Clozapine Guidelines V4

SH CP 114
Clozapine Guidelines
(including clozapine initiation both inpatient and community, long term
monitoring and treatment, actions following a red result and GP
reference guide)
Version: 4
Summary: The UK product licence of Clozapine (Clozaril®) allows for

initiation as an inpatient or outpatient with intensive
community support.
Keywords (minimum of 5): Clozapine, Clozaril®, initiation of clozapine, restarting

(To assist policy search engine) clozapine, blood tests, red results, smoking, clozapine GP
guide, treatment resistant schizophrenia, constipation
Target Audience: All Mental Health Practitioners involved in clozapine use.
Next Review Date: November 2021
Approved & Ratified by: Medicines Management Date of meeting:

Committee 21 March 2018
Chair approval 12 December 2018
Date issued: December 2018
Author: Juliet Wells, Principal Pharmacist (AMH and LD)
Sponsor: Dr. Karl Marlowe, Medical Director
SH CP 114 Clozapine Guideline

Version: 4
December 2018 1
Version Control
Change Record
Date Author Versi Page Reason for Change

on
September Rebecca 2 Policy Review
2016 Henry
March Rebecca 3 28 Insert Appendix 7, Guide to Interpretation of Clozapine
2017 Henry Plasma Levels. Add Norclozapine paragraph.
February Alex Weston 3 9 Added new information as point 4.16 about initiation of
2018 treatment in patients 60 years or older from Clozaril SPC
February Alex Weston 3 55 Removed “GP information leaflet” as formatting difficulties
2018 and incorrect advice. and problems reading due to font
colour. Appendix 10 covers the pertinent points.
February Alex Weston 3 All Formatting reviewed throughout
2018
February Alex Weston 3 8 Reviewed dose recommendations in line with Summary of
2018 Product Characteristics, Clozapine Handbook and Maudsley
Prescribing Guidelines. Referenced. Moved from
prescription initiation charts to section 4.6
February Alex Weston 3 Through Replaced Novartis with Mylan as new owner of Clozaril
2018 out brand
February Alex Weston 3 4,8 Updated appendix numbers in flow diagram and text
2018
March Alex Weston 3 37,38 Updated titration charts as per Maudsley guidelines as
2018 discussed with Vanessa Lawrence
March Alex Weston 3 Through Checked body of text to ensure appendix numbers still
2018 out correct
March Ed Horne 3 Through Added constipation poster as appendix 20
2018 out
April 2018 J Wells 4 Through Review of acceptance criteria, responsibilities, monitoring for
out community initiation patients and myocarditis risks and
appendix 16
May 2018 J Wells 4 S5.3 p36 Removed valproate (see MHRA drug safety alerts 2017 and
R Henry Appendix 18) and replaced with lamotrigine. Addition of HbA1c
9 throughout
Appendice Constipation advice/Porirura Protocol added to GP letter and
s 1, 5.0 & throughout
5.3
August J Wells 4 Appendix Review of GP letter. Addition of guidance of how to add to
2018 T Orchel 9 GP systems
R Ellenby
November J Wells 4 4.15 Addition of by secondary care to Annual Review (SHFT
2018 holds the whole economy)
20/2/19 Update author details on front cover.
10/5/19 A Weston 4 Review date reset Oct 2018 to Nov 2021
Reviewers/contributors
Name Position Version Reviewed &
Date
Medicines Management Committee Version 1, April 2014
Medicines Management Team Version 1, April 2014
Medicines Management Committee V2 July 2016
Medicines Management Committee V3 March 2018
Medicines Management Committee V3 May 2018
Medicines Management Committee V4 Nov 2018

Version: 4
December 2018 2
Contents
Page
Summary of the Initiation of Clozapine 4

1. Criteria for Acceptance 5
2. Responsibilities of the consultant 6
3. Responsibilities of the care coordinator 7
4. Treatment Programme 8
5. Restarting Clozapine following an unplanned discontinuation 10
Further reading 11
Appendices
1 Potential side effects 12

2 Clozapine initiation checklist 13
3 Baseline physical health monitoring 15
4 Clozapine physical monitoring sheet 16
5 Clozapine in the community contact monitoring sheet 20
6 Guidelines for the management of a red clozapine result 23
7 Guide to Interpretation of Clozapine Plasma Levels. 28
8 Smoking Cessation – effect on clozapine 30
9 Suggested GP letter 32
10 Shared care guideline: information for the GP 34
11 Clozapine initiation prescriptions 39
12 Clozapine outpatient prescriptions 41
13 Blood monitoring form 42
14 On-going physical health monitoring parameters 43
15 Clozapine clinic monitoring form 44
16 Clozapine cardiac induced side – effects flow chart 45
17 Information check list for patients on clozapine 46
18 Re-challenge to Clozapine following a red result 48
19 Clozapine brand change procedure 52
20 Clozapine side effect rating scale (GASS-C) 53
21 Constipation poster 54

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December 2018 3
SUMMARYOF THE INITIATION OF CLOZAPINE (for both in-patients and out-patients)
The patient meets the Acceptance Criteria for the initiation


Give patient/carer appropriate information.
Obtain valid consent and record in patient’s records, or obtain second opinion.
Obtain new T2 or T3 if needed

Review current medication and smoking status for concurrent side-effects and drug interactions and medical conditions to
ensure that it is appropriate to start clozapine resulting in which team initiates clozapine.
.

Take initial blood tests (FBC, Troponin I or T and CRP). Complete baseline physical health monitoring (appendix 3).
Complete patient registration form and fax it to the Clozaril Patient Monitoring Service (CPMS) or Denzapine (DMS).
Inform clozapine clinic, pharmacy department, GP, AMHT and the ward team as appropriate and complete risk assessment.
Write relevant clozapine-related care plans to include monitoring requirements and specific information regarding relevant
medical conditions.

Green blood result – clozapine can be started
If not seek advice from the CPMS/DMS and SHFT Pharmacist

Complete initiation forms and baseline monitoring (see appendix 2 and 3 ), send to AMHT with referral if appropriate.

(Start within 10 days of initial blood test)
Prescribe dose at 12.5mg daily, at night for inpatients and in the morning for community patients, and then follow the titration
chart (appendix 11).
Avoid increasing the dose when there is no medical cover (e.g. at weekends and bank holidays) Obtain supply of clozapine
from the pharmacy. Inform the nursing team of the titration schedule.

Day 1
Observations –see appendix 4 and 5 (pulse, temp, respiration and lying down and standing BP) three times, at baseline and
ideally at 2 and 6 hours post dose and for community patients, four contacts in all (the other contact may be by phone)

Day 2
Observations before the morning dose is given, ideally 2 and 6 hours post dose and for community patients an additional
phone contact.

Day 3 to 7
Repeat Blood test (weekly thereafter in line with local procedures) Include Trop T or I and CRP for the first month.
Observations twice daily, before the morning dose and 6 hrs post dose and 3 contacts in all (1 phone contact)

Day 8 to 14
Observations once daily and community patients three contacts in all (2 phone contacts)

Day 14 Onwards
Daily observations to continue until there are no unacceptable side effects and the dose is stable

Stable dose
Inform clozapine clinic and CMHT if appropriate, and CPMS when changing teams or consultant. For ongoing monitoring see
appendix 14 Full physical health check at 3 months, 6 months and then annually including RiO physical health questionnaire.
Ensure GP is aware of ongoing clozapine prescription, refer to GP brief reference guide. Update care plan. Enter all results
and communications in the electronic patient record.

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Guidelines for Initiating Patients on Clozapine
(including reinstating clozapine after non-compliance)
The UK product licence of Clozapine (Clozaril®) allows for initiation as an inpatient or outpatient with
intensive community support.
1. Criteria for Acceptance
1.1 The patient is willing and able to accept the required level of physical health monitoring and attend
necessary appointments either as an inpatient or outpatient, or enable staff contact e.g. through
home visits to enable monitoring
1.2 The patient must accept regular blood tests.
1.3 The patient fulfils the standard licensed product criteria for receiving clozapine. The use of
clozapine outside of the product’s licence will be at the responsible clinician’s discretion and should
be documented in the medical notes. A standard letter should also be completed acknowledging
the consultant’s responsibility, and returned to the manufacturer i.e.Mylan.
1.4 Patients with medical co-morbidities will require increased monitoring under AMHT until at a stable
dose, to identify any change in their condition and each patient should be considered on an
individual basis. This should be recorded in the patient’s notes and Care Plan.
Proceed with additional caution (i.e. slower dose titration and increased monitoring) in adolescent
and elderly patients.
The patient must also have their ability to self medicate a complex regimen assessed, including
previous concordance history. If there are reasonable concerns and hence the patient’s health may
be at risk with non-concordance, then the decision not to proceed should be made by the team and
documented. If there are concerns with the ability to manage the initiation regimen, then intensive
support should be provided by AMHT, or as an inpatient.The outcome of this assessment should
be documented along with the decision to proceed with clozapine therapy or not.
The results of a baseline tests and ECG should be recorded in the patient’s records. If the patient
has any complications the risks versus benefits needs to be considered and, if they are in the
community, to admit the patient for intensive monitoring be considered. If the risks of clozapine
treastment are high, then the patient should not be accepted for clozapine treatment, and this
outcome should be recorded in the patient’s notes and the patient and carer informed.
1.5 If the patient has a history of previous problems particularly respiratory (including Obstructive Sleep
Apnoea), cardiac or seizures, then inpatient titration must be considered. The outcome of this
decision should be recorded in the patient’s medical notes.
1.6 Community patients must have a carer willing and able to monitor the patient particularly at
night and at weekends, on initiation. Where there is no such carer and the patient is alone then,
review the appropriateness of community initiation and initiate as an inpatient or under AMHT
until at a stable dose. Every effort, however, needs to be made to acquire a suitable carer to
ensure maximum safety. Record details in the patient’s records.

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2. Responsibilities of the consultant
The patient’s responsible clinician must ensure:
2.1 The decision to start the patient in the community will need to be made by the team and agreement
by all parties sought and the acceptance criteria met.
2.2 That they are satisfied that the patient has given valid consent to commencing treatment or if
lack capacity that it is in their best interest
Consent is valid when;
 The patient has been given information about the treatment in a form that can be understood,
and is clearly explained, including information about possible side effects, physical monitoring,
blood tests, on-going appointments/ home visits,concordance with the treatment regimen, and
the likely consequences of not having the proposed treatment.
 The patient has been given information about alternative treatment options in a form that can
be understood, and is clearly explained The patient has the capacity to make the decision
about their treatment.
 The patient has the freedom to make a choice.
 An entry in the patient’s records confirming this has been carried out.
2.3 A doctor from the prescribing team is readily available to give advice to the community, primary
care or inpatient staff.
2.4 Existing medication and smoking status is reviewed, particularly for drug interactions and
concurrent side-effects, and it is appropriate and safe to start clozapine.
Some drugs will need to be discontinued (for example carbamazepine and antipsychotic depot
injections) before clozapine initiation. Concurrent antipsychotic depot/Long Acting Injections make
treatment with clozapine off-licence use, as there are increased risks (see 1.3).
2.5 The doctor must ensure the following are informed, and document
 The patient’s GP, supply GP with information on clozapine (see appendix 10 for the GP risk
management/shared care guideline), start date and emergency contact numbers, before
initiation for community patients and prior to discharge for inpatients.
 All appropriate members of the mental health care team, including care co-ordinators.
2.8 For community patients the responsibility remains with the community consultant. They may need
to negotiate/coordinate with the AMHT or inpatient consultant. There should be regular specialist
medical reviews (at least 6 to 12 monthly), particularly where there are changes in physical
monitoring or deteriation in physical health.
2.9 Ensuring the prescription chart is complete, including a named care co-ordinator and contact
details. This will be an inpatient drug chart or the community clozapine chart (see appendix 11).
Both will need regular review and re-writing in a timely manner and communicating with all parties
involved.
3. Responsibilities of the care coordinator
3.1 When making the decision to proceed with clozapine initiation in the community or inpatient wards
the care coordinator or senior nurse in the team will identify staff competent to monitor the patient’s
physical health (see appendix 4). This includes blood pressure, temperature, pulse, respiration and

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December 2018 6
weight. This is to be recorded on the paper work and track and trigger tool, as appropriate. If a
non-qualified member of staff is completing the monitoring, then changes must be reported to a
qualified member of staff.
3.2 All nurse/practitioners involved must be familiar with:

 Potential side effects of Clozapine and how these present.
 The information that the patient will need about taking Clozapine (see
www.choiceandmedication.org.uk/southernhealth ).
 The treatment programme.
 The Clozaril Summary of Product Characteristics. The up to date version is available from
www.medicines.org.uk.
 Physical health monitoring required while on clozapine and what to do if concerned about any
results.
3.3 It is the role of the nurse/practitioners to.

 Monitor and report the development of any side effects.
 Observe and report the patient’s progress and discuss management with the Consultant or
available physician where there are concerns and at regular specialist medical review. It may
be helpful to refer to the document ‘Potential side effects’ (Appendix 1).
 Provide information and support to the patient and carers including patient information leaflets.
 Document all discussions and observations on the electronic patient record (RIO)
 Maintain an appropriate Care Plan fo clozapine.
 Report and act on any concerns with obtaining physical monitoring, attendance for
appointments/clozapine clinic and concordance issues.
3.4 Nurse/practitioners should confirm information has been given and understood by the patient and
carer. This is to include:
 Common side effects, their symptoms and what to do if they occur
 To report constipation or change in bowel habit to healthcare professionals as a matter of
urgency.
 The importance of not travelling alone or driving for at least 2 weeks (due to a small but known
risk of collapse). Also to expect sedation which will effect their ability to drive and use
machinery.
 The signs of neutropenia including sustained temperature elevation with flu like symptoms or a
sore throat.
 Why regular blood tests are mandatory.
 To report feeling unwell and any symptoms of illness including fever, cough, chest pain,
shortness of breath, diarrhea, increased salivation, increased pulse/tachycardia, nausea,
vomiting, sore throat, myalgia, headache, sweatiness, and urinary discomfort or frequency
change.
 Why regular observations are required.
 To give advice on weight management and diet. Consider both written and verbal.
 Smoking status; to record smoking status and to inform and seek advice from a member of
their team if considering stopping/starting smoking and why (see Appendix 8).
 Breaks in treatment. If stopped for longer than 48 hours the dose must build up again from
12.5mgs. See section 5.1 for further information. If more than 72 hours, blood tests will need to
go back to weekly for at least 6 weeks. Also advice why concordance with the reimen is
required and to report any problems.
 Provide the patient and carer with the patient information leaflets.
 The importance of informing anyone else treating him/her that they are on clozapine.
 To provide the patient and carer with the name of their care co-ordinator, consultant and team
and contact details.

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3.5 With community patients it is the role of nurse/practitioners to ensure that the patient and carer
know when and who to notify should problems arise both within normal working hours and
out of hours.
3.6 If the patient decides to stop clozapine, the nurse must ensure that the patient discusses this
decision with the Consultant. To reduce the risk of rebound psychosis and discontinuation
symptoms the medication should be reduced slowly.
4. Treatment Programme
4.1 When a decision is made to initiate clozapine, there must be a clear Care Plan written to ensure
close monitoring of any underlying medical conditions. If the community team is unable to
support the frequency of monitoring then clozapine should be started by inpatient initiation or
with intensive support from AMHT.
4.2 A time is set to take the initial blood test in order to register the patient with the Clozaril Patient
Monitoring Service (CPMS/ Mylan). Within ten days of the initial satisfactory blood test a date
needs to be set to start treatment. For community patients the start date of the treatment should
ideally be on a Monday (non-bank holiday weeks) to maximise the time available for professionals
working 9-5, weekdays. Following the initial blood tests the patient should be registered with the
CPMS.
4.3 Arrangements should be made for the blood tests to be taken at the Clozapine Clinic, by inpatient
staff or at the local medical hospital. For community patients the nurse/practitioner or care co-
ordinator should ensure that someone accompanies the patient to these appointments initially.
Further, initial blood tests will require Troponin T or I and CRP also to be measured.
4.4 On the third day of treatment a further blood test should be taken and the results sent/reported
back to the CPMS/ Mylan. Within a week of the second blood test a further blood test needs to be
taken.
4.5 The prescription should be written and sent (delivered,faxed or by secure email) to the appropriate
pharmacy for supply. Clozapine tablets cannot be supplied without a prescription and a green
blood result.
After the initiation is complete and the patient discharged from hospital or AMHT, an outpatient
prescription will be required, this is to be organised by the co-ordinating nurse or clozapine clinic.
4.6 The initial dose should be 12.5mgs, either given at a time to allow monitoring during working
day or taken last thing at night. If tolerated the dosage should be doubled. Thereafter dose
titration will need to be adjusted in accordance with the patient’s response to treatment. See
appendix 11 All medication given should be documented. Dose increases for outpatients should
not take place when there is no medical cover e.g. weekends and bank holidays, in some
areas. For the effect of smoking on clozapine levels and dosage see Appendix 8
Target maintenance doses:

 Patients with drug-induced psychosis in Parkinson’s Disease:25-37.5mg1. A dose of
50mg/day should only be exceeded in exceptional cases, a maximum of 100mg/day must
never be exceeded1
 Patients over 60 years old with resistant schizophrenia: 50-100mg daily2
 Adult female non-smokers: 250mg daily2
 Adult male non-smokers: 350mg2
 Adult female smokers: 450mg2
 Adult male smokers: 550mg2

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References:
1. Summary of Product Characteristics (Clozaril). Accessed via www.medicines.org.uk
(9/2/18)
2. Taylor D, Paton C, Kapur S. The Maudsley Prescribing Guidelines. 12th edition. London:
Informa Healthcare; 2015
3. Bleakley S, Taylor D. Clozapine Handbook 1st Edition. Malta: Lloyd-Reinhold
Communications 2013 (www.clozapine.co.uk)
4.7 During the first day observations (BP and pulse lying down and standing, plus respiration
and temperature) should be undertaken as a baseline before the dose is given and then twice
daily, ideally two hours and six hours after the initial dose. There is no need to monitor the
patient after the night time doses. For community patients there should be at least 4 contacts -
three face-to-face during observations and at least one telephone contact ensuring contact is
distributed evenly throughout the day. Contacts should ascertain the patient’s general condition
and report and document any side effects. If either the contacts or observations indicate a
cause for concern the team or on call doctor should be contacted to discuss management. If
there is a sustained rise (e.g. two successive measurements) in temperature or other concerns
about pulse, respiration, blood pressure or other side effects a report should be made to the
doctor. Observations should be documented on the track and trigger tool and RiO.
4.8 On the second day, observations should be done three times; before the dose is given, then two
and six hours after the morning dose. However for community patients there should be four
contacts in all.
4.9 For the remainder of the week observations should be made at twice a day; before the morning
dose is taken and ideally 6 hours after. For community patients four contacts should be made on
each day.
4.10 For the second week of treatment, three contacts should be made and observations made at least
once but ideally twice a day. After two weeks of treatment a medical review should take place and
future management decided. If there have been unacceptable side effects, or until the dose is
stable, the observations should remain daily, ideally two hours after the morning dose. It may be
appropriate for the patient to attend the clozapine clinic for weekly.
4.11 At all contacts with the patient the patient should be asked about illness and side-effects; feeling
unwell and any symptoms of illness including fever, cough, chest pain, shortness of breath,
diarrhea, constipation, increased salivation, increased pulse/tachycardia, nausea, vomiting, sore
throat, myalgia, headache, sweatiness, and urinary discomfort or frequency change. Compliance
with the treatment regimen and smoking status should also be checked. This should then be
documented on RiO, the care plan checked, and concerns/changes raised with the team and
responsible clinician.
4.12 When the patient is on a stable dose the observations should be weekly for the first 18 weeks then,
full physical health check at 3 months, 6 months and then annually, including RiO Physical
History and Monitoring Form (see appendix 14).
4.13 Appendix 3 and 4 should be completed to demonstrate that monitoring has occurred and been
documented on RiO, but all observations must be entered on RiO Physical History and
Monitoring Form.
4.14 Abnormal results/concerns should be acted upon and consideration given to a specialist
medical review. The Care Plan should be updated accordingly.
4.15 Annual Monitoring

BP and P (sit and stand), temperature, respiratory rate, lipids (including cholesterol and
triglycerides), weight, BMI, waist circumference, blood sugar/ HbA1c. Then if clinically indicated

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Troponin I/T, CRP, ECG, EEG (<= 16 yo) and clozapine/norclozapine levels. Check for side
effects including constipation, sedation and hypersalivation. This is by secondary care.
4.16 Clozapine titration for adolescents: is slower than that recommended for adults to minimise
side effects and twice daily monitoring should continue until a therapeutic dose is reached. The
titration should pause when the dose is 150mg daily and a clozapine blood level taken.
Although side effects and monitoring of clozapine are generally the same in both adult and
adolescent populations there are some reports of a higher seizure risk in those under 16. EEG
monitoring (baseline and once the dose is stabilised) should be considered for any patient
under 16 receiving clozapine.
4.17 Clozapine titration for patients 60 years of age and older: initiation is recommended at a
particularly low dose (12.5mg given once on the first day) with subsequent dose increments
restricted to 25mg/day.
4.18 Support for community initiation patient: this should be reviewed regularly as per care plan
to ensure the required contacts are being made, and that there are no concerns with blood
tests, physical monitoring and concordance with the regimen. If there are concerns the patient
should be medically reviewed, consideration to the remaining initiation occurring as an inpatient
should happen. This should be documented on RiO.
4.19 Clozapine is available as several different brands. In Southern Health we provide Clozaril® tablets
and Denzapine® 50mg/ml suspension. They presently require separate registration and monitoring.
See appendix 16 for procedures for changing brands.
4.20 Denzapine® suspension must be shaken well for 90 seconds before administering and it can be
diluted with water. It should not be transferred from the manufacturer’s original container.
Pharmacy will supply whole containers for ward patient stock and if it is essential to supply smaller
quantities for a short term leave TTO pharmacy will supply an overage.
Clozapine and Denzapine® are therapeutically equivalent but require different registration.
5. Restarting Clozapine following an Unplanned Discontinuation
Once clozapine has been discontinued the plasma level drops very quickly. Based on an average
half-life between 7 to 14 hours after 35-70 hours (5 times the half-life) there will be no detectable
clozapine left. Along with the rapid decline in plasma levels the tolerability to the side effects
rapidly declines. Patients who have had no clozapine for 48 hours (taken from the last dose given)
should be re-titrated from 12.5mg per day, as above. The speed of the titration depends on the
original acceptance and tolerability of clozapine, however it should be noted that a slow titration is
preferable to prevent adverse reactions. Hypotension, tachycardia, seizures and drowsiness are
particular risks when re-starting clozapine.
5.1 Mylan (Clozaril®) On/off treatment-assessment guidelines

The time off clozapine is taken from the last dose administered.
For clozapine patients on weekly white cell count monitoring
Monitoring OFF clozapine OFF > 48HRS OFF for

frequency for less than 48 BUT < 7 DAYS 7 DAYS OR
HRS MORE
Weekly No change to No change to Restart the 18
blood monitoring monitoring weeks of weekly
frequency. Re-titration dose monitoring. Re-
Continue as as per initial titration dose as
normal titration. for initial titration

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For clozapine patients on fortnightly or 4 weekly white cell count monitoring
Monitoring OFF <48 HRS OFF > 48HRS OFF 4 DAYS OFF
frequency BUT < 4 WHOLE OR MORE > 28 DAYS
DAYS BUT< 28
WHOLE DAYS
Fortnightly and No change to No change to TREATMENT Restart 18

4 weekly monitoring monitoring BREAK weeks of weekly
frequency. frequency Weekly for 6 monitoring. Re-
Continue as Re-titrate dose as weeks and then titrate dose.
normal per initial titration. back to previous
monitoring
frequency. Re-
titrate dose.
Further reading
Bleakley S, Taylor D. Clozapine Handbook 1st Edition. Malta: Lloyd-Reinhold Communications 2013
(www.clozapine.co.uk)

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Appendix 1: Potential side effects
This list is not exhaustive. More information can be obtained from the Clozaril Patient Monitoring
Service or clozapine handbook. Seek advice if you are unsure. Be cautious when prescribing
other medicines with similar side effects to clozapine.
Constipation Usually persists, adjust diet, high fibre and adequate fluid. Give a bulk-forming and stimulant
laxative if needed. Ensure adequate fluid intake. Constipation should not be ignored, it can be
rapidly fatal. Review other medications which may cause constipation. Consider the using the
Porirua Protocol (CNS Drugs. 2017 Jan;31(1):75-85. doi: 10.1007/s40263-016-0391-y.
The Porirua Protocol in the Treatment of Clozapine-Induced Gastrointestinal Hypomotility and
Constipation: A Pre- and Post-Treatment Study. Every-Palmer S et al) and
https://otago.ourarchive.ac.nz/bitstream/handle/10523/6763/Porirua%20protocol.pdf?sequence=1&i
sAllowed=y
Tachycardia Very common in early stages of treatment, but usually benign. Tachycardia, if persistent at rest
and associated with fever, hypotension or chest pain, may indicate myocarditis. Signs and
symptoms of myocarditis or cardiomyopathy include persistent tachycardia at rest, palpitations,
arrhythmias, chest pain and other signs and symptoms of heart failure (e.g. unexplained fatigue,
dyspnoea, tachypnoea), or symptoms that mimic myocardial infarction. Refer to a cardiologist
urgently. Clozapine should be stopped if tachycardia occurs in the context of chest pain, heart
failure or raised Trop I or T or CRP.
Pyrexia o
Temperature above 38 C is often normal in the first three weeks of treatment. However, a blood
sample should be taken to exclude agranulocytosis and exclude causes of infection. Paracetamol
may be beneficial. Beware myocarditis and neuroleptic malignant syndrome.
Seizures Especially with rapid dose titration and high clozapine levels/ doses. Stop clozapine for 24 hours.
Restart at half the original dose. Consider adding sodium valproate or lamotrigine. Refer for EEG
and neurological examination if appropriate. May be more common in those under 16 years old.
Drowsiness This is usually within the first four weeks, but may persist. Can be managed by giving more of the
dose at bedtime and increasing the dose more slowly.
Hypersalivation Appears early on in the treatment, may persist and may be worse at night. If troublesome consult
doctor/pharmacist. Hyoscine hydrobromide is usually an effective treatment either as the tablets
(Kwells® 300-900mcg at night or in divided doses) sucked or chewed or patches (1.5mg every 72
hours). An alternative pirenzepine 50-150mg at night or in divided doses (unlicensed).
Hypotension Usually occurs in the first four weeks. Instruct patient to stand slowly; support stockings may be of
use. Split the dose, with a larger proportion at bedtime, slow the titration or reduce the dose
Weight gain Can be significant. Give advice about exercise and diet. Refer to dietician. It’s easier to minimise
weight gain over the first few months than try to lose it afterwards.
Cholesterol Full lipid profile including triglycerides, ideally fasting, after 1, 3 and 6 months, and then every 6
check months. Treat if necessary.
Diabetes Plasma glucose, ideally fasting, after 1, 3 and 6 months, and then every 6 months. Consider
check checking HbA1c also. Treat if necessary.
Blood Reduction in white blood cells occurs in 3% of people exposed to clozapine. More common in the
disorders first year of clozapine treatment. The white blood cell count monitoring is a mandatory requirement
of prescribing and supplying clozapine.

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Appendix 2: Clozapine initiation checklist
File in secondary notes
Patient details
Name Date of birth / /
Address Hosp/ NHS No.
Tel No.
Consultant
GP name: Tel no:
Care coordinator Tel no:
Care-coordinator or named nurse
Sign, date and give details as required

Baseline physical health monitor is complete
(appendix 4)
Patient information leaflet given (see
www.choiceandmedication.org/southernhealth) and
advice (see section 3)
For community patients a carer has agreed to be Name:
involved in the programme Contact no:
For community patients document the Name and Name:

contact no. of team doctor who will be available Contact no:
throughout treatment programme.
CPMS Reg no CPMS No:
Date of first blood test (must be within 10 days prior to
start date).
Hospital Pharmacy informed
Clozapine Clinic informed, if applicable
A Care Plan is in place. This should include reference
to appropriate appendices for intiation and/or
monitoring in this document.
Smoking status is recorded (see Appendix 8)
Dietary advice given (to prevent weight gain and
constipation)
Doctor
Sign, date and give details as required

Patient fulfils standard criteria for receiving clozapine
( see section 1).
Patient has had a review of medical co-morbidities

including history of epilepsy, cardiovascular,
constipation, renal and hepatic disorder. Risk versus
benefits considered
Baseline ECG, Troponin I/T and CRP checked.
Please specify.
Patient has no history of other medical problems
associated with clozapine. Please specify

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Medication reviewed
Does the patient have a history of any adverse

reactions to antipsychotics? Please specify.
Has consent or SOAD authorisation been obtained

and documented?
Entry in records made with regard to patient
consenting to treatment
Complete baseline physical health monitoring
(appendix 3)
Write prescription and obtain medication from hospital
pharmacy. Do not increase dose over the weekend if
there is no medical cover.
Dates of planned consultant appointments during
titration, if known
Inform patient to consult with their psychiatrist before
driving and that DVLA will need to be informed.
GP informed of clozapine initiation and ongoing
prescribing. Have they been sent a copy of the GP
clozapine guidelines?

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Appendix 3 Baseline physical health monitoring
To be completed pre Clozapine, no more than one month prior to initiation,
(reproduced with permission from Clozapine Handbook 1st edition, 2013).
File in secondary file
Monitoring parameters Sign /

date
Blood Pressure (lying down and standing)
Pulse
Temperature
Respiratory rate
Urea and electrolytes (including eGFR)
Full blood count (WBCs, Neutrophils, Eosinophils)
ECG
Blood lipids, ideally a fasting sample (full lipid profile including triglycerides)
Troponin T or I (depending on what is available at the local lab)
C-reactive protein CRP
Echocardiography if suspected underlying heart disease
Weight (including BMI, and abdominal circumference)
Plasma glucose (fasting sample ideally), HbA1C
Liver Function Tests (ALT, AST, bilirubin, albumin, prothrombin) Fasting sample ideally.
EEG (Under 16 year olds only)
Investigate potential problems with prescribed, purchased or herbal medication, illicit drugs, and
alcohol. Assess ability to self medicate.
Record current smoking status (see Appendix 8), caffeine intake, lifestyle and diet.
Investigate for any previous history of blood disorders, seizures, DVTs, PEs, cardiac, bowel or
bladder dysfunction, glaucoma, OCD and liver or renal impairment.
Record physical health information on electronic record.
Signed By Doctor or Nurse

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Appendix 4: Clozapine Physical Monitoring Sheet (to be kept with medication chart). The track and trigger tool may be
used in place of the monitoring sheet but the frequency of monitoring should be the same.
Patients name
CPMS no: Hospital/NHS No.
Clozapine start date
Baseline observations time: date: Wt…………… Height............BMI………
Temp: Pulse: BP (standing): BP standing / lying: Respiration:
During initiation: Omit if temperature >38.5’C, postural drop >30mmHg or pulse > +/- 15% baseline, and inform the
Doctor.
Observations
Respiratory Lying Standing

Day (use the Date Time Temp Pulse rate BP BP Other side effects, Outcome if Dr Sign
morning particularly flu-like informed
(normal
dose where symptoms,
possible)
rate 12-18 hypersalivation,
breaths per palpitations, chest
minute) pain, constipation,
GASS-C
1
Before dose
2hrs post, if
awake
6hrs post, if
awake
2
Before dose
2hrsafter
dose
6hrs after
dose
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(normal
possible)
GASS-C
3
Before dose
6hrs after
dose
4
Before dose
6hrs after
dose
5
Before dose
6hrs after
dose
6
Before dose
6hrs after
dose
7
Before dose
6hrs after
dose
8
10

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(normal
possible)
GASS-C
11
12
13
14
15
16
17
18
19
20
21
22
23

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(normal
possible)
GASS-C
24
25
26
27
28

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Appendix 5: Clozapine in the Community Contact Monitoring Sheet (to be kept with
medication chart)
Patients name
CPMS no: Hospital/NHS No.
Clozapine start date
Baseline observations time: date: Wt…………… Height............BMI………
Temp: Pulse: BP (standing): BP (lying): Respiration:
Contacts
Day Date Time Contacted by Method Outcome
1

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9
10
11
12
13
14
15
16
17
18
19

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20
21
22
23
24
25
26
27
28

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Appendix 6: Guidelines for the Management of a Red Clozapine Result.
1) Background information:
The CPMS categorise blood results according to the following colour-coded system:
Colour alert WBC count x 109/L Neutrophil count x

109/L
Green > 3.5 > 2.0
Amber 3.0 – 3.5 1.5 – 2.0
Red <3.0 <1.5
If a patient has an amber blood result, a full blood count must be performed twice weekly until
the blood count stabilises in this range or increases.
2) Management of a Red Alert:
If a patient’s WBC is less than 3.0 x 109 /L and/or the neutrophil count is less than 1.5 x
109/L, this is known as a red alert and the following action must be taken:
 STOP CLOZAPINE TREATMENT IMMEDIATELY.

 Check the patient for any signs of infection (refer to details below) and contact the
CPMS as soon as possible.
 Make arrangements to undertake confirmatory blood counts on the 2 days following the
date of the red alert sample. If either of these follow up blood counts is in the red alert
range then red alert status is taken to be confirmed.
 If the red alert is confirmed, THE PATIENT MUST NOT RESTART CLOZAPINE
TREAMENT.
 Full blood counts with differential white cell counts must be performed DAILY whilst the
blood counts remain in the RED range, and the patient must be observed closely for
infection (e.g. sore throat, fever). The results should be reported to the CPMS as soon
as they are available.
 If antipsychotic medication is considered essential, use agents with low potential to
cause neutropenia and avoid depot preparations.
 Review all other medication. Consider stopping those agents with potential to adversely
affect neutrophil counts. If necessary, introduce a more appropriate alternative.
If a patient’s neutrophil count falls to less than 1.0 x 109/L or the WBC falls to less than
2.0 x109 /L OR if the patient develops a fever, please observe the following additional
recommendations:
It is extremely important to contact a specialist haematologist, or failing this, a general

medical physician, regarding the most appropriate treatment for the patient. This will probably
involve transferring the patient to a ward with facilities for the care of neutropenic patients. If
unable to contact the hospital haematologist immediately, please refer to the guidelines below:
 Check the patient’s temperature, blood pressure and pulse FOUR hourly.
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December 2018 23
 Nurse patient in a single room, taking care to wash hands before and after contact with
the patient, wear aprons etc.
 Avoid salads, yoghurt, unpeeled fruit, paté or soft cheese in the patient’s diet. Give
sterilised milk, water or canned drinks. Remove flowers from the patient’s room.
 Give patient an antibacterial and antifungal mouthwash prophylactically (eg.
chlorhexidine 10mls QDS and nystatin suspension 1ml QDS )
Granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating

factors have been used in the management of clozapine induced agranulocytosis although this
is not a licensed indication. The cost of such drugs if used will be reimbursed by CPMS.
Effect of sudden discontinuation of clozapine:

When a patient has a red alert it is essential to stop clozapine immediately. This sudden
cessation of treatment can lead to physical and mental withdrawal effects which may occur
within 2 – 3 days and usually within the first 2 weeks. Patients may experience a rapid
deterioration in their mental state with rebound psychosis. In addition, abrupt withdrawal of
clozapine has been associated with symptoms such as nausea, vomiting, diarrhoea,
headache, restlessness, agitation and sweating and it has been suggested that these are a
result of cholinergic rebound since clozapine has strong anticholinergic action.

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SOUTHERN HEALTH NHS FOUNDATION TRUST
GUIDELINES FOR THE MANAGEMENT OF A RED CLOZAPINE RESULT

LOCAL PRACTICAL ACTION
A pharmacist is available at CPMS 24 hours a day, for the provision of

patient specific pharmaceutical advice.
o Telephone number 9am – 5pm Monday to Friday: 0845 7698269

option 2
o Out of hours service: 01276 692504
ACTION SIGNATURE DATE

1. Ensure the patient’s consultant, care coordinator and
the clozapine clinic staff are aware of the red result
and management implications as soon as possible
and discuss and determine an individual care plan on
RIO for monitoring bloods mental and physical health
and review of medication. For out-patients, inform
the patient’s GP.
2. Ensure that all involved are aware of contact details

and are in receipt of these guidelines.
3. Care coordinator to ensure that adequate systems

are in place so that the:
3.1 Patient does not receive any more clozapine until

advised that this can be reintroduced by the CPMS.
If the patient is off clozapine for more than 48
hours, this will need to be retitrated.
3.2 Patient is monitored for mental state (possibility of

rebound psychosis following abrupt clozapine
withdrawal).
3.3 Patient is monitored for any physical health problems

including temperature as they will be less able to
combat these due to the low white cell count.
ACTION SIGNATURE DATE

3.4 Arrangements are in place for daily full blood count
tests which will need to be analysed as soon as
possible and the results phoned through to the
CPMS. Doctor on call should do bloods if out of
hours There will need to be at least 2 days worth of
daily follow up blood tests; these will continue until
advised by the CPMS that they are no longer
required (at least 2 consecutive non red results).
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3.5 The team responsible for care over a weekend has
available the patient’s full notes, including up to date
risk assessment, details of current medication, a
description of the patient and emergency contact
details (eg next of kin), on-call services at group
homes.
3.6 In order to facilitate all of the above, for patients for

whom admission is not appropriate or necessary and
where follow-up is needed over the weekend, is likely
to be the most appropriate course of action. This
team will then need to liaise with the on-call duty
doctor to ensure the daily blood tests occur at a
suitable time and venue on each day.

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Appendix 7: Guide to Interpretation of Clozapine Plasma Levels
Reference: Northumberland, Tyne and Wear NHS Foundation Trust Appendix 2 – Guide to Interpretation of
Clozapine Plasma Levels Part of PPT-PGN-04–Therapeutic Drug Monitoring of Clozapine Plasma Levels – V02 –
Issue 1 – Sep 12
‘Trough’
Clinical Comment
clozapine
response
(mg/L)
<0.01 Any Clozapine is unlikely to have been taken for at least a week
‘not detected’ before sampling except perhaps in the very early stages of dose
escalation (dose 100mg/day or less).
Good Consider repeating assay at 6 months, then annually unless
< 0.35
response deteriorates or side-effects become troublesome.
Poor/ incomplete If poor adherence is suspected, consider psychoeducation or

supervised administration. Please note if a suspension of crushed
clozapine tablets is prepared care must be taken to ensure that
the bottle is shaken well before administering the suspension to
the patient. Review patient and repeat assay after adherence
intervention. Consider cautious dose increase (especial caution if
dose already 450 mg/d or above due to increased risk of side-
effects, in particular seizures). Monitor mental state and side-
effects. Review patient again and repeat assay after at least 1
week on new dose.
Good Consider repeating assay at 6 months, then annually unless
0.35-0.50
response deteriorates or side-effects are troublesome. If side-
effects are persistent/serious consider cautious dose reduction
(e.g. 25 mg/d in week 1, further 25 mg/d in week 2, etc.), but bear
in mind possible loss of response.
Poor/ incomplete If clozapine treatment has continued at least 3-6 months at

current dose, consider psychosocial intervention. Augmentation
with other psychoactive drugs to be of benefit, although this is not
recommended in the SPC. It is important any such attempts
should be carefully considered with respect to side-effects
(including the risk of neutropenia) and possible interactions.
Clozapine should not be used with drugs known to have a
substantial potential for causing agranulocytosis.
Good – no Review. Consider a cautious dose reduction (e.g. 25 mg/d in week

0.51-0.99
clinical features 1, further 25 mg/d in week 2, etc.), but balance against risk of
of toxicity diminishing the response to clozapine. Consider using an
anticonvulsant (not carbamazepine) as prophylaxis against
seizures, if dose reduction thought inadvisable. Monitor mental
state. Repeat assay after at least 1 week on a new dose,
otherwise 3-monthly.
Poor/ Cautious dose reduction (see above) to bring plasma clozapine

incomplete/ below 0.6 mg/L. Monitor mental state. Repeat assay after at least
reduced and/or 1 week on a new dose.
clinical features
of toxicity

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‘Trough’
Clinical Comment
clozapine
response
(mg/L)
Good – no Review. Consider a cautious dose reduction (e.g. 25 mg/d in
1.0-1.9
clinical features week 1, further 25 mg/d in week 2, etc.) to bring plasma
of toxicity clozapine below 1.0 and possibly below 0.6 mg/L, but balance
against risk of diminishing the response to clozapine. Consider
using anticonvulsant prophylaxis (not carbamazepine). Monitor
mental state. Repeat assay after at least 1 week on a new dose,
otherwise 3-monthly. Plasma clozapine may continue to rise in
the short term even after the dose has been reduced.
Poor, Cautious dose reduction (see above) to bring plasma clozapine
incomplete or below 1.0 and possibly below 0.6 mg/L. Monitor mental state.
reduced and/ Repeat assay after at least 1 week on a new dose. Plasma
or clinical clozapine may continue to rise in the short term even after the
features of dose has been reduced.
Good – no
toxicity Urgent review. Consider cautious dose reduction (e.g. 25 mg/d in
2 & above
clinical features week 1, further 25 mg/d in week 2, etc.) to bring plasma clozapine
of toxicity below 1.0 mg/L, and possibly below 0.6 mg/L. Consider
anticonvulsant prophylaxis (not carbamazepine). Monitor mental
state. Repeat assay after at least 1 week on a new dose. Plasma
clozapine may continue to rise in the short term even after the
dose has been reduced.
Poor, Urgent review. If patient is in the community, consider admitting
incomplete or for observation. Withhold Clozaril for 24 h and re-start at 75 % of
reduced and/or last dose, thereafter reduce dose slowly (e.g. 25 mg/d in week 1,
clinical featuresfurther 25 mg/d in week 2, etc.) to bring plasma clozapine below
of toxicity 1.0 mg/L, and possibly below 0.6 mg/L. Consider anticonvulsant
prophylaxis (not carbamazepine). Monitor mental state. Repeat
assay after at least 1 week on a new dose. Plasma clozapine may
continue to rise in the short term even after the dose has been
reduced.
Norclozapine is one of the main metabolites of clozapine. It has a longer half-life than clozapine so less
effected by daily fluctuations and not dependent on a trough sampling time.
Mean clozapine to norclozapine levels and ratios

st
Reference: Bleakley S, Taylor D. Clozapine Handbook. 1 Ed. Lloyd-Reinhold Communications LLP, Dorsington, UK)
Clozapine level Median clozapine to norclozapine Norclozapine level
ratio
<350mcg/L 1.25 <280mcg/L
350-600mcg/L 1.55 280-387mcg/L
601-1000mcg/L 1.78 343-562mcg/L
>1000mcg/L 2.08 >481mcg/L

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Appendix 8: Smoking Cessation – Effect on Clozapine
Summary.
Smoking increases the clearance of clozapine thus smokers will often require more clozapine
than non-smokers. Stopping smoking can dangerously increase clozapine levels. During
smoking cessation the clozapine dose will need reducing.
Background.
The hydrocarbons in tobacco smoke induce the production or activity of various liver enzymes,
in particular cytochrome CYP1A2, an enzyme associated with the metabolism of several
psychotropic drugs including clozapine. Therefore, in response to smoking cessation it is
possible that the metabolism of these drugs will decrease and plasma levels will rise. This is
particularly the case for clozapine where it is possible that plasma levels may be elevated to
toxicity.
Note – CYP1A2 activity is affected by hydrocarbons and not by nicotine. Therefore nicotine
replacement therapy (NRT) will not alliterate the clozapine vs smoking interaction.
When stopping smoking while receiving clozapine, clozapine levels may rise by as much as
50-70%.
For clozapine:
1. Review preadmission (outpatient) serum clozapine levels (if available) and order a new
baseline serum clozapine level as soon as practicable. (Note – no ‘call-out’ is required, as
dose reduction need not be immediate. Arrange bloods in normal ‘office hours’).
2. Review side-effects history and, if possible, check against the serum clozapine levels at
which they occurred.
3. Assess the risk of toxicity (i.e. if level exceeds 1000mcg/l) by using the non-smoking
serum clozapine level using the formula below if appropriate :
Serum clozapine (Non-smoker) = [1.5 x Serum clozapine (Smoker) ] + 50
eg. smoking level of 500mcg/l gives a non-smoking level of 800mcg/l
nb. The formula is considered to give a suitably accurate result in approximately 80% of cases.
However, in patients with higher smoking clozapine levels or doses, (eg. above 700mcg/l or above
700mg daily), the CYP1A2 enzyme may have been saturated resulting in much higher rates of
metabolism. Greatly increased levels may then occur in these patients when they stop smoking
and the formula may be wildly inaccurate.
4. Set a target (non-smoking) serum clozapine level, taking into consideration the patient’s current
condition and clinical response to current dose / level. If indicated, adjust the clozapine dose
accordingly. (Note – if compliance has been poor prior to admission, the baseline level may be
artificially low. This should be taken into consideration).
eg. Smoker admitted on clozapine 600mg daily and serum level found to be 480mcg/l. Compliant with
medication but clinically unwell on this dose and considered to need a higher level. Estimated
serum level on cessation of smoking is (1.5 x 480) + 50 = 770mcg/l. If clinician considers that a
target serum level of 770mcg/l is appropriate then no adjustment of dose may be necessary.

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However, if it is felt that the target level should be in the region of 600mcg/l, then the patient’s
dose may need reducing to 350mg or 375mg daily.
5. Necessary reductions in daily dose should be made at a rate of approximately 10% per
day.
6. Monitor serum clozapine level at day 3 and then weekly (until stabilised to target level).
Also, pre-discharge level (unless done in previous 48 hours).
7. Monitor for adverse effects – bearing in mind that some may take as long as 2 to 3 weeks
after adjustment of dose to become apparent.
8. On discharge or leave, reassess patient’s likelihood to recommence smoking and the

potential reduction in serum clozapine level in response. If this occurs it is likely that the
clozapine dose will have to be increased.
9. Post-discharge, monitor serum clozapine level once each week, (or fortnightly if total dose
change was less than 20%), until stable.

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Appendix 9: Suggested GP letter

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Appendix 10: Shared care guidelines: Information for the GP
Clozapine Risk Management Guidelines for

Primary and Secondary Care
Name of patient treated under this guideline (PID):
This shared care guideline has been produced to support prescribing and monitoring of
patients between secondary and primary care, and provides an information resource to
support clinicians providing care to the patient. It does not replace discussion about sharing
care on an individual patient basis.
This guideline was prepared using information available at the time of preparation, but users
should always refer to the manufacturer’s current edition of the Summary of Product
Characteristics (SPC or “data sheet”) available at www.medicines.org.uk
1.0 Status of Clozapine
Clozapine (Clozaril®) is a red drug. This means that treatment will be initiated and retained by
secondary care. However, because of the extensive adverse reactions, interactions and
monitoring of clozapine it is essential for all GPs to be fully aware which of their patients are
receiving clozapine and the relevant prescribing issues.
2.0 Indications and Dose
Clozapine is indicated for treatment-resistant schizophrenia and in schizophrenia patients who

have severe, untreatable neurological adverse reactions to other antipsychotic agents.
Treatment resistance is defined as a lack of satisfactory clinical improvement despite the use
of adequate doses of at least two different antipsychotic agents, including an atypical
antipsychotic agent, prescribed for adequate duration.
Clozapine is also indicated in psychotic disorders occurring during the course of Parkinson's
disease, in cases where standard treatment has failed.
3.0 Referral Criteria
Not applicable. Clozapine will only be initiated in secondary care.
4.0 Patient Selection
Not applicable. Clozapine will only be initiated in secondary care

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5.0 Safety Issues
Clozapine (Clozaril®) is a effective atypical antipsychotic used when other treatment strategies
have failed. Approximately 3% of patients treated with clozapine will develop neutropenia
(around 1% will progress to agranulocytosis) which makes them vulnerable to serious
infections. Detection of neutropenia is achieved by regular haematological monitoring, through
the Clozaril Patient Monitoring Service (CPMS).
All patients receiving clozapine must be registered with the CPMS and monitored for the
complete duration of therapy. In the event of an abnormal blood result the CPMS will contact
the psychiatric team immediately to request an additional blood sample if necessary.
The patient, and if appropriate their carer, should regularly be reminded to remain vigilant for
any signs of infection, e.g. fever or sore throat, which may indicate the presence of
neutropenia. While it is unlikely that such symptoms are related to the development of
clozapine-induced neutropenia, an immediate full blood count (WBC and neutrophil counts are
required) will be necessary to exclude the possibility. Patients should be advised to contact
their GP, or hospital team, if they experience signs of infection. If neutropenia is confirmed the
patient must immediately be referred to the consultant for continued monitoring,
haematological referral if required and management of the patient’s psychiatric condition. All
clozapine supplies will be removed and withheld in the event of agranulocytosis.
It has also been suggested that clozapine is associated with rare reports of myocarditis and
cardiomyopathy. Myocarditis seems to occur within 6-8 weeks of starting clozapine while
cardiomyopathy may occur later (median 9 months). The risk of myocarditis is estimated to be
around 1%. Patients should be monitored for symptoms such as tachycardia, fever, flu-like
symptoms, fatigue, dyspnoea and chest pains. Any signs of heart failure should provoke the
immediate discontinuation of clozapine. Successful re-challenge is possible with specialist
advice.
Constipation and gastrointestinal hypomotility is common (14 – 60% of users), under-
investigated and associated with rare, but fatal consequences. There are now more deaths
with clozapine from gastrointestinal adverse reactions than from blood disorders in the UK.
Bowel habits most be regularly monitored, actively questioned for with open questions, advice
given on diet, fluid intake, exercise and laxatives considered. Consider the Poirua Protocol
https://otago.ourarchive.ac.nz/bitstream/handle/10523/6763/Porirua%20protocol.pdf?sequenc
e=1&isAllowed=y ( There should be a low thresh-hold for treatment and investigation. Bleakley
S, Taylor D. Clozapine Handbook 1st Edition. Malta: Lloyd-Reinhold Communications 2013
(www.clozapine.co.uk). See also MHRA alert 2017.
5.1 Contra-indications (see current BNF or SPC)

Hypersensitivity to the active substance or to any of the excipients.
• Patients unable to undergo regular blood tests.
• History of toxic or idiosyncratic granulocytopenia/agranulocytosis (with the exception of
granulocytopenia/agranulocytosis from previous chemotherapy).
• History of Clozaril induced agranulocytosis.
• Impaired bone marrow function.
• Uncontrolled epilepsy.
• Alcoholic and other toxic psychoses, drug intoxication, comatose conditions.
• Circulatory collapse and/or CNS depression of any cause.
• Severe renal or cardiac disorders (e.g. myocarditis).

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• Active liver disease associated with nausea, anorexia or jaundice; progressive liver disease,
hepatic failure.
• Paralytic ileus.
• Clozaril treatment must not be started concurrently with substances known to have a
substantial potential for causing agranulocytosis; concomitant use of depot/ long-acting
injection antipsychotics is to be discouraged (listed under contra-indications in the SPC).
5.2 Cautions (see BNF or SPC)
See general guidance or common adverse effects.
5.3 Common Side Effects (See BNF or SPC)

Clozapine is associated with a number of adverse effects, some of which are listed below. For
a complete list please refer to the BNF or www.medicines.org.uk. Consider using GASS –C
and documenting reults on RiO
ADRs Time course Potential treatments
Sedation Usually 4 weeks Give a larger dose in the

evening
Hypersalivation May persist Hyoscine Hydrobromide
300mcgs nocte
(occasionally up to
900mcgs / day)
Constipation (which may Usually persists Increase fibre, consider
lead to impaction and long-term laxatives.
perforation) Consider the Porirua
Protocol.
Tachycardia Worse first 4 weeks Stop or Slow down titration
If persists refer to
cardiologist
Hypotension First 4 weeks Reduce or slow titration
Hypertension First 4 weeks, sometimes As per hypertension
longer guidelines
Weight gain First year Dietary counselling

Nocturnal enuresis Any time Avoid fluids at bedtime,
altering the timing of doses
may help,
Emerging diabetes Any time As per diabetic guidelines
Seizures / myoclonic jerks Any time Dose / dose increase
related, withhold clozapine
for 24hours, introduce at a
lower dose, consider
lamotrigine. Take clozapine/
norclozapine levels.

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Management in the community is generally possible for most adverse effects by referral
to/discussion with secondary care prescribers; however those requiring immediate referral to
hospital include:
Neutropenia/agranulocytosis, persistent tachycardia, persistent or troublesome nocturnal
enuresis, chest pain, shortness of breath, severe drowsiness, seizures, severe constipation or
any other serious event.
5.4 Drug Interactions (see BNF or SPC)
All drugs which have the potential to cause neutropenia (e.g. carbamazepine, cephalosporins,
quinolones, trimethoprim, cytotoxics and long acting depot antipsychotics) should be avoided.
Clozapine is metabolised by many liver enzymes so drugs which may alter these enzymes can
either increase toxicity or increase the risk of relapse of symptoms.
Drugs which should be Drugs which may be used with

avoided caution (extra monitoring for
clozapine adverse reactions
required)
Carbamazepine Fluoxetine
Fluvoxamine Paroxetine
Erythromycin Sertraline
Rifampicin Warfarin (increased INR possible)
Ciprofloxacin Antihypertensives
Lithium
Other drugs which cause constipation
This list is not exhaustive please refer to the current BNF or www.medicines.org.uk
Smoking cessation interaction

Patients who smoke usually require a higher dose than non-smokers due to the effects
cigarette smoke has on clozapine levels. When giving up smoking clozapine levels can
increase by as much as 50%, thus the dose of clozapine will need reducing. Nicotine
replacement therapy does not negate this interaction. Refer to specialist advice when a
clozapine patient wishes to give up smoking.
6.0 Role of Secondary Care Team
(a) To assess the suitability of the patient for clozapine and counsel patient and carer about
implications of diagnosis and treatment.
(b) To carry out initial and on-going physical health monitoring. The GP may be asked to
conduct and interpret some of the physical health tests depending on local arrangement,
however the responsibility for ensuring monitoring is complete rests with the secondary care
team.
(c) To give the patient the appropriate drug information leaflets.
(d) To explain the possible side effects of the medication to the patient.
(e) To emphasise the need for continued compliance and the need for regular blood tests.
(f) To initiate treatment, arrange for the clozapine community card to be prescribed and
arrange ongoing supplies of clozapine through hospital pharmacy.
(g) To write to the GP (see Appendix 9) informing them of the ongoing prescribing, monitoring
and supply of clozapine. This shared care guideline should be included in correspondence.

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(h) To keep the GP informed of any changes in doses, mental state or prescribing status of
clozapine.
(i) To keep the GP informed of any physical tests performed and on-going physical health
concerns regarding clozapine.
7.0 Role of GP
(a) To ensure clozapine is recorded in the GP records (see second page of the GP letter).
(b) To notify the psychiatric team of any changes in mental state, physical state, any
suspected adverse drug reactions or changes in non-clozapine medication.
(c) To ensure all relevant staff within the practice are aware of the shared care
guidelines and the concerns surrounding clozapine
(d) To consider the precautions, interactions and adverse reactions ofclozapine when co-
prescribing for clozapine patients.
(e) To notify the psychiatric team when the patient wishes to give up smoking and smoking
cessation advice is given.
8.0 Responsibilities of the patient / carer
a) To monitor mental state and report and deterioration in symptoms

b) Assist with adherence or discuss with the GP or secondary care team concerns with
adherence.
c) Report any side effects or physical health concerns
9.0 Cessation of treatment
Clozapine often represents the patient’s best hope of recovery from enduring and treatment
resistant schizophrenia. Cessation of treatment should be avoided except in life threatening
conditions which are linked to clozapine use. Any patient wishing to discontinue treatment
should be referred back to secondary care services.
Patients who have had no clozapine for 48 hours (taken from the last dose given) should be
retitrated at 12.5mg per day, as above. The speed of the titration depends on the original
acceptance and tolerability of clozapine, however it should be noted that a slower titration is
preferable to prevent adverse reactions. Hypotension, tachycardia and seizures are particular
risks when re-starting clozapine.
Further reading
Bleakley S, Taylor D. Clozapine Handbook: Lloyd-Reinhold Communications LLP.
Warwickshire 2013.

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December 2018 38
Appendix 11a: Clozapine Outpatient initiation prescription (only 18-60 years old)
(Suggested guide only: note that much faster titrations can be undertaken in many patients
where tolerability allows)
Surname: Consultant:
First name(s): CMHT:
Date of birth: NHS number:

Address: Service User contact telephone numbers:
Allergies / previous serious Mental Health Act

adverse drug reactions: Section:
Date T2/T3 due:
T2/T3 copy attached: Yes / No (circle))
Date Day Clozapine Given Clozapine Given Dr. Total Pharm

to po Sign and po Sign and Signature daily screen
start Mane date Nocte date and date Dose
(mg) (mg) mgs
1: Mon 6.25 6.25 12.5
2: Tues 6.25 6.25 12.5
3: Wed 6.25 6.25 12.5
4: Thur 6.25 12.5 18.75
5: Fri 12.5 12.5 25
6: Sat 12.5 12.5 25
7: Sun 12.5 12.5 25
8: Mon 12.5 25 37.5
9: Tues 12.5 25 37.5
10: Wed 25 25 50
11: Thur 25 37.5 62.5
12: Fri 25 37.5 62.5
13: Sat 25 37.5 62.5
14: Sun 25 37.5 62.5
15: Mon 37.5 37.5 75
16: Tues 37.5 37.5 75
17: Wed 37.5 50 87.5
18: Thur 37.5 50 87.5
19: Fri 50 50 100
20: Sat 50 50 100
21: Sun 50 50 100
22: Mon 50 75 125
23: Tues 50 75 125
24: Wed 75 75 150
25: Thur 75 75 150
26: Fri 75 100 175
27: Sat 75 100 175
28: Sun 75 100 175
For target maintenance doses, see section 4.6. Ref: Maudsley Prescribing Guidelines 12th Ed.
Version: 4
December 2018 39
Appendix 11b: Clozapine Inpatient initiation prescription (only 18-60 years old)
(Suggested guide only: slower titrations will be required in the elderly (>60 years),
adolescents, those with a medical co-morbidity or a previous poor tolerability to clozapine)
Add a reference to this on the main drug chart e.g. CLOZAPINE – see separate titration chart
Surname: Consultant:
First name(s): CMHT:
Date of birth: NHS number:

Address: Service User contact telephone numbers:
Allergies / previous serious Mental Health Act

adverse drug reactions: Section:
Date T2/T3 due:
T2/T3 copy attached: Yes / No (circle))

Date Day Clozapine Given Clozapine Given Dr. Total Pharm
to po Sign and po Sign and Signature daily screen
start Mane date Nocte date and date Dose
mgs
1 12.5mg 12.5
2 12.5mg 12.5mg 25
3 25mg 25mg 50
4 25mg 25mg 50
5 25mg 50mg 75
6 25mg 50mg 75
7 50mg 50mg 100
8 50mg 75mg 125
9 75mg 75mg 150
10 75mg 100mg 175
11 100mg 100mg 200
12 100mg 125mg 225
13 125mg 125mg 250
14 125mg 150mg 275
15 150mg 150mg 300
16 150mg 150mg 300
17 150mg 150mg 300
18 150mg 200mg 350
19 150mg 200mg 350
20 150mg 200mg 350
21 200mg 200mg 400
22 200mg 200mg 400
23 200mg 200mg 400
24 200mg 200mg 400
25 200mg 200mg 400
26 200mg 200mg 400
27 200mg 200mg 400
28 200mg 250mg 450
For target maintenance doses, see section 4.6. Ref: Maudsley Prescribing Guidelines 12th Ed.

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December 2018 40
Appendix 12: Clozapine Outpatient Prescription
Name: Date of birth: / / .
Address:
Hospital Number: CPMS No.: Allergies/ intolerances: .
Care co-ordinator: Tel: Consultant: Clinic: .
Medicine and Form Dose Frequency/ Maximum Review date Doctor’s signature Date Pharmacist
Time supply screen
(subject to
blood tests)
A Clozapine Please circle Please tick
1 month
MDS Yes/ No (please circle) Weekly 3 months
Fortnightly 6 months
Monthly
Other medication to be supplied: (only in exceptional circumstances)
B
C
D
E
F
G
H
Repeat supplies Items (please code) Maximum Review date Doctor’s signature Date Pharmacist
supply screen
Repeat one
Repeat two
Repeat three
Version: 4
December 2018 41
Appendix 13: Blood Monitoring Form

Version: 4
December 2018 42
Appendix 14: On-going physical health monitoring parameters
st
Parameter 1 month only At 3 months At 6 months Yearly
Blood Pressure (lying down Frequently in the first ✓ ✓ ✓
and standing) month
Pulse Frequently in the first ✓ ✓ ✓
month
Temperature Frequently in the first ✓ ✓ ✓
month
Respiratory rate Frequently in the first Repeat if clinically indicated
month
Urea and electrolytes ✓ ✓
(including eGFR)
Full blood count (WBCs, As per National / company guidelines
Neutrophils, Eosinophils)
Troponin T or I (depending Weekly in the first month Repeat if clinically indicated
on local availability)
C-reactive protein Weekly in the first month Repeat if clinically indicated
ECG Repeat if clinically indicated
Blood lipids (full lipid profile ✓ ✓ ✓ ✓
including triglycerides),
Fasting sample ideally.
Weight (including BMI, and ✓ ✓ ✓ ✓
abdominal circumference)
Plasma glucose (fasting ✓ ✓ ✓ ✓
sample ideally) and/or
HbA1c
Liver Function Tests (ALT, ✓ ✓ ✓ ✓
AST, bilirubin, albumin,
prothrombin)
Monitor for hypersalivation ✓ ✓ ✓ ✓
Actively monitor for ✓ ✓ ✓ ✓
constipation
Monitor for sedation ✓ ✓ ✓ ✓
EEG (Under 16s only) Repeat if clinically indicated

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December 2018 43
Appendix 15: Clozapine Clinic Monitoring Form
Patient name CMPS no GP/Surgery
DOB Clozapine commenced GP Phone no
NHS no Pick up point Registered CPMS Clinician
Address Known Allergies Care coordinator
Phone Number MHA Status Contact

Mobile Number Smoker Height Contact no
Date Weight BMI Pulse Comments/Checks Signed Physical
Dose BP Checks Baseline Current Frequency
1/12 3/12 6/12 Yearly
Glucose*/
HbA1c
Lipids
U+Es
LFT
ECG
Rethink
Cloz level
Requirements in first year of treatment

At One Month: Pulse, BP, BMI, Glucose/HbA1c, Clozapine level
At Three and Six Months: Pulse, BP, BMI, Glucose/HbA1c, Lipids,
U+Es, LFT, ECG and Rethink
At 12 Months: Pulse, BP, BMI, Glucose/HbA1c, Lipids, U+Es, LFT,
ECG, Rethink Questionnaire Form. Clozapine level if clinically
indicated.
Requirements after one year of treatment.

Monthly: Pulse, BP, BMI,
Yearly: Pulse, BP, BMI, Glucose/HbA1c, Lipids, U+Es, LFT and ECG,
Rethink Questionnaire Form. Clozapine/Norclozapine levels if clinically
indicated/change of smoking status
*Fasting Glucose if possible or repeat fasting if random glucose outside

normal range

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December 2018 44
Appendix 16: Clozapine Cardiac induced Side–Effects
A flowchart to aid the screening, monitoring and management of cardiac side – effects, such
tachycardia and myocarditis in all patients on clozapine.
Patient starting or restarting clozapine
Cardiac Baseline Monitoring ( + see Appendix 4)

 Sitting and standing BP and Pulse
 Temperature, respiratory rate
 CRP
 Troponin I or T
 ECG (see SH CP 204 ECG Policy)
 + echocardiography, if suspected underlying cardiac disease
If meets acceptance criteria start clozapine initiation If does NOT meet acceptance criteria and/or
(community or inpatient) and baseline tests acceptable baseline tests NOTacceptable. Send for medical
review and consider inpatient or AMHT initiation if
still suitable for clozapine treatment
Increased monitoring requirement hence AMHT

supported initiation or admission to inpatient unit STOP
Physical monitoring
Ask patients at each contact and advise
BP, P, T, RR as per schedule
(see Appendices 3, 4, 5, & 14 as appropriate) patient/carer;
 To report feeling unwell and any symptoms of
illness, including;
fever, cough, chest pain, shortness of breath,
diarrhoea, vomiting, nausea, sore throat, myalgia,
Once every week for the first 4 headache, sweatiness, dizziness and urinary
weeks and at 8 weeks if retitrating discomfort and frequency.
 Check concordance
CRP  Check smoking status
Troponin I ot T
If the Patient develops:
 Signs or Symptoms of unidentified illness (see above) OR,  Troponin elevation > lab normal level OR,
 HR > 120 bpm or increased by > 30 bpm (repeat ECG) OR,  rises 20% above baseline value OR,
 CRP 50 – 100mg/L  CRP > 100 mg/L
Continue clozapine with increased monitoring STOP clozapine

 Consider slowing down titration if symptomatic Perform urgent echocardiogram
 Check Troponin and CRP daily and monitor for developing Urgent referral to cardiology
illness
 If Troponin > normal lab levels seek urgent cardiology advice Use of beta blockers
and perform urgent echocardiogram  Can exacerbate postural hypotension
 If features do not normalize within 4 weeks, arrange  Do not use routinely
echocardiogram and refer to cardiology  If symptoms of palpitations significant, consider
small doses

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December 2018 45
Appendix 17: Information Checklist for Patients on Clozapine
The following information must be given to the patient when commencing clozapine
and reinforced when arranging the persons discharge or transfer to another team.
Any member of the MDT can complete this form but it is the care coordinators
responsibility to ensure it is completed.
Initiation of clozapine / review appointments Signature of Date
healthcare
professional
The indication for clozapine has been explained
including who will review treatment.
The reasons for clozapine physical health

monitoring has been explained.
The common side effects have been explained

and actions to take should they occur (see
appendix 1), in particular cardiac side-effects
Sedation – driving/handling machinery warning

given
Explain the signs and symptoms of an infection
and what to do should they occur.
Constipation – advice to promptly contact the

team
Discuss the importance of regular blood tests and
what may happen if they miss their blood test.
The reason for a slow titration of clozapine has

been explained.
Explain to the patient who will take the physical

health checks and how often they will be visited
at home (if applicable).
Discuss why it is important to continue clozapine

and what to do if they miss a dose, especially if
they miss more than 48 hours of doses.
Explain the importance of informing other

healthcare professionals (GP, Dentist or
Pharmacist) that you are on clozapine.
Who to contact in an emergency both with hours

and out of hours.
Give dietary and lifestyle advice. Add advice on

alcohol consumption (ideally avoid or no more
than 2-3 units per day).

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December 2018 46
Explain how smoking can affect clozapine levels
and the importance of letting the team know if you
are intending to stop or cut down smoking (if
applicable).
Give written appropriate advice (see
www.choiceandmedication.org/southernhealth)
On discharge or transfer to another team

Advise when and how the patient will receive
ongoing clozapine supplies and the required
blood tests.
Give dosing advice and allow time for questions.

Reinforce the information given above.
Ensure the GP is aware of the clozapine (see

appendix 8). Send the GP a copy of the shared
care risk management guidelines (see appendix
9).
To be completed by the patient:

I understand the risks and benefits of taking clozapine. I confirm that I have had the
chance to discuss and understand the information that I have been given.
Signed……………………………………………………. Date

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December 2018 47
Appendix 18: Protocol* for First Re-Exposure to Clozapine after a Blood Dyscrasia
Requiring Discontinuation
Clozapine prescribing is strictly controlled by the Summary of Product Characteristics
(SPCs) requiring regular blood monitoring throughout treatment. The SPCs state that
clozapine prescribing is contra-indicated in someone with a history of clozapine-induced
agranulocytosis, and once therapy has been discontinued for haematological reasons,
patients must not be re-exposed to clozapine.
Reuse of clozapine after a “red” result is thus unlicensed. All manufacturers have a form
that allows re-exposure but it is the Consultant’s “decision and clinical responsibility alone”
and includes the disclaimer that “I waive any rights I or the hospital may have against” the
suppliers.
Clozapine can be a life-changing therapy and re-exposure to clozapine can both improve
mental state and not necessarily lead on to a second dyscrasia.
Incidence of recurrence on first rechallenge
A review of 53 patients rechallenged with clozapine after a leucopenia or neutropenia,

showed 38% had a further dyscrasia and in most it was more severe, longer-lasting and
occurred more quickly. Of the 53, 55% were rechallenged successfully and remained in
treatment1. A second dyscrasia incidence peaks at 5.5 weeks (range up to 150 days). A
recent review has stated that “Uncertainty over the likely cause of blood dyscrasia in
people taking clozapine, coupled with uncertainty over the mechanism by which clozapine
causes both neutropenia and agranulocytosis, makes any attempt to restart clozapine a
high-risk venture requiring the utmost caution.”2
Protocol for re-exposure following a previous dyscrasia
A protocol is a detailed plan that must be followed for a course of medical treatment. This
is a protocol*. The Trust will not support anyone acting outside this protocol. This is in
recognition that the mechanism for clozapine-induced neutropenia or agranulocytosis is
unknown, nor the extraneous factors involved, and so extreme caution must be exercised
if re-exposing someone to clozapine after a dyscrasia.
In exceptional circumstances, the Trust supports re-exposure to clozapine after

agranulocytosis as follows:
The Consultant must obtain in writing:
1. A second opinion supporting the need for clozapine

2. Advice from a haematologist regarding the dyscrasia and its likely relationship with
clozapine, possible other causes and any other relevant factors and a care plan put in
place
3. Advice from the relevant senior specialist clinical pharmacist
4. Informed consent from the patient, including the risks (1 in 3 chance of a repeat
dyscrasia) and benefits, assuring that the patient is able to retain this information. The
person's capacity to consent should be considered and documented. If patient lacks
capacity the Mental Capacity Act should be followed.

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December 2018 48
 This should be in collaboration with any relatives or an advocate. However, since in
law no one person can give consent for another, it should be made clear he or she
will be advising relatives/advocates but that they cannot consent.
If clozapine is re-prescribed:
1. Minimise the potential from contributing drugs e.g. any that might have been
implicated in the original dyscrasia, any other drugs associated with blood dyscrasias.
2. Increase blood monitoring frequency and alertness, and document clear actions to be
taken. The minimum should be:
 Twice weekly for the first ten weeks, then weekly to 18 weeks, then fortnightly to
one year plus TWO samples before re-starting to establish an adequate baseline
 This should be more frequent (eg 3 times a week) should 3 falls in a row occur or if
there is any suspicion of a dyscrasia developing
 A slightly slower dose escalation should be considered, although there is little
evidence as to whether this reduces the risk or not.
3. Clear action plan made in the notes and copied to pharmacy should a dyscrasia recur:
 Emergency contacts 24/7 (patient, carer, RMO, pharmacy) haematologist
 Discontinuing therapy plan
 Replacement therapies or management options
 The patient must be an inpatient.
4. Service user educated about the relevance of any physical changes, particularly fever,
sore throat or other signs or symptoms of infection, and to whom these must be
reported and information leaflet given.
Second rechallenge to clozapine
Personal communication with Mylan/CPMS (Feb 2011)

 3 patients have been rechallenged with clozapine for the second time. 1 is still
continuing with green blood results
 It was difficult to identify the patients on clozapine and GCSF. It appears that 6
patients are continuing with green results due to GCSF. It is not clear if these patients
have had one or two clozapine rechallenges.
 No deaths have occurred.
No information available from manufacturers of generic clozapine .
References
1. Rechallenge with clozapine following leucopenia or neutropenia during previous therapy.
Dunk, Annan and Andrews, Br J Psychiatry 2006;188:255-63.
2. Restarting clozapine after neutropenia: evaluating the possibilities and practicalities.
Whiskey and Taylor, CNS Drugs 2007;21:25-35.

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Checklist for clozapine re-challenge
The following checklist should be completed, retained in the notes and a copy sent to
pharmacy. The re-supply of clozapine will not occur unless all of the below has been
completed and approved in pharmacy and this form is signed and dated.
Action Yes/No * Notes

Has a written report been obtained from a YES/NO This must/should be a Consultant
second opinion supporting the need for Psychiatrist from the same speciality and
clozapine re-challenge? not a member of another profession (as
in ‘second opinion’ under MHA).
Name:
Has advice been sought from a consultant YES/NO Please state name of haematologist
haematologist regarding the dyscrasia, other and date of contact:
causes and relevant factors and a written
report obtained?
Has the advice been documented and YES/NO Include emergency contact names and
incorporated into care plan for dyscrasia.? numbers (including out of hours )
Advice from specialist clinical pharmacist has YES/NO Clinical Pharmacists should review notes
been sought and received and enter any relevant comments in
them. eg confounding factors for
dyscrasias
Name of Pharmacist:
Written, informed consent obtained, discussion YES/NO If unable to consent, MHA commissioners
to include should be contacted.
 Risk of repeat dyscrasia (1 in 3 Should include written information to the
 Assessment as to capacity to consent service user about what physical changes
considered and documented. to report, particularly fever, sore throat or
OR other signs or symptoms of infection
 MHA commissioners contacted
Discussion with relatives and carers or YES/NO Cannot consent for patient. They can
advocate as to the nature of the treatment and only advise (see note above)
relative risks
Discussion and understanding of the YES/NO Twice weekly for 10 weeks
commitment to increased blood test frequency Weekly from weeks 11 to 18 (inclusive)
Fortnightly to week 52 (inclusive)
Then monthly ongoing
Clear direction in notes for increased blood YES/NO Should 3 falls in WBC occur then
test monitoring if falls in WBC counts occur frequency of testing should increase to 3
three times in a row times per week at minimum.
Action plan completed with input from the YES/NO See attached “Action plan after re-
haematologist and placed in notes and occurrence of blood dyscrasia after
pharmacy should a dyscrasia occur clozapine re-challenge.”
* If answering “no” to any of these questions refer to pharmacy.
Consultant’s Name and

Signature.
Dated:

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December 2018 50
Action plan should there be a re-occurrence of blood dyscrasia after clozapine re-
challenge
This form should be retained in the notes and a copy sent to pharmacy.
Emergency Contacts:
Doctor to complete details.
Patient Carer/ RMO (within Pharmacy Out of

nearest hours) (within Hours
relative hours) phone (if
applicable)
Name:
Address:
Post Code
Home
Phone No.
Mobile
Phone No.
Discontinuation Advice:
Replacement therapy and management options should blood dyscrasia recur.
Consultant Psychiatrist signature: Consultant Haematologist signature:
Date: Date:

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Appendix 19: Clozapine Brand Change Procedure
Please note a patient cannot be registered on two databases at the same time.
Clozaril® (Mylan) to Denzapine® (Genus)
1. Consultant to complete a brand transfer form, obtained from Medicines

management team or Denzapine/Genus website.
2. Ward to fax completed form to Genus on 03332004142
3. Once the form has been received Genus will contact Mylan to transfer the
patient and information onto the new system.
4. Pharmacy will check the website and supply the new medication.
Denzapine® (Genus) to Clozaril® (Mylan)
1. HCP (nurse, Doctor or medicines management team) to contact Mylan to

request a patient be transferred.
2. Please supply patient name, DOB, ward and consultant details, including
fax/email address.
3. Mylan will fax/email a form for the consultant to complete.
4. Once completed fax/email form to Mylan on 08457698541.
5. Mylan will contact Genus to transfer the patient and information onto the new
system.
6. Pharmacy will check the website and supply the new medication.

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Appendix 20: Clozapine side effect rating scale (GASS-C)
See:
http://intranet.southernhealth.nhs.uk/_resources/assets/inline/full/0/86242.pdf

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December 2018 53
Appendix 21: Constipation poster
Struggling to go? Let us know!

We want to know about a change in your bowel habits.
Constipation may be caused by medicines like clozapine,

procyclidine and amitriptyline.

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December 2018 54

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SH CP 114

Summary: The UK product licence of Clozapine (Clozaril®) allows for

Keywords (minimum of 5): Clozapine, Clozaril®, initiation of clozapine, restarting

Target Audience: All Mental Health Practitioners involved in clozapine use.

Next Review Date: November 2021

Approved & Ratified by: Medicines Management Date of meeting:

Author: Juliet Wells, Principal Pharmacist (AMH and LD)

Sponsor: Dr. Karl Marlowe, Medical Director

SH CP 114 Clozapine Guideline

Date Author Versi Page Reason for Change

SH CP 114 Clozapine Guideline

Summary of the Initiation of Clozapine 4

1 Potential side effects 12

SH CP 114 Clozapine Guideline

The patient meets the Acceptance Criteria for the initiation

SH CP 114 Clozapine Guideline

1. Criteria for Acceptance

1.2 The patient must accept regular blood tests.

SH CP 114 Clozapine Guideline

The patient’s responsible clinician must ensure:

Consent is valid when;

3. Responsibilities of the care coordinator

SH CP 114 Clozapine Guideline

3.2 All nurse/practitioners involved must be familiar with:

3.3 It is the role of the nurse/practitioners to.

SH CP 114 Clozapine Guideline

Target maintenance doses:

SH CP 114 Clozapine Guideline

4.15 Annual Monitoring

SH CP 114 Clozapine Guideline

5. Restarting Clozapine following an Unplanned Discontinuation

5.1 Mylan (Clozaril®) On/off treatment-assessment guidelines

For clozapine patients on weekly white cell count monitoring

Monitoring OFF clozapine OFF > 48HRS OFF for

SH CP 114 Clozapine Guideline

Fortnightly and No change to No change to TREATMENT Restart 18

SH CP 114 Clozapine Guideline

SH CP 114 Clozapine Guideline

Care-coordinator or named nurse

Sign, date and give details as required

For community patients document the Name and Name:

Sign, date and give details as required

Patient has had a review of medical co-morbidities

SH CP 114 Clozapine Guideline

Does the patient have a history of any adverse

Has consent or SOAD authorisation been obtained

SH CP 114 Clozapine Guideline

(reproduced with permission from Clozapine Handbook 1st edition, 2013).

File in secondary file

Monitoring parameters Sign /

Record physical health information on electronic record.

Signed By Doctor or Nurse

SH CP 114 Clozapine Guideline

Respiratory Lying Standing

SH CP 114 Clozapine Guideline

SH CP 114 Clozapine Guideline

SH CP 114 Clozapine Guideline

SH CP 114 Clozapine Guideline

SH CP 114 Clozapine Guideline

SH CP 114 Clozapine Guideline