine has been shown to positively affect execu-
tive function and working memory in numerous studies.31-33
In an open-label study of 255 clinically stable patients, ar
ipiprazole and olanzapine improved working memory from Prolactin Elevation. Dopamine antagonists may elevate se-
baseline after eight weeks of treatment, while aripiprazole rum prolactin levels by decreasing the prolactin inhibitory
showed a greater improvement than olanzapine in verbal effects of dopamine in the hypothalamus. Prolactin eleva-
learning at weeks 8 and 26.34 tion has been reported to cause an irregular or suppressed
menstrual cycle,49 galactorrhea,50 gynecomastia, and sexual
Adverse Effects dysfunction51 in the short term. With long-term elevation of
plasma prolactin levels, suppression of estrogen and testos-
One of the primary advantages of second-generation anti terone may occur. These effects may lead to a decrease in
psychotics in the chronic treatment of psychotic disorders is bone mineral density and to osteoporosis.52
the improved tolerability profile over older antipsychotics. The degree of prolactin elevation that an antipsychotic
Adverse effects related to dopamine blockade in the central agent may exert appears to be related to its dopamine- and
nervous system tend to occur less frequently in individuals serotonin-binding properties. Significant prolactin elevation
treated with second-generation antipsychotics compared and its associated adverse effects can occur with moderate-
with those receiving traditional antipsychotics. However, the to-high doses of the traditional antipsychotics and risperi-
newer drugs have been associated with different problems done.52 Risperidone has been consistently associated with the
that can affect drug therapy. greatest degree of prolactin elevation among the second-gen-
eration antipsychotics.53,54 In a prospective trial, olanzapine
Motor Symptoms. Treatment with conventional antipsychot was found to cause a low and transient increase in prolactin
ics has long been associated with both acute and chronic levels across its dosage range, compared with the significant,
adverse motor effects. Acute extrapyramidal symptoms— persistent hyperprolactinemia associated with haloperidol.55
dystonia, pseudoparkinsonism, and akathisia (a syndrome The effect of quetiapine treatment across its dosage range on
of subjective anxiety and restlessness)—are thought to be plasma prolactin levels was comparable to placebo, while
related to drug-induced blockade of dopamine receptors in significant elevations were associated with haloperidol.20
the nigrostriatal pathway in the brain. Second-generation Similarly, aripiprazole has been shown to be comparable
antipsychotics, possibly through a combination of 5-HT2- to placebo for prolactin elevation.24 Antipsychotic-associ
receptor antagonism and rapid dissociation from D2 recep ated prolactin elevation has been successfully managed by
tors,35 produce antipsychotic effects with a lower likelihood switching to an antipsychotic agent with a lower propensity
of acute extrapyramidal symptoms.36 toward increasing prolactin.56,57
Tardive dyskinesia, a potentially irreversible chronic
motor disorder caused by long-term exposure to dopamine Weight Gain. The metabolic effects of antipsychotic drug
antagonists, has been another serious concern with con- therapy have become a source of concern for clinicians and
ventional antipsychotics. Though not completely eliminat- patients. Psychotic disorders and antipsychotic drug treat-
ing the risk, second-generation antipsychotics have been ment have long been associated with comorbid obesity58
shown to have a lower risk of treatment-emergent tardive and its related conditions: type 2 diabetes mellitus59,60 and
dyskinesia with maintenance treatment. Using data pooled cardiovascular disease.61 In addition, drug treatments62 and
from three controlled comparative studies, Tollefson et al.37 lifestyle changes63,64 aimed at weight reduction may be inef-
reported that 50 (7.1%) of 707 olanzapine-treated patients fective or difficult to implement in this population.
manifested symptoms of tardive dyskinesia during the trials, Varying degrees of weight gain have been reported
compared with 32 (16.2%) of 197 individuals treated with with chronic use of traditional and second-generation anti
haloperidol (p < 0.001). In a nine-month prospective study psychotics. Among the traditional antipsychotics, loxa-
of outpatients age 45 years or older, the risk of developing pine65 and molindone66,67 are notable for weight-loss or
tardive dyskinesia was over four times greater for patients weight-neutral profiles. Of the second-generation antipsy-
treated with haloperidol than for those receiving risperidone chotics, ziprasidone and aripiprazole have been associated
(p = 0.045).38 Similar results have been found in other con- with the lowest likelihood for causing weight gain. A large
trolled and noncontrolled studies of risperidone, olanzapine, meta-analysis by Allison et al.68 was conducted to compare
and quetiapine.39-41 the weight gain associated with the use of various antipsy-
Clozapine appears to have an especially favorable chotic drugs that were approved or under investigation in
profile for the prevention and management of antipsy- the United States. Table 4 lists estimated weight gain after
chotic-induced movement disorders. In comparative trials, 10 weeks of treatment on drugs for which sufficient data are
clozapine exhibited little to no evidence of inducing treat- available. Clozapine and olanzapine were associated with
ment-emergent extrapyramidal symptoms.13,42,43 The risk of more weight gain than all other agents included in this re-
tardive dyskinesia associated with clozapine treatment also view. The small weight loss associated with placebo may
appears to be minimal.44 In fact, clozapine has been used to have been due to discontinuation of antipsychotic therapy as
successfully treat preexisting tardive dyskinesia. Remission the subjects entered the studies.
of symptoms has been reported in some, but not all, cases The antipsychotic agents also appear to differ in the
of preexisting tardive dyskinesia treated with clozapine.45-47 duration and rate of weight changes. In one study, weight
In addition, withdrawal of clozapine in patients with tardive increases with continuous clozapine treatment occurred un
dyskinesia has resulted in either maintenance of reduced til about 46 months of treatment, with the greatest amount
movements46 or worsening of dyskinesias. The inconsistent of weight being gained during the first 12 months.69 Weight
nature of tardive dyskinesia treatment makes prevention of gain with olanzapine may plateau after 4-5 months.70
this syndrome a very important consideration in the pharma-
cotherapy of psychotic disorders.48
Table 4. lipoproteins with second-generation antipsychotics have not

Estimated Body Weight always correlated with significant weight gain.76
Changes at 10 Weeks in Patients A retrospective analysis of long-term inpatients treated
Receiving Antipsychotics68 with risperidone and olanzapine was conducted to determine
trends of various metabolic values.77 The investigator re-
Weight Gain
Treatment ported that the average increase in triglyceride concentra-
(kg)
tions was 104.8 mg/dL with olanzapine versus 31.7 mg/dL
Placebo –0.74
with risperidone after one year. Total cholesterol increased
Molindone –0.39
Ziprasidone
by 30.7 mg/dL with olanzapine and 7.2 mg/dL with risperi-
0.04
Fluphenazine 0.43 done. A naturalistic study of clozapine treatment revealed
Haloperidol 1.08 a significant increase in serum triglyceride level over five
Risperidone 2.10 years of treatment.69 In CATIE, olanzapine was associated
Chlorpromazine 2.58 with the greatest exposure-adjusted increases in serum cho-
Thioridazine- lesterol and triglycerides.25
mesoridazine 3.19 In November 2003, a consensus panel that included
Olanzapine 4.15 experts from the American Diabetes Association, American
Clozapine 4.45 Psychiatric Association, American Association of Clinical
Endocrinologists, and the North American Association for
the Study of Obesity was convened. Using data collected
Diabetes Mellitus. New-onset hyperglycemia and diabetes during a comprehensive literature review and presentations
mellitus have also been observed with antipsychotic treat- from representatives from the pharmaceutical industry and
ment. In some instances, the initial presentation consists FDA, the consensus panel developed a statement outlining
of life-threatening diabetic ketoacidosis or hyperosmolar the metabolic risks of treatment with second-generation
coma.71 Frequently, clinically significant weight gain does antipsychotics.78 The panel recommended careful consider
not occur before the diagnosis of diabetes.72 Koller et al.73 ation of metabolic risks whenever second-generation anti
reviewed cases of hyperglycemic episodes associated with psychotics are initiated, especially in high-risk patients. The
risperidone and haloperidol reported to the Food and Drug panel also recommended considering switching antipsychot
Administration’s (FDA’s) MedWatch surveillance program. ics in patients who gain 5% or more of their initial weight,
Of the 131 cases of hyperglycemia associated with anti experience worsening hyperglycemia, or develop worsening
psychotic monotherapy with risperidone, 78 were clearly hyperlipidemia.
identified as newly diagnosed hyperglycemia. In the cases
for which adequate data were available, 71% of cases with Cardiac Toxicity. Certain traditional and second-genera
preexisting hyperglycemia and 48% of cases of new-onset tion antipsychotics have been associated with clinically sig-
hyperglycemia occurred within the first three months of ris- nificant prolongation of the corrected Q-T (Q-Tc) interval,
peridone monotherapy. which may lead to torsades de pointes, a fatal ventricular ar-
Sernyak et al.74 conducted a large analysis of a national rhythmia. The risk of cardiac mortality associated with psy-
sample of patients treated for schizophrenia in Veterans chotropic drug treatment is particularly troublesome because
Affairs medical centers to investigate a possible association of its spontaneous and unpredictable nature.
between the use of antipsychotic medications and develop- The traditional antipsychotics thioridazine, me-
ment of diabetes mellitus. Patients were identified as being soridazine, pimozide, and droperidol have been impli-
treated with clozapine, olanzapine, quetiapine, risperidone, cated in numerous cases of sudden unexpected death.79
or traditional antipsychotics. When the patients were strati- Electrocardiographic data have revealed that patients receiv
fied by age, significantly higher rates of comorbid diabetes ing droperidol and thioridazine are more likely to have an
were found in patients treated with second-generation an- abnormally long Q-Tc interval.80 Numerous reports of pa
tipsychotics. Overall, clozapine, olanzapine, and quetiapine tient fatalities and the availability of safer alternatives have
were most frequently implicated. The strongest relationships prompted FDA to recommend that thioridazine, mesorida
were found in individuals less than 40 years of age. zine, pimozide, and droperidol only be used as alternative
Plasma glucose regulation in individuals receiving an- agents with extreme caution.
tipsychotics and in healthy controls was assessed using oral Although regulatory scrutiny for cardiac assess
glucose tolerance tests.75 Olanzapine-treated patients dem- ment heightened during the development of second-
onstrated significantly elevated plasma glucose levels while generation antipsychotics, these agents are generally associ-
fasting and at 15, 45, and 75 minutes postload compared ated with a low risk of electrocardiographic abnormalities.
with controls and patients treated with traditional antipsy- Ziprasidone was found to be associated with modest Q-Tc
chotics. Clozapine-treated patients had significant elevations prolongation during its premarketing studies. A comparative
while fasting and at 75 minutes postload compared with con- study that sought to determine the extent of Q-Tc prolonga-
trols and patients receiving traditional antipsychotics. With tion seen with the target therapeutic dosages of haloperidol,
risperidone, the elevations in plasma glucose were seen in risperidone, olanzapine, quetiapine, and ziprasidone was
the fasting state and at 45 and 75 minutes postload and were later presented to FDA.81 Thioridazine was also assessed
significantly higher compared with healthy controls. in this study at half its maximum recommended dosage.
Thioridazine was associated with an average Q-Tc-inter
Dyslipidemias. Hyperlipidemia is another significant car- val increase of 35.6 milliseconds. Of the second-generation
diac risk associated with second-generation antipsychotic agents included in this study, ziprasidone was associated
treatment. Increases in serum triglycerides and low-density with the greatest mean increase in the Q-Tc interval—20.3
milliseconds. Haloperidol-treated subjects had an average not been widely observed among patients with psychotic
Q-Tc-interval increase of 4.7 seconds, the smallest change disorders. It would therefore be advisable to consider stroke
observed in this study. Coadministration of other interact- prophylaxis in all elderly patients receiving antipsychotic
ing drugs (e.g., cytochrome P-450 isoenzyme inhibitors) drugs, particularly high-risk patients.
did not lead to significant changes in Q-Tc measurement.
Ziprasidone’s labeling warned of its greater potential of Q- Hematologic Toxicity, Respiratory Depression, and Seizures.
Tc-interval prolongation and discouraged use in patients Despite its superior efficacy for treatment-resistant psychotic
with electrolyte abnormalities, cardiac comorbidity, or con- disorders, the use of clozapine has remained restricted due
comitant use of metabolic inhibitors.82 to the potential of severe adverse effects not commonly
Clozapine has been associated with treatment-emer- seen with other antipsychotics. Agranulocytosis has been
gent myocarditis and cardiomyopathy. Myocarditis associ- estimated to occur in 1–2% of patients treated with cloza-
ated with clozapine treatment presents as an acute inflamma- pine.87 Episodes tend to occur between two and six months
tion of the myocardium, which may lead to congestive heart after initiation of treatment.88 Fatal infectious complications
failure.83 With over 180,000 patient exposures to clozapine may occur as a result of reduced white blood cell count.
during the first 10 years of its clinical use in the United Clozapine-induced agranulocytosis can be reversed with the
States, FDA received 28 reports of myocarditis, including prompt discontinuation of treatment.
18 deaths.84 The greatest risk of fatal events appears to exist In the United States, clozapine is available only under
during the first month of therapy. Cardiomyopathy associ- the surveillance of one of the national manufacturer-operated
ated with clozapine is an insidious process characterized by registries that monitor weekly complete blood counts from
ventricular dilatation, impaired contraction, and symptoms individuals taking this agent. Consistent monitoring has re
of congestive heart failure.83 A total of 41 cases of cardiomy sulted in a markedly reduced rate of agranulocytosis and
opathy, including 10 deaths, were reported to FDA between mortality associated with clozapine-induced agranulocyto-
1989 and 1999.84 sis.89 Furthermore, the continual monitoring mandated by
the clozapine registry programs likely allows for improved
Cerebrovascular Events. The use of second-generation an treatment adherence and outcomes.90
tipsychotics for the treatment of dementia-related agitation Other toxicities that are more common with cloza-
and psychosis in elderly patients is an unlabeled use that is pine than with other second-generation antipsychotics are
generally supported by efficacy data in published controlled respiratory depression and seizures. Respiratory collapse
clinical trials.85 However, post hoc analyses of the safety has been associated with rapid dosage adjustment and con-
data for these trials revealed an elevated risk of cerebrovas comitant benzodiazepine use. It is therefore recommended
cular adverse events (CVAEs), including stroke and transient that clozapine dosage be gradually adjusted from the starting
ischemic attacks, among patients treated with second-gen dose if the patient is new to clozapine treatment or if two or
eration antipsychotics. These data led FDA to issue a public more days have elapsed since the last dose. A dose-related
health advisory warning of the potential for fatal CVAEs in reduction of the seizure threshold has been observed with
patients with dementia being treated with second-generation clozapine.91 Precautions should be taken for patients with
antipsychotics. The manufacturers of second-generation seizure disorders receiving clozapine treatment.
antipsychotic agents were also requested to place a black-
box warning describing this treatment risk on the labeling Drug Selection and Dosing
of these products.
A closer look at the applicable safety data reveals that
Considerations
the patients in the dementia trials were often at elevated risk
With the notable exception of clozapine, the principal dif-
for CVAEs because of advanced age, poor control of chronic
ferences among the available second-generation antipsy-
cardiovascular disease, and the underlying etiology of the
chotics lie in their adverse-effect profiles and dosage forms.
dementia.86 Cases of CVAEs included nonspecific events,
Selection of an initial treatment for a patient whose psy
such as hypotensive episodes, periods of unresponsiveness,
chosis is not considered to be treatment resistant should be
and slurred speech. For example, the pooled results of six
individualized based on the patient’s specific tolerability
placebo-controlled randomized studies of risperidone for
and compliance concerns.92 Individuals with a sensitivity to
the treatment of behavioral disturbances in patients with de-
extrapyramidal symptoms may benefit from quetiapine or
mentia revealed 33 CVAEs (3.3%) in 1009 subjects receiv-
aripiprazole. Patients with preexisting obesity or diabetes
ing the drug. The frequency of CVAEs was 1.1% (8 of 712)
mellitus may benefit from an initial trial with ziprasidone or
among placebo-treated patients (p = 0.004). However, seri-
aripiprazole. The availability of orally disintegrating formu-
ous CVAEs (fatal events, life-threatening events, or CVAEs
lations of olanzapine, risperidone, and aripiprazole; liquid
associated with hospitalization or disability) occurred in
formulations of risperidone and aripiprazole; and a long-act
15 (1.5%) of 1009 patients treated with risperidone and 4
ing injectable formulation of risperidone provides options
(0.6%) of 712 patients treated with placebo, a difference that
for patients with a history of poor treatment adherence or
failed to reach statistical significance. Furthermore, most pa-
who have difficulty taking standard oral tablets or capsules.
tients experiencing stroke had risk factors, including hyper-
The traditional antipsychotics may be an initial choice for
tension, atrial fibrillation, and previous strokes.86
those who are at low risk for movement disorders25 or for
The nature of this type of safety data makes it difficult
whom the newer drugs may be cost-prohibitive.
to determine causality. It has been postulated that the ad-
The importance of appropriate dosing of second-
verse effects of sedation, hypotension, pseudoparkinsonism,
generation antipsychotics was highlighted in an analysis con-
and enhanced platelet aggregation may contribute to the ob-
ducted by Love et al.93 Results of the premarketing studies for
served increase in CVAEs.86 In addition, these findings have
risperidone suggested that the dose–efficacy curve peaked symptoms (e.g., suspiciousness, hallucinations) are expected
at 6 mg/day, leading to the recommendation on the prod- with adequate treatment.
uct labeling that risperidone be adjusted to this dosage over Monitoring for metabolic adverse effects of second-
the first three days of treatment. After the introduction of generation antipsychotic therapy should consist of regular
risperidone to the mass market, numerous reports94–96 dem- assessments of body weight, glucose levels, and lipid values
onstrated that the optimal dosage of risperidone for efficacy (Table 5).103 Treatment with clozapine requires weekly as-
was between 4 and 6 mg/day, a dosage range not assessed in sessments of complete blood count and absolute neutrophil
the original large efficacy studies. Aggregate computerized count for the first six months. If no evidence of neutropenia
pharmacy records from state inpatient psychiatry facilities or granulocytopenia is found, the monitoring frequency can
in Maryland revealed significantly higher discharge rates be reduced to every two weeks for the next six months and
for patients receiving 2–4 mg/day than for those receiving then every four weeks thereafter.
6 mg/day. It is now recommended that clinicians attempt to Despite the lower propensity for causing adverse motor
stabilize patients on risperidone 2–4 mg/day before initiat effects, all patients receiving second-generation antipsychot-
ing a trial at higher dosages.93 ics should be monitored for symptoms of dystonia, parkin-
In general, clinical studies suggest that for most of the sonism, akathisia, and tardive dyskinesia.103 Patients should
other second-generation antipsychotics indicated for first- be evaluated for acute extrapyramidal symptoms weekly un
line treatment, a more linear dose–response curve is appli- til two weeks after dose stabilization when antipsychotics
cable. Patients may require dosage adjustment to 10–20 mg/ are initiated or adjusted. Assessments for tardive dyskinesia
day of olanzapine, 300–800 mg/day of quetiapine, 80–160 should be conducted at least once yearly for individuals re-
mg/day of ziprasidone, or 10–30 mg/day of aripiprazole for ceiving continuous treatment with antipsychotics.103
13–24
control of acute psychotic symptoms. Maintenance ther- Measurement of antipsychotic plasma levels is not
apy can frequently be achieved with lower dosages, thereby clinically indicated, except to assess for treatment adherence
reducing toxicity. Special populations, such as the elderly or suspected drug interactions. However, a minimum plasma
or individuals with hepatic impairment, may require lower clozapine concentration of 350 ng/mL has been correlated
doses due to increased sensitivity to adverse effects. In some with treatment response among patients whose psychosis
individuals with a history of suboptimal response to antipsy has been identified as treatment resistant.104,105 In a study
chotic treatment, additional benefit has been gained using of the use of therapeutic drug monitoring in long-term treat-
second-generation antipsychotics with doses higher than the ment with clozapine, relapse was more frequently associated
maximum recommended in the product labeling.97 with a decrease from a stable drug level than maintenance of
In the event of nonresponse to an initial trial of anti a threshold minimum concentration.106
psychotic medication, most treatment guidelines recommend
sequential trials of second-generation antipsychotics with a Treatment Outcomes
minimum of three weeks duration at therapeutic doses.98–100
A trial of clozapine is generally warranted for patients who Schizophrenia and related disorders are characterized by
demonstrate a suboptimal response to two or more trials chronic courses and periodic exacerbations. Exacerbations
with first-line antipsychotic agents. Traditional antipsychot- in the positive symptoms of schizophrenia may precipitate
ics may also have a role for patients who fail treatment with costly hospitalizations and may result in encounters with the
second-generation antipsychotics. In addition, the adjunc- legal system, while the negative and cognitive symptoms af-
tive use of antidepressants, mood stabilizers, or anxiolytics fect independent functioning, employment, and quality of
may be beneficial in selected patients. The combined use of life. Hospitalizations in specialty psychiatric facilities may
more than one antipsychotic drug is
a controversial and costly practice.101
Very little published evidence sup- Table 5.
ports the use of multiple oral antipsy Monitoring Guidelines for Patients Treated with Second-Generation
chotics, except when attempting to Antipsychotics
transition a patient from one agent to
another.102 Assessment Monitoring Frequency
Fasting blood glucose All drugs: Baseline, then monthly for the first 3
Patient Monitoring mo and every 6 mo thereafter. More frequent
assessments are indicated for individuals noted
to be gaining weight.
Frequent and continuous monitoring
Weight assessment All drugs: Baseline and monthly thereafter. (Self-
is necessary for individuals treated monitoring of weight should be encouraged.)
with antipsychotics in order to assess Electrocardiogram Clozapine and ziprasidone: Baseline and annually
for therapeutic response and adverse thereafter. More frequent assessments may
effects. For the second-generation be indicated in patients over age 50 yr and in
antipsychotics intended for first-line patients with a history of cardiac arrhythmias.
use, the recommended minimum trial Complete blood count with Clozapine: Weekly for the first 6 mo. Every other wk
duration is three weeks after adjust- differential for the next 6 mo, and every 4 wk thereafter if no
ment to a recommended therapeutic abnormalities are noted.
dose. A longer trial is generally war- Fasting total cholesterol, All drugs: Baseline and every 2 yr thereafter if
low- and high-density no abnormalities are noted. Every 6 mo for
ranted for clozapine. Gradual reduc-
lipoproteins, and individuals noted to have hyperlipidemia or
tions in the severity of psychotic triglycerides receiving lipid-lowering therapy.
result in lengths of stay measured in months or years. Thus, conventional antipsychotics and placebo, second-generation
the single greatest component of the cost of schizophrenia antipsychotics demonstrate improved efficacy for psychotic
is the cost of hospital stay. In contrast, drugs are thought to and cognitive symptoms. In controlled trials, these agents pro-
account for less than 10% of the direct costs of treating these duce fewer disabling extrapyramidal adverse effects, such as
illnesses. akathisia and parkinsonism. These effects result in improved
Studies addressing the effect of second-generation an- adherence to prescribed regiments, less interference with
tipsychotics on hospitalization have repeatedly found that socialization and occupational function, and a feeling of im-
these agents reduce the length of stay and readmission rate proved well-being compared with the effects of conventional
compared with conventional antipsychotics. Rabinowitz et antipsychotics.
al.107 calculated a two-year rehospitalization rate of 31–33%
for patients discharged from inpatient psychiatric hospital- Summary
ization receiving olanzapine or risperidone, compared with
a 48% rate for patients discharged on conventional antipsy Psychotic disorders are chronic illnesses that impart a con-
chotics (p = 0.02). In a landmark double-blind trial of ris- siderable burden on patients, families, and society. Although
peridone versus haloperidol, Csernansky et al.108 measured no known drug therapies can cure these illnesses, antipsy-
relapse by examining rehospitalization, signs of clinical de chotic agents are a mainstay for the management of acute
compensation, and increasing requirements for supervision. illness and prevention of relapse. The second-generation
They found significantly lower relapse rates at one year and antipsychotics—risperidone, olanzapine, quetiapine, zipra
longer times to relapse with risperidone treatment. FDA ac- sidone, aripiprazole, and paliperidone—offer numerous
cepted this trial as sufficient evidence to allow the manufac- advantages over the older agents, including a lower risk of
turer to indicate in the product labeling the drug’s efficacy in extrapyramidal motor symptoms and elevated serum prolac-
delaying relapse. tin levels, as well as improvements in cognitive symptoms.
A variety of studies have focused on the cost of sec- These advantages have led to improved long-term outcomes
ond-generation antipsychotics in comparison with each and cost-effectiveness, despite the higher acquisition costs
other109,110 and conventional agents.111 In general, the gener- of these drugs. Clozapine has demonstrated a unique level
ically available first-generation antipsychotics are less ex- of efficacy for individuals with treatment-resistant psychotic
pensive than the newer second-generation agents. However, disorders and for individuals at high risk for suicide and is
when overall costs of care are calculated, second-generation very valuable in these subgroups, despite the additional ad-
antipsychotics often demonstrate lower hospital utilization, verse hematologic and cardiovascular effects. Metabolic ad-
improved symptomatic control, and fewer adverse effects, verse effects, including weight gain, glucose abnormalities,
resulting in lower or equal total costs for the second-genera- and hyperlipidemias, cause significant concern for patients
tion agents versus first-generation antipsychotics.112 receiving second-generation antipsychotics and must be
While most studies examining outcomes with second- managed proactively by clinicians. Health care profession-
generation antipsychotics have focused on cost, hospital- als in all settings should play an active role in assisting in
ization, and relapse, fewer have examined issues related to the selection of an appropriate antipsychotic agent, ensuring
quality of life. Chouinard and Albright113 addressed these appropriate monitoring, and providing counseling to ensure
issues by conducting a cost–utility analysis of risperidone that patients remain compliant with treatment. Additional
versus haloperidol in association with a randomized clinical readings and resources are listed in the appendix.
trial. Patients taking risperidone gained almost three qual
ity-adjusted life years over those who received haloperidol.
Franz et al.114 conducted quality-of-life interviews with pa- References
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114. Franz M, Lis S, Pluddemann K, et al. Conventional ver-
Approved by the ASHP Board of Directors on June 24, 2006.
sus second-generation neuroleptics: subjective quality
Developed through the ASHP Council on Therapeutics.
of life in schizophrenic patients. Br J Psychiatry. 1997;
170:422–5.
Jason M. Noel, Pharm.D., BCPP, is gratefully acknowledged for
115. Roy A. Depression, attempted suicide, and suicide in
authoring this therapeutic position statement. At the time of pub-
patients with chronic schizophrenia. Psychiatr Clin
lication, Dr. Noel was Assistant Professor, University of Maryland
North Am. 1986; 9:193–206.
School of Pharmacy, Baltimore, and Director of Clinical Pharmacy
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Services, Rosewood Center, Owings Mills, MD.
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Marshall E. Cates, Pharm.D., BCPP, FASHP; Beth Dubisar, Pharm.
117. Cohen LJ, Test MA, Brown RL. Suicide and schizo-
D.; Julie A. Dopheide, Pharm.D., BCPP; W. Kennedy Klugh, Pharm.
phrenia: data from a prospective community treatment
D.; Dan LeGrady, Pharm.D., FNIH; Rex S. Lott, Pharm.D.; Lisa
study. Am J Psychiatry. 1990; 147:602–7.
Mican, Pharm.D.; Virginia Stauffer, Pharm.D.; and the American
118. Meltzer HY, Okayli G. Reduction of suicidality during
Academy of Nurse Practitioners are acknowledged for reviewing
clozapine treatment of neuroleptic-resistant schizo-
drafts of this document.
phrenia: impact on risk-benefit assessment. Am J
Psychiatry. 1995; 152:183–90.
119. Meltzer HY, Alphs L, Green AI, et al. Clozapine treat-
ment for suicidality in schizophrenia: International
Suicide Prevention Trial (InterSEPT). Arch Gen
Psychiatry. 2003; 60:82–91. The bibliographic citation for this document is as follows: Noel JM.
ASHP therapeutic position statement on the use of second-genera-
tion antipsychotic medications in the treatment of adults with psy-
chotic disorders. Am J Health-Syst Pharm. 2007; 64:863–76.
Appendix—Additional
Readings and Resources
Andreasen NC. Scale for the assessment of negative symp-
toms (SANS). Br J Psychiatry. 1989; 155(suppl 7):53–8.
ASHP
Therapeutic Guidelines
600 ASHP Therapeutic Guidelines
Clinical Practice Guidelines for

Antimicrobial Prophylaxis in Surgery
These guidelines were developed jointly by the American evidence base are noted within each individual procedure
Society of Health-System Pharmacists (ASHP), the section of the guidelines. Published guidelines with recom-
Infectious Diseases Society of America (IDSA), the Surgical mendations by experts in a procedure area (e.g., American
Infection Society (SIS), and the Society for Healthcare College of Obstetricians and Gynecologists [ACOG]) and
Epidemiology of America (SHEA). This work represents noted general guidelines (e.g., Centers for Disease Control
an update to the previously published ASHP Therapeutic and Prevention [CDC], Scottish Intercollegiate Guidelines
Guidelines on Antimicrobial Prophylaxis in Surgery,1 as well Network, Medical Letter, SIS, SHEA/IDSA) were also con-
as guidelines from IDSA and SIS.2,3 The guidelines are in- sidered.2,3,5–11
tended to provide practitioners with a standardized approach Recommendations for the use of antimicrobial pro-
to the rational, safe, and effective use of antimicrobial agents phylaxis are graded according to the strength of evidence
for the prevention of surgical-site infections (SSIs) based on available. The strength of evidence represents only support
currently available clinical evidence and emerging issues. for or against prophylaxis and does not apply to the antimi-
Prophylaxis refers to the prevention of an infection crobial agent, dose, or dosage regimen. Studies supporting
and can be characterized as primary prophylaxis, secondary the recommendations for the use of antimicrobial therapy
prophylaxis, or eradication. Primary prophylaxis refers to were classified as follows:
the prevention of an initial infection. Secondary prophylaxis
refers to the prevention of recurrence or reactivation of a • Level I (evidence from large, well-conducted, ran-
preexisting infection. Eradication refers to the elimination domized, controlled clinical trials or a meta-analysis),
of a colonized organism to prevent the development of an • Level II (evidence from small, well-conducted, ran-
infection. These guidelines focus on primary perioperative domized, controlled clinical trials),
prophylaxis. • Level III (evidence from well-conducted cohort stud-
ies),
Guidelines Development and Use • Level IV (evidence from well-conducted case–control
studies),
Members of ASHP, IDSA, SIS, and SHEA were appointed • Level V (evidence from uncontrolled studies that were
to serve on an expert panel established to ensure the valid- not well conducted),
ity, reliability, and utility of the revised guidelines. The work • Level VI (conflicting evidence that tends to favor the
of the panel was facilitated by faculty of the University of recommendation), or
Pittsburgh School of Pharmacy and University of Pittsburgh • Level VII (expert opinion or data extrapolated from
Medical Center Drug Use and Disease State Management evidence for general principles and other procedures).
Program who served as contract researchers and writers for
the project. Panel members and contractors were required This system has been used by the Agency for
to disclose any possible conflicts of interest before their ap- Healthcare Research and Quality, and ASHP, IDSA, SIS,
pointment and throughout the guideline development pro- and SHEA support it as an acceptable method for organizing
cess. Drafted documents for each surgical procedural section strength of evidence for a variety of therapeutic or diagnostic
were reviewed by the expert panel and, once revised, were recommendations.4 Each recommendation was categorized
available for public comment on the ASHP website. After ad- according to the strength of evidence that supports the use
ditional revisions were made to address reviewer comments, or nonuse of antimicrobial prophylaxis as category A (levels
the final document was approved by the expert panel and the I–III), category B (levels IV–VI), or category C (level VII).
boards of directors of the above-named organizations. When higher-level data are not available, a category
C recommendation represents a consensus of expert panel
Strength of Evidence and Grading of Recommendations. members based on their clinical experience, extrapola-
The primary literature from the previous ASHP Therapeutic tion from other procedures with similar microbial or other
Guidelines on Antimicrobial Prophylaxis in Surgery1 was clinical features, and available published literature. In these
reviewed together with the primary literature published be- cases, the expert panel also extrapolated general principles
tween the date of the previous guidelines, 1999, and June and evidence from other procedures. Some recommenda-
2010, identified by searches of MEDLINE, EMBASE, and tions include alternative approaches in situations in which
the Cochrane Database of Systematic Reviews. Particular panel member opinions were divided.
attention was paid to study design, with greatest credence A major limitation of the available literature on anti-
given to randomized, controlled, double-blind studies. microbial prophylaxis is the difficulty in establishing sig-
There is a limited number of adequately powered random- nificant differences in efficacy between prophylactic antimi-
ized controlled trials evaluating the efficacy of antimicrobial crobial agents and controls (including placebo, no treatment,
prophylaxis in surgical procedures. Guidelines development or other antimicrobial agents) due to study design and low
included consideration of the following characteristics: va- SSI rates for most procedures. A small sample size increases
lidity, reliability, clinical applicability, flexibility, clarity, the likelihood of a Type II error; therefore, there may be no
and a multidisciplinary nature as consistent with ASHP’s apparent difference between the antimicrobial agent and pla-
philosophy on therapeutic guidelines.4 The limitations of the cebo when in fact the antimicrobial has a beneficial effect.12
ASHP Therapeutic Guidelines 601
A valid study is placebo controlled and randomized with a These guidelines reflect current knowledge of antimi-
sufficient sample in each group to avoid a Type II error. Of crobial prophylaxis in surgery. Given the dynamic nature of
note, prophylaxis is recommended in some cases due to the scientific information and technology, periodic review, up-
severity of complications of postoperative infection (e.g., dating, and revisions are to be expected.
an infected device that is not easily removable) necessitat-
ing precautionary measures despite the lack of statistical Special Patient Populations. Pediatric patients. Pediatric
support. patients undergo a number of procedures similar to adults
that may warrant antimicrobial prophylaxis. Although pedi-
Summary of Key Updates. These guidelines reflect sub- atric-specific prophylaxis data are sparse, available data have
stantial changes from the guidelines published in 1999.1 been evaluated and are presented in some of the procedure-
Highlights of those changes are outlined here. specific sections of these guidelines. Selection of antimi-
Preoperative-dose timing. The optimal time for admin- crobial prophylactic agents mirrors that in adult guidelines,
istration of preoperative doses is within 60 minutes before with the agents of choice being first- and second-generation
surgical incision. This is a more-specific time frame than cephalosporins, reserving the use of vancomycin for patients
the previously recommended time, which was “at induction with documented b-lactam allergies.19,20 While the use of a
of anesthesia.” Some agents, such as fluoroquinolones and penicillin with a b-lactamase inhibitor in combination with
vancomycin, require administration over one to two hours; cefazolin or vancomycin and gentamicin has also been stud-
therefore, the administration of these agents should begin ied in pediatric patients, the number of patients included in
within 120 minutes before surgical incision. these evaluations remains small.20–23 As with adults, there is
Selection and dosing. Information is included regard- little evidence supporting the use of vancomycin, alone or
ing the approach to weight-based dosing in obese patients in combination with other antimicrobials, for routine peri-
and the need for repeat doses during prolonged proce- operative antimicrobial prophylaxis in institutions that have
dures.13–18 Obesity has been linked to an increased risk for a high prevalence of methicillin-resistant Staphylococcus
SSI. The pharmacokinetics of drugs may be altered in obese aureus (MRSA). Vancomycin may be considered in children
patients, so dosage adjustments based on body weight may known to be colonized with MRSA and, in one retrospective
be warranted in these patients. For all patients, intraopera- historical cohort study, was shown to decrease MRSA infec-
tive redosing is needed to ensure adequate serum and tis- tions.21 Mupirocin use has been studied in and is efficacious
sue concentrations of the antimicrobial if the duration of in children colonized with MRSA, but there are limited data
the procedure exceeds two half-lives of the drug or there supporting its use perioperatively.24–30 However, there is
is excessive blood loss during the procedure (Table 1). little reason to think that the impact and effect would be any
Recommendations for selection of antimicrobial agents for different in children, so its use may be justified. Additional
specific surgical procedures and alternative agents (e.g., for studies in this setting are needed to establish firm guidelines.
patients with allergies to b-lactam antimicrobials) are pro- Unless noted in specific sections, all recommendations
vided in Table 2. for adults are the same for pediatric patients, except for dos-
Duration of prophylaxis. New recommendations for a ing. In most cases, the data in pediatric patients are limited
shortened postoperative course of antimicrobials involving and have been extrapolated from adult data; therefore, nearly
a single dose or continuation for less than 24 hours are pro- all pediatric recommendations are based on expert opinion.
vided. Further clarity on the lack of need for postoperative In some sections, pediatric efficacy data do not exist and
antimicrobial prophylaxis based on the presence of indwell- thus are not addressed in these guidelines. Fluoroquinolones
ing drains and intravascular catheters is included. should not be routinely used for surgical prophylaxis in pedi-
Common principles. A section addressing concepts atric patients because of the potential for toxicity in this pop-
that apply to all types of surgical procedures has been added. ulation. The same principle of preoperative dosing within
Expanded and new recommendations are provided for plas- 60 minutes before incision has been applied to pediatric pa-
tic, urology, cardiac, and thoracic procedures, as well as clar- tients.20–23 Additional intraoperative dosing may be needed
ity on prophylaxis when implantable devices are inserted. if the duration of the procedure exceeds two half-lives of the
The latest information on the use of mupirocin and on the antimicrobial agent or there is excessive blood loss during
role of vancomycin in surgical prophylaxis is summarized in the procedure.19,21 As with adult patients, single-dose pro-
these updated guidelines. phylaxis is usually sufficient. If antimicrobial prophylaxis is
continued postoperatively, the duration should be less than
Application of Guidelines to Clinical Practice. Recom- 24 hours, regardless of the presence of intravascular cathe-
mendations are provided for adult (age 19 years or older) ters or indwelling drains.19,22,23,31,32 There are sufficient phar-
and pediatric (age 1–18 years) patients. These guidelines do macokinetic studies of most agents to recommend pediatric
not specifically address newborn (premature and full-term) dosages that provide adequate systemic exposure and, pre-
infants. While the guidelines do not address all concerns sumably, efficacy comparable to that demonstrated in adults.
for patients with renal or hepatic dysfunction, antimicrobial Therefore, the pediatric dosages provided in these guidelines
prophylaxis often does not need to be modified for these pa- are based largely on pharmacokinetic data and the extrapo-
tients when given as a single preoperative dose before surgi- lation of adult efficacy data to pediatric patients. Because
cal incision. few clinical trials have been conducted in pediatric surgical
The recommendations herein may not be appropriate patients, strength of evidence criteria have not been applied
for use in all clinical situations. Decisions to follow these to these recommendations. With few exceptions (e.g., ami-
recommendations must be based on the judgment of the cli- noglycoside dosages), pediatric dosages should not exceed
nician and consideration of individual patient circumstances the maximum adult recommended dosages. Generally, if
and available resources. dosages are calculated on a milligram-per-kilogram basis for
Table 1.
Recommended Doses and Redosing Intervals for Commonly Used Antimicrobials for Surgical Prophylaxis
Recommended Dose Recommended
Half-life in Adults Redosing Interval
With Normal Renal (From Initiation of
Antimicrobial Adultsa Pediatricsb Function, hr19 Preoperative Dose), hrc
Ampicillin–sulbactam 3g 50 mg/kg of the 0.8–1.3 2
(ampicillin 2 g/ ampicillin component
sulbactam 1 g)
Ampicillin 2g 50 mg/kg 1–1.9 2
Aztreonam 2g 30 mg/kg 1.3–2.4 4
Cefazolin 2 g, 3 g for pts 30 mg/kg 1.2–2.2 4
weighing ≥120 kg
Cefuroxime 1.5 g 50 mg/kg 1–2 4
d
Cefotaxime 1g 50 mg/kg 0.9–1.7 3
Cefoxitin 2g 40 mg/kg 0.7–1.1 2
Cefotetan 2g 40 mg/kg 2.8–4.6 6

e
Ceftriaxone 2g 50–75 mg/kg 5.4–10.9 NA
f
Ciprofloxacin 400 mg 10 mg/kg 3–7 NA
Clindamycin 900 mg 10 mg/kg 2–4 6
Ertapenem 1g 15 mg/kg 3–5 NA
Fluconazole 400 mg 6 mg/kg 30 NA
Gentamicing 5 mg/kg based on 2.5 mg/kg based on 2–3 NA
dosing weight dosing weight
(single dose)
Levofloxacinf 500 mg 10 mg/kg 6–8 NA
Metronidazole 500 mg 15 mg/kg 6–8 NA
Neonates weighing
<1200 g should
receive a single 7.5-
mg/kg dose
Moxifloxacinf 400 mg 10 mg/kg 8–15 NA
Piperacillin– 3.375 g Infants 2–9 mo: 80 mg/ 0.7–1.2 2
tazobactam kg of the piperacillin
component
Children >9 mo and ≤40
kg: 100 mg/kg of the
piperacillin component
Vancomycin 15 mg/kg 15 mg/kg 4–8 NA
Oral antibiotics for colorectal surgery prophylaxis (used in conjunction with a mechanical bowel preparation)
Erythromycin base 1g 20 mg/kg 0.8–3 NA
Metronidazole 1g 15 mg/kg 6–10 NA
Neomycin 1g 15 mg/kg 2–3 (3% absorbed NA
under normal
gastrointestinal
conditions)
a
Adult doses are obtained from the studies cited in each section. When doses differed between studies, expert opinion used the most-often
recommended dose.
b
The maximum pediatric dose should not exceed the usual adult dose.
c
For antimicrobials with a short half-life (e.g., cefazolin, cefoxitin) used before long procedures, redosing in the operating room is
recommended at an interval of approximately two times the half-life of the agent in patients with normal renal function. Recommended redosing
intervals marked as “not applicable” (NA) are based on typical case length; for unusually long procedures, redosing may be needed.
d
Although FDA-approved package insert labeling indicates 1 g,14 experts recommend 2 g for obese patients.
e
When used as a single dose in combination with metronidazole for colorectal procedures.
f
While fluoroquinolones have been associated with an increased risk of tendinitis/tendon rupture in all ages, use of these agents for single-dose
prophylaxis is generally safe.
g
In general, gentamicin for surgical antibiotic prophylaxis should be limited to a single dose given preoperatively. Dosing is based on the
patient’s actual body weight. If the patient’s actual weight is more than 20% above ideal body weight (IBW), the dosing weight (DW) can be
determined as follows: DW = IBW + 0.4(actual weight – IBW).
Table 2.
Recommendations for Surgical Antimicrobial Prophylaxis
Strength of
Type of Procedure Recommended Agentsa,b Alternative Agents in Patients with b-Lactam Allergy Evidencec
Cardiac
Coronary artery bypass Cefazolin, cefuroxime Clindamycin,d vancomycind A
Cardiac device insertion procedures (e.g., pacemaker Cefazolin, cefuroxime Clindamycin, vancomycin A
implantation)
Ventricular assist devices Cefazolin, cefuroxime Clindamycin, vancomycin C
Thoracic
Noncardiac procedures, including lobectomy, pneumonectomy, Cefazolin, ampicillin–sulbactam Clindamycin,d vancomycind A
lung resection, and thoracotomy
Video-assisted thoracoscopic surgery Cefazolin, ampicillin–sulbactam Clindamycin,d vancomycind C
Gastroduodenale
Procedures involving entry into lumen of gastrointestinal tract Cefazolin Clindamycin or vancomycin + aminoglycosideg or A
(bariatric, pancreaticoduodenectomyf) aztreonam or fluoroquinoloneh-j
Procedures without entry into gastrointestinal tract (antireflux, Cefazolin Clindamycin or vancomycin + aminoglycosideg or A
highly selective vagotomy) for high-risk patients aztreonam or fluoroquinoloneh-j
Biliary tract
Open procedure Cefazolin, cefoxitin, cefotetan, ceftriaxone,k Clindamycin or vancomycin + aminoglycosideg or A
ampicillin–sulbactamh aztreonam or fluoroquinoloneh-j
Metronidazole + aminoglycosideg or fluoroquinoloneh-j
Laparoscopic procedure
Elective, low-riskl None None A
l k g
Elective, high-risk Cefazolin, cefoxitin, cefotetan, ceftriaxone, Clindamycin or vancomycin + aminoglycoside or A
ampicillin–sulbactamh aztreonam or fluoroquinoloneh-j
Appendectomy for uncomplicated appendicitis Cefoxitin, cefotetan, cefazolin + metronidazole Clindamycin + aminoglycosideg or aztreonam or A
fluoroquinoloneh-j
Small intestine
Nonobstructed Cefazolin Clindamycin + aminoglycosideg or aztreonam or C
fluoroquinoloneh-j
Obstructed Cefazolin + metronidazole, cefoxitin, cefotetan Metronidazole + aminoglycosideg or fluoroquinoloneh-j C
Hernia repair (hernioplasty and herniorrhaphy) Cefazolin Clindamycin, vancomycin A
Strength of
Colorectalm Cefazolin + metronidazole, cefoxitin, cefotetan, Clindamycin + aminoglycosideg or aztreonam or A
ampicillin–sulbactam,h ceftriaxone + fluoroquinoloneh-j metronidazole + aminoglycosideg
metronidazole,n ertapenem or fluoroquinoloneh-j
Head and neck
Clean None None B
Clean with placement of prosthesis (excludes tympanostomy Cefazolin, cefuroxime Clindamycind C
tubes)
Clean-contaminated cancer surgery Cefazolin + metronidazole, cefuroxime + Clindamycind A
metronidazole, ampicillin–sulbactam
Other clean-contaminated procedures with the exception of Cefazolin + metronidazole, cefuroxime + Clindamycind B
tonsillectomy and functional endoscopic sinus procedures metronidazole, ampicillin–sulbactam
Neurosurgery
Elective craniotomy and cerebrospinal fluid-shunting Cefazolin Clindamycin,d vancomycind A
procedures
Implantation of intrathecal pumps Cefazolin Clindamycin,d vancomycind C
g
Cesarean delivery Cefazolin Clindamycin + aminoglycoside A
Hysterectomy (vaginal or abdominal) Cefazolin, cefotetan, cefoxitin, ampicillin– Clindamycin or vancomycin + aminoglycosideg or A
sulbactamh aztreonam or fluoroquinoloneh-j
Ophthalmic Topical neomycin–polymyxin B–gramicidin or None B
fourth-generation topical fluoroquinolones
(gatifloxacin or moxifloxacin) given as 1 drop
every 5–15 min for 5 doseso
Addition of cefazolin 100 mg by subconjunctival
injection or intracameral cefazolin 1–2.5 mg
or cefuroxime 1 mg at the end of procedure is
optional
Orthopedic
Clean operations involving hand, knee, or foot and not involving None None C
implantation of foreign materials
Spinal procedures with and without instrumentation Cefazolin Clindamycin,d vancomycind A
Hip fracture repair Cefazolin Clindamycin,d vancomycind A
Strength of
Implantation of internal fixation devices (e.g., nails, screws, Cefazolin Clindamycin,d vancomycind C
plates, wires)
Total joint replacement Cefazolin Clindamycin,d vancomycind A
Urologic
Lower tract instrumentation with risk factors for infection Fluoroquinolone,h-j trimethoprim– Aminoglycosideg with or without clindamycin A
(includes transrectal prostate biopsy) sulfamethoxazole, cefazolin
Clean without entry into urinary tract Cefazolin (the addition of a single dose of an Clindamycin,d vancomycind A
aminoglycoside may be recommended for
placement of prosthetic material [e.g., penile
prosthesis])
Involving implanted prosthesis Cefazolin ± aminoglycoside, cefazolin ± Clindamycin ± aminoglycoside or aztreonam, A
aztreonam, ampicillin–sulbactam vancomycin ± aminoglycoside or aztreonam
Clean with entry into urinary tract Cefazolin (the addition of a single dose of an Fluoroquinolone,h-j aminoglycosideg with or without A
aminoglycoside may be recommended for clindamycin
placement of prosthetic material [e.g., penile
prosthesis])
Clean-contaminated Cefazolin + metronidazole, cefoxitin Fluoroquinolone,h-j aminoglycosideg + metronidazole or A
clindamycin
Vascularp Cefazolin Clindamycin,d vancomycind A
q
Heart, lung, heart–lung transplantation
Heart transplantationr Cefazolin Clindamycin,d vancomycind A (based on
cardiac
procedures)
Lung and heart–lung transplantationr,s Cefazolin Clindamycin,d vancomycind A (based on
cardiac
procedures)
Liver transplantationq,t Piperacillin–tazobactam, cefotaxime + ampicillin Clindamycin or vancomycin + aminoglycosideg or B
aztreonam or fluoroquinoloneh-j
Pancreas and pancreas–kidney transplantationr Cefazolin, fluconazole (for patients at high risk Clindamycin or vancomycin + aminoglycosideg or A
of fungal infection [e.g., those with enteric aztreonam or fluoroquinoloneh-j
drainage of the pancreas])
Strength of
Plastic surgery Cefazolin Clindamycin or vancomycin + aminoglycosideg or A
aztreonam or fluoroquinoloneh-j
Clean with risk factors or clean-contaminated Cefazolin, ampicillin–sulbactam Clindamycin,d vancomycind C
a
The antimicrobial agent should be started within 60 minutes before surgical incision (120 minutes for vancomycin or fluoroquinolones). While single-dose prophylaxis is usually sufficient, the duration of prophylaxis
for all procedures should be less than 24 hours. If an agent with a short half-life is used (e.g., cefazolin, cefoxitin), it should be readministered if the procedure duration exceeds the recommended redosing interval (from
the time of initiation of the preoperative dose [see Table 1]). Readministration may also be warranted if prolonged or excessive bleeding occurs or if there are other factors that may shorten the half-life of the prophylactic
agent (e.g., extensive burns). Readministration may not be warranted in patients in whom the half-life of the agent may be prolonged (e.g., patients with renal insufficiency or failure).
b
For patients known to be colonized with methicillin-resistant Staphylococcus aureus, it is reasonable to add a single preoperative dose of vancomycin to the recommended agent(s).
c
Strength of evidence that supports the use or nonuse of prophylaxis is classified as A (levels I–III), B (levels IV–VI), or C (level VII). Level I evidence is from large, well-conducted, randomized controlled clinical trials.
Level II evidence is from small, well-conducted, randomized controlled clinical trials. Level III evidence is from well-conducted cohort studies. Level IV evidence is from well-conducted case–control studies. Level V
evidence is from uncontrolled studies that were not well conducted. Level VI evidence is conflicting evidence that tends to favor the recommendation. Level VII evidence is expert opinion.
d
For procedures in which pathogens other than staphylococci and streptococci are likely, an additional agent with activity against those pathogens could be considered. For example, if there are surveillance data
showing that gram-negative organisms are a cause of surgical-site infections (SSIs) for the procedure, practitioners may consider combining clindamycin or vancomycin with another agent (cefazolin if the patient is not
b-lactam allergic; aztreonam, gentamicin, or single-dose fluoroquinolone if the patient is b-lactam allergic).
e
Prophylaxis should be considered for patients at highest risk for postoperative gastroduodenal infections, such as those with increased gastric pH (e.g., those receiving histamine H2-receptor antagonists or proton-
pump inhibitors), gastroduodenal perforation, decreased gastric motility, gastric outlet obstruction, gastric bleeding, morbid obesity, or cancer. Antimicrobial prophylaxis may not be needed when the lumen of the
intestinal tract is not entered.
f
Consider additional antimicrobial coverage with infected biliary tract. See the biliary tract procedures section of this article.
g
Gentamicin or tobramycin.
h
Due to increasing resistance of Escherichia coli to fluoroquinolones and ampicillin–sulbactam, local population susceptibility profiles should be reviewed prior to use.
i
Ciprofloxacin or levofloxacin.
j
Fluoroquinolones are associated with an increased risk of tendonitis and tendon rupture in all ages. However, this risk would be expected to be quite small with single-dose antibiotic prophylaxis. Although the use
of fluoroquinolones may be necessary for surgical antibiotic prophylaxis in some children, they are not drugs of first choice in the pediatric population due to an increased incidence of adverse events as compared with
controls in some clinical trials.
k
Ceftriaxone use should be limited to patients requiring antimicrobial treatment for acute cholecystitis or acute biliary tract infections which may not be determined prior to incision, not patients undergoing
cholecystectomy for noninfected biliary conditions, including biliary colic or dyskinesia without infection.
l
Factors that indicate a high risk of infectious complications in laparoscopic cholecystectomy include emergency procedures, diabetes, long procedure duration, intraoperative gallbladder rupture, age of >70 years,
conversion from laparoscopic to open cholecystectomy, American Society of Anesthesiologists classification of 3 or greater, episode of colic within 30 days before the procedure, reintervention in less than one month
for noninfectious complication, acute cholecystitis, bile spillage, jaundice, pregnancy, nonfunctioning gallbladder, immunosuppression, and insertion of prosthetic device. Because a number of these risk factors are not
possible to determine before surgical intervention, it may be reasonable to give a single dose of antimicrobial prophylaxis to all patients undergoing laparoscopic cholecystectomy.
m
For most patients, a mechanical bowel preparation combined with oral neomycin sulfate plus oral erythromycin base or with oral neomycin sulfate plus oral metronidazole should be given in addition to i.v.
prophylaxis.
n
Where there is increasing resistance to first- and second-generation cephalosporins among gram-negative isolates from SSIs, a single dose of ceftriaxone plus metronidazole may be preferred over the routine use of
carbapenems.
o
The necessity of continuing topical antimicrobials postoperatively has not been established.
p
Prophylaxis is not routinely indicated for brachiocephalic procedures. Although there are no data in support, patients undergoing brachiocephalic procedures involving vascular prostheses or patch implantation
(e.g., carotid endarterectomy) may benefit from prophylaxis.
q
These guidelines reflect recommendations for perioperative antibiotic prophylaxis to prevent SSIs and do not provide recommendations for prevention of opportunistic infections in immunosuppressed transplantation
patients (e.g., for antifungal or antiviral medications).
r
Patients who have left-ventricular assist devices as a bridge and who are chronically infected might also benefit from coverage of the infecting microorganism.
s
The prophylactic regimen may need to be modified to provide coverage against any potential pathogens, including gram-negative (e.g., Pseudomonas aeruginosa) or fungal organisms, isolated from the donor
lung or the recipient before transplantation. Patients undergoing lung transplantation with negative pretransplantation cultures should receive antimicrobial prophylaxis as appropriate for other types of cardiothoracic
surgeries. Patients undergoing lung transplantation for cystic fibrosis should receive 7–14 days of treatment with antimicrobials selected according to pretransplantation culture and susceptibility results. This treatment
may include additional antibacterial or antifungal agents.
t
The prophylactic regimen may need to be modified to provide coverage against any potential pathogens, including vancomycin-resistant enterococci, isolated from the recipient before transplantation.
children weighing more than 40 kg, the calculated dosage tion, and colonization with microorganisms. Antimicrobial
will exceed the maximum recommended dosage for adults; prophylaxis may be justified for any procedure if the patient
adult dosages should therefore be used. has an underlying medical condition associated with a high
Patients with prosthetic implants. For patients with risk of SSI or if the patient is immunocompromised (e.g.,
existing prosthetic implants who undergo an invasive pro- malnourished, neutropenic, receiving immunosuppressive
cedure, there is no evidence that antimicrobial prophylaxis agents).
prevents infections of the implant. However, updated guide- Antimicrobial prophylaxis may be beneficial in surgi-
lines from the American Heart Association (AHA) suggest cal procedures associated with a high rate of infection (i.e.,
that prophylaxis may be justified in a limited subset of pa- clean-contaminated or contaminated procedures) and in cer-
tients for the prevention of endocarditis.11 tain clean procedures where there are severe consequences
of infection (e.g., prosthetic implants), even if infection is
Common Principles and Procedure-Specific Guidelines. unlikely. While prophylactic antimicrobials are not indicated
The Common Principles section has been developed to for some clean surgical procedures,8 available data suggest
provide information common to many surgical proce- that the relative risk reduction of SSI from the use of anti-
dures. These principles are general recommendations based microbial prophylaxis is the same in clean and in higher-risk
on currently available data at the time of publication that procedures.38 The decision to use prophylaxis depends on
may change over time; therefore, these principles need to the cost of treating and the morbidity associated with infec-
be applied with careful attention to each clinical situation. tion compared with the cost and morbidity associated with
Detailed information pertinent to specific surgical proce- using prophylaxis. Antimicrobial prophylaxis is justified for
dures is included in the procedure-specific sections of these most clean-contaminated procedures. The use of antimicro-
guidelines. bial agents for dirty procedures (Appendix A) or established
In addition to patient- and procedure-specific consid- infections is classified as treatment of presumed infection,
erations, several institution-specific factors must be consid- not prophylaxis. See the procedure-specific sections for de-
ered by practitioners before instituting these guidelines. The tailed recommendations.
availability of antimicrobial agents at the institution may be
restricted by local antimicrobial-use policy or lack of ap- Quality-Improvement Efforts. National, state, local, and
proval for use by regulatory authorities. Medications that are institutional groups have developed and implemented col-
no longer available or not approved for use by the Food and laborative efforts to improve the appropriateness of surgi-
Drug Administration (FDA) are so noted. Local resistance cal antimicrobial prophylaxis. Various process and out-
patterns should also be considered in selecting antimicrobial comes measures are employed, and results are disseminated.
agents and are discussed in the colonization and resistance Institutional epidemiology and infection-control programs,
patterns section of the Common Principles section. state-based quality-improvement campaigns (e.g., the
Michigan Surgical Quality Collaborative, the Washington
Requirements for Effective State Surgical Clinical Outcomes Assessment Program39,40),
Surgical Prophylaxis CDC, NHSN, the National Surgical Quality Improvement
Program, the Joint Commission, and the National Quality
Appendix A lists the wound classification criteria currently Forum have been instrumental in developing programs to
used by the CDC National Healthcare Safety Network prevent SSIs.
(NHSN) and Healthcare Infection Control Practices Over the past decade or more, several organizations,
Advisory Committee (HICPAC).33–35 payers, and government agencies, including the Centers
Criteria for defining an SSI have also been established for Medicare and Medicaid Services (CMS), have estab-
by NHSN (Appendix B).8,36 These definitions assist in evalu- lished national quality-improvement initiatives to further
ating the importance of providing antimicrobial prophylaxis improve the safety and outcomes of health care, including
and the potential consequences of infection, including the surgery.41–47 One area of focus in these initiatives for patients
need for treatment. Some criteria vary slightly by procedure. undergoing surgical procedures is the prevention of SSIs.
Although antimicrobial prophylaxis plays an impor- The performance measures used, data collection and report-
tant role in reducing the rate of SSIs, other factors such as ing requirements, and financial implications vary among the
attention to basic infection-control strategies,37 the surgeon’s initiatives. The Surgical Care Improvement Project (SCIP)
experience and technique, the duration of the procedure, began in 2002 as the Surgical Infection Prevention (SIP)
hospital and operating-room environments, instrument- project, focusing on the timing, selection, and duration of
sterilization issues, preoperative preparation (e.g., surgical prophylactic antimicrobial agents.41,42 The SIP project was
scrub, skin antisepsis, appropriate hair removal), periopera- expanded to SCIP to include additional process measures
tive management (temperature and glycemic control), and surrounding patient safety and care during surgical proce-
the underlying medical condition of the patient may have a dures, including glucose control, venous thromboembolism
strong impact on SSI rates.5,8 These guidelines recognize the prophylaxis, hair removal, and temperature control. Similar
importance of these other factors but do not include a dis- measures have been adopted by the Joint Commission.43
cussion of or any recommendations regarding these issues The Physicians Quality Reporting System was established
beyond the optimal use of prophylactic antimicrobial agents. in 2006 to provide financial incentives to physicians meeting
Patient-related factors associated with an increased risk of performance standards for quality measures, including sur-
SSI include extremes of age, nutritional status, obesity, gery-related measures similar to those reported for SCIP and
diabetes mellitus, tobacco use, coexistent remote body-site the Joint Commission.44 Data are required to be collected
infections, altered immune response, corticosteroid therapy, by institutions and reported to payers.42,44,46 Data for CMS
recent surgical procedure, length of preoperative hospitaliza- and the Physicians Quality Reporting System measures are
displayed on public websites to allow consumers to com- vitro antibacterial activity) result in lower rates of postoperative
pare performance among hospitals. Institutional data col- SSI compared with older antimicrobial agents with a narrower
lection and reporting are required, with financial incentives spectrum of activity. However, comparative studies are limited
tied to performance to varying degrees, including payment by small sample sizes, resulting in difficulty detecting a signifi-
for reporting, payment increases for meeting or exceeding cant difference between antimicrobial agents; therefore, anti-
minimum levels of performance, payment reduction for poor microbial selection is based on cost, safety profile, ease of ad-
performance, and lack of payment for the development of ministration, pharmacokinetic profile, and bactericidal activity.
surgical complications, such as mediastinitis.
Quality-improvement initiatives and mandated perfor- Common Surgical Pathogens
mance reporting are subject to change, so readers of these
guidelines are advised to consult their local or institutional The agent chosen should have activity against the most com-
quality-improvement departments for new developments in mon surgical-site pathogens. The predominant organisms
requirements for measures and data reporting that apply to causing SSIs after clean procedures are skin flora, includ-
their practice. ing S. aureus and coagulase-negative staphylococci (e.g.,
Staphylococcus epidermidis).61 In clean-contaminated pro-
Cost Containment. Few pharmacoeconomic studies have cedures, including abdominal procedures and heart, kidney,
addresed surgical antimicrobial prophylaxis; therefore, a and liver transplantations, the predominant organisms in-
cost-minimization approach was employed in developing clude gram-negative rods and enterococci in addition to skin
these guidelines. The antimicrobial agent recommendations flora. Additional details on common organisms can be found
are based primarily on efficacy and safety. Individual institu- in procedure-specific sections of these guidelines.
tions must consider their acquisition costs when implement- Recommendations for the selection of prophylactic
ing these guidelines. antimicrobials for various surgical procedures are provided
Additional cost savings may be realized through colin Table 2. Adult and pediatric dosages are included in Table
laborative management by pharmacists and surgeons to se- 1. Agents that are FDA-approved for use in surgical antimi-
lect the most cost-effective agent and minimize or eliminate crobial prophylaxis include cefazolin, cefuroxime, cefoxitin,
postoperative dosing.48–50 The use of standardized antimi- cefotetan, ertapenem, and vancomycin.62–67
crobial order sets, automatic stop-order programs, and edu-
cational initiatives has been shown to facilitate the adoption Trends in Microbiology. The causative pathogens associ-
of guidelines for surgical antimicrobial prophylaxis.51–58 ated with SSIs in U.S. hospitals have changed over the past
two decades. Analysis of National Nosocomial Infections
Common Principles Surveillance (NNIS) System data found that the percent-
age of SSIs caused by gram-negative bacilli decreased from
Ideally, an antimicrobial agent for surgical prophylaxis 56.5% in 1986 to 33.8% in 2003.68 S. aureus was the most
should (1) prevent SSI, (2) prevent SSI-related morbidity common pathogen, causing 22.5% of SSIs during this time
and mortality, (3) reduce the duration and cost of health care period. NHSN data from 2006 to 2007 revealed that the
(when the costs associated with the management of SSI are proportion of SSIs caused by S. aureus increased to 30%,
considered, the cost-effectiveness of prophylaxis becomes with MRSA comprising 49.2% of these isolates.61 In a study
evident),51,52 (4) produce no adverse effects, and (5) have no of patients readmitted to U.S. hospitals between 2003 and
adverse consequences for the microbial flora of the patient 2007 with a culture-confirmed SSI, the proportion of infec-
or the hospital.53 To achieve these goals, an antimicrobial tions caused by MRSA increased significantly from 16.1%
agent should be (1) active against the pathogens most likely to 20.6% (p < 0.0001).69 MRSA infections were associated
to contaminate the surgical site, (2) given in an appropriate with higher mortality rates, longer hospital stays, and higher
dosage and at a time that ensures adequate serum and tissue hospital costs compared with other infections.
concentrations during the period of potential contamination,
(3) safe, and (4) administered for the shortest effective pe- Spectrum of Activity. Antimicrobial agents with the narrow-
riod to minimize adverse effects, the development of resis- est spectrum of activity required for efficacy in preventing
tance, and costs.8,59,60 infection are recommended in these guidelines. Alternative
The selection of an appropriate antimicrobial agent for antimicrobial agents with documented efficacy are also
a specific patient should take into account the characteristics listed herein. Individual health systems must consider lo-
of the ideal agent, the comparative efficacy of the antimicro- cal resistance patterns of organisms and overall SSI rates at
bial agent for the procedure, the safety profile, and the patient’s their site when adopting these recommendations. Resistance
medication allergies. A full discussion of the safety profile, patterns from organisms causing SSIs—in some cases pro-
including adverse events, drug interactions, contraindications, cedure-specific resistance patterns—should take precedence
and warnings, for each antimicrobial agent is beyond the scope over hospitalwide antibiograms.
of these guidelines. Readers of these guidelines should review
the FDA-approved prescribing information and published data Vancomycin. In 1999, HICPAC, an advisory committee to
for specific antimicrobial agents before use. For most proce- CDC and the Secretary of the Department of Health and
dures, cefazolin is the drug of choice for prophylaxis because it Human Services, collaborated with other major organiza-
is the most widely studied antimicrobial agent, with proven ef- tions to develop recommendations for preventing and con-
ficacy. It has a desirable duration of action, spectrum of activity trolling vancomycin resistance.70 The recommendations are
against organisms commonly encountered in surgery, reason- echoed by these and other guidelines.6,7,41,71 Routine use of
able safety, and low cost. There is little evidence to suggest that vancomycin prophylaxis is not recommended for any pro-
broad-spectrum antimicrobial agents (i.e., agents with broad in cedure.8 Vancomycin may be included in the regimen of
choice when a cluster of MRSA cases (e.g., mediastinitis The question of what antimicrobial surgical prophy-
after cardiac procedures) or methicillin-resistant coagulase- laxis to use for patients known to be colonized or recently
negative staphylococci SSIs have been detected at an insti- infected with multidrug-resistant pathogens cannot be an-
tution. Vancomycin prophylaxis should be considered for swered easily or in a manner that can be applied uniformly
patients with known MRSA colonization or at high risk for to all patient scenarios. Whether prophylaxis should be ex-
MRSA colonization in the absence of surveillance data (e.g., panded to provide coverage for these pathogens depends on
patients with recent hospitalization, nursing-home residents, many factors, including the pathogen, its antimicrobial sus-
hemodialysis patients).5,41,72 In institutions with SSIs at- ceptibility profile, the host, the procedure to be performed,
tributable to community-associated MRSA, antimicrobial and the proximity of the likely reservoir of the pathogen to
agents with known in vitro activity against this pathogen the incision and operative sites. While there is no evidence
may be considered as an alternative to vancomycin. on the management of surgical antimicrobial prophylaxis in
Each institution is encouraged to develop guidelines a patient with past infection or colonization with a resistant
for the proper use of vancomycin. Although vancomycin is gram-negative pathogen, it is logical to provide prophylaxis
commonly used when the risk for MRSA is high, data sug- with an agent active against MRSA for any patient known
gest that vancomycin is less effective than cefazolin for to be colonized with this gram-positive pathogen who will
preventing SSIs caused by methicillin-susceptible S. aureus have a skin incision; specific prophylaxis for a resistant
(MSSA).73,74 For this reason, vancomycin is used in combi- gram-negative pathogen in a patient with past infection or
nation with cefazolin at some institutions with both MSSA colonization with such a pathogen may not be necessary for
and MRSA SSIs. For procedures in which pathogens other a purely cutaneous procedure. Similarly, a patient colonized
than staphylococci and streptococci are likely, an additional with vancomycin-resistant enterococci (VRE) should re-
agent with activity against those pathogens should be conceive prophylaxis effective against VRE when undergoing
sidered. For example, if there are surveillance data showing liver transplantation but probably not when undergoing an
that gram-negative organisms are a cause of SSIs for the pro- umbilical hernia repair without mesh placement. Thus, pa-
cedure, practitioners may consider combining vancomycin tients must be treated on a case-by-case basis, taking into
with another agent (cefazolin if the patient does not have a account multiple considerations.
b-lactam allergy; an aminoglycoside [gentamicin or tobra- Patients receiving therapeutic antimicrobials for a
mycin], aztreonam, or single-dose fluoroquinolone if the remote infection before surgery should also be given anti-
patient has a b-lactam allergy). The use of vancomycin for microbial prophylaxis before surgery to ensure adequate
MRSA prophylaxis does not supplant the need for routine serum and tissue levels of antimicrobials with activity
surgical prophylaxis appropriate for the type of procedure. against likely pathogens for the duration of the operation. If
When vancomycin is used, it can almost always be used as a the agents used therapeutically are appropriate for surgical
single dose due to its long half-life. prophylaxis, administering an extra dose within 60 minutes
before surgical incision is sufficient. Otherwise, the antimi-
Colonization and Resistance. A national survey determined crobial prophylaxis recommended for the planned procedure
that S. aureus nasal colonization in the general population should be used. For patients with indwelling tubes or drains,
decreased from 32.4% in 2001–02 to 28.6% in 2003–04 (p consideration may be given to using prophylactic agents
< 0.01), whereas the prevalence of colonization with MRSA active against pathogens found in these devices before the
increased from 0.8% to 1.5% (p < 0.05) during the same procedure, even though therapeutic treatment for pathogens
time periods.75 Colonization with MRSA was independently in drains is not indicated at other times. For patients with
associated with health care exposure among men, having chronic renal failure receiving vancomycin, a preoperative
been born in the United States, age of >60 years, diabetes, dose of cefazolin should be considered instead of an extra
and poverty among women. Similarly, children are colo- dose of vancomycin, particularly if the probable pathogens
nized with S. aureus and MRSA, but colonization varies by associated with the procedure are gram-negative. In most
age. Children under 5 years of age have the highest rates, circumstances, elective surgery should be postponed when
mirroring rates seen in patients over age 60 years.76 The rates the patient has an infection at a remote site.
drop in children between 5 and 14 years of age and gradu-
ally increase to rates seen in the adult population. Lo et al.77 Allergy to b-Lactam Antimicrobials. Allergy to b-lactam
reported that in a large cohort of children, 28.1% were colo- antimicrobials may be a consideration in the selection of
nized with S. aureus between 2004 and 2006. Between 2007 surgical prophylaxis. The b-lactam antimicrobials, including
and 2009, 23.3% of children were colonized with S. aureus, cephalosporins, are the mainstay of surgical antimicrobial
but the proportion of children colonized with MRSA had in- prophylaxis and are also the most commonly implicated
creased from 8.1% in 2004 to 15.1% in 2009. drugs when allergic reactions occur. Because the predomi-
Surgical antimicrobial prophylaxis can alter individual nant organisms in SSIs after clean procedures are gram-
and institutional bacterial flora, leading to changes in coloni- positive, the inclusion of vancomycin may be appropriate
zation rates and increased bacterial resistance.78–84 Surgical for a patient with a life-threatening allergy to b-lactam an-
prophylaxis can also predispose patients to Clostridium timicrobials.
difficile-associated colitis.81 Risk factors for development Although true Type 1 (immunoglobulin E [IgE]-
of C. difficile-associated colitis include longer duration of mediated) cross-allergic reactions between penicillins,
prophylaxis or therapy and use of multiple antimicrobial cephalosporins, and carbapenems are uncommon, cepha-
agents.85 Limiting the duration of antimicrobial prophylaxis losporins and carbapenems should not be used for surgical
to a single preoperative dose can reduce the risk of C. dif- prophylaxis in patients with documented or presumed IgE-
ficile disease. mediated penicillin allergy. Confusion about the defini-
tion of true allergy among patients and practitioners leads
to recommendations for alternative antimicrobial therapy whose infusions were started more than 180 minutes before
with the potential for a lack of efficacy, increased costs, surgical incision (OR, 2.1; 95% CI, 0.82–5.62).93
and adverse events.86,87 Type 1 anaphylactic reactions to In a large, prospective, multicenter study from the Trial
antimicrobials usually occur 30–60 minutes after adminis- to Reduce Antimicrobial Prophylaxis Errors (TRAPE) study
tration. In patients receiving penicillins, this reaction is a group, the timing, duration, and intraoperative redosing of
life-threatening emergency that precludes subsequent use of antimicrobial prophylaxis and risk of SSI were evaluated in
penicillins.88 Cephalosporins and carbapenems can safely be 4472 patients undergoing cardiac surgery, hysterectomy, or
used in patients with an allergic reaction to penicillins that hip or knee arthroplasty.94 The majority of patients (90%) re-
is not an IgE-mediated reaction (e.g., anaphylaxis, urticaria, ceived antimicrobial prophylaxis per the SCIP guidelines.41
bronchospasm) or exfoliative dermatitis (Stevens-Johnson Patients were assigned to one of four groups for analysis.
syndrome, toxic epidermal necrolysis), a life-threatening Group 1 (n = 1844) received a cephalosporin (or other anti-
hypersensitivity reaction that can be caused by b-lactam microbial with a short infusion time) administered within 30
antimicrobials and other medications.88,89 Patients should minutes before incision or vancomycin or a fluoroquinolone
be carefully questioned about their history of antimicrobial within one hour before incision. Group 2 (n = 1796) received
allergies to determine whether a true allergy exists before a cephalosporin 31–60 minutes before incision or vancomy-
selection of agents for prophylaxis. Patients with allergies to cin 61–120 minutes before incision. Group 3 (n = 644) was
cephalosporins, penicillins, or both have been excluded from given antimicrobials earlier than recommended, and group
many clinical trials. Alternatives to b-lactam antimicrobials 4 (n = 188) received their initial antimicrobial doses after
are provided in Table 2 based mainly on the antimicrobial incision. The infection risk was lowest in group 1 (2.1%),
activity profiles against predominant procedure-specific or- followed by group 2 (2.4%) and group 3 (2.8%). The risk of
ganisms and available clinical data. infection was highest in group 4 (5.3%, p = 0.02 compared
with group 1). When cephalosporins and other antimicro-
Drug Administration bials with short infusion times were analyzed separately (n
= 3656), the infection rate with antimicrobials administered
The preferred route of administration varies with the type of within 30 minutes before incision was 1.6% compared with
procedure, but for a majority of procedures, i.v. administra- 2.4% when antimicrobials were administered 31–60 minutes
tion is ideal because it produces rapid, reliable, and predict- before incision (p = 0.13).
able serum and tissue concentrations. In a multicenter Dutch study of 1922 patients undergo-
ing total hip arthroplasty, the lowest SSI rate was seen in pa-
Timing of Initial Dose. Successful prophylaxis requires tients who received the antimicrobial during the 30 minutes
the delivery of the antimicrobial to the operative site before before incision.95 The highest risk for infection was found in
contamination occurs. Thus, the antimicrobial agent should patients who received prophylaxis after the incision.
be administered at such a time to provide serum and tissue It seems intuitive that the entire antimicrobial dose
concentrations exceeding the minimum inhibitory concen- should be infused before a tourniquet is inflated or before
tration (MIC) for the probable organisms associated with any other procedure that restricts blood flow to the surgical
the procedure, at the time of incision, and for the duration site is initiated; however, a study of total knee arthroplasties
of the procedure.41,90 In 1985, DiPiro et al.91 demonstrated compared cefuroxime given 10–30 minutes before tourni-
that higher serum and tissue cephalosporin concentrations at quet inflation with cefuroxime given 10 minutes before tour-
the time of surgical incision and at the end of the procedure niquet deflation and found no significant difference in SSI
were achieved when the drugs were given intravenously at rates between the two groups.96
the time of anesthesia induction compared with administra- Overall, administration of the first dose of antimicro-
tion in the operating room. The average interval between an- bial beginning within 60 minutes before surgical incision
timicrobial administration and incision was 17–22 minutes91 is recommended.41,94,97 Administration of vancomycin and
(Dellinger EP, personal communication, 2011 May). fluoroquinolones should begin within 120 minutes before
A prospective evaluation of 1708 surgical patients re- surgical incision because of the prolonged infusion times
ceiving antimicrobial prophylaxis found that preoperative required for these drugs. Because these drugs have long
administration of antimicrobials within 2 hours before surgi- half-lives, this early administration should not compromise
cal incision decreased the risk of SSI to 0.59%, compared serum levels of these agents during most surgical proce-
with 3.8% for early administration (2–24 hours before surgi- dures. Although the recent data summarized above sug-
cal incision) and 3.3% for any postoperative administration gest lower infection risk with antimicrobial administration
(any time after incision).92 In a study of 2048 patients under- beginning within 30 minutes before surgical incision, these
going coronary bypass graft or valve replacement surgery data are not sufficiently robust to recommend narrowing
receiving vancomycin prophylaxis, the rate of SSI was low- the optimal window to begin infusion to 1–30 minutes be-
est in those patients in whom an infusion was started 16–60 fore surgical incision. However, these data do suggest that
minutes before surgical incision.93 This time interval (16–60 antimicrobials can be administered too close to the time of
minutes before incision) was compared with four others, and incision. Although a few articles have suggested increased
the rates of SSIs were significantly lower when compared infection risk with administration too close to the time of
with infusions given 0–15 minutes before surgical incision incision,93,96,97 the data presented are not convincing. In fact,
(p < 0.01) and 121–180 minutes before incision (p = 0.037). all of these articles confirm the increased rate of SSI for an-
The risk of infection was higher in patients receiving infu- timicrobials given earlier than 60 minutes before incision.
sions 61–120 minutes before incision (odds ratio [OR], 2.3; In one article, the infection rate for patients given an antimi-
95% confidence interval [CI], 0.98–5.61) and for patients crobial within 15 minutes of incision was lower than when
antimicrobials were given 15–30 minutes before incision.97
In another article, small numbers of patients were reported, in morbidly obese patients than in the normal-weight pa-
and an assertion of high infection rates for infusion within tients.101 The concentrations in morbidly obese patients also
15 minutes of incision was made, but no numeric data or were lower than the MICs needed for prophylaxis against
p values were provided.98 In a third article, only 15 of over gram-positive cocci and gram-negative rods. In the second
2000 patients received antimicrobials within 15 minutes be- phase of the study, adequate blood and tissue cefazolin con-
fore incision.93 Earlier studies found that giving antimicrobi- centrations were achieved in morbidly obese patients receiv-
als within 20 minutes of incision and as close as 7 minutes ing preoperative doses of cefazolin 2 g, and the rate of SSIs
before incision resulted in therapeutic levels in tissue at the was significantly lower in these patients compared with
time of incision.41,90,91,94,97,98 morbidly obese patients receiving 1-g doses during the first
phase of the study.
Dosing. To ensure that adequate serum and tissue concen- While the optimal cefazolin dose has not been estab-
trations of antimicrobial agents for prophylaxis of SSIs are lished in obese patients, a few pharmacokinetic studies have
achieved, antimicrobial-specific pharmacokinetic and phar- investigated the cefazolin concentrations in serum and tis-
macodynamic properties and patient factors must be consid- sue during surgical procedures.13,105 Two small pharmaco-
ered when selecting a dose. One of the earliest controlled kinetic studies found that administering 1- or 2-g doses of
studies of antimicrobial prophylaxis in cardiac surgery found cefazolin may not be sufficient to produce serum and tis-
a lower rate of infection in patients with detectable concen- sue concentrations exceeding the MIC for the most common
trations of the drug in serum at the end of surgery compared pathogens. In a small, single-center study, 38 adults under-
with patients in whom the drug was undetectable.99 In an- going Roux-en-Y gastric bypass surgery were classified by
other study, higher levels of antimicrobial in atrial tissue at body mass index (BMI) in one of three groups.13 All patients
the time of starting the pump for open-heart surgery were as- were given cefazolin 2 g i.v. 30–60 minutes before the inci-
sociated with fewer infections than were lower antimicrobial sion, followed by a second 2-g i.v. dose three hours later.
concentrations.100 In patients undergoing colectomy, infec- The mean serum drug concentration before the second dose
tion levels were inversely related to the serum gentamicin of cefazolin was lower than the resistance breakpoint in all
concentration at the time of surgical closure.17 In general, it three BMI groups. Serum drug concentrations were lower in
seems advisable to administer prophylactic agents in a man- patients with a high BMI than in patients with lower BMI
ner that will ensure adequate levels of drug in serum and values. Tissue drug concentrations were lower than a tar-
tissue for the interval during which the surgical site is open. geted concentration of 8 mg/mL at all measurement times,
Weight-based dosing. The dosing of most antimicro- except the time of skin closure in the patients with the lowest
bials in pediatric patients is based on body weight, but the BMIs. These results suggest that a 1-g dose of cefazolin may
dosing of many antimicrobials in adults is not based on body be inadequate for obese patients undergoing gastric bypass
weight, because it is safe, effective, and convenient to use surgery. A weakness of the literature on drug dosing in mor-
standardized doses for most of the adult patient population. bidly obese patients is the practice of reporting results by
Such standardized doses avoid the need for calculations and BMI rather than weight.
reduce the risk for medication errors. However, in obese pa- Doubling the normal dose of cephalosporins or mak-
tients, especially those who are morbidly obese, serum and ing fewer adjustments based on renal dysfunction may
tissue concentrations of some drugs may differ from those produce concentrations in obese patients similar to those
in normal-weight patients because of pharmacokinetic al- achieved with standard doses in normal-weight patients.103
terations that depend on the lipophilicity of the drug and Considering the low cost and favorable safety profile of
other factors.101 Limited data are available on the optimal cefazolin, increasing the dose to 2 g for patients weighing
approach to dosing of antimicrobial agents for obese pa- more than 80 kg and to 3 g for those weighing over 120 kg
tients.102,103 If weight-based dosing is warranted for obese can easily be justified.41 For simplification, some hospitals
patients, it has not been determined whether the patient’s have standardized 2-g cefazolin doses for all adult patients.
ideal body weight or total (i.e., actual) body weight should Gentamicin doses have been compared for prophy-
be used. In theory, using the ideal body weight as the basis laxis only in colorectal surgery, where a single dose of gen-
for dosing a lipophilic drug (e.g., vancomycin) could result tamicin 4.5 mg/kg in combination with metronidazole was
in subtherapeutic concentrations in serum and tissue, and the more effective in SSI prevention than multiple doses of
use of actual body weight for dosing a hydrophilic drug (e.g., gentamicin 1.5 mg/kg every eight hours.16,17 In obese pa-
an aminoglycoside) could result in excessive concentrations tients who weigh 20% above their ideal body weight, the
in serum and tissue. Pediatric patients weighing more than dose of gentamicin should be calculated using the ideal body
40 kg should receive weight-based doses unless the dose or weight plus 40% of the difference between the actual and
daily dose exceeds the recommended adult dose.104 ideal weights.106 If gentamicin will be used in combination
Conclusive recommendations for weight-based dos- with a parenteral antimicrobial with activity against anaero-
ing for antimicrobial prophylaxis in obese patients cannot be bic agents for prophylaxis, it is probably advisable to use
made because data demonstrating clinically relevant decreases 4.5–5 mg/kg as a single dose.16 This dose of gentamicin has
in SSI rates from the use of such dosing strategies instead of been found safe and effective in a large body of literature
standard doses in obese patients are not available in the pub- examining the use of single daily doses of gentamicin for
lished literature. therapeutic indications.106–113 When used as a single dose for
In a small, nonrandomized, two-phase study of mor- prophylaxis, the risk of toxicity from gentamicin is very low.
bidly obese adults undergoing gastroplasty and normal- Obese patients are often underrepresented in clinical
weight adults undergoing upper abdominal surgery, blood trials and are not currently considered a special population
and tissue concentrations of cefazolin after the adminis- for whom FDA requires separate pharmacokinetic stud-
tration of a 1-g preoperative dose were consistently lower ies during antimicrobial research and development by the
drug manufacturer. Obesity has been recognized as a risk bial resistance (cephalosporin-resistant Enterobacteriaceae
factor for SSI; therefore, optimal dosing of antimicrobial and VRE) compared with short-term prophylaxis (OR, 1.6;
prophylaxis is needed in these patients.114 While a BMI of 95% CI, 1.1–2.6).
>30 kg/m2 is commonly used to define obesity, the body fat There are no data to support the continuation of anti-
percentage (>25% in men and >31% in women) may bet- microbial prophylaxis until all indwelling drains and intra-
ter predict SSI risk, because the BMI may not reflect body vascular catheters are removed.19,31,32,41,131–134
composition. In a recent prospective cohort study of 590 pa-
tients undergoing elective surgery, there was no significant Topical Administration of Irrigations,
difference in SSI rates in nonobese and obese patients when Pastes, and Washes
the BMI was used to define obesity (12.3% versus 11.6%,
respectively).115 However, when the body fat percentage I.V. and oral antimicrobial administration are the main fo-
(determined by bioelectrical impedance analysis) was used cus of these guidelines, and these routes of administration
as the basis for identifying obesity (>25% in men and >31% are used for most surgical procedures addressed by these
in women), obese patients had a fivefold-higher risk of SSI guidelines, with the exception of ophthalmic procedures, for
than did nonobese patients (OR, 5.3; 95% CI, 1.2–23.1; p which topical administration is the primary route of admin-
= 0.03). These findings suggest that body fat percentage is istration. Limited high-quality data are available regarding
a more sensitive and precise measurement of SSI risk than the use of antimicrobial irrigations, pastes, and washes that
is the BMI. are administered topically. Studies published in the early
Redosing. Intraoperative redosing is needed to ensure 1980s demonstrated that prophylactic topical administration
adequate serum and tissue concentrations of the antimicro- of antimicrobials in the surgical incision during various non-
bial if the duration of the procedure exceeds two half-lives of ophthalmic procedures is superior to placebo but not supe-
the antimicrobial or there is excessive blood loss (i.e., >1500 rior to parenteral administration, and topical administration
mL).17,41,94,116–121 The redosing interval should be measured does not increase the efficacy of parenteral antimicrobials
from the time of administration of the preoperative dose, not when used in combination for prophylaxis.135–138 Additional
from the beginning of the procedure. Redosing may also be high-quality data on the safety and efficacy of topical an-
warranted if there are factors that shorten the half-life of the timicrobial administration as an adjunct to i.v. administra-
antimicrobial agent (e.g., extensive burns). Redosing may tion are needed to determine the role of topical antimicrobial
not be warranted in patients in whom the half-life of the prophylaxis.
antimicrobial agent is prolonged (e.g., patients with renal One area of interest for topical administration of anti-
insufficiency or renal failure). See Table 1 for antimicrobial- microbials, mainly gentamicin and vancomycin, is applica-
specific redosing recommendations. tion to the sternum during cardiac procedures in combina-
Duration. The shortest effective duration of antimicro- tion with i.v. agents to prevent mediastinitis. This strategy
bial administration for preventing SSI is not known; however, has been evaluated in cohort and randomized controlled
evidence is mounting that postoperative antimicrobial ad- studies.139–142 While the studies found a significantly lower
ministration is not necessary for most procedures.6,7,41,122–124 rate of SSI with topical antimicrobials compared with stan-
The duration of antimicrobial prophylaxis should be less dard prophylaxis,140 placebo,142 and a historical control,139 a
than 24 hours for most procedures. Cardiothoracic proce- smaller, randomized, placebo-controlled study found no dif-
dures for which a prophylaxis duration of up to 48 hours ference between groups.141
has been accepted without evidence to support the practice More recently, implantable gentamicin collagen
is an area that remains controversial. The duration of cardio- sponges failed to show any efficacy in reducing SSIs in a
thoracic prophylaxis in these guidelines is based on expert large prospective study of patients undergoing cardiac sur-
panel consensus because the available data do not delineate gery and resulted in an increased infection rate in patients
the optimal duration of prophylaxis. In these procedures, undergoing colectomy.143,144 The safety and efficacy of topi-
prophylaxis for the duration of the procedure and certainly cal antimicrobials have not been clearly established; there-
for less than 24 hours is appropriate. fore, routine use of this route cannot be recommended in
A 1992 meta-analysis of studies comparing first- cardiac or other procedures.145
generation cephalosporins and antistaphylococcal antimi-
crobials (e.g., penicillins) with second-generation cepha- Preoperative Screening and
losporins in patients undergoing cardiothoracic surgery Decolonization
found a reduction in the rate of SSI with second-generation
cephalosporins but no benefit from continuing surgical pro- S. aureus is the most common pathogen causing SSIs, ac-
phylaxis beyond 48 hours.125 Reports published in 1980,126 counting for 30% of SSIs in the United States. Colonization
1993,127 1997,128 and 2000129 involving seven studies that with S. aureus, primarily in the nares, occurs in roughly one
compared single-dose prophylaxis or prophylaxis only dur- in four persons and increases the risk of SSI by 2- to 14-
ing the operation with durations of one to four days failed fold.146–152 A national survey assessing nasal colonization
to show any reduction in SSIs with the longer durations of with S. aureus in the general population conducted from
prophylaxis. In a more-recent observational four-year cohort 2001 through 2004 found that while the rate of colonization
study of 2641 patients undergoing coronary artery bypass with S. aureus decreased from 32.4% in 2001–02 to 28.6%
graft (CABG) surgery, the extended use of antimicrobial in 2003–04 (p < 0.01), the rate of colonization with MRSA
prophylaxis (>48 hours) instead of a shorter duration of pro- increased from 0.8% to 1.5% (p < 0.05).75
phylaxis (<48 hours) failed to reduce the risk of SSI (OR, Preoperative screening for S. aureus carriage and de-
1.2; 95% CI, 0.8–1.6).130 Moreover, prolonged prophylaxis colonization strategies have been explored as means to re-
was associated with an increased risk of acquired antimicro- duce the rate of SSIs. Anterior nasal swab cultures are most
commonly used for preoperative surveillance, but screen- cin–chlorhexidine-treated group (4 of 441 patients) versus
ing additional sites (pharynx, groin, wounds, rectum) can 4.4% of the placebo group (16 of 367 patients) (relative risk,
increase detection rates.153 Such preoperative surveillance 0.21; 95% CI, 0.07–0.62). The reduction in superficial SSIs
swabs that can be cultured on selective or nonselective was less marked (1.6% versus 3.5%; relative risk, 0.45; 95%
media or sent for rapid polymerase chain reaction (PCR)- CI, 0.18–1.11). It is plausible that this approach would be
based screening can be used to identify colonized patients beneficial in a setting of MRSA, but it has not been proven.
in the preoperative period. When properly used, all of these Most studies conclude that the use of preoperative
techniques can identify MSSA and MRSA. However, not all intranasal mupirocin in colonized patients is safe and po-
PCR-based systems will identify both MRSA and MSSA so tentially beneficial as an adjuvant to i.v. antimicrobial
verification with the laboratory is needed. While many stud- prophylaxis to decrease the occurrence of SSIs. However,
ies have focused specifically on MRSA screening in high- the optimal timing and duration of administration are not
risk hospitalized patients in an effort to prevent MRSA SSI standardized. In most studies, mupirocin was used for five
and hospital-acquired infections, the risk of developing an days before the operation. While S. aureus resistance to mu-
SSI remains elevated for any S. aureus carrier. While some pirocin has been detected,148,162 raising concerns about the
authors advocate screening for MRSA carriage in the general potential for widespread problems with resistance from rou-
population, the data supporting universal screening in the tine use of this agent, resistance has only rarely been seen
surgical population are more controversial.154,155 Screening in the preoperative setting. Low-level resistance is associ-
has been advocated to both identify candidates for S. aureus ated with an increased rate of failure of decolonization and
decolonization and inform the selection of optimal prophy- has been seen in institutions that use standardized mupirocin
lactic antimicrobials, such as the addition of vancomycin for decolonization protocols.163 Therefore, when decolonization
those colonized with MRSA. therapy (e.g., mupirocin) is used as an adjunctive measure
FDA has approved intranasal mupirocin to eradicate to prevent S. aureus SSI, surveillance of susceptibility of S.
MRSA nasal colonization in adult patients and health care aureus isolated from SSIs to mupirocin is recommended.164
workers.156 It is noted in the prescribing information that While universal use of mupirocin is discouraged, specific
there are insufficient data to support use in prevention of recommendations for the drug’s use can be found in the car-
autoinfection of high-risk patients from their own nasal diac and orthopedic sections of these guidelines.
colonization with S. aureus. However, additional data have
demonstrated that the use of intranasal mupirocin in nasal
Future Research
carriers of S. aureus decreases the rate of S. aureus infec-
tions.157,158 One meta-analysis of seven studies focused on
Additional research is needed in several areas related to
surgical patients only157; the other meta-analysis of nine surgical antimicrobial prophylaxis. The risks and benefits
studies included high-quality studies in dialysis patients.158 of continuing antimicrobial prophylaxis after the conclu-
Recent studies have confirmed that S. aureus decolo- sion of the operative procedure, including dosing and du-
nization of the anterior nares decreases SSI rates in many ration, need to be further evaluated. Insight is needed to
surgical patients.159 The data are most compelling in cardiac make specific recommendations for intraoperative repeat
and orthopedic surgery patients. There are fewer data in gen- dosing, weight-based dosing in obese patients, and timing
eral surgery patients. A large, randomized controlled trial of of presurgical antimicrobials that must be administered over
general, cardiac, and neurosurgical patients (n = 3864) re- a prolonged period (e.g., vancomycin, fluoroquinolones).
vealed that prophylactic intranasal application of mupirocin Additional clarification is needed regarding targeted anti-
did not significantly reduce the overall rate of S. aureus SSIs microbial concentrations and intraoperative monitoring of
(2.3% in the mupirocin group versus 2.4% in the control antimicrobial serum and tissue concentrations to optimize
group) but did decrease the rate of S. aureus SSI among S. efficacy. The role of topical administration of antimicrobial
aureus carriers (3.7% in the mupirocin group versus 5.9% in agents as a substitute for or an adjunct to i.v. antimicrobial
the control group).160 prophylaxis needs to be further evaluated. Additional data
Another randomized controlled trial found no signifi- are needed to guide the selection of antimicrobial agents
cant difference in the rate of postoperative S. aureus SSIs for prophylaxis, particularly combination regimens, for pa-
among cardiac surgery patients receiving intranasal mupi- tients with allergies to b-lactam antimicrobials. Data are also
rocin and those receiving placebo, but the study was limited
needed to devise strategies to optimize antimicrobial pro-
by the small numbers of patients (n = 257) and reported SSIs
phylaxis in patients and facilities with a high risk or high
(n = 5).161 Among elective orthopedic patients undergoing
prevalence of resistant organisms implicated in SSIs (e.g.,
implantation and other procedures, a randomized clinical MRSA). Optimal strategies for screening for S. aureus and
trial demonstrated a nonsignificant reduction in the rate of decolonization for certain procedures need to be identified.
postoperative S. aureus SSIs in patients receiving mupirocin Finally, outcomes studies are needed to assess the impact of
(n = 315, 3.8%) compared with those receiving placebo (n using quality measures and pay-for-performance incentives
= 299, 4.7%).150 designed to reduce surgical morbidity and mortality.
A recent randomized, double-blind, placebo-controlled,
multicenter study conducted in the Netherlands found that
the use of mupirocin nasal ointment and chlorhexidine Cardiac Procedures
baths in identified S. aureus carriers reduced the risk of
hospital-associated S. aureus infections.162 In the study, a Background. Cardiac procedures include CABG proce-
real-time PCR assay was used to rapidly identify S. aureus dures, valve repairs, and placement of temporary or per-
nasal carriers; all of the S. aureus isolates were susceptible manent implantable cardiac devices, including ventricular
to methicillin. Deep SSIs occurred in 0.9% of the mupiro- assist devices (VADs). SSIs, including mediastinitis and
sternal wound infection, are rare but serious complications microbial prophylaxis in institutions that have a high preva-
after cardiac procedures. In patients undergoing CABG, the lence of MRSA.8,11,41,72,73,116,200 Vancomycin should be con-
mean frequency of SSIs depending on NHSN SSI risk index sidered in patients who are colonized with MRSA.41,116,201
category ranges from 0.35 to 8.49 per 100 operations when The accepted alternative antimicrobial for b-lactam-allergic
donor sites are included.165 The mean frequency of SSIs de- patients undergoing cardiac procedures is vancomycin or
pending on NHSN SSI risk index category for patients un- clindamycin for gram-positive coverage.41,116,201,202 The ad-
dergoing CABG with only chest incisions ranges from 0.23 dition of an aminoglycoside, aztreonam, or a fluoroquino-
to 5.67 per 100 operations.165 Most of these infections are lone may be prudent when gram-negative pathogens are a
superficial in depth. Patient-related and procedure-related concern.8,116
risk factors for SSIs after cardiac procedures have been Mupirocin. The proportion of infections related to S.
identified from several single-center cohort and case–con- aureus among patients undergoing cardiac surgery and the
trol studies.117,128,166–176 These include diabetes,166,169,171–175 increase in MRSA as a cause of SSIs at some institutions
hyperglycemia,177–182 peripheral vascular disease,171,172,174 have led to investigations of methods for preoperative eradi-
chronic obstructive pulmonary disease,166,174,175 obesity cation, particularly with intranasal mupirocin.203 Readers are
(BMI of >30 kg/m2),166–168,171,173–176 heart failure,171,172 referred to the Common Principles section of these guide-
advanced age,117,128,166,172 involvement of internal mam- lines for discussion of the use of intranasal mupirocin. Of
mary artery,168–172 reoperation,169–171 increased number of note, the data demonstrated a 45% reduction in S. aureus
grafts,171 long duration of surgery,117,166,167,176 and S. aureus SSIs with the use of preoperative mupirocin among patients
nasal colonization.146,160 known to be colonized with S. aureus who undergo cardiac
Patients requiring extracorporeal membrane oxygen- procedures.157,193 Institutions should monitor for mupirocin
ation (ECMO) as a bridge to cardiac or lung transplantation resistance periodically.
should be treated with a similar approach. If there is no Topical administration. Additional information on
history of colonization or previous infection, the general topical administration of antimicrobials can be found in
recommendations for SSI antimicrobial prophylaxis for the
the Common Principles section of these guidelines. Use of
specific procedure should be followed. For ECMO patients
topical antimicrobials, mainly gentamicin or vancomycin,
with a history of colonization or previous infection, chang-
applied to the sternum during cardiac procedures in com-
ing the preoperative antimicrobial prophylaxis to cover
bination with i.v. agents to prevent mediastinitis has been
these pathogens must be considered, weighing whether the
evaluated in both cohort139 and randomized controlled stud-
pathogen is relevant to SSIs in the planned procedure.
ies.140–142 While the studies found a significantly lower rate
of SSIs with topical antimicrobials compared with stan-
Organisms. Almost two thirds of organisms isolated in both
dard prophylaxis,140 placebo,142 and a historical control,139
adult and pediatric patients undergoing cardiac procedures
a smaller randomized, placebo-controlled study found no
are gram-positive, including S. aureus, coagulase-negative
difference between groups.141 More recent studies of gen-
staphylococcus, and, rarely, Propionibacterium acnes. Gram-
negative organisms are less commonly isolated in these pa- tamicin collagen sponges failed to show any efficacy in a
tients and include Enterobacter species, Pseudomonas ae- large prospective study of cardiac surgery.143 The safety and
ruginosa, Escherichia coli, Klebsiella pneumoniae, Proteus efficacy of topical antimicrobials have not been clearly es-
mirabilis, and Acinetobacter species.93,139,146,183–192 tablished and therefore cannot be recommended for routine
use in cardiac procedures.139–142
Efficacy. The SSI rate in cardiac procedures is low, but there Cardiopulmonary bypass. Cardiopulmonary bypass
are potential consequences if infection occurs. Multiple (CPB) is a common surgical technique in cardiac procedures
studies have found that antimicrobial prophylaxis in cardiac that alters the volume of distribution and bioavailability of
procedures lowers the occurrence of postoperative SSI up medications administered during the procedure.116,204,205
to fivefold.125 Several small cohort or comparative studies128,204–213 have
Choice of agent. Cephalosporins have been the most evaluated the serum and tissue concentrations of several rou-
studied antimicrobials for the prevention of SSIs in cardiac tinely used antimicrobial prophylactic agents (i.e., cefazolin,
procedures. Both first-generation (cefazolin) and second- cefuroxime, gentamicin, and vancomycin) in patients under-
generation (cefamandole and cefuroxime) cephalosporins going CPB during cardiac procedures. Until further clinical
have been shown to be effective in reducing SSI in cardiac outcomes data and well-designed studies become available
surgery; however, the superiority of one class over another to inform alternative dosing strategies, routinely used doses
has not been proven.125,127,193–199 of common antimicrobial agents should be used in patients
A meta-analysis comparing cephalosporins with gly- undergoing CPB during cardiac procedures.
copeptides (e.g., vancomycin) as antimicrobial prophylaxis Duration. The optimal duration of antimicrobial pro-
regimens for cardiac procedures found a higher frequency of phylaxis for cardiac procedures continues to be evaluated.
postoperative chest and deep-chest SSIs and a trend toward Data support a duration ranging from a single dose up to
an increased risk of gram-positive SSI in the glycopeptide 24 hours postoperatively.41,99,131,191,214–217 No significant dif-
group but a lower frequency of SSIs caused by resistant ferences were found in several small studies in patients un-
gram-positive pathogens.72 The routine use of vancomy- dergoing cardiac procedures between these dosing strategies
cin for the prevention of SSIs is not recommended, based in patients primarily receiving first- or second-generation
on limited evidence of efficacy and concerns of increased cephalosporins. Although a recent meta-analysis suggested
glycopeptide resistance of microorganisms.8,116 There is no the possibility of increased efficacy with cardiac surgical
clear evidence to support the use of vancomycin, alone or prophylaxis extending beyond 24 hours, the authors noted
in combination with other antimicrobials, for routine anti- that the findings were limited by the heterogeneity of an-
timicrobial regimens used and the risk of bias in the pub- six months can be 6.5–7.5 mg/kg and that dosing schedules
lished studies.218 The comparisons of varying durations for younger patients may be complicated.
were performed with different antimicrobials with differing
efficacy and do not support longer durations. Consequently, Recommendations. For patients undergoing cardiac proce-
this meta-analysis does not provide evidence to support dures, the recommended regimen is a single preincision dose
changing the currently accepted prophylaxis duration of less of cefazolin or cefuroxime with appropriate intraoperative
than 24 hours, particularly given the evidence from studies redosing (Table 2). Currently, there is no evidence to sup-
involving noncardiac operations. The currently accepted du- port continuing prophylaxis until all drains and indwelling
ration of prophylaxis for cardiac procedures is less than 24 catheters are removed. Clindamycin or vancomycin is an ac-
hours, but prophylaxis should be continued for the duration ceptable alternative in patients with a documented b-lactam
of the procedure.41,59,126–129,131,201 allergy. Vancomycin should be used for prophylaxis in pa-
Two small studies did not support the continuation of tients known to be colonized with MRSA. If organizational
antimicrobial prophylaxis until intravascular catheters or in- SSI surveillance shows that gram-negative organisms cause
traaortic balloon pumps were removed, due to a lack of in- infections for patients undergoing these operations, practi-
fluence on infections or catheter colonization compared with tioners should combine clindamycin or vancomycin with
short-course (24 hours) cefazolin or cefuroxime.219,220 The another agent (cefazolin if the patient is not b-lactam aller-
practice of continuing antimicrobial prophylaxis until all in- gic; aztreonam, aminoglycoside, or single-dose fluoroquino-
vasive lines, drains, and indwelling catheters are removed lone if the patient is b-lactam allergic). Mupirocin should be
cannot be supported due to concerns regarding the develop- given intranasally to all patients with documented S. aureus
ment of drug-resistant organisms, superinfections, and drug colonization. (Strength of evidence for prophylaxis = A.)
toxicity.41,131
Cardiac Device Insertion Procedures
Pediatric Efficacy. The rate of SSI in pediatric cardiac pro-
cedures is sometimes higher than in adult patients.20,31,221 Background. Antimicrobial prophylaxis is the standard of
Significant risk factors in pediatric patients with a mediasti- care for patients undergoing cardiac implantable device in-
nal SSI included the presence of other infections at the time sertion (e.g., pacemaker implantation).227 Based on available
of the procedure, young age (newborns and infants), small data and perceived infection risk, antimicrobial prophylaxis
body size, the duration of the procedure (including CPB is not routinely recommended for cardiac catheterization or
time), the need for an intraoperative blood transfusion, an transesophageal echocardiogram.228
open sternum postoperatively, the need for a reexploration NHSN has reported a mean SSI rate after pacemaker
procedure, the length of stay in the intensive care unit, an placement of 0.44 per 100 procedures.165 This rate may under-
NNIS/NHSN risk score of 2, and the performance of emer- estimate the risk of late SSI and complications.229 Risk factors
gency procedures.20,31,221 for device-related infection after implantation of cardioverter–
The organisms of concern in pediatric patients are the defibrillator systems or pacemakers identified in two large,
same as those in adult patients.20,21,31,221 However, MRSA prospective, multicenter cohort studies230,231 and a large
is rarely a concern in this population as a risk factor for case–control study232 included fever within 24 hours before
SSI.221 Pediatric patients considered at high risk for MRSA implantation, temporary pacing before implantation, and
infection are those with preoperative MRSA colonization early reintervention for hematoma or lead replacement230;
or a history of MRSA infection, neonates younger than one corticosteroid use for more than one month during the pre-
month of age, and neonates under three months of age who ceding year and more than two leads in place compared with
have been in the hospital since birth or have a complex car- two leads232; and development of pocket hematoma.231 In all
diac disorder.21 Strategies such as intranasal mupirocin and of the evaluations, antimicrobial prophylaxis was found to
changes in antimicrobial prophylactic agent to vancomycin be protective against device-related infection.230–232 Limited
led to decreased rates of MRSA carriage and the absence of data are available on the efficacy and optimal dose and du-
MRSA infections in one time-series evaluation; however, the ration of antimicrobial prophylaxis in patients undergoing
overall clinical impact of these efforts is still unclear.21,221 implantation of a new pacemaker, pacing system, or other
No well-controlled studies have evaluated the efficacy cardiac device.
of antimicrobial prophylaxis in pediatric patients undergoing A meta-analysis of 15 prospective, randomized, con-
cardiac procedures. Therefore, the efficacy of antimicrobial trolled, mainly open-label studies evaluated the effective-
prophylaxis is extrapolated from adult studies and should be ness of systemic antimicrobial prophylaxis compared with
considered the standard of care for pediatric cardiac surgery controls (no antimicrobials) on infection rates after pace-
patients.19 maker implantation.227 Antibiotics included penicillins or
No well-designed studies or consensus has established cephalosporins with a duration ranging from a single preop-
the appropriate doses for common antimicrobial prophylac- erative dose to four days postoperatively. A consistent and
tic agents for use in pediatric cardiac patients. Antibiotic significant protective effect of antimicrobial prophylaxis
doses have been extrapolated from guidelines for the pre- was found and encouraged the routine use of antimicrobial
vention of bacterial endocarditis.11 In recent evaluations, prophylaxis in patients undergoing permanent pacemaker
doses of cefazolin have ranged from 25 to 50 mg/kg,19–21,31 implantation. A prospective, single-center cohort study
and vancomycin doses have ranged from 10 to 20 mg/kg.19– found a low rate (1.7%) of SSI complications with a single
21,31,222–226
Gentamicin doses used in studies have included 2-g dose of cefazolin in patients undergoing implantation of
2.520 and 5 mg/kg22; however, the study authors22 felt that a new pacemaker, pulse-generator replacement, or upgrad-
the higher dose was excessive. The expert panel recognizes ing of a preexisting pacing system.233 A notable limitation
that the usual total daily dose for pediatric patients older than of the study was the exclusion of patients with temporary
percutanous cardiac stimulators who are at high risk of in- Studies have found that the reported rate of SSIs after tho-
fection. racic procedures in patients receiving antimicrobial prophy-
A large, randomized, double-blind, placebo-controlled laxis ranged from 0.42% to 4%.238–241 One study found an
study found a significantly lower rate of SSI with a single 1-g SSI rate of 14% when prophylaxis was not used.239 The re-
dose of cefazolin (0.64%) compared with placebo (3.28%) ported rates of pneumonia and empyema with antimicrobial
(p = 0.016) given immediately before device implantation or prophylaxis are 3–24% and 0–7%, respectively.237,239–244
generator replacement in a permanent pacemaker, implant- Video-assisted thoracoscopic surgery (VATS) is com-
able cardioverter defibrillator, or cardiac resynchronization monly used for thoracic procedures. In some settings, VATS
device in a surgical operating room.231 The expert panel constitutes one third or more of all thoracic surgical proce-
noted that the cefazolin dose was not adjusted for patient dures.245 Since VATS uses small incisions, the rate of SSIs
weight. Recently, AHA produced evidence-based guidelines is lower compared with the rate associated with open tho-
that recommend the use of a single dose of a preoperative racic surgical procedures.246 A prospective cohort study (n
antimicrobial.229 = 346) confirmed a low rate of SSIs (1.7%) after minimally
VADs are increasingly used to bridge patients to trans- invasive VATS procedures.240 An additional prospective
plantation or to support individuals who do not respond to study of 988 lung resection patients confirmed that the SSI
medical therapy for congestive heart failure. Very limited rate was significantly lower (5.5%) in VATS patients than
data exist on infection rates, and there are no published stud- in open thoracotomy patients (14.3%).247 Furthermore, SSI
ies that demonstrate the effectiveness of preoperative anti- correlated with the duration of surgery, serum albumin, con-
microbial therapy. Using 2006–08 data from the Interagency current comorbidity, age, and forced expiratory volume in
Registry for Mechanically Assisted Circulatory Support, one second. Antimicrobial prophylaxis recommendations in
Holman and colleagues234 reported that most infections re- this section refer to both open thoracotomy and VATS proce-
lated to mechanical cardiac support devices were bacterial dures. Based on available data and perceived infection risk,
(87%), with the remainder associated with fungal (9%), viral antimicrobial prophylaxis is not routinely recommended for
(1%), protozoal (0.3%), or unknown (2%) causes. Driveline chest tube insertion.
infections are primarily caused by staphylococcal species Results of a prospective cohort and case–control study
from the skin. Fungal organisms also play an important role revealed the following independent risk factors for pneu-
in VAD infections, most notably Candida species, and carry monia after thoracic procedures: extent of lung resection,
a high risk of mortality. A recent survey of antimicrobial sur- intraoperative bronchial colonization, chronic obstructive
gical prophylaxis with VADs illustrates the variability and pulmonary disease, BMI of >25 kg/m2, induction therapy
lack of consensus with regimens, using anywhere from one (chemotherapy, radiotherapy, or chemoradiotherapy), ad-
to four drugs for a duration of 24–72 hours.235 Immediate vanced age (≥75 years old), and stage III or IV cancer.243,244
postoperative infections are caused by gram-positive organ-
isms. Complications from long-term infections should not Organisms. The organisms reported from SSIs in patients
be confused with immediate postprocedure SSIs.236 Based undergoing thoracic procedures were S. aureus and S. epi-
on the consensus of the expert panel, antimicrobial prophy- dermidis.237 Organisms isolated in patients with postopera-
laxis for replacement of a VAD due to ongoing or recent tive pneumonia included gram-positive (Streptococcus and
infection should incorporate coverage directed at the offend- Staphylococcus species), gram-negative (Haemophilus influ-
ing organism or organisms. While many centers use vanco- enzae, Enterobacter cloacae, K. pneumoniae, Acinetobacter
mycin plus ciprofloxacin plus fluconazole, this practice is species, P. aeruginosa, and Moraxella catarrhalis), and fun-
not based on the published evidence. gal (Candida species) pathogens.237,239–243
Recommendation. A single dose of cefazolin or cefurox- Efficacy. Antimicrobial prophylaxis is the standard of care
ime is recommended for device implantation or generator for patients undergoing noncardiac thoracic surgery, includ-
replacement in a permanent pacemaker, implantable caring pulmonary resection.11,201,237 One randomized, double-
dioverter defibrillator, or cardiac resynchronization device. blind, placebo-controlled, single-center study of patients in
(Strength of evidence for prophylaxis = A.) There is lim- Spain undergoing pulmonary resection, persistent pneumo-
ited evidence to make specific recommendations for VADs, thorax without thoracotomy tube before surgery, and non-
and each practice should tailor protocols based on pathogen pulmonary thoracic surgical procedures, excluding those
prevalence and local susceptibility profiles. Clindamycin or involving the esophagus and exploratory thoracotomies,
vancomycin is an acceptable alternative in patients with a compared a single dose of cefazolin 1 g i.v. and placebo
documented b-lactam allergy. Vancomycin should be con- given 30 minutes before the procedure.239 The study was
sidered for prophylaxis in patients known to be colonized stopped early due to the significant difference in SSI rates
with MRSA. between groups (1.5% with cefazolin versus 14% with pla-
cebo, p < 0.01). No differences in the rates of pneumonia
Thoracic Procedures and empyema were seen between groups, but these were not
endpoints of the study.
Background. Noncardiac thoracic procedures include lo- Choice of agent. There is no clear optimal choice for
bectomy, pneumonectomy, thoracoscopy, lung resection, antimicrobial prophylaxis in thoracic procedures. The need
and thoracotomy. In addition to SSIs, postoperative nosoco- to consider pneumonia and empyema as well as SSIs after
mial pneumonia and empyema are of concern after thoracic thoracic procedures has been raised in the literature.237,241–244
procedures.237 There are a limited number of small, single-center, random-
NHSN has reported that the rate of infection associ- ized controlled or cohort studies that evaluated several anti-
ated with thoracic surgery ranges from 0.76% to 2.04%.165 microbial agents. One small, randomized controlled study
and one cohort study found that ampicillin–sulbactam was (NOTES) is a developing operative technique using natural
significantly better than cephalosporins (cefazolin and ce- orifices (e.g., vagina, anus, mouth, stomach) for entry into
famandole) for preventing pneumonia.242,243 No statisti- the abdomen that leaves no visible scar.248 No studies on an-
cally significant difference was found between cefuroxime timicrobial prophylaxis using NOTES have been published.
and cefepime in the rate of postoperative SSI, pneumonia, SSI rates reported in patients not receiving antimicrobial
or empyema in a small, randomized controlled study in pa- prophylaxis were 6% after vagotomy and drainage, 13% af-
tients undergoing elective thoracotomy.241 Lower rates of inter gastric ulcer procedures, 6.8–17% after procedures for
fections and susceptibility of all organisms were noted with gastric cancer,249–253 8% for pancreaticoduodenectomy,254
cefuroxime compared with cefepime. Therefore, the study and 23.9–26% after PEG insertion.255,256
authors concluded that cefuroxime was marginally more ef- The stomach is an effective barrier to bacterial colo-
fective and was more cost-effective than cefepime. nization; this is at least partially related to its acidity. The
Duration. No clear consensus on the duration of an- stomach and the duodenum typically contain small num-
timicrobial prophylaxis has been established. Studies have bers of organisms (<104 colony-forming units [CFU]/mL),
evaluated different dosing strategies for cephalosporins the most common of which are streptococci, lactobacilli,
or penicillins, with most studies using single doses given diphtheroids, and fungi.257,258 Treatment with agents that
preoperatively within 60 minutes before surgical inci- increase gastric pH increases the concentration of gastric or-
sion.237,239,240,242,244 Studies found differing results when ganisms.259–261 Alterations in gastric and duodenal bacterial
comparing agents given for 24 hours (cefepime, ampicil- flora as a result of increases in gastric pH have the potential
lin–sulbactam) and 48 hours (cefuroxime, cefamandole); to increase the postoperative infection rate.262,263
however, these findings may be attributable to the different The risk of postoperative infection in gastroduodenal
antimicrobials tested.241,243 Additional discussion on dos- procedures depends on a number of factors, including the
ing is provided in the Common Principles section of these gastroduodenal procedure performed. Patients who are at
guidelines. highest risk include those with achlorhydria, including those
receiving pharmacotherapy with histamine H2-receptor an-
Recommendations. In patients undergoing thoracic tagonists or proton-pump inhibitors,264 gastroduodenal per-
procedures, a single dose of cefazolin or ampicillin– foration, decreased gastric motility, gastric outlet obstruc-
sulbactam is recommended (Appendix B). Clindamycin or tion, morbid obesity, gastric bleeding, or cancer.265 Similar
vancomycin is an acceptable alternative in patients with a to other types of surgical procedures, risk factors for SSIs
documented b-lactam allergy. Vancomycin should be used related to gastroduodenal procedures include long proce-
for prophylaxis in patients known to be colonized with dure duration,252,266,267 performance of emergency proce-
MRSA. If organizational SSI surveillance shows that gram- dures,250,261 greater than normal blood loss,251,252 American
negative organisms are associated with infections during Society of Anesthesiologists (ASA) classification of ≥3, and
these operations or if there is risk of gram-negative con- late administration of antimicrobials.268
tamination of the surgical site, practitioners should combine
clindamycin or vancomycin with another agent (cefazolin if Organisms. The most common organisms cultured from SSIs
the patient is not b-lactam allergic; aztreonam, aminoglyco- after gastroduodenal procedures are coliforms (E. coli, Proteus
side, or single-dose fluoroquinolone if the patient is b-lactam species, Klebsiella species), staphylococci, streptococci, en-
allergic). (Strength of evidence for prophylaxis for VATS = terococci, and occasionally Bacteroides species.101,269–276
C; strength of evidence for prophylaxis for other thoracic
procedures = A.) Efficacy. Randomized controlled trials have shown that
prophylactic antimicrobials are effective in decreasing
Gastroduodenal Procedures postoperative infection rates in high-risk patients after gas-
troduodenal procedures. The majority of available stud-
Background. The gastroduodenal procedures considered in ies were conducted in single centers outside of the United
these guidelines include resection with or without vagotomy States. Relative to other types of gastrointestinal tract pro-
for gastric or duodenal ulcers, resection for gastric carci- cedures, the number of clinical trials evaluating antimicro-
noma, revision required to repair strictures of the gastric bial prophylaxis for gastroduodenal procedures is limited.
outlet, percutaneous endoscopic gastrostomy (PEG) inser- In placebo-controlled trials, infection rates ranged from
tion, perforated ulcer procedures (i.e., Graham patch repair), 0% to 22% for patients receiving cephalosporins or peni-
pancreaticoduodenectomy (Whipple procedure), and bar- cillins and from 1.7% to 66% for patients receiving pla-
iatric surgical procedures (gastric bypass, gastric banding, cebo.270,271,273–275,277–284 The difference was significant in
gastroplasty, other restrictive procedures, biliopancreatic most studies.
diversion). Studies specifically addressing antimicrobial Data support antimicrobial prophylaxis for patients
prophylaxis for gastroesophageal reflux disease procedures undergoing PEG insertion.264,285–287 A Cochrane review of
(Nissen fundoplication) or highly selective vagotomy for systemic antimicrobial prophylaxis for PEG procedures that
ulcers (usually done laparoscopically) could not be identi- included 11 randomized controlled trials and 1196 patients
fied. Antireflux procedures and highly selective vagotomy found a statistically significant reduction in peristomal in-
are clean procedures in contrast to essentially all other gas- fections with antimicrobial prophylaxis (OR, 0.35; 95%
troduodenal procedures that are clean-contaminated. Other CI, 0.23–0.48).288 Two meta-analyses found statistically
procedures that are generally performed using laparoscopic significant decreases in SSIs with antimicrobial prophy-
or endoscopic techniques (e.g., endoscopic retrograde chol- laxis compared with placebo or controls, from 23.9–26% to
angiopancreatography) are not specifically discussed in this 6.4–8%, respectively.255,256 Most well-designed, randomized
document. Natural orifice transluminal endoscopic surgery controlled studies found a significant decrease in postopera-
tive SSIs or peristomal infections with single i.v. doses of a found that piperacillin–tazobactam in combination with
cephalosporin or penicillin, ranging from 11% to 17%, com- ciprofloxacin or gentamicin was the most active regimen
pared with from 18% to 66% with placebo or no antimicro- against bacteria recovered from bile in pancreatoduodenec-
bials.279–282,288 Conflicting results have been seen in studies tomy patients.302
evaluating the use of preoperative patient MRSA screening, Duration. The majority of studies evaluated a single
decontamination washes and shampoos, five-day preopera- dose of cephalosporin or penicillin.256,279–284,288,290,297 The
tive treatment with intranasal mupirocin, and single-dose available data indicate that single-dose and multiple-dose
teicoplanin preoperative prophylaxis to decrease postopera- regimens are similarly effective. Three studies compared
tive MRSA infections during PEG insertion.289,290 single- and multiple-dose regimens of cefamandole,294
While there have been no well-designed clinical tri- amoxicillin–cluvulanate,299 and ampicillin–sulbactam and
als of antimicrobial prophylaxis for patients undergoing cefazolin.253 There were no significant differences in SSI
bariatric surgical procedures, treatment guidelines support rates. Multiple-dose regimens of first-generation (cefazo-
its use based on morbid obesity and additional comorbidi- lin) or second-generation (cefotiam) cephalosporins of four
ties as risk factors for postoperative infections.264,291 There days, operative day only, and three days in duration did not
is no consensus on the appropriate antimicrobial regimen; differ in overall SSI rates.295
however, higher doses of antimicrobials may be needed for
adequate serum and tissue concentrations in morbidly obese Recommendations. Antimicrobial prophylaxis in gastrodu-
patients.13,268,291 odenal procedures should be considered for patients at high-
A notable risk factor for SSIs after esophageal and est risk for postoperative infections, including risk factors
gastroduodenal procedures is decreased gastric acidity and such as increased gastric pH (e.g., patients receiving acid-
motility resulting from malignancy or acid-suppression ther- suppression therapy), gastroduodenal perforation, decreased
apy.264,276 Therefore, antimicrobial prophylaxis is indicated gastric motility, gastric outlet obstruction, gastric bleeding,
for patients undergoing gastric cancer procedures (including morbid obesity, ASA classification of ≥3, and cancer.
gastrectomy) and gastroduodenal procedures related to gas- A single dose of cefazolin is recommended in proce-
tric and duodenal ulcer disease or bariatric surgery or pan- dures during which the lumen of the intestinal tract is en-
creaticoduodenectomy. Evaluations of practice for pancre- tered (Table 2). (Strength of evidence for prophylaxis = A.)
aticoduodenectomy show that antimicrobials are typically A single dose of cefazolin is recommended in clean proce-
given due to concerns of bile contamination. Prophylaxis for dures, such as highly selective vagotomy, and antireflux pro-
gastroduodenal procedures that do not enter the gastrointes- cedures only in patients at high risk of postoperative infec-
tinal tract, such as antireflux procedures, should be limited tion due to the presence of the above risk factors. (Strength
to high-risk patients due to lack of data supporting general of evidence for prophylaxis = C.) Alternative regimens for
use in all patients. Furthermore, laparoscopic antireflux patients with b-lactam allergy include clindamycin or van-
procedures are associated with very low SSI rates (0.3%) comycin plus gentamicin, aztreonam, or a fluoroquinolone.
compared with open antireflux procedures (1.4%), just as Higher doses of antimicrobials are uniformly recommended
laparoscopic gastric bypass procedures are associated with in morbidly obese patients undergoing bariatric procedures.
lower rates than in open procedures (0.4% versus 1.2%).292 Higher doses of antimicrobials should be considered in sig-
Choice of agent. The most frequently used nificantly overweight patients undergoing gastroduodenal
agents for gastroduodenal procedures were first- and endoscopic procedures.
generation271,273,277,278,284,293–297 and second-genera-
tion269,270,274,275,280,293,294,298 cephalosporins. No differences
in efficacy between first- and second-generation cephalo- Biliary Tract Procedures
sporins were found. Amoxicillin–clavulanate279,282,283,299 and
ciprofloxacin269,300 were also evaluated with similar results. Background. Biliary tract procedures include cholecystec-
Relatively few studies have compared the efficacy of differ- tomy, exploration of the common bile duct, and choledo-
ent agents in reducing postoperative infection rates. choenterostomy. These guidelines pertain only to patients
One meta-analysis recommended using a single dose undergoing biliary tract procedures with no evidence of
of an i.v. broad-spectrum antimicrobial for SSI prophylaxis acute biliary tract infection and to patients with community-
in these patients,256 while another found no differences be- acquired acute cholecystitis of mild-to-moderate severity.
As noted in the Common Principles section, patients receiv-
tween penicillin- or cephalosporin-based regimens and three-
dose or single-dose regimens.255 In a comparative study, oral ing therapeutic antimicrobials for an infection before sur-
or i.v. ciprofloxacin and i.v. cefuroxime were similarly ef- gery should be given additional antimicrobial prophylaxis
fective in upper gastrointestinal procedures, including gas- before surgery.
trectomy, vagotomy, and fundoplication.300 No differences These guidelines do not address patients requiring bili-
ary tract procedures for more-severe infections, including
in efficacy were seen between ceftriaxone and combination
community-acquired acute cholecystitis with severe physi-
ceftriaxone and metronidazole for PEG insertion in pediatric
ological disturbance, advanced age, or immunocompro-
patients.301 An open-label study found a significant decrease
mised state; acute cholangitis; and health-care-associated or
in local peristomal and systemic infection (i.e., pneumonia)
nosocomial biliary infections. These biliary tract infections
after PEG insertion after a single 1-g i.v. dose of ceftriaxone
are treated as complicated intraabdominal infections.303 All
was given 30 minutes before surgery when compared with
placebo (13.3% and 36.3%, respectively; p < 0.05).281 No patients with a suspected biliary tract infection who undergo
biliary tract surgery should receive preoperative i.v. antimi-
differences were noted between cefotaxime and piperacillin–
crobials.
tazobactam for PEG SSIs.288 Ampicillin–sulbactam and
The majority of published literature regarding SSIs
cefazolin had equal efficacy in gastrectomy.253 One study
in biliary tract procedures focuses on cholecystectomy.
The overall reported rate of postoperative infection in open and dosage regimens were at the discretion of the medical
biliary tract procedures with antimicrobial prophylaxis is center and surgeon. Antimicrobials used included first-,
1–19%.292,304–311 Infection rates after laparoscopic chole- second-, and third-generation cephalosporins or penicillins
cystectomy range from 0% to approximately 4% in pa- alone or in combination with metronidazole, gentamicin,
tients without antimicrobial prophylaxis308,312–320 and from or both metronidazole and gentamicin. The most common
0% to 7% with prophylaxis.292,304–323 Several studies found cephalosporin used was ceftriaxone, allowing its data to be
that laparoscopic cholecystectomy SSI rates were signifi- separated from data for other antimicrobials. Antimicrobial
cantly lower than those associated with open cholecystec- prophylaxis was administered to 2217 patients (ceftriaxone
tomy.292,306–311 [n = 787 laparoscopic and n = 188 open] and other antimi-
Risk factors associated with postoperative SSIs after crobials [n = 229 laparoscopic and n = 229 open]); none was
biliary procedures include performance of emergency pro- given to 1328 laparoscopic and 932 open cholecystectomy
cedures,305 diabetes,305,306,311,315,317 longer procedure dura- patients. Significantly lower overall infectious complica-
tion (over 120 minutes),305,317,324 intraoperative gallbladder tions occurred in patients receiving antimicrobial prophy-
rupture,305 age of >70 years,6,311,315,317,325 open cholecys- laxis (0.8% ceftriaxone and 1.2% other antimicrobials),
tectomy,7,311 conversion of laparoscopic to open cholecys- compared with 5% of those who received no prophylaxis (p
tectomy,7 higher ASA classification (≥3),306,310,317 episode < 0.05). The overall rates of infectious complications were
of biliary colic within 30 days before the procedure,315,316 0.6%, 0.8%, and 3.3% in patients undergoing laparoscopic
reintervention in less than a month for noninfectious com- cholecystectomy receiving ceftriaxone, other antimicrobi-
plications,310 acute cholecystitis,6,7,306 bile spillage,7 jaun- als, and no prophylaxis, respectively, and 1.6%, 3.9%, and
dice,6,7,306 pregnancy,7 nonfunctioning gallbladder,6 and im- 7.4%, respectively, for patients undergoing open cholecys-
munosuppression.7 tectomy. Significantly lower rates of SSIs and postoperative
The biliary tract is usually sterile. Patients with bacte- pneumonia were noted in patients receiving antimicrobials
ria in the bile at the time of surgery may be at higher risk of compared with those who did not receive prophylaxis (p <
postoperative infection305,326,327; however, some studies have 0.05). SSI rates were significantly decreased in laparoscopic
found no association between the presence of bacteria in the cholecystectomy patients who received ceftriaxone (0.1%)
bile and infection.305,315,316,319,321 Obesity (a BMI of >30 kg/ or other antimicrobials (0.2%) compared with those who re-
m2) was found to be a risk factor in some studies306 but not in ceived no antimicrobial prophylaxis (1.6%). SSI rates were
others.315,319 Laparoscopic cholecystectomy was associated significantly decreased in open cholecystectomy patients
with a significantly decreased risk for SSI.292,310,324,325 who received ceftriaxone (1.0%) or other antimicrobials
(2.6%) compared with those who received no antimicrobial
Organisms. The organisms most commonly associated prophylaxis (4.4%). The study authors concluded that anti-
with infection after biliary tract procedures include E. coli, microbial prophylaxis should be administered to all patients
Klebsiella species, and enterococci; less frequently, other undergoing cholecystectomy, regardless of approach. The
gram-negative organisms, streptococci, and staphylococci study had several limitations, including lack of randomiza-
are isolated.305,306,312,315,316,318,319,321,326,328–338 Anaerobes are tion, lack of adequate controls, and lack of clear definition of
occasionally reported, most commonly Clostridium species. patient selection for the antimicrobial regimens. The statisti-
Recent studies have documented increasing antimi- cal analysis was not clearly defined. The study appears to
crobial resistance in the causative pathogens in biliary tract have compared only the use and lack of use of antimicrobi-
infections and other intra-abdominal infections, with up to als (with ceftriaxone and other antimicrobials combined for
40% of E. coli isolates resistant to ampicillin–sulbactam and analysis) and did not specifically compare the laparoscopic
fluoroquinolones.339–341 Due to this increasing resistance of and open approaches.
E. coli to fluoroquinolones and ampicillin–sulbactam, lo- The findings of this study contrast with those of sev-
cal population susceptibility profiles should be reviewed to eral other published studies. A meta-analysis of 15 random-
determine the optimal antimicrobials for SSI prevention in ized controlled studies evaluated the need for antimicrobial
biliary tract procedures. prophylaxis in elective laparoscopic cholecystectomy for
patients at low risk of infection.313 Low risk was defined
Efficacy. Numerous studies have evaluated the use of pro- as not having any of the following: acute cholecystitis, a
phylactic antimicrobials during biliary tract procedures, with history of acute cholecystitis, common bile duct calculi,
a focus on laparoscopic cholecystectomy. Laparoscopic cho- jaundice, immune suppression, and prosthetic implants. A
lecystectomy has replaced open cholecystectomy as the stan- total of 2961 patients were enrolled in the studies, includ-
dard of practice because of the reduction in recovery time ing 1494 who received antimicrobial prophylaxis, primarily
and shorter hospital stay. The majority of studies of antimi- with cephalosporins, vancomycin, fluoroquinolones, met-
crobial prophylaxis for laparoscopic cholecystectomy were ronidazole, and amoxicillin–clavulanate, and 1467 controls
underpowered and varied in control groups used (placebo, receiving placebo or no treatment. No significant difference
active, or no treatment), follow-up (from 30 to 60 days, while was found in the rates of infectious complications (2.07% in
some studies did not clearly define length of time), and how patients receiving antimicrobial prophylaxis versus 2.45% in
SSIs were detected and reported.308,312–316,318,319,321,322 Some controls) or SSIs (1.47% in patients receiving antimicrobial
studies included patients who were converted from laparo- prophylaxis versus 1.77% in controls). The authors of the
scopic to open cholecystectomy and others did not. meta-analysis concluded that antimicrobial prophylaxis was
A large, multicenter, quality-assurance study in not necessary for low-risk patients undergoing elective lapa-
Germany assessed the effectiveness of antimicrobial prophy- roscopic cholecystectomy. An additional meta-analysis of 9
laxis in laparoscopic and open cholecystectomies.308 This randomized controlled trials (n = 1437) also concluded that
study included 4477 patients whose antimicrobial choice
prophylactic antimicrobials do not prevent infections in low- sion. Additional doses were given as follows: one dose 12
risk patients undergoing laparoscopic cholecystectomy.342 hours after administration of the initial dose,352 two doses
A small, prospective, nonrandomized study compared 12 and 24 hours after administration of the initial dose,338
the use of cefotaxime 1 g i.v. during surgery with an ad- two doses every 6338 or 8317,319 hours after surgery, and one
ditional two i.v. doses given eight hours apart after surgery dose 24 hours after surgery315 and five days after surgery.352
(n = 80) with no antimicrobial prophylaxis (n = 86) in pa- In one study, a second dose of amoxicillin–clavulanate or
tients undergoing elective laparoscopic cholecystectomy cefotaxime was administered for procedures lasting longer
with accidental or incidental gallbladder rupture and spill- than 4 hours.354
age of bile.317 Patients who had spillage of gallstone calculi
or whose operations were converted to open operations were Recommendations. A single dose of cefazolin should be
excluded from the study. The rate of SSIs did not signifi- administered in patients undergoing open biliary tract pro-
cantly differ between treatment groups (2.5% with antimi- cedures (Table 2). (Strength of evidence for prophylaxis =
crobials versus 3.4% without antimicrobial prophylaxis). A.) Alternatives include ampicillin–sulbactam and other
Based on results of multivariate analysis, routine antimicro- cephalosporins (cefotetan, cefoxitin, and ceftriaxone).
bial prophylaxis was not recommended for these patients Alternative regimens for patients with b-lactam allergy in-
unless they were diabetic, were older than 60 years, or had clude clindamycin or vancomycin plus gentamicin, aztreo-
an ASA classification of ≥3 or the duration of the procedure nam, or a fluoroquinolone; or metronidazole plus gentami-
exceeded 70 minutes. cin or a fluoroquinolone.
Current data do not support antimicrobial prophylaxis Antimicrobial prophylaxis is not necessary in low-risk
for low-risk patients undergoing elective laparoscopic cho- patients undergoing elective laparoscopic cholecystecto-
lecystectomies or those with incidental or accidental gall- mies. (Strength of evidence against prophylaxis for low-risk
bladder rupture. Antimicrobial prophylaxis should be con- patients = A.) Antimicrobial prophylaxis is recommended
sidered for patients at high risk of infection, including those in patients undergoing laparoscopic cholecystectomy who
undergoing open cholecystectomy, as described above, or have an increased risk of infectious complications. Risk fac-
who are considered to be at high risk for conversion to an tors include performance of emergency procedures, diabe-
open procedure. tes, anticipated procedure duration exceeding 120 minutes,
Choice of agent. The data do not indicate a significant risk of intraoperative gallbladder rupture, age of >70 years,
difference among first-, second-, and third-generation ceph- open cholecystectomy, risk of conversion of laparoscopic to
alosporins. First-generation,307,308,312,315,319,323,330,336,338,343,344 open cholecystectomy, ASA classification of ≥3, episode of
second-generation,308,314,315,318,323,327–329,331,332,335,344–352 and biliary colic within 30 days before the procedure, reinterven-
third-generation308,309,315–317,321,322,332,333,338,349,353,354 cepha- tion in less than a month for noninfectious complications of
losporins have been studied more extensively than other prior biliary operation, acute cholecystitis, anticipated bile
antimicrobials. Limited data are available for ampicillin spillage, jaundice, pregnancy, nonfunctioning gallbladder,
with gentamicin,355 piperacillin,356 amoxicillin–clavula- and immunosuppression. Because some of these risk fac-
nate,305,338,351,354 ciprofloxacin,320,333,352,357 and cephalospo- tors cannot be determined before the surgical intervention,
rins or penicillins alone or in combination with metronida- it may be reasonable to give a single dose of antimicrobial
zole, gentamicin, or both metronidazole and gentamicin.308 prophylaxis to all patients undergoing laparoscopic chole-
Several studies have compared first-generation cystectomy. (Strength of evidence for prophylaxis for high-
cephalosporins with second- or third-generation risk patients = A.)
agents.315,336,338,344–347,353,358 With one exception,347 there
was no significant difference in efficacy among agents. Appendectomy Procedures
Other studies found no significant differences in efficacy
between ampicillin and cefamandole,335 ciprofloxacin and Background. Cases of appendicitis can be described as
ceftriaxone,333 amoxicillin–clavulanate and cefotaxime,354 complicated or uncomplicated on the basis of the pa-
amoxicillin–clavulanate and cefamandole,351 ceftriaxone thology. Patients with uncomplicated appendicitis have
and ceftazidime,321 and oral and i.v. ciprofloxacin and i.v. an acutely inflamed appendix. Complicated appen-
cefuroxime.352,357 One study found that i.v. ampicillin– dicitis includes perforated or gangrenous appendici-
sulbactam was associated with significantly lower rates of tis, including peritonitis or abscess formation. Because
infection compared with cefuroxime306 and that patients complicated appendicitis is treated as a complicated intra-
treated with oral ceftibuten had significantly lower infection abdominal infection,303 it has not been addressed separately
rates than those who received amoxicillin–clavulanate.338 in these guidelines. All patients with a suspected clinical di-
Duration. The effect of duration of prophylaxis on out- agnosis of appendicitis, even those with an uncomplicated
come has been evaluated. A single dose of a cephalosporin was case, should receive appropriate preoperative i.v. antimicro-
compared with multiple doses in several studies; no signifi- bials for SSI prevention, which, due to the common micro-
cant differences in efficacy were found.327,329,330,348,349,353,359 biology encountered, requires similar antimicrobial choices
The largest study compared one dose of cefuroxime with to those used to treat complicated appendicitis.
three doses in 1004 patients with risk factors for infection Approximately 80% of patients with appendicitis have
who were undergoing biliary tract surgery.327 There was no uncomplicated disease.59 SSI has been reported in 9–30% of
significant difference in the rates of minor or major SSIs be- patients with uncomplicated appendicitis who do not receive
tween the single- and multiple-dose groups. In the majority prophylactic antimicrobials, though some reports suggest
of studies, one dose of an antimicrobial was administered lower complication rates in children with uncomplicated
at induction of anesthesia,306,312,338,352,354 within 30 minutes appendicitis.165,360–365 Mean SSI rates for appendectomy re-
before incision,338 or 1315,316,320,321 or 2338 hours before inci- ported in the most recent NHSN report (2006–08) were 1.15%
(60 of 5211) for NHSN risk index categories 0 and 1 versus tals were similar. Patients who received both cefazolin and
3.47% (23 of 663) for NHSN risk index categories 2 and 3.165 metronidazole had a significantly lower infection rate com-
Laparoscopic appendectomy has been reported to produce pared with the other groups.384 Consistent with the antibac-
lower rates of incisional (superficial and deep) SSIs than terial spectrum of the agents, a prospective study of anti-
open appendectomy in adults and children in multiple meta- microbial prophylaxis for colorectal procedures found that
analyses and several randomized clinical trials.292,310,366–371 the combination of metronidazole with aztreonam did not
However, the rate of organ/space SSIs (i.e., intra- show adequate coverage of gram-positive organisms.385 The
abdominal abscesses) was significantly increased with lapa- Common Principles section of these guidelines provides ad-
roscopic appendectomy. ditional considerations for weight-based dosing.
Duration. In most of the studies of second- or third-
Organisms. The most common microorganisms isolated generation cephalosporins or metronidazole combinations,
from SSIs after appendectomy are anaerobic and aerobic a single dose376–378,380,383 or two or three doses364,379,382 were
gram-negative enteric organisms. Bacteroides fragilis is the given. Although direct comparisons were not made, there
most commonly cultured anaerobe, and E. coli is the most was no discernible difference in postoperative SSI rates
frequent aerobe, indicating that the bowel flora constitute between single-dose and multidose administration in most
a major source for pathogens.59,372,373 Aerobic and anaero- studies. A randomized trial specifically comparing differ-
bic streptococci, Staphylococcus species, and Enterococcus ent durations of regimens found no statistical difference be-
species also have been reported. P. aeruginosa has been re- tween a single preoperative dose, three doses (preoperative
ported infrequently. dose plus two additional doses), or a five-day regimen.386 A
large cohort study found that single doses of metronidazole
Efficacy. Antibiotic prophylaxis is generally recognized as and gentamicin in patients undergoing open appendectomy
effective in the prevention of postoperative SSIs in patients were effective and sufficient in decreasing the SSI rate.387
undergoing appendectomy when compared with placebo.374
Choice of agent. Randomized controlled trials have
Pediatric Efficacy. In pediatric patients, as with adults,
failed to identify an agent that is clearly superior to other
preoperative determination of complicated versus uncom-
agents in the prophylaxis of postappendectomy infectious
plicated appendicitis is difficult. A comprehensive review
complications. An appropriate choice for SSI prophylaxis
is not provided here, but this topic has been addressed by
in uncomplicated appendicitis would be any single agent or
SIS.388
combination of agents that provides adequate gram-negative
Two pediatric studies demonstrated no difference in
and anaerobic coverage. The second-generation cephalospo-
SSI rates between placebo and several antimicrobials. The
rins with anaerobic activity and a first-generation cephalo-
first study compared metronidazole, penicillin plus tobra-
sporin plus metronidazole are the recommended agents on
mycin, and piperacillin.389 The second study compared sin-
the basis of cost and tolerability. Given the relatively equiva-
gle-dose metronidazole and single-dose metronidazole plus
lent efficacy between agents, a cost-minimization approach
is reasonable; the choice of agents should be based on local cefuroxime.390 A meta-analysis including both adult and pe-
drug acquisition costs and antimicrobial sensitivity patterns. diatric studies found that for pediatric patients, antimicrobial
A wide range of antimicrobials have been evaluated prophylaxis trended toward being beneficial, but the results
for prophylaxis in uncomplicated appendicitis. The most were not statistically significant.374 A retrospective chart re-
commonly used agents were cephalosporins. In general, a view questioned the routine need for antimicrobial prophy-
second-generation cephalosporin with anaerobic activity laxis in children with simple appendicitis, due to relatively
(cefoxitin or cefotetan) or third-generation cephalosporins low infection rates in children not receiving prophylaxis.365
with partial anaerobic activity (cefotaxime) were effective, However, these and other study authors have suggested anti-
with postoperative SSI rates of <5% in most studies.364,375–381 microbial prophylaxis may be considered due to the morbid-
Piperacillin 2 g was comparable to cefoxitin 2 g in a ity associated with infectious complications (e.g., prolonged
well-controlled study.381 Metronidazole used alone was less hospitalization, readmission, reoperation) and due to the in-
effective than cefotaxime, with infection rates above 10%.376 ability to preoperatively identify appendicitis.
However, when metronidazole was combined with cefazo- As a single agent, metronidazole was no more effec-
lin, ampicillin,382 or gentamicin,378,383 the post-operative SSI tive than placebo in two double-blind studies that included
rates were 3–6%. children 10 years of age or older360 and 15 years of age or
A double-blind, randomized, controlled trial was older.363 In a randomized study that included pediatric pa-
conducted at two hospitals to evaluate the effect of metro- tients, ceftizoxime and cefamandole were associated with
nidazole, which is effective against most anaerobes, and significantly lower infection rates and duration of hospital-
cefazolin, which is effective against many aerobic organization than placebo.391 Both cefoxitin and a combination of
isms, singly and in combination, on the rate of sepsis after gentamicin and metronidazole were associated with a lower
appendectomy.384 Patients were randomized into one of four rate of postoperative infection in a randomized study that in-
groups: metronidazole and placebo, cefazolin and placebo, cluded pediatric patients younger than 16 years.378 Second-
metronidazole and cefazolin, or double placebo. Patients generation cephalosporins with anaerobic activity (cefoxi-
with generalized peritonitis were excluded for ethical rea- tin or cefotetan) and third-generation cephalosporins with
sons. Treatment was started before the procedure and con- anaerobic activity (cefotaxime) were effective, with post-
tinued every 8 hours for 24 hours. All patients in the trial operative infection rates of <5% in two studies that included
were followed for about two weeks after discharge from the pediatric patients younger than 12 years.364,378,379 A single
hospital, and their surgical sites were inspected. A total of dose of gentamicin with clindamycin was found to be safe
271 patients were assessed. Sepsis rates at the two hospi- and effective in children with simple appendicitis.392
Recommendations. For uncomplicated appendicitis, the rec- Staphylococcus species, and Enterococcus species also have
ommended regimen is a single dose of a cephalosporin with been reported.
anaerobic activity (cefoxitin or cefotetan) or a single dose The microbiology of 2280 SSIs after upper or lower
of a first-generation cephalosporin (cefazolin) plus metroni- abdominal surgery conducted from 1999 to 2006 was de-
dazole (Table 2). For b-lactam-allergic patients, alternative scribed in the Prevalence of Infections in Spanish Hospitals
regimens include (1) clindamycin plus gentamicin, aztreo- (EPINE) study.402 The most frequent microorganisms iso-
nam, or a fluoroquinolone and (2) metronidazole plus genta- lated were E. coli (28%), Enterococcus species (15%),
micin or a fluoroquinolone (ciprofloxacin or levofloxacin). Streptococcus species (8%), P. aeruginosa (7%), and S. au-
(Strength of evidence for prophylaxis = A.) reus (5%; resistant to methicillin, 2%). The microbiology
of SSIs after upper abdominal tract surgery did not show
Small Intestine Procedures any significant differences compared with SSIs of the lower
tract, though there were relatively more staphylococci, K.
Background. Small intestine procedures, or small bowel pneumoniae, Enterobacter species, Acinetobacter species,
surgery as defined by NHSN, include incision or resection and Candida albicans isolates and fewer E. coli, B. fragi-
of the small intestine, including enterectomy with or with- lis, and Clostridium species in the upper abdominal surgery
out intestinal anastomosis or enterostomy, intestinal bypass, group.402
and strictureoplasty; it does not include small-to-large bowel
anastomosis. Efficacy. Antibiotic prophylaxis is generally recognized as
The risk of SSI in small bowel surgery is variable. The effective in the prevention of postoperative SSIs in patients
Surgical Site Infection Surveillance Service in England (data undergoing small bowel surgery when compared with pla-
collected by 168 hospitals in 13 categories of surgical proce- cebo. However, there are no prospective placebo-controlled
dures between 1997 and 2002) reported an SSI rate of 8.9% trials to definitively establish the efficacy of prophylactic
(94 of 1056).393 Mean SSI rates for small bowel procedures antimicrobials in this patient population.
reported in the most recent NHSN report (2006–08) were Choice of agent. The antimicrobials selected for pro-
3.44% for NHSN risk index category 0 versus 6.75% for phylaxis must cover the expected pathogens for the small
NHSN risk index categories 1, 2, and 3. A study of 1472 intestine. The microbial ecology of the proximal small in-
patients undergoing bowel surgery (small bowel and colon) testine (i.e., jejunum) is similar to that of the duodenum,
at 31 U.S. academic medical centers between September and whereas the microbial flora of the ileum are similar to those
December 2002 found an SSI rate of 8.7% for all wound of the colon. In patients with small intestine obstruction, the
categories. For patients with clean-contaminated wounds, microbial flora are similar to those of the colon.
the SSI rate was 7.9%; for those with contaminated or dirty- No randomized controlled trials have confirmed that
infected wounds, the SSI rates were 12.0% and 20.4%, re- one antimicrobial agent is superior to other agents for SSI
spectively.394 prophylaxis in small bowel surgery. An appropriate antimi-
In a study of 178 penetrating stomach and small bowel crobial choice for SSI prophylaxis in small bowel surgery
injuries, 94% of which were operated on within six hours of is any single agent or combination of agents that provides
presentation, SSIs occurred in nearly 20% of cases. When adequate coverage for the small intestinal microbes. In pa-
associated colon injuries were excluded, SSIs occurred in tients with small bowel obstruction, additional coverage of
16% of gastric injuries and 13% of small bowel injuries. anaerobic bacteria is also desirable.
Although 74% of patients received antimicrobials, the spe- For small intestine procedures with no evidence of
cific timing of antimicrobial administration was not pro- obstruction, a first-generation cephalosporin (cefazolin) is
vided.395 Other studies of small bowel injury confirm similar recommended. For patients with small intestine obstruc-
SSI rates.396–400 tion, a first-generation cephalosporin with metronidazole or
Antimicrobial prophylaxis is recommended for a second-generation cephalosporin with anaerobic activity
small bowel surgery, based on inferring effectiveness (cefoxitin or cefotetan) is the recommended agent. The choice
from other clean-contaminated procedures. No specific of agents should be based on local drug acquisition costs and
prospective randomized studies could be identified that antimicrobial sensitivity patterns. The Common Principles
addressed antimicrobial prophylaxis for small bowel sur- section of these guidelines provides additional considerations
gery. Antimicrobial prophylaxis for small bowel surgical for weight-based dosing.
procedures related to a diagnosis of complicated intra- Duration. Preoperative dosing of antimicrobials for
abdominal infection is not addressed separately in these SSI prevention, with additional intraoperative antimicrobial
guidelines, as antimicrobial therapy for established intraab- dosing dependent on the duration of the operation and no
dominal infection should be initiated preoperatively. postoperative dosing, is recommended for patients undergo-
ing small bowel surgery.
Organisms. The most common microorganisms isolated
from SSIs after small bowel surgery are aerobic gram- Pediatric Efficacy. In pediatric patients, as with adults, an-
negative enteric organisms. Among the species isolated from timicrobial prophylaxis for SSI prevention in small bowel
patients with SSI after small intestine surgery are gram- surgery is recommended.
negative bacilli of gastrointestinal enteric origin (aerobic
and anaerobic) and gram-positive species, such as strepto- Recommendations. For small bowel surgery without ob-
cocci, staphylococci, and enterococci, which is consistent struction, the recommended regimen is a first-generation
with similar studies.401 E. coli is the most frequently identi- cephalosporin (cefazolin) (Table 2). For small bowel surgery
fied aerobe, indicating that the bowel flora constitute a ma- with intestinal obstruction, the recommended regimen is a
jor source of pathogens. Aerobic and anaerobic streptococci, cephalosporin with anaerobic activity (cefoxitin or cefotetan)
or the combination of a first-generation cephalosporin (ce- aerobic gram-positive organisms. Aerobic streptococci,
fazolin) plus metronidazole. For b-lactam-allergic patients, Staphylococcus species, and Enterococcus species are com-
alternative regimens include (1) clindamycin plus gentami- mon, and MRSA is commonly found in prosthetic mesh in-
cin, aztreonam, or a fluoroquinolone and (2) metronidazole fections.411
plus gentamicin or a fluoroquinolone (ciprofloxacin or levo-
floxacin). (Strength of evidence for prophylaxis = C.) Efficacy. Antibiotic prophylaxis is generally recognized as
effective when compared with placebo in the prevention of
Hernia Repair Procedures (Hernioplasty postoperative SSIs in patients undergoing herniorrhaphy and
hernioplasty.
and Herniorrhaphy) Choice of agent. Randomized controlled trials have
failed to identify an agent that is clearly superior to other
Background. All patients who undergo hernioplasty (pros-
agents for SSI prophylaxis in hernia repair. A first-genera-
thetic mesh repair of hernia) or herniorrhaphy (suture repair
tion cephalosporin is the recommended agent on the basis
of hernia) should receive appropriate preoperative i.v. an-
of cost and tolerability. The Common Principles section
timicrobials for SSI prevention. The risk of SSIs is higher
of these guidelines provides additional considerations for
in hernioplasty compared with herniorrhaphy.403 There is a
weight-based dosing.
significant risk of requiring prosthetic mesh removal in her-
Duration. Based on the evidence to date, a single pre-
nioplasty patients who develop an SSI, and determination of
operative dose of antimicrobial is recommended in hernio-
whether mesh placement will be required for hernia repair is
plasty and herniorrhaphy, with redosing as recommended in
not always possible in the preoperative period.
the Common Principles section of these guidelines (if the
Mean SSI rates for herniorrhaphy reported in the most
procedure duration exceeds the recommended redosing in-
recent NHSN report (2006–08) were 0.74% (21 of 2852) for
terval from the time of initiation of the preoperative dose or
NHSN risk index category 0, 2.42% (81 of 3348) for NHSN
if there is prolonged or excessive bleeding).
risk index category 1, and 5.25% (67 of 1277) for NHSN
risk index categories 2 and 3.165
Recommendations. For hernioplasty and herniorrhaphy, the
A Cochrane meta-analysis of 17 randomized trials (n =
recommended regimen is a single dose of a first-generation
7843; 11 hernioplasty trials, 6 herniorrhaphy trials) in elec-
cephalosporin (cefazolin) (Table 2). For patients known to
tive open inguinal hernia repair reported SSI rates of 3.1%
be colonized with MRSA, it is reasonable to add a single
versus 4.5% in the antimicrobial prophylaxis and control
preoperative dose of vancomycin to the recommended
groups, respectively (OR, 0.64; 95% CI, 0.50–0.82).404 The
agent. For b-lactam-allergic patients, alternative regimens
subgroup of patients with herniorrhaphy had SSI rates of
include clindamycin and vancomycin. (Strength of evidence
3.5% and 4.9% in the prophylaxis and control groups, re-
for prophylaxis = A.)
spectively (OR, 0.71; 95% CI, 0.51–1.00). The subgroup of
patients with hernioplasty had SSI rates of 2.4% and 4.2% in
the prophylaxis and control groups, respectively (OR, 0.56; Colorectal Procedures
95% CI, 0.38–0.81).
A meta-analysis of nine randomized trials of open her- Background. SSIs have been reported to occur in ap-
nioplasty for inguinal hernia documented SSI rates of 2.4% proximately 4–10% of patients undergoing colon proce-
(39 of 1642) in the antimicrobial group and 4.2% (70 of dures, 3–7% in small bowel procedures, and 3–27% in
1676) in the control group. Antibiotics showed a protective patients after rectal procedures, based on the risk index.165
effect in preventing SSI after mesh inguinal hernia repair However, when patients are followed carefully in clinical
(OR, 0.61; 95% CI, 0.40–0.92). Antibiotic prophylaxis did trials, rates tend to be considerably higher (17–26%).412
reduce the rate of SSI in hernia patients undergoing mesh Other septic complications, such as fecal fistula, intra-
hernioplasty.405 abdominal abscesses, peritonitis, and septicemia, are serious
Based on the results of these two systematic reviews, concerns but are much less common.413 Infectious complica-
preoperative antimicrobial prophylaxis for SSI prevention tion rates range from 30% to 60% without antimicrobial pro-
is recommended for both herniorrhaphy and hernioplasty. phylaxis59,414 and are <10% with appropriate antimicrobial
Compared with open hernia repair, laparoscopic hernia re- prophylaxis. A pooled analysis of clinical trials of antimicro-
pair has been reported to produce lower rates of incisional bial prophylaxis in colon procedures demonstrated that an-
(superficial and deep) SSIs in randomized clinical tri- timicrobial use significantly reduced mortality rates (11.2%
als.406–408 In a recent multicenter randomized trial of lapa- for control versus 4.5% for treatment) and SSI rates.415
roscopic versus open ventral incisional hernia repair (n = The type and duration of the procedure can affect the
162), SSI was significantly less common in the laparoscopic risk of infection. Rectal resection is associated with a higher
group than in the open repair group (2.8% versus 21.9%; risk of infection than is intraperitoneal colon resection.416–418
OR, 10.5; 95% CI, 2.3–48.2; p = 0.003).409 A meta-analysis Other risk factors include extended procedure duration (e.g.,
of eight randomized trials comparing laparoscopic and open >3.5 hours),59,412,418,419 impaired host defenses,418 age of >60
incisional or ventral hernia repair with mesh revealed that years,418 hypoalbuminemia,419,420 bacterial or fecal contami-
laparoscopic hernia repair was associated with decreased nation of the surgical site,418,420 inadvertent perforation or
SSI rates (relative risk, 0.22; 95% CI, 0.09–0.54) and a trend spillage,412,421 corticosteroid therapy,419 perioperative trans-
toward fewer infections requiring mesh removal.410 fusion of packed red blood cells,394,418 hypothermia,422 hy-
perglycemia,423,424 and obesity.412,418
Organisms. The most common microorganisms iso-
lated from SSIs after herniorrhaphy and hernioplasty are Organisms. The infecting organisms in colorectal proce-
dures are derived from the bowel lumen, where there are high
concentrations of organisms. B. fragilis and other obligate as is the current practice, was suggested as a possible reason
anaerobes are the most frequently isolated organisms from for the resistance and colitis observed.
the bowel, with concentrations 1,000–10,000 times higher I.V. regimens. A wide range of i.v. antimicrobials have
than those of aerobes.425 E. coli is the most common aerobe. been evaluated for prophylaxis in colorectal procedures.
B. fragilis and E. coli comprise approximately 20–30% of Cephalosporins are the most common agents, usually ad-
the fecal mass. They are the most frequently isolated patho- ministered as a single agent. The majority of studies found
gens from infected surgical sites after colon procedures. that single-agent first-generation cephalosporins (cefazolin
and cephalothin)445,448–451 were ineffective, with postopera-
Efficacy. Results from randomized controlled trials and tive SSI rates ranging from 12% to 39%.448,449 The lack of
a Cochrane review of 182 studies of over 30,000 patients efficacy is likely due to their lack of B. fragilis activity. The
support the routine use of prophylactic antimicrobials in all combination of cefazolin and metronidazole provides ad-
patients undergoing colorectal procedures.426 equate coverage of pathogens and may be a cost-effective
Choice of agent. The agent chosen for antimicrobial prophylaxis strategy.6,41
prophylaxis in colorectal procedures should have activity Second-generation cephalosporins with anaerobic
against the anaerobic and aerobic floras of the bowel. The activity, such as cefoxitin and cefotetan, have been widely
most appropriate regimen for antimicrobial prophylaxis for evaluated. In single-agent therapy, SSI rates ranged from 0%
colorectal procedure (e.g., oral, i.v, oral–i.v. combination) to 17%91,417,445,452–459; however, more than half of the studies
and the optimal choice of antimicrobial agent have not been found SSI rates of >10%.
fully resolved. Third-generation agents, cefotaxime and ceftriaxone,
Oral regimens. The efficacy of oral prophylactic anti- have been evaluated in a few trials; postoperative SSI rates
were 8–19% with single-agent use.456,460,461 In some studies,
microbial agents has been established in studies only when
second- or third-generation cephalosporins were combined
used with mechanical bowel preparation (MBP). A variety
with other i.v. agents, most commonly metronidazole.452,459–462
of oral agents administered after MBP have been evaluated
However, in all but one of these studies, a combination of a
for prophylaxis for colorectal procedures. The most com-
second- or third-generation cephalosporin plus metronida-
mon combinations include an aminoglycoside (neomycin
zole was no more effective than the cephalosporin alone.
and, less often, kanamycin, which is only available in in-
The use of third- or fourth-generation cephalosporins for
jectable form in the United States) plus a medication with
routine antimicrobial prophylaxis is not recommended as
anaerobic activity, usually erythromycin427–434 or metroni-
use may lead to development of resistant organisms.6,41,444,463
dazole.432,433,435–439 In placebo-controlled studies, the oral
However, in institutions where there is increasing gram-
combination was significantly more effective than placebo
negative resistance from isolates to first- and second-genera-
in reducing SSIs.427,433,434,439,440 Postoperative SSI rates were tion cephalosporins, a single dose of ceftriaxone plus metro-
0–11% with neomycin plus erythromycin427–432 and 2–13% nidazole may be preferred over routine use of carbapenems.
with neomycin and metronidazole.436–438 Combinations of Three small studies, with under 200 patients each,
neomycin and tetracycline,440 neomycin and clindamycin,436 found i.v. ampicillin–sulbactam or amoxicillin–clavulanate
and neomycin and tinidazole441 have also been used success- to be as effective as i.v. combinations of gentamicin and
fully, with postoperative SSI rates of <10%. The use of met- metronidazole,464 gentamicin and clindamycin,465 and ce-
ronidazole as a single agent appears to be less effective, with fotaxime and metronidazole for preventing SSIs in elective
reported SSI rates of 12–15%.442–444 colorectal procedures.
Oral antimicrobials have been compared with i.v. A randomized controlled study of adult patients under-
agents in a few studies. Oral neomycin plus oral erythromy- going elective colon or rectal procedures evaluated the use
cin was similarly effective as i.v. cefoxitin in one study429 of a single high dose of gentamicin 4.5 mg/kg i.v. plus met-
but inferior in another445 and was similarly effective as i.v. ronidazole 500 mg i.v. in sequential order over 30 minutes
ceftriaxone plus i.v. metronidazole in patients undergoing compared with multiple standard doses of gentamicin 1.5
elective colorectal procedures.431 The addition of i.v. cef mg/kg plus metronidazole given preoperatively and every
amandole to oral neomycin plus oral erythromycin did not 8 hours for 24 hours postoperatively.16 All patients under-
improve efficacy.430 In one of these studies, oral neomycin went MBP before surgery. Patients with a serum creatinine
and erythromycin were more effective than i.v. cefoxitin concentration exceeding 1.7 mg/L were excluded from the
for procedures lasting longer than 4 hours.445 A randomized study. No statistically significant differences were seen in
controlled study was stopped early due to the significantly deep and superficial incisional SSI rates between groups.
higher rate of infection in the oral neomycin and erythro- Significantly fewer superficial SSIs were seen in the single-
mycin group (41%) compared with the single-dose i.v. dose group compared with the multidose group in proce-
metronidazole and ceftriaxone group (9.6%) (p < 0.01).446 dures lasting longer than 3.5 hours (22.2% versus 55%, p
Similarly, a study of oral metronidazole and kanamycin = 0.021). A pharmacodynamic study of these patients found
compared with the same medications given intravenously the gentamicin concentration at the time of surgical-site clo-
found an increased rate of postoperative sepsis (36% versus sure as the strongest independent factor for infection.17 Of
6.5%, respectively) (p < 0.001), greater numbers of E. coli note, the infection rate was 80% in 10 patients with gentami-
resistant to kanamycin, more bacterial overgrowth, and an- cin concentrations of <0.5 mg/L.
timicrobial-associated pseudomembranous colitis in the oral Other i.v. agents that have been evaluated either
group.447 However, the oral antimicrobials were not given on alone or in combination include aminoglycosides,464,466–469
a schedule expected to be effective, as they were discontin- clindamycin,466 ampicillin,467,469–471 penicillins plus b-lacta-
ued 36 hours before the procedure. The fact that oral antibi- mase inhibitors,464,465,468,472,473 doxycycline,470,474–476 piper-
otics were given for three days rather than less than one day, acillin,91,473 imipenem,462 and ciprofloxacin.300
Ertapenem, a broad-spectrum carbapenem, is ap- resection were 23% and 11%, respectively, for patients re-
proved by FDA for the prophylaxis of SSIs after elective ceiving i.v. cefoxitin and cefoxitin plus oral neomycin and
colorectal procedures.67 Cefotetan is also FDA approved erythromycin.417
for surgical prophylaxis in clean-contaminated procedures The safety and tolerability of oral antimicrobials have
(e.g., gastrointestinal procedures) in adult patients under- been investigated in two studies. One case–control study
going elective colon or rectal procedures.62 A large, multi- found an increased incidence of C. difficile colitis among pa-
center, randomized controlled study compared a single 1-g tients with oral plus i.v. antimicrobials and MBP compared
i.v. dose of ertapenem with cefotetan 2 g i.v. infused within with i.v. antimicrobials and MBP alone.485 However, another
60 minutes before surgical incision.412 All patients received case–control study found a lower rate (not statistically sig-
MBP preoperatively. SSI rates were significantly lower in nificant) of C. difficile infection in patients who had received
the ertapenem group versus cefotetan in the per-protocol oral antimicrobials compared with those who had not (1.6%
(18.1% and 31.1%, respectively) and the modified intent-to- versus 2.9%, p = 0.09).486 A randomized controlled study
treat (17.1% and 50.9%) populations. Ertapenem was found of 300 patients undergoing elective colorectal procedures
to be superior to cefotetan for SSI prevention. Although not found significantly higher rates of nausea and vomiting
statistically significant, higher rates of skin-related events among patients receiving three doses of oral antimicrobials
(i.e., pruritis and rash), gastrointestinal events, and C. dif- (neomycin and metronidazole, 44% and 31%, respectively)
ficile infection were seen in the ertapenem group. The study in combination with i.v. cefoxitin and MBP compared with
authors concluded that ertapenem is an acceptable alterna- regimens including one dose of oral antimicrobials (18%
tive to cefotetan and cefoxitin. Routine use of ertapenem for and 11%, respectively) and no oral antimicrobials (13%
surgical prophylaxis remains controversial due to theoretical and 9%, respectively).487 No difference was noted between
concerns regarding increases in resistant organisms and a groups for rates of abdominal pain, SSIs, or intraabdominal
potential increase in adverse events.477 abscesses. An increased number of gastrointestinal adverse
Alternative agents for patients with a high likelihood events was also reported in another comparative study in the
of past serious adverse event or allergy to b-lactams include combination oral and i.v. group (2.9%) compared with the
(1) clindamycin plus an aminoglycoside, aztreonam, or a i.v.-only group (2.1%), although the results were not statisti-
fluoroquinolone and (2) metronidazole plus an aminoglyco- cally significant.484 Overall, the evidence suggests that the
side or a fluoroquinolone.41 combination of oral antimicrobials with MBP in addition to
Combination oral and i.v. regimens. Combinations i.v. prophylactic antimicrobials reduces the rate of postop-
of oral and i.v. antimicrobials have been used in an attempt erative infections compared with i.v. antimicrobials alone
to further reduce postoperative infection rates. Regimens without MBP, although the addition of oral antimicrobials
include oral neomycin and erythromycin plus i.v. adminis- increases gastrointestinal symptoms.
tration of a cephalosporin,416,417,429,445,449,478,479 metronida- Duration. Single and multiple doses were compared
zole,480,481 and gentamicin plus clindamycin.466 Postoperative in several studies.454–456,461,471,475 However, only two of these
SSI rates in these studies ranged from 0% to 7%. With one studies compared single doses with multiple doses of the
exception,416 there was no significant difference between same antimicrobial.471,475 There was no significant differ-
oral neomycin–erythromycin plus an i.v. antimicrobial ence in infection rates between single-dose and multidose
and oral neomycin–erythromycin alone.429,449,466,478 When administration. One study found a single dose of cefotax-
combination oral and i.v. agents were compared with i.v.
ime plus metronidazole was significantly more effective
agents alone, combination therapy was favored in five of six
than three doses of cefotaxime alone.461 The most recent
studies417,429,445,449,480,482; the difference was significant in
Cochrane review found no benefit to extending the duration
three.417,449,482 The most recent Cochrane review found that
of prophylaxis (p = 0.58).426 Generally, antimicrobial pro-
the infection rate was significantly lower with the combina-
phylaxis should be continued for no more than 24 hours and
tion of oral plus i.v. prophylaxis when compared with i.v.
can typically be stopped when the procedure is completed
alone (relative risk, 0.55; p = 0.000084) or with oral pro-
and the surgical site is closed.6,41,444 No evidence supports
phylaxis alone (relative risk, 0.34; p = 0.024).426 A recent
greater efficacy for doses given after the completion of the
report of over 2000 patients recorded prospectively in the
procedure. Additional discussion on this topic is found in the
Michigan Surgical Quality Collaborative—Colectomy Best
Common Principles section of these guidelines.
Practices Project and analyzed retrospectively revealed a
significantly lower rate of postoperative infections when Consideration should be given to an additional dose
370 colectomy patients received MBP and oral antimicro- of the i.v. antimicrobial if an agent with a short half-life is
bial prophylaxis compared with propensity-matched patients used and the procedure duration exceeds the recommended
receiving i.v. prophylaxis alone.483 redosing interval (starting from the time of initiation of
A multicenter, randomized, controlled study of 491 pa- the preoperative dose) and if intraoperative blood loss oc-
tients who received MBP plus oral antimicrobials (kanamy- curs.6,41,120,418,444,445 No significant difference was seen in
cin and erythromycin) with i.v. cefmetazole (not available SSI rates with single-dose cefazolin, single-dose cefotetan,
in the United States but noted by the expert panel to have a and cefazolin given as one preoperative dose and a second
similar spectrum of activity as cefotetan) or i.v. cefmetazole dose three hours later for procedures with a duration of less
alone found no difference in SSI between groups for colon than three hours.118 SSI rates were significantly higher with
procedures.484 However, the combination of oral and i.v. a single dose of cefazolin for procedures with a duration of
antimicrobials was significantly better than i.v. alone for greater than three hours. Using an agent with a longer half-
rectal procedures, particularly abdominoperineal excision. life can decrease the necessity to redose the antimicrobial
Another study found the postoperative SSI rates after rectal during long procedures.
Pediatric Efficacy. No well-controlled studies have evalu- of the malignancy may also affect infection risk.497,498,502–504
ated the efficacy of antimicrobial prophylaxis in pediatric Procedure-related risk factors for infection include radical or
patients undergoing colorectal procedures. However, there bilateral neck dissections501,508 and reconstruction with myo-
is no reason to suspect that prophylaxis efficacy would be cutaneous flaps or microvascular-free flaps.497–499,508
different. The safety, efficacy, tolerability, and cost-effec-
tiveness of intestinal lavage have been demonstrated in two Organisms. The normal floras of the mouth and the orophar-
studies of 20 and 21 pediatric patients.488,489 ynx are responsible for most infections that follow clean-
contaminated head and neck procedures.6,8,496,498,499,506,509–519
Recommendations. A single dose of second-generation Anaerobic and aerobic bacteria are abundant in the oro-
cephalosporin with both aerobic and anaerobic activities pharynx. As a result, postoperative SSIs are usually poly-
(cefoxitin or cefotetan) or cefazolin plus metronidazole is microbial and involve both aerobic and anaerobic bacte-
recommended for colon procedures (Table 2). In institutions ria. The predominant oropharyngeal organisms include
where there is increasing resistance to first- and second- various streptococci (aerobic and anaerobic species),
generation cephalosporins among gram-negative isolates other oral anaerobes including Bacteroides species (but
from SSIs, the expert panel recommends a single dose of not B. fragilis), Peptostreptococcus species, Prevotella
ceftriaxone plus metronidazole over routine use of car- species, Fusobacterium species, Veillonella species,
bapenems. An alternative regimen is ampicillin–sulbactam. Enterobacteriaceae, and staphylococci. Nasal flora includes
In most patients, MBP combined with a combination of oral Staphylococcus species and Streptococcus species.
neomycin sulfate plus oral erythromycin base or oral neo-
mycin sulfate plus oral metronidazole should be given in Efficacy. Clean procedures. Systemic administration of
addition to i.v. prophylaxis. The oral antimicrobial should prophylactic antimicrobials has not been proven effective
be given as three doses over approximately 10 hours the af- in reducing SSI rates in patients undergoing clean proce-
ternoon and evening before the operation and after the MBP. dures of the head and neck and are not recommended for
Alternative regimens for patients with b-lactam allergies in- routine use.6–8,497,520 One randomized, double-blind, multi-
clude (1) clindamycin plus an aminoglycoside, aztreonam, center study of 500 patients undergoing thyroid procedures
or a fluoroquinolone and (2) metronidazole plus an amino- for goiter or carcinoma found no difference in postoperative
glycoside or a fluoroquinolone. Metronidazole plus aztreo- SSI rates in those who received antimicrobial prophylaxis
nam is not recommended as an alternative because this com- (0.8%) and those who did not (0.4%).491
bination has no aerobic gram-positive activity.385 (Strength Clean-contaminated procedures. Based on the best
of evidence for prophylaxis = A.) available evidence, current guidelines and review articles
recommend the use of antimicrobial prophylaxis for the
Head and Neck Procedures majority of clean-contaminated procedures.6–8,497,520,521
However, antimicrobial prophylaxis did not lower infection
Background. Elective procedures of the head and neck are risk in randomized controlled trials of patients undergoing
predominantly clean or clean-contaminated.490 Clean pro- adenoidectomy, tonsillectomy,522,523 and septoplasty,524 and
cedures include thyroidectomy and lymph node excisions. systematic reviews have not recommended prophylaxis for
Clean-contaminated procedures include all procedures in- these procedures.7,525,526
volving an incision through the oral or pharyngeal mucosa, The efficacy of antimicrobial prophylaxis is best es-
ranging from parotidectomy, submandibular gland excision, tablished for head and neck cancer surgery. Several small
tonsillectomy, adenoidectomy, and rhinoplasty to compli- randomized, controlled trials found high infection rates in
cated tumor-debulking and mandibular fracture repair pro- placebo groups (24–78%) and markedly lower infection
cedures requiring reconstruction. The frequency of SSIs rates in the prophylaxis groups (5.8–38%) using a variety of
reported for clean procedures without antimicrobial pro- regimens, including cefazolin, third-generation cephalospo-
phylaxis is <1%.491,492 In contrast, infection rates in patients rins, and ampicillin plus cloxacillin. Although these studies
undergoing complicated head and neck cancer surgery are were small, the results are concordant, and the high infection
quite high, with infection occurring in 24–87% of patients rates allowed the studies to reach statistical significance de-
without antimicrobial prophylaxis.493–497 While many of spite the small sample sizes. Similar results were reported in
these head and neck cancer procedures are clean-contami- several additional small, uncontrolled studies.500,527–529
nated, these procedures can fall into different wound clas- Choice of agent. Several randomized, single-center
sifications. Head and neck cancer patients often have many studies have compared antimicrobial regimens for clean-
of the risk factors for infection mentioned below.498 contaminated procedures. In one study, 189 patients under-
Postoperative SSI rates are affected by age, nutritional going head and neck cancer procedures were randomized
status, and the presence of concomitant medical conditions to receive cefazolin 1 g (n = 92) or amoxicillin–clavula-
such as diabetes mellitus, anemia, and peripheral vascu- nate (n = 97), both given within one hour of incision and
lar disease.496,499–504 Use of tobacco,498,505 alcohol,505,506 or every eight hours postoperatively for three doses.511 The
drugs of abuse507 has also been associated with a higher postoperative SSI rates were 24% with cefazolin and 21%
risk of postoperative infection, particularly in patients with with amoxicillin–clavulanate; there was no statistically sig-
mandibular fracture. The hospital course, including length nificant difference in infection rates in this underpowered
of hospitalization before operation, duration of antimicro- study. Two studies have compared ampicillin–sulbactam
bial use before operation, length of operation, presence of to clindamycin and yielded discordant results. One study
implants, and previous tracheotomy can also affect postop- of 242 patients (169 evaluable) undergoing head and neck
erative SSI rates.496,497,501–504,508 In patients with cancer, pre- cancer procedures compared ampicillin–sulbactam 1.5 g (n
operative radiation and chemotherapy as well as the stage = 119) and clindamycin 600 mg (n = 123) given within one
to two hours of incision and every six hours postoperatively dure. A classification system for neurosurgery, vali-
for a total of four doses.510 No difference in SSIs was found, dated by Narotam et al.,537 divides procedures into
with 15 infections reported in each group (13% for the ampi- five categories: clean, clean with foreign body, clean-
cillin–sulbactam group and 12% for the clindamycin group). contaminated, contaminated, and dirty. Risk factors for post-
There was no significant difference in adverse events be- operative infections after neurological procedures include
tween groups. There was a higher rate of C. difficile-positive an ASA classification of ≥2,538 postoperative monitoring of
patients in the clindamycin group (n = 7) than in the ampi- intracranial pressure538,539 or ventricular drains536,538 for five
cillin–sulbactam group (n = 1), with no reported statistical or more days, cerebrospinal fluid (CSF) leak,539–541 proce-
analysis. Another study of 212 patients undergoing clean- dure duration of more than two to four hours,540,542–544 dia-
contaminated head and neck oncology surgery found signifi- betes,544 placement of foreign body,536 repeat or additional
cantly fewer infections in the ampicillin–sulbactam group neurosurgical procedures,538,541–543 concurrent (remote, inci-
(13.3%) compared with the clindamycin group (27.1%) (p = sion, or shunt) or previous shunt infection,536,539,545,546 and
0.02).530 A greater number of gram-negative pathogens were emergency procedures.542,545
recovered from patients randomized to the clindamycin
group. The combination of gentamicin and clindamycin was Organisms. Data from most published clinical trials indi-
superior to cefazolin in one older clinical trial.531 cate that SSIs are primarily associated with gram-positive
Duration. Studies of clean-contaminated head and bacteria, S. aureus, and coagulase-negative staphylo-
neck procedures found no difference in efficacy between cocci.6,8,537–545,547–554 Several cohort studies revealed high
regimens of 24 hours and longer regimens of three, five, or rates (up to 75–80% of isolates) of MRSA540–543,548–552 and
seven days.499–501,505,507,512,524,531–534 Limited data exist on coagulase-negative staphylococci among patients undergo-
single-dose prophylaxis in these procedures. ing a variety of neurosurgical procedures.539,540,543,549 Other
One study of patients undergoing free-flap reconstruc- skin organisms such as P. acnes may be seen after CSF
tion after head and neck procedures found a significantly shunt placement, craniotomy, and other procedures.536,555,556
lower rate of acquisition and infection with MRSA in pa- Gram-negative bacteria have also been isolated as the sole
tients receiving short-term cefuroxime and metronidazole cause of postoperative neurosurgical SSIs in approximately
(one dose during induction of anesthesia and one dose eight 5–8% of cases and have been isolated in polymicrobial in-
hours postoperatively) compared with long-term therapy fections.537–539,541–545,547–550,552,553
(same antimicrobials with additional doses every eight hours
for up to five days) (p = 0.005 and p = 0.01, respectively, for Efficacy. Clean procedures. Antimicrobial prophylaxis
acquisition and infection).535 is recommended for adult and pediatric patients under-
going craniotomy and spinal procedures.7,520 One meta-
Recommendations. Clean procedures. Antimicrobial pro- analysis of six studies found decreased odds of meningitis
phylaxis is not required in patients undergoing clean surgi- in patients undergoing craniotomy who received antimicro-
cal procedures of the head and neck. If there is placement bial prophylaxis (1.1%) versus no prophylaxis (2.7%) (p
of prosthetic material, a preoperative dose of cefazolin or = 0.03).557 Two cohort studies540,543 in patients undergoing
cefuroxime is reasonable, though there are few data support- craniotomy at the same institution found that antimicrobial
ing the efficacy of prophylaxis in this setting (Table 2). A prophylaxis with cloxacillin or amoxicillin–clavulanate,
reasonable alternative for patients with b-lactam allergies clindamycin for b-lactam-allergic patients, and other anti-
is clindamycin. (Strength of evidence against prophylaxis microbials (not detailed) had a significantly lower infection
without prosthesis placement = B; strength of evidence for rate (5.8%) than no prophylaxis (9.7%) (p < 0.0001).543 A
prophylaxis with prosthesis placement = C.) significantly lower infection rate of 4.6% was seen in low-
Clean-contaminated procedures. Antimicrobial pro- risk patients (clean craniotomy, no implant) with antimicro-
phylaxis has not been shown to benefit patients undergoing bial prophylaxis compared with those without prophylaxis
tonsillectomy or functional endoscopic sinus procedures. (4.6% versus 10%, p < 0.0001). A significantly lower rate
The preferred regimens for patients undergoing other clean- of scalp infections, bone flap osteitis, and abscess or empy-
contaminated head and neck procedures are (1) cefazolin or ema was seen with antimicrobial prophylaxis compared with
cefuroxime plus metronidazole and (2) ampicillin–sulbac- no prophylaxis. Antimicrobial prophylaxis demonstrated no
tam. Clindamycin is a reasonable alternative in patients with difference in postoperative meningitis540,543 and infection
a documented b-lactam allergy. The addition of an amino- rates in high-risk patients (those undergoing emergency,
glycoside to clindamycin may be appropriate when there is clean-contaminated, and dirty procedures or reoperation or
an increased likelihood of gram-negative contamination of with operative times exceeding four hours).543
the surgical site. (Strength of evidence for prophylaxis in Prospective studies involving large numbers of patients
cancer surgery patients = A; strength of evidence for prophy- have also demonstrated lower neurosurgical postoperative
laxis for other clean-contaminated procedures except tonsil- infection rates when antimicrobial prophylaxis is used.558–561
lectomy and functional endoscopic sinus procedures = B.) One such study of patients undergoing craniotomy, spinal, or
shunting procedures was stopped early because of an exces-
Neurosurgery Procedures sive number of SSIs in the placebo group.562
Choice of agent. Studies of clean neurosurgical proce-
Background. Nosocomial central nervous system (CNS) dures reported antimicrobial regimens including clindamy-
infections do not often occur but have potentially seri- cin,540,543,557 vancomycin,542,557 cefotiam (not marketed in
ous consequences and poor outcomes, including death.536 the United States),557 piperacillin,557 cloxacillin,540,543,557
One of the greatest risks for these infections in chil- oxacillin,542,557 cefuroxime,547 cefotaxime,548 sulfamethoxa-
dren and adults is undergoing a neurosurgical proce- zole–trimethoprim,548 cefazolin,542,544 penicillin G,542 and
amoxicillin–clavulanate.540,542,543 A meta-analysis found no with antimicrobial-impregnated shunts.545 At this time, rou-

significant difference in the rates of postcraniotomy menin- tine use of antimicrobial-impregnated devices is not recom-
gitis with various antimicrobial regimens (single-dose regi- mended; additional well-designed studies are needed to es-
mens of clindamycin, vancomycin, or cefotiam; three doses tablish their place in therapy.7,578
of piperacillin; four doses of cloxacillin; and six doses of Choice of agent. In CSF-shunting procedures, no
oxacillin).557 single antimicrobial agent has been demonstrated to have
A randomized, open-label, multicenter study of 613 greater efficacy than others.546,548,551–554,579 There is a lack
adult patients undergoing elective craniotomy, shunt, or of data on the necessity of antimicrobials with CNS pen-
stereotactic procedures found no difference in single doses etration relating to prevention of infection in CNS shunting
of cefotaxime and trimethoprim–sulfamethoxazole in post- procedures.
operative abscess formation, SSIs, and shunt infections.548 Duration. The majority of studies support the use of
Duration. The majority of studies included single single-dose prophylaxis regimens or regimens with a dura-
doses of antimicrobials; therefore, the use of single-dose tion of 24–48 hours postoperatively.6–8,520,539,546,549–552,579
antimicrobial prophylaxis given within 60 minutes before There is a lack of data evaluating the continuation of EVDs
surgical incision in patients undergoing neurosurgery is gen- with and without antimicrobial prophylaxis. The interna-
erally recommened.6,7,520,540,543,547,548,557,563 tional survey mentioned above asked respondents to indicate
their recommended duration for antimicrobial prophylaxis
Efficacy for CSF-Shunting Procedures. Antimicrobial with EVDs as either periprocedural, for 24 hours, for the
prophylaxis is recommended for adults undergoing place- first three days, for the entire time the device is in place,
ment of a CSF shunt.7 Prophylaxis in patients undergoing or other.135 The respondents from the specialties of neuro-
ventriculostomy or intraventrical prophylaxis at the time of surgery, neurocritical care, and critical care had similar re-
ventriculoperitoneal shunt insertion has shown some benefit sults, with 28–31% using or recommending periprocedural
in reducing infection but remains controversial due to lim- antimicrobials, 4–10% for 24 hours, 2–4% for the first three
ited evidence.6,7 days, 43–64% for the entire time the device is in place, and
Because CNS infections after shunting procedures are 0–14% for other. The infectious diseases specialists reported
responsible for substantial mortality and morbidity, espe- rates of 62%, 19%, 4%, 12%, and 4%, respectively.
cially in children, the possible role of prophylactic antimi- One retrospective single-center cohort study of 308
crobials in such procedures has been studied in numerous patients with EVDs placed for three days or more received
small, well-conducted, randomized controlled trials.564–571 antimicrobial prophylaxis for the duration of EVD use (n =
Meticulous surgical and aseptic techniques and short pro- 209) compared with patients receiving cefuroxime 1.5 g i.v.
cedure times were determined to be important factors in every eight hours for three doses or less frequently peripro-
lowering infection rates after shunt placement. Although the cedurally (timing not clearly defined in article) (n = 99).580
number of patients studied in each trial was small, two meta- The overall rate of bacterial ventriculitis was 3.9%, with 8
analyses of these data demonstrated that antimicrobial pro- patients (3.8%) in the extended-use group and 4 patients
phylaxis use in CSF-shunting procedures reduced the risk of (4%) in the short-term prophylaxis group, the difference of
infection by approximately 50%.572,573 which was not significant. The study authors concluded that
Intrathecal pump placement involves the implantation there was no benefit to the use of a prolonged duration of
of a permanent intrathecal catheter to allow instillation of antimicrobial prophylaxis.
medication. CNS infections may occur after these proce-
dures, which are performed in both pediatric and adult popu- Pediatric Efficacy for CSF-Shunting Procedures.
lations. Several retrospective series have reported infection Antimicrobial prophylaxis is recommended for children un-
rates of 4.5–9% after intrathecal baclofen pump place- dergoing a CSF-shunting procedure.7 The efficacy of antimi-
ment.574–576 There are minimal published trial data regarding crobial prophylaxis is extrapolated from adult studies.
appropriate prophylaxis for intrathecal pump procedures. It A retrospective pediatric study of 384 CSF-shunting
has been suggested that prophylaxis for intrathecal pump procedures found a lower infection rate in patients who re-
procedures be managed similarly to prophylaxis for CSF- ceived antimicrobials (2.1%) compared with those who did
shunting procedures.577 not (5.6%), but this difference failed to reach statistical sig-
There is no consensus on the use of antimicrobial pro- nificance.581 Two randomized, prospective studies that in-
phylaxis in patients with extraventricular drains (EVDs) or cluded pediatric patients did not demonstrate a significant
intracranial pressure monitors.134 An international survey of difference in infection rates between the control group and
neurosurgeons and critical care medicine and infectious dis- the groups that received cefotiam571 (not available in the
eases specialists illustrates the difference in practices. The United States) or methicillin.568 A randomized, double-blind,
majority of neurosurgeons used or recommended the use placebo-controlled study that included pediatric patients
of antimicrobial prophylaxis with EVDs (73.5%) and other undergoing ventriculoperitoneal shunt surgeries failed to
monitoring devices (59%), compared with rates of 46–59% demonstrate that the use of perioperative sulfamethoxazole–
for critical care medicine specialists and 35% for infectious trimethoprim reduced the frequency of shunt infection.564
diseases specialists. The majority of specialists did not rec- Other studies have demonstrated efficacy for prophy-
ommend or use antimicrobial-coated EVD catheters. lactic antimicrobials.566,582 A single-center, randomized, dou-
Two randomized controlled studies comparing antimi- ble-blind, placebo-controlled trial of perioperative rifampin
crobial-impregnated shunts to standard, non-antimicrobial- plus trimethoprim was performed in pediatric patients.582
impregnated shunts along with antimicrobial prophylaxis Among patients receiving rifampin plus trimethoprim, the
with i.v. cephalosporin found a decrease in rates of shunt infection rate was 12%, compared with 19% in patients re-
infections549 and a significant decrease in CSF infection ceiving placebo. The study was ended because of the high in-
fection rates before significance could be achieved. Infection monly isolated organisms from SSIs include Staphylococcus
rates at the study institution had been 7.5% in the years before species and enterococci.
the study. An open-label randomized study, including pediat-
ric patients, demonstrated a lower infection rate in a group Efficacy. While the use of antimicrobial prophylaxis in
receiving oxacillin (3.3%) than in a control group (20%).566 low-risk procedures (i.e., those with no active labor and no
rupture of membranes) has been brought into question by
Recommendations. A single dose of cefazolin is recom- the results of several randomized, placebo-controlled stud-
mended for patients undergoing clean neurosurgical pro- ies that found no reduction in infectious complications (fe-
cedures, CSF-shunting procedures, or intrathecal pump ver, SSI, urinary tract infection, or endometritis) with the
placement (Table 2). Clindamycin or vancomycin should use of prophylaxis, the majority of these evaluations were
be reserved as an alternative agent for patients with a docu- underpowered and included administration of antimicrobial
mented b-lactam allergy (vancomycin for MRSA-colonized prophylaxis at cord clamping.593–599 However, the efficacy
patients). (Strength of evidence for prophylaxis = A.) of antimicrobial prophylaxis in cesarean delivery has been
shown in several studies and two meta-analyses for both
Cesarean Delivery Procedures elective and nonelective procedures. Therefore, prophylaxis
is recommended for all patients undergoing cesarean deliv-
Background. Approximately 1.2 million infants are born ery.584,592
by cesarean delivery in the United States annually.583 The One meta-analysis that reviewed 7 placebo-controlled
infection rate after cesarean delivery has been reported to randomized trials in low-risk elective cesarean delivery
be 4–15%,583 though recent NHSN data showed an infection found that prophylaxis was associated with a significant de-
rate of 2–4%.165 crease in endometritis and fever.592 A larger meta-analysis
Postpartum infectious complications are common af- of 81 randomized trials with 11,937 women undergoing
ter cesarean delivery. Endometritis (infection of the uterine both elective and nonelective cesarean delivery found that
lining) is usually identified by fever, malaise, tachycardia, antimicrobial prophylaxis was associated with a significant
abdominal pain, uterine tenderness, and sometimes abnor- reduction in risk of fever, endometritis, SSI, urinary tract
mal or foul-smelling lochia.584 Fever may also be the only infection, and serious infection.585 The relative risk for en-
symptom of endometritis. dometritis in elective cesarean section was 0.38 (95% CI,
Endometritis has been reported to occur in up to 24% 0.22–0.64) in those receiving antimicrobial prophylaxis
of patients in elective cesarean delivery and up to approxi- compared to those receiving no prophylaxis.
mately 60% of patients undergoing nonelective or emer- Choice of agent. Although several different antimicro-
gency section.584,585 Risk factors for endometritis include ce- bials used alone or in combination for antimicrobial prophy-
sarean delivery, prolonged rupture of membranes, prolonged laxis during cesarean delivery have been evaluated, the use
labor with multiple vaginal examinations, intrapartum fever, of first-generation cephalosporins (specifically cefazolin)
and low socioeconomic status.585,586 Patients with low so- has been advocated by ACOG and the American Academy
cioeconomic status may have received inadequate prenatal of Pediatrics (AAP), based on their efficacy, narrow spec-
care. trum of activity, and low cost.584 This recommendation is
The factor most frequently associated with infectious supported by a meta-analysis of 51 randomized controlled
morbidity in postcesarean delivery is prolonged labor in trials comparing at least two antimicrobial regimens that
the presence of ruptured membranes. Intact chorioamni- concluded that ampicillin and first-generation cephalospo-
otic membranes serve as a protective barrier against bacte- rins have similar efficacy.600
rial infection. Rupture of the membrane exposes the uterine Newer prospective randomized controlled and co-
surface to bacteria from the birth canal. The vaginal fluid hort studies have evaluated the addition of metronidazole,
with bacterial flora is drawn into the uterus when it relaxes azithromycin,601–603 or doxycycline601 to a first- or second-
between contractions during labor. Women undergoing labor generation cephalosporin to extend the spectrum of activ-
for more than six to eight hours in the presence of ruptured ity against common organisms isolated from endometrial
membranes should be considered at high risk for develop- and surgical-site cultures, specifically U. urealyticum and
ing endometritis.587 Other risk factors for SSIs after cesarean Mycoplasma species. These studies found significantly lower
delivery include systemic illness, poor hygiene, obesity, and rates of postoperative infections (including endometritis and
anemia.587,588 SSI) and a shorter duration of hospital stay compared with
prophylaxis with a first- or second-generation cephalosporin
Organisms. The normal flora of the vagina include staphy- alone.601–604 Antibiotic administration occurred either post-
lococci, streptococci, enterococci, lactobacilli, diphthe- operatively or after cord clamping in these studies. Further
roids, E. coli, anaerobic streptococci (Peptococcus spe- study, particularly with preoperative antimicrobial adminis-
cies and Peptostreptococcus species), Bacteroides species tration, is needed to confirm these preliminary findings and
(e.g., Bacteroides bivius, B. fragilis), and Fusobacterium establish a place in therapy for this practice.
species.584,587,589–592 Endometritis infections are often poly- Timing. Historically, administration of antimicrobials
microbial and include aerobic streptococcus (particularly in cesarean delivery was delayed until after cord clamp-
group B b-hemolytic streptococcus and enterococci), gram- ing.600,605,606 The principal reasons were to avoid suppression
negative aerobes (particularly E. coli), gram-negative an- of the neonate’s normal bacterial flora that could promote
aerobic rods (particularly B. bivius), and anaerobic cocci the selection of resistant organisms and concern that the an-
(Peptococcus species and Peptostreptococcus species). timicrobials could potentially mask neonatal infection, com-
Ureaplasma urealyticum has been commonly isolated from plicating evaluation of neonatal sepsis. However, more con-
endometrial and surgical-site cultures. Additional com- temporary data support the administration of antimicrobial
prophylaxis before surgical incision to protect against bacte- in patients with extension of their cancer. Hysterectomies
rial contamination of the surgical site and decrease the risk are performed by a vaginal or abdominal approach using
of infection. The practice of antimicrobial prophylaxis ad- a laparoscopic- or robot-assisted method. During a vaginal
ministration before surgical incision is endorsed by ACOG hysterectomy, the procedure is completed through the va-
and AAP.584,607 See the Common Principles section of these gina with no abdominal incision. Abdominal hysterectomy
guidelines for additional discussion on antimicrobial timing. involves an abdominal incision. Laparoscopic and robotic
A meta-analysis of three randomized controlled tri- methods involve small incisions and require additional
als and two nonrandomized controlled studies provided equipment, increased operator experience, and increased
evidence that preoperative antimicrobial administration length of procedures.611,612 In the United States, between
significantly decreased the rate of endometritis compared 2000 and 2004, the abdominal approach for hysterectomy
with administration after cord clamping (3.9% and 8.9%, was used in 67.9% of surgical procedures and the vaginal
respectively; p = 0.012).605 A lower SSI rate was also seen approach in 32.1%. Of hysterectomies performed via the
with preoperative antimicrobial administration (3.2% ver- vaginal approach, 32.4% also used laparoscopy.609 The
sus 5.4%), though this difference was not significant. The ACOG Committee on Gynecologic Practice recommends
overall rate of infection-related morbidity was also signifi- vaginal hysterectomy as the approach of choice for benign
cantly lower. No differences between the groups were seen disease, based on evidence of better outcomes and fewer
in neonatal outcomes, including sepsis, sepsis workups, and complications.613 Laparoscopic abdominal hysterectomy is
neonatal intensive care unit admissions. The largest study an alternative when the vaginal route is not indicated or fea-
included in this meta-analysis was a prospective, random- sible.613,614 Of note, ACOG has stated that the supracervical
ized, controlled, double-blind, single-center, double-dummy approach—removal of the uterus with preservation of the
study of 357 patients comparing cefazolin 1 g i.v. given pre- cervix—should not be recommended as a superior technique
operatively and after cord clamping, which had results con- for hysterectomy due to the lack of advantage in postopera-
sistent with the overall meta-analysis.606 tive complications, urinary symptoms, or sexual function
In a recent randomized trial of more than 1100 women and the increased risk of future trachelectomy to remove the
undergoing cesarean section between 2004 and 2010, Witt cervical stump.615
and colleagues608 found no difference in SSI rates for pa- Infections after hysterectomy include superficial and
tients having antimicrobial administration before surgical organ/space (vaginal cuff infection, pelvic cellulitis, and pel-
incision compared with those who received antimicrobial vic abscess) SSIs.589 The reported SSI rates between January
prophylaxis at the time of cord clamping. All patients re- 2006 and December 2008 in the United States, based on
ceived a single dose of cefazolin 2 g. NNIS risk index category, were 0.73–1.16 per 100 proce-
Duration. A meta-analysis of 51 studies found that dures for vaginal hysterectomy and 1.10–4.05 per 100 proce-
multidose regimens provided no apparent benefit over single- dures for abdominal hysterectomy.165 A multicenter surveil-
dose regimens.600 The use of single-dose prophylaxis is sup- lance study found a mean infection rate of 2.53% associated
ported by ACOG and AAP for procedures lasting less than with all types of hysterectomy and a significantly lower
two hours.584 Additional intraoperative doses may be war- mean rate of infection with laparoscopic versus abdominal
ranted for patients with excessive blood loss or for whom the hysterectomies (1.15% versus 3.44%, respectively).325
duration of the procedure is extended. Risk factors for infection after vaginal or abdominal
For additional discussion of dosing, see the Common hysterectomy include longer duration of surgery, young age,
Principles section of these guidelines. diabetes, obesity, peripheral vascular disease, collagen dis-
ease, anemia, transfusion, poor nutritional status, and previ-
Recommendation. The recommended regimen for all ous history of postsurgical infection.590,616–622 The depth of
women undergoing cesarean delivery is a single dose of subcutaneous tissue is also a significant risk factor for infec-
cefazolin administered before surgical incision (Table 2). tion after abdominal hysterectomy.623 Additional risk factors
(Strength of evidence for prophylaxis = A.) For patients for infection after radical hysterectomy for cervical cancer
with b-lactam allergies, an alternative regimen is clindamy- include the presence of malignancy, prior radiation therapy,
cin plus gentamicin. and the presence of indwelling drainage catheters.619,620
Hysterectomy Procedures Organisms. The vagina is normally colonized with a wide

variety of bacteria, including gram-positive and gram-
Background. Hysterectomy is second only to cesarean de- negative aerobes and anaerobes. The normal flora of the
livery as the most frequently performed major gynecological vagina includes staphylococci, streptococci, enterococci,
procedure in the United States, with over 600,000 hyster- lactobacilli, diphtheroids, E. coli, anaerobic streptococci,
ectomies performed annually.609 Uterine fibroid tumors ac- Bacteroides species, and Fusobacterium species.589,624
count for 40% of all presurgical diagnoses leading to hys- Postoperative vaginal flora differs from preoperative flora;
terectomy.609 Other common diagnoses are dysfunctional the amount of enterococci, gram-negative bacilli, and
uterine bleeding, genital prolapse, endometriosis, chronic Bacteroides species increases postoperatively. Postoperative
pelvic pain, pelvic inflammatory disease, endometrial hy- changes in flora may occur independently of prophylactic
perplasia, and cancer. antimicrobial administration and are not by themselves pre-
Hysterectomy involves the removal of the uterus and, dictive of postoperative infection.589,625,626 Postoperative in-
occasionally, one or two fallopian tubes, the ovaries, or a fections associated with vaginal hysterectomy are frequently
combination of ovaries and fallopian tubes.610 Radical hys- polymicrobial, with enterococci, aerobic gram-negative
terectomy entails removal of the uterus, fallopian tubes, and bacilli, and Bacteroides species isolated most frequently.
ovaries and extensive stripping of the pelvic lymph nodes Postoperative SSIs after abdominal and radical hysterecto-
mies are also polymicrobial; gram-positive cocci and enteric A randomized controlled study of 511 patients under-
gram-negative bacilli predominate, and anaerobes are fre- going laparoscopic gynecological procedures at one center
quently isolated.626,627 in Italy compared single doses of amoxicillin–clavulanate
2.2 g and cefazolin 2 g i.v. administered 20–30 minutes be-
Efficacy. A meta-analysis of 25 randomized controlled tri- fore the procedure.654 A second dose was given if the surgery
als demonstrated the efficacy of antimicrobial prophylaxis, lasted over three hours or there was extensive blood loss
including first- and second-generation cephalosporins and (>1500 mL). No significant differences in the rates of any
metronidazole, in the prevention of infections after abdomi- postoperative infection, including SSIs, were found between
nal hysterectomy.628 The infection rates were 21.1% with groups. The statistical power of the study was not stated.
placebo or no prophylaxis and 9.0% with any antimicrobial. In light of the organisms encountered in the vaginal
Another meta-analysis found that the rate of postoperative canal and comparative studies conducted among different
infection (surgical and pelvic sites) in women undergoing classes of cephalosporins, cefazolin, cefotetan, cefoxitin, ce-
vaginal hysterectomy who received placebo or no prophy- furoxime, and ampicillin–sulbactam have been supported as
lactic antimicrobial ranged from 14% to 57%, which was appropriate first-line choices for prophylaxis during vaginal
significantly higher than the 10% rate reported with antimi- or abdominal hysterectomy.6,9,41 Alternative agents for pa-
crobials.629 tients with a history of immediate hypersensitivity to peni-
Malignant disease as the reason for hysterectomy is cillin include either clindamycin or metronidazole plus an
a common exclusion from studies of antimicrobial prophy- aminoglycoside or a fluoroquinolone (ciprofloxacin, levo-
laxis. Older, prospective, placebo-controlled studies found a floxacin, or moxifloxacin) or aztreonam (with clindamycin
lower rate of SSIs with antimicrobial prophylaxis after radi- only).
cal hysterectomy.619,630–633 The applicability of these results Duration. Studies comparing single doses of one anti-
is limited by small sample size and the inclusion of antimi- microbial with multidose regimens of a different antimicro-
crobials not available in the United States. Radical hysterec- bial have shown the two regimens to be equally effective in
tomy is primarily completed through an abdominal approach reducing the postoperative infection rate in women undergo-
but can also be performed by a vaginal approach and using ing vaginal and abdominal hysterectomies.635–643,645–650,655–663
laparoscopic or robotic methods.634 Therefore, antimicrobial The limited comparative trials involving single-dose cefazo-
prophylaxis would be warranted, regardless of approach. No lin637,654,655,664 or ampicillin–sulbactam654,663 indicate that
placebo-controlled studies have been conducted to evalu- a single dose of antimicrobial is sufficient prophylaxis for
ate the efficacy of antimicrobial prophylaxis when used for SSIs for vaginal hysterectomy. Single doses of cefotetan,
laparoscopic hysterectomy. ceftizoxime, or cefotaxime appear to be as effective as mul-
Choice of agent. Cephalosporins are the most fre- tiple doses of cefoxitin.644–649,665 A second dose of antimi-
quently used and studied antimicrobials for prophylaxis crobial is warranted when the procedure lasts three hours or
in vaginal and abdominal hysterectomies. Studies directly longer or if blood loss exceeds 1500 mL.9,654
comparing different cephalosporins have found no signifi-
cant differences in rates of infection in vaginal hysterec- Recommendation. The recommended regimen for women
tomy and have indicated that first-generation cephalospo- undergoing vaginal or abdominal hysterectomy, using an
rins (primarily cefazolin) are equivalent to second- and open or laparoscopic approach, is a single dose of cefazolin
third-generation agents.635–644 In abdominal hysterectomy, (Table 2). Cefoxitin, cefotetan, or ampicillin–sulbactam may
no significant differences in the rates of serious infections also be used. Alternative agents for patients with a b-lactam
were noted between second- and third-generation cephalo- allergy include (1) either clindamycin or vancomycin plus
sporin regimens.641,645–649 Few comparisons have been made an aminoglycoside, aztreonam, or a fluoroquinolone and (2)
between second-generation cephalosporins and cefazolin. metronidazole plus an aminoglycoside or a fluoroquinolone.
Cefazolin has been at least as effective in preventing infec- (Strength of evidence for prophylaxis = A.)
tious complications as second- and third-generation cepha-
losporins.636,650–652 However, one double-blind controlled Ophthalmic Procedures
study of 511 women undergoing abdominal hysterectomy
found that the risk of major SSIs requiring antimicrobial Background. Ophthalmic procedures include cataract ex-
therapy was significantly higher in the group receiving pre- tractions, vitrectomies, keratoplasties, intraocular lens
operative cefazolin 1 g (11.6%; relative risk, 1.84; 95% CI, implantation, glaucoma procedures, strabotomies, retinal
1.03–3.29) than in those treated with cefotetan 1 g (6.3%).617 detachment repair, laser in situ keratomileusis, and laser-
A multicenter, randomized, double-blind, active- and pla- assisted subepithelial keratectomy. Most of the available
cebo-controlled study compared single doses of ampicillin, data regarding antimicrobial prophylaxis involve cataract
cefazolin, and placebo administered to women undergoing procedures. The goal of prophylaxis is primarily to reduce
elective total abdominal hysterectomy at two centers in acute postoperative endophthalmitis, defined as severe intra-
Thailand.653 The study found a significantly lower rate of ocular inflammation due to infection, which can lead to loss
infection, including superficial and deep SSIs, urinary tract of vision if untreated.666 Since 2000, the reported frequency
infections, vaginal cuff infection, and pneumonia, with ce- of endophthalmitis after ophthalmic procedures is low
fazolin (10.3%) compared with placebo (26.9%) and ampi- worldwide, ranging from 0% to 0.63%.667–680 The reported
cillin (22.6%). No difference was seen between ampicillin time from procedure to diagnosis of endophthalmitis ranges
and placebo. The study authors concluded that cefazolin was from one day to six weeks, with the majority of infections
more effective than ampicillin for elective total abdominal identified within one week.666,669,671,673,674,681–683
hysterectomy. Potential risk factors for postoperative ophthalmic
infections include preoperative factors such as diabetes,666
active ocular infection or colonization,666,684 lacrimal drain- procedure with intracameral cefazolin added to the previous
age system infection or obstruction, age of >85 years,685 routine prophylaxis of preoperative eyelid cleansing with
and immunodeficiency.684 Procedure-related risk factors in- soap for three days670 and povidone–iodine eye area prepara-
clude clear corneal incisions (as opposed to scleral tunnel tion,670,674 topical antimicrobial, and corticosteroid prepara-
incisions),680,686 any surgical complication, vitreous loss,684 tions given at the end of the procedure and postoperatively.
posterior capsule tear,681,684,685 silicone intraocular lens im- One study found a significant decrease and a relative risk
plantation,677,680 and the nonuse of facemasks in the operat- reduction of 88.7% in postoperative endophthalmitis with
ing theater.681 intracameral cefazolin.670 The other found a decrease from
0.63% to 0.055% in postoperative endophthalmitis with
Organisms. Among organisms isolated from patients intracameral cefazolin.674 No statistical analysis was per-
developing postoperative endophthalmitis after cata- formed in this study.
ract procedure, approximately 25–60% were coagulase- A retrospective cohort study of patients undergoing
negative Staphylococcus species, primarily S. epider- cataract procedure at one center in Canada between 1994
midis.668,670,671,673,674,678,683,684,686 Other gram-positive and 1998 found no significant difference in the rate of post-
organisms identified included S. aureus, Streptococcus spe- operative endophthalmitis with preoperative topical antimi-
cies, Enterococcus species, P. acnes, and Corynebacterium crobials compared with none.668 A significant decrease in
species. Gram-negative organisms isolated included Serratia endophthalmitis was seen with subconjunctival administra-
species, Klebsiella species, P. mirabilis, and P. aeruginosa. tion of antimicrobials at the end of the procedure compared
These organisms represent the normal flora isolated pre- with no antimicrobials.
operatively in a number of studies.675,687–693 Several prospective studies have shown decreases in
ocular flora, measured by bacterial isolate and CFU counts,
Efficacy. Data on antimicrobial prophylaxis efficacy in oph- with preoperative antimicrobial irrigation,675 topical anti-
thalmic procedures to prevent endophthalmitis are limited; microbials,687,688,691,692,698–700 and intracameral antimicrobi-
however, prophylaxis is common.684 The low rate of post- als.682 These studies did not report rates of endophthalmitis,
operative endophthalmitis makes it difficult to complete an limiting the application of the results.
adequately powered study to show efficacy of antimicrobial Choice of agent. Along with careful site preparation
prophylaxis in ophthalmic procedures; therefore, surrogate and disinfection, the ideal antimicrobial prophylaxis agent
markers of eradication of normal flora bacteria and reduc- should be bactericidal against common pathogens of postop-
tion of bacterial count on the conjunctiva, lower and upper erative endophthalmitis and be used safely in the eye.6,8,684
eyelids, eyelashes, and inner canthus (corner of the eye) pre- There is no consensus on the agent of choice for antimicro-
operatively and postoperatively are used. Many of the avail- bial prophylaxis in ophthalmic procedures, and no agent is
able studies are flawed with retrospective or uncontrolled FDA-approved for this indication. There are limited studies
design, inadequate follow-up, variations in surgical tech- evaluating the efficacy of a particular choice of antimicrobial
niques (including disinfection, antimicrobial prophylaxis prophylaxis for ophthalmic surgeries. The most efficacious
strategies, and methods for performing procedures), and antimicrobial cannot be determined from the available data
limited reporting of clinical outcomes. due to study flaws and a lack of direct comparisons. Local
The large, randomized, partially-masked, placebo- ocular flora resistance patterns should be monitored to aid in
controlled, multinational, multicenter study conducted by the selection of appropriate agents for prophylaxis.683,689,701
the European Society of Cataract and Refractive Surgeons Based on the available literature, use of povidone–
(ESCRS) compared the rate of postoperative endophthalmi- iodine as a preoperative antiseptic agent is recommended to
tis in over 16,600 patients undergoing routine cataract pro- decrease ocular microbes and thereby prevent endophthal-
cedures at 24 centers in Europe randomized to one of four mitis.6,684,702 Povidone–iodine 5% or 10% is instilled in the
perioperative prophylaxis groups.679,680,694 Patients received conjunctival sac and applied topically to the ocular skin sur-
no antimicrobial prophylaxis, intracameral cefuroxime at the face.703 The most effective protocol has not been established,
end of the procedure alone, perioperative levofloxacin 0.5% as povidone–iodine is frequently used in combination with
ophthalmic solution given within the hour before the pro- other antimicrobials.670,674,675,678,687,704 Chlorhexidine has
cedure, or both intracameral cefuroxime and perioperative been used as an effective alternative to povidone–iodine,
levofloxacin. All patients had the eye area disinfected with particularly in patients who are iodine allergic.682,703
povidone–iodine 5% preoperatively and received topical Ophthalmic surgeons surveyed in the United Kingdom
levofloxacin postoperatively. The study was stopped after reported that commonly used antimicrobial prophylactic
an interim analysis due to results of a multivariate analysis agents included cephalosporins, aminoglycosides, vanco-
indicating that patients not receiving intracameral cefurox- mycin, chloramphenicol, neomycin alone or in combination
ime were approximately five times more likely to develop with polymyxin, and fluoroquinolones.695,703 A similar sur-
endophthalmitis. The study has been questioned for its high vey of members of the American Society of Cataract and
rate of endophthalmitis, selection of cefuroxime due to gaps Refractive Surgery found that over 90% of respondents used
in gram-negative coverage, unknown drug concentrations in fluoroquinolones (mainly fourth-generation agents), van-
the aqueous humor, risks of hypersensitivity, the lack of a comycin, and cephalosporins.697 These antimicrobials have
commercially available preparation, the lack of a subcon- been recommended in practice guidelines.6
junctival cefuroxime treatment group, selection of topical Cephalosporins, specifically cef azolin, cefuroxime,
levofloxacin, and methods for statistical analysis.695–697 and ceftazidime, have been shown to be safe and effective
Two single-center, historical-controlled studies in in decreasing postoperative endophthalmitis when added
hospitals in Spain reported decreases in acute postopera- to regimens of povidone–iodine and topical antimicrobi-
tive endophthalmitis among patients undergoing cataract als.670,674,677,679,680,699 Vancomycin has been shown to de-
crease cultures and reach adequate concentrations to prevent third-generation agents ciprofloxacin and ofloxacin (1.97
and treat most corneal pathogens.675,705 Aminoglycosides per 1000 surgeries) (p = 0.0011).671
alone687 or in combination with an antiseptic agent Route. There is no consensus on the most effective
(chlorhexidine)682 showed no significant difference in the re- route of antimicrobial administration for the prevention of
duction of culture results compared with an antiseptic alone endophthalmitis. The routes of antimicrobial administration
(povidone–iodine or chlorhexidine)682,690 and no antimicro- used in ophthalmic procedures include preoperative topical
bial prophylaxis. antimicrobial ophthalmic drops, addition of antimicrobials
A randomized controlled study compared the antimi- to the irrigation solution, instillation of antimicrobials intra-
crobial activity and safety of trimethoprim 0.1%–polymyxin camerally at the end of surgery, subconjunctival injection of
B sulfate 10,000 units/mL ophthalmic solution and tobramy- antimicrobials, and postoperative topical application of anti-
cin 0.3% ophthalmic solution in patients undergoing cataract microbials.6,684,702,717
procedures.692 All patients received one drop and a subcon- The ESCRS randomized controlled study mentioned
junctival injection of corticosteroids and gentamicin post- above found that patients not receiving intracameral cefu-
operatively followed by one drop of study medication four roxime were approximately six times more likely to develop
times daily for five to seven days. No significant differences postoperative endophthalmitis.679,680,694 Surveys of the im-
were seen between groups for positive culture results from pact of the ESCRS study findings found that there was an
conjunctiva at baseline, at procedure, or at postoperative increase in the use of intracameral over subconjunctival ce-
days 5–7 or in lid margin culture at baseline and postopera- furoxime based on preliminary study results.703 For respon-
tive days 5–7. A higher rate of positive cultures at procedure dents who had not adopted this practice, the reported reasons
was seen in the trimethoprim–polymyxin group (37 of 59 for not using intracameral cefuroxime included the need for
cultures, 63%) compared with 13 (41%) of 32 cultures in the further study, concerns about risk and cost of therapy, the
tobramycin group (p = 0.043). Both medications eradicated lack of a subconjunctival comparator group, the high rate of
the majority of bacteria on the day of procedure and post- endophthalmitis in the control groups, concerns about statis-
operative days 5–7. Aqueous humor concentrations did not tical analysis, and questions regarding the selection of cefu-
achieve the MICs of S. aureus or S. epidermidis and were roxime due to gaps in ophthalmic pathogen coverage.695,697
undetectable for polymyxin B sulfate. The adverse events There is no commercially available cefuroxime formulation
of irritation and allergic reaction were experienced by three for intracameral administration, which was reported as one
patients in the trimethoprim–polymyxin group. The study of the main barriers to use of this route. Concerns regard-
ing compounded intracameral antimicrobials expressed by
authors concluded that there was no difference between tri-
survey respondents included inflammation, dilution errors,
methoprim and tobramycin in ocular flora reduction.
corneal endothelial injury, and the risk for bacterial contami-
A randomized controlled study compared conjunctiva
nation and infection.
and contact lens culture results after treatment with tobra-
A retrospective cohort study compared the efficacy of
mycin 0.3% versus ofloxacin 0.3% ophthalmic solutions in
intracameral cefuroxime versus subconjunctival cefurox-
patients undergoing photorefractive keratectomy.693 No dif-
ime in reducing the rate of endophthalmitis after cataract
ferences were seen among preoperative, postoperative, or
procedures at one center in northeast England.718 A total of
contact lens cultures between treatment groups. Although
19,425 patients received antimicrobial prophylaxis with pre-
not statistically significant, logistic regression found that cul-
operative povidone–iodine 5% in the conjunctival sac and
tures from patients treated with tobramycin were two times subconjunctival injection of cefuroxime 50 mg at the end
more likely to be positive than those treated with ofloxacin. of the procedure, and 17,318 patients received intracameral
The study had low power and did not compare baseline and cefuroxime 1 mg at the end of the procedure. There were two
posttreatment culture results for any treatment group. groups of patients excluded from the analysis: protocol vio-
Fluoroquinolones have been found in studies to sig- lators who received no prophylaxis and patients who were
nificantly decrease the ocular culture results from base- enrolled in the ESCRS study. The overall rate of endophthal-
line667,673,691,698,700,706; achieve aqueous humor, vitreal, mitis in analyzed patients was 35 cases in 36,743 procedures
and corneal tissue concentrations adequate to prevent and (0.95 per 1,000 cases). Of these, 27 occurred in the subcon-
treat common ocular pathogens705,707–710; and result in im- junctival cefuroxime group (1.39 per 1,000 cases), and 8 oc-
proved ocular measurements (i.e., visual acuity, epithelial curred in the intracameral group (0.46 per 1,000 cases) (OR,
cell counts, and epithelial healing).711–716 A retrospective 3.01; 95% CI, 1.37–6.63; p = 0.0068).
multicenter case series of 20,013 patients who underwent Several studies found a lower rate of endophthalmitis
uncomplicated cataract surgeries and received fourth- with the addition of intracameral cephalosporins (cefazolin
generation fluoroquinolones preoperatively and postopera- and cefuroxime) at the end of the surgical procedure after
tively reported the rates of postoperative endophthalmitis.673 routine perioperative and postoperative topical antimicrobial
Endophthalmitis occurred in 9 (0.06%) of 16,209 surgeries prophylaxis regimens.670,674 A case–control study revealed a
in patients treated with gatifloxacin 0.3% ophthalmic solu- 5.7 times increased likelihood of developing postoperative
tion (95% CI, 0.03–0.1%) and in 5 (0.1%) of 3,804 surgeries endophthalmitis with topical antimicrobial prophylaxis only
in patients treated with moxifloxacin 0.5% ophthalmic solu- (including gentamicin 0.3% and chlorhexidine 0.05%) com-
tion (95% CI, 0.05–0.3%). There were no significant differ- pared with the addition of intracameral cefuroxime 1 mg
ences in efficacy between agents. to the regimen in cataract procedure.677 Both intracameral
In a retrospective cross-sectional study conducted over cephalosporins and moxifloxacin have been shown as safe,
a 10-year period with third- and fourth-generation fluoroqui- with no adverse events and no effects on visual acuity and
nolones, significantly lower rates of endophthalmitis were endothelial cell counts.670,674,699,715,716
reported for the fourth-generation agents moxifloxacin and One study involving healthy adult volunteers found
gatifloxacin (0.56 per 1000 cataract surgeries) than for the that orally administered levofloxacin and moxifloxacin
achieved adequate aqueous humor concentrations to provide A randomized controlled study compared the effec-
activity against gram-positive and most gram-negative ocu- tiveness of topical ofloxacin in the reduction or elimination
lar pathogens without adverse events.707 of conjunctival bacterial flora when given as one drop ev-
The addition of subconjunctival antimicrobials to ex- ery five minutes for three applications one hour before the
isting topical antimicrobial prophylaxis regimens has also procedure alone (control group) or combined with ofloxacin
been shown to reduce the rate and risk of endophthalmitis in one drop four times daily for three days (study group) before
intraocular procedures compared with topical antimicrobials cataract procedures.688 No differences in positive conjuncti-
alone.668,681,686 Topical antimicrobials have been shown to be val cultures were seen between groups five days before topi-
safe and effective in lowering rates of endophthalmitis,671,673 cal antimicrobials or before the administration of ofloxacin
decreasing bacterial organisms and CFUs in conjunc- on the day of the procedure. Significantly higher positive
tiva,667,675,691,692,698,700 and achieving adequate concentrations culture rates were seen in the control group than in the study
to be effective against most ocular pathogens,705,706,708–710,719 group one hour after the administration of the preoperative
with no notable adverse events.711–714 antimicrobial and before povidone–iodine, immediately be-
Duration and timing. There are a lack of clear evidence fore the procedure, and at the conclusion of the procedure.
and no consensus on the appropriate duration and timing of Mean CFU counts did not significantly differ five days pre-
antimicrobial prophylaxis in ophthalmic procedures.6,684 operatively and immediately before the procedure but were
Commonly reported times of antimicrobial prophylaxis significantly higher in the control group at all other time
include preoperatively, intraoperatively, at the end of the points. Neither outcomes of endophthalmitis nor patient
procedure, and postoperatively.684 Few studies have inves- compliance with antimicrobial use was reported. The study’s
tigated the differences between the timing and duration of authors concluded that three days of topical ofloxacin was
antimicrobial prophylaxis regimens. Many of the regimens more effective than administration just one hour before the
are used in combination, making it difficult to determine the procedure in reducing the number of positive bacterial cul-
optimal timing and duration. Preoperative antimicrobial tim- tures at several time points perioperatively.
ing reported in the literature has ranged from one to multiple Numerous studies have evaluated the efficacy of in-
drops within an hour preoperatively on the day of the pro- tracameral and subconjunctival injections of antimicrobi-
cedure671,673,679,680,692–694,698,703,709,710,716 or one to three days als given at the end of surgery.6,674,677,679–682,697,699,703,716,718
before the procedure.667,698,700,703,708,710,712,714 The most commonly reported dose of intracameral cefu-
Two topical moxifloxacin regimens were compared for roxime was 1 mg,677,679,680,682,699,718 and the most commonly
conjunctival bacterial flora and aqueous humor concentra- reported subconjunctival dose was 50 mg.718 Doses of 2.5
tions in a randomized controlled study of patients undergo- or 1 mg of intracameral cefazolin were studied,670,674 as
ing cataract procedures.691,719 In one regimen, patients were were 250- and 500-mg doses of intracameral moxifloxa-
administered moxifloxacin 0.5% four times a day beginning cin.715,716 Postoperative dosing strategies reported in the
one day before the procedure plus one drop two hours before literature include four times daily for 3–7 days667,670,671,673–
675,679,680,692,711,712,715
the procedure (total of five drops before the procedure); the and for up to 15 days713,714 or until the
716
other group received moxifloxacin 0.5% two hours before bottle was empty.
surgery and every 15 minutes for the first hour of the proce- Despite the lack of well-controlled trials, the conse-
dure (total of five drops). There were no cases of postopera- quences of bacterial endophthalmitis support the use of pro-
tive endophthalmitis up to six months after the procedure in phylactic antimicrobials. No definitive studies have clearly de-
any patient. Administration of moxifloxacin on the day of lineated superiority of antimicrobial route, timing, or duration.
the procedure was found to result in a significant decrease in
median CFU compared with baseline and was found (based Recommendation. Due to the lack of robust data from trials,
on change in log CFU) to be more effective than antimicro- specific recommendations cannot be made regarding choice,
bial administration on the day before the procedure. Mean route, or duration of prophylaxis. As a general principle,
aqueous humor concentrations of moxifloxacin at the begin- the antimicrobial prophylaxis regimens used in ophthalmic
ning of the procedure were significantly higher in the group procedures should provide coverage against common ocu-
who received the drug on the day of the procedure. lar pathogens, including Staphylococcus species and gram-
A small, randomized controlled study compared aque- negative organisms, particularly Pseudomonas species.
ous humor concentrations of levofloxacin and ciprofloxacin Preoperative antisepsis with povidone–iodine is rec-
in patients undergoing a cataract procedure with routine ommended, based on available evidence. Appropriate topi-
phacoemulsification given as (1) one or two drops four times cal antimicrobials include commercially available neomy-
daily for two days before the procedure, with the last dose cin–polymyxin B–gramicidin solution or fluoroquinolones
given immediately before bedtime on the night before the (particularly fourth-generation agents) given as one drop
procedure, (2) five doses (one or two drops) delivered every every 5–15 minutes for five doses within the hour before the
10 minutes in the hour before the procedure, or (3) a combi- start of the procedure (Table 2). The addition of subconjunc-
nation of both dosing strategies.706 Aqueous humor concen- tival cefazolin 100 mg or intracameral cefazolin 1–2.5 mg
trations of levofloxacin were significantly higher than those or cefuroxime 1 mg at the end of the procedure is optional.
of ciprofloxacin. Significantly higher doses of drug were While some data have shown that intracameral antimicrobi-
delivered to the aqueous humor in the group receiving same- als may be more effective than subconjunctival antimicro-
day prophylaxis than in patients receiving levofloxacin or bials, there are no commercially available antimicrobials
ciprofloxacin two days before surgery. No cases of endo- approved for these routes of administration. (Strength of
phthalmitis or ocular or systemic toxicities were reported. evidence for prophylaxis = B.)
Orthopedic Procedures ther MRSA or MSSA.150,151,157,741,749–755 Readers are referred

to additional discussion in the Common Principles section
Background. Orthopedic procedures considered in these of these guidelines.
guidelines include clean orthopedic procedures (not involv-
ing replacement or implantations), spinal procedures with or Clean Orthopedic Procedures Not
without instrumentation, repair of hip fractures, implanta- Involving Implantation of Foreign
tion of internal fixation devices (screws, nails, plates, and Materials
pins), and total-joint-replacement procedures. Grade III
open fractures (extensive soft tissue damage and crushing) Background. In clean orthopedic procedures, such as knee,
are often associated with extensive surgical-site contamina- hand, and foot procedures, and those not involving the im-
tion and are routinely managed with empirical antimicrobial plantation of foreign materials, the need for antimicrobial
treatment and surgical debridement, for which guidelines prophylaxis is not well established.738,749,756 Antimicrobial
have been published separately.720 Available guidelines rec- prophylaxis in patients undergoing diagnostic and operative
ommend that antimicrobial prophylaxis in grade I (clean arthroscopic procedures is controversial.6,757–760 The risks of
wound with ≤1-cm laceration) and grade II (clean wound SSI and long-term sequelae are low for procedures not in-
with >1-cm laceration without extensive soft tissue damage) volving implantation.
open fractures be handled similarly to other clean orthopedic
procedures.721–724 Efficacy. The efficacy of antimicrobial prophylaxis in clean
Between 2006 and 2008, SSIs were reported nation- orthopedic procedures was first investigated in the middle
ally, based on risk category, in approximately 0.7–4.15 per part of the 20th century. A number of these studies and re-
100 procedures for patients undergoing spinal fusion, 0.72– views have since been found to be flawed, as patients were
2.3 per 100 procedures in patients undergoing laminectomy, not randomized to treatment groups and the timing and du-
0.67–2.4 per 100 procedures in patients undergoing hip ration of antimicrobial prophylaxis were not studied.761,762
prosthesis, and 0.58–1.60 per 100 procedures in patients un- Further, patients were administered prophylactic antimi-
dergoing knee prosthesis.165 Postoperative SSI is one of the crobials after the surgical procedure, which may have led
most costly complications of orthopedic procedures due to to invalid results. The low rate of infection and absence of
hospital readmissions, extended hospital length of stay, the serious morbidity failed to justify the expense or potential
need for additional procedures (often removal and reimplan- for toxicity and resistance associated with routine use of
tation of implanted hardware), convalescent or nursing home antimicrobial prophylaxis in the setting of clean orthopedic
care between procedures, and significant increases in direct procedures.
hospital costs (e.g., prolonged antimicrobial therapy).725,726
Studies have found that the estimated economic impact of Recommendations. Antimicrobial prophylaxis is not recom-
one deep SSI was $100,000 in hospital costs alone after hip mended for patients undergoing clean orthopedic procedures,
arthroplasty and $60,000 after knee arthroplasty.727–731 including knee, hand, and foot procedures, arthroscopy, and
In light of the serious consequences, antimicrobial other procedures without instrumentation or implantation of
prophylaxis is well accepted in procedures involving the foreign materials. (Strength of evidence against prophylaxis =
implantation of foreign materials.8,732 Prophylaxis is also in- C.) If the potential for implantation of foreign materials is un-
dicated in spinal procedures without instrumentation, where known, the procedure should be treated as with implantation.
an SSI would pose catastrophic risks.726,733–738
Organisms. Skin flora are the most frequent organisms in- Spinal Procedures with and without
volved in SSIs after orthopedic procedures. The most com- Instrumentation
mon pathogens in orthopedic procedures are S. aureus,
gram-negative bacilli, coagulase-negative staphylococci (in- Background. Data support the use of antimicrobial pro-
cluding S. epidermidis), and b-hemolytic streptococci.739–743 phylaxis for orthopedic spinal procedures with and with-
Spinal procedures may be complicated by polymicrobial in- out instrumentation, including fusions, laminectomies, and
fection that includes gram-negative bacteria.740 minimally invasive disk procedures, to decrease the rate of
A contributing factor to SSIs in arthroplasty is the postoperative spinal infection.8,543,563,732,733,739,763–766 SSIs
formation of bacterial biofilm, particularly with S. aureus after orthopedic spinal procedures, including minimally in-
and S. epidermidis, on inert surfaces of orthopedic devices. vasive disk procedures, are associated with high morbidity.
Bacterial biofilm confers antimicrobial resistance and makes Invasion of the epidural space in organ/space SSIs is of par-
antimicrobial penetration difficult.744–748 ticular concern after spinal procedures.8,145,767
There is increasing concern regarding the emergence SSI rates vary with the complexity of the procedure.
of SSIs due to resistant microorganisms, specifically VRE One retrospective, multicenter study of 1274 adult patients
and MRSA in surgical patients. Several studies have investi- found an overall SSI rate of 0.22% with antimicrobial pro-
gated MRSA colonization and SSIs and evaluated the effect phylaxis after minimally invasive spinal procedures (i.e.,
of decolonization, including the use of topical mupirocin, in any spinal procedures performed through a tubular retractor-
orthopedic procedures.150,157,741,749–753 Mupirocin decoloni- type system).768 Procedures included simple decompressive
zation protocols as an adjunct to i.v. cephalosporin prophy- procedures (such as microscopic or endoscopic discectomy
laxis in orthopedic patients resulted in significant decreases or foraminotomy or decompression of stenosis), minimally
in nasal MRSA carriage150,751 and overall SSIs.157,750–752 invasive arthrodeses with percutaneous instrumentation, and
Preoperative decolonization with intranasal mupirocin may minimally invasive intradural procedures. The SSI rate in
have utility in patients undergoing elective orthopedic pro- patients receiving antimicrobial prophylaxis undergoing spi-
cedures who are known to be colonized or infected with ei- nal procedures with instrumentation has ranged from 2.8%
to 9.7%.165,764,765,769,770 Monosegmental instrumentation has microbial infections, including those caused by gram-nega-
a reported SSI rate of <2%, compared with 6.7% for instru- tive bacteria.563,769
mentation at multiple levels.771 Clindamycin and vancomycin have adequate activity
Several case–control studies of adults undergoing spi- against the most common pathogens involved in orthope-
nal procedures with and without instrumentation have found dic procedures and would be acceptable alternatives under
the following notable patient-related risk factors for SSI: certain circumstances, such as prophylaxis for patients with
prolonged preoperative hospitalization,771 diabetes,767,772–775 a b-lactam allergy. Vancomycin should be included with ce-
elevated serum glucose concentration (>125 mg/dL preoper- fazolin or used as an alternative agent for routine antimicro-
atively [within 30 days] or >200 mg/dL postoperatively),773 bial prophylaxis for patients who are known to be colonized
older age,767,776 smoking and alcohol abuse,776 previous pro- with MRSA.6,8,41,733,781
cedure complicated by infection,774–776 and obesity.770–775,777 Duration. The majority of available studies of antimi-
Procedure-related risk factors include extended duration of crobial prophylaxis in spinal procedures have used single
procedure (defined in studies as two to five hours or greater doses or regimens of <24 hours’ duration.732 There is no
than five hours,775 greater than three hours,771 and greater high-quality evidence supporting a duration of >24 hours,782
than five hours776), excessive blood loss (>1 L),771,775 staged and some sources recommend only a single preoperative
procedure,776 multilevel fusions,777 foreign-body placement dose.8,769,778
(e.g., screw, rod, plate),767 combined anterior and posterior
fusion,776 and suboptimal antimicrobial timing (>60 minutes Pediatric Efficacy. While no studies have evaluated the ef-
before or after incision).773 A significant decrease in SSIs ficacy of antimicrobial prophylaxis in pediatric patients un-
was seen with procedures at the cervical spine level772,773 or dergoing spinal procedures with or without instrumentation,
with an anterior surgical approach.775 the incidence and risk factors for SSIs in this population
have been reported. The frequencies of SSIs in pediatric pa-
Efficacy. Despite the lack of comparative studies evaluating tients undergoing spinal fusion were 3.5% (<18 years old),783
prophylaxis for spinal procedures with and without instru- 3.8% (<19 years old),784 4.4% (ages 1–22 years old), and
mentation (implantation of internal fixation devices), anti- 5.2% (<17 years old)764 for varying conditions, including
Scheuermann’s kyphosis,784 myelodysplasia,764 idiopathic
microbial prophylaxis is recommended due to the associated
scoliosis,783,785 neuromuscular scoliosis,785 kyphosis,783 and
morbidity and assumed costs of SSIs.771 A meta-analysis of
spondylolisthesis.783 The majority of patients in studies re-
six studies with 843 patients undergoing spinal procedures
porting antimicrobial prophylaxis received cefazolin, van-
(types of procedures were not differentiated in the analy-
comycin, or clindamycin.764,783,785
sis) demonstrated an overall effectiveness of antimicrobial
Risk factors for SSIs after spinal procedures with
prophylaxis.732 Antimicrobials studied included single-dose
instrumentation in a pediatric population include myelo-
or multidose regimens of <24 hours’ duration of cephalori-
dysplasia,764 procedure at the sacral spine, obesity,785 ASA
dine (a first-generation cephalosporin no longer available in
classification of >2, a complex medical condition (including
the United States), vancomycin and gentamicin, cefazolin
spinal bifida, cerebral palsy, Marfan syndrome, achondro-
with and without gentamicin, piperacillin, and oxacillin. The
plasia, osteogenesis imperfecta, other unspecified genetic
pooled SSI rate with antimicrobial prophylaxis was 2.2%, disease, muscular dystrophy, spinal muscular atrophy, or
compared with 5.9% in controls (OR, 0.37; 95% CI, 0.17– other debilitating myopathies),783 and previous spinal pro-
0.78; p < 0.01). One randomized controlled study of 1237 cedures. One study found a decreased risk of infection with
adult patients undergoing spinal procedures to repair a her- hypothermia (core body temperature of <35.5 °C for the du-
niated disk (hemilaminectomy, laminectomy, flavectomy, ration of the procedure).785
spondylosyndesis) found no significant difference in the rate Two studies found suboptimal antimicrobial prophy-
of SSIs between single-dose cefuroxime 1.5 g i.v. (1.3%) laxis as a risk factor for SSIs in spinal procedures.764,783
and placebo (2.9%) given within 60 minutes before surgi- Optimal antimicrobial prophylaxis was defined as cefazo-
cal incision. No significant difference was seen between lin 20 mg/kg (up to 2 g) given within 30 minutes764 or 60
treatment groups for incisional SSIs (0.98% and 1.12%, re- minutes783 before surgical incision, vancomycin 10 mg/kg
spectively) or deep SSIs (0.33% and 0.32%, respectively), (up to 1 g) given within 60 minutes783 or 150 minutes764 be-
but the difference in organ/space infections was significant fore surgical incision, or clindamycin 10 mg/kg (up to 600
between groups (0% and 1.44%, respectively; p < 0.01).778 mg) given within 60 minutes before surgical incision.783
Choice of agent. There is no clearly superior antimi- Intraoperative redosing was defined as appropriate for ce-
crobial agent or regimen for spinal procedures.563,769 The an- fazolin if administered for procedures lasting more than four
timicrobials most often studied for prophylaxis in orthopedic hours and for vancomycin or clindamycin for procedures
procedures are first-generation cephalosporins, particularly lasting more than six hours in one study783 and for cefazolin
cefazolin. Cefazolin has been noted as a suitable agent for administered every eight hours in the other study.764 A third
spinal procedures with its spectrum of activity (e.g., against study found that use of clindamycin as the perioperative an-
Staphylococcus species and gram-negative bacilli such as E. timicrobial increased the risk of SSI.785
coli) and adequate tissue121 and disk concentrations.779,780
Second- and third-generation cephalosporins offer no Recommendations. Antimicrobial prophylaxis is recom-
major advantages over first-generation agents. Their routine mended for orthopedic spinal procedures with and without
use is not recommended due to their higher cost and poten- instrumentation. The recommended regimen is cefazolin
tial to promote resistance, particularly among health-care- (Table 2). (Strength of evidence for prophylaxis in ortho-
associated gram-negative bacilli.8 Broader coverage may be pedic spinal procedures = A.) Clindamycin and vancomycin
considered for instrumented fusion due to the risk of poly- should be reserved as alternative agents as described in the
Common Principles section. If there are surveillance data a b-lactam allergy. Vancomycin should be included with ce-
showing that gram-negative organisms are a cause of SSIs fazolin or used as an alternative agent for routine antimicro-
for the procedure, practitioners may consider combining bial prophylaxis for patients who are known to be colonized
clindamycin or vancomycin with another agent (cefazolin with MRSA.6,8,41,733,781
if the patient is not b-lactam allergic; aztreonam, gentami- Duration. For effective prophylaxis, the MIC of the
cin, or single-dose fluoroquinolone if the patient is b-lactam antimicrobial needs to be exceeded at the target site from
allergic). Mupirocin should be given intranasally to all pa- the moment of incision until surgical-site closure.788 Two
tients known to be colonized with S. aureus. meta-analyses demonstrating the efficacy of antimicrobial
prophylaxis in long-bone and hip fracture procedures also
Hip Fracture Repair showed that multiple perioperative doses did not offer an
advantage over a single preoperative dose.787,788 These stud-
Background. Data support the use of antimicrobial pro- ies support a duration of antimicrobial prophylaxis of ≤24
phylaxis for hip fracture repair to reduce the rate of SSIs, hours.
particularly in procedures that involve internal fixation (e.g.,
nails, screws, plates, wires). SSIs after hip fracture repair Recommendations. The recommended regimen in hip frac-
can result in extensive morbidity, including prolonged and ture repair or other orthopedic procedures involving inter-
repeated hospitalization, sepsis, persistent pain, device renal fixation is cefazolin. Clindamycin and vancomycin
placement, and possible death.726,739,786–790 should be reserved as alternative agents, as described in the
Common Principles section. If there are surveillance data
Efficacy. The efficacy of antimicrobial prophylaxis in showing that gram-negative organisms are a cause of SSIs
hip fracture repair has been illustrated in two meta-analy- for the procedure, practitioners may consider combining
ses.787,788 One meta-analysis of 15 hip fracture procedure clindamycin or vancomycin with another agent (cefazolin if
trials (the majority of procedures involved closed, proximal the patient is not b-lactam allergic; aztreonam, gentamicin,
femoral, or trochanteric fractures with internal fixation) or single-dose fluoroquinolone if the patient is b-lactam al-
demonstrated that any dose and duration of prophylaxis are lergic). Mupirocin should be given intranasally to all patients
superior to no prophylaxis with respect to preventing SSIs with documented colonization with S. aureus. (Strength of
(deep and superficial SSIs were analyzed together).787 The evidence for prophylaxis = A.)
rate of SSIs was 10.4% in controls versus 5.39% in treat-
ment groups. A second meta-analysis of 22 studies reiterated Total Joint Replacement
the efficacy of antimicrobial prophylaxis in fracture proce-
dures.788 The analysis included the same hip fracture studies Background. In 2005, more than 750,000 hip or knee replace-
examined in the first meta-analysis, with additional studies ments were performed in the United States.793 The reported
of long-bone fracture repair (i.e., closed ankle fracture and frequency of SSIs complicating hip, knee, elbow, ankle, or
other closed fractures, some noted with internal fixation). shoulder replacement ranges from 0.6% to 12%.743,786,794–797
This second meta-analysis reviewed 10 studies of 1896 pa- SSI rates as high as 11% after hip replacement and 12% after
tients receiving a preoperative and two or more postopera- elbow replacement have been reported.786,797 However, for
tive doses of a parenteral antimicrobial compared with a pla- hip and knee replacements, the most common joint arthro-
cebo or with no treatment. The authors found a relative risk plasties, infection rates are typically less than 2%.165
of deep SSIs of 0.36 (95% CI, 0.21–0.65) and a relative risk The introduction of antimicrobial prophylaxis, strin-
of superficial SSIs of 0.48 (95% CI, 0.28–0.81) associated gent infection-control protocols, and the use of ultraclean
with antimicrobial use. operating rooms has led to a substantial reduction in SSI
Choice of agent. The antimicrobials most often studied rates (to ≤1%).734,786,796,798,799 Postoperative prosthetic joint
for prophylaxis in orthopedic procedures are first-generation infection is an organ/space SSI that occurs early (within 3
cephalosporins due to their ease of administration, low cost, months postoperatively), is delayed (3–12 months postoper-
and safety profile.787,788,791 Second- and third-generation atively), or occurs late (>12 months after surgery).748 These
cephalosporins have not been shown to offer clear advan- infections frequently require removal of the prosthesis, a
tages over first-generation agents. These agents are not rec- prolonged course of antimicrobials, and one- or two-stage
ommended for routine use due to their higher cost, potential reimplantation of the prosthesis and may result in perma-
to promote resistance, and association with adverse events nent disability.796,800 Studies have shown an estimated eco-
(e.g., C. difficile-associated diarrhea).8,790,792 nomic impact of one deep SSI of $100,000 in hospital costs
Alternative regimens may be needed for institutions alone after hip arthroplasty and $60,000 after knee arthro-
with highly resistant organisms, such as MRSA or C. dif- plasty.727–731
ficile. Success in decreasing rates of C. difficile-associated Common risk factors for prosthetic joint infection748
disease and mortality was seen in a single-center study with include advanced age; obesity; diabetes mellitus; corticoste-
the antimicrobial prophylaxis regimen change from three roid use; malignancy; rheumatoid arthritis; previous arthro-
doses of cefuroxime790,792 to a single preoperative dose of plasty on the same joint; arthroplasty undertaken to treat a
cefuroxime plus gentamicin.792 In another study, C. difficile- fracture; type of joint replaced (e.g., risk is greater for the
associated disease decreased after the prophylaxis regimen knee than the hip); perioperative surgical-site complica-
was changed from cefuroxime to amoxicillin–clavulanate.790 tions, including superficial SSI; hematoma; and persistent
Clindamycin and vancomycin have adequate activity surgical-site drainage. Operative risk factors include ASA
against the most common pathogens involved in orthope- classification of ≥3, duration of procedure exceeding the
dic procedures and would be acceptable alternatives under 75th percentile for the procedure or exceeding three hours,
certain circumstances, such as prophylaxis for patients with surgical site classified as contaminated or dirty, and no sys-
temic antimicrobial prophylaxis. Excluding the presence of superior to i.v. antimicrobials,808,809 there is evidence that
a systemic antimicrobial, patients with these operative risk supports the combination of using antimicrobial-laden bone
factors are at the greatest risk of developing an SSI. cement together with systemic antimicrobial prophylaxis.
A contributing factor to SSIs in arthroplasty is the for- Although the evidence for the prophylactic use of an-
mation of bacterial biofilm, particularly with S. aureus and timicrobial-laden bone cement in primary joint arthroplasty
S. epidermidis, on inert surfaces of orthopedic devices to looks favorable, a recent multicenter evaluation of risk fac-
confer antimicrobial resistance and difficulty in antimicro- tors for SSI in patients undergoing total hip arthroplasty did
bial penetration.744–748 not find that use of antimicrobial-laden bone cement reduced
the risk for infection.95 In addition, questions remain regard-
Efficacy. The majority of studies that have evaluated anti- ing the risk for antimicrobial resistance and allergy, as well
microbial prophylaxis in joint replacements have been con- as the increased cost.41,802–807,810–813 Readers are referred to
ducted in patients undergoing total hip or total knee arthro- reviews of this topic for additional information about tissue
plasty.801 There is a lack of efficacy data involving elbow, penetration, clinical application, and safety.805,810–815
shoulder, and ankle arthroplasty; however, the same antimi- Duration. The duration of prophylaxis in joint replace-
crobial prophylaxis principles can be applied. In light of the ment procedures has been controversial. More recent data
serious potential consequences, antimicrobial prophylaxis is and clinical practice guidelines do not support prophylaxis
well accepted in procedures involving the implantation of beyond 24 hours.6,41,133,723 Studies involving total hip re-
foreign materials.8,543,732,733 placement have used antimicrobials for 12 hours to 14 days
A meta-analysis supports the use of antimicrobial pro- postoperatively.726,734–737,816 A duration of 24 hours was sup-
phylaxis for SSI reduction in patients undergoing total joint ported in a randomized trial of 358 patients undergoing to-
replacement.801 Of the 26 randomized controlled studies ex- tal hip arthroplasty, total knee arthroplasty, or hip fracture
amined, 24 included patients undergoing total hip or total repair that compared prophylaxis that lasted 24 hours ver-
knee arthroplasty. The meta-analysis noted that the studies sus 7 days of either nafcillin or cefazolin started 20 minutes
did not clearly state if the arthroplasties were primary or re- before the procedure.816 The difference in SSI rates between
vision. The SSIs were defined as visible purulent exudates at groups was not significant. There is no evidence of benefit
the surgical site (deep or superficial) in the included studies. of antimicrobial administration until all drains or catheters
Seven studies (n = 3065 patients) pooled to compare antimi- are removed.32,41,133
crobial prophylaxis with placebo found a relative risk reduc-
tion of SSIs of 81%. Recommendations. The recommended regimen for patients
Choice of agent. There are no data supporting superi- undergoing total hip, elbow, knee, ankle, or shoulder replace-
ority of one class of antimicrobials over another for antimi- ment is cefazolin. Clindamycin and vancomycin should be
crobial prophylaxis in total joint replacement. A meta-analy- reserved as alternative agents, as described in the Common
sis of studies, mainly in total hip or total knee replacement, Principles section. If there are any surveillance data show-
found no difference in SSIs between cephalosporins with ing that gram-negative organisms are a cause of SSIs for the
teicoplanin (not available in the United States) in five stud- procedure, practitioners may consider combining clindamy-
ies with 2625 patients, cephalosporins and penicillin deriva- cin or vancomycin with another agent (cefazolin if the pa-
tives in three studies of 386 patients, and first- and second- tient is not b-lactam allergic; aztreonam, gentamicin, or a
generation cephalosporins in eight studies of 2879 pa- single-dose fluoroquinolone if the patient is b-lactam aller-
tients.801 Selection should be based on cost, availability, and gic). Mupirocin should be given intranasally to all patients
local resistance patterns. First-generation cephalosporins are with documented colonization with S. aureus. (Strength of
the agents most commonly studied and used for antimicro- evidence for prophylaxis = A.)
bial prophylaxis in joint replacement procedures.
Clindamycin and vancomycin have adequate activity Urologic Procedures
against the most common pathogens involved in orthopedic
procedures and would be acceptable alternatives under cer- Background. The goals of antimicrobial prophylaxis in
tain circumstances, such as prophylaxis for patients with a b- urologic procedures are the prevention of bacteremia and
lactam allergy. Vancomycin should be included with cefazo- SSIs and the prevention of postoperative bacteriuria.59
lin or used as an alternative agent for routine antimicrobial Postoperative urinary tract infections (UTIs) are the main
prophylaxis in institutions that have a high prevalence of concern for morbidity in patients after urologic proce-
MRSA SSIs and for patients who are known to be colonized dures.817,818 Bacteriuria, defined as >103 or >104 CFU/mL
with MRSA.6,8,41,733,781 Readers are referred to the section on in symptomatic UTI and >105 CFU/mL in asymptomatic
implantation of internal fixation devices for further discus- bacteriuria, within 30 days postoperatively is a frequent pri-
sion of antimicrobial prophylaxis choice. mary outcome in urologic procedure studies.819–825 The ben-
Antimicrobial-laden bone cement. The use of antimi- efits of preventing postoperative bacteriuria are not clearly
crobial-laden bone cement in conjunction with i.v. antimi- known.825
crobial prophylaxis is common worldwide, particularly for In addition to general risk factors discussed in the
the prevention of infection in primary hip and knee arthro- Common Principles section of these guidelines, urologic-
plasties.802–806 FDA has approved premixed aminoglycoside specific risk factors include anatomic anomalies of the uri-
(i.e., gentamicin and tobramycin) in bone cement products nary tract,818 urinary obstruction,826 urinary stone,817,825,826
for use in hip, knee, or other joints in second-stage revision and indwelling or externalized catheters.817,818,822,826
of total joint arthroplasty.807 The products are not approved Preoperative UTI, particularly if recurrent, is recognized
for prophylaxis in primary joint replacement procedures. as a high-risk factor for postoperative infection, which is
While antimicrobial bone cement has not been shown to be typically treated before procedures and is a common ex-
clusion criterion from studies of efficacy of antimicrobial bacteremia, as well as the need for additional postopera-
prophylaxis in urologic procedures.817,826–828 Additional uro- tive antimicrobials.847 An additional multicenter, open-label,
logic operation-specific risk factors include length of post- randomized, active- and placebo-controlled trial in patients
operative catheterization,829 mode of irrigation (closed ver- with sterile urine undergoing TURP found a decreased rate
sus open), and postoperative pyuria.821 of bacteriuria (≥5 CFU/mL) with antimicrobial prophylaxis
(21% with levofloxacin and 20% with sulfamethoxazole–
Organisms. E. coli is the organism most commonly isolated trimethoprim) compared with placebo (30%) (p = 0.009).822
in patients with postoperative bacteriuria; however, other Three randomized, placebo-controlled studies of pa-
gram-negative bacilli and enterococci may also cause infec- tients undergoing transrectal needle biopsy of the prostate
tion.818,821,827,830–839 Organisms such as S. aureus, coagulase- found significant differences in infectious complications
negative Staphylococcus species, and group A Streptococcus (including bacteriuria, positive urine cultures, and UTI) in
species are also a concern in procedures entering the skin with patients treated with single doses of oral antimicrobial pro-
or without entering the urinary tract.818,827,830–832,838,840,841 phylaxis compared with placebo.819,837,838 These three stud-
There is also some concern with biofilm-forming bacteria ies support the routine use of antimicrobial prophylaxis in all
(S. epidermidis and P. aeruginosa) in patients with prosthe- patients undergoing transrectal needle biopsy of the prostate.
sis implantation.842 Of note, all patients undergoing transrectal needle biopsy of
the prostate received a cleansing enema before the proce-
Efficacy. The efficacy of antimicrobial prophylaxis in select dure.819,837,838 Use of MBP has been reported in urologic pro-
urologic procedures has been investigated in several clini- cedures that involve entering the gastrointestinal tract (e.g.,
cal trials. Of note, many of these placebo-controlled studies urinary diversion).844,846
have excluded patients with risk factors for infection, those The use of antimicrobial prophylaxis in patients un-
requiring antimicrobial prophylaxis for another indication dergoing extracorporeal shock wave lithotripsy (ESWL)
(e.g., infective endocarditis), and those with preoperative and ureterorenoscopy is supported by the results of a meta-
UTI or bacteriuria. analysis847 and a small randomized controlled trial.848 The
The efficacy of antimicrobial prophylaxis in clean meta-analysis included eight randomized controlled trials
procedures among patients at low risk of complications has with 885 patients and six clinical case series involving 597
been variable. One randomized, placebo-controlled study patients undergoing ESWL.845 The overall rate of UTI in the
of oral antimicrobials in 2083 patients undergoing flexible randomized controlled trials ranged from 0% to 7.7% with
cystoscopy found a positive urine culture (bacteriuria with antimicrobial prophylaxis and from 0% to 28% in the control
>105 CFU/mL) in 9.1% of patients receiving placebo, 4.6% groups (relative risk, 0.45; 95% CI, 0.22–0.93). A random-
of patients receiving trimethoprim, and 2.8% of patients re- ized, placebo-controlled study of 113 patients undergoing
ceiving ciprofloxacin.839 The rates of bacteriuria compared ureterorenoscopy found a rate of postoperative bacteriuria
with baseline were significantly higher with placebo and of 1.8% with antimicrobial prophylaxis and 12.5% without
significantly lower with use of antimicrobials compared (p = 0.0026).848 No patients had symptomatic UTI or inflam-
with placebo. A randomized, placebo-controlled study of mation complications of the urogenital tract postoperatively.
517 patients undergoing prostate brachytherapy found no There are no studies of antimicrobial prophylaxis in
significant difference in postimplantation epididymitis with major open or laparoscopic procedures (cystectomy, radical
or without antimicrobial prophylaxis (0.4% and 1.5%, re- prostatectomy, and nephrectomy); therefore, data have been
spectively).843 A meta-analysis of eight randomized, pla- extrapolated from other major intraabdominal procedures.
cebo-controlled or no-treatment-controlled studies with 995 Choice of agent. No single antimicrobial regimen ap-
patients undergoing urodynamic studies found a decrease in pears superior for urologic procedures. A wide range of antimi-
bacteriuria with antimicrobial prophylaxis (OR, 0.39; 95% crobial regimens, including cephalosporins,658,835,836,843,849–855
CI, 0.24–0.61).820 The number needed to treat was 13 to pre- aminoglycosides,856,857 piperacillin–tazobactam,849,858,859
vent one episode of asymptomatic bacteriuria using a pooled trimethoprim–sulfamethoxazole,822,838,860 trimeth
rate of 13.7% for bacteriuria. One study found that not using oprim,839 nitrofurantoin,861 and fluoroquino-
antimicrobial prophylaxis was a significant risk factor for lones, 819,821,822,824,831,835–837,839,840,843,848,851,853–855,862,863
bacteriuria caused by urinary dynamic studies.821 have been evaluated in urologic procedures. The effi-
Antimicrobial prophylaxis has been studied in uro- cacy of fluoroquinolones for antimicrobial prophylaxis
logic procedures involving entry into the gastrointestinal in urologic surgical procedures has been well estab-
tract, with the majority of the literature on transurethral lished. One study found better reduction of bacteriuria
resection of the prostate (TURP) and prostate biopsy. Two with either ciprofloxacin or trimethoprim compared with
large meta-analyses have suggested prophylactic antimi- placebo,839 while other studies found no difference in
crobials may be effective in all patients undergoing TURP, efficacy between a fluoroquinolone and sulfamethoxazole–
including low-risk patients and those with preoperatively trimethoprim, both of which were better than placebo.822,838
sterile urine.844,845 One meta-analysis of 32 trials with 4260 No differences were found in studies between oral or i.v. fluo-
patients found that prophylactic antimicrobials decreased roquinolones (ciprofloxacin or ofloxacin) compared with i.v.
the combined bacteriuria (>105 CFU/mL) event rate from or intramuscular cephalosporins (ceftriaxone, cefotaxime, or
26% to 9.1%, for a relative risk reduction of 65% (95% CI, cefazolin) and intramuscular penicillin (piperacillin–tazo-
–55 to –72), and the combined clinical septicemia episode bactam) in various urologic procedures.835,836,851,854,855,858 In
rate from 4.4% to 0.7% in TURP patients, including low-risk several studies, fluoroquinolones were administered orally,
patients.846 Another meta-analysis of 28 trials that included which appears to be feasible in patients undergoing proce-
a total of 4694 patients found prophylactic antimicrobials dures not involving opening the urinary or gastrointestinal
decreased the post-TURP rate of bacteriuria, fever, and tract, when the i.v. route would be preferred.822,836,838,851,855,858
Recently, resistance to fluoroquinolones has been emerg- a fluoroquinolone or aminoglycoside given with either met-
ing; the fact that most of the literature was published be- ronidazole or clindamycin. The medical literature does not
fore resistance became prevalent should be considered, support continuing antimicrobial prophylaxis until urinary
since resistance may decrease the relevance of these stud- catheters have been removed. See the colorectal procedures
ies.836,846,847,858,864 Local resistance patterns to fluoroquino- section of these guidelines for recommendations pertaining
lones, particularly with E. coli, should be evaluated to help to procedures entering the gastrointestinal tract. (Strength of
guide antimicrobial selection. evidence for prophylaxis = A.)
Broad-spectrum antimicrobials, such as third-genera-
tion cephalosporins and carbapenems, are no more effective Vascular Procedures
than first- or second-generation cephalosporins, aminogly-
cosides, or oral agents (trimethoprim–sulfamethoxazole, Background. Infection after vascular procedures occurs
nitrofurantoin, or fluoroquinolones) and should be reserved with low frequency but can be associated with extensive
for patients with active infection or who require additional morbidity and mortality.867,868 Postoperative infections in-
coverage for intestinal organisms.6,826,827 Their routine use volving vascular graft material can result in limb loss and
is not recommended due to their higher cost and potential to life-threatening conditions.868 As a result, antimicrobial
promote resistance, particularly among health-care-associ- prophylaxis is widely used in procedures that involve im-
ated gram-negative bacilli.8 plantation of prosthetic material and procedures for which
Duration. While longer durations of postoperative pro- there is greater risk of infection, such as aneurysm repair,
phylaxis (up to three weeks) have been studied,856,858,860,861 thromboendarterectomy, and vein bypass.6,41,867,869 Patients
more-recent data support the use of shorter durations (i.e., a undergoing brachiocephalic procedures (e.g., carotid end-
single dose or less than 24 hours’ duration) in urologic pro- arterectomy, brachial artery repair) without implantation of
cedures.658,817,818,823,824,826,831,832,834,836,846,853,857,859,862,865,866 prosthetic graft material do not appear to benefit from rou-
Based on bioavailability, oral antimicrobial prophylaxis tine antimicrobial prophylaxis.6,41,867,870
should be administered 1–2 hours before surgical incision or Risk factors for postoperative SSI in patients under-
start of the procedure.817,819–822,824,826,836,838,840,848,851,855 going vascular procedures include lower-extremity sites,
delayed procedures after hospitalization, diabetes mellitus,
Pediatric Efficacy. Limited data on antimicrobial prophy- and a history of vascular or aortocoronary bypass proce-
laxis are available for pediatric patients undergoing urologic dures.871,872 Currently, prospective data from well-designed
procedures. One prospective, open-label, nonrandomized studies on prophylaxis for endovascular stenting do not ex-
study of boys undergoing hypospadias repair with tabular- ist. However, if prophylaxis is desired, the same antimicro-
ized incision plate urethroplasty allocated patients to receive bials and short duration of therapy used for open vascular
cefonicid (no longer available in the United States) with one procedures should be given. Risk factors that warrant con-
i.v. dose before the procedure only or the addition of oral sideration of prophylaxis in patients undergoing endovascu-
cephalexin three times daily starting on postoperative day lar stenting include prolonged procedures (more than two
1 until 2 days after catheter removal (median, 8.3 days).833 hours), reintervention at the surgical site within seven days,
More patients in the single-dose group had bacteriuria and vascular stent placement in the groin through a hematoma or
complications (urethrocutaneous fistula and meatal ste- sheath, procedures in immunosuppressed patients, and the
nosis); however, the rate of infection and infection-related presence of another intravascular prosthesis.873–877
complications did not significantly differ between groups.
Organisms. The predominant organisms involved include
Recommendations. No antimicrobial prophylaxis is recom- S. aureus, S. epidermidis, and enteric gram-negative bacilli.
mended for clean urologic procedures in patients without MRSA is an emerging organism of concern.
risk factors for postoperative infections. Patients with pre- Several studies evaluated the rate of colonization, car-
operative bacteriuria or UTI should be treated before the riage, and infection with MRSA in patients undergoing vari-
procedure, when possible, to reduce the risk of postoperative ous vascular procedures.878–884 Independent risk factors for
infection. For patients undergoing lower urinary tract instru- MRSA infection included MRSA colonization, open abdom-
mentation with risk factors for infection, the use of a fluoro- inal aortic aneurysm, tissue loss, and lower-limb bypass.878
quinolone or trimethoprim–sulfamethoxazole (oral or i.v.) or Patients who have or develop MRSA infections before vas-
cefazolin (i.v. or intramuscular) is recommended (Table 2). cular procedures have increased risk of inhospital death,
For patients undergoing clean urologic procedures without intensive care unit admission, repeat surgeries, increased
entry into the urinary tract, cefazolin is recommended, with length of stay, and delayed wound healing, compared with
vancomycin or clindamycin as an alternative for those pa- patients without infections.880–883
tients allergic to b-lactam antimicrobials. For patients under-
going clean urologic procedures with entry into the urinary Efficacy. Prophylactic antimicrobials decrease the rate of
tract, cefazolin is recommended, with alternative antimicro- infection after procedures involving the lower abdominal
bials to include a fluoroquinolone, the combination of an vasculature and procedures required to establish dialysis
aminoglycoside plus metronidazole, or an aminoglycoside access. The follow-up time for patients with late surgical-
plus clindamycin. For clean-contaminated procedures of the site complications was at least once after hospital discharge
urinary tract (often entering the gastrointestinal tract), anti- (not further defined) for most studies,829,865,871,885–887 at one
microbials as recommended for elective colorectal surgery month,869,871,888,889 at six months,872 and at three years.138
are recommended. This would generally include the combi- A meta-analysis of 10 randomized controlled trials in
nation of cefazolin with or without metronidazole, cefoxitin, patients undergoing peripheral arterial reconstruction with
or, for patients with b-lactam allergy, a combination of either biological or prosthetic graft procedures found an overall
consistent reduction in SSIs with systemic antimicrobial bials for b-lactam-allergic patients receiving vancomycin
prophylaxis compared with placebo (relative risk, 0.25; may include a fluoroquinolone or aztreonam.6
95% CI, 0.17–0.38; p < 0.00001).890 An overall reduction Duration. A meta-analysis of three randomized con-
was found among 5 studies evaluating early graft infection trolled studies involving vascular procedures, including
(relative risk, 0.31; 95% CI, 0.11–0.85; p = 0.02), though no lower-limb reconstruction and open arterial procedures,
individual study found a significant reduction in SSIs. found no additional benefit of continuing prophylactic an-
The largest study included in the meta-analysis above timicrobials for over 24 hours postoperatively compared
was a randomized, prospective, double-blind, placebo- with no more than 24 hours (relative risk, 1.28; 95% CI,
controlled study of patients undergoing peripheral vascular 0.82–1.98).890
procedures (n = 462). The infection rate was significantly A randomized, double-blind study compared infection
lower with cefazolin than with placebo (0.9% and 6.8%, rates of a one-day and a three-day course of cefuroxime with
respectively).885 Four deep graft infections were observed placebo in 187 patients undergoing peripheral vascular pro-
in the placebo group; none occurred in the patients who re- cedures.888 The infection rates were 16.7%, 3.8%, and 4.3%
ceived cefazolin. No infections were observed in patients in the placebo, one-day, and three-day groups, respectively.
who underwent brachiocephalic (n = 103), femoral artery (n The difference in the infection rates between the one- and
= 56), or popliteal (n = 14) procedures. three-day groups was not significant.
Patients undergoing vascular access procedures for he- A randomized controlled study compared one day and
modialysis may benefit from the administration of antistaph- five days of amoxicillin–clavulanate 1.2 g in 100 patients
ylococcal antimicrobials. A placebo-controlled study of 408 undergoing 108 lower-limb reconstruction procedures.892
patients undergoing permanent vascular access placement No difference was seen in the postoperative SSI rate be-
demonstrated an upper-extremity prosthetic polytetrafluoro- tween groups (9 patients [16%] and 12 patients [23%], re-
ethylene graft infection rate of 6% with placebo compared spectively). The study authors selected the agent based on
with 1% with vancomycin (p = 0.006).869 extended spectrum of activity and good tissue penetration.
Choice of agent. Cefazolin remains the preferred and However, they concluded that due to the high rate of infec-
most cost-effective prophylactic agent for use in vascular tion observed, the use of antimicrobial prophylaxis might
procedures.6,8,41,872,886,887 There was no significant differ- not be as effective as once thought.
ence in infection rates between cefazolin and cefuroxime in A randomized controlled study compared ticarcil-
patients undergoing abdominal aortic and lower-extremity lin–clavulanate 3.1 g given as a single dose at induction of
peripheral vascular procedures,886 between cefazolin and anesthesia with multiple doses given at induction and every
cefamandole (no longer available in the United States) in 6 hours postoperatively until venous access lines were re-
patients undergoing aortic or infrainguinal arterial proce- moved or a maximum of 20 doses (total of five days) in pa-
dures,887 or between cefazolin and ceftriaxone in patients tients undergoing open arterial procedures.893 Significantly
undergoing arterial reconstruction involving infraclavicular more SSIs occurred in the single-dose group (28 [18%] of
sites.872 153 patients) compared with the multidose group (15 [10%]
A multicenter, randomized, double-blind, prospective of 149 patients) (relative risk, 2; 95% CI, –1.02 to 3.92; p =
trial of 580 patients undergoing arterial procedures involv- 0.041). Ticarcillin–clavulanate has a short duration of action
ing the groin who received either two doses of ciprofloxacin and is not recommended as a routine agent for antimicrobial
750 mg orally or three doses of cefuroxime 1.5 g i.v. on the prophylaxis. Practice guidelines recommend single-dose
day of the procedure found an SSI rate of 9.2% (27 patients) prophylaxis in vascular procedures or a maximum duration
and 9.1% (26 patients), respectively, within 30 days of the of therapy of 24 hours postoperatively, regardless of the
procedure.889 Although oral ciprofloxacin was shown to be presence of invasive drains.6,41
as effective as i.v. cefuroxime, this study did not address
concerns about resistance with routine use of fluoroquino- Recommendations. The recommended regimen for patients
lones.891 Therefore, i.v. cefazolin remains the first-line agent undergoing vascular procedures associated with a higher risk
for this indication. The efficacy of oral agents for prophy- of infection, including implantation of prosthetic material,
laxis needs to be further evaluated. is cefazolin (Table 2). (Strength of evidence for prophylaxis
There are limited data regarding the choice of an anti- = A.) Clindamycin and vancomycin should be reserved as
microbial for b-lactam-allergic patients undergoing vascular alternative agents as described in the Common Principles
procedures. The main alternative agents are vancomycin and section of these guidelines. If there are surveillance data
clindamycin, since prophylaxis is largely directed against showing that gram-negative organisms are a cause of SSIs
gram-positive cocci. Vancomycin can also be used for pro- for the procedure, practitioners may consider combining
phylaxis in institutions with MRSA or methicillin-resistant clindamycin or vancomycin with another agent (cefazolin if
S. epidermidis (MRSE) clusters or in patients with b-lactam the patient is not b-lactam allergic; aztreonam, gentamicin, or
allergy.6,8,41 Clindamycin may be an acceptable alternative to single-dose fluoroquinolone if the patient is b-lactam aller-
vancomycin, though local antimicrobial resistance patterns gic), due to the potential for gastrointestinal flora exposure.
should be taken into account.
An aminoglycoside may be added to vancomycin for Heart, Lung, and Heart–Lung
the addition of aerobic gram-negative bacilli coverage if Transplantation
the procedure involves the abdominal aorta or a groin inci-
sion, due to the potential for gastrointestinal flora. See the Background. Solid-organ transplant recipients are at high
Common Principles section of these guidelines for further risk for infections due to the complexity of the surgical pro-
discussion of the use of vancomycin. Alternative antimicro- cedures, donor- or recipient-derived infections, reactivation
of recipient-associated latent infections, preoperative re-
cipient colonization, exposure to community pathogens, and has been identified as an independent risk factor for SSIs.170
opportunistic infections due to immunosuppression.894–897 Other independent risk factors for SSIs in heart transplanta-
Infections occur more frequently in the first year after tion include age,905 receipt of ciprofloxacin alone for prophy-
transplantation, due to aggressive immunosuppression. laxis,906 positive wire cultures,907 a BMI of >30 kg/m2, fe-
Transplant recipients with infections are commonly as- male sex,908 previous cardiac procedures, previous left VAD
ymptomatic or have nonspecific symptoms or sequelae of placement, and hemodynamic instability requiring inotropic
infection, which makes detection and diagnosis of infec- support.903,904 Unfavorable functional outcomes were seen in
tions difficult.855,857,894 Postoperative infections caused by patients who developed infections within the first year after
bacterial, viral, and fungal pathogens, including SSIs, UTIs, heart transplantation associated with lung, bloodstream, and
bloodstream infections, and pneumonia, are of greater CMV infections.909 Independent predictors of mortality in
concern within the first month after transplantation.895–897 heart transplant recipients included serum creatinine levels,
Opportunistic infections that result from immunosuppres- amyloid etiology, history of hypertension, pulmonary infec-
sion typically occur after the first month of transplantation. tion, and CNS infection. Additional predisposing factors for
It is routine for transplant recipients to receive antimicro- infection in heart transplantation include exposure to patho-
bial prophylaxis to prevent opportunistic infections.894–897 A gens from the donor or transplant recipient, the time from
discussion of the prophylactic strategies for prevention of organ recovery to reperfusion, and the immunosuppressive
cytomegalovirus (CMV) infection, herpes simplex virus in- regimens used.897,904,910 Similar risk factors for infection are
fection, pneumocystis, UTI in kidney transplant recipients, noted in pediatric transplant recipients, with the addition of a
Aspergillus infection in lung transplant recipients, and other naive immune system to several pathogens, most notably vi-
opportunistic infections outside of the immediate posttrans- ruses, as well as incomplete primary immunization series.897
plantation period is beyond the scope of these guidelines. Patients with an indwelling VAD at the time of heart
Few well-designed, prospective, comparative studies transplantation have additional prophylaxis concerns.
of antimicrobial prophylaxis have been conducted with pa- Recipients who do not have a driveline infection and have
tients undergoing solid-organ transplantation, and no formal
no history of either colonization or infection should receive
recommendations are available from expert consensus pan-
prophylaxis as described for recipients without a VAD in
els or professional organizations; however, there are reviews
place. Patients with a history of colonization or previous
that provide guidance.8,41,894
infection should have the antimicrobial sensitivities of that
The recommendations given for each of the solid-
organism considered when choosing the SSI prophylactic
organ transplant procedures are intended to provide guide-
regimen administered, though the duration should still be
lines for safe and effective surgical prophylaxis based on
less than 24 hours. Heart transplant recipients with an active
the best available literature. Antimicrobial surgical prophy-
VAD driveline infection at the time of heart transplantation
laxis practice will vary considerably among transplantation
should be given appropriate antimicrobials specifically for
centers throughout the United States, based on the organ in-
the treatment of that infection. This intervention will usu-
volved, preexisting recipient and donor infections, and local
antimicrobial susceptibilities.894–897 ally determine the actual perioperative prophylaxis regi-
men as well as the duration of therapy beyond the period
Heart Transplantation. Background. Heart transplantation of prophylaxis.
is an option for selected patients with end-stage cardiac Patients requiring ECMO as a bridge to heart trans-
disease. In 2007, the United Network for Organ Sharing plantation should be treated with a similar approach. If there
(UNOS) reported that 2209 heart transplants were per- is no history of colonization or previous infection, then the
formed in the United States, including 327 in children (<18 general recommendations for SSI antimicrobial prophylaxis
years of age).898 The mean graft survival rate 10 years after for the specific procedure should be followed. In ECMO pa-
heart transplantation is approximately 49%. Infection con- tients with a history of colonization or previous infection,
tinues to be an important cause of morbidity and mortality changing the preoperative antimicrobial prophylaxis to cover
after heart transplantation and is a primary cause of death these pathogens must be considered, weighing whether the
in approximately 14% of patients within the first year after pathogen is relevant to SSIs in the planned procedure.
transplantation.899 Because heart transplantation is similar to other car-
Despite the large number of heart transplantation pro- diac and thoracic procedures, similar considerations regard-
cedures performed, few studies have specifically examined ing the need for antimicrobial prophylaxis apply (see the
postoperative SSI rates in this population. General cardio- cardiac and thoracic sections).911 These guidelines do not
thoracic procedures have been associated with SSI rates address antimicrobial prophylaxis for infective endocarditis.
ranging from 9% to 55% in the absence of antimicrobial Readers are referred to the current guidelines for prevention
prophylaxis.214,900,901 Studies of general cardiothoracic proof infective endocarditis from AHA.11,228
cedures, including heart transplantation, found SSIs, particu- Organisms. As with other types of cardiothoracic pro-
larly mediastinitis, in 3–6% of patients who received anti- cedures, gram-positive organisms, mainly Staphylococcus
microbial prophylaxis.170,902 The frequency was highest in species, are the primary pathogens that cause SSI after heart
heart transplant recipients. The SSI rates reported in patients transplantation.902,905–907,912,913 MRSA was reported in 12–
undergoing heart transplantation who received antimicrobial 21% of SSIs in several cohort studies.903,905,906 Vancomycin-
prophylaxis ranged from 5.8% to 8.8%, including mediasti- resistant Enterococcus faecalis was noted in 15% of infec-
nitis in 3–7% of patients.903,904 tions in one cohort study.903 Other gram-positive pathogens
Several independent risk factors for SSIs after cardiac (e.g., coagulase-negative staphylococci, Enterococcus
and thoracic procedures have been identified (see the cardiac species)903,905–907,913 and gram-negative organisms (e.g.,
and thoracic sections of this article). Heart transplantation Enterobacteriaceae, P. aeruginosa, Stenotrophomonas
maltophilia) are also a concern for SSIs in heart transplant prophylaxis in institutions that have a high prevalence of
recipients, as are Candida species.903,906 MRSA, for patients who are colonized with MRSA, or for
Efficacy. Despite the paucity of literature on anti- patients with a true b-lactam allergy.8 Additional doses may
microbial prophylaxis for the prevention of SSIs in heart be needed intraoperatively for procedures >4 hours in dura-
transplantation, the efficacy noted in other cardiac surgical tion, for patients with major blood loss, or for extended use
procedures has made it the standard of practice during trans- of CPB depending on the half-life of the prophylactic anti-
plantation.896 microbial. Fluoroquinolones are not routinely recommended
No randomized controlled trials have specifically ad- in pediatric patients.
dressed the use of antimicrobial prophylaxis in heart trans- Recommendations. Based on data for other types of
plantation. In an open-label noncomparative study, the SSI cardiothoracic procedures, antimicrobial prophylaxis is in-
rate was 4.5% among 96 patients administered cefotaxime dicated for all patients undergoing heart transplantation (see
plus floxacillin preoperatively and for 72 hours after cardiac cardiac and thoracic sections). The recommended regimen is
procedures.912 This rate of infection was similar to that seen a single dose of cefazolin (Table 2). There is no evidence to
in other cardiothoracic, nonheart transplantation procedures support continuing prophylaxis until chest and mediastinal
in which antimicrobial prophylaxis was used. drainage tubes are removed. Alternatives include vancomy-
Choice of agent. Antimicrobial prophylaxis for heart cin or clindamycin with or without gentamicin, aztreonam,
transplantation should be similar to that used for other or a single fluoroquinolone dose. (Strength of evidence for
types of cardiothoracic procedures.911 First- and second- prophylaxis = A.) The optimal duration of antimicrobial pro-
generation cephalosporins are considered to be equally ef- phylaxis for patients who do not have their chest primarily
ficacious and are the preferred agents. There appear to be closed is unclear. No recommendation is made for these pa-
no significant differences in efficacy among prophylactic tients. Patients who have left VADs as a bridge and who are
regimens using agents such as cefazolin and cefuroxime.914 chronically infected might also benefit from coverage of the
The use of antistaphylococcal penicillins, either alone or in infecting microorganism.
combination with aminoglycosides or cephalosporins, failed
to demonstrate superior efficacy to that of cephalosporin Lung and Heart–Lung Transplantation. Background. Lung
monotherapy (see the cardiac and thoracic sections) in other transplantation is an accepted option for a variety of end-
cardiothoracic procedures. stage, irreversible lung diseases. The most common diseases
Several cohort studies examined antimicrobial prophy- for which lung transplantation is performed are idiopathic
lactic agents used for patients undergoing heart transplanta- pulmonary fibrosis, chronic obstructive pulmonary disease,
tion but did not evaluate efficacy.902,903,905,906 Ciprofloxacin emphysema, cystic fibrosis, a-1-antitrypsin deficiency, and
alone was found to be an independent risk factor for inci- idiopathic pulmonary arterial hypertension.915,916 UNOS re-
sional SSIs.906 ported that in the United States in 2007, 1468 lung transplan-
Duration. There is no consensus on the optimal dura- tations and 31 heart–lung transplantations were conducted
tion of antimicrobial prophylaxis in cardiothoracic proce- in adults, and 52 lung transplantations and 3 heart–lung
dures, including heart transplantation. Cohort evaluations of transplantations were performed in children.898,917 Ten-year
patients undergoing heart transplantation reported durations survival rates were reported as 29.7% of double-lung, 17.5%
of antimicrobial prophylaxis with cefazolin or vancomycin of single-lung, and 25.8% of heart–lung transplant recipi-
of 24 or 48 hours postoperatively.902,903,905 Data from car- ents.899 The reported three-year survival rate for pediatric
diothoracic procedures also support a range of prophylaxis lung transplant recipients was 57%.89
durations, from a single dose to 24 or 48 hours postopera- Infections are the most common complications after
tively.41,131 The currently accepted duration for these proce- lung and heart–lung transplantations.899,915,918,919 In an anal-
dures, which do not include transplantation, is 24–48 hours ysis of UNOS data over an 18-year period, infection was the
postoperatively.41,59,131,201 The duration of antimicrobial pro- number one cause of death within the first year of transplan-
phylaxis for patients who do not have their chest primarily tation, occurring in 24.8% of lung and 18.3% of heart–lung
closed is unclear; most centers continue prophylaxis until transplant recipients.899 Among the top 10 primary causes of
the chest is closed, but there is no evidence to support this death within the first year after lung and heart–lung trans-
practice. plantations were sepsis, pneumonia, fungal infection (lung
Pediatric efficacy. No randomized controlled stud- only), and CMV infection.899 A study of two cohorts of pa-
ies have specifically addressed antimicrobial prophylaxis tients undergoing heart, lung, and heart–lung transplanta-
for heart transplantation in pediatric patients. Infants are tions who received antimicrobial prophylaxis evaluated the
at risk for mediastinitis caused by gram-negative as well rate of SSIs and mediastinitis.904,908 The rate of SSI among
as gram-positive organisms. Pediatric patients undergoing all transplant recipients was 12.98%, with the majority of
heart transplantation should be treated according to recom- infections (72%) being organ/space infections, followed by
mendations for other types of cardiothoracic procedures. deep incisional infections (17%) and superficial incisional
The recommended regimen for pediatric patients undergo- infections (10%).908 The overall rate of mediastinitis in a
ing cardiothoracic procedures is cefazolin 25–50 mg/kg similar cohort was 2.7%, with rates of 5.2% in heart–lung
i.v. within 60 minutes before surgical incision and every 8 transplant recipients and 3.2% in bilateral lung transplant re-
hours for up to 48 hours. Cefuroxime 50 mg/kg i.v. within cipients.904 Pneumonia was reported in 26.4% of transplan-
60 minutes before surgical incision and every 8 hours for up tation patients overall, with rates of 20.7% in lung transplant
to 48 hours is an acceptable alternative. Vancomycin 10–20 recipients and 40% in heart–lung transplant recipients.908 A
mg/kg i.v. over 60–120 minutes, with or without gentami- cohort of lung transplant recipients reported a rate of 2.2 epi-
cin 2 mg/kg i.v., should be reserved as an alternative on the sodes of pneumonia per patient during a median follow-up
basis of guidelines from HICPAC for routine antimicrobial period of 412 days (range, 1–1328 days).920
Bronchial anastomotic infections, especially fungal Stenotrophomonas species, Alcaligenes species, and fungi,
infections, can be serious and are potentially fatal in lung including Aspergillus species.897
transplant recipients.921,922 The lung allocation score (LAS) The donor lung appears to be a major route of trans-
is a rating system adopted by the Organ Procurement and mission of pathogens; 75–90% of bronchial washings from
Transplant Network and UNOS in 2005 to improve organ donor organs are positive for at least one bacterial organ-
allocation and transplantation outcomes. The LAS is based ism.920,924,925 Organ recipients may also be the source of in-
on the risk of death while on the waiting list for transplanta- fection of the transplanted organ. This is particularly true in
tion and the expected 1-year survival after transplantation. patients with cystic fibrosis because of the frequent presence
Patients with a low LAS are unlikely to undergo transplanta- of P. aeruginosa in the upper airways and sinuses before
tion. A study of lung transplant recipients age 12 years or transplantation.896,919 These pathogens are often multidrug
older revealed a higher rate of infection and other morbidities resistant, likely due, in large part, to frequent administra-
and a lower 1-year survival rate in patients with a high LAS tion of broad-spectrum antimicrobials during the course of
at the time of transplantation than in patients with a low LAS the disease. Multidrug-resistant strains of B. cepacia and S.
at the time of transplantation.923 Thus, the potential for bron- maltophilia may be a problem in cystic fibrosis patients in
chial anastomotic infection and a poor posttransplantation some transplantation centers.919,926
outcome needs to be considered in patients undergoing lung Efficacy. Although much has been published about
transplantation. Among lung transplantation patients, risk general infectious complications associated with lung
factors for nosocomial infections included a-1-antitrypsin transplantation, no randomized controlled trials regarding
deficiency and repeat transplantation. Risk factors for pneu- antimicrobial prophylaxis for lung or heart–lung transplan-
monia included colonized or infected donor bronchus and tation have been published; however, antimicrobial prophy-
perfusate and preoperative colonization with gram-negative laxis is considered standard practice in these patients.896
rods. Risk factors for mortality among the transplant recipi- Antimicrobial prophylaxis is routinely administered to pa-
ents were cystic fibrosis, nosocomial infection, and ventila- tients undergoing lung or heart–lung transplantation, with
tion before transplantation.908 Risk factors for mediastinitis the aim of preventing pneumonia as well as SSIs. The rate
after heart, lung, and heart–lung transplantation were degree of pneumonia within the first two weeks postoperatively has
of immunosuppression, impaired renal function, previous reportedly been decreased from 35% to approximately 10%
sternotomy, and reexploration due to bleeding.904 There was by routine antimicrobial prophylaxis.927–929 Improvements
a positive association between pretransplantation colonizing in surgical technique and postoperative patient care are also
microorganisms from suppurative lung disease patients and important factors in the apparently lower rates of pneumonia
pneumonia after transplantation.920 Transplantation alters after lung transplantation.
the physiological function of lungs, including the impair- Choice of agent. No formal studies have addressed
ment of mucociliary clearance and interruption of the cough optimal prophylaxis for patients undergoing lung transplan-
reflex, leading to a higher risk of pulmonary infections.896 tation. Antimicrobial prophylaxis for lung and heart–lung
In patients requiring ECMO as a bridge to lung trans- transplantation should generally be similar to that used
plantation who have no history of colonization or previous for other cardiothoracic procedures (see the cardiac and
infection, the general recommendations for SSI antimicro- thoracic sections). First- and second-generation cephalo-
bial prophylaxis for the procedure should be followed. In sporins are considered equally efficacious and are the pre-
ECMO patients with a history of colonization or previous ferred agents for these procedures. However, prophylactic
infection, changing the preoperative antimicrobial prophy- regimens should be modified to include coverage for any
laxis to cover these pathogens must be considered, weigh- potential bacterial pathogens, including gram-negative and
ing whether the pathogen is relevant to SSIs in the planned fungal organisms, that have been isolated from the recipi-
procedure. ent’s airways or the donor lung through preoperative cul-
Organisms. While gram-positive and gram-negative tures.894,896,904,908,915,920 Patients with end-stage cystic fibro-
organisms are of concern in heart transplantation, there is in- sis should receive antimicrobials on the basis of the known
creased concern regarding gram-negative and fungal patho- susceptibilities of pretransplant isolates, particularly P. aeru-
gens in mediastinitis and pneumonia in patients undergoing ginosa, B. cepacia complex, and Aspergillus species.
lung transplantation.894,904,908 The most frequent organisms Antimicrobial prophylaxis regimens reported in co-
found in SSIs or mediastinitis in two cohort studies were hort evaluations of thoracic transplantation, including lungs,
P. aeruginosa,904,908 Candida species, S. aureus (including have varied.904,908,920 One study used ceftazidime, floxacil-
MRSA),908 enterococci, coagulase-negative staphylococci lin, tobramycin, and itraconazole in these patients.908 In ad-
(e.g., S. epidermidis), Burkholderia cepacia,904 E. coli, and dition, all patients received nebulized amphotericin B and
Klebsiella species. oral itraconazole as antifungal prophylaxis. Another cohort
Patients undergoing lung transplantation are also at study used cefepime for lung transplant recipients without
risk for bacterial or fungal pneumonia due to colonization known colonization; for those with known colonization, the
or infection of the lower and upper airways of the donor, selection of agents was based on organism susceptibility.920
recipient, or both.915 Organisms reported to cause pneu- A third cohort reported use of metronidazole and aztreonam
monia in lung transplantation patients include P. aerugi- as prophylaxis for patients with a septic lung (positive spu-
nosa,894,896,904,908,920 S. aureus (including MRSA),894,896,904,908 tum culture).904
B. cepacia,896,904,908 Enterobacter species,908 S. malto- Antifungal prophylaxis should be considered, espe-
philia, Klebsiella species,904,908 S. epidermidis,904 E. coli, cially when pretransplantation cultures reveal fungi in the
Aspergillus species,920 and VRE.894 Similarly, organisms donor lung915 or the recipient’s airway. There is no consen-
frequently seen in pediatric lung infections are nonferment- sus on the appropriate antifungal agent for lung transplant
ing gram-negative bacteria, such as Pseudomonas species, recipients.894,896,930 Selection is recommended based on pa-
tient risk factors for infection (e.g., cystic fibrosis) and colo- 95%932,935–938 and from 80% to 91.7% for pediatric pa-
nization, pretransplantation and posttransplantation cultures, tients.934,939–942 Survival at 3 and 5 years ranged from 68.5%
and local fungus epidemiology.894,896,897,930 Because of the to 80.9%934 and from 61.6% to 76.5%932,933 in adult patients,
serious nature of fungal infections in the early posttransplan- respectively. In pediatric patients, 3- and 5-year survival
tation period and the availability of antifungal agents, pro- ranged from 73.2% to 86%897,934,941 and from 69.2% to
phylaxis should be considered when Candida or Aspergillus 80.1%,934 respectively. One-year graft survival rates ranged
species are isolated from the donor lung915 or recipient’s from 74.2% to 94% in adults934–936,938 and from 72.1% to
airway. 86.1% in pediatric patients.934,941,942 Graft survival at 3
Duration. No well-conducted studies have addressed and 5 years ranged from 58.9% to 75.5% and from 51.6%
the optimal duration of antimicrobial prophylaxis for lung to 70.5%, respectively, in adults and from 62.5% to 77.6%
or heart–lung transplantation. In the absence of positive and from 68.4% to 71.4%, respectively, in pediatric pa-
cultures from the donor or the recipient, prophylactic regi- tients.934,941 No significant differences were noted in graft or
mens of 48–72 hours and no longer than 7 days have been patient survival between cadaveric and living-related donors
reported.896,904,905,931 In patients with positive pretransplanta- in adult and pediatric liver transplant recipients.934 Infection
tion cultures from donor or recipient organs or patients with remains a major cause of morbidity and mortality in liver
positive cultures after transplantation, postoperative antimi- transplant recipients. Infections may occur in 31–83% of
crobial treatment for 7–14 days or longer has been reported, patients within three months of transplantation and are the
particularly for patients with cystic fibrosis and previous P. cause of death in 4–53% of patients.934,936,940,943–950 These
aeruginosa and multidrug-resistant infections.896,915,919 Such rates are highly variable and do not seem to have changed
antimicrobial administration is viewed as treatment and not despite advances in surgical technique and medical manage-
as surgical prophylaxis. Treatment may include additional ment. SSIs within 30 days after transplantation ranged from
antibacterial agents or antifungal agents. 4% to 48% with antimicrobial prophylaxis in several cohort
Recommendations. Based on data from other types of and controlled studies.935–938,941,942,948,949,951–964 Superficial
cardiothoracic procedures, all adult patients undergoing lung SSIs are seen most often within the first two to three weeks
transplantation should receive antimicrobial prophylaxis, postoperatively, whereas organ/space infections and deep in-
because of the high risk of infection. Patients with nega- fections are seen after three to four weeks.
tive pretransplantation cultures should receive antimicrobial Liver transplantation is often considered to be the
prophylaxis as appropriate for other types of cardiothoracic most technically difficult of the solid-organ transplanta-
procedures. tion procedures. Surgical procedures lasting longer than
The recommended regimen is a single dose of cefazo- 8–12 hours have been consistently identified as one of
lin (Table 2). There is no evidence to support continuing the most important risk factors for early infectious com-
prophylaxis until chest and mediastinal drainage tubes are plications, including SSIs, intraabdominal infections, and
removed. Alternatives include vancomycin with or without biliary tract infections.896,938,939,945,947,957 Other important
gentamicin, aztreonam, and a single fluoroquinolone dose. risk factors for infectious complications related to liver
(Strength of evidence for prophylaxis = A.) The optimal du- transplantation surgery include previous hepatobiliary
ration of antimicrobial prophylaxis for patients who do not surgery,896,939,945,947,952,963 previous liver or kidney trans-
have their chest primarily closed is unclear. No recommen- plantation,937,951,952,965 and surgical complications such as
dation is made for these patients. anastomotic leakage.896,938,939,945,947,951,952 Patient-related
The prophylactic regimen should be modified to pro- risk factors for infection after liver transplantation include
vide coverage against any potential pathogens, including antimicrobial use within three to four months before trans-
gram-negative (e.g., P. aeruginosa) and fungal organisms, plantation,935,954 low pretransplantation serum albumin
isolated from the donor lung or the recipient pretransplanta- concentration,938,958,963 high pretransplantation serum bili-
tion. The prophylactic regimen may also include antifungal rubin concentration,939,945,947 ascites,938 obesity,963 diabetes,
agents for Candida and Aspergillus species based on patient and hemochromatosis.966 Procedure-related risk factors
risk factors for infection (e.g., cystic fibrosis) and coloni- for infection include transfusion of >4 units of red blood
zation, pretransplantation and posttransplantation cultures, cells,896,951 bacterial contamination due to entry into the
and local fungus epidemiology. Patients undergoing lung gastrointestinal tract,963 surgical incision method,963 and use
transplantation for cystic fibrosis should receive treatment of muromonab-CD3 within the first week after transplanta-
for at least seven days with antimicrobials selected accord- tion.938
ing to pretransplantation culture and susceptibility results.
(Strength of evidence for prophylaxis = B.) Organisms. The pathogens most commonly associated with
early SSIs and intraabdominal infections are those derived from
Liver Transplantation the normal flora of the intestinal lumen and the skin. Aerobic
gram-negative bacilli, including E. coli,935,937,939,940,942,945,947–
949,951,967,968
Background. Liver transplantation is a lifesaving proce- Klebsiella species,933,936,937,939,940,945,947–949,967–969
dure for many patients with end-stage hepatic disease for Enterobacter species,936,939,940,942,945,947,952,959,964,967,968
whom there are no other medical or surgical options.932,933 Acinetobacter baumannii,935–937,942,951 and Citrobacter
In 2007, UNOS reported that 6494 liver transplantations species,939,940,945,947,952,959,967,968 are common causes of
were performed in the United States, 96% of which had a SSIs and intraabdominal infections and account for up to
cadaveric donor and 4% had a living-related donor source.934 65% of all bacterial pathogens. Infections due to P. aeru-
These liver transplantations were performed in 5889 adults ginosa may also occur but are much less common in the
and 605 pediatric (<18 years old) patients. Reported 1-year early postoperative period.936,937,939,940,942,945,947,948,952,959,969
patient survival rates for adults ranged from 76.9% to Enterococci are particularly common pathogens and may
be responsible for 20–46% of SSIs and intraabdominal of these regimens compared with cefotaxime plus ampi-
infections. 894,933,935,937,938,940,943,945–947,951,952,955,964,965,969 cillin is difficult to assess due to different definitions of
S. aureus (frequently MRSA) and coagulase-negative infection used in the available studies and variability of
staphylococci are also common causes of postoperative study design (many single-center cohort studies) in differ-
SSIs.936–938,940,942,943,945–949,955,957–961,964,965,970,971 Candida ent countries. One prospective nonrandomized study found
species commonly cause both early and late postoperative no difference in the frequency of SSIs in orthotopic liver
infections.933,936,937,940,942,943,945–947,949,951,969 transplant recipients with cefazolin alone and amoxicil-
Several studies have noted increasing concern about lin–clavulanate alone, both given one hour before surgical
antimicrobial resistance based on detection of resistant incision, with a second dose given in cases of significant
organisms, including E. coli,935,937 Enterococcus spe- bleeding or surgery lasting over six hours, as antimicrobial
cies,933,937,964,965 Enterobacter species,964 Klebsiella spe- prophylaxis.935 The study did find a significantly higher rate
cies,933,937 coagulase-negative staphylococci,937,964 and S. of A. baumannii in the cefazolin group than the amoxicillin–
aureus.937,948,957–961,970 General information on antimicrobial clavulanate group. The routine use of vancomy-
resistance is provided in the Common Principles section of cin as antimicrobial prophylaxis is not recommended
these guidelines. Of specific concern to the transplantation because of the risk of developing vancomycin-
community is the emergence of multidrug-resistant A. bau- resistant organisms,8,950 but vancomycin may be reserved for
mannii,972 carbapenem-resistant Enterobacteriaceae,973,974 centers with an MRSA or MRSE cluster.8,950,957–959 No ran-
K. pneumoniae carbapenemase-producing organisms,975 and domized controlled studies have been conducted to compare
C. difficile.976–978 the efficacy of other antimicrobial prophylactic regimens in
the prevention of early postoperative infections. For patients
Efficacy. Although there remains a high rate of infection known to be colonized with MRSA, VRE, or resistant gram-
directly related to the liver transplantation procedure, there negative pathogens, it is reasonable to consider prophylaxis
are few well-controlled studies concerning optimal antimi- specifically targeted at these organisms. See the Common
crobial prophylaxis. In evaluating the efficacy of prophylac- Principles section for further discussion.
tic regimens, it is important to differentiate between early Postoperative infections with Candida species after
infections (occurring within 14–30 days after surgery) and liver transplantation are common, particularly in the abdo-
late infections (occurring more than 30 days after surgery). men, and are frequently considered organ/space SSIs. For
Infections occurring in the early postoperative period are this reason, the use of antifungal prophylaxis in the periop-
most commonly associated with biliary, vascular, and ab- erative period has become common. Efficacy has been dem-
dominal surgeries involved in the transplantation procedure onstrated for fluconazole,964–984 lipid complex amphoteri-
itself and are thus most preventable with prophylactic anti- cin B,985–987 and caspofungin.988 Finally, one meta-analysis
microbial regimens.939,940,943,945 The frequency of these in- found a decreased risk of fungal infection and death asso-
fections varies from 10% to 55% despite antimicrobial pro- ciated with fungal infection, though not overall mortality,
phylaxis.939,940,943,945,979 It is difficult to assess the efficacy among patients given antifungal prophylaxis.989 Universal
of prophylactic regimens in reducing the rate of infection, antifungal prophylaxis is probably not necessary, since the
because prophylaxis has been routinely used in light of the risk of invasive candidiasis is low in uncomplicated cases.
complexity of the surgical procedure; therefore, reliable Instead, prophylaxis is generally reserved for patients with
rates of infection in the absence of prophylaxis are not avail- two or more of the following risk factors: need for reop-
able. No controlled studies have compared prophylaxis with eration, retransplantation, renal failure, choledochojejunos-
no prophylaxis. tomy, and known colonization with Candida species.15 Risk
Choice of agent. Antimicrobial prophylaxis should be is also increased with prolonged initial procedure or transfu-
directed against the pathogens most commonly isolated from sion of >40 units of cellular blood products, but this cannot
early infections (i.e., gram-negative aerobic bacilli, staphy- be predicted before the procedure.
lococci, and enterococci). Traditional prophylactic regimens Selective bowel decontamination to eliminate aerobic
have therefore consisted of a third-generation cephalosporin gram-negative bacilli and yeast from the bowel before the
(usually cefotaxime, because of its antistaphylococcal activ- transplantation procedure has been evaluated in several stud-
ity) plus ampicillin.936,937,943,944,946–948,951,952,954,962,965,967,979 ies and a meta-analysis.936,943,949,955,956,967,968,980,990,991 These
The use of cefoxitin and ampicillin–sulbactam, cefotaxime studies used combinations of nonabsorbable antibacterials
and ampicillin–sulbactam and gentamicin,957–959 cefurox- (aminoglycosides, polymyxin B or E), antifungals (nystatin,
ime and metronidazole,971 ceftriaxone and metronidazole,980 amphotericin B), and other antimicrobials (cefuroxime in
cefotaxime and metronidazole,953 ceftriaxone and ampicil- suspension) administered orally and applied to the oropha-
lin,949 ceftizoxime alone,955 cefotaxime and tobramycin,956 ryngeal cavity in combination with systemically adminis-
cefoxitin alone,960,961 cefazolin alone,951 amoxicillin–clavu- tered antimicrobials. Results are conflicting, with no differ-
lanate and gentamicin,970 amoxicillin–clavulanate alone,951 ences in patient outcomes (e.g., infection rates, mortality)
glycopeptides and antipseudomonal penicillin,951 quinolone or cost and concerns of increasing gram-positive infections
and amoxicillin–clavulanate or glycopeptide,951 vancomy- with potential resistance in several studies939,955,956,980,991
cin and aztreonam,951,981 and piperacillin–tazobactam964,970 and others with positive results.936,949 Two randomized
has also been reported. Alternative prophylaxis regimens controlled studies found significantly fewer bacterial infec-
for b-lactam-allergic patients have included cefuroxime tions with early enteral nutrition plus lactobacillus and fi-
and metronidazole,970 clindamycin and gentamicin or az- bers.971,980 Based on currently available data, the routine use
treonam,948,960–962 ciprofloxacin and metronidazole,970 and of selective bowel decontamination or lactic acid bacteria
vancomycin or ciprofloxacin.936 Imipenem alone was used and fibers in patients undergoing liver transplantation is not
in one study for patients with renal failure.956 The efficacy recommended.
Duration. No studies have assessed the optimal dura- transplantations, with allograft survival rates of 86.1–95.1%
tion of antimicrobial prophylaxis in liver transplantation. at 1 year and 54.2–92.5% at 3 years. Reported patient sur-
Although antimicrobials have been administered in studies vival rates in SPK are 91.7–97.6% at 1 year and 84.4–94.1%
for five days937,944,946,949,957–959 and seven days,964 the majority at 3 years. During pancreas transplantation, surgical compli-
of recent studies have limited the duration of prophylaxis to cations with portal-hepatic drainage significantly decreased
72 hours,981 48 hours,936,943,945,952,955,956,960,961,967,970,979,980,991 the 1-year and 3-year survival rates to 48% and 44%, respec-
36 hours,981 24 hours,935,948,962,970 and a single dose,963 with tively, in one cohort study.999
no apparent differences in early infection rates. A prospec- Infectious complications are a major source of mor-
tive, nonrandomized, controlled study found no difference in bidity and mortality in patients undergoing pancreas or
bacterial infections within the first three months after liver SPK transplantation; the frequency of SSI is 7–50% with
transplantation in patients receiving cefotaxime and ampicil- antimicrobial prophylaxis.993–997,1000–1009 The majority of
lin as short-term antimicrobial prophylaxis for two to three SSIs occurred within the first 30 days to three months after
days, compared with long-term prophylaxis for five to seven transplantation.1000–1002,1005,1008,1009 UTIs are also a signifi-
days.954 Of note, 5 of the 11 patients in the long-term pro- cant concern during the same time frame, with rates rang-
phylaxis group had detectable C. difficile toxin B in the feces ing from 10.6% to 49% in pancreas transplant recipients
and developed enteritis. No patients in the short-term group who received antimicrobial prophylaxis, and are much more
had detectable C. difficile. Two recent review articles noted common in recipients with bladder drainage compared with
that antimicrobial prophylaxis duration should be less than enteric drainage.1000–1008
three days.896,950 Pancreas and SPK transplantation patients may be at
increased risk of SSIs and other infections because of the
Pediatric Efficacy. There are few data specifically con- combined immunosuppressive effects of diabetes mellitus
cerning antimicrobial prophylaxis in liver transplantation and the immunosuppressive drugs used to prevent graft re-
in pediatric patients. The combination of cefotaxime plus jection.995,1000 Other factors associated with increased SSI
ampicillin has been reportedly used in children undergoing rates include prolonged operating and ischemic times (>4
living-related donor liver transplantation; the efficacy of this hours), organ donor age of >55 years, and enteric rather
regimen appeared to be favorable.946 A small, retrospective, than bladder drainage of pancreatic duct secretions.895,995,1000
single-center cohort study reported outcomes of children un- Prolonged organ preservation time (>20 hours) was shown
dergoing liver, heart, small bowel, or lung transplantation to increase the risk of complications, including duodenal
receiving piperacillin–tazobactam 120–150 mg/kg/day be- leaks and decreased graft survival in cadaveric pancreas
ginning before surgical incision and continuing for 48 hours transplant recipients.1003 Risk factors for UTI are reviewed
postoperatively and found favorable results, with a superfi- in the kidney transplant section.
cial SSI rate of 8% and no deep SSIs.992
Organisms. A majority of superficial SSIs after pancreas
Recommendations. The recommended agents for patients or SPK transplantation are caused by Staphylococcus spe-
undergoing liver transplantation are (1) piperacillin–tazo- cies (both coagulase-positive and coagulase-negative) and
bactam and (2) cefotaxime plus ampicillin (Table 2). gram-negative bacilli (particularly E. coli and Klebsiella
(Strength of evidence for prophylaxis = B.) For patients who species).993–997,1000–1002,1004–1006,1009–1011 Deep SSIs also are
are allergic to b-lactam antimicrobials, clindamycin or van- frequently associated with gram-positive (Enterococcus
comycin given in combination with gentamicin, aztreonam, species, Streptococcus species, and Peptostreptococcus spe-
or a fluoroquinolone is a reasonable alternative. The dura- cies) and gram-negative organisms (Enterobacter species,
tion of prophylaxis should be restricted to 24 hours or less. Morganella species, and B. fragilis), as well as Candida
For patients at high risk of Candida infection, fluconazole species.993–997,1000–1002,1004–1006,1009–1011 Although anaerobes
adjusted for renal function may be considered. (Strength of are occasionally isolated, the necessity for specific treat-
evidence for prophylaxis = B.) ment of anaerobes in SSIs after pancreas transplantation
remains unclear.
Pancreas and Pancreas–Kidney
Transplantation Efficacy. Although no placebo-controlled studies have been
conducted, several open-label, noncomparative, single-center
Background. Pancreas transplantation is an accepted ther- studies have suggested that antimicrobial prophylaxis sub-
apeutic intervention for type 1 diabetes mellitus; it is the stantially decreases the rate of superficial and deep SSIs af-
only therapy that consistently achieves euglycemia with- ter pancreas or SPK transplantation. SSI rates were 7–33%
out dependence on exogenous insulin.993–997 Simultaneous with various prophylactic regimens,995,1000–1002,1004,1005 com-
pancreas–kidney (SPK) transplantation is an accepted pro- pared with 7–50% for historical controls in the absence of
cedure for patients with type 1 diabetes and severe diabetic prophylaxis.1009,1010 The reason for the wide disparity in in-
nephropathy. In 2007, UNOS reported that 469 pancreas fection rates observed with prophylaxis is not readily appar-
transplantations and 862 SPK transplantations were per- ent but may include variations in SSI definitions, variations
formed in the United States, of which 60 and 4 patients, re- in antimicrobial prophylaxis, immunosuppression protocols,
spectively, were under age 18 years.998 Pancreas graft 1-year and variations in surgical techniques.999–1002,1005,1007,1008
survival rates ranged from 70.2% to 89%, and the 3-year Choice of agent. Because of the broad range of po-
rates ranged from 48% to 85.8%.998–1002 Patient survival tential pathogens, several studies have used multidrug pro-
with pancreas transplantation has been reported between phylactic regimens, including imipenem–cilastatin plus van-
75% and 97% at 1 year and between 54% and 92.5% at 3 comycin995; tobramycin, vancomycin, and fluconazole1010;
years.998 Allograft survival is higher in recipients of SPK cefotaxime, metronidazole, and vancomycin1012; cefotax
ime, vancomycin, and fluconazole1008; ampicillin and cefo- amoxicillin–clavulanate,1001,1002 and piperacillin–tazobac-
taxime1007; and piperacillin–tazobactam and fluconazole.1006 tam1000–1002 1–7 days in duration, with the majority using the
HICPAC recommendations for SSI prevention include regimen 48–72 hours after transplantation. The duration of
limiting the use of vancomycin unless there is an MRSA or fluconazole ranged from 7 to 28 days.1002
MRSE cluster or as an alternative for b-lactam-allergic pa-
tients, though transplantation procedures were not specifi- Recommendations. The recommended regimen for pa-
cally covered in the guidelines.8 Limited data are available tients undergoing pancreas or SPK transplantation is ce-
on the use of vancomycin as antimicrobial prophylaxis in fazolin (Table 2). (Strength of evidence for prophylaxis =
kidney or pancreas transplantation, or both. A small, ran- A.) For patients who are allergic to b-lactam antimicrobi-
domized, active-controlled, single-center study evaluated the als, clindamycin or vancomycin given in combination with
impact of vancomycin-containing antimicrobial prophylaxis gentamicin, aztreonam, or a fluoroquinolone is a reasonable
regimens in kidney and pancreas (alone or SPK) transplant alternative. The duration of prophylaxis should be restricted
recipients on the frequency of gram-positive infections.1004 to 24 hours or less. The use of aminoglycosides in com-
Renal transplantation patients received either vancomycin bination with other nephrotoxic drugs may result in renal
and ceftriaxone or cefazolin, and pancreas transplantation dysfunction and should be avoided unless alternatives are
patients received either vancomycin and gentamicin or ce- contraindicated. (Strength of evidence for prophylaxis = C.)
fazolin and gentamicin. There was no statistically significant For patients at high risk of Candida infection, fluconazole
difference in the risk of developing gram-positive infections adjusted for renal function may be considered.
between antimicrobial prophylaxis regimens with and with-
out vancomycin. The study was not powered to detect a dif- Kidney Transplantation
ference in efficacy between the antimicrobial regimens. For
patients known to be colonized with MRSA, VRE, or resis- Background. In 2007, UNOS reported that 16,628 kidney
tant gram-negative pathogens, it is reasonable to consider transplantations were performed in the United States; of
prophylaxis targeted specifically for these organisms. See these, 796 patients were younger than 18 years.998 The rate
the Common Principles section for further discussion. of postoperative infection after this procedure has been re-
An evaluation of the surgical complications of pan- ported to range from 10% to 56%, with the two most com-
creas transplant recipients with portal-enteric drainage mon infections being UTIs and SSIs.1004,1014–1024 Graft loss
found an intraabdominal infection rate of 12% in the 65 pa- due to infection occurs in up to 33% of cases.1017,1023 One
tients undergoing SPK transplantation and no cases in those study of adult and pediatric kidney transplant recipients
undergoing pancreas transplantation alone.999 All patients (both living-related and cadaveric donor sources) found
received either cefazolin 1 g i.v. every eight hours for one patient survival rates at 7 years after transplantation of
to three days, or vancomycin if the patient had a b-lactam 88.9% and 75.5%, respectively, and graft survival of 75%
allergy. and 55.5%, respectively.1025 No patients developed an SSI.
One study evaluated SSI rates in SPK transplantation Mortality associated with postoperative infections is substan-
after single-agent, single-dose prophylaxis with cefazolin 1 tial and ranges from approximately 5% to 30%.1015,1017,1019,
g i.v. to donors and recipients, as well as cefazolin 1-g/L 1022,1026,1027
bladder and intraabdominal irrigation in the recipient.1009 The frequency of SSIs in kidney transplant recipi-
Superficial SSIs developed in 2 patients (5%), and deep SSIs ents has ranged from 0% to 11% with antimicrobial pro-
associated with bladder anastomotic leaks or transplant pan- phylaxis1023–1025,1028,1029 to 2% to 7.5% without systemic
creatitis occurred in 4 additional patients (11%). This study prophylaxis.1030,1031 The majority of these infections were
reported similar SSI rates as with multidrug, multidose regi- superficial in nature and were detected within 30 days af-
mens. ter transplantation.1023,1028–1030 Risk factors for SSI after
Based on the regularity of isolation of Candida species kidney transplantation include contamination of organ per-
from SSIs after pancreas transplantation and the frequent fusate1027; pretransplantation patient-specific factors, such
colonization of the duodenum with yeast, fluconazole is as diabetes,1029,1030 chronic glomerulonephritis,1030 and
commonly added to prophylactic regimens. Although never obesity1027,1030,1032; procedure-related factors, such as ure-
studied in a randomized trial, a lower fungal infection rate teral leakage and hematoma formation1027; immunosuppres-
was found in one large case series with the use of fluconazole sive therapy1024,1027,1029; and postoperative complications,
(6%) compared with no prophylaxis (10%).1013 Although en- such as acute graft rejection, reoperation, and delayed graft
teric drainage of the pancreas has been identified as a risk function.1030 In one study, the frequency of SSI was 12%
factor for postoperative fungal infections, many institutions in patients receiving immunosuppression with azathioprine
use fluconazole for prophylaxis with bladder-drained organs plus prednisone but only 1.7% in patients receiving cyclo-
as well. In settings with a high prevalence of non-albicans sporine plus prednisone.1033 A significant difference in SSI
Candida species, a lipid-based formulation of amphoteri- rates was noted after kidney transplantation between immu-
cin B has been recommended in infectious diseases guide- nosuppression regimens including mycophenolate mofetil
lines from the American Society of Transplantation and the (45 [3.9%] of 1150 patients) versus sirolimus (11 [7.4%] of
American Society of Transplant Surgeons.15 144 patients).1029 Sirolimus-containing immunosuppression
Duration. Studies evaluating the use of antimicrobial was found to be an independent risk factor for SSIs. These
prophylaxis regimens in pancreas and SPK transplanta- recommendations refer to kidney transplant recipients; rec-
tion, summarized above, ranged from a single preopera- ommendations for living kidney donors can be found in the
tive dose of cefazolin to multidrug regimens of 2–5 days’ discussion of nephrectomy in the urologic section.
duration.995,1005,1009,1010,1012 More recent studies reported
monotherapy regimens with cefazolin or vancomycin,999
Organisms. Postoperative SSIs in kidney transplant re- Choice of agent. The available data do not indicate a
cipients are caused by gram-positive organisms, particu- significant difference between single-drug and multidrug an-
larly Staphylococcus species (including S. aureus and timicrobial regimens.1014,1018,1021 In addition, there appears to
S. epidermidis) and Enterococcus species, gram-nega- be no significant differences between single-agent regimens
tive organisms, E. coli, Enterobacter species, Klebsiella employing antistaphylococcal peni cillins and first-, sec-
species, P. aeruginosa, and yeast with Candida spe- ond-, or third-generation cephalosporins.1016,1017,1033–1035,1037
cies.1004,1014–1021,1023,1024,1026,1028,1030,1034 One study site Studies have directly compared antimicrobial regimens in
in Brazil reported a high level of antimicrobial resis- a prospective, controlled fashion. Single-agent prophylaxis
tance.1030 Organisms recovered from infections included with both cefazolin and ceftriaxone has been reported to re-
MRSA (77%), methicillin-resistant coagulase-negative sult in SSI rates of 0%.1016,1024,1037
Staphylococcus (53.5%), extended-spectrum b-lactamase- A survey of 101 kidney transplant centers in 39 coun-
producing K. pneumoniae (80%), and carbapenem-resistant tries reported that 65% of the centers used single antimicro-
P. aeruginosa (33.3%). Another center in Brazil reported a bial prophylaxis regimens, 20.8% used two-drug regimens,
significant difference in resistance to broad-spectrum anti- and 3% used three drugs; no prophylaxis was used in 11%
microbials in pathogens isolated in UTIs from cadaveric kid- of centers.1036 Cephalosporins were used in 68 centers (55
ney transplant recipients (n = 21, 19.1%) compared with liv- alone, 7 in combination with penicillin, and 6 with other an-
ing-related donor kidney transplant recipients (n = 2, 3.7%) timicrobials). Penicillins were used by 28 centers (13 alone,
(p = 0.008).1024 One center in the United States reported 94% 7 with cephalosporin, and 8 with other antimicrobials).
susceptibility to vancomycin of Enterococcus species within Other antimicrobials (specifics were not reported) were used
the first month after transplantation, while E. coli, cultured in 2 centers as the single agent.
most commonly more than six months after transplantation, As noted above, HICPAC recommendations for SSI
was 63% resistant to sulfamethoxazole–trimethoprim.1023 prevention include limiting the use of vancomycin to situ-
This resistance may be related to the routine use of sulfa- ations in which there is an MRSA or MRSE cluster or as an
methoxazole–trimethoprim in prophylaxis of Pneumocystis alternative for b-lactam-allergic patients.8 Transplantation
carinii pneumonia and UTI. procedures were not specifically covered in the guidelines.
Duration. Studies have used various prophylactic
Efficacy. A number of studies have clearly demonstrated regimens, ranging from a single-drug cephalosporin regi-
that antimicrobial prophylaxis significantly decreases post- men, administered as a single preoperative dose or for up
operative infection rates in patients undergoing kidney to 24 hours postoperatively, to multidrug regimens of
transplantation. These have included at least one random- two to five days’ duration.981,1004,1014–1018,1021,1023,1024,1028,
ized controlled trial1014 and many prospective and retro- 1029,1033,1036,1038
Cefazolin for 24 hours was equivalent to
spective studies comparing infection rates with prophylaxis seven days of surgical prophylaxis in living-related kid-
and historical infection rates at specific transplantation cen- ney transplant donors.1039 There appear to be no significant
ters.1015–1018,1021,1033–1035 Based on the available literature, the differences in SSI rates between single-dose, 24-hour, and
routine use of systemic antimicrobial prophylaxis is justified multidose regimens; therefore, the duration of antimicrobial
in patients undergoing kidney transplantation. should be restricted to 24 hours.
Two studies that evaluated a triple-drug regimen con-
sisting of an aminoglycoside, an antistaphylococcal penicil- Pediatric Efficacy. Although pediatric patients were in-
lin, and ampicillin found infection rates of <2%, compared cluded in studies demonstrating the efficacy of antimicrobial
with 10–25% with no antimicrobial prophylaxis.1018,1019 prophylaxis, there are few data specific to pediatric patients.
More specifically, infection rates in patients without anti- One cohort of 96 pediatric patients who underwent
microbial prophylaxis (45 cadaveric and 44 living-related 104 renal transplants (63% cadaveric and 37% living-related
donors) were 10.1% in total (8.9% and 11.4%, respectively), donors) ranged in age from six months to 18 years (mean
compared with 1.5% in total (1.5% and 0%, respectively) age, 8.2 ± 5.5 years).1040 Antimicrobial prophylaxis included
with antimicrobial prophylaxis.1018 Infection rates were as one dose of cefotaxime 30-mg/kg i.v. bolus at the start of
high as 33% in living-related patients with no antimicro- the procedure and cefotaxime 90 mg/kg/day in three divided
bial prophylaxis and 0–1% in both cadaveric and living- doses during the intensive care unit stay, which averaged one
related transplant recipients with antimicrobial prophy- to two days. No SSIs were reported.
laxis.1021 Piperacillin plus cefuroxime was also shown to
be efficacious; infection rates were 3.7%, compared with Recommendations. The recommended agent for patients
19% in cadaveric transplant recipients not receiving pro- undergoing kidney transplantation is cefazolin (Table 2).
phylaxis.1018 Several studies have shown that single-agent (Strength of evidence for prophylaxis = A.) For patients who
prophylaxis with an antistaphylococcal penicillin,1029,1034 a are allergic to b-lactam antimicrobials, clindamycin or van-
first-generation cephalosporin,1016,1017,1023,1024,1029 a second- comycin given in combination with gentamicin, aztreonam,
generation cephalosporin,1028,1035,1036 or a third-generation or a fluoroquinolone is a reasonable alternative. The dura-
cephalosporin (e.g., cefoperazone, cefotaxime, ceftriax- tion of prophylaxis should be restricted to 24 hours or less.
one)1024,1029,1033,1037 can reduce postoperative infection rates The use of aminoglycosides in combination with other neph-
to 0–8.4%. All studies included cadaveric transplant recipi- rotoxic drugs may result in renal dysfunction and should be
ents, whereas living-related transplant recipients were also avoided unless alternatives are contraindicated. (Strength of
included in select studies.1017,1024,1028,1036 Where compared evidence for prophylaxis = C.) For patients at high risk of
directly, infection rates between cadaveric and living-related Candida infection, fluconazole adjusted for renal function
transplant recipients receiving antimicrobial prophylaxis may be considered.
were not statistically different.1024
Plastic Surgery and Breast Procedures Guidelines also support no antimicrobial prophylaxis
in patients undergoing clean facial or nasal procedures with-
Background. Plastic surgery encompasses a broad range of out an implant.7 For patients undergoing facial or nasal pro-
procedures focused on reconstructive, dermatological, and cedures with an implant, antimicrobial prophylaxis should
cosmetic procedures.1041 The primary goal of these proce- be considered.7
dures is to restore function to the affected area, with a sec- A randomized, double-blind, controlled trial of 207
ondary goal of improving appearance. The scope of proce- patients evaluated the use of three antimicrobial prophy-
dures ranges from simple primary surgical-site closure, skin laxis regimens in patients undergoing abdominoplasty pro-
grafts, and skin flaps to composite tissue transplantations. cedures.1066 The reported SSI rates were 13% for patients
Composite tissue transplantation for tissue reconstruction of receiving no antimicrobial prophylaxis, 4.3% for those re-
the knee joint, larynx, uterus, abdominal wall, hand, face, ceiving preoperative antimicrobials only, and 8.7% for those
and penis has been performed in a small number of pa- receiving one preoperative dose and three days of postopera-
tients.1042,1043 tive antimicrobials. There was a significantly lower infec-
Most dermatological, breast (reduction and recon- tion rate in the group receiving preoperative antimicrobials
structive), clean head and neck, and facial procedures have only compared with the placebo group (p < 0.05). The infec-
an associated SSI rate of <5%.1044–1053 Oral procedures, such tion rate was slightly but not significantly higher in patients
as wedge excision of lip or ear, flaps on the nose,1046,1054 who received postoperative antimicrobials.
and head and neck flaps, have SSI rates of approximately Choice of agent. There is no consensus on the appro-
5–10%.1053,1055–1060 In addition to general risk factors as priate antimicrobial agent to use for prophylaxis in plastic
described in the Common Principles section, factors that surgery procedures.1055,1073 Agents with good gram-positive
increase the risk of postoperative infectious complications coverage and, depending on the site of surgery, activity
for plastic surgery procedures include implants,1061 skin ir- against common gram-negative organisms are recommended
radiation before the procedure, and procedures below the for patients undergoing clean plastic surgery procedures
waist.1062,1063 with risk factors (listed in the Common Principles section
and the background discussion of this section) or clean-
Organisms. The most common organisms in SSIs after plastic contaminated procedures. Cefazolin or ampicillin–sulbactam
surgery procedures are S. aureus,1045,1049,1050,1053,1054,1056,1063–1068 is sufficient in most cases, with clindamycin and vancomy-
other staphylococci, and streptococci.1045,1054,1064,1066,1067 cin as alternatives for patients with b-lactam allergy. There
Procedures involving macerated, moist environments (e.g., are no studies assessing the impact of MRSA on patients un-
under a panus or axilla of an obese individual), below the dergoing plastic surgery procedures or regarding the need to
waist, or in patients with diabetes are associated with a higher alter prophylaxis regimens in patients without known colo-
rate of infection with gram-negative organisms such as P. nization with MRSA. When vancomycin or clindamycin is
aeruginosa,1068 Serratia marcescens, or Enterobacteriaceae, used and if a gram-negative organism is highly suspected,
including E. coli,1065,1068 Klebsiella species,1068 and P. mira- practitioners should consider adding cefazolin if the patient
bilis.1065 is not b-lactam allergic; if the patient is b-lactam allergic, the
addition of aztreonam, gentamicin, or single-dose fluoroqui-
Efficacy. The efficacy of antimicrobial prophylaxis in select nolone should be considered. If the surgical site involves the
plastic surgery procedures has been investigated in several ear, an antipseudomonal fluoroquinolone may be considered
clinical trials and cohort studies. to cover Pseudomonas species.1045
Most placebo-controlled and retrospective studies for Although oral agents such as cephalexin, amoxicillin,
many clean plastic surgery procedures have found that an- clindamycin, and azithromycin have been recommended
timicrobial prophylaxis does not significantly decrease the in reviews of antimicrobial prophylaxis in clean derma-
risk of infection. These studies have evaluated head and neck tological surgery, there is no evidence that supports their
procedures (facial bone fracture, tumor excision and recon- use.13,1045,1046,1054
struction, radical neck dissection, rhinoplasty),1049 flexor Duration. Antimicrobial prophylaxis should be lim-
tendon injury repairs,1051 augmentation mammoplasty using ited to the shortest duration possible to prevent SSIs (even
periareolar submuscular technique,1052 carpal tunnel,1069 and if a drain or a catheter is left in place or an implant is in-
breast procedures (reduction mammoplasty, lumpectomy, serted), limit adverse events, and prevent antimicrobial re-
mastectomy, axillary node dissection).1056,1058,1070,1071 sistance.8,512,1047,1048,1054,1056
However, a Cochrane review of seven randomized, Multiple studies have found no significant differences
placebo-controlled trials of 1984 patients undergoing breast in SSI rates after breast surgery with single-dose preoperative
cancer procedures (axillary lymph node dissection and pri- cephalosporin compared with extended-duration regimens
mary nonreconstructive surgery) evaluated the effectiveness that last from one to five days postoperatively.1048,1054,1056
of preoperative or perioperative antimicrobial prophylaxis A randomized, single-blind, controlled trial of 74 pa-
(n = 995) compared with placebo or no treatment (n = 989) tients undergoing surgical ablation of head and neck ma-
in reducing the rate of postoperative infections.1072 Pooled lignancies with immediate free-flap reconstruction found
study results revealed a significant difference in SSI rates no significant differences in SSI rate between clindamycin
with antimicrobial prophylaxis (80 [8%] of 995), compared 900 mg i.v. every eight hours for 3 doses compared with 15
with 10.5% (104 of 989) for no antimicrobial prophylaxis doses.1057 Both groups were given clindamycin 900 mg i.v.
(relative risk, 0.72; 95% CI, 0.53–0.97). Review authors immediately preoperatively, in addition to the postoperative
concluded that antimicrobial prophylaxis is warranted to regimens.
decrease the risk of SSIs in nonreconstructive breast cancer In a controlled study, 200 patients undergoing septo-
procedures. rhinoplasty were randomized to a single preoperative dose
of amoxicillin–clavulanate 2.2 g i.v. administered 30 min- tals. Infect Control Hosp Epidemiol. 2008; 29(suppl
utes before surgical incision only (n = 100) or in combina- 1):S51–61.
tion with postoperative oral amoxicillin–clavulanate 1000 6. Antimicrobial prophylaxis for surgery. Treat Guidel
mg twice daily for seven days.533 There was no significant Med Lett. 2009; 7:47–52.
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35:189–96. Site Infection (SSI)8,36
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antibiotic prophylaxis and wound infection follow- Superficial Incisional SSI: Occurs within 30 days post-
ing breast surgery. J Antimicrob Chemother. 1993; operatively and involves skin or subcutaneous tissue of the
31(suppl B):43–8. incision and at least one of the following: (1) purulent drain-
1071. Kompatscher P, von Planta A, Spicher I, et al. age from the superficial incision, (2) organisms isolated from
Comparison of the incidence and predicted risk of an aseptically obtained culture of fluid or tissue from the
early surgical site infections after breast reduction. superficial incision, (3) at least one of the following signs or
Aesthetic Plast Surg. 2003; 27:308–14. symptoms of infection: pain or tenderness, localized swell-
1072. Bunn F, Cunningham ME, Handscomb K. Prophylactic ing, redness, or heat, and superficial incision is deliberately
antibiotics to prevent surgical site infection after breast opened by surgeon and is culture-positive or not cultured (a
cancer surgery. Cochrane Database Syst Rev. 2006; culture-negative finding does not meet this criterion), and
2:CD005360. (4) diagnosis of superficial incisional SSI by the surgeon or
1073. Perrotti JA, Castor SA, Perez PC, et al. Antibiotic use attending physician.
in aesthetic surgery: a national survey and literature
review. Plast Reconstr Surg. 2002; 109:1685–93. Deep Incisional SSI: Occurs within 30 days after the opera-
1074. Smyth AG, Knepil GJ. Prophylactic antibiotics and tive procedure if no implant is left in place or within one year
surgery for primary clefts. Br J Oral Maxillofac Surg. if implant is in place and the infection appears to be related
2008; 46:107–9. to the operative procedure, involves deep soft tissues (e.g.,
1075. Cocco JF, Antonetti JW, Burns JL, et al. fascial and muscle layers) of the incision, and the patient has
Characterization of the nasal, sublingual and oropha- at least one of the following: (1) purulent drainage from the
ryngeal mucosa microbiota in cleft lip and palate in- deep incision but not from the organ/space component of the
dividuals before and after surgical repair. Cleft Palate surgical site, (2) a deep incision spontaneously dehisces or is
Craniofac J. 2010; 47:151–5. deliberately opened by a surgeon and is culture-positive or
not cultured and the patient has at least one of the following
signs or symptoms: fever (>38 °C) or localized pain or ten-
Appendix A—National Healthcare derness (a culture-negative finding does not meet this crite-
Safety Network Criteria rion), (3) an abscess or other evidence of infection involving
for Classifying Wounds35 the deep incision is found on direct examination, during re-
operation, or by histopathologic or radiologic examination,
Clean: An uninfected operative wound in which no inflam- and (4) diagnosis of a deep incisional SSI by a surgeon or
mation is encountered and the respiratory, alimentary, geni- attending physician.
tal, or uninfected urinary tracts are not entered. In addition,
clean wounds are primarily closed and, if necessary, drained Organ/Space SSI: Involves any part of the body, excluding
with closed drainage. Operative incisional wounds that fol- the skin incision, fascia, or muscle layers, that is opened or
low nonpenetrating (blunt) trauma should be included in this manipulated during the operative procedure. Specific sites
category if they meet the criteria. are assigned to organ/space SSI to further identify the lo-
cation of the infection (e.g., endocarditis, endometritis, me-
Clean-Contaminated: Operative wounds in which the respi- diastinitis, vaginal cuff, and osteomyelitis). Organ/space
ratory, alimentary, genital, or urinary tracts are entered under SSI must meet the following criteria: (1) infection occurs
controlled conditions and without unusual contamination. within 30 days after the operative procedure if no implant
Specifically, operations involving the biliary tract, appendix, is in place or within 1 year if implant is in place and the
vagina, and oropharynx are included in this category, pro- infection appears to be related to the operative procedure,
vided no evidence of infection or major break in technique (2) infection involves any part of the body, excluding the
is encountered. skin incision, fascia, or muscle layers, that is opened or ma-
nipulated during the operative procedure, and (3) the patient
Contaminated: Open, fresh, accidental wounds. In addition, has at least one of the following: (a) purulent drainage from
operations with major breaks in sterile technique (e.g., open a drain that is placed through a stab wound into the organ/
cardiac massage) or gross spillage from the gastrointestinal space, (b) organisms isolated from an aseptically obtained
tract and incisions in which acute, nonpurulent inflammation culture of fluid or tissue in the organ/space, (c) an abscess or
is encountered are included in this category. other evidence of infection involving the organ/space that is
found on direct examination, during reoperation, or by his-
Dirty or Infected: Includes old traumatic wounds with re- topathologic or radiologic examination, and (d) diagnosis of
tained devitalized tissue and those that involve existing clin- an organ/space SSI by a surgeon or attending physician.
ical infection or perforated viscera. This definition suggests
that the organisms causing postoperative infection were
present in the operative field before the operation. The following individuals are acknowledged for their signifi-
cant contributions to this manuscript: Sandra I. Berríos-Torres,
M.D.; Rachel Bongiorno-Karcher, Pharm.D.; Colleen M. Culley,
Pharm.D., BCPS; Susan R. Dombrowski, M.S., B.S.Pharm.; and Diseases. Drs. Bolon, Napolitano, Olsen, Steinberg, Slain, and
Susan J. Skledar, B.S.Pharm., M.P.H., FASHP. Weinstein have declared no potential conflicts of interest.
Financial support provided by Emory University, Johns Hopkins Copyright © 2013, American Society of Health-System Pharmacists,
University, Northwestern University, Rush University, University Inc. All rights reserved.
of Colorado, University of Michigan, University of Oklahoma,
University of Nebraska, University of Virginia, University of The bibliographic citation for this article is as follows: Bratzler DW,
Washington, and West Virginia University. Dellinger EP, Olsen KM, et al. Clinical practice guidelines for an-
timicrobial prophylaxis in surgery. Am J Health-Syst Pharm. 2013;
70:195–283.
Dr. Bratzler is a consultant for Telligen; Dr. Dellinger has received
honoraria for participation on advisory boards and consultation for
Merck, Baxter, Ortho-McNeil, Targanta, Schering-Plough, WebEx,
Astellas, Durata, Pfizer, Applied Medical, Rib-X, 3M, the American
Hospital Association, Premier Inc., Oklahoma Foundation for
Medical Quality, and the Hospital Association of New York State;
Dr. Perl serves on the advisory boards of Hospira and Pfizer and
has received a grant from Merck; Dr. Auwaerter serves on the advi-
sory panel of Genentech; Dr. Fish serves on the advisory board and
speakers’ bureau of Merck; and Dr. Sawyer serves as a consultant
for Pfizer, Merck, Wyeth, 3M, and Ethicon and has received an R01
grant from the National Institute of General Medical Sciences and
a T32 grant from the National Institute of Allergy and Infectious
Clinical Practice Guidelines for Sustained

Neuromuscular Blockade in the
Adult Critically Ill Patient
The decision to treat a patient in the intensive care unit (ICU) Adult skeletal muscle retains an ability to synthesize both
with neuromuscular blocking agents (NMBAs) (for reasons the mature adult nAChR as well as an immature nAChR variant
other than the placement of an endotracheal tube) is a difficult in which a gamma subunit is substituted for the normal epsilon
one that is guided more commonly by individual practitioner subunit. Synthesis of immature (fetal) receptors may be trig-
preference than by standards based on evidence-based medicine. gered in the presence of certain diseases (e.g., Guillain-Barré
Commonly cited reasons for the use of NMBAs in the ICU are syndrome, stroke) and other conditions producing loss of nerve
to facilitate mechanical ventilation or different modes of me- function. These immature nAChRs are distinguished by three
chanical ventilation and to manage patients with head trauma features. First, immature receptors are not localized to the mus-
or tetanus. Independent of the reasons for using NMBAs, we cle endplate but migrate across the entire membrane surface.2
emphasize that all other modalities to improve the clinical situ Second, the immature receptors are metabolically short-lived
ation must be tried, using NMBAs only as a last resort. (<24 hours) and more ionically active, having a 2- to 10-fold
In 1995 the American College of Critical Care longer channel “open time.” Lastly, these immature receptors
Medicine (ACCM) of the Society of Critical Care Medicine are more sensitive to the depolarizing effects of such drugs as
(SCCM) published guidelines for the use of NMBAs in
succinylcholine and more resistant to the effects of competitive
the ICU. The present document is the result of an attempt
antagonists, such as pancuronium. This increase in the number
to reevaluate the literature that has appeared since the last
of immature acetylcholine receptors may account for the tachy
guidelines were published and, based on that review, to up-
phylaxis seen with NMBAs and some of the complications
date the recommendations for the use of NMBAs in the ICU.
associated with their use. For the remainder of this document,
Appendix A summarizes our recommendations. Using meth-
only nondepolarizing NMBAs will be discussed.
ods previously described to evaluate the literature and grade
the evidence, the task force reviewed the physiology of the
neuromuscular receptor, the pharmacology of the NMBAs Pharmacology of Neuromuscular-
currently used in the ICU, the means to monitor the degree Receptor Blockers
of blockade, the complications associated with NMBAs, and
the economic factors to consider when choosing a drug. Aminosteroidal Compounds. The aminosteroidal com-
pounds include pancuronium, pipecuronium, vecuronium,
Neuromuscular Junction in and rocuronium (Tables 1 and 2).3–11
Health and Disease Pancuronium. Pancuronium, one of the original NMBAs
used in ICUs, is a long-acting, nondepolarizing compound that
The neuromuscular junction consists of a motor nerve termi- is effective after an intravenous bolus dose of 0.06–0.1 mg/kg
nus, the neurotransmitter acetylcholine, and the postsynaptic for up to 90 minutes. Though it is commonly given as an i.v.
muscle endplate (Figure 1). The impulse of an action potential bolus, it can be used as a continuous infusion12 by adjusting
causes the release of acetylcholine from synaptic vesicles (each the dose to the degree of neuromuscular blockade that is de-
containing about 10,000 molecules of acetylcholine) diffusing sired (Table 1). Pancuronium is vagolytic (more than 90% of
across the 20-nm gap to the postsynaptic endplate. The motor ICU patients will have an increase in heart rate of ≥10 beats/
endplate contains specialized ligand-gated, nicotinic acetylcho- min), which limits its use in patients who cannot tolerate an
line receptors (nAChRs), which convert the chemical signal increase in heart rate.12 In patients with renal failure or cirrho-
(i.e., binding of two acetylcholine molecules) into electrical sis, pancuronium’s neuromuscular blocking effects are pro-
signals (i.e., a transient permeability change and depolarization longed because of its increased elimination half-life and the
in the postsynaptic membrane of striated muscle). decreased clearance of its 3-hydroxypancuronium metabolite
There are depolarizing and nondepolarizing NMBAs. that has one-third to one-half the activity of pancuronium.
Depolarizing NMBAs physically resemble acetylcholine Pipecuronium. Pipecuronium is another long-acting
and, therefore, bind and activate acetylcholine receptors. NMBA with an elimination half-life of about two hours, simi-
Succinylcholine is currently the only available depolarizing lar to pancuronium’s. Khuenl-Brady and colleagues13 con-
NMBA and is not used for long-term use in ICUs. ducted an open-label evaluation of pipecuronium compared
Nondepolarizing NMBAs also bind acetylcholine re- with pancuronium in 60 critically ill patients to determine the
ceptors but do not activate them—they are competitive an- minimum doses required for ventilatory management. The ad-
tagonists. The difference in the mechanism of action also ministration of 8 mg of either drug followed by intermittent
accounts for different effects in certain diseases. If there is boluses of 4–6 mg when needed resulted in optimal paraly-
a long-term decrease in acetylcholine release, the number sis. Patients were paralyzed for a mean duration of 62.6 hours
of acetylcholine receptors within the muscle increases. This (45–240 hours) and 61.5 hours (46–136 hours) with pan-
upregulation causes an increased response to depolarizing curonium and pipecuronium, respectively. No adverse effects
NMBAs but a resistance to nondepolarizing NMBAs (i.e., were attributed to either drug. Perhaps because of this lack of
more receptors must be blocked). Conditions in which there difference and because there are no recent studies examining
are fewer acetylcholine receptors (e.g., myasthenia gravis) pipecuronium’s use in the ICU, most clinicians continue to
lead to an increase in sensitivity to nondepolarizing NMBAs. use the more familiar drug, pancuronium.
Figure 1. Neuromuscular Junction. Schematic model of the organization and structure of the neuromuscular junction, with focus and enlargement
on the postsynaptic membrane. Agrin is the nerve-derived protein that triggers receptor clustering during synapse formation. Receptor aggregation
appears to occur in distinct steps, however, initiated with acetylcholine receptors (AChR) localized together by rapsyn. Meanwhile, D-dystroglycan,
the extracellular component of dystrophin-associated glycoprotein complex (DGC), is the agrin receptor which transduces final AChR clustering.
This process utilizes the structural organization of additional proteins like utrophin, which stabilize the mature, immobile domains by interaction with
the underlying cytoskeleton (actin). When completed, this process concentrates AChR density 1000-fold compared to typical muscle membrane.
ACh = acetylcholine, MuSK = muscle-specific-receptor kirase, MASC = MuSK-accessory specificity component. (Reprinted with permission, from
Wall MH, Prielipp RC. Monitoring the neuromuscular junction. In: Lake C, Blitt CD, Hines RL, eds. Clinical Monitoring: Practical Applications
for Anesthesia and Critical Care. Philadelphia: W.B. Saunders, 2000, Figure 10-3.)
Vecuronium. Vecuronium is an intermediate-acting corticosteroids, the opinion of the task force was that patients
NMBA that is a structural analogue of pancuronium and is not receiving vecuronium and corticosteroids were at increased
vagolytic. An i.v. bolus dose of vecuronium 0.08–0.1 mg/kg, risk of prolonged weakness once the drug was discontinued.
produces blockade within 60–90 seconds that typically lasts Rocuronium. Rocuronium is a newer nondepolarizing
25–30 minutes. After an i.v. bolus dose, vecuronium is given NMBA with a monoquaternary steroidal chemistry that has
as a 0.8–1.2-μg/kg/min continuous infusion, adjusting the an intermediate duration of action and a very rapid onset.
rate to the degree of blockade desired. Because up to 35% of When given as a bolus dose of 0.6–1 mg/kg, blockade is
a dose is renally excreted, patients with renal failure will almost always achieved within two minutes, with maximum
have decreased drug requirements. Similarly, because up to blockade occurring within three minutes. Continuous infu-
50% of an injected dose is excreted in bile, patients with he- sions are begun at 10 μg/kg/min.8 Rocuronium’s metabolite,
patic insufficiency will also have decreased drug requirements 17-des-acetylrocuronium, has only 5–10% activity com-
to maintain adequate blockade. The 3-desacetylvecuronium pared with the parent compound.
metabolite has 50% of the pharmacologic activity of the par- Sparr, Khuenl-Brady, and colleagues8,9 studied the
ent compound, so patients with organ dysfunction may have dose requirements, recovery times, and pharmacokinetics of
increased plasma concentrations of both the parent compound rocuronium in 32 critically ill patients, 27 of whom were
and the active metabolite, which contributes to the prolonga- given intermittent bolus doses, and 5 received a continu-
tion of blockade if the dose is not adjusted. Vecuronium has ous infusion. The median duration of drug administration
been reported to be more commonly associated with pro- was 29 hours and 63.4 hours in the bolus dose and infusion
longed blockade once discontinued, compared with other groups, respectively. The mean dose of rocuronium required
NMBAsa. Members of the task force believe that vecuronium to maintain 80% blockade was 0.34 mg/kg, and the median
is being used with decreased frequency in the ICU. infusion rate required to maintain one twitch of the TOF was
Vecuronium has been studied in open-label prospective 0.54 mg/kg/hr. The median time from the last bolus dose to
trials.14,15 In one of these studies, the mean infusion rate for the appearance of TOF response was 100 minutes; in the
vecuronium was 0.9 ± 0.1 μg/kg/min for a mean duration of infusion group, the TOF response returned 60 minutes after
80 ± 7 hours. Recovery of a train-of-four (TOF) ratio of ≥0.7 the infusion was stopped.
was significantly longer than with cisatracurium.15 Recovery
Rapacuronium. Rapacuronium, a propionate analogue
time averaged 1–2 hours but ranged from ≤30 minutes to
of vecuronium, was marketed as a nonde polarizing NMBA
more than 48 hours.
as an alternative to succinylcholine. It was withdrawn from
Although Rudis, et al.14 observed no difference in the
the market on March 27, 2001, because of reports of mor-
incidence of prolonged blockade between patients receiving
bidity (bronchospasm) and mortality associated with its use.
vecuronium with and without concomitant administration of
Table 1.
Selected Neuromuscular Blocking Agentsa for ICU Use
Benzylisoquinolinium Drugs
d-Turbocurarine Cisatracurium Atracurium Doxacurium Mivacurium
Variable (Curare) (Nimbex) (Tracrium) (Nuromax) (Mivacron)
Introduced (yr) 1942 1995 1983 1991 1992
ED95b dose (mg/kg) 0.51 0.05 0.25 0.025–0.03 0.075
Initial dose (mg/kg) 0.1–0.2 0.1–0.2 0.4–0.5 0.025–0.05 0.15–0.25
Duration (min) 80 45–60 25–35 120–150 10–20
Infusion described . . . Yes Yes Yes Yes
Infusion dose . . . 2.5–3 4–12 0.3–0.5 9–10
(μg/kg/min)
Recovery (min) 80–180 90 40–60 120–180 10–20
% Renal excretion 40-45 Hofmann 5–10 (uses 70 Inactive
elimination Hofmann metabolites
elimination)
Renal failure Increased duration No change No change Increased duration Increased duration
% Biliary excretion 10–40 Hofmann Minimal (uses Insufficient data . . .
elimination Hofmann
elimination)
Hepatic failure Minimal change to Minimal to no Minimal to no . . . Increased duration
mild increased change change
effect
Active metabolites No No No, but can . . . No
accumulate
laudanosine
Histamine release Marked No Minimal but dose No Minimal but dose
hypotension dependent dependent
Vagal block Minimal No No No No
tachycardia
Ganglionic Marked No Minimal to none No No
blockade
hypotension
Prolonged ICU . . . Rare Rare Insufficient data Insufficient data
block
Aminosteroidal Drugs
Pancuronium Vecuronium Pipecuronium Rocuronium
(Pavulon) (Norcuron) (Arduan) (Zemuron)
Introduced (yr) 1972 1984 1991 1994
ED95b dose (mg/kg) 0.05 0.05 0.05 0.3
Initial dose (mg/kg) 0.06–0.1 0.08–0.1 0.085–0.1 0.6–1
Duration (min) 90–100 35–45 90–100 30
Infusion described Yes Yes No Yes
Infusion dose (μg/ 1–2 0.8–1.2 0.5–2 10–12
kg/min)
Recovery (min) 120–180 45–60 55–160 20–30
% Renal excretion 45–70 50 50+ 33
Renal failure Increased effect Increased effect, Increased duration Minimal
especially
metabolites
% Biliary excretion 10–15 35–50 Minimal <75
Hepatic failure Mild increased effect Variable, mild Minimal Moderate
Active metabolites Yes, 3-OH and 17-OH- Yes, 3-desacetyl– Insufficient data No
pancuronium vecuronium
Histamine release No No No No
hypotension
Vagal block Modest to marked No No Some at higher
tachycardia doses
Ganglionic No No No No
blockade
hypotension
Prolonged ICU block Yes Yes Insufficient data Insufficient data
a
Based on drugs for use in a 70-kg man. Modified with permission from Prielipp and Coursin. Reference 3.
b
ED95 = effective dose for 95% of patients studied.
Benzylisoquinolinium Compounds. The benzylisoquino d-Tubocurarine. Tubocurarine was the first nonde-
linium compounds include D-tubocuranine, atracurium, polarizing NMBA to gain acceptance and usage in the ICU.
cisatracurium, doxacurium, and mivacurium (Tables 1 This long-acting benzylisoquinolinium agent is rarely used
and 3).12,15,16,31 in ICUs because it induces histamine release and autonomic
Table 2.
ICU Studies of Aminosteroidal Drugsa
Level of
Reference Type of Study Patients Results Evidence
4 Prospective, observational, 30 Median time to recovery with pancuronium was 3.5 hr in 3
cohort infusion group vs. 6.3 hr in the bolus dose group.
5 Prospective, open-label 25 PICU Increased infusion requirements for pancuronium with 3
anticonvulsants.
6 Prospective, open-label 6 Vecuronium clearance increased in 3 and decreased in 2 3
patients. VD did not change.
7 Survey . . . Neuromuscular blockade monitored clinically with only 5
8.3% using TOF. All respondents indicated concomitant
use of sedatives and/or opioids (75%).
8 Prospective, open-label 30 SICU 25 trauma patients received rocuronium 50-mg i.v. 3
bolus dose followed by maintenance doses of 25 mg
whenever TOF = 2, five patients were on continuous
infusion at 25 mg/hr. Duration 1–5 days, recovery
approximately 3 hr, and plasma clearance similar
between groups.
9 Prospective, open-label 32 An initial dose of rocuronium 50 mg followed by 3
maintenance doses of 25 mg with TOF = 2 (n = 27)
or by continuous infusion to maintain TOF (n = 5).
Pharmacokinetic data tabulated. Crossover with
patients reported by Khuenl-Brady, et al.8
10 Prospective, randomized, 20 CABG Pancuronium (n = 10) was compared to rocuronium 2
controlled (n = 10). Incidence of residual block higher with
pancuronium than rocuronium. No effect on time to
extubation.
11 Prospective, open-label 12 ICU 12 patients, 4 with MODS. Patients given 0.6-mg/kg bolus 3
dose of rocuronium followed by repeated bolus
(n = 2) or continuous infusion (n = 10) started at
10–12 μg/kg/min and adjusted to TOF = 1–4. No
evidence of prolonged blockade.
a
PICU = pediatric intensive care unit, SICU = surgical intensive care unit, CABG = coronary artery bypass grafting, ICU = intensive care unit,
TOF = train-of-four, VD = volume of distribution, MODS = multiple organ dysfunction syndrome.
Table 3.
ICU Studies of Benzylisoquinolinium Drugsa
Type of Level of
Reference Study Patients Dose Results Evidence
16 Review . . . . . . Review of pharmacokinetics 5
17 Prospective, 14 with Cisatracurium 0.1-mg/ VD greater in liver patients but no 5
open-label, hepatic kg i.v. bolus dose differences in elimination t½ or in
controlled failure vs. duration of action
11 controls
18 Prospective, 20 ICU Cisatracurium (n = 12) Similar mean recovery time 2
randomized, 0.25 mg/kg/hr
single-blind Atracurium (n = 8)
0.62 mg/kg/hr
19 Prospective, 12 ICU Cisatracurium 0.1-mg/kg Measured VD, Cl, T½. Laudanosine 2
randomized bolus dose + 0.18-mg/ concentration was lower in patients
kg/hr infusion on cisatracurium
Atracurium: 0.5 mg/kg + 0.6-
mg/kg/hr infusion
20 Randomized, 61 ICU Cisatracurium (n = 26) 0.1- 118 ± 19 min recovery no change in 3
open-label mg/kg bolus, followed HR, BP, and ICP with bolus
by an infusion of 3 μg/
kg/min; 14 pts infusion
only
Atracurium (n = 18) 0.5
mg/kg bolus followed
by an infusion of 10
μg/kg/min; 3 pts
infusion only
Infusion adjusted to one twitch
(Continued on Next Page)
Table 3 (continued)
Level of
Reference Type of Study Patients Dose Results Evidence
15 Prospective, 58 ICU Cisatracurium 2.5-μg/kg/ Recovery profiles were significantly different with more 1
randomized, min prolonged recovery noted for vecuronium. TOF
double-blind, Vecuronium 1-μg/kg/min monitoring could not eliminate prolonged recovery
multicenter and myopathy
21 Prospective, 14 with brain Cisatracurium 0.15 mg/kg No change in ICP, CPP, CBF, MAP, ETCO2, and HR 2
blinded, injury bolus and no histamine-related symptoms, with 3×ED95
cross-over Atracurium 0.75 mg/kg cisatracurium. With 3×ED95 tracurium, ICP, CPP,
bolus CBF, and MAP decreased within 2–4 min. Five
patients had typical histamine reaction; excluding
these five patients, there was no difference in any
variable compared with cisatracurium
22 Observational, 24 with brain 0.1 or 0.2-mg/kg No change from baseline in ICP, CPP, MAP, ETCO2, 5
prospective, injury cisatracurium bolus HR, and CBF velocity in both groups
open-label dose
23 Case . . . . . . . . . 4
24 Case . . . . . . . . . 4
25 Review . . . . . . . . . 4
26 Editorial . . . . . . . . . 4
27 Review . . . . . . . . . 5
28 Review . . . . . . . . . 5
12 Multicenter, 40 critically ill Doxacurium 0.04-mg/kg No difference in adverse reactions or onset of 1

prospective, bolus dose, 0.025- blockade; pancuronium had a more prolonged and
double-blind, mg/kg maintenance; variable recovery time
randomized pancuronium: 0.07 mg/
kg bolus dose, 0.05-
mg/kg maintenance
29 Prospective, 8 mechanical Doxacurium: 0.03-mg/kg DO2 + VO2 decreased, pHi increased; VO2 is 5
open-label ventilated load; 0.03-mg/kg/hr decreased and pHi increased. NMBA causes
ICU with HD infusion redistribution of blood flow to splanchnic beds
monitoring
and pHi <7.35
30 Prospective, 8 ICU with Doxacurium 0.05 mg/kg No significant effect in HR, BP, ICP. No adverse effects 5
open-label traumatic then 0.25 μg/kg/min
study head injury
31 Case report 4 with atracurium Doxacurium 0.25–0.75 No tachyphylaxis noted 5

tachyphylaxis μg/kg/min
a
ICU = intensive care unit, TOF = train-of-four, VD = volume of distribution, HR = heart rate, BP = blood pressure, ICP = intracranial pressure,
CPP = cerebral perfusion pressure, CBF = cerebral blood flow, MAP = mean arterial pressure, NMBA = neuromuscular blocking agent, ETCO2 = end
tidal carbon dioxide, ED95 = effective dose for 95% of patients studied, HD = hemodynamic flow, pHi = gastric mucosal pH, DO2 = oxygen delivery,
VO2 = oxygen consumption, CBF = cerebral blood flow.
ganglionic blockade. Hypotension is rare, however, when to 20 μg/kg/min with doses adjusted to clinical endpoints or
the agent is administered slowly in appropriate dosages by TOF monitoring. Infusion durations ranged from ≤24 hours
(e.g., 0.1–0.2 mg/kg). Metabolism and elimination are af- to >200 hours. Recovery of normal neuromuscular activity
fected by both renal and hepatic dysfunction. usually occurred within one to two hours after stopping the
Atracurium.Atracurium is an intermediate-acting NMBA infusions and was independent of organ function. Long–term
with minimal cardiovascular adverse effects and is associated infusions have been associated with the development of toler
with histamine release at higher doses. It is inactivated in plas- ance, necessitating significant dose increases or conversion to
ma by ester hydrolysis and Hofmann elimination so that renal or other NMBAs.31,33 Atracurium has been associated with persis
hepatic dysfunction does not affect the duration of blockade. tent neuromuscular weakness as have other NMBAs.34–38
Laudanosine is a breakdown product of Hofmann Cisatracurium. Cisatracurium, an isomer of atra-
elimination of atracurium and has been associated with cen- curium, is an intermediate-acting benzyliso-quinolinium
tral nervous system excitation. This has led to concern about NMBA that is increasingly used in lieu of atracurium. It pro-
the possibility of precipitating seizures in patients who have duces few, if any, cardiovascular effects and has a lesser ten-
received extremely high doses of atracurium or who are in dency to produce mast cell degranulation than atracurium.
hepatic failure (laudanosine is metabolized by the liver). Bolus doses of 0.1–0.2 mg/kg result in paralysis in an aver-
There has been only one report of a surgical patient who had age of 2.5 minutes, and recovery begins at approximately 25
a seizure while receiving atracurium.32 minutes; maintenance infusions should be started at 2.5–3
Atracurium has been administered to various critically ill μg/kg/min. Cisatracurium is also metabolized by ester hy-
patient populations, including those with liver failure,17 brain drolysis and Hofmann elimination, so the duration of block-
injury,21 or multiple organ dysfunction syndrome (MODS), to ade should not be affected by renal or hepatic dysfunction.
facilitate mechanical ventilation. In these reports, atracurium Prolonged weakness has been reported following the use of
infusion rates varied widely, but they typically ranged from 10 cisatracurium.38
Cisatracurium has been compared with atracurium and accumulation, analgesia, and amnesia; and limiting com-
vecuronium for facilitating mechanical ventilation in sev plications related to prolonged or excessive blockade; and
eral open-label prospective trials.15,18–21 Cisatracurium infu improving economics. However, in many ICUs, NMBAs are
sion rates ranged from 2 to 8 μg/kg/min and were adjusted administered continuously, achieving adequate paralysis and
to clinical endpoints or to TOF count. Infusion durations faster recovery with TOF monitoring.
varied from 4 to 145 hours. Recovery of a TOF ratio >0.7
occurred within 34–85 minutes after drug discontinuation Facilitate Mechanical Ventilation. Numerous reports have
and was independent of organ function. These recovery described the use of NMBAs to facilitate mechanical venti
times are similar to those seen with atracurium18,21 and less lation. Most of the reports are limited to case studies, small
than those observed with vecuronium.15 prospective open-label trials, and small randomized open-
Doxacurium. Doxacurium, a long-acting benzyliso- label and double-blind trials enrolling a wide variety of
quinolinium agent, is the most potent NMBA currently critically ill patients to whom NMBAs were given to pre-
available. Doxacurium is essentially free of hemodynamic vent respiratory dysynchrony, stop spontaneous respiratory
adverse effects. Initial doses of doxacurium 0.05–0.1 mg/kg efforts and muscle movement, improve gas exchange, and
may be given with maintenance infusions of 0.3–0.5 μg/kg/ facilitate inverse ratio ventilation. However, none of these
min and adjusted to the degree of blockade desired. An initial reports compared NMBAs to placebos.
bolus dose lasts an average of 60–80 minutes. Doxacurium
is primarily eliminated by renal excretion. In elderly patients Manage Increased ICP. The data supporting the use of
and patients with renal dysfunction, a significant prolonga- NMBAs to control ICP are limited to a case report and an
tion of effect may occur. open-label trial. Prielipp30 evaluated doxacurium use in eight
Murray and colleagues12 conducted a prospective, ran- patients with severe head injury in an open-label prospective
domized, controlled, multicenter comparison of intermittent study. NMBAs were given to facilitate ventilation or to man-
doses of doxacurium and pancuronium in 40 critically ill pa- age brain injuries. Patients received an initial bolus injection
tients requiring neuromuscular blockade to optimize mechanical of doxacurium 0.05 mg/kg followed by a continuous infu
ventilation or to lower intracranial pressure (ICP). Patients were sion of 0.25 μg/kg/min adjusted to maintain one twitch of the
given another bolus dose based on TOF monitoring and were TOF. Doxacurium had no effect on ICP, heart rate, or blood
paralyzed for a mean duration of 2.6 days with doxacurium or pressure. Infusion rates were similar at the beginning (1 ± 0.1
2.2 days with pancuronium. There was a clinically significant mg/hr) and at the end (1.3 ± 0.2 mg/hr) of the study. TOF re-
increase in heart rate after the initial bolus dose of pancuronium sponses returned at 118 minutes; a TOF ratio of 0.7 was mea-
compared with baseline (120 ± 23 versus 109 ± 22 beats/min, sured at 259 ± 24 minutes. No adverse events were reported.
respectively) without any differences after the initial dose of McClelland, et al.40 treated three patients with atracu-
doxacurium (107 ± 21 versus 109 ± 21 beats/min, respectively). rium for four to six days to manage increased ICP. patients
Once the drugs were discontinued, the pancuronium group had could undergo a neurologic examination within minutes
a more prolonged and variable recovery time (279 ± 229 min) after discontinuing atracurium. No adverse events were re-
than the doxacurium group (135 ± 46 min). ported. There have been no controlled studies evaluating the
Mivacurium. Mivacurium is one of the shortest-acting role of NMBAs in the routine management of increased ICP.
NMBAs currently available. It consists of multiple stereo-
isomers and has a half-life of approximately two minutes, Treat Muscle Spasms. Case studies describe the use of
allowing for rapid reversal of the blockade. There are little NMBAs in the treatment of muscle contractures associated
data to support its use as a continuous infusion in the ICU. with tetanus, drug overdoses, and seizures; many were pub-
lished before 1994.
Indications Anandaciva and Koay41 administered a continuous ro-
curonium infusion to control muscle tone in patients with
NMBAs are indicated in a variety of situations (Table 4).8,9,12– tetanus. Muscle spasms recurred at an infusion rate of 8 μg/
15,17–21,30,39,42
There have been no studies randomizing kg/min, and neither administering a bolus dose of 0.9 mg/
patients who are considered candidates for NMBAs to a pla- kg nor increasing the infusion rate to 10 μg/kg/min con-
cebo versus an NMBA. We therefore reviewed many studies trolled the muscle contractures but did increase heart rate.
comparing one NMBA to another to assess the clinical indi- Switching to a different NMBA could control the spasms.
cations for enrolling patients in these studies. The most com-
mon indications for long-term administration of NMBAs Decrease Oxygen Consumption. Freebairn, et al.42 evaluated
included facilitation of mechanical ventilation, control of the effects of vecuronium on oxygen delivery, oxygen con-
ICP, ablation of muscle spasms associated with tetanus, and sumption, oxygen extraction ratios, and gastric intramuco
decreasing oxygen consumption (Figure 2). NMBAs are of- sal pH in a randomized, placebo-controlled crossover trial
ten used to facilitate ventilation and ablate muscular activity in 18 critically ill patients with severe sepsis. Although the
in patients with elevated ICP or seizures but have no direct infusion of vecuronium achieved an adequate level of pa-
effect on either condition. Patients who are being treated for ralysis and improved respiratory compliance, it did not alter
seizures who also take NMBAs should have electroenceph- intramucosal pH, oxygen consumption, oxygen delivery, or
alographic monitoring to ensure that they are not actively oxygen extraction ratios.
seizing while paralyzed.
With the exception of atracurium and cisatracurium, Recommended Indications
which need to be given continuously because of their short
half-lives, bolus administration of NMBAs offers potential There are no prospective, randomized, controlled trials as-
advantages for controlling tachyphylaxis; monitoring for signing patients to an NMBA versus a placebo with a goal
Table 4.
Indications for the Long-Term Use of Neuromuscular Blocking Agents in Critically III Patientsa
Indication Agents (n) Study Design Underlying Diseases Reference Level of Evidence
Facilitate Mechanical Ventilation
Facilitate management Cisatracurium (40), Randomized, open-label Hepatic failure, sepsis, cardiogenic shock, ARDS 20 2
atracurium (21)
Beneficial to management Cisatracurium (12), Randomized, single-blind Cardiac arrest, respiratory failure, postneurosurgery, trauma, 18 2
atracurium (8) multiorgan failure, asthma, cardiogenic shock
Facilitate management Cisatracurium (6), Randomized, open-label Multiple 19 2
atracurium (6)
Facilitate management Cisatracurium (28), Randomized, double-blind Head trauma, intracranial hemorrhage, trauma, ARDS, sepsis, 15 2
vecuronium (30) hepatic or renal failure, tetanus
Optimize mechanical Doxacurium (19), Prospective, randomized, Not reported 12 2

ventilation, increase ICP pancuronium (21) double-blind
Facilitate mechanical Pipecuronium (30), Prospective, open-label Head injury, multiple trauma, sepsis, multiorgan failure 13 3
ventilation pancuronium (30)
Facilitate mechanical Rocuronium (32) Prospective, open-label Respiratory failure, multiple trauma, blunt brain trauma 9 3
ventilation; dose-finding
pharmacokinetic study
Facilitate mechanical Rocuronium (30) Prospective, open-label Multiple trauma and/or blunt brain trauma 8 3
ventilation; dose-finding
pharmacokinetic study
Deterioration in gas Vecuronium and Case report Respiratory failure in a kidney/pancreas transplant patient 39 5
exchange atracurium (1)
Control ICP
Facilitate mechanical Doxacurium (8) Prospective, open-label Severe head injury 30 3
ventilation and/or
management of traumatic
brain injury
Control ICP Atracurium (4) Case report Severe head injury 40 5
Control Muscle Spasms
Control tetanospasms Rocuronium (1) Case report Tetanus 41 5
Decrease Oxygen
Consumption
Determine effect on oxygen Vecuronium (18) Prospective, randomized, Severe sepsis and septic shock 42 2
delivery, consumption, controlled, cross-over
and gastric intramucosal
pH
a
ARDS = acute respiratory distress syndrome, ICP = intracranial pressure.
Figure 2. Use of neuromuscular blocking agents (NMBAs) in the ICU. that is based on interpretation of the se-
verity of the patient’s underlying cardio-
vascular disease. For example, a patient
with a history of atrial fibrillation now
in sinus rhythm and otherwise hemo-
dynamically stable might better tolerate
pancuronium than a patient who is hos-
pitalized with cardiogenic pulmonary
edema and managed with mechanical
ventilation. The clinician should choose
an NMBA on the basis of other patient
characteristics. Any benzylisoquino
linium compound or aminosteroidal
compound could be substituted for pan-
curonium in these circumstances.
There are no ideal PRCTs that
support this recommendation, but there
are data suggesting that patients re-
cover more quickly following adminis-
tration of cisatracurium or atracurium
compared with patients receiving other
NMBAs if they have evidence of he-
patic or renal disease.
Recommendations: The majority

of patients in an ICU who are pre-
scribed an NMBA can be managed
effectively with pancuronium.
(Grade of recommendation = B)
For patients for whom vagoly

sis is contraindicated (e.g., those
with cardiovascular disease),
a
NMBAs other than pancuronium
Monitor train-of-four ratio, protect eyes, position patient to protect pressure points, and address
deep venous thrombosis prophylaxis. Reassess every 12–24 hours for continued NMBA indication.
may be used. (Grade of recom-
mendation = C)
of documenting if such patients could be managed by means Because of their unique metabolism, cisatracurium or
other than NMBA therapy. atracurium is recommended for patients with significant
hepatic or renal disease. (Grade of recommendation = B)
Recommendation: NMBAs should be used for an adult
patient in an ICU to manage ventilation, manage in- Monitoring
creased ICP, treat muscle spasms, and decrease oxygen
consumption only when all other means have been tried Monitoring neuromuscular blockade is recommended
without success. (Grade of recommendation = C) (Table 5).12,14,43–55 Monitoring the depth of neuromuscu-
lar blockade may allow use of the lowest NMBA dose
Recommended Drugs and may minimize adverse events. No PRCT has reported
that reducing the dose of an NMBA can prevent persis-
There has, in essence, been no study since the last guidelines tent weakness. Despite this lack of evidence and the lack
were published that questions the use of pancuronium for the of a standardized method of monitoring, assessment of
majority of patients in an ICU. Those prospective, random- the depth of neuromuscular blockade in ICU patients is
ized, controlled trials (PRCTs) that have been conducted do recommended.43
not clearly show the benefits of using newer agents or any Visual, tactile, or electronic assessment of the pa-
other agents instead of pancuronium. tient’s muscle tone or some combination of these three
There are no well-designed studies with sufficient power is commonly used to monitor the depth of neuromuscu-
to make this a level A recommendation, but there is evidence lar blockade. Observation of skeletal muscle movement
in the literature that patients on pancuronium fare as well as or and respiratory effort forms the foundation of clinical
better than patients receiving any other NMBA. assessment; electronic methods include the use of ven-
The two adverse effects of pancuronium that are com- tilator software allowing plethysmographic recording of
mented on frequently are vagolysis and an increase in heart rate. pulmonary function to detect spontaneous ventilatory ef-
Therefore, patients who would not tolerate an increase in heart forts and “twitch monitoring,” i.e., the assessment of the
rate, i.e., those with cardiovascular disease, should probably re- muscular response by visual, tactile, or electronic means
ceive an NMBA other than pancuronium. The indications for to a transcutaneous delivery of electric current meant to
the use of an NMBA must outweigh the risk of tachycardia, and induce peripheral nerve stimulation (PNS).
Table 5.
Monitoring the Degree of Neuromuscular Blockadea
Level of
Monitoring Method Study Design Reference Evidence
TOF vs. clinical assessment to guide dosing Prospective, randomized, single-blind 14 2
TOF vs. clinical assessment to compare depth of Prospective, nonrandomized 43 4
neuromuscular blockade
Complications with various monitoring methods Retrospective, nonrandomized cohort 44 4
Use of TOF in comparing NMBAs Multicenter, double-blind, PRCT 12 2
Methods of monitoring NMBAs Editorial 45 6
Methods of monitoring NMBAs Review 46 6
Comparison of common NMBAs/pharmacology Review 25 6
Frequency of NMBA monitoring methods Nonrandomized, historic, descriptive 47 4
Comparison of NMBA monitoring methods Editorial 48 6
Comparison of NMBA monitoring methods Expert opinion 49 6
Comparison of NMBA monitoring methods Expert opinion 50 6
Technical aspects and problems in NMBA monitoring Review 51 6
Technical problems with NMBAs monitoring Review 52 6
Technical problems with NMBA monitoring Review 53 5
Methods of assessing depth of NMBA Prospective, randomized, blinded 54 2
Patient assessment during NMBA use Review 55 6
a
TOF = train-of-four, NMBA = neuromuscular blocking agent, PRCT = prospective, randomized, controlled trial.
Since the last practice guidelines were published, only which PNS is utilized.47 The low correlation of blockade
two studies have examined the best method of monitoring measured peripherally compared with that of the phrenic
the depth of neuromuscular blockade, and none have com- nerve and diaphragm underscores the importance of three
pared the efficacy or accuracy of specific techniques. The issues: (1) more than one method of monitoring should be
first study was a prospective, randomized, single-blinded utilized, (2) poor technique in using any device will invari-
trial of 77 patients in a medical ICU who were administered ably produce inaccurate results, and (3) more clinical studies
vecuronium based on either clinical parameters (patient are necessary to determine the best techniques.
breathed above the preset ventilatory rate) or TOF monitor-
ing, with a goal of one of four twitches.44 PNS resulted in a
significantly lower total dose and lower mean infusion rate Recommendations for Monitoring
of NMBA as well as a faster time to recovery of neuromus- Degree of Blockade
cular function and spontaneous ventilation.
A second study sought to compare the depth of block- Even though the patient may appear quiet and “comfort-
ade induced by atracurium either by “best clinical assess- able,” experienced clinicians understand the indications and
ment” (i.e., maintenance of patient-ventilator synchrony and therapeutic limits of NMBAs. Despite multiple admonitions
prevention of patient movement) or TOF monitoring (with that NMBAs have no analgesic or amnestic effects, it is not
a goal of three of four twitches). Analysis of the 36 medi- uncommon to find a patient’s degree of sedation or comfort
cal ICU patients in this prospective, nonrandomized trial significantly overestimated or even ignored. It is difficult to
revealed no difference in the total dose, mean dose, or the assess pain and sedation in the patient receiving NMBAs, but
mean time to clinical recovery.43 This may have been due to patients must be medicated for pain and anxiety, despite the
sample size or study design. lack of obvious symptoms or signs. In common practice, seda-
An additional study examining the results of the imple- tive and analgesic drugs are adjusted until the patient does not
mentation of a protocol using PNS to monitor the level of block- appear to be conscious and then NMBAs are administered.
ade in patients receiving a variety of NMBAs found a reduction There have been no studies of the use of electrophysiologic
in the incidence of persistent neuromuscular weakness.49 monitoring in assessing adequacy of sedation or analgesia.
Other methods of electronic monitoring of the depth In a phenomenological study of 11 critically ill adult
of blockade are fraught with difficulties; TOF monitoring trauma patients who required therapeutic NMBA, patients
of PNS remains the easiest and most reliable method avail compared their feelings of vagueness to dreaming.56 Few pa-
able,43,44,46–50 despite its shortcomings and technical pit tients recalled pain or painful procedures. Family members
falls.51–53 Currently, there is no universal standard for twitch understood the rationale for the use of the drugs and remem-
monitoring. The choice of the number of twitches necessary bered being encouraged to touch and talk with patients. The
for “optimal” blockade is influenced by the patient’s overuse of effective pain and sedation protocols and a liberalized
all condition and level of sedation. The choice of the “best” visiting policy may have affected the findings.
nerve for monitoring may be influenced by site accessibility,
risk of false positives, considerations for the effect of stimu- Recommendations: Patients receiving NMBAs should
lation on patient visitors, and whether faint twitches should be assessed both clinically and by TOF monitoring
be included in the assessment of blockade.54–56 Despite these (Grade of recommendation = B), with a goal of adjust-
gaps in research-generated knowledge, evidence-based prac ing the degree of neuromuscular blockade to achieve
tice appears to be influencing the increasing frequency with one or two twitches. (Grade of recommendation = C)
Before initiating neuromuscular blockade, patients metabolite is estimated to be 80% as potent as the parent
should be medicated with sedative and analgesic compound. The 3-desacetyl vecuronium metabolite is poorly
drugs to provide adequate sedation and analgesia in dialyzed, minimally ultrafiltrated, and accumulates in patients
accordance with the physician’s clinical judgment to with renal failure because hepatic elimination is decreased
optimize therapy. (Grade of recommendation = C) in patients with uremia. Thus, the accumulation of both 3–
desacetyl vecuronium and its parent compound, vecuronium,
Complications in patients with renal failure contributes to a prolonged recov-
ery by this ICU subpopulation. Other explanations have been
Skeletal muscle weakness in ICU patients is multifactorial, proposed. One suggests that the basement membrane of the
producing a confusing list of names and syndromes, includ- neuromuscular junction acts as a reservoir of NMBAs, main-
ing acute quadriplegic myopathy syndrome (AQMS), floppy taining NMBAs at the nAChRs long after the drug has disap-
man syndrome, critical illness polyneuropathy (CIP), acute peared from the plasma.63
myopathy of intensive care, rapidly evolving myopathy, Drug–drug interactions that potentiate the depth of
acute myopathy with selective lysis of myosin filaments, motor blockade (Table 7) may also prolong recovery. The
acute steroid myopathy, and prolonged neurogenic weak- specific interaction of NMBAs and exogenous corticoste
ness (Table 6).57,58 roids is discussed later.57,62–65
There are probably two adverse events related to pro- Physiologic changes of the nAChRs are enhanced
longed paralysis following discontinuation of NMBAs. We when patients are immobilized or denervated secondary to
define the first, “prolonged recovery from NMBAs,” as an in- spinal cord injury, and perhaps during prolonged NMBA
crease (after cessation of NMBA therapy) in the time to recov- drug-induced paralysis. The nAChRs may be triggered to re
ery of 50–100% longer than predicted by pharmacologic param- vert to a fetal–variant structure (Figure 3), characterized by
eters. This is primarily due to the accumulation of NMBAs or an increase in total number, frequent extrajunctional prolif-
metabolites. By comparison, the second, AQMS, presents with eration, and resistance to nondepolarizing NMBAs. The pro-
a clinical triad of acute paresis, myonecrosis with increased cre- liferation and distribution of these altered receptors across
atine phosphokinase (CPK) concentration, and abnormal elec- the myomembrane may account for tachyphylaxis and the
tromyography (EMG). The latter is characterized by severely neuromuscular blocking effects of these drugs.
reduced compound motor action potential (CMAP) amplitudes
and evidence of acute denervation. In the beginning, these syn- AQMS. AQMS, also referred to as postparalytic quadriparesis,
dromes are characterized by neuronal dysfunction; later (days is one of the most devastating complications of NMBA therapy
or weeks), muscle atrophy and necrosis may develop.59 and one of the reasons that indiscriminate use of NMBAs is dis-
couraged (Table 8).65,66 This entity must be differentiated from
Prolonged Recovery from NMBAs. The steroid-based other neuromuscular pathologies (Table 6) seen in an ICU and
NMBAs are associated with reports of prolonged recovery requires extensive testing. Reports of AQMS in patients receiv-
and myopathy.57,60 This association may reflect an increased ing NMBAs alone are quite limited; no experimental model has
risk inferred by these NMBAs or may reflect past practice been able to produce the histopathology of this syndrome by
patterns in which these drugs may have been more com- administering NMBAs. Afflicted patients demonstrate diffuse
monly used.61 Steroid-based NMBAs undergo extensive weakness that persists long after the NMBA is discontinued and
hepatic metabolism, producing active drug metabolites. For the drug and its active metabolites are eliminated. Neurologic
instance, vecuronium produces three metabolites: 3-des-, examination reveals a global motor deficit affecting muscles
17-des-, and 3,17-desacetyl vecuronium.62 The 3-desacetyl in both the upper and lower extremities and decreased mo-
tor reflexes. However, extraocular muscle function is usually
preserved. This myopathy is characterized by low-amplitude
Table 6.
CMAPs, and muscle fibrillations but normal (or nearly normal)
Weakness in ICU Patients: Etiologies and
sensory nerve conduction studies.63,67 Muscle biopsy shows
Syndromesa
prominent vacuolization of muscle fibers without inflammatory
1. Prolonged recovery from NMBAs (secondary infiltrate, patchy type 2 muscle fiber atrophy, and sporadic myo-
to parent drug, drug metabolite, or drug–drug fiber necrosis.64 Modest CPK increases (0 to 15-fold above nor-
interaction) mal range) are noted in approximately 50% of patients and are
2. Myasthenia gravis probably dependent on the timing of enzyme measurements and
3. Lambert-Eaton syndrome
the initiation of the myopathic process. Thus, there may be some
4. Muscular dystrophy
justification in screening patients with serial CPK determina-
5. Guillain-Barré syndrome
tions during infusion of NMBAs, particularly if the patients are
6. Central nervous system injury or lesion
concurrently treated with corticosteroids. Also, since AQMS de-
7. Spinal cord injury
8. Steroid myopathy velops after prolonged exposure to NMBAs, there may be some
9. Mitochondrial myopathy rationale to daily “drug holidays” (i.e., stopping the drugs for a
10. HIV-related myopathy few to several hours and restarting them only when necessary).
11. Acute myopathy of intensive care However, no one has demonstrated that drug holidays decrease
12. Disuse atrophy the frequency of AQMS. Other factors that may contribute to the
13. Critical illness polyneuropathy development of the syndrome include nutritional deficiencies,
14. Severe electrolyte toxicity (e.g., hypermagnesemia) concurrent drug administration with aminoglycosides or cyclo-
15. Severe electrolyte deficiency (e.g., sporine, hyperglycemia, renal and hepatic dysfunction, fever,
hypophosphatemia) and severe metabolic or electrolyte disorders.
a
ICU = intensive care unit, NMBAs = neuromuscular blocking
Evidence supports, but occasionally refutes,14 the as-
agents, HIV = human immunodeficiency virus. sociation of concurrent administration of NMBAs and cor-
Table 7. Acute myopathy in ICU patients is

Drug–Drug Interactions of Neuromuscular Blocking Agents (NMBAs) also reported after administration of the
benzylisoquinolinium NMBAs (i.e., atra-
Drugs that Potentiate the Action Drugs that Antagonize the Actions
curium, cisatracurium, doxacurium).24,34,69
of Nondepolarizing NMBAs of Nondepolarizing NMBAs
Common to all these reports is the coad-
Local anesthetics Phenytoin
Lidocaine
ministration of benzyliso-quinolinium
Carbamazepine
Antimicrobials (aminoglycosides, polymyxin NMBAs and large doses of corticosteroids,
Theophylline
B, clindamycin, tetracycline) aminoglycosides, or other drugs that affect
Antiarrhythmics (procainamide, quinidine) Ranitidine neuromuscular transmission.
Magnesium
Calcium channel blockers Recommendations: For patients
β-Adrenergic blockers receiving NMBAs and corticosteroids,
Immunosuppresive agents (cyclophospha every effort should be made to dis-
mide, cyclosporine) continue NMBAs as soon as possible.
Dantrolene
Diuretics
(Grade of recommendation = C)
Lithium carbonate
Drug holidays (i.e., stopping
NMBAs daily until forced to restart them
Figure 3. Acetylcholine Receptor. The mature nicotinic acetylcholine receptor (AChR) based on the patient’s condition) may de-
(left) with its glycoprotein subunits arranged around the central cation core. Two molecules crease the incidence of AQMS. (Grade of
of acetylcholine bind simultaneously to the two alpha subunits to convert the channel to an recommendation = C)
open state. The immature, or fetal-variant, receptor is shown on the right, with a single subunit
substitution which follows major stress such as burns or denervation. These immature receptors
are characterized by 10-fold greater ionic activity, rapid metabolic turnover, and extrajunctional
Other nerve and muscle disorders
proliferation. (Reprinted, with permission, from Martyn JAJ, White DA, Gronert GA, et al. Up- have been recognized in the last decade in
and-down regulation of skeletal muscle acetylcholine receptors. Anesthesiology. 1992; 76:825.) ICU patients (Table 6). For instance, CIP is
a sensory and motor polyneuropathy iden
tified in elderly, septic patients or those
with MODS.58,66,70 EMG testing reveals
decreased CMAP, fibrillation potentials,
and positive sharp waves.60,63,64 CIP is pri-
marily an axonopathy and may be related
to microvascular ischemia of the nerve
but is not directly related to the use of
NMBAs. Recovery from ICU myopathy
requires a protracted (weeks or months)
hospitalization. One economic analysis of
10 patients who developed AQMS showed
the median additional hospital charge to
be $66,000 per patient.65 As for any criti-
cally ill patient, particularly immobilized
patients, deep venous thrombosis (DVT)
prophylaxis and physical therapy to main-
tain joint mobility are important.
ticosteroids with AQMS.59,63,68,69 The incidence of myopathy Patients receiving NMBAs are also at risk of de-
may be as high as 30% in patients who receive corticoste veloping keratitis and corneal abrasion. Prophylactic eye
roids and NMBAs. While no period of paralysis is risk free, care is highly variable and recommendations may include
NMBA administration beyond one or two days increases the methylcellulose drops, ophthalmic ointment, taping the
risk of myopathy in this setting.63 Similarly, there is an in- eyelids shut to ensure complete closure, or eye patches.
consistent correlation with the dose of corticosteroids, but In a study of 69 paralyzed or heavily sedated patients by
total doses in excess of 1 g of methylprednisolone (or equiv- Lenart and Garrity,71 there was strong evidence that the
alent) probably increase the risk. Afflicted patients manifest use of an artificial tear ointment prevented corneal ex-
an acute, diffuse, flaccid weakness and an inability to wean posure. In this randomized study, patients served as their
from mechanical ventilation. Sensory function is generally own controls.
preserved.63 Muscle biopsy shows extensive type 2 fiber
atrophy, myonecrosis, disarray of sarcomere architecture, Myositis Ossificans (Heterotopic Ossification). Myositis
and an extensive, selective loss of myosin. Experimental ossificans can develop in patients who are paralyzed
evidence in animals shows that denervation for ≥24 hours for long periods of time, but inflammation is not char-
induces profound negative nitrogen balance and increases acteristic of the ailment. The name is misleading be
expression of steroid receptors in muscle. Such denervation cause the process involves connective tissue (not mus-
sensitizes muscle to even normal corticosteroid concentra- cle). The name originates from the ossification that
tions, and evidence suggests that the combination of denerva- occurs within the connective tissue of muscle but may
tion and high-dose corticosteroids precipitates myosinolysis. also be seen in ligaments, tendons, fascia, aponeuroses,
Table 8. medication-related cost savings

Potential Complications of Neuromuscular Blockade Use in the ICUa were found when voluntary pre-
scribing guidelines for NMBAs
Complications and Contraindications of General Complications Associated with
were initiated in the operating room
Succinylcholine in the ICU NMBAs in the ICU
of a university hospital.73 In another
Loss of airway Awake, paralyzed patient–anxiety and
study that involved randomization to
panic
one of three NMBAs, there were no
Hyperkalemia Risk of ventilator disconnect or airway
mishap significant cost differences between
Plasma pseudocholinesterase Autonomic and cardiovascular effects (i.e., atracurium, vecuronium, and ro-
deficiency vagolytic) curonium for surgeries lasting two
Decreased lymphatic flow hours or less, but vecuronium and
Risk of generalized deconditioning rocuronium were economically ad-
Skin breakdown vantageous if the duration of surgery
Peripheral nerve injury was two to four hours.74 In a third
Corneal abrasion, conjunctivitis retrospective study, long-acting
Myositis ossificans NMBAs (e.g., D-tubocurarine and
Risk of prolonged muscle weakness, AQMS pancuronium) were associated with
Potential central nervous system toxicity prolonged postoperative recovery
a
NMBA = neuromuscular blocking agent, AQMS = acute quadriplegic myopathy syndrome. compared with shorter-acting agents
(e.g., atracurium, mivacurium, and
and joint capsules. The acquired form of the disease may occur vecuronium). The authors noted in the discussion section
at any age in either sex, especially around the elbows, thighs, of the paper that based on intrainstitutional recovery room
and buttocks. The basic defect is the inappropriate differentia- costs, delays in recovery times seen with the longer-
tion of fibroblasts into osteoblasts and is usually triggered by acting agents offset the expected savings in drug costs.75
trauma and muscle injury, paraplegia or quadriplegia, tetanus, For patients transferred to the ICU, this may not be a major
and burns. Treatment consists of promoting an active range of problem.
motion around the affected joint and surgery when necessary. Two pharmacoeconomic investigations involving
NMBAs in the ICU evaluated the costs associated with pro-
Tachyphylaxis. For reasons mentioned earlier, tachyphy- longed recovery following discontinuation of nondepolarizing
laxis to NMBAs can and does develop. NMBAs. In one study, overall costs were lower when TOF
Coursin and colleagues31 administered doxacurium to monitoring was employed.76 In another study, patients who
four patients who developed tolerance to atracurium infusions had prolonged motor weakness after discontinuing NMBAs
(range, 16 to 40 μg/kg/min). Patients were successfully blocked were compared with a control group77; ICU and hospital
with infusion rates of doxacurium 0.25–0.75 μg/kg/min. costs were substantially higher in the patients with pro-
Tschida, et al.72 described a patient whose atracurium longed weakness.
requirement escalated from 5 to 30 μg/kg/min over 10 days. A study involving 40 academic medical centers with
The patient was successfully blocked with a pancuronium patients undergoing coronary artery bypass graft surgery
infusion of 10–50 μg/kg/min for a period of five days. found no significant differences in duration of intubation
Fish and Singletary33 describe a patient who was inad- or duration of ICU or hospital stay among patients who re-
equately blocked with a 60-μg/kg/min infusion of atracurium ceived pancuronium (n = 732), vecuronium (n = 130), or
but adequately paralyzed for seven days with 2.3-mg/kg/hr both (n = 242) agents.78 It is unknown if these results pertain
infusion of vecuronium. Tachyphylaxis then developed to ve to subgroups of patients, such as those with renal or hepatic
curonium which prompted discontinuation of NMBAs. Two dysfunction. If the results of this study are confirmed, the
days later, 50–μg/kg/min atracurium infusions were required choice of agent could be based solely on cost minimization
with high-dose midazolam and fentanyl infusions to achieve using medication purchase cost information and equipotent
adequate oxygenation and acceptable airway pressures. dosage regimens.
A prospective, randomized trial comparing TOF to
Recommendations: Patients receiving NMBAs standard clinical assessment showed decreased NMBA us-
should have prophylactic eye care (Grade of recom- age and faster return of spontaneous ventilation with TOF
mendation = B), physical therapy (Grade of recom- monitoring.14 TOF has the potential to decrease costs associ-
mendation = C), and DVT prophylaxis. (Grade of ated with NMBA use in ICUs.
recommendation = C) Appendix B describes the basic steps involved in
conducting a cost-effectiveness analysis of the NMBAs.
Patients who develop tachyphylaxis to one NMBA Consequently, intrainstitutional data and assumptions
should try another drug if neuromuscular blockade is can be used to perform the analysis along with local
still required. (Grade of recommendation = C) value judgments involved in selecting the appropriate
agent(s).
Economics
Recommendations: Institutions should perform an economic
analysis using their own data when choosing NMBAs for
There have been few formal pharmacoeconomic evalua
use in an ICU. (Grade of recommendation = C)
tions of NMBAs. In one of these economic evaluations,
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74. Loughlin KA, Weingarten CM, Nagelhout J, et al. A 11. Institutions should perform an economic analysis using
pharmacoeconomic analysis of neuromuscular block- their own data when choosing NMBAs for use in an
ing agents in the operating room. Pharmacotherapy. ICU. (Grade of recommendation = C)
1996; 16:942–50.
75. Ballantyne JC, Chang Y. The impact of choice of mus- Appendix B—Determination of
cle relaxant on postoperative recovery time: a retro-
spective study. Anesth Analg. 1997; 85:476–82.
Cost Effectiveness Using
76. Zarowitz BJ, Rudis MI, Lai K, et al. Retrospective Intrainstitutional Dataa
pharmacoeconomic evaluation of dosing vecuronium
by peripheral nerve stimulation versus standard clinical 1. For each adverse effect (e.g., prolonged recovery) of any
assessment in critically ill patients. Pharmacotherapy. given neuromuscular blocking agent (NMBA), add all
1997; 17:327–32. associated costs together and multiply this figure by the
77. Rudis MI, Guslits BJ, Peterson EL, et al. Economic probability of the occurrence of the adverse effect. If ad-
impact of prolonged motor weakness complicating verse effects A, B, and C are associated with an NMBA,
neuromuscular blockade in the intensive care unit. Crit then
Care Med. 1996; 24:1749–56. (Drug cost + cost Al) (probability of occurrence ex-
78. Butterworth J, James R, Prielipp RC, et al. Do shorter- pressed as a decimal) = $U
acting neuromuscular blocking drugs or opioids as (Drug cost + cost B1) (probability of occurrence ex-
sociate with reduced intensive care unit or hospital pressed as a decimal) = $V
length of stay after coronary artery bypass grafting?
(Drug cost + cost C1) (probability of occurrence ex-
Anesthesiology. 1998; 88:1437–46.
pressed as a decimal) = $W
Appendix A—Summary 2. Calculate the product of the drug cost multiplied by

of Recommendations the probability of occurrence of no adverse effects ex-
pressed as a decimal; add this product to the cost mul-
1. NMBAs should be used for an adult patient in an ICU tiplied by the probability factor for each adverse effect
to manage ventilation, manage increased ICP, treat calculated in step 1.
muscle spasms, and decrease oxygen consumption only (Drug cost) (probability of occurrence of no adverse ef-
when all other means have been tried without success.1 fects) + $U + $V + $W = average cost of all pathways
(Grade of recommendation = C) for agent
2. The majority of patients in an ICU who are prescribed
an NMBA can be managed effectively with pan Note: The probabilities of all adverse effects plus the
curonium. (Grade of recommendation = B) probability of no adverse effects associated with the
3. For patients for whom vagolysis is contraindicated NMBA must add up to 1.
(e.g., those with cardiovascular disease), NMBAs other
than pancuronium may be used. (Grade of recommen- 3. Determine the cost effectiveness of the agent by
dation = C) dividing the total costs associated with the agent by
4. Because of their unique metabolism, cisatracurium or the probability of occurrence of no adverse effects ex-
atracurium is recommended for patients with significant pressed as a decimal.
hepatic or renal disease. (Grade of recommendation = B) Example using pancuronium:
5. Patients receiving NMBAs should be assessed both a. [$224 (drug cost for 4 days of therapy) + $1000 (es-
clinically and by TOF monitoring (Grade of recom- timated cost of 1 extra day of ICU stay due to pro-
mendation = B), with a goal of adjusting the degree longed paralysis resulting from renal dysfunction)]
of neuromuscular blockade to achieve one or two [0.07 (estimated probability of renal dysfunction)]
twitches. (Grade of recommendation = C) = $85.68 [$224 (drug cost for 4 days of therapy) +
6. Before initiating neuromuscular blockade, patients $1000 (estimated cost of 1 extra day of ICU (inten-
should be medicated with sedative and analgesic drugs sive care unit) stay due to prolonged paralysis re-
to provide adequate sedation and analgesia in accor- sulting from hepatic dysfunction)] [0.04 (estimated
dance with the physician’s clinical judgment to opti- probability of hepatic dysfunction)] = $48.96
mize therapy. (Grade of recommendation = C) b. [$224 (drug cost for 4 days of therapy, assuming no
7. For patients receiving NMBAs and corticosteroids, adverse effects) × 0.89 (estimated probability of no
every effort should be made to discontinue NMBAs as adverse effects)] + $85.68 + $48.96 = $334.00
soon as possible. (Grade of recommendation = C) c. Cost effectiveness of pancuronium = 334.00/0.89
8. Drug holidays (i.e., stopping NMBAs daily until forced to (probability of no adverse effects) = $375.28
restart them based on the patient’s condition) may decrease
the incidence of AQMS. (Grade of recommendation = C) a
Note that the term “adverse effects” includes problems such as
9. Patients receiving NMBAs should have prophylactic prolonged paralysis resulting from decreased medication elimination
eye care (Grade of recommendation = B), physical due to impaired organ function. If a neuromuscular blocking agent
is eliminated by more than one organ (e.g., kidney and liver),
therapy (Grade of recommendation = C), and DVT pro- prolonged paralysis may result from impaired elimination due to a
phylaxis. (Grade of recommendation = C) combination of organ problems. For example, one adverse effect
may be prolonged paralysis associated with renal dysfunction, while
10. Patients who develop tachyphylaxis to one NMBA another adverse effect may be prolonged paralysis associated with
should try another drug if neuromuscular blockade is hepatic dysfunction, while a third adverse effect may be prolonged
still required. (Grade of recommendation = C) paralysis associated with combined renal and hepatic dysfunction.
Professor and Chairman, Department of Anesthesiology, Keck
Developed through the Task Force of the American College of Critical School of Medicine of USC, Los Angeles, CA; William T. McGee,
Care Medicine (ACCM) of the Society of Critical Care Medicine M.D., M.H.A., Critical Care Division, Departments of Medicine
(SCCM), in collaboration with the American Society of Health- & Surgery, Baystate Medical Center, Springfield, MA; William
System Pharmacists (ASHP), and in alliance with the American T. Peruzzi, M.D., FCCM, Associate Professor of Anesthesiology,
College of Chest Physicians; and approved by the Board of Regents Northwestern University School of Medicine, Chief, Section of
of ACCM and the Council of SCCM on November 15, 2001 and the Critical Care Medicine, Northwestern Memorial Hospital, Chicago,
ASHP Board of Directors on November 17, 2001. IL; Richard C. Prielipp, M.D., FCCM, Section Head, Critical Care
and Department of Anesthesiology, Wake Forest University School
Members of the 2001–2002 Commission on Therapeutics are of Medicine, Medical Center Boulevard, Winston-Salem, NC; Greg
William L. Greene, Pharm.D., BCPS, FASHP, Chair; Mary Lea Gora- Susla, Pharm.D., FCCM, Clinical Center Pharmacy Department,
Harper, Pharm.D., BCPS, Vice Chair; Kate Farthing, Pharm.D.; National Institutes of Health, Bethesda, MD; Ann N. Tescher, R.N.,
Charles W. Ham, Pharm.D., M.B.A.; Rita K. Jew, Pharm.D.; Rex S. Clinical Nurse Specialist, Mayo Clinic, Rochester, MN; Cynthia L.
Lott, Pharm.D.; Keith M. Olsen, Pharm.D., FCCP; Joseph J. Saseen, LaCivita, Pharm.D., Clinical Affairs Associate, ASHP Staff Liaison;
Pharm.D., BCPS; Beth A. Vanderheyden, Pharm.D., BCPS; Amy Deborah L. McBride, Director of Publications, SCCM Staff Liaison.
M. Blachere, R.Ph., Student Member; Jill E. Martin, Pharm.D.,
FASHP, Board Liaison; Dennis Williams, Pharm.D., FASHP, FCCP, Reviewers: American College of Chest Physicians; American
FAPHA, BCPS, Liaison Section of Clinical Specialist; and Cynthia Academy of Neurology; American Association of Critical Care
L. LaCivita, Pharm.D., Secretary. Nurses; American Nurses Association; American Pharmaceutical
Association; American College of Clinical Pharmacy; Joe Dasta,
Members of the Neuromuscular Blockade Task Force are Michael Pharm.D.; Doug Fish, Pharm.D.; Erkan Hassan, Pharm.D.; H.
J. Murray, M.D., Ph.D., FCCM, Chair, Professor and Chair of Mathilda Horst, M.D.; Carlayne E. Jackson, M.D.; Karen Kaiser,
Anesthesiology, and Dean, Mayo School of Health Sciences, Mayo R.N.; Kathleen M. Kelly, M.D.; Carl Schoenberger, M.D.; Lori
Clinic Jacksonville, FL; Stanley Nasraway, Jr., M.D., FCCM, Exec Schoonover, R.N.; and Gayle Takaniski, Pharm.D.
utive Director of Task Force, Associate Professor, Surgery, Medicine,
and anesthesia, Tufts-New England Medical Center, Boston, MA; The recommendations in this document do not indicate an exclusive
Jay Cowen, M.D., Director, Medical Intensive Care Unit, LeHigh course of treatment to be followed. Variations, taking into account
Valley Hospital, Allentown, PA; Heidi F. DeBlock, M.D., Department individual circumstances, may be appropriate.
of Surgery, Albany Medical Center, Albany, NY; Brian L. Erstad,
Pharm.D., FCCM, Department of Pharmacy Practice & Science, Copyright © 2002, American Society of Health-System Pharmacists,
College of Pharmacy, University of Arizona, Tucson, AZ; Anthony Inc. and the Society of Critical Care Medicine. All rights reserved.
W. Gray, Jr., M.D., FCCM, Section of Pulmonary and Critical Care,
Medicine and Surgical Critical Care, Lahey Clinic Medical Center, The bibliographic citation is as follows: Society of Critical Care Medicine
Burlington, MA; Judith Jacobi, Pharm.D., FCCM, BCPS, Critical and American Society of Health-System Pharmacists. Clinical practice
Care Pharmacy Specialist, Methodist Hospital–Clarian Health guidelines for sustained neuromuscular blockade in the adult critically
Partners, Indianapolis, IN; Philip D. Lumb, M.B., B.S., FCCM, ill patient. Am J Health Syst Pharm. 2002; 59:179–95.
Clinical Practice Guidelines for the Management

of Pain, Agitation, and Delirium in Adult Patients
in the Intensive Care Unit
Objective: To revise the “Clinical Practice Guidelines for the Conclusion: These guidelines provide a roadmap for de-
Sustained Use of Sedatives and Analgesics in the Critically Ill veloping integrated, evidence-based, and patient-centered
Adult” published in Critical Care Medicine in 2002. protocols for preventing and treating pain, agitation, and
delirium in critically ill patients. (Crit Care Med. 2013;
Methods: The American College of Critical Care Medicine 41:263–306)
assembled a 20-person, multidisciplinary, multi-institutional
task force with expertise in guideline development, pain, ag- Key Words: agitation; analgesia; critical care medicine; de-
itation and sedation, delirium management, and associated lirium; evidence-based medicine; GRADE; guidelines; in-
outcomes in adult critically ill patients. The task force, di- tensive care; outcomes; pain; protocols; sedation
vided into four subcommittees, collaborated over 6 yr in per-
son, via teleconferences, and via electronic communication. Statements and Recommendations
Subcommittees were responsible for developing relevant
clinical questions, using the Grading of Recommendations 1. Pain and Analgesia
Assessment, Development and Evaluation method (http:// a. Incidence of pain
www.gradeworkinggroup.org) to review, evaluate, and sum- i. Adult medical, surgical, and trauma ICU pa-
marize the literature, and to develop clinical statements (de- tients routinely experience pain, both at rest
scriptive) and recommendations (actionable). With the help and with routine ICU care (B).
of a professional librarian and Refworks® database soft- ii. Pain in adult cardiac surgery patients is com-
ware, they developed a Web-based electronic database of mon and poorly treated; women experience
over 19,000 references extracted from eight clinical search more pain than men after cardiac surgery (B).
engines, related to pain and analgesia, agitation and seda- iii. Procedural pain is common in adult ICU pa-
tion, delirium, and related clinical outcomes in adult ICU tients (B).
patients. The group also used psychometric analyses to b. Pain assessment
evaluate and compare pain, agitation/sedation, and delirium i. We recommend that pain be routinely moni-
assessment tools. All task force members were allowed to tored in all adult ICU patients (+1B).
review the literature supporting each statement and recom- ii. The Behavioral Pain Scale (BPS) and the
mendation and provided feedback to the subcommittees. Critical-Care Pain Observation Tool (CPOT)
Group consensus was achieved for all statements and rec- are the most valid and reliable behavioral pain
ommendations using the nominal group technique and the scales for monitoring pain in medical, post-
modified Delphi method, with anonymous voting by all task operative, or trauma (except for brain injury)
force members using E-Survey (http://www.esurvey.com). adult ICU patients who are unable to self-re-
All voting was completed in December 2010. Relevant stud- port and in whom motor function is intact and
ies published after this date and prior to publication of these behaviors are observable. Using these scales
guidelines were referenced in the text. The quality of evi- in other ICU patient populations and translat-
dence for each statement and recommendation was ranked ing them into foreign languages other than
as high (A), moderate (B), or low/very low (C). The strength French or English require further validation
of recommendations was ranked as strong (1) or weak (2), testing (B).
and either in favor of (+) or against (–) an intervention. A iii. We do not suggest that vital signs (or observa-
strong recommendation (either for or against) indicated that tional pain scales that include vital signs) be
the intervention’s desirable effects either clearly outweighed used alone for pain assessment in adult ICU
its undesirable effects (risks, burdens, and costs) or it did patients (–2C).
not. For all strong recommendations, the phrase “We recom- iv. We suggest that vital signs may be used as
mend …” is used throughout. A weak recommendation, ei- a cue to begin further assessment of pain in
ther for or against an intervention, indicated that the tradeoff these patients, however (+2C).
between desirable and undesirable effects was less clear. For c. Treatment of pain
all weak recommendations, the phrase “We suggest …” is i. We recommend that preemptive analgesia
used throughout. In the absence of sufficient evidence, or and/or nonpharmacologic interventions (e.g.,
when group consensus could not be achieved, no recommen- relaxation) be administered to alleviate pain in
dation (0) was made. Consensus based on expert opinion adult ICU patients prior to chest tube removal
was not used as a substitute for a lack of evidence. A consis- (+1C).
tent method for addressing potential conflict of interest was ii. We suggest that for other types of invasive
followed if task force members were coauthors of related re- and potentially painful procedures in adult
search. The development of this guideline was independent ICU patients, preemptive analgesic therapy
of any industry funding. and/or nonpharmacologic interventions may
also be administered to alleviate pain (+2C).
iii. We recommend that intravenous (IV) opioids ii. We do not recommend that objective mea-
be considered as the first-line drug class of sures of brain function (e.g., auditory evoked
choice to treat non-neuropathic pain in criti- potentials [AEPs], Bispectral Index [BIS],
cally ill patients (+1C). Narcotrend Index [NI], Patient State Index
iv. All available IV opioids, when titrated to [PSI], or state entropy [SE]) be used as the pri-
similar pain intensity endpoints, are equally mary method to monitor depth of sedation in
effective (C). noncomatose, nonparalyzed critically ill adult
v. We suggest that nonopioid analgesics be con- patients, as these monitors are inadequate
sidered to decrease the amount of opioids substitutes for subjective sedation scoring
administered (or to eliminate the need for IV systems (–1B).
opioids altogether) and to decrease opioid- iii. We suggest that objective measures of brain
related side effects (+2C). function (e.g., AEPs, BIS, NI, PSI, or SE) be
vi. We recommend that either enterally adminis- used as an adjunct to subjective sedation as-
tered gabapentin or carbamazepine, in addi- sessments in adult ICU patients who are re-
tion to IV opioids, be considered for treatment ceiving neuromuscular blocking agents, as
of neuropathic pain (+1A). subjective sedation assessments may be unob-
vii. We recommend that thoracic epidural anes- tainable in these patients (+2B).
thesia/ analgesia be considered for postopera- iv. We recommend that EEG monitoring be used
tive analgesia in patients undergoing abdomi- to monitor nonconvulsive seizure activity in
nal aortic aneurysm surgery (+1B). adult ICU patients with either known or sus-
viii. We provide no recommendation for using a pected seizures, or to titrate electrosuppres-
lumbar epidural over parenteral opioids for sive medication to achieve burst suppression
postoperative analgesia in patients undergo- in adult ICU patients with elevated intracra-
ing abdominal aortic aneurysm surgery, due to nial pressure (+1A).
a lack of benefit of epidural over parenteral c. Choice of sedative
opioids in this patient population (0,A). i. We suggest that sedation strategies using
ix. We provide no recommendation for the use nonbenzodiazepine sedatives (either propofol
of thoracic epidural analgesia in patients un- or dexmedetomidine) may be preferred over
dergoing either intrathoracic or nonvascular sedation with benzodiazepines (either mid-
abdominal surgical procedures, due to insuf- azolam or lorazepam) to improve clinical out-
ficient and conflicting evidence for this mode comes in mechanically ventilated adult ICU
of analgesic delivery in these patients (0,B). patients (+2B).
x. We suggest that thoracic epidural analgesia 3. Delirium
be considered for patients with traumatic rib a. Outcomes associated with delirium
fractures (+2B). i. Delirium is associated with increased mortal-
xi. We provide no recommendation for neuraxial/ ity in adult ICU patients (A).
regional analgesia over systemic analgesia in ii. Delirium is associated with prolonged ICU
medical ICU patients, due to lack of evidence and hospital LOS in adult ICU patients (A).
in this patient population (0, No Evidence). iii. Delirium is associated with the develop-
2. Agitation and Sedation ment of post-ICU cognitive impairment in
a. Depth of sedation vs. clinical outcomes adult ICU patients (B).
i. Maintaining light levels of sedation in adult b. Detecting and monitoring delirium
ICU patients is associated with improved clin- i. We recommend routine monitoring of delir-
ical outcomes (e.g., shorter duration of me- ium in adult ICU patients (+1B).
chanical ventilation and a shorter ICU length ii. The Confusion Assessment Method for the
of stay [LOS]) (B). ICU (CAM-ICU) and the Intensive Care
ii. Maintaining light levels of sedation increases Delirium Screening Checklist (ICDSC) are
the physiologic stress response, but is not as- the most valid and reliable delirium monitor-
sociated with an increased incidence of myo- ing tools in adult ICU patients (A).
cardial ischemia (B). iii. Routine monitoring of delirium in adult ICU
iii. The association between depth of sedation patients is feasible in clinical practice (B).
and psychological stress in these patients re- c. Delirium risk factors
mains unclear (C). i. Four baseline risk factors are positively and
iv. We recommend that sedative medications be significantly associated with the development
titrated to maintain a light rather than a deep of delirium in the ICU: preexisting dementia,
level of sedation in adult ICU patients, unless history of hypertension and/or alcoholism,
clinically contraindicated (+1B). and a high severity of illness at admission (B).
b. Monitoring depth of sedation and brain function ii. Coma is an independent risk factor for the
i. The Richmond Agitation-Sedation Scale development of delirium in ICU patients (B).
(RASS) and Sedation-Agitation Scale (SAS) iii. Conflicting data surround the relationship be-
are the most valid and reliable sedation assess- tween opioid use and the development of de-
ment tools for measuring quality and depth of lirium in adult ICU patients (B).
sedation in adult ICU patients (B). iv. Benzodiazepine use may be a risk factor for
the development of delirium in adult ICU pa- a. We recommend either daily sedation interruption
tients (B). or a light target level of sedation be routinely used in
v. There are insufficient data to determine the mechanically ventilated adult ICU patients (+1B).
relationship between propofol use and the de- b. We suggest that analgesia-first sedation be used
velopment of delirium in adult ICU patients in mechanically ventilated adult ICU patients (+2B).
(C). c. We recommend promoting sleep in adult ICU pa-
vi. In mechanically ventilated adult ICU patients tients by optimizing patients’ environments, using
at risk of developing delirium, dexmedetomi- strategies to control light and noise, clustering pa-
dine infusions administered for sedation may tient care activities, and decreasing stimuli at night
be associated with a lower prevalence of de- to protect patients’ sleep cycles (+1C).
lirium compared to benzodiazepine infusions d. We provide no recommendation for using specific
(B). modes of mechanical ventilation to promote sleep
d. Delirium prevention in mechanically ventilated adult ICU patients, as
i. We recommend performing early mobiliza- insufficient evidence exists for the efficacy of these
tion of adult ICU patients whenever feasible interventions (0, No Evidence).
to reduce the incidence and duration of de- e. We recommend using an interdisciplinary ICU team
lirium (+1B). approach that includes provider education, pre-
ii. We provide no recommendation for using a printed and/or computerized protocols and order
pharmacologic delirium prevention protocol forms, and quality ICU rounds checklists to facili-
in adult ICU patients, as no compelling data tate the use of pain, agitation, and delirium manage-
demonstrate that this reduces the incidence or ment guidelines or protocols in adult ICUs (+1B).
duration of delirium in these patients (0,C).
iii. We provide no recommendation for using a Since these guidelines were last published, we have made
combined nonpharmacologic and pharmaco- significant advances in our understanding of how to provide
physical and psychological comfort for patients admitted
logic delirium prevention protocol in adult
to the ICU.1 The development of valid and reliable bedside
ICU patients, as this has not been shown to
assessment tools to measure pain, sedation, agitation, and
reduce the incidence of delirium in these pa-
delirium in ICU patients has allowed clinicians to manage
tients (0,C).
patients better and to evaluate outcomes associated with
iv. We do not suggest that either haloperidol or
both nonpharmacologic and pharmacologic interventions.2,3
atypical antipsychotics be administered to
Our expanded knowledge of the clinical pharmacology of
prevent delirium in adult ICU patients (–2C).
medications commonly administered to treat pain, agitation,
v. We provide no recommendation for the use
and delirium (PAD) in ICU patients has increased our ap-
of dexmedetomidine to prevent delirium in
preciation for both the short- and long-term consequences of
adult ICU patients, as there is no compelling prolonged exposure to these agents.4–6 We have learned that
evidence regarding its effectiveness in these the methods of administering and titrating these medications
patients (0,C). can affect patient outcomes as much as drug choice.7–16 For
e. Delirium treatment most ICU patients, a safe and effective strategy that ensures
i. There is no published evidence that treatment patient comfort while maintaining a light level of sedation is
with haloperidol reduces the duration of de- associated with improved clinical outcomes.9–13,16–20
lirium in adult ICU patients (No Evidence). Ensuring that critically ill patients are free from pain,
ii. Atypical antipsychotics may reduce the dura- agitation, anxiety, and delirium at times may conflict with
tion of delirium in adult ICU patients (C). other clinical management goals, such as maintaining car-
iii. We do not recommend administering rivastig- diopulmonary stability while preserving adequate end-
mine to reduce the duration of delirium in ICU organ perfusion and function.21,22 Management goals may be
patients (–1B). further complicated by the growing number of “evidence-
iv. We do not suggest using antipsychotics in pa- based” bundles and clinical algorithms, some of which have
tients at significant risk for torsades de pointes been widely adopted by regulatory agencies and payers.23–30
(i.e., patients with baseline prolongation of Finally, tremendous worldwide variability in cultural, philo-
QTc interval, patients receiving concomitant sophical, and practice norms, and in the availability of man-
medications known to prolong the QTc inter- power and resources, makes widespread implementation of
val, or patients with a history of this arrhyth- evidence-based practices challenging.31–36
mia) (–2C). The goal of these clinical practice guidelines is to rec-
v. We suggest that in adult ICU patients with ommend best practices for managing PAD to improve clini-
delirium unrelated to alcohol or benzodiaz- cal outcomes in adult ICU patients. We performed a rigorous,
epine withdrawal, continuous IV infusions of objective, transparent, and unbiased assessment of the rel-
dexmedetomidine rather than benzodiazepine evant published evidence. We balanced this evidence against
infusions be administered for sedation to re- the values and preferences of ICU patients, family members,
duce the duration of delirium in these patients caregivers, and payer and regulatory groups, and important
(+2B). ICU clinical outcomes, to develop relevant statements and
4. Strategies for Managing Pain, Agitation, and Delirium to recommendations that can be applied at the bedside.
Improve ICU Outcomes The scope of these guidelines includes short- and long-
term management of PAD in both intubated and nonintubated
adult medical, surgical, and trauma ICU patients. These
guidelines only briefly address the topic of analgesia and rameters included published (or in press) English-only man-
sedation for procedures, which is described in more detail uscripts on adult humans (> 18 yr), from December 1999
in the American Society of Anesthesiologists guidelines on (the search limit for the 2002 guidelines) through December
conscious sedation.37 The American College of Critical Care 2010. Studies with less than 30 patients, editorials, narrative
Medicine (ACCM) is currently developing separate guide- reviews, case reports, animal or in vitro studies, and letters
lines on analgesia and sedation for pediatric ICU patients. to the editor were excluded. Biweekly automated searches
This version of the guidelines places a greater emphasis were continued beyond this date, and relevant articles were
on the psychometric aspects of PAD monitoring tools. It in- incorporated into the guidelines through July 2012, but stud-
cludes both pharmacologic and nonpharmacologic approaches ies published after December 2010 were not included in the
to manage PAD in ICU patients. There is also greater empha- evidence review and voting process. The 2002 guideline
sis placed on preventing, diagnosing, and treating delirium, references were also included in the database, and targeted
reflecting our growing understanding of this disease process searches of the literature published before December 1999
in critically ill patients. These guidelines are meant to help were performed as needed. Over 19,000 references were ul-
clinicians take a more integrated approach to manage PAD in timately included in the Refworks database.
critically ill patients. Clinicians should adapt these guidelines The statements and recommendations in this 2012
to the context of individual patient care needs and the avail- version of the guidelines were developed using the Grading
able resources of their local health care system. They are not of Recommendations, Assessment, Development and
meant to be proscriptive or applied in absolute terms. Evaluation (GRADE) methodology, a structured system for
rating quality of evidence and grading strength of recom-
Methods mendation in clinical practice (http://www.gradeworking-
group.org).38–40 Subcommittees worked with members of
The ACCM’s 20-member multidisciplinary task force, with the GRADE Working Group (R.J., D.C., H.S., G.G.) to
expertise in PAD management, was charged with revising phrase all clinical questions in either “descriptive” or “ac-
the 2002 “Clinical Practice Guidelines for the Sustained tionable” terms. They structured actionable questions in the
Use of Sedatives and Analgesics in the Critically Ill Adult.”1 Population, Intervention, Comparison, Outcomes format
Subcommittees were assigned one of the four subtopic ar- and classified clinical outcomes related to each intervention
eas: pain and analgesia, agitation and sedation, delirium, and as critical, important, or unimportant to clinical decision
related ICU outcomes. Each subcommittee developed rel- making. Only important and critical outcomes were included
evant clinical questions and related outcomes, identified, re- in the evidence review, and only critical outcomes were in-
viewed, and evaluated the literature, crafted statements and cluded in developing recommendations.
recommendations, and drafted their section of the article. Subcommittee members searched the database for
To facilitate the literature review, subcommittees de- relevant articles and uploaded corresponding PDFs to fa-
veloped a comprehensive list of related key words. A profes- cilitate group review. Two subcommittee members indepen-
sional librarian (C.K., University of Cincinnati) expanded dently completed a GRADE evidence profile summarizing
and organized this key word list; developed correspond- the findings of each study and evaluated the quality of evi-
ing medical subject heading (MeSH) terms (Supplemental dence. The quality of evidence was judged to be high (level
Digital Content 1, http://links.lww.com/CCM/A590); A), moderate (level B), or low/very low (level C), based on
searched relevant clinical databases; and created an elec- both study design and specific study characteristics, which
tronic, Web-based, password-protected database using could result in a reviewer either downgrading or upgrading
Refworks software (Bethesda, MD). Eight databases were the quality of the evidence (Table 1). If multiple studies re-
included in all searches: PubMed, MEDLINE, Cochrane lated to a particular outcome demonstrated disparate results,
Database of Systematic Reviews, Cochrane Central Register and no published systematic reviews on the topic existed, a
of Controlled Trials, CINAHL, Scopus, ISI Web of Science, meta-analysis of the relevant literature was performed by a
and the International Pharmaceutical Abstracts. Search pa- member of the GRADE Working Group (R.J.).
Table 1.
Factors That Affect the Quality of Evidencea
Level of Evidence Quality of Evidence Type of Evidence Definition
A High High quality RCT Further research is unlikely to change our
confidence in the estimate of effect.
B Moderate RCT with significant limitations Further research is likely to have an important
(downgraded),b or high- impact on our confidence in the estimate of
quality OS (upgraded)c effect and may change the estimate.
C Low OS Further research is very likely to have an
important impact on our confidence in the
estimate of effect and is likely to change the
estimate.
RCT = randomized controlled trial; OS = observational study.
a
Adapted from Guyatt, et al.40
b
RCTs with significant limitations: 1) study design limitations (planning, implementation bias); 2) inconsistency of results; 3) indirectness of
evidence; 4) imprecision of results; 5) high likelihood of reporting bias.
c
High-quality OS: 1) large magnitude of treatment effect; 2) evidence of a dose-response relationship; 3) plausible biases would decrease the
magnitude of an apparent treatment effect.
Subcommittees collectively reviewed the evidence in no recommendation being made. For a recommendation
profiles for each question, and using a nominal group tech- to be graded as strong rather than weak, at least 70% of those
nique, determined the overall quality of evidence (for both voting had to vote for a strong recommendation, otherwise
descriptive and actionable questions), the strength of rec- it received a weak recommendation. This method for reach-
ommendation (for actionable questions only), and drafted ing consensus has been proposed by the GRADE Working
evidence summaries for review by other task force mem- Group and was adopted by the 2008 Sepsis Guidelines Panel
bers. The strength of recommendations was defined as either to ensure fairness, transparency, and anonymity in the cre-
strong (1) or weak (2), and either for (+) or against (–) an ation of guideline recommendations.46,47 Polling results and
intervention, based on both the quality of evidence and the comments were then summarized and distributed to all PAD
risks and benefits across all critical outcomes (Table 2).41,42 guideline task force members for review. When one round
A no recommendation (0) could also be made due to either a of voting failed to produce group consensus, additional dis-
lack of evidence or a lack of consensus among subcommit- cussion and a second and/or third round of voting occurred.
tee members. Consensus statements based on expert opinion Polling for all questions was completed by December 2010.
alone were not used when evidence could not support a rec- Distribution of the final voting tallies along with comments
ommendation. A strong recommendation either in favor of by task force members for each statement and recommen-
(+1) or against (–1) an intervention implied that the majority dation is summarized in Supplemental Digital Content 2
of task force members believed that the benefits of the in- (http://links.lww.com/CCM/A591).
tervention significantly outweighed the risks (or vice versa) Task force members completed required, annual, con-
and that the majority of patients and providers would pur- flict of interest statements. Those with significant potential
sue this course of action (or not), given the choice. A weak conflicts of interest (e.g., manuscript coauthorship) recused
recommendation either in favor of (+2) or against (–2) an themselves from reviewing and grading evidence and from
intervention implied that the benefits of the intervention developing a subcommittee’s evidence statements and rec-
likely outweighed the risks (or vice versa), but that task force ommendations for related questions. All task force members
members were not confident about these trade-offs, either be- voted anonymously on the final strength of evidence and
cause of a low quality of evidence or because the trade-offs strength of recommendations for all questions. No industry
between risks and benefits were closely balanced. On the ba- funding or support was used to develop any aspect of these
sis of this information, most people might pursue this course guidelines.
of action (or not), but a significant number of patients and
providers would choose an alternative course of action.40,43,44 Psychometric Analyses. These guidelines include statements
Throughout these guidelines, for all strong recommenda- and recommendations about using a variety of bedside be-
tions, the phrase “We recommend …” was used, and for all havioral assessment tools used to 1) detect and evaluate pain,
weak recommendations, “We suggest …” was used. 2) assess depth of sedation and degree of agitation, and 3)
Group consensus for all statements and recommenda- detect delirium in critically ill adult patients who are unable
tions was achieved using a modified Delphi method with to communicate clearly. To date, a comparative assessment
an anonymous voting scheme.41,45 Task force members re- of the psychometric properties (i.e., reliability and validity)
viewed the subcommittees’ GRADE Evidence Summaries, and feasibility related to the use of these tools in ICU patients
and statements and recommendations, and voted and com- has not been published. Scale reliability refers to the overall
mented anonymously on each statement and recommen- accuracy of the use of a scale in replicating pain, sedation,
dation using an on-line electronic survey tool (E-Survey, or delirium scores over time (i.e., test–retest reliability) or
http://www.esurvey.com, Scottsdale, AZ). Consensus on the between raters (i.e., inter-rater reliability).48 Validity refers to
strength of evidence for each question required a majority the conclusions that can be drawn from the results of a test
(> 50%) vote. Consensus on the strength of recommendations or scale (e.g., does a delirium assessment tool actually detect
was defined as follows: a recommendation in favor of an in- delirium?).49 Content, criterion, and discriminant validation
tervention (or the comparator) required at least 50% of all are specific strategies of validity testing. A tool can be shown
task force members voting in favor, with less than 20% vot- to be both reliable and valid when used for a specific purpose
ing against; failure to meet these voting thresholds resulted with specified individuals in a given context.48,49 Feasibility
Table 2.
Factors That Affect the Strength of Recommendationsa
Considerations Effect on Strength of Recommendation
Quality of evidence Lower quality of evidence reduces the likelihood of a strong
recommendation, and vice versa
Uncertainty about the balance between desirable and Higher degree of uncertainty about the balance between
undesirable effects risks and benefits reduces the likelihood of a strong
recommendation, and vice versa
Uncertainty or variability in values and preferences Wide variability in values and preferences across groups
reduces the likelihood of a strong recommendation, and vice
versa
Uncertainty about whether the intervention represents a wise A higher the overall cost of treatment reduces the likelihood of
use of resources a strong recommendation, and vice versa
a
Adapted from Guyatt, et al.40
refers to the ease with which clinicians can apply a particular in critically ill adults are major priorities and have been the
scale in the clinical setting (e.g., in the ICU). subject of research for over 20 yr.60 Despite this fact, the
The task force evaluated and compared the psycho- incidence of significant pain is still 50% or higher in both
metric properties of behavioral pain scales (BPSs) used in medical and surgical ICU patients.61,62
adult ICU patients and compared their analyses to a previ- In addition to experiencing pain at rest61 and pain re-
ously published process.50 Similar scoring systems were not lated to surgery, trauma, burns, or cancer, patients also expe-
available to evaluate and compare the psychometric prop- rience procedural pain.63–70 This was highlighted in the first
erties of sedation and delirium scales, which have different practice guideline published on acute pain management 20
validation strategies from those used for pain scales. With yr ago by the Agency for Health Care Policy and Research.71
input from three psychometric testing experts (D.S., C.J., Pain related to procedures is ubiquitous, and inadequate
C.W.), the task force developed similar scoring systems to treatment of procedural pain remains a significant problem
assess and compare sedation and delirium scales.48 for many ICU patients.68
The psychometric properties of pain, sedation, and The negative physiologic and psychological conse-
delirium scales were evaluated based on: 1) item selection quences of unrelieved pain in ICU patients are significant
and content validation, 2) reliability, 3) validity, 4) feasibil- and long-lasting. For many years, ICU patients have identi-
ity, and 5) relevance or impact of implementation on patient fied pain as their greatest concern and a leading cause of in-
outcomes. Psychometric raw scores ranged from 0 to 25 sufficient sleep.72 More recently, studies on ICU-discharged
for pain scales, 0 to 18 for sedation scales, and 0 to 21 for but still-hospitalized patients showed that 82% (n = 75)56
delirium scales. Weighted scores were established for each remembered pain or discomfort associated with the endo-
criterion to address variations in scores and to facilitate the tracheal tube and 77% (n = 93) remembered experiencing
interpretation of results, resulting in a total weighted score moderate to severe pain during their ICU stay.73 One week
0 to 20 for all three domains. The details of each of the after discharge from the ICU, 82% (n = 120) of cardiac sur-
three psychometric scoring systems used are summarized gery patients reported pain as the most common traumatic
in Supplemental Digital Content 3 (http://links.lww.com/ memory of their ICU stay; 6 months later, 38% still recalled
CCM/A592). Scales with weighted scores ranging from 15 pain as their most traumatic ICU memory.74 Granja and col-
to 20 had very good psychometric properties, 12 to 14.9 had leagues75 noted that 17% (n = 313) of patients remembered
moderate psychometric properties, 10 to 11.9 had some ac- experiencing severe pain 6 months after an ICU stay and
ceptable psychometric properties which required validation 18% were at high risk of developing posttraumatic stress
in additional studies, and 0 to 9.9 had very few psychomet- disorder (PTSD). Schelling and colleagues25 conducted a
ric properties reported and/or unacceptable results. Scales long-term follow-up (median, 4 yr) questionnaire study
with moderate to very good psychometric properties (i.e., of 80 patients who had been treated in the ICU for acute
weighted score ≥ 12) were considered to be sufficiently valid respiratory distress syndrome. In comparison with normal
and reliable scales for use in adult ICU patients. The quality controls, both medical and surgical patients who recalled
of evidence for each individual scale was also evaluated us- pain and other traumatic situations while in the ICU had a
ing categories similar to those used in the GRADE system, higher incidence of chronic pain (38%) and PTSD symp-
with modifications adapted for the psychometric analyses. toms (27%), and a lower health-related quality of life (21%).
All studies were reviewed, and all scales were scored inde- The stress response evoked by pain can have delete-
pendently by two reviewers. rious consequences for ICU patients. Increased circulating
catecholamines can cause arteriolar vasoconstriction, impair
Pain and Analgesia. Incidence of pain in ICU patients. The tissue perfusion, and reduce tissue-oxygen partial pressure.76
International Association for the Study of Pain defines pain Other responses triggered by pain include catabolic hyper-
as an “unpleasant sensory and emotional experience asso- metabolism resulting in hyperglycemia, lipolysis, and break-
ciated with actual or potential tissue damage, or described down of muscle to provide protein substrate.77 Catabolic
in terms of such damage.”51 This definition highlights the stimulation and hypoxemia also impair wound healing and
subjective nature of pain and suggests that it can be pres- increase the risk of wound infection. Pain suppresses natu-
ent only when reported by the person experiencing it. Most ral killer cell activity,78,79 a critical function in the immune
critically ill patients will likely experience pain sometime system, with a decrease in the number of cytotoxic T cells
during their ICU stay52 and identify it as a great source of and a reduction in neutrophil phagocytic activity.80 Acute
stress.53–56 However, many critically ill patients may be un- pain may be the greatest risk factor for developing debilitat-
able to self-report their pain (either verbally or with other ing chronic, persistent, often neuropathic pain.81 Unrelieved
signs) because of an altered level of consciousness, the use acute pain in adult ICU patients is ubiquitous and far from
of mechanical ventilation, or high doses of sedative agents benign, with both short- and long-term consequences.
or neuromuscular blocking agents.57 Yet, the ability to reli- Adequately identifying and treating pain in these patients
ably assess patient’s pain is the foundation for effective pain require focused attention.
treatment. As the International Association for the Study Pain assessment in ICU patients. Treating pain in criti-
of Pain also states, “the inability to communicate verbally cally ill patients depends on a clinician’s ability to perform
does not negate the possibility that an individual is expe- a reproducible pain assessment and to monitor patients over
riencing pain and is in need of appropriate pain-relieving time to determine the adequacy of therapeutic interventions
treatment.”58 Therefore, clinicians must be able to reliably to treat pain. A patient’s self-report of pain is considered
detect pain, using assessment methods adapted to a patient’s the “gold standard,” and clinicians should always attempt
diminished communication capabilities. In such situations, to have a patient rate his or her own pain first. Chanques
clinicians should consider patients’ behavioral reactions as and colleagues82 demonstrated that a 0–10 visually enlarged
surrogate measures of pain, as long as their motor function is horizontal numeric rating scale was the most valid and fea-
intact.59 Detection, quantification, and management of pain sible of five pain intensity rating scales tested in over 100
ICU patients. Yet when critically ill patients are unable to IV acetaminophen has been recently approved for use in the
self-report their pain, clinicians must use structured, valid, United States and has been shown to be safe and effective
reliable, and feasible tools to assess patients’ pain.83 It is es- when used in conjunction with opioids for postoperative
sential that pain in ICU patients be assessed routinely and re- pain in surgical ICU patients following major or cardiac
petitively in a manner that is efficient and reproducible. No surgery.80,86–89 Neuropathic pain, poorly treated with opioids
objective pain monitor exists, but valid and reliable bedside alone, can be treated with enterally administered gabapentin
pain assessment tools that concentrate primarily on patients’ and carbamazepine in ICU patients with sufficient gastro-
behaviors as indicators of pain do exist. intestinal absorption and motility.90,91
Although reviews of behavioral pain assessment tools Methods of dosing analgesics are another treatment
have been published, an updated discussion is needed about consideration. The choice of intermittent vs. continuous IV
their development, validation, and applicability to ICU pa- strategies may depend on drug pharmacokinetics, frequency
tients.50,84 A detailed, systematic review of the processes of and severity of pain, and/or the patient’s mental status.92
item selection and psychometric properties of pain scales Enteral administration of opioids and other pain medications
(i.e., validity and reliability) may encourage clinicians to should be limited to patients with adequate gastrointestinal
adopt pain scales and to standardize their use in ICU pa- absorptive capacity and motility. Regional or neuraxial (spi-
tients. Recent studies have demonstrated that implementing nal or epidural) modalities may also be used for postopera-
behavioral pain scales improves both ICU pain management tive analgesia following selected surgical procedures.93,94
and clinical outcomes, including better use of analgesic and Complementary, nonpharmacologic interventions for
sedative agents and shorter durations of mechanical ventila- pain management, such as music therapy and relaxation
tion and ICU stay.2,3,85 techniques, may be opioid-sparing and analgesia-enhancing;
Treatment of pain. Opioids, such as fentanyl, hydro- they are low cost, easy to provide, and safe. Although a mul-
morphone, methadone, morphine, and remifentanil, are the timodal approach to pain management in ICU patients has
primary medications for managing pain in critically ill pa- been recommended, few studies have been published on the
tients (Table 3).62 The optimal choice of opioid and the dos- effectiveness of nonpharmacologic interventions in these
ing regimen used for an individual patient depends on many patients.52,95
factors, including the drug’s pharmacokinetic and pharma- Pain occurs commonly in adult ICU patients, regard-
codynamic properties.52 The use of meperidine is generally less of their admitting diagnoses. Pain can preclude patients
avoided in ICU patients because of its potential for neuro- from participating in their ICU care (e.g., early mobiliza-
logic toxicity.52 tion, weaning from mechanical ventilation). Thus, clinicians
Several other types of analgesics or pain-modulating should frequently reassess patients for pain and carefully
medications, such as local and regional anesthetics (e.g., titrate analgesic interventions to prevent potential negative
bupivacaine), nonsteroidal anti-inflammatory medications sequelae due to either inadequate or excessive analgesic
(e.g., ketorolac, ibuprofen), IV acetaminophen, and anti- therapy. Clinicians should perform routine and reproduc-
convulsants, can be used as adjunctive pain medications to ible pain assessments in all critically ill patients, using ei-
reduce opioid requirements (Table 4). However, their safety ther patient self-report or systematically applied behavioral
profile and effectiveness as sole agents for pain management measures. Pain management can be facilitated by identifying
have not been adequately studied in critically ill patients. and treating pain early rather than waiting until it becomes
Pharmacologic treatment principles extrapolated from non- severe.52
ICU studies may not be applicable to critically ill patients.52
Table 3.
Pharmacology of Opiate Analgesics1,128,440,472
Equi-Analgesic Dose (mg)
Elimination Context-Sensitive
Opiates IV PO Onset (IV) Half-Life Half-Life Metabolic Pathway
Fentanyl 0.1 N/A 1–2 min 2–4 hr 200 min (6 hr infusion); N-dealkylation
300 min (12 hr CYP3A4/5 substrate
infusion)a
Hydromorphone 1.5 7.5 5–15 min 2–3 hr N/A Glucuronidation
Morphine 10 30 5–10 min 3–4 hr N/A Glucuronidation
Methadone N/Ac N/Ac 1–3 d 15–60 hr N/A N-demethylation
CYP3A4/5, 2D6, 2B6,
1A2 substrate
Remifentanil N/A N/A 1–3 min 3–10 min 3–4 min Hydrolysis by plasma
esterases
PO = oral; N/A = not applicable; IBW = ideal body weight.
a
After 12 hrs, and in cases of end-organ dysfunction, the context-sensitive half-life increases unpredictably.
b
May increase dose to extend dosing interval; hydromorphone 0.5 mg IV every 3 hrs, or morphine 4–8 mg IV every 3–4 hrs.
c
Equianalgesic dosing tables may underestimate the potency of methadone. The morphine- or hydromorphone-to-methadone conversion ratio
increases (i.e., the potency of methadone increases) as the dose of morphine or hydromorphone increases. The relative analgesic potency ratio of
oral to parenteral methadone is 2:1, but the confidence intervals are wide.
d
QTc is the Q-T interval (corrected) of the electrocardiographic tracing.
Pharmacology of Opiate Analgesics1,128,440,472
Active Metabolites Intermittent Dosing IV Infusion Rates Side Effects and Other Information
None 0.35–0.5 μg/kg IV q0.5–1 hr 0.7–10 μg/kg/hr Less hypotension than with morphine.
Accumulation with hepatic
impairment.
None 0.2–0.6 mg IV q1–2 hrb 0.5–3 mg/hr Therapeutic option in patients tolerant to
morphine/fentanyl. Accumulation with
hepatic/renal impairment.
6- and 3-glucuronide 2–4 mg IV q1–2 hrb 2–30 mg/hr Accumulation with hepatic/renal
metabolite impairment. Histamine release.
N-demethylated derivative IV/PO: 10–40 mg q6–12 hr Not recommended May be used to slow the development of
IV: 2.5–10 mg q8–12 hr tolerance where there is an escalation
of opioid dosing requirements.
Unpredictable pharmacokinetics;
unpredictable pharmacodynamics in
opiate naïve patients. Monitor QTc.d
None N/A Loading dose: 1.5 μg/ No accumulation in hepatic/renal failure.
kg IV Use IBW if body weight >130% IBW.
Maintenance dose: 0.5–15
μg/kg/hr IV
Pain and Analgesia: Questions, Statements, and with age64,66 and is greater in non-Caucasians than
Recommendations. in Caucasians.64,66,68 Differences in procedural pain
1. Incidence of Pain between nonsurgical and surgical patients vary ac-
cording to procedure.64,66 Hemodynamic changes
a. Question: Do adult ICU patients experience non- are not valid correlates of procedural pain.99
procedural pain in the ICU and, if so, what events Available information suggests that preemptive an-
or situations are related to pain? (descriptive) algesia has benefits, but the risks of procedural pain
Answer: Adult medical, surgical, and trauma ICU pa- and the lack of preemptive treatment are unclear.
tients routinely experience pain, both at rest and with 2. Pain Assessment
routine ICU care (B). Pain in adult cardiac surgery a. Question: Should pain assessments be routinely
patients is common and poorly treated; women expe- performed in adult ICU patients? (actionable)
rience more pain than men after cardiac surgery (B). Answer: We recommend that pain be routinely mon-
Rationale: Medical, surgical, and trauma ICU pa- itored in all adult ICU patients (+1B).
tients experience significant pain, even at rest.61,63,73
Rationale: Routine pain assessments in adult ICU
Therefore, all adult patients in any ICU should be
patients are associated with improved clinical out-
evaluated for pain. Pain at rest should be consid-
comes. Pain assessment, especially if protocolized,
ered a major clinical diagnostic syndrome. In car-
has been significantly associated with a reduction
diac surgery patients, pain related to the surgery,
in the use of analgesic medications, ICU length of
coughing, respiratory care procedures, and mobili-
stay (LOS), and duration of mechanical ventila-
zation remains prevalent and poorly treated; women
tion.3,62 Pain assessment is essential for appropriate
experience more pain than men after cardiac sur-
treatment, especially when part of a comprehensive
gery.73,96–98 Therefore, activity pain in cardiac sur-
pain management protocol. Although the quality
gery patients must be assessed and treated. Pain
of evidence is moderate, a strong recommendation
management should be individualized according to
for performing routine pain assessments in all ICU
the patient’s experience of pain, with special atten-
patients is appropriate, as the benefits strongly out-
tion to its occurrence in women.97
weigh the risks.
Question: What is the pain experienced by adult b. Question: What are the most valid and reliable be-
ICU patients undergoing procedures? (descriptive) havioral measures of pain in critically ill adult pa-
Answer: Procedural pain is common in adult ICU tients who are unable to self-report? (descriptive)
patients (B).
Answer: The Behavioral Pain Scale (BPS) and the
Rationale: Pain associated with nonsurgical proce- Critical-Care Pain Observation Tool (CPOT) are
dures such as chest tube removal or wound care is the most valid and reliable behavioral pain scales
prevalent in adult ICU patients.68,99 Generally at a for monitoring pain in medical, postoperative, or
moderate level,68 pain is influenced by preproce- trauma (except for brain injury) adult ICU patients
dural pain levels and the administration of analge- who are unable to self-report, and in whom motor
sics.100 Less than 25% of patients receive analge- function is intact and behaviors are observable.
sics before the procedures.68 Procedural pain varies
Table 4.
Pharmacology of Nonopiate Analgesics1,91,132,440
Active
Nonopiates (Route) Onset Elimination Half-Life Metabolic Pathway Metabolites
Ketamine (IV) 30–40 sec 2–3 hr N-demethylation Norketamine
Acetaminophen (PO) 30–60 min variable 2–4 hr Glucuronidation, sulfonation None
Acetaminophen (PR)
Acetaminophen (IV) 5–10 min 2 hr Glucuronidation, sulfonation. None
a
Ketorolac (IM/IV) 10 min 2.4–8.6 hr Hydroxylation, conjugation/ None
renal excretion
Ibuprofen (IV) N/A 2.2–2.4 hr Oxidation None
Ibuprofen (PO) 25 min 1.8–2.5 hr Oxidation None
Gabapentin (PO) N/A 5–7 hr Renal excretion None
Carbamazepine immediate 4–5 hr 25–65 hrs initially, then Oxidation None
release (PO) 12–17 hr
PO = orally; PR = rectally; max = maximum; IM = intramuscular; N/A = not applicable.
a
For patients > 65 yr or < 50 kg, 15 mg IV/IM every 6 hrs to a maximum dose of 60 mg/day for 5 days.
Using these scales in other ICU patient populations Answer: We do not suggest that vital signs (or ob-
and translating them into foreign languages other servational pain scales that include vital signs) be
than French or English require further validation used alone for pain assessment in adult ICU patients
testing (B). (–2C). We suggest that vital signs may be used as
Rationale: A total of six behavioral pain scales were a cue to begin further assessment of pain in these
analyzed: BPS; BPS—Non-Intubated (BPS-NI); patients, however (+2C).
CPOT; Non-Verbal Pain Scale (NVPS), both initial Rationale: Observational studies with major limita-
and revised (NVPS-I, NVPS-R); Pain Behavioral tions provide inconsistent evidence of the validity
Assessment Tool (PBAT); and the Pain Assessment, of vital signs for the purpose of pain assessment in
Intervention, and Notation (PAIN) Algorithm. medical, postoperative, and trauma ICU patients.
Table 5 summarizes their psychometric scores. Even if there is a trend for vital signs to increase
Observational studies, although somewhat limited, when critically ill patients are exposed to painful
provide consistent evidence that the BPS (3–12 total procedures, these increases are not reliable predic-
score) and CPOT (0–8 total score) scales have good tors of pain.66,101,105,107,110 Vital signs have been re-
psychometric properties in terms of: inter-rater reli- ported to increase both during nociceptive and non-
ability,101–109 discriminant validity,101,102,104,107,109,110 nociceptive procedures109 or to remain stable during
and criterion validity,103–105,109,110 in medical, post- nociceptive exposure.99 Vital signs do not correlate
operative, and trauma ICU patients. A CPOT score with either patients’ self-report of pain105,110 or be-
of greater than 2 had a sensitivity of 86% and a havioral pain scores.101,107 But because vital signs
specificity of 78% for predicting significant pain in may change with pain, distress, or other factors,
postoperative ICU adults exposed to a nociceptive they can be a cue to perform further pain assess-
procedure.111,112 Investigators suggested a similar ments in these patients.118
cutoff score for the BPS (> 5), on the basis of de- 3. Treatment of Pain
scriptive statistics in nonverbal ICU adults during a. Question: Should procedure-related pain be treated
nociceptive procedures compared with patients at pre-emptively in adult ICU patients? (actionable)
rest.62 The CPOT and BPS can be successfully im- Answer: We recommend that preemptive analgesia
plemented in the ICU following short, standardized and/or nonpharmacologic interventions (e.g., relax-
training sessions.2,85 Their regular use can lead to ation) be administered to alleviate pain in adult ICU
better pain management and improved clinical outpatients prior to chest tube removal (+1C). We sug-
comes in ICU patients.2,3,85 The BPS-NI is derived gest that for other types of invasive and potentially
from the BPS and adapted for nonintubated ICU pa- painful procedures in adult ICU patients, preemp-
tients,113 but it has been tested in a group of only 30 tive analgesic therapy and/or nonpharmacologic
patients so far, and replication studies are needed interventions may also be administered to alleviate
to support its psychometric properties. More stud- pain (+2C).
ies are also necessary to examine the psychometric
Rationale: Our strong recommendation is that pa-
properties of the NVPS,114 NVPS-R,115 PBAT,116
tients undergoing chest tube removal should be
and PAIN.117
preemptively treated for pain, both pharmaco-
c. Question: Should vital signs be used to assess pain
logically and non-pharmacologically. Significantly
in adult ICU patients? (actionable)
lower pain scores were reported by patients if they
received IV morphine plus relaxation,119 topical
Dosing Side Effects and Other Information
Loading dose 0.1–0.5 mg/kg IV followed by 0.05–0.4 mg/kg/hr Attenuates the development of acute tolerance to opioids. May
cause hallucinations and other psychological disturbances.
325–1000 mg every 4–6 hr; May be contraindicated in patients with significant hepatic
max dose ≤ 4 g/day dysfunction.
650 mg IV every 4 hrs – 1000 mg IV every 6 hr;
max dose ≤ 4 g/day
30 mg IM/IV, then 15–30 mg IM/IV every 6 hr up to 5 days; Avoid nonsteroidal anti-inflammatory drugs in following
max dose = 120 mg/day × 5 days conditions: renal dysfunction; gastrointestinal bleeding;
platelet abnormality; concomitant angiotensin converting
enzyme inhibitor therapy, congestive heart failure, cirrhosis,
asthma. Contraindicated for the treatment of perioperative
pain in coronary artery bypass graft surgery.
400–800 mg IV every 6 hr infused over > 30 mins; Avoid nonsteroidal anti-inflammatory drugs in following
max dose = 3.2 g/day conditions: renal dysfunction; gastrointestinal bleeding;
platelet abnormality; concomitant angiotensin converting
enzyme inhibitor therapy, congestive heart failure, cirrhosis,
asthma. Contraindicated for the treatment of perioperative
pain in coronary artery bypass graft surgery.
400 mg PO every 4 hrs;
max dose = 2.4 g/day
Starting dose = 100 mg PO three times daily; maintenance Side effects: (common) sedation, confusion, dizziness, ataxia.
dose = 900–3600 mg/day in 3 divided doses Adjust dosing in renal failure pts. Abrupt discontinuation
associated with drug withdrawl syndrome, seizures.
Starting dose = 50–100 mg PO bid; maintenance dose = Side effects: (common) nystagmus, dizziness, diplopia,
100–200 mg every 4–6 hr; max dose = 1200 mg/day lightheadedness, lethargy; (rare) aplastic anemia, and
agranulocytosis; Stevens–Johnson syndrome or toxic
epidermal necrolysis with HLA-B1502 gene. Multiple drug
interactions due to hepatic enzyme induction.
valdecoxib,120 IV sufentanil, or fentanyl121 prior are associated with similar clinical outcomes (e.g.,
to chest tube removal. According to these studies, duration of mechanical ventilation, LOS) when
the desirable consequences outweigh undesirable titrated to similar pain intensity endpoints. For
effects. One can reasonably assume that most ICU non-neuropathic pain, nonopioids such as IV acet-
patients would want their pain preemptively treated aminophen,87 oral, IV, or rectal cyclooxygenase in-
with nonpharmacologic and/or pharmacologic inhibitors,122,123,135 or IV ketamine132,137 can be used in
terventions prior to other painful procedures as well. addition to opioids. Using nonopioids may also de-
b. Question: What types of medications should be crease the overall quantity of opioids administered
administered for pain relief in adult ICU patients? and the incidence and severity of opioid-related side
(actionable) effects. In patients with neuropathic pain, IV opioid
Answer: We recommend that IV opioids be con- use plus oral gabapentin or carbamazepine provides
sidered as the first-line drug class of choice to treat superior pain relief in mechanically ventilated pa-
non-neuropathic pain in critically ill patients (+1C). tients compared to IV opioid use alone.90,91 A lack of
All available IV opioids, when titrated to similar direct comparisons between opioids and nonopioids
pain intensity endpoints, are equally effective (C). hinders conclusions regarding the effect of non-
We recommend that either enterally administered opioid analgesics, particularly in ICU patients.
gabapentin or carbamazepine, in addition to IV opi- c. Question: What mode of analgesic delivery (i.e.,
oids, be considered for the treatment of neuropathic either neuraxial or parenteral) is recommended for
pain (+1A). We suggest that nonopioid analgesics pain relief in critically ill adults who have under-
be considered to decrease the amount of opioids ad- gone either thoracic or abdominal surgery or who
ministered (or to eliminate the need for IV opioids have traumatic rib fractures (including both me-
altogether) and to decrease opioid-related side ef- chanically ventilated and nonmechanically venti-
fects (+2C). lated ICU patients)? (actionable)
Rationale: For non-neuropathic pain, evidence sup- Answer: We recommend that thoracic epidural an-
ports using an opiate-based regimen to decrease esthesia/analgesia be considered for postoperative
pain intensity.87,90,91,122–136 Apart from drug cost analgesia in patients undergoing abdominal aortic
and resource utilization, all opioids administered surgery (+1B). We provide no recommendation
IV appear to exhibit similar analgesic efficacy and for using a lumbar epidural over parenteral opioids
Table 5.
Psychometric Scores for Pain Scales
Scales
Pain
Critical Pain Assessment
Care Pain Behavioral and
Observation BPS Nonverbal Pain Assessment Intervention
Psychometric Criteria Scored Tool BPS Nonintubated Scalea Tool Notation
Item selection description 2 2 2 1 2 1
Content validation 2 0 0 1 1 1
Limitations presented 1 0 0 1 1 1
Internal consistency 2 1 2 I = 1/Rev = 2 0 0
Inter-rater reliability 2 2 2 2 0 0
Inter-rater reliability tested with 1 1 1 1 1 1
nonresearch team
Intra-rater reliability tested if 0 0 N/A I = N/A /Rev = 0 0 0
inter-rater reliability is low or
inconsistent
Total number of participants 2 2 1 2 2 1
Criterion validation: correlation 1 2 0 0 1 0
with “gold standard”
Criterion validation: sensitivity 1 0 0 0 0 0
Criterion validation: specificity 2 0 0 0 0 0
Discriminant validation 2 2 2 2 2 0
Feasibility 1 1 0 0 0 0
Directives of use 1 0 1 0 1 1
Relevance of scale in practice 0 1 0 0 0 1
Total score (range: 0–25) 20 14 11 I = 11/Rev = 12 11 7
Weighted scoreb (range: 0–20) 14.70 12.00 10.20 I = 9.2/Rev = 8.7 7.50 5.90
Quality of psychometric evidence M M L VL L VL
(based on weighted score)
BPS = Behavioral Pain Scale; I = initial; Rev = revised; N/A = not applicable; M = moderate; L = low; VL = very low.
a
Nonverbal pain scale has two versions: I and Rev.
b
Weighted score range (0–20): Very good psychometric properties(Very good): 15–20; Good psychometric properties (M): 12–14.9; Some
acceptable psychometric properties, but remain to be replicated in other studies (L): 10–11.9; Very few psychometric properties reported, or
unacceptable results (VL): < 10.
for postoperative analgesia in patients undergoing dural catheter is placed preoperatively provides su-
abdominal aortic aneurysm surgery, due to a lack perior pain relief to parenteral opioids alone; rare
of benefit when these routes of administration are complications of thoracic epidurals in these patients
compared in this patient population (0,A). We pro- include postoperative heart failure, infections, and
vide no recommendation for the use of thoracic respiratory failure.138,139 High-quality evidence
epidural analgesia in patients undergoing either demonstrates no benefit with lumbar epidural com-
intrathoracic or nonvascular abdominal surgical pared with parenteral opioids in these patients.139–141
procedures, because of insufficient and conflicting Several shortcomings in research design make it dif-
evidence for this mode of analgesic delivery in these ficult to recommend the use of thoracic epidural an-
patients (0,B). We suggest that thoracic epidural analgesia in patients undergoing either intrathoracic or
algesia be considered for patients with traumatic rib nonvascular abdominal surgical procedures.142–149
fractures (+2B). We provide no recommendation for Epidural analgesia administered to patients with rib
neuraxial/regional analgesia over systemic analge- fractures improved pain control, especially during
sia in medical ICU patients, due to lack of evidence coughing or deep breathing, lowered the incidence
in this patient population (0, No Evidence). of pneumonia, but increased the risk of hypoten-
Rationale: High-quality evidence suggests that sion.150,151 No evidence supports using neuraxial/
thoracic epidural anesthesia/analgesia in patients regional analgesia in medical ICU patients.
undergoing abdominal aortic surgery when the epi-
Agitation and Sedation. Indications for sedation. Agitation when administered with other medications that inhibit cyto-
and anxiety occur frequently in critically ill patients and are chrome P450 enzyme systems and/or glucuronide conjuga-
associated with adverse clinical outcomes.152–156 Sedatives tion in the liver.173–175 The elimination half-life and duration
are commonly administered to ICU patients to treat agitation of clinical effect of lorazepam are also increased in patients
and its negative consequences.157 Prompt identification and with renal failure.176,177 The active metabolites of mid-
treatment of possible underlying causes of agitation, such azolam and diazepam may accumulate with prolonged ad-
as pain, delirium, hypoxemia, hypoglycemia, hypotension, ministration, especially in patients with renal dysfunction.178
or withdrawal from alcohol and other drugs, are important. Benzodiazepine clearance decreases with age.175,179,180
Efforts to reduce anxiety and agitation, including mainte- Delayed emergence from sedation with benzodiaz-
nance of patient comfort, provision of adequate analgesia, epines can result from prolonged administration of benzodi-
frequent reorientation, and optimization of the environment azepines (due to saturation of peripheral tissues), advanced
to maintain normal sleep patterns, should be attempted be- age, hepatic dysfunction, or renal insufficiency.171,175,181
fore administering sedatives. Because of the greater potency and slower clearance of loraz-
Sedatives can be titrated to maintain either light (i.e., epam, emergence from short-term sedation (1–2 days) with
patient is arousable and able to purposefully follow simple lorazepam may be longer than with midazolam. However,
commands) or deep sedation (i.e., patient is unresponsive comparative studies on the prolonged use of these drugs in
to painful stimuli). Multiple studies have demonstrated the ICU patients suggest greater variability and longer time to
negative consequences of prolonged, deep sedation, and awakening with midazolam than with lorazepam.171,175,182–184
the benefits of maintaining lighter sedation levels in adult Diazepam has a prolonged duration of action due to satura-
ICU patients.10,14,15,20,158 The use of sedation scales, sedation of peripheral tissues and active metabolites that can ac-
tion protocols designed to minimize sedative use, and the cumulate in patients with renal insufficiency.185
use of nonbenzodiazepine medications are associated with Parenteral formulations of lorazepam contain pro-
improved ICU patient outcomes, including a shortened dura- pylene glycol as a diluent, which can cause toxicity in
tion of mechanical ventilation, ICU and hospital LOS, and ICU patients.186–190 Propylene glycol toxicity manifests as
decreased incidences of delirium and long-term cognitive metabolic acidosis and acute kidney injury. Because these
dysfunction.7–10,12,13,18,19,159–162 conditions occur frequently in critically ill patients, their
Clinical pharmacology of sedatives. Historically, ben- possible association with lorazepam administration may be
zodiazepines (i.e., midazolam and lorazepam) and propofol overlooked. Although initially thought to accumulate only
have commonly been used to sedate ICU patients. The 2002 in patients receiving very high lorazepam doses via con-
guidelines recommended midazolam only for short-term se- tinuous infusion (i.e., 15–25 mg/hr), current evidence sug-
dation, lorazepam for long-term sedation, and propofol for gests that total daily IV doses as low as 1 mg/kg can cause
patients requiring intermittent awakenings.1 Recent surveys propylene glycol toxicity.191 The serum osmol gap has been
assessing sedation practices demonstrate that midazolam used as a reliable screening and surveillance tool; an osmol
and propofol remain the dominant medications used for gap greater than 10–12 mOsm/L may help identify patients
ICU sedation, with decreasing lorazepam use, and rare use receiving lorazepam who have significant propylene glycol
of barbiturates, diazepam, and ketamine in the ICU.62,163–166 accumulation.187,191
Dexmedetomidine, approved in the United States shortly Propofol. Propofol is an IV sedative that binds to
before completion of the 2002 guidelines, is now more com- multiple receptors in the central nervous system to interrupt
monly administered for ICU sedation.166–168 The clinical neural transmission, including GABAA, glycine, nicotinic,
pharmacology of sedatives prescribed for ICU patients is and M1 muscarinic receptors.192–194 Propofol has sedative,
summarized in Table 6. hypnotic, anxiolytic, amnestic, antiemetic, and anticonvul-
Benzodiazepines. Benzodiazepines activate sant properties, but no analgesic effects.195,196 In ICU pa-
γ-aminobutyric acid A (GABAA) neuronal receptors in the tients, propofol’s amnestic effects at light sedation levels are
brain. They have anxiolytic, amnestic, sedating, hypnotic, less than that of benzodiazepines.197 Propofol is highly lipid
and anticonvulsant effects, but no analgesic activity.169,170 soluble and quickly crosses the blood-brain barrier, resulting
Their amnestic effects extend beyond their sedative ef- in the rapid onset of sedation. Because of its high lipid solu-
fects.171 Lorazepam is more potent than midazolam, which bility, propofol also rapidly redistributes into peripheral tis-
is more potent than diazepam. Midazolam and diazepam are sues. This rapid redistribution, combined with high hepatic
more lipid soluble than lorazepam, resulting in a quicker on- and extrahepatic clearance, results in a rapid offset of effect
set of sedation and a larger volume of distribution than for lo- following short-term propofol administration. Because of its
razepam. Elderly patients are significantly more sensitive to short duration of sedative effect, propofol may be useful in
the sedative effects of benzodiazepines.171 Benzodiazepines patients requiring frequent awakenings for neurologic as-
can cause respiratory depression and systemic hypoten- sessments and it may facilitate daily sedation interruption
sion, especially when administered in conjunction with protocols.183,198,199 However, long-term propofol administra-
other cardiopulmonary depressants, particularly opioids.172 tion can lead to the saturation of peripheral tissues and pro-
Benzodiazepine-induced cardiopulmonary instability is longed emergence.198
more likely to occur in critically ill patients with baseline Propofol causes dose-dependent respiratory depres-
respiratory insufficiency and/or cardiovascular instability.172 sion and hypotension due to systemic vasodilation. These
Tolerance to benzodiazepines develops with long-term ad- effects may be more pronounced when propofol is ad-
ministration. ministered with other sedative and opioid medications.
All benzodiazepines are metabolized by the liver. Cardiopulmonary instability with propofol administration
Benzodiazepine clearance is reduced in patients with hepatic is more likely to occur in patients with baseline respiratory
dysfunction and other disease states, in elderly patients, and insufficiency and/or cardiovascular instability. Other side
Table 6.
Clinical Pharmacology of Sedative Medications1
Onset After
IV Loading Elimination Active Loading Maintenance
Agent Dose Half-Life Metabolites Dose (IV) Dosing (IV) Adverse Effects
a
Midazolam 2–5 min 3–11 hr Yes 0.01–0.05 0.02–0.1 mg/ Respiratory depression,
mg/kg kg/hr hypotension
over
several
minutes
Lorazepam 15–20 min 8–15 hr None 0.02–0.04 0.02–0.06 mg/ Respiratory depression,
mg/kg kg q2–6 hypotension; propylene
(≤ 2 mg) hr prn or glycol-related acidosis,
0.01–0.1 nephrotoxicity
mg/kg/hr
(≤10 mg/hr)
Diazepam 2–5 min 20–120 hr Yesa 5–10 mg 0.03–0.1 mg/ Respiratory depression,
kg q0.5–6 hypotension, phlebitise
hr prn
Propofol 1–2 min Short-term None 5 μg/kg/min 5–50 μg/kg/ Pain on injectionf,
use = 3–12 hr over 5 min hypotension,
long-term use minb respiratory depression,
= 50 ± 18.6 hr hypertriglyceridemia,
pancreatitis, allergic
reactions, propofol-
related infusion
syndrome; deep
sedation with propofol
is associated with
significantly longer
emergence times than
with light sedation
Dexmedetomidine 5–10 min 1.8–3.1 hr None 1 μg/kg over 0.2–0.7 μg/kg/ Bradycardia, hypotension;
10 minc hrd hypertension with
loading dose; loss of
airway reflexes
a
Active metabolites prolong sedation, especially in patients with renal failure.
b
Administer IV loading dose of propofol only in those patients in whom hypotension is unlikely to occur.
c
Avoid IV loading doses of dexmedetomidine in hemodynamically unstable patients.
d
Dexmedetomidine maintenance infusion rate may be increased to 1.5 μg/kg/h as tolerated.
e
Phlebitis occurs when diazepam is injected into peripheral veins.
f
Pain at the injection site occurs commonly when propofol is administered through peripheral veins.
effects include hypertriglyceridemia, acute pancreatitis, kg/min), but it may also occur with low-dose infusions.208,209
and myoclonus.200–204 Propofol is dissolved in a 10% lipid The incidence of PRIS with propofol infusions is approxi-
emulsion containing egg lecithin and soybean oil, which can mately 1%.210 Mortality from PRIS is high (up to 33%) and
precipitate allergic reactions in patients with either egg or may occur even after discontinuing the infusion.202 The vari-
soybean allergies. Some generic formulations of propofol able presentation, lack of diagnostic specificity, and infre-
contain sulfite preservatives, which may also cause allergic quent occurrence of PRIS make detection of this potentially
reactions.196 life-threatening condition difficult. Early recognition and
Propofol administration is rarely associated with de- discontinuation of propofol in patients with suspected PRIS
veloping propofol infusion syndrome (PRIS). The signs are critically important. Management of patients with PRIS
and symptoms of PRIS vary but may include worsening is otherwise supportive.
metabolic acidosis, hypertriglyceridemia, hypotension with Dexmedetomidine. Dexmedetomidine is a selective
increasing vasopressor requirements, and arrhythmias. a2-receptor agonist with sedative, analgesic/opioid sparing,
Acute kidney injury, hyperkalemia, rhabdomyolysis, and and sympatholytic properties, but with no anticonvulsant
liver dysfunction have also occasionally been reported with properties.211,212 Dexmedetomidine produces a pattern of se-
PRIS.205,206 Possible PRIS mechanisms include mitochon- dation that differs considerably from other sedative agents.
drial dysfunction, impaired fatty acid oxidation, diversion Patients sedated with dexmedetomidine are more easily
of carbohydrate metabolism to fat substrates, and propofol arousable and interactive, with minimal respiratory depres-
metabolite accumulation.207 PRIS is usually associated with sion.213,214 The onset of sedation occurs within 15 mins and
prolonged administration of high propofol doses (> 70 µg/ peak sedation occurs within 1 hr of starting an IV infusion
of dexmedetomidine.167,215 Sedation onset may be hastened ger durations of mechanical ventilation and ICU
by administering an initial IV loading dose of dexmedetomi- LOS.10,14,15,20,158 Three studies demonstrated evidence
dine, but this is more likely to cause hemodynamic instabil- of increased physiologic stress in terms of elevated
ity in critically ill patients.216 Dexmedetomidine is rapidly catecholamine concentrations and/or increased oxygen
redistributed into peripheral tissues and is metabolized by the consumption at lighter sedation levels,232,235,236 whereas
liver.217 In patients with normal liver function, the elimina- one study did not.233 The clinical significance of this is
tion half-life is approximately 3 hrs.215 Patients with severe unclear, because no clear relationship was observed be-
hepatic dysfunction have impaired dexmedetomidine clear- tween elevated markers of physiologic stress and clini-
ance, can experience prolonged emergence, and may require cal outcomes, such as myocardial ischemia, in these
lower dexmedetomidine doses.218 Although dexmedetomi- patients.232–234
dine has only been approved in the United States for short- Four studies examined the relationship between depth of
term sedation of ICU patients (< 24 hrs) at a maximal dose sedation and post-ICU psychological stress.20,231,237,238
of 0.7 µg/kg/hr (up to 1.0 µg/kg/h for procedural sedation), One showed that a protocol of daily sedation interrup-
several studies demonstrate the safety and efficacy of dexme- tion did not cause adverse psychological outcomes,231
detomidine infusions administered for greater than 24 hrs (up whereas another found a low incidence of such events
to 28 days) and at higher doses (up to 1.5 µg/kg/hr).216,219–222 in patients who were lightly sedated.20 A third study
The most common side effects of dexmedetomidine showed that deeper sedation levels were associated
are hypotension and bradycardia.223 IV loading doses can with a lower incidence of recall, but that delusional
cause either hypotension or hypertension.215,224 Because memories did not correlate with lighter levels of seda-
dexmedetomidine does not significantly affect respira- tion.238 However, in the fourth study, periods of wake-
tory drive, it is the only sedative approved in the United fulness were associated with recall of stressful ICU
States for administration in nonintubated ICU patients, and memories.237 The overall quality of evidence evaluat-
infusions can be continued as needed following extuba- ing the relationship between depth of ICU sedation and
tion.225–227 However, dexmedetomidine can cause a loss of post-ICU psychological stress is low, and these study
oropharyngeal muscle tone which can lead to airway ob- results are conflicting. Thus, the overall benefits of
struction in nonintubated patients, so continuous respiratory maintaining a light sedation level in ICU patients ap-
monitoring for both hypoventilation and hypoxemia in these pear to outweigh the risks.
patients is indicated.225 Dexmedetomidine’s opioid-sparing 2. Monitoring Depth of Sedation and Brain Function
effect may reduce opioid requirements in critically ill pa- a. Sedation scales
tients.219,220,224,228 The mechanism of action for the analge-
Question: Which subjective sedation scales are the
sic properties of dexmedetomidine remains controversial.229
most valid and reliable in the assessment of depth
Although a2 receptors are located in the dorsal region of
and quality of sedation in mechanically ventilated
the spinal cord and in supraspinal sites, dexmedetomidine’s
adult ICU patients? (descriptive)
nonspinal analgesic effects have been documented.230 One
recent study suggests that ICU patients receiving dexme- Answer: The Richmond Agitation-Sedation Scale
detomidine may have a lower prevalence of delirium than (RASS) and Sedation-Agitation Scale (SAS) are the
patients sedated with midazolam.220 most valid and reliable sedation assessment tools
for measuring quality and depth of sedation in adult
Agitation and Sedation: Questions, Statements, and ICU patients (B).
Recommendations. Rationale: Several subjective sedation scales exist
1. Depth of Sedation and Clinical Outcomes for monitoring depth of sedation and agitation in
Question: Should adult ICU patients be maintained at a adult ICU patients, and their psychometric proper-
light level of sedation? (actionable) ties are well described. But the cumulative degree
of psychometric properties tested and the quality of
Answer: Maintaining light levels of sedation in adult
evidence vary widely among scales. We reviewed
ICU patients is associated with improved clinical out-
the psychometric properties of ten subjective seda-
comes (e.g., shorter duration of mechanical ventilation
tion scales, each developed for evaluating the depth
and a shorter ICU LOS) (B). Maintaining light levels of
and quality of sedation in adult ICU patients: 1)
sedation increases the physiologic stress response, but
Observer’s Assessment of Alertness/Sedation Scale
is not associated with an increased incidence of myo-
(OAA/S); 2) Ramsay Sedation Scale (Ramsay);
cardial ischemia (B). The association between depth of
3) New Sheffield Sedation Scale (Sheffield); 4)
sedation and psychological stress in these patients re-
Sedation Intensive Care Score (SEDIC); 5) Motor
mains unclear (C). We recommend that sedative medi-
Activity Assessment Scale (MAAS); 6) Adaptation
cations be titrated to maintain a light rather than deep
to the Intensive Care Environment (ATICE); 7)
level of sedation in adult ICU patients, unless clinically
Minnesota Sedation Assessment Tool (MSAT); 8)
contraindicated (+1B).
Vancouver Interaction and Calmness Scale (VICS);
Rationale: Thirteen studies examined the direct re- 9) SAS; and 10) RASS. We reviewed 27 studies
lationship between sedative depth and clinical out- including 2,805 patients2,239–264: 26 were observa-
comes in ICU patients, including duration of mechani- tional studies and one used a blinded and random-
cal ventilation, ICU LOS, measures of physiologic ized format to evaluate videos of previously scored
stress, and assessments of post-ICU psychological patient sedation levels.253 Table 7 summarizes the
stress.10,14,15,20,158,231–238 Five studies demonstrated psychometric scores for all ten sedation scales.
that deeper sedation levels are associated with lon-
The RASS and SAS yielded the highest psychomet- Ramsay, and OAA/S scales had a lower quality of
ric scores (i.e., inter-rater reliability, convergent or evidence; replication studies and psychometric test-
discriminant validation) and had a robust number ing of reliability and validity for determining the
of study participants. Both scales demonstrated a depth and quality of sedation in ICU patients are
high degree of inter-rater reliability, which included needed.239,241,242,245,247–249,251–253,255,261,262,264
ICU clinicians.240,262,263 Both scales were able to In summary, our comparative assessment of the
discriminate different sedation levels in various psychometric properties of sedation scales revealed
clinical situations.246,250,258,261 Moderate to high cor- RASS and SAS to be the most valid and reliable
relations were found between the sedation scores of for use in critically ill patients, whereas ATICE,
these scales and either electroencephalogram (EEG) MSAT, and VICS are moderately valid and reliable.
or bispectral index (BIS) values.244,246,258 In addi- Additional testing of the remaining scales is needed
tion, the RASS consistently provided a consensus to better assess their reliability and validity in deter-
target for goal-directed delivery of sedative agents, mining depth of sedation in critically ill patients.
demonstrating feasibility of its usage.2,246,254 b. Neurologic monitoring
We found that the ATICE, MSAT, and VICS i. Question: Should objective measures of brain
had good quality of psychometric evidence, but function (e.g., auditory evoked potentials
some psychometric properties (e.g., conver- [AEPs], bispectral index [BIS], Narcotrend
gent or discriminant validation) have not been Index [NI], Patient State Index [PSI], or state
tested.242,243,249,259,260 The MAAS, SEDIC, Sheffield, entropy [SE]) be used to assess depth of seda-
Table 7.
Psychometric Scores for Sedation Scales
Sedation Scale
Observer’s Assessment
Psychometric Criteria of Alertness/Sedation Ramsay Sedation New Sheffield Sedation Intensive
Scored Scale Scale Sedation Scale Care Score
Item selection 0 0 2 1
description
Content validation 0 0 0 0
Limitations presented 0 0 1 0
Interrater reliability 0 1 2 2
Interrater reliability 0 1 1 1
tested with
nonresearch team
Interrater reliability N/A 0 N/A N/A
tested if interrater
reliability is low or
inconsistent
Total number of 1 2 0 1
participants
Criterion validation 1 2 0 0
Discriminant validation 0 0 0 2
Feasibility 0 0 0 0
Directives of use 1 0 1 0
Relevance of scale in 0 0 0 0
practice
Total score (range: 3 6 7 7
0–18)
Weighted scorea 3.7 7.7 8.5 10.5
(range: 0–20)
Quality of psychometric VL VL VL L
evidence (based on
weighted scores)
N/A = not applicable; VL = very low; L = low; M = moderate; VG = very good.
a
Weighted score range (0–20): Very good psychometric properties (VG): 15–20; Good psychometric properties (M): 12–14.9; Some acceptable
psychometric properties, but remain to be replicated in other studies (L): 10–11.9; Very few psychometric properties reported, or unacceptable
results (VL): < 10.
tion in noncomatose, adult ICU patients who iii. Question: Should EEG monitoring be used to
are not receiving neuromuscular blocking detect nonconvulsive seizure activity and to
agents? (actionable) titrate electrosuppressive medication to obtain
Answer: We do not recommend that objective burst suppression in adult ICU patients with
measures of brain function (e.g., AEPs, BIS, either known or suspected seizures? (action-
NI, PSI, or SE) be used as the primary method able)
to monitor depth of sedation in noncomatose, Answer: We recommend that EEG monitoring
nonparalyzed critically ill adult patients, as be used to monitor nonconvulsive seizure ac-
these monitors are inadequate substitutes for tivity in adult ICU patients with either known
subjective sedation scoring systems (–1B). or suspected seizures, or to titrate electrosup-
ii. Question: Should objective measures of brain pressive medication to achieve burst suppres-
function (e.g., AEPs, BIS, NI, PSI, or SE) be sion in adult ICU patients with elevated intra-
used to measure depth of sedation in adult cranial pressure (+1A).
ICU patients who are receiving neuromuscu- Rationale: We reviewed 18 studies com-
lar blocking agents? (actionable) paring objective monitors of sedation to
Answer: We suggest that objective measures sedation scoring systems in adult ICU pa-
of brain function (e.g., AEPs, BIS, NI, PSI, or tients.244,248,258,265–279 Objective monitors in-
SE) be used as an adjunct to subjective seda- cluded both raw and processed EEG and AEP
tion assessments in adult ICU patients who monitors. Processed EEG monitors (i.e., con-
are receiving neuromuscular blocking agents, version of a raw EEG signal to an index by an
as subjective sedation assessments may be un- algorithm) included the Bispectral Index (BIS)
obtainable in these patients (+2B). and Bispectral Index XP (BIS-XP SE), NI,
Psychometric Scores for Sedation Scales
Sedation Scale
Adaptation Minnesota Vancouver Richmond
Motor Activity to the Sedation Interaction Sedation- Agitation-
Psychometric Criteria Assessment Intensive Care Assessment and Calmness Agitation Sedation
Scored Scale Environment Tool Scale Scale Scale
Item selection 0 2 2 2 1 2
description
Content validation 0 1 1 1 1 0
Limitations presented 0 1 1 1 1 0
Interrater reliability 2 2 2 2 2 2
Interrater reliability 1 1 1 1 1 1
tested with
nonresearch team
Interrater reliability N/A N/A N/A N/A N/A N/A
tested if interrater
reliability is low or
inconsistent
Total number of 2 2 2 2 2 2
participants
Criterion validation 1 0 0 0 2 2
Discriminant validation 0 0.5 1 2 2 2
Feasibility 0 0 0 0 0 1
Directives of use 1 1 1 1 1 1
Relevance of scale in 0 0 0 0 0 1
practice
Total score (range: 7 10.5 11 12 13 14
0–18)
Weighted scorea 11 12.3 13 14.3 16.5 19
(range: 0–20)
Quality of psychometric L M M M VG VG
evidence (based on
weighted scores)
and the PSI. The overall evidence is conflict- tion, increased ICU LOS, and the development of de-
ing. Fifteen studies of moderate quality found lirium.29,183,220,286–293 These findings had not been con-
that objective sedation monitors based on ei- sistently reported, however.197,222,285,294–297
ther AEP or processed EEG signals, including
BIS, NI, SE, and PSI, may be useful adjuncts We reviewed 13 studies of 1,551 ICU patients compar-
to subjective sedation assessments in criti- ing clinical outcomes in patients sedated with either benzodi-
cally ill patients.244,248,258,266,267,271–273,276,278–283 azepines (midazolam or lorazepam) or nonbenzodiazepines
However, most of these studies reported that (propofol or dexmedetomidine) and found no consistent dif-
electromyographic signals negatively af- ferences in ICU LOS.183,197,220,222,285,286,292–298 However, our
fected the correlation between the objective meta-analysis of six trials ranked as moderate to high quality
measure in question and sedation scores. Five suggested that sedation with benzodiazepines may increase
additional studies of moderate quality found ICU LOS by approximately 0.5 days compared with nonben-
no benefit in using objective monitors over zodiazepine sedation (p = 0.04) (Fig. 1).183,197,220,222,292,295–297
subjective scoring systems to assess depth Limited data suggested that mechanical ventilation is pro-
of sedation.268–270,277,284 In most studies, ob- longed with benzodiazepine-based sedation.183,220,292,298
jective monitors distinguished only between There was no apparent difference in mortality with benzo-
deep and light levels of sedation, but their diazepine vs. nonbenzodiazepine sedation.220,222,285,295 Six
values correlated poorly with specific seda- trials evaluated the influence of benzodiazepine-based seda-
tion scores and were negatively influenced tion on the cost of ICU care;194,222,286,294,299,300 only one study
by electromyographic signal artifact. Several found that benzodiazepine-based sedation (i.e., midazolam
studies demonstrated that continuous EEG infusion) was associated with higher ICU costs than sedation
monitoring is useful for detecting noncon- with dexmedetomidine.300
vulsive seizure activity in ICU patients either When we compared outcome studies in ICU patients
with known seizure activity or who are at risk sedated with propofol vs. either midazolam or lorazepam,
for seizures (e.g., traumatic brain injury, intra- we found several studies demonstrating that propofol use
cerebral hemorrhage, cerebral vascular acci- may be associated with a shorter duration of mechanical
dents, patients with an unexplained depressed ventilation, but this effect varied across patient popula-
level of consciousness).275,281 Continuous tions,183,197,291,292,294–297 and did not necessarily translate into
EEG monitoring may also be useful in titrat- a shorter ICU LOS. There was no apparent difference in the
ing electrosuppressive medications to achieve incidence of self-extubation with propofol vs. benzodiaz-
burst suppression in critically ill patients with epine sedation.183 A separate systematic review evaluated 16
increased intracranial pressure.275,281 randomized, controlled trials comparing clinical outcomes
3. Choice of Sedative in ICU patients receiving either propofol or another seda-
Question: Should nonbenzodiazepine-based sedation, tive agent.291 When this meta-analysis was restricted to a
instead of sedation with benzodiazepines, be used in comparison of propofol and midazolam, there was no dif-
mechanically ventilated adult ICU patients? (action- ference in mortality, a slight reduction in the duration of me-
able) chanical ventilation with propofol, but no difference in ICU
Answer: We suggest that sedation strategies using LOS. The relationship between using either propofol or ben-
nonbenzodiazepine sedatives (either propofol or dex- zodiazepines for sedation and the development of delirium
medetomidine) may be preferred over sedation with is unclear. Only two relevant studies have been published
benzodiazepines (either midazolam or lorazepam) to comparing the incidence of delirium in ICU patients receiv-
improve clinical outcomes in mechanically ventilated ing propofol vs. benzodiazepines for sedation.285, 286 In both
adult ICU patients (+2B). studies, patients were randomized to receive propofol, mid-
Rationale: In general, the choice of sedative agent used azolam, or dexmedetomidine for sedation, and the incidence
in ICU patients should be driven by: 1) specific indica- of delirium was similar in patients receiving either propofol
tions and sedation goals for each patient; 2) the clinical or midazolam, but the quality of evidence was low.
pharmacology of the drug in a particular patient, in- We reviewed five studies comparing outcomes in
cluding its onset and offset of effect and its side effect ICU patients receiving either dexmedetomidine or a ben-
profile; and 3) the overall costs associated with using zodiazepine (either midazolam or lorazepam) for seda-
a particular sedative. Outcomes studies of the effects tion.220,222,285,286,293 Three of the four studies evaluating dura-
of sedative agents in ICU patients typically compare tion of mechanical ventilation showed no difference between
a benzodiazepine (either midazolam or lorazepam) to these groups.222,285,286 However, the largest study did demon-
a nonbenzodiazepine (either propofol or dexmedeto- strate a significant reduction in the time to liberation from
midine) for sedation. At the time of our literature re- mechanical ventilation with dexmedetomidine (3.7 days)
view, only two low-quality studies had been published compared with midazolam (5.6 days).220 Dexmedetomidine
comparing clinical outcomes in ICU patients receiving was not associated with a lower incidence of self-extubation
propofol vs. dexmedetomidine for sedation.285,286 No compared with benzodiazepines.222 Four of the five studies
studies have compared clinical outcomes in ICU pa- showed no difference in ICU LOS.220,222,285,286 Five stud-
tients sedated with either ketamine or other sedative ies, including a subgroup analysis from the Maximizing
agents. Several studies we reviewed suggested that Efficacy of Targeted Sedation and Reducing Neurological
the sustained use of benzodiazepine-based sedative Dysfunction trial, evaluated the development of delirium in
regimens is associated with adverse clinical outcomes, patients receiving either dexmedetomidine or a benzodiaz-
such as prolonged dependence on mechanical ventila- epine for sedation.220,222,285,286,298 Delirium was reported in
Mean
Benzodiazepine Non-Benzodiazepine Difference
IV, Random, Mean Difference IV,
Study or Subgroup Mean SD Total Mean SD Total Weight 95% Cl Random, 95% Cl
Hall 2001-72+, M/P, 9.14 3.99 10 8.46 4.83 4 1.0% 0.68
SD [–4.66, 6.02]
Hall 2001-24-72, M/P, 6.31 5.94 17 6.59 8.34 21 1.4% –0.28
SD [–4.83, 4.27]
Pandharipande 2007, 9 6.66 51 7.5 10.36 52 2.5% 1.50
L/D, IQR [–1.86, 4.86]
Carson 2006, L/P, IQR 10.4 7.47 64 8.3 7.4 68 4.2% 2.10
[–0.44, 4.64]
Hall 2001-24, M/P, SD 2.48 1.99 26 2.95 3.9 21 7.8% –0.47
[–2.31, 1.37]
Riker 2009, M/D, SD, 7.6 5.35 122 5.9 5.18 244 17.5% 1.70
median [0.55, 2.85]
Searle 1997, M/P, SD 3.9 1.7 20 3.7 1.7 21 20.5% 0.20
[–0.84, 1.24]
Huey-Ling 2008, M/P, 3.1 1.12 28 2.8 1.13 32 45.1% 0.30
-4 -2 0 2 4
SD [–0.27, 0.87]
Favors Favors
0.57 benzodiazepine non-benzodiazepine
Total (95% Cl) 338 463 100.0% [0.03, 1.10]
Heterogeneity: Tau2 = 0.08; Chi2 = 8.03, df = 7 (p = 0.33), I2 = 13%
Test for overall effect Z = 2.08 (p = 0.04)
Figure 1. ICU length of stay meta-analysis of high and moderate-quality studies comparing benzodiazepine to nonbenzodiazepine sedation. CI
= confidence interval; IQR = interquartile range. L/D = lorazepam vs. dexmedetomidine; L/P = lorazepam vs. propofol; M/P = midazolam vs.
propofol; M/D = midazolam vs. dexmedetomidine; SD = standard deviation.
terms of frequency of occurrence, prevalence, and delirium- zodiazepines pose higher risks than dexmedetomidine.220
free days. Three studies favored dexmedetomidine,286,288,300 Additional recommendations to prevent or treat delirium
although only one was of high quality.220 The subgroup anal- can be found in the Delirium section of these guidelines.
ysis trial favored dexmedetomidine over lorazepam in septic Dexmedetomidine may offer an advantage in ICU resource
patients only.298 One trial showed no relationship between consumption compared to midazolam infusions in health
benzodiazepine use and delirium.222 One very low-quality care institutions that are efficient in transferring patients
trial suggested a higher rate of delirium with dexmedetomi- out of the ICU.300 Despite the apparent advantages in using
dine, but suffered from serious methodological flaws includ- either propofol or dexmedetomidine over benzodiazepines
ing imprecision in the measurement of delirium.285 for ICU sedation, benzodiazepines remain important for
The results of two high-quality, randomized, double- managing agitation in ICU patients, especially for treating
blind, comparative trials of dexmedetomidine vs. either anxiety, seizures, and alcohol or benzodiazepine withdrawal.
midazolam or propofol for ICU sedation were published Benzodiazepines are also important when deep sedation,
after the guideline task force had completed its voting and amnesia, or combination therapy to reduce the use of other
developed its recommendations.301 The relevant outcomes sedative agents is required.166,302
in both studies included duration of mechanical ventilation,
and ICU and hospital LOS. Except for a longer duration of Delirium
mechanical ventilation with midazolam use, no differences
between groups were seen. These results are consistent with Epidemiology of Delirium in ICU Patients. Delirium is a
both our analysis of previously published data and subse- syndrome characterized by the acute onset of cerebral dys-
quent recommendation for benzodiazepine-based vs. non- function with a change or fluctuation in baseline mental
benzodiazepine-based sedation. status, inattention, and either disorganized thinking or an
In summary, the current literature supports modest altered level of consciousness.303–309 The cardinal features
differences in outcomes with benzodiazepine-based vs. of delirium are: 1) a disturbed level of consciousness (i.e.,
nonbenzodiazepine-based sedation. Our meta-analysis of a reduced clarity of awareness of the environment), with a
moderate to high-quality trials indicates that benzodiazepine reduced ability to focus, sustain, or shift attention; and 2)
sedation is associated with an increased ICU LOS. Moderate either a change in cognition (i.e., memory deficit, disori-
to high-quality data favor using propofol over lorazepam183 entation, language disturbance), or the development of a
and dexmedetomidine over midazolam220 to limit the dura- perceptual disturbance (i.e., hallucinations, delusions).310 A
tion of mechanical ventilation. The clinical significance of common misconception is that delirious patients are either
the comparative deliriogenic effects of benzodiazepines re- hallucinating or delusional, but neither of these symptoms is
mains uncertain, with one high-quality trial indicating ben- required to make the diagnosis. Other symptoms commonly
associated with delirium include sleep disturbances, abnor- ics in this patient population are similarly sparse. A recent
mal psychomotor activity, and emotional disturbances (i.e., Cochrane Review on using antipsychotics for the treatment
fear, anxiety, anger, depression, apathy, euphoria). Patients of delirium did not address the issue of antipsychotic use
with delirium may be agitated (hyperactive delirium), calm in ICU patients.340 Robust data on haloperidol in non-ICU
or lethargic (hypoactive delirium), or may fluctuate between patients that could potentially be applied to the ICU patient
the two subtypes. Hyperactive delirium is more often asso- population are lacking. Further research is needed to deter-
ciated with hallucinations and delusions, while hypoactive mine the safety and efficacy of using antipsychotics in gen-
delirium is more often characterized by confusion and seda- eral, including haloperidol, to treat delirium in ICU patients.
tion, and is often misdiagnosed in ICU patients.
Delirium in critically ill patients is now recognized as Delirium due to Drug and/or Alcohol Withdrawal. During
a major public health problem, affecting up to 80% of me- their ICU stay, critically ill patients may develop a subcate-
chanically ventilated adult ICU patients, and costing $4 to gory of delirium related to either drug or alcohol withdrawal,
$16 billion annually in the United States alone.311–314 Over which usually manifests as a hyperactive type of delirium.
the past decade, the study of delirium in ICU patients has Withdrawal symptoms may result from abrupt discontinua-
expanded significantly.315–319 But the underlying pathophys- tion of: 1) illicit or prescription drugs that patients were tak-
iology of delirium in critically ill patients remains poorly ing chronically; 2) sedatives or opioids administered as part
understood.320–322 of routine ICU care; or 3) chronic ethanol use. An exhaustive
review of the pathophysiology, diagnosis, and treatment of
Impact of Delirium on ICU Patient Outcomes. Delirium, as drug and alcohol withdrawal is beyond the scope of these
a manifestation of acute brain dysfunction, is an important guidelines. Clinicians are referred to other clinical practice
independent predictor of negative clinical outcomes in ICU guidelines for more detail.341–343
patients, including increased mortality, hospital LOS, cost Patients with long-term exposure to high-dose opi-
of care, and long-term cognitive impairment consistent with ates or sedatives may develop physiologic dependence, and
a dementia-like state.313,320–324 ICU team practices affect abrupt discontinuation may cause drug withdrawal symp-
the incidence of delirium and its consequences.220,222,325–329 toms.344 Signs and symptoms of acute opiate withdrawal in-
Critical care professionals strive to understand which as- clude sweating, piloerection, mydriasis, lacrimation, rhinor-
pects of delirium are predictable, preventable, detectable, rhea, vomiting, diarrhea, abdominal cramping, tachycardia,
and treatable. hypertension, fever, tachypnea, yawning, restlessness, irri-
tability, myalgias, increased sensitivity to pain, and anxiety.
Preventing, Detecting, and Treating Delirium in ICU The onset of symptoms can occur < 12 hrs following discon-
Patients. Delirium may be a disease-induced syndrome (e.g., tinuation of opioids, or be precipitated by either the adminis-
organ dysfunction in severe sepsis), for which timely man- tration of the opioid antagonist, naloxone, or mixed agonist/
agement of the cause or causes is essential in order to reduce antagonists such as nalbuphine.345,346 Prolonged benzodi-
the incidence, severity, and duration of delirium. Iatrogenic azepine use in ICU patients may lead to withdrawal symp-
(e.g., exposure to sedative and opioid medications) or envi- toms when the drug is abruptly discontinued, manifesting as
ronmental (e.g., prolonged physical restraints or immobiliza- anxiety, agitation, tremors, headaches, sweating, insomnia,
tion) factors may also contribute to delirium in ICU patients. nausea, vomiting, myoclonus, muscle cramps, hyperactive
ICU patients should be evaluated for identifiable and avoid- delirium, and occasionally seizures.344 Reversing the seda-
able risk factors, and therapeutic interventions should be as- tive effects of benzodiazepines following long-term expo-
sessed in terms of their likelihood of either causing or exac- sure with the benzodiazepine receptor antagonist flumazenil
erbating delirium in individual patients. Delirium prevention may induce symptoms of benzodiazepine withdrawal.347,348
strategies can be categorized as nonpharmacologic (e.g., Adult ICU patients receiving dexmedetomidine infusions
early mobilization), pharmacologic, and combined pharma- for up to 7 days have developed withdrawal symptoms, most
cologic/nonpharmacologic approaches. Monitoring critically commonly nausea, vomiting, and agitation, within 24–48
ill patients for delirium with valid and reliable delirium as- hrs of discontinuing dexmedetomidine.349 In the largest
sessment tools enables clinicians to potentially detect and study to date looking prospectively at the effects of seda-
treat delirium sooner, and possibly improve outcomes. tion of ICU patients with dexmedetomidine vs. midazolam,
Patients are frequently given various medications to the incidence of withdrawal following discontinuation of
reduce the severity and duration of delirium once it has oc- dexmedetomidine was 4.9% vs. 8.2% in midazolam-treated
curred. Although no double-blind, randomized, placebo- patients (p = 0.25).220 Signs and symptoms of opioid and
controlled trials which are adequately powered have estab- sedative withdrawal in critically ill patients may be over-
lished the efficacy or safety of any antipsychotic agent in looked or attributed to other causes, such as alcohol or illicit
the management of delirium in ICU patients, administration drug withdrawal.
of antipsychotic medications is endorsed by various inter- In the past decade, little was published on the patho-
national guidelines,330–339 and most critical care specialists physiology and incidence of drug withdrawal from opioids
use these medications to treat delirious patients.164 In the and sedative agents administered to adult ICU patients. Most
previous version of these guidelines, the recommended use studies are retrospective and include patients who have re-
of haloperidol for the treatment of delirium was a Level C ceived a variety of sedative and analgesic agents, making it
recommendation based only on a case series. These data did difficult to determine specific incidences and risk factors for
not meet the evidence standard for this version of the guide- drug withdrawal in these patients.344,350 One small prospec-
lines. No recent prospective trials have verified the safety tive study assessed adult ICU patients for signs and symp-
and efficacy of haloperidol for the treatment of delirium in toms of withdrawal following discontinuation of sufentanil
adult ICU patients. Data on the use of other antipsychot- infusions used concurrently with either midazolam or propo-
fol infusions.351 Patients in the sufentanil/midazolam group 4), 30 days (n = 1), 3 months (n = 1), 6 months (n =
were sedated for 7.7 days vs. 3.5 days for the sufentanil/ 3), and 12 months (n = 1).318,319,321,322,359–365 All studies
propofol group. Withdrawal symptoms occurred more fre- classified delirium as present on one or more ICU days;
quently in the midazolam group (35% vs. 28% with propo- three studies also examined the relationship between
fol). Although specific recommendations are lacking for the delirium duration and mortality.320,321,366 Delirium was
prophylaxis or treatment of opioid or sedative withdrawal an independent predictor of mortality in 11 of 15 stud-
in ICU patients, opioids and/or sedatives administered for ies, including the three studies with a high quality of
prolonged periods (i.e., days) should be weaned over several evidence.320,321,366 Duration of delirium (after adjust-
days in order to reduce the risk of drug withdrawal. ing for coma and in some cases psychoactive medica-
Ethanol (ETOH) dependence is present in 15%–20% tion exposure) was significantly associated with 6- and
of all hospitalized patients.352 Between 8% and 31% of 12-month mortality rates. In two cohort studies, dura-
hospitalized patients with ETOH dependence, especially tion of delirium consistently portended a 10% increased
surgical and trauma patients, will go on to develop Alcohol risk of death per day (after adjusting for covariates and
Withdrawal Syndrome (AWS) during their hospital stay, appropriately treating delirium as a time-dependent
with signs and symptoms of neurologic and autonomic covariate).320,321
dysfunction.353–355 Symptoms of AWS range from mild to Nine prospective cohort studies examined the rela-
life-threatening.356 Up to 15% of hospitalized patients with tionship between one or more days of delirium in the
AWS experience generalized tonic-clonic seizures, and 5% ICU and ICU and/or hospital LOS, as well as duration
develop delirium tremens (DTs), a life-threatening combina- of mechanical ventilation.318,319,322,323,360,361,363,364,367
tion of central nervous system excitation (agitation, delirium, Delirium was an independent predictor of duration of
and seizures) and hyperadrenergic symptoms (hypertension, mechanical ventilation in four studies360,363,364,367 and
tachycardia, arrhythmias).357 ICU patients with severe AWS of ICU LOS in four studies.318,319,364,367 Both of these
may exhibit prolonged ventilator dependence and extended outcome variables are particularly at risk for immor-
ICU stays as a result of persistent delirium.353–355 tal time bias, which is introduced when the exposure
Prior ethanol dependence is often underestimated to a treatment or independent variable (in this case,
in ICU patients, making identification of patients at risk delirium) can change daily during the actual outcome
for AWS or DTs difficult. Screening tools for AWS or measurement (in this case, either duration of mechani-
DTs have not been fully validated in the critical care set- cal ventilation or ICU LOS).368 It is therefore important
ting. Differentiating between delirium due to alcohol that the predictive relationship between delirium and
withdrawal vs. other causes may be difficult. Symptom- hospital LOS was also strong in seven of nine stud-
oriented treatment of AWS symptoms with drug dosing as ies,318,319,322,323,361,364,367 including three high-quality
needed to specifically target agitation, psychosis, and au- studies that accounted for immortal time bias.318,322,368
tonomic hyperactivity decreases the severity and duration
Two prospective cohort studies examined the rela-
of AWS, and medication requirements in ICU patients.358
tionship between delirium in the ICU and subsequent
Benzodiazepines are considered the mainstay of alcohol
cognitive impairment. One study of moderate quality
withdrawal treatment, despite uncertainty about their ef-
described an association between the presence of de-
fectiveness and safety.320 To date, no published studies have
lirium on one or more ICU days and a higher incidence
compared the safety and efficacy of treating symptoms of
of cognitive dysfunction at hospital discharge.322 In a
severe AWS with dexmedetomidine vs. benzodiazepines.
recent prospective cohort study of moderate quality, in-
Diagnosis and management of delirium due to AWS in ICU
creasing duration of delirium in ICU patients was asso-
patients remains challenging. It is beyond the scope of these
ciated with significantly greater cognitive impairment
guidelines to describe the validity of alcohol withdrawal
in these patients at 3 and 12 months.324
measurement tools, of alcohol withdrawal prevention, or of
2. Detecting and Monitoring Delirium
its treatment in the critical care setting.
a. Question: Should ICU patients be monitored rou-
tinely for delirium with an objective bedside delir-
Delirium: Questions, Statements, and Recommendations.
ium instrument? (actionable)
1. Outcomes Associated With Delirium in ICU Patients
Answer: We recommend routine monitoring for de-
Question: What outcomes are associated with delirium
lirium in adult ICU patients (+1B).
in adult ICU patients? (descriptive)
Rationale: Delirium is common in both mechani-
Answer: Delirium is associated with increased mortal-
cally ventilated14,220,222,308,360,369,370 and nonmechan-
ity (A), prolonged ICU and hospital LOS (A), and de-
ically ventilated ICU patients.309,359,371–379 ICU per-
velopment of post-ICU cognitive impairment in adult
sonnel often underestimate the presence of delirium
ICU patients (B).
in patients because it frequently presents as hypo-
Rationale: Numerous prospective cohort studies have active rather than hyperactive delirium.372,380
demonstrated that patients who develop delirium are at Delirium can be detected in both intubated and
increased risk for adverse outcomes both in the ICU and nonintubated ICU patients using valid and reliable
after discharge. This risk is independent of preexisting tools. In most studies, delirium detection was im-
comorbidities, severity of illness, age, and other covari- proved when caregivers used a valid and reliable
ates that might be merely associative. Eleven prospec- delirium assessment tool,367 also allowing them
tive cohort studies examined the relationship between to reassure frightened and disoriented patients.381
delirium while in the ICU and mortality at various time Delirium monitoring rationale includes: 1) most in-
points: ICU discharge (n = 5), hospital discharge (n = formed patients at moderate to high risk want to be
monitored for delirium; 2) high-quality cohort data Since completing our review and analysis of the
relating delirium to critical outcomes shows high literature in 2010 on delirium monitoring tools,
delirium “miss rates” in the absence of monitoring; several additional studies have been published ana-
3) clinicians have successfully implemented ICU lyzing the sensitivity, specificity, and reliability of
delirium monitoring programs on a large-scale, us- delirium assessment tools in clinical practice.391–394
ing assessment tools recommended in these guide- A meta-analysis of five ICU delirium screening tools
lines; and 4) policy makers can adopt delirium found that the CAM-ICU and ICDSC were the most
assessment as part of routine, high-quality care in sensitive and specific tools for detecting delirium,
most ICUs.254,372,374,382,383 Based on moderate evi- consistent with our recommendation.392 A separate
dence, we issue a strong recommendation that ICU meta-analysis of studies comparing the CAM-ICU
patients at moderate to high risk for delirium (e.g., to the ICDSC also found a high degree of sensitivity
patients: with a baseline history of alcoholism, cog- and specificity for both tools.393 Additional studies
nitive impairment, or hypertension; with severe sep- are needed to assess the performance of delirium
sis or shock; on mechanical ventilation; or receiving monitoring tools in routine clinical practice across
parenteral sedative and opioid medications) should different types of ICU patients.391,394
be routinely monitored, at least once per nursing c. Question: Is implementation of routine delirium
shift, for the development of delirium using a valid monitoring feasible in clinical practice? (descriptive)
and reliable delirium assessment tool. Answer: Routine monitoring of delirium in adult
b. Question: Which instruments available for delirium ICU patients is feasible in clinical practice (B).
monitoring have the strongest evidence for validity
Rationale: Moderate-quality evidence suggests that
and reliability in ventilated and nonventilated medi-
routine monitoring of delirium is feasible in clinical
cal and surgical ICU patients? (descriptive)
practice. Numerous implementation studies includ-
Answer: The Confusion Assessment Method for the ing over 2,000 patients across multiple institutions
ICU (CAM-ICU) and the Intensive Care Delirium showed delirium monitoring compliance rates in
Screening Checklist (ICDSC) are the most valid and excess of 90%. Practicing ICU nurses and physi-
reliable delirium monitoring tools in adult ICU pa- cians demonstrated high inter-rater reliability with
tients (A). trained experts using several of the recommended
Rationale: Five delirium monitoring tools were delirium monitoring tools.254,372,374,382,383 Although
evaluated for use in ICU patients: Cognitive Test for studies show that implementation of delirium moni-
Delirium (CTD), CAM-ICU, Delirium Detection toring is feasible in the ICU, lack of physician buy-
Score (DDS), ICDSC, and Nursing Delirium in is a significant barrier.395 Successful strategies for
Screening Scale (Nu-DESC). Table 8 compares overcoming this hurdle requires a focus on human
their psychometric properties. Both the CAM- factors and changing ICU culture.316 A more recent
ICU308,359,371–374,384–387 and ICDSC309,371 demonstrate study of delirium monitoring implementation (pub-
very good psychometric properties (i.e., validity lished after evidence was graded for this topic), that
and reliability), and are explicitly designed for use included over 500 ICU patients (medical, surgical,
in ICU patients both on and off mechanical ventila- and cardiac) and over 600 ICU nurses over a 3-yr
tion. Translated into over 20 languages, these tools period, reinforces the conclusion that routine de-
are currently in use worldwide.315 The CAM-ICU lirium monitoring is feasible in clinical practice.394
and ICDSC have shown high inter-rater reliability 3. Delirium Risk Factors
when tested by ICU nurses and intensivists.308,309,373 a. Question: What baseline risk factors are associated
They both demonstrated high sensitivity and speci- with the development of delirium in the ICU? (de-
ficity when tested against the American Psychiatric scriptive)
Association’s criteria for delirium.319,359,379 Answer: Four baseline risk factors are positively
Predictive validation of the presence of delirium, and significantly associated with the development
as detected with the CAM-ICU or ICDSC, was as- of delirium in the ICU: preexisting dementia; his-
sociated with clinical outcomes such as increased tory of hypertension and/or alcoholism; and a high
ICU and hospital LOS318,319,322,323,360,361,363,364,367 severity of illness at admission (B).
and higher risk of mortality.318,319,321,322,359–365 Based
Rationale: The following baseline risk factors have
on our review of the literature, both the CAM-ICU
been reported as significant in two or more multi-
and ICDSC are valid, reliable, and feasible tools
variable analyses: preexisting dementia329,375,396;
to detect delirium in ICU patients.254,309 While the
history of baseline hypertension318,397; alcoholism,
CTD388–390 and Nu-DESC379 reached the minimum
defined as ingestion of two to three or more drinks
weighted psychometric score of 12 in our analysis,
daily318,396; and a high severity of illness at admis-
some psychometric properties remain to be tested
sion.318,328,329,398 Although age has been identified
for these tools, including inter-rater reliability in a
as one of the most significant risk factors for de-
nonresearch setting and clinical feasibility. Further
lirium outside the ICU, only two studies reported
psychometric testing of the DDS347 is needed in or-
it to be significant in ICU patients,328,398 while four
der to better assess its overall validity, reliability,
studies reported it as insignificant.318,375,396,399 More
and feasibility as a delirium monitoring tool in criti-
research is needed to confirm the relationship be-
cally ill patients.
tween age and the development of delirium in ICU
patients.
Table 8.
Psychometric Scores for Delirium Monitoring Tools
Delirium Monitoring Tools
Confusion Intensive
Assessment Care Delirium
Psychometric Criteria Method for the Screening Cognitive Test for Nursing Delirium Delirium
Scored ICU Checklist Delirium Screening Scale Detection Score
Item selection description 2 1 2 1 1
Content validation 1 0 2 0 0
Limitations presented 1 1 1 0 1
Interrater reliability 2 2 2 2 2
Interrater reliability tested 1 1 0 0 0
with nonresearch team
Interrater reliability tested if N/A N/A N/A N/A 0
interrater reliability is low
or inconsistent
Total number of participants 2 2 2 2 2
Criterion validation: 2 2 2 2 0
sensitivity
Criterion validation: 2 1 2 2 2
specificity
Predictive validation 2 2 0 1 0
Feasibility 1 0 0 0 0
Directives of use 1 1 1 1 1
Relevance of scale in 1 1 0 0 0
practice
Total score (range: 0–19 18/19 14/19 14/19 11/19 9/21
or 21)
Weighted scorea (range: 19.6 16.8 13.0 12.4 8.2
0–20)
Quality of psychometric VG VG M M VL
evidence (based on
weighted scores)
VG, very good; M = moderate; VL = very low; NA = not applicable.
a
Weighted score range (0–20): Very good psychometric properties (VG): 15–20; Good psychometric properties (M): 12–14.9; Some acceptable
psychometric properties, but remain to be replicated in other studies (Low): 10–11.9; Very few psychometric properties reported, or unacceptable
results (VL): < 10.
b. Question: Is coma a risk factor for the development c. Question: Which ICU treatment-related (acquired)
of delirium in the ICU? (descriptive) risk factors (i.e., opioids, benzodiazepines, propo-
Answer: Coma is an independent risk factor for fol, and dexmedetomidine) are associated with the
the development of delirium in ICU patients. development of delirium in adult ICU patients? (de-
Establishing a definitive relationship between scriptive)
various subtypes of coma (i.e., medication-related, Answer: Conflicting data surround the relationship
structural, neurological, medical) and delirium in between opioid use and the development of delir-
ICU patients will require further study (B). ium in adult ICU patients (B). Benzodiazepine use
Rationale: Several reports have shown coma to may be a risk factor for the development of delirium
be an independent risk factor for delirium in ICU in adult ICU patients (B). There are insufficient
patients.318,399 One study further classified coma data to determine the relationship between propofol
into three categories: medical coma (i.e., due to a use and the development of delirium in adult ICU
primary neurological condition), sedative-induced patients (C). In mechanically ventilated adult ICU
coma, and multifactorial coma (both medical and patients at risk for developing delirium, dexmedeto-
sedative-induced coma).318 In this study, sedative- midine infusions administered for sedation may be
induced coma and multifactorial coma were signifi- associated with a lower prevalence of delirium com-
cantly associated with the development of delirium, pared to benzodiazepine infusions administered (B).
but medical coma was not.318 Rationale: Study designs including opioids var-
ied greatly. Some reported individual medications
used,288,328,397,398 while others provided only the cologic regimen for maintaining sleep-wake cycles
medication class,363 and still others combined opi- in hospitalized patients following gastrointestinal
oids with sedatives or other analgesics.318,329,396 surgery, with questionable value and applicability to
Study results also varied considerably. Most stud- critical care practice.403 A more recent prospective,
ies reported either an increased risk of delirium with placebo-controlled, blinded, randomized study did
opioids or no association.288,318,328,329,363,396–398 One show benefit to administering low doses of halo-
study400 found that opioids reduced the risk of de- peridol prophylactic to elderly surgical ICU patients
lirium in burn patients. Only one high-quality study in order to prevent delirium.404 However, these pa-
explicitly addressed the association between propo- tients were not very ill, and most were not mechani-
fol and delirium risk in ICU patients, and found no cally ventilated. More study is needed to determine
significant relationship.328 Benzodiazepines were the safety and efficacy of using a pharmacologic
included in several delirium risk factor studies. As delirium prevention protocol in ICU patients.
with opioids, study designs varied greatly. Some c. Question: Should a combined nonpharmacologic
moderate-quality studies reported a strong relation- and pharmacologic delirium prevention protocol be
ship between benzodiazepine use and the develop- used in the ICU to reduce the incidence or duration
ment of delirium,288,328 while others found no sig- of delirium? (actionable)
nificant relationship.318,363,396–399 Two randomized Answer: We provide no recommendation for the
controlled trials comparing sedation with benzo- use of a combined nonpharmacologic and pharma-
diazepines vs. dexmedetomidine reported a lower cologic delirium prevention protocol in adult ICU
prevalence of delirium (~20%) in patients random- patients, as this has not been shown to reduce the
ized to receive dexmedetomidine.220,298 Although incidence of delirium in these patients (0, C).
these data do not prove that benzodiazepines are
Rationale: One before/after study evaluated the im-
causal or that dexmedetomidine is protective, this
pact of a multidisciplinary protocol for managing
literature suggests that benzodiazepines may be a
PAD in ICU patients. Patients managed with this
risk factor for the development of delirium in the
protocol had a reduced incidence of subsyndromal
ICU. Whether dexmedetomidine reduces the risk
delirium but not delirium, improved pain control,
of ICU patients developing delirium is now under
and a 15% reduction in their total ICU costs.327,405
study.
Subsyndromal delirium in ICU patients is defined
4. Prevention of Delirium
as patients who have less than four points on the
a. Question: Should a nonpharmacologic delirium
ICDSC; patients with subsyndromal delirium have
protocol be used in the ICU to reduce the incidence
worse clinical outcomes than those without de-
or duration of delirium? (actionable)
lirium.319 Further research is needed to determine
Answer: We recommend performing early mobili- whether a combined nonpharmacologic and phar-
zation of adult ICU patients whenever feasible to re- macologic protocol reduces the incidence or dura-
duce the incidence and duration of delirium (+1B). tion of full-blown delirium in ICU patients.
Rationale: Early mobilization was initially studied d. Question: Should haloperidol or atypical antipsy-
in the critical care setting as a nonpharmacologic in- chotics be used prophylactically to prevent delirium
tervention aiming to improve functional outcomes. in ICU patients? (actionable)
In the first multicenter randomized controlled trial Answer: We do not suggest that either haloperidol
of early mobility,326 and in a subsequent implemen- or atypical antipsychotics be administered to pre-
tation study,401 investigators also noted striking re- vent delirium in adult ICU patients (–2C).
ductions in the incidence of delirium, depth of seda-
Rationale: No high-quality studies with sufficient
tion, and hospital and ICU LOS, with an increase in
sample size or effect size demonstrate a benefit of
ventilator-free days. These studies suggest that early
administering prophylactic antipsychotics to the
and aggressive mobilization is unlikely to harm ICU
general ICU population. A recent moderate-quality
patients, but may reduce the incidence and duration
trial demonstrated that low-dose IV haloperidol pro-
of delirium, shorten ICU and hospital LOS, and
phylaxis may reduce the prevalence of delirium in
lower hospital costs. While more broadly targeted,
low acuity elderly postoperative patients who are
high-quality non-pharmacologic protocols have
admitted to the ICU.404 Whether these data can be
shown favorable results in non-ICU hospitalized
applied to a more diverse population of sicker ICU
patients,402 such multifaceted interventions have not
patients is uncertain. A well-designed, but under-
been adequately studied in the ICU setting.
powered, multicenter, randomized controlled trial
b. Question: Should a pharmacologic delirium preven-
of delirium prophylaxis with either haloperidol or
tion protocol be used in the ICU to reduce the inci-
ziprasidone vs. placebo did not show any benefit
dence or duration of delirium? (actionable)
with either treatment group as compared to pla-
Answer: We provide no recommendation for using cebo.370 One moderate-quality study suggested that
a pharmacologic delirium prevention protocol in a single dose of sublingual risperidone administered
adult ICU patients, as no compelling data demon- immediately postoperatively to cardiac surgery pa-
strate that this reduces the incidence or duration of tients reduced the incidence of delirium.406 Further
delirium in these patients (0, C). research is needed to better define the safety and
Rationale: One prospective, unblinded, random- efficacy of typical and atypical antipsychotics for
ized controlled trial assessed a nocturnal pharma- delirium prevention in ICU patients.
e. Question: Should dexmedetomidine be used pro- tients had more severe and longer delirium, with
phylactically to prevent delirium in ICU patients? a trend toward higher mortality. In another study
(actionable) (published after the evidence analysis for this rec-
Answer: We provide no recommendation for the use ommendation), perioperative rivastigmine was
of dexmedetomidine to prevent delirium in adult administered for delirium prophylaxis in patients
ICU patients, as there is no evidence regarding its undergoing elective cardiac surgery (n = 120, pa-
effectiveness in these patients (0, C). tients > 65 yr), and had no effect on the incidence of
postoperative delirium in these patients.410
Rationale: One cardiovascular ICU study (n = 306) d. Question: Should haloperidol and atypical antipsy-
addressed the issue of dexmedetomidine and delir- chotics be withheld in patients at high risk for tors-
ium prophylaxis in ICU patients.407 Delirium lasted ades de pointes? (actionable)
2 days in the dexmedetomidine group compared
with 5 days in the morphine group (p = 0.03), but Answer: We do not suggest using antipsychotics in
delirium prevalence was not significantly reduced patients at significant risk for torsades de pointes
(9% vs. 15%, respectively, p = 0.09). Until more (i.e., patients with baseline prolongation of QT in-
data become available, we provide no recommen- terval, patients receiving concomitant medications
known to prolong the QT interval, or patients with a
dation for delirium prophylaxis with dexmedeto-
history of this arrhythmia) (–2C).
midine, given the risks of treatment without clear
benefit. Rationale: Torsades de pointes is a dangerous com-
5. Treatment of Delirium plication associated with antipsychotic administra-
a. Question: Does treatment with haloperidol reduce tion. Original case reports warned of this arrhyth-
the duration of delirium in adult ICU patients? (de- mia in patients receiving IV haloperidol411,412 and
scriptive) its association with a prolonged QT interval.413,414
Although torsades has also been described without
Answer: There is no published evidence that treat-
QT prolongation.415,416 Torsades has also occurred
ment with haloperidol reduces the duration of de-
in patients receiving atypical antipsychotics, such
lirium in adult ICU patients (No Evidence).
as ziprasidone417 and risperidone,418 and recent re-
b. Question: Does treatment with atypical antipsychot-
ports have warned of drug interactions that could
ics reduce the duration of delirium in adult ICU pa-
heighten this risk.419 Although the quality of evi-
tients? (descriptive)
dence is low, the morbidity and mortality associated
Answer: Atypical antipsychotics may reduce the du- with this complication is high.
ration of delirium in adult ICU patients (C). e. Question: For mechanically ventilated, adult ICU
Rationale: In a single small prospective, random- patients with delirium who require continuous IV
ized, double-blind, placebo-controlled study (n infusions of sedative medications, is dexmedetomi-
= 36), ICU patients with delirium who received dine preferred over benzodiazepines to reduce the
quetiapine had a reduced duration of delirium.408 duration of delirium? (actionable)
Patients with delirium who were being treated with Answer: We suggest that in adult ICU patients with
haloperidol were randomized to additionally re- delirium unrelated to alcohol or benzodiazepine
ceive either quetiapine 50 mg or placebo every 12 withdrawal, continuous IV infusions of dexmedeto-
hrs. The quetiapine dose was increased by 50 mg if midine rather than benzodiazepine infusions be ad-
more than one dose of haloperidol was given in the ministered for sedation in order to reduce the dura-
previous 24 hrs. All patients were allowed to receive tion of delirium in these patients (+2B).
IV haloperidol 1–10 mg every 2 hrs as needed. The Rationale: Two randomized controlled trials com-
use of haloperidol was not significantly different be- paring sedation with benzodiazepines vs. dexme-
tween the groups. Comparable data are not available detomidine reported a significant daily reduction
for treatment with haloperidol alone. Sufficiently (~20%) in delirium prevalence in patients receiving
powered, carefully designed, multicenter, placebo- dexmedetomidine.220,370,420 These data are inconclu-
controlled trials are needed to address the hypothe- sive about whether benzodiazepines raised the risk
sis that antipsychotics are beneficial in the treatment of delirium, or dexmedetomidine reduced the risk,
of delirium in critically ill patients. and further investigations are needed to address
c. Question: Should treatment with cholinesterase in- this question. But data from these two clinical tri-
hibitors (rivastigmine) be used to reduce the dura- als (which included a high percentage of patients at
tion of delirium in ICU patients? (actionable) risk for delirium), coupled with delirium risk factor
Answer: We do not recommend administering riv- data from observational trials, suggest that benzodi-
astigmine to reduce the duration of delirium in ICU azepines may be a risk factor for the development
patients (–1B). of delirium in the ICU. These findings led to this
recommendation for using dexmedetomidine rather
Rationale: Rivastigmine, a cholinesterase inhibi-
than benzodiazepines for sedation in ICU patients
tor, may be useful in treating delirium in demented
with delirium not due either to benzodiazepine or
elderly patients. However, rivastigmine was com-
ethanol withdrawal. There are insufficient data to
pared to placebo in critically ill patients in an in-
make recommendations regarding the risks and ben-
vestigation stopped for futility and potential harm409
efits of using other non-benzodiazepine sedatives,
This multicenter trial was halted after 104 patients
such as propofol, to reduce the duration of delirium
were enrolled because the rivastigmine-treated pa-
in ICU patients.
Management of PAD Defining Depth of Sedation. Although there are obvious

benefits to minimizing sedation in critically ill patients, no
to Improve ICU Outcomes
clear consensus exists on how to define “light” vs. “deep”
sedation. The overarching objectives for the management
Use of Integrated PAD Protocols to Optimize ICU Patient
of pain, agitation, and delirium in ICU patients should be to
Care. Our ability to effectively manage PAD in critically ill
consistently focus on patient safety and comfort, while avoid-
patients enables us to develop potential management strate-
ing short- and long-term complications associated with either
gies that reduce costs, improve ICU outcomes, and allow pa-
excessive or inadequate treatment. Traditionally, the goals of
tients to participate in their own care.9–13,16–20 Yet the appli-
ICU analgesia and sedation have been to facilitate mechani-
cation of these guideline recommendations poses significant
cal ventilation, to prevent patient and caregiver injury, and to
challenges to critical care practitioners. A successful strategy
avoid the psychological and physiologic consequences of in-
is to implement an evidence-based, institutionally-specific,
adequate treatment of pain, anxiety, agitation, and delirium.
integrated PAD protocol, and to assess, treat and prevent
Avoiding complications of over-sedation, such as muscle
PAD, using an interdisciplinary team approach. Protocols
atrophy and weakness, pneumonia, ventilator dependency,
facilitate the transfer of evidence-based “best practices” to
thromboembolic disease, nerve compression, pressure sores,
the bedside, limit practice variation, and reduce treatment
and delirium, are also important.11,325,326,429 A more precise
delays.2,3 A protocolized approach can also significantly im-
definition of light vs. deep sedation is offered to guide the
prove patient outcomes and serve as a guide for quality as-
creation and implementation of sedation protocols that pro-
surance efforts.13,327,421,422
vide sufficient patient comfort without inducing coma.
In spite of these recognized advantages, widespread
Central to these guidelines are the principles that: 1)
adoption of integrated PAD protocols is lagging. Only 60%
pain, depth of sedation, and delirium should be frequently
of ICUs in the United States have implemented PAD proto-
monitored using valid and reliable assessment tools; 2) pa-
cols, and even when instituted, protocol adherence is low,
tients should receive adequate and preemptive treatment for
which negatively impacts patient outcomes.163,199 Despite
pain; 3) patients should receive sedation only if required; and
> 20 yr of emphasis on the importance of systematic pain
4) that sedatives should be titrated to allow patient respon-
assessment and management, data suggest that: 1) preemp-
siveness and awareness that is demonstrated by their ability
tive analgesia for painful procedures is used only 20% of the
to purposefully respond to commands (i.e., a combination
time in ICU patients; 2) pain and discomfort remain leading
of any three of the following actions upon request: open
sources of patient stress; and 3) at least 40% of ICU patients
eyes, maintain eye contact, squeeze hand, stick out tongue,
still report experiencing moderate to severe pain.2,60,73,423
and wiggle toes).15,16,326 This degree of responsiveness and
Medication-induced coma has long been thought of as a
awareness goes beyond patients being merely “sleepy but
“humane” therapeutic goal for many ICU patients. But this
arousable” and is essential for the evaluation of pain through
strategy leads to increased mortality, prolonged duration
patient self-report, for assessing patients’ readiness to wean
of ventilation and ICU LOS, and possibly long-term neu-
and extubate, for performing delirium assessments, and for
ropsychological dysfunction and functional decline of pa-
implementing early mobility efforts. It remains unclear as to
tients.75,238,287,318,424–426 In spite of the published benefits of
whether it’s better to titrate sedation to a goal that allows pa-
ICU sedation strategies that minimize the use of sedatives
tients to be consistently awake, cooperative, and calm, or to
and depth of sedation in patients, adoption of these sedation
provide deeper sedation with a daily awakening trial.16,430 In
practices is not widespread.
the final analysis, both strategies have been shown to reduce
ICU protocols that combine routine pain and sedation
the incidence of deep sedation and its associated risks.431
assessments, with pain management and sedation-minimizing
strategies (i.e., daily sedative interruption or protocols that
Outcomes: Questions, Statements, and Recommendations.
otherwise target light levels of sedation), along with de-
1. Sedation Strategies to Improve Clinical Outcomes
lirium monitoring and prevention, may be the best strategy
for avoiding the complications of over sedation. Protocols
can also facilitate communication between bedside nurses a. Question: Should a protocol that includes either
and other members of the ICU team, helping them to de- daily sedative interruption or a light target level of
fine appropriate pain and sedation management goals, and sedation be used in mechanically ventilated adult
to assess the effectiveness of treatment strategies for each ICU patients? (actionable)
individual patient.3,14,62,259, 427,428 Although the impact of rou- Answer: We recommend either daily sedation inter-
tine delirium monitoring on ICU outcomes has never been ruption or a light target level of sedation be routinely
rigorously evaluated, early recognition of delirium may used in mechanically ventilated adult ICU patients
nevertheless facilitate patient reassurance, help to identify (+1B).
reversible causative factors, and permit implementation of Rationale: Five unblinded randomized controlled
effective delirium treatments. Early detection and treatment trials involving 699 patients evaluated daily seda-
of delirium may in turn allow for a patient to be conscious, tion interruption.14–16,432,433 All but one432 were re-
yet cooperative enough to potentially participate in ventila- stricted to medical ICU patients; a single pilot trial
tor weaning trials and early mobilization efforts. However, targeted light sedation as the comparator.16 One
delirium can only be assessed in patients who are able to suf- low-quality trial suggested harm, but suffered from
ficiently interact and communicate with bedside clinicians. serious methodological issues.433 Data suggest daily
Optimal pain management and a light level of sedation are sedation interruption reduces the time that patients
essential for this to occur. spend on the ventilator (or increases ventilator-free
days in survivors) and ICU LOS.
An alternative strategy using protocols to maintain High-quality study data are scarce in support of
light sedation (without daily sedation interruption) using one opiate over another in ICU patients re-
was described in 11 unblinded studies involving ceiving analgesia-first sedation.127,134,407 Clinicians
3,730 patients. The data suggest this approach re- should rely on pharmacology, safety, and cost-
duces the amount of time that patients spend on the effectiveness when making opioid treatment deci-
ventilator (or increases ventilator-free days for sur- sions.440 Analgesics that are short-acting and easily
vivors).7–13,18,19,434 The effect of protocolization on titratable may offer an advantage by facilitating fre-
ICU LOS was inconsistent with little data suggest- quent neurologic evaluations.
ing any detrimental effect.7–13,17–19,327,434 Conflicting The benefits of analgesia-first approach must be
data in two studies were likely related to the simi- balanced by the potential for opiates to interfere
larity of control group sedation practices to those with respiratory drive, reduce gastric motility, and
offered by the intervention.18,19 Healthcare systems complicate the provision of enteral nutrition.134,441
that employ bedside care models with 1:1 nurse-to- Possible pain recurrence and withdrawal upon an-
patient ratios or institutions where sedation mini- algesic discontinuation should be anticipated.130
mization is a goal may not benefit.435 Data are in- Furthermore, 18% to 70% of patients treated with
sufficient to draw firm conclusions on the effect of analgesia-first strategies will require supplementa-
either daily sedation interruption or protocolization tion with other traditional sedative agents.436–439
to maintain a level of light sedation on ventilator-
Although data suggest potential additional benefits
associated pneumonia (VAP), delirium prevalence,
with analgesia-first sedation, the ultimate role of
patient comfort, or cost of ICU care.
this strategy remains unclear because one moderate-
In summary, daily sedation interruption is associ- quality study439 required a 1:1 nurse-to-patient ratio
ated with clinical benefit in medical ICU patients, and the availability of patient “sitters,” and no rig-
but the benefits remain uncertain in those who are orous published studies have specifically compared
alcohol-dependent or not admitted to a medical ICU analgesia-first sedation with conventional GABA-
service. Studies investigating the efficacy and safety based sedation strategies. Preliminary data suggest
of this strategy in surgical, trauma, neurologic, and that analgesia-first sedation strategies do not have a
neurosurgical patients are needed. Protocolized negative impact on long-term psychological func-
management strategies (e.g., hourly titration) to tion.442 These data should be confirmed and ex-
avoid deep sedation are also associated with clinical panded to explore the influence of analgesia-first
benefit, but it remains unclear whether combining sedation on outcomes such as delirium, self-extu-
sedation protocolization with daily sedative inter- bation, VAP, mortality, and cost of ICU care, and
ruption would lead to additional benefits.16 on long-term cognitive function. Although these
b. Question: Should analgesia-first sedation (i.e., anal- studies administered an opioid as the primary anal-
gosedation) or sedative-hypnotic-based sedation be gesic, future studies in critically ill patients should
used in mechanically ventilated ICU patients? (ac- evaluate a multimodal analgesic approach using a
tionable) combination of opioids and nonopioid analgesics.52
Answer: We suggest that analgesia-first sedation be c. Sleep promotion in ICU patients
used in mechanically ventilated adult ICU patients i. Question: Should nonpharmacologic inter-
(+2B). ventions be used to promote sleep in adult
Rationale: Providing analgesia-first sedation for ICU patients? (actionable)
many ICU patients is supported by the high fre- Answer: We recommend promoting sleep in
quency of pain and discomfort as primary causes adult ICU patients by optimizing patients’
of agitation and by reports implicating standard environments, using strategies to control light
hypnotic-based sedative regimens as having nega- and noise, clustering patient care activities,
tive clinical and quality-of-life outcomes. Four and decreasing stimuli at night to protect pa-
unblinded studies including 630 medical and sur- tients’ sleep cycles (+1C).
gical ICU patients examined an analgesia-first Rationale: Sleep deprivation is detrimental in
approach.436–439 Data from one moderate-quality humans, and sleep disruption is common in
study suggested that analgesia-first sedation is as- ICU patients.443,444 They have few complete
sociated with longer ventilator-free time during a sleep cycles, numerous awakenings due to
28-day period, and shorter ICU LOS.439 Otherwise, environmental disruptions (noise, light, and
no consistent advantages of analgesia-first sedation physical stimulation), and infrequent rapid-
over sedative-hypnotic-based sedation were found. eye-movement sleep.443,445–448 Sleep depri-
Optimal analgesia and sedation were achieved dur- vation impairs tissue repair and cellular im-
ing 97% of the time with either strategy.436,438 One mune function, and may affect the healing
trial did not demonstrate any harm from the inter- response.449 In critically ill patients, sleep
vention on rates of self-extubation or VAP, but the deprivation may contribute to the develop-
incidence of agitated delirium was higher in the ment of delirium450–454 and increased levels of
analgesia-first sedation group.439 Data on delirium, physiologic stress.455,456
self-extubation, VAP, mortality, or cost of ICU care Sleep science in the ICU has not advanced in
are insufficient to draw firm conclusions about the the past decade. Because few studies identify
influence of this intervention. pharmacologic effects of sedatives on sleep
in critically ill patients, we focused on non- Rationale: The bulk of data from 12 unblinded stud-
pharmacologic interventions to promote sleep ies involving 2,887 patients suggests that one or more
in the ICU. Two recently published stud- interventions, along with the protocol implementation
ies (n > 30, prospective cohort, before/after to provide patient comfort in the ICU, reduces the dura-
study design) demonstrated that implement- tion of mechanical ventilation (or increases ventilator-
ing quiet time on both day and night shifts free days for survivors).7–10,12,13,18,19,159–162 Interventions
and clustering patient care activities reduce to implement protocols had inconsistent impact on ICU
disturbances and promote both observed and LOS, with little data suggesting harm within the 11
perceived sleep in adult ICU patients.457,458 studies involving 2,707 patients.7–10,12,13,18,19,159,160,162
Another descriptive study further confirmed There was no evidence for harm with this intervention
that mechanically ventilated ICU patients when the incidence of self-extubation was examined.
do not have uninterrupted periods for sleep Lastly, data were insufficient to support a recommen-
to occur.459 From these findings, we hypoth- dation based on the time patients spent within their de-
esized that nurses should select time periods fined sedation goal or on patient or nurse satisfaction.
to promote sleep by avoiding routine ICU Data suggest that the primary benefit of using one or
care activities (such as the daily bath), turning more interventions (e.g., education, additional staff,
down the lights, and reducing ambient noise electronic reminders) is to limit time on mechanical
during these periods. In three studies suggest- ventilation, but the overall benefit is uncertain. Low
ing scheduled rest periods, the periods most risk and minimal cost are associated with implement-
likely to be uninterrupted in the ICU were 2–4 ing one or more strategies to improve the use of an in-
AM,458 12–5 AM,457 and around 3 AM.459 tegrated sedation protocol in the ICU.
Another study, using indirect evidence from
nursing home patients, suggested that the Tools for Facilitating the Application
amount of daytime light exposure may affect
a hospitalized elderly patient’s quality and
of These Recommendations
consolidation of sleep at night.460 These find- to Bedside Care
ings must be validated in an ICU patient popu-
lation. Further research is needed to support Closing the gap between the evidence highlighted in these
the positive effects of using eye patches or guidelines and ICU practice will be a significant challenge
ear plugs to limit the aversive effects of noise for ICU clinicians465,466 and is best accomplished using a
and light.461 High doses of sedative agents multifaceted, interdisciplinary approach.4,467 The recom-
and mechanical ventilation disrupt sleep pat- mendations supported by clinical practice guidelines should
terns in critically ill patients.459,462 There is no be adapted to local practice patterns and resource availabil-
evidence that light levels of sedation promote ity, and used as a template for institution-specific protocols
sleep in the ICU. and order sets. Successful implementation will require aug-
mentation with education, engagement of local thought lead-
ii. Question: Should specific modes of mechani-
cal ventilation be used to promote sleep in ers, point-of-use reminders, and caregiver-specific practice
ventilated ICU patients? (actionable) feedback, together with continuous protocol evaluation and
Answer: We provide no recommendation for modification.7–10,12,13,18,19,159–162,468 Incorporating electroni-

using specific modes of mechanical ventila- cally based guidelines into clinical decision-support tools
tion to promote sleep in adult ICU patients, as may facilitate bedside knowledge transfer and applica-
insufficient evidence exists for the efficacy of tion.465,466 To support this effort, we have developed a pocket
these interventions (0, No evidence). card summarizing these guideline recommendations (Fig. 2)
Rationale: Two small studies (n < 30) have and a template for a PAD care bundle (Fig. 3).469
demonstrated that modes of mechanical ven- Care bundles have facilitated translation of practice
tilation that reduce the risk of central apnea guidelines to the bedside to manage a number of complex
events may improve the quality of sleep in ICU problems, including VAP, catheter-associated blood-
adult ICU patients.463,464 Larger, well-designed stream infections, and sepsis.470,471 A care bundle includes
prospective clinical trials are needed to validate elements most likely to improve patient outcomes. Elements
these findings. should be: easy to implement, beneficial, supported by
2. Strategies to Facilitate Implementation of ICU sound scientific and clinical reasoning, and relevant across
Analgesia, Sedation, and Delirium Guidelines patient populations and healthcare systems.31 Adherence to
each bundle element should be measurable and linked to one
Question: Should an interdisciplinary educational and
or more specific patient outcomes. Quality assurance data
behavioral strategy be used to facilitate the implemen-
should facilitate caregiver feedback and allow rapid-cycle
tation of sedation protocols and guidelines in adult
improvement to further customize bundles. This PAD Care
ICUs? (actionable)
Bundle is based on systematically identifying and managing
Answer: We recommend using an interdisciplinary ICU PAD in an integrated fashion, and assessing the effective-
team approach that includes provider education, pre- ness of these strategies (Fig. 3).
printed and/or computerized protocols and order forms,
and quality ICU rounds checklists to facilitate the use
of PAD management guidelines or protocols in adult
ICUs (+1B).
Summary 3. Payen JF, Bosson JL, Chanques G, et al. DOLOREA

Investigators: Pain assessment is associated with de-
The goal of these guidelines is to define best practices for creased duration of mechanical ventilation in the inten-
optimizing the management of PAD in adult ICU patients. sive care unit: A post Hoc analysis of the DOLOREA
These guidelines were developed by performing a rigorous, study. Anesthesiology. 2009; 111:1308–16.
objective, transparent, and unbiased assessment of the rele- 4. Vasilevskis EE, Ely EW, Speroff T, et al. Reducing
vant published evidence based on the GRADE methodology. iatrogenic risks: ICU-acquired delirium and weak-
Statements and recommendations were developed by taking ness—Crossing the quality chasm. Chest. 2010;
into consideration not only the quality of the evidence but 138:1224–33.
also important clinical outcomes and the values and prefer- 5. Riker RR, Fraser GL. Altering intensive care seda-
ences of ICU stakeholders. We believe that these guidelines tion paradigms to improve patient outcomes. Crit
provide a practical roadmap for developing evidence-based, Care Clin. 2009; 25:527–38, viii.
best practice protocols for integrating the management of 6. Arnold HM, Hollands JM, Skrupky LP, et al.
PAD in critically ill patients. Optimizing sustained use of sedation in mechani-
cally ventilated patients: Focus on safety. Curr Drug
Saf. 2010; 5:6–12.
Acknowledgments 7. Arabi Y, Haddad S, Hawes R, et al. Changing seda-
tion practices in the intensive care unit—Protocol
Special thanks to Charles P. Kishman, Jr, MSLS, Information implementation, multifaceted multidisciplinary ap-
Services Librarian (University of Cincinnati, Cincinnati, proach and teamwork. Middle East J Anesthesiol.
OH), for his invaluable contributions to these guidelines. 2007; 19:429–47.
Mr. Kishman was instrumental in helping us to develop our 8. Arias-Rivera S, Sánchez-Sánchez Mdel M, Santos-
search strategies, creating and maintaining the large Web- Díaz R, et al. Effect of a nursing-implemented seda-
based guidelines database, and for creating and managing the tion protocol on weaning outcome. Crit Care Med.
guidelines bibliography. Additional thanks to Christopher 2008; 36:2054–60.
D. Stave, MLS (Lane Medical Library, Stanford University 9. Brattebø G, Hofoss D, Flaatten H, et al. Effect of a
School of Medicine, Stanford, CA); Psychometric experts scoring system and protocol for sedation on duration
David Streiner, PhD (University of Toronto, Department of patients’ need for ventilator support in a surgical
of Psychiatry, Toronto, Ontario, Canada; and McMaster intensive care unit. BMJ. 2002; 324:1386–9.
University, Department of Clinical Epidemiology and 10. Brook AD, Ahrens TS, Schaiff R, et al. Effect of a
Biostatistics, Hamilton, Ontario, Canada), Celeste Johnston, nursing-implemented sedation protocol on the dura-
RN, DEd (School of Nursing, McGill University, Montreal, tion of mechanical ventilation. Crit Care Med. 1999;
Quebec, Canada), and Carolyn Waltz, RN, PhD, FAAN 27:2609–15.
(School of Nursing, University of Maryland, Baltimore, 11. De Jonghe B, Bastuji-Garin S, Fangio P, et al.
MD); GRADE Working Group members Gordon H. Guyatt, Sedation algorithm in critically ill patients without
MD (Departments of Medicine and Clinical Epidemiology acute brain injury. Crit Care Med. 2005; 33:120–7.
and Biostatistics, McMaster University, Hamilton, ON, 12. Quenot JP, Ladoire S, Devoucoux F, et al. Effect of
Canada), Holger Schunemann, MD, PhD (Department a nurse-implemented sedation protocol on the inci-
of Clinical Epidemiology & Biostatistics, McMaster dence of ventilator-associated pneumonia. Crit Care
University Health Sciences Centre, Hamilton, ON, Canada), Med. 2007; 35:2031–6.
and Deborah Cook, MD (Department of Medicine, Clinical 13. Robinson BR, Mueller EW, Henson K, et al. An
Epidemiology & Biostatistics, McMaster University, analgesia-delirium-sedation protocol for critically ill
Hamilton, ON, Canada); Patricia Rohr, Medical Editor trauma patients reduces ventilator days and hospital
(Stanford University School of Medicine, Stanford, CA); Ina length of stay. J Trauma. 2008; 65:517–26.
Lee, PharmD, Neuro-ICU clinical pharmacist (University of 14. Girard TD, Kress JP, Fuchs BD, et al. Efficacy and
Washington/Harborview Medical Center, Seattle, WA); and safety of a paired sedation and ventilator weaning
to Kathy Ward and Laura Kolinski (Society of Critical Care protocol for mechanically ventilated patients in in-
Medicine, Mount Prospect, IL) for their technical assistance tensive care (Awakening and Breathing Controlled
with these guidelines. trial): A randomised controlled trial. Lancet. 2008;
371:126–34.
References 15. Kress JP, Pohlman AS, O’Connor MF, et al. Daily
interruption of sedative infusions in critically ill pa-
1. Jacobi J, Fraser GL, Coursin DB, et al. Task Force tients undergoing mechanical ventilation. N Engl J
of the American College of Critical Care Medicine Med. 2000; 342:1471–7.
(ACCM) of the Society of Critical Care Medicine 16. Mehta S, Burry L, Martinez-Motta JC, et al.
(SCCM), American Society of Health-System Canadian Critical Care Trials Group: A randomized
Pharmacists (ASHP), American College of Chest trial of daily awakening in critically ill patients man-
Physicians: Clinical practice guidelines for the sus- aged with a sedation protocol: A pilot trial. Crit Care
tained use of sedatives and analgesics in the critically Med. 2008; 36:2092–9.
ill adult. Crit Care Med. 2002; 30:119–41. 17. Adam C, Rosser D, Manji M. Impact of introducing
2. Chanques G, Jaber S, Barbotte E, et al. Impact of a sedation management guideline in intensive care.
systematic evaluation of pain and agitation in an in- Anaesthesia. 2006; 61:260–3.
tensive care unit. Crit Care Med. 2006; 34:1691–9.
A
• Agitation in critically ill patients may result from inadequately treated pain, anxiety, delirium, and/or ventilator dysynchrony.
• Detection and treatment of pain, agitation, and delirium should be reassessed often in these patients.
• Patients should be awake and able to purposely follow commands in order to participate in their care unless a clinical
indication for deeper sedation exists.
• For a comprehensive list of Guideline Statements, Recommendations and GRADES, see back of card.
Assess and
Treat Statements and Recommendations
• Pain assessment should be routinely performed in all lCU patients (1B).

• Self report is preferred over the use of behavioral pain scales to assess pain in ICU patients who are
able to communicate (B).
• The BPS and CPOT are the most valid and reliable behavioral pain scales for use in ICU patients who
cannot communicate (B).
• Vital signs should not be used alone to assess pain, but they may be used adjunctively for pain
assessments (2C).
• Preemptively treat chest tube removal with either analgesics and/or non-pharmacologic therapy (1C).
PAIN
• Suggest preemptively treating other types of procedural pain with analgesic and/or non-pharmacologic
therapy (2C).
• Use opioids as first line therapy for treatment of non-neuropathic pain (1C).
• Suggest using non-opioid analgesics in conjunction with opioids to reduce opioid requirements and
opioid-related side effects (2C).
• Use gabapentin or carbamazepine, in addition to intravenous opioids, for treatment of neuropathic pain
(1A).
• Use thoracic epidural for postoperative analgesia in abdominal aortic surgery patients (1B).
• Suggest thoracic epidural analgesia be used for patients with traumatic rib fractures (2B).
• Depth and quality of sedation should be routinely assessed in all lCU patients (1B).
• The RASS and SAS are the most valid and reliable scales for assessing quality and depth of sedation in
ICU patients (B).
• Suggest using objective measures of brain function to adjunctively monitor sedation in patients
AGITATION
receiving neuromuscular blocking agents (2B).

• Use EEG monitoring either to monitor non-convulsive seizure activity in ICU patients at risk for seizures,
or to titrate electrosuppressive medication to achieve burst suppression in ICU patients with elevated
intracranial pressure (1A).
• Target the lightest possible level of sedation and/or use daily sedative interruption (1B).
• Use sedation protocols and checklists to facilitate ICU sedation management (1B).
• Suggest using analgesia-first sedation for intubated and mechanically ventilated ICU patients (2B).
• Suggest using non-benzodiazepines for sedation (either propafol or dexmedetomidine) rather than
benzodiazepines (either midazolam or lorazepam) in mechanically ventilated adult ICU patients (2B).
• Delirium assessment should be routinely performed in all lCU patients (1B).
• The CAM-ICU and ICDSC delirium monitoring tools are the most valid and reliable scales to assess
delirium in ICU patients (A).
DELIRIUM
• Mobilize ICU patients early when feasible to reduce the incidence and duration of delirium, and to
improve functional outcomes (1B).
• Promote sleep in ICU patients by controlling light and noise, clustering patient care activities, and
decreasing stimuli at night (1C).
• Avoid using rivastigmine to reduce the duration of delirium in ICU patients (1B).
• Suggest avoiding the use of anti psychotics in patients who are at risk for torsades de pointes (2B).
• Suggest not using benzodiazepines in lCU patients with delirium unrelated to ETOH/benzodiazepine
withdrawal (2B).
Figure 2. A, Pocket card operationalizing the PAD guideline recommendations (front side) (continued).
18. Bucknall TK, Manias E, Presneill JJ. A randomized mental health after critical illness. Crit Care Med.
trial of protocol-directed sedation management for 2009; 37:2527–34.
mechanical ventilation in an Australian intensive 21. Griffiths RD, Jones C. Seven lessons from 20 years
care unit. Crit Care Med. 2008; 36:1444–50. of follow-up of intensive care unit survivors. Curr
19. Elliott R, McKinley S, Aitken LM, et al. The effect of Opin Crit Care. 2007; 13:508–13.
an algorithm-based sedation guideline on the duration 22. Milbrandt EB, Angus DC. Bench-to-bedside review:
of mechanical ventilation in an Australian intensive Critical illness-associated cognitive dysfunction—
care unit. Intensive Care Med. 2006; 32:1506–14. Mechanisms, markers, and emerging therapeutics.
20. Treggiari MM, Romand JA, Yanez ND, et al. Crit Care. 2006; 10:238.
Randomized trial of light versus deep sedation on
B
Summary of PAD Guidelines
1. lCU patients routinely experience pain at rest and with lCU care (B). Pain in cardiac surgery patients,
especially women, is poorly treated (B). Procedural pain is common in lCU patients (B).
2. Perform routine pain assessment in all patients (1B). In motor intact patients unable to self report, we
suggest using behavioral pain scales rather than vital signs to assess pain (2C). The BPS and CPOT
are the most valid and reliable behavioral pain scales (B). Vital signs should only be used as a cue for
ANALGESIA
PAIN AND
further pain assessment (2C).

3. For non-neuropathic pain, use intravenous opioids as first line analgesic therapy (1C); use non-
opioid analgesics to reduce opioid side effects (1C); and use either gabapentin or carbamazepine in
conjunction with intravenous opioids for neuropathic pain (1A).
4. Suggest preemptively treating procedural pain (2C), especially chest tube removal (1C).
5. Use thoracic epidural analgesia for abdominal aortic surgery (1B), and suggest also using for traumatic
rib fractures (2B). No evidence guides the use of lumbar epidural analgesia for abdominal aneurysm
surgery (OA), or thoracic epidural analgesia for either intrathoracic or nonvascular abdominal surgical
procedures (OB). No evidence guides the use of regional vs. systemic analgesia in medical lCU
patients (0).
1. Maintaining lighter levels of sedation in ICU patients is associated with improved clinical outcomes (B);
light levels of sedation should be maintained in these patients (1B).
AND SEDATION
2. The RASS and SAS scales are most valid and reliable instruments for assessing adequacy and depth of
sedation (B).
AGITATION
3. Use Brain Function monitors only as adjuncts to subjective sedation scales in unparalyzed patients
(1B), but suggest using brain function monitors to primarily monitor depth of sedation in patients
receiving neuromuscular blocking agents (2B).
4. Use EEG monitoring to monitor non-convulsive seizure activity in lCU patients at risk for seizures, and to
titrate burst suppression therapy in lCU patients with elevated intracranial pressure (1A).
5. Use either daily sedative interruption or titrate sedative medications to maintain light levels of sedation
(1B). Suggest using Analgesia-first sedation (2B). Suggest using non-benzodiazepines rather than
benzodiazepine infusions for sedation (2B). Use sedation protocols and daily checklists to integrate and
to facilitate management of pain, sedation, and delirium in ICU patients (1B).
1. Delirium is associated with increased mortality (A), prolonged lCU and hospital LOS (A), and post-lCU
cognitive impairment (B).
2. Delirium risk factors include: pre-existing dementia, HTN, history of alcoholism, and a high severity of
illness at baseline (B); coma (B); and benzodiazepine use (B). Mechanically ventilated lCU patients at
risk for delirium have a lower delirium prevalence when treated with dexmedetomidine rather than with
benzodiazepines (B).
3. Routinely monitor lCU patients for delirium (1B). The CAM-ICU and lCDSC are the most valid and
DELIRIUM
reliable instruments for this purpose (A).

4. Pursue early mobilization to reduce the incidence and duration of delirium (1B).
5. Suggest not using either haloperidol or atypical antipsychotics prophylactically to prevent delirium (2C).
6. Promote sleep in adult ICU patients by optimizing patients’ environments, using strategies to control
light and noise, to cluster patient care activities, and to decrease stimuli at night in order to protect
patients’ sleep cycles (1C).
7. Do not use rivastigmine to reduce the duration of delirium in lCU patients (1C).
8. Suggest withholding antipsychotics in patients with baseline QT prolongation, a history of Torsades de
Pointes, or in those receiving concomitant medications known to prolong the QT interval (2C).
9. When sedation is required in delirious lCU patients, suggest using dexmedetomidine rather than
benzodiazepine infusions for sedation in these patients, unless delirium is related to either alcohol or
benzodiazepine withdrawal (2B).
Figure 2 (continued). B, Pocket card summarizing specific pain, agitation, and delirium (PAD) guideline statements and recommendations (back
side). BPS = Behavioral Pain Scale; CPOT = Critical-Care Pain Observation Tool; RASS = Richmond Agitation and Sedation Scale; SAS =
Sedation-Agitation Scale; EEG = electroencephalography; CAM-ICU = Confusion Assessment Method for the ICU; ICDSC = ICU Delirium
Screening Checklist; ETOH = ethanol; LOS = length of stay; HTN = hypertension.
23. Larson MJ, Weaver LK, Hopkins RO. Cognitive matic stress disorder-related symptoms after inten-
sequelae in acute respiratory distress syndrome pa- sive care. Crit Care Med. 2001; 29:573–80.
tients with and without recall of the intensive care 25. Schelling G, Stoll C, Haller M, et al. Health-related
unit. J Int Neuropsychol Soc. 2007; 13:595–605. quality of life and posttraumatic stress disorder in
24. Jones C, Griffiths RD, Humphris G, et al. Memory, survivors of the acute respiratory distress syndrome.
delusions, and the development of acute posttrau- Crit Care Med. 1998; 26:651–9.
A
Pain Agitation Delirium
Assess pain ≥4x/shift & prn Assess agitation, sedation ≥4x/shift Assess delirium Q shift & prn
Preferred pain assessment tools: & prn Preferred delirium assessment
• Patient able to self-report Preferred sedation assessment tools: tools:
→NRS (0-10) • RASS (-5 to +4) or SAS (1 to 7) • CAM-lCU (+ or -)
• Unable to self-report →BPS • NMB → suggest using brain • lCDSC (0 to 8)
(3-12) or CPOT (0-8) function monitoring
Patient is in significant pain if Delirium present if:
ASSESS
NRS ≥4, BPS > 5, or CPOT ≥3 Depth of agitation, sedation defined • CAM-lCU is positive
as: • lCDSC ≥4
• agitated if RASS = +1 to +4, or
SAS = 5 to 7
• awake and calm if RASS = 0, or
SAS = 4
• lightly sedated if RASS = -1 to -2,
or SAS = 3
• deeply sedated if RASS = -3 to -5,
or SAS = 1 to 2
Treat pain within 30’ then Targeted sedation or DSI (Goal: • Treat pain as needed
reassess: patient purposely follows • Reorient patients;
• Non-pharmacologic commands without agitation): familiarize surroundings;
treatment–relaxation therapy RASS= -2–0, SAS = 3–4 use patient’s eyeglasses,
• Pharmacologic treatment: • If under sedated (RASS >0, hearing aids if needed
–– Non-neuropathic pain → SAS >4) assess/treat pain → • Pharmacologic treatment of
TREAT
IV opioids treat w/sedatives prn (non- delirium:

± non-opioid analgesics benzodiazepines preferred, –– Avoid benzodiazepines
–– Neuropathic pain unless ETOH or benzodiazepine unless ETOH or
→ gabapentin or withdrawal is suspected) benzodiazepine
carbamazepine, + IV • If over sedated (RASS <-2, SAS <3) withdrawal is suspected
opioids hold sedatives until at target, then –– Avoid rivastigmine
–– S/p AAA repair, rib restart at 50% of previous dose –– Avoid antipsychotics if
fractures → thoracic ↑ risk of Torsades de
epidural pointes
• Administer pre-procedural • Consider daily SBT, early mobility • Identify delirium risk
analgesia and/or non- and exercise when patients are factors: dementia,
pharmacologic interventions at goal sedation level, unless HTN, ETOH abuse,
(e.g., relaxation therapy) contraindicated high severity of illness,
• Treat pain first, then sedate • EEG monitoring if: coma, benzodiazepine
–– at risk for seizures administration
PREVENT
–– burst suppression therapy is • Avoid benzodiazepine

indicated for ↑ ICP use in those at ↑ risk for
delirium
• Mobilize and exercise
patients early
• Promote sleep (control
light, noise; cluster patient
care activities; decrease
nocturnal stimuli)
• Restart baseline psychiatric
meds, if indicated
Figure 3. A, ICU pain, agitation, and delirium (PAD) care bundle.469 B, ICU PAD care bundle metrics; NRS = Numeric Rating Scale; BPS =
Behavioral Pain Scale; CPOT = Critical-Care Pain Observation Tool; nonpharmacologic therapy = relaxation therapy, especially for chest tube
removal; IV = intravenous; AAA = abdominal aortic aneurysm; NMB = neuromuscular blockade; RASS = Richmond Agitation and Sedation
Scale; SAS = sedation-Agitation Scale; brain function monitoring = auditory evoked potentials (AEP), Bispectral Index (BIS), Narcotrend Index
(NI), Patient State Index (PSI), or State Entropy (SE); DSI = daily sedation interruption (also referred to as Spontaneous Awakening Trial [SAT]);
ETOH = ethanol; nonbenzodiazepines, propofol (use in intubated/mechanically ventilated patients), dexmedetomidine (use in either intubated or
nonintubated patients); SBT = spontaneous breathing trial; EEG = electroencephalography; ICP = intracranial pressure; CAM-ICU = Confusion
Assessment Method for the ICU; ICDSC = ICU Delirium Screening Checklist (continued).
B
Pain Agitation Delirium
• % of time patients are • % of time sedation assessments • % of time delirium
monitored for pain ≥4x/shift are performed ≥4x/shift assessments are
ASSESS
• Demonstrate local • Demonstrate local compliance and performed Q shift
compliance and implementation integrity over time • Demonstrate local
implementation integrity over in the use of ICU sedation scoring compliance and
time in the use of ICU pain systems implementation integrity
scoring systems over time in the use of ICU
delirium assessment tools
• % of time ICU patients are in • % of time patients are either • % of time delirium is
significant pain (i.e., NRS ≥4, optimally sedated or successfully present in ICU patients
BPS ≥6, or CPOT ≥3) achieve target sedation during (CAM-ICU is positive or
• % of time pain treatment DSI trials (i.e., RASS = -2–0, SAS ICDSC ≥ 4)
TREAT
is initiated within 30” of = 3–4) • % of time benzodiazepines

detecting significant pain • % of time ICU patients are under are administered to
sedated (RASS >0, SAS>4) patients with documented
• % of time ICU patients are either delirium (not due to
over sedated (non-therapeutic ETOH or benzodiazepine
coma, RASS <-2, SAS <3) or fail to withdrawal)
undergo DSI trials
• % of time patients • % failed attempts at SBTs due to • % of patients receiving
receive pre-procedural either over or under sedation daily physical therapy and
analgesia therapy and/ • % of patients undergoing EEG early mobility
PREVENT
or nonpharmacologic monitoring if: • % compliance with ICU

interventions –– at risk for seizures sleep promotion strategies
• % compliance with –– burst suppression therapy is • % compliance with
institutional-specific ICU pain indicated for ↑ ICP institutional-specific ICU
management protocols • % compliance with institutional- delirium prevention and
specific ICU sedation/agitation treatment protocols
management protocols
Figure 3 (continued). A, ICU pain, agitation, and delirium (PAD) care bundle.469 B, ICU PAD care bundle metrics; NRS = Numeric Rating Scale;
BPS = Behavioral Pain Scale; CPOT = Critical-Care Pain Observation Tool; nonpharmacologic therapy = relaxation therapy, especially for chest
tube removal; IV = intravenous; AAA = abdominal aortic aneurysm; NMB = neuromuscular blockade; RASS = Richmond Agitation and Sedation
Scale; SAS = sedation-Agitation Scale; brain function monitoring = auditory evoked potentials (AEP), Bispectral Index (BIS), Narcotrend Index
(NI), Patient State Index (PSI), or State Entropy (SE); DSI = daily sedation interruption (also referred to as Spontaneous Awakening Trial [SAT]);
ETOH = ethanol; nonbenzodiazepines, propofol (use in intubated/mechanically ventilated patients), dexmedetomidine (use in either intubated or
nonintubated patients); SBT = spontaneous breathing trial; EEG = electroencephalography; ICP = intracranial pressure; CAM-ICU = Confusion
Assessment Method for the ICU; ICDSC = ICU Delirium Screening Checklist.
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G uidance documents, in particular, evolve because of advances in technology, new

Editor: Bruce Hawkins

Published by the American Society of Health-System Pharmacists, 7272 Wisconsin Avenue,

Page Locator for Guidance Documents by Type and Title.................................... xiii

Drug Distribution and Control

0232 - Pharmacist’s Role in Drug Procurement, Distribution, Surveillance,

PREPARATION AND HANDLING

Education and Training

0913 - Pharmacy Student Experiences in Medically Underserved Areas...........................149

Formulary Management (Medication-Use Policy Development)

9601 - Standardization of Drug Medication Formulary Systems.......................................169

Government, Law, and Regulation

1003 - FDA Authority on Recalls........................................................................................199

Medication Therapy and Patient Care

ORGANIZATION AND DELIVERY OF SERVICES

Statements: Confidentiality of Patient Health Care Information............................................................263

SPECIFIC PRACTICE AREAS

*Pharmacist’s Role in Substance Abuse Prevention, Education, and Assistance.................309

DRUG PRODUCTS, LABELING, AND PACKAGING

0714 - Restricted Drug Distribution....................................................................................398

COMPENSATION AND REIMBURSEMENT

0112 - Professional Development as a Retention Tool........................................................449

ASHP Therapeutic Position Statements

ASHP Therapeutic Guidelines

Page Locator for Guidance Documents

Use of Dietary Supplements ........................................................................................................................328

Safe Use of Automated Dispensing Devices .................................................................................................61

ASHP Technical Assistance Bulletins

Author: Mark Siska, M.B.A./TM, B.S.Pharm.

*Review does not imply endorsement.

Natalie Dayneka, B.Sc.Pharm., ACPR, Cyndy A. Clegg, M.H.A.

Jody Jacobson Wedret, FASHP, FCSHP* Christopher J. Scott, Pharm.D.

*The ASHP Board of Directors voted in November 1997 to discon-

Development of Guidance Documents Therapeutic Guidelines—The development of these docu-

3. ASHP solicits multidisciplinary expert input on the Opportunities to Be a Part of Guidance

Mission Statement of the American Society

Vision Statement of the American Society

Automation and Information Technology

ASHP Statement on Bar-Code-Enabled Medication

Suggested Readings or Other Resources

ASHP Statement on Bar-Code Verification

Position In addition, for BCMA to function, a vast majority of doses

Background Initial estimates of the contribution of pharmacy dispens-

6. Ragan R, Bond J, Major K et al. Improved control of

ASHP Statement on the Pharmacist’s Role

ASHP Statement on the Pharmacist’s Role with

ASHP Statement on the Pharmacy Technician’s Role

Conclusion The following individuals and organizations are gratefully ac-

ASHP Statement on Use of Social Media

ASHP Guidelines on the Design of Database-Driven

Figure 1. Types of clinical decision support (CDS).

The alerts give all practice These alerts utilize a large

MedIA System & HL7 message

ASHP Guidelines on Pharmacy Planning for

Purpose and Scope CPOE and the Electronic Health Record

Medication Order Types

Oral solids Medical staff protocols that include medications

Medication Order Processes