Clarithromycin - Drug Information - UpToDate PDF

6/16/2020 Clarithromycin: Drug information - UpToDate
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(For additional information see "Clarithromycin: Patient drug information" and see "Clarithromycin: Pediatric drug
information")
For abbreviations and symbols that may be used in Lexicomp (show table)
Brand Names: US
Biaxin [DSC]
Brand Names: Canada

ACT Clarithromycin XL; APO-Clarithromycin; APO-Clarithromycin XL; Biaxin; Biaxin XL; DOM-
Clarithromycin; GEN-Clarithromycin; M-Clarithromycin; MYLAN-Clarithromycin [DSC]; PMS-
Clarithromycin; RAN-Clarithromycin; RIVA-Clarithromycin; SANDOZ Clarithromycin; TARO-
Clarithromycin; TEVA-Clarithromycin
Pharmacologic Category
Antibiotic, Macrolide
Dosing: Adult
General dosing note: IR and ER formulations are available; 500 mg every 12 hours of
immediate release is equivalent to 1 g of extended release (two 500 mg ER tablets) once daily.
Bartonella spp. infection (off-label use):
Bacillary angiomatosis, peliosis hepatitis, bacteremia, or osteomyelitis in patients with

HIV:
Note: Not to be used for endocarditis or CNS infections (HHS [OI adult] 2019).
Primary treatment (alternative agent): Oral: Immediate release: 500 mg twice

daily for at least 3 to 4 months (HHS [OI adult] 2019).
Long-term suppression for patients with relapse after ≥3 months of primary

treatment: Oral: Immediate release: 500 mg twice daily; may discontinue if
completed 3 to 4 months of therapy and CD4 >200 cells/mm3 for ≥6 months.
Note: Some experts discontinue only if Bartonella titers have also decreased
4-fold (HHS [OI adult] 2019).
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Cat scratch disease, lymphadenitis (alternative agent): Oral: Immediate release: 500
mg twice daily for 7 to 10 days (Spach 2020).
Bronchiolitis obliterans (off-label use): Oral: Immediate release: 250 to 500 mg once
daily (Kadota 2003; King 2020).
Chronic obstructive pulmonary disease, acute exacerbation: Oral: Immediate release:

500 mg every 12 hours for 3 to 7 days (Falagas 2008; GOLD 2019; Hunter 2001; Sethi
2020). Note: Some experts reserve clarithromycin for outpatients without risk factors for
poor outcomes (eg, age <65 years without major comorbidities, FEV1 ≥50% predicted,
infrequent exacerbations) (Sethi 2020).
Endocarditis prophylaxis, dental or invasive respiratory tract procedure (alternative

agent for patients with penicillin allergy) (off-label use): Oral: Immediate release: 500
mg administered 30 to 60 minutes prior to procedure. Note: Reserve for select situations
(cardiac condition with the highest risk of adverse endocarditis outcomes and procedure
likely to result in bacteremia with an organism that can cause endocarditis) (AHA [Wilson
2007]).
Helicobacter pylori eradication : Note: Avoid clarithromycin-based therapy in patients

with risk factors for macrolide resistance (eg, prior macrolide exposure, local clarithromycin
resistance rates ≥15% [which is assumed in the United States] or eradication rates with
clarithromycin triple therapy ≤85%) (ACG [Chey 2017]; Crowe 2020; Fallone 2016).
Oral: Immediate release: 500 mg twice daily for 7 to 14 days as part of an appropriate
combination regimen (ACG [Chey 2017]; Crowe 2020; Fallone 2016; McNicholl 2020).
Mycobacterial (nontuberculous) infection:
Mycobacterium avium complex infection:
Disseminated disease in patients with HIV:
Treatment: Oral: Immediate release: 500 mg twice daily as part of an

appropriate combination regimen for a minimum of 12 months; subsequently
may discontinue once there are no signs/symptoms of Mycobacterium avium
complex disease and the CD4 count has exceeded 100 cells/mm3 for >6
months in response to antiretroviral therapy (ART) (HHS [OI adult] 2019).
Primary prophylaxis: Note: Not routinely recommended; reserve for patients

with CD4 count <50 cells/mm3 who are not initiated on fully suppressive ART.
Oral: Immediate release: 500 mg twice daily; may discontinue prophylaxis

when patient is initiated on effective ART (HHS [OI adult] 2019; IAS-USA
[Saag 2018]).
Pulmonary disease, nonsevere noncavitary nodular/bronchiectatic disease in

patients without cystic fibrosis (off-label use): Oral: Immediate release: 500 mg
twice daily 3 times weekly as part of an appropriate combination regimen; continue
treatment until patient is culture negative on therapy for ≥1 year (ATS/IDSA [Griffith
2007]; BTS [Haworth 2017]).
Pulmonary disease, severe nodular/bronchiectatic disease, cavitary disease, or

disease in patients with cystic fibrosis (off-label use): Oral: Immediate release: 500
mg twice daily as part of an appropriate combination regimen; 250 mg twice daily
can be used in patients without cystic fibrosis who are <50 kg or >70 years of age
to avoid GI intolerance. Continue treatment until patient is culture negative on
therapy for ≥1 year (ATS/IDSA [Griffith 2007]; BTS [Haworth 2017]; CFF/ECFS
[Floto 2016]).
Mycobacterium abscessus infection (off-label use): Note: Perform susceptibility testing

before and after ≥14 days of clarithromycin incubation to evaluate for the presence of
an inducible erm gene, which can result in decreased macrolide susceptibility even with
a “susceptible” MIC result and may preclude use of clarithromycin (CFF/ECFS [Floto
2016]; Griffith 2020).
Pulmonary, skin, soft tissue, or bone infection: Oral: Immediate release: 500 mg
twice daily as part of an appropriate combination regimen and continued for ≥6 to
12 months (ATS/IDSA [Griffith 2007]; CFF/ECFS [Floto 2016]; Griffith 2020). Note:
Patients should be under the care of a clinician with expertise in managing
mycobacterial infection.
Pertussis (off-label use):
Treatment: Note: Treatment should be initiated within 21 days of cough onset. After this
interval, some experts reserve treatment for pregnant women, patients >65 years of
age, and those with asthma, chronic obstructive pulmonary disease, or
immunocompromising conditions (Cornia 2020).
Oral: Immediate release: 500 mg twice daily for 7 days (CDC [Tiwari 2005]).
Postexposure prophylaxis: Note: Postexposure prophylaxis should be administered,

regardless of vaccination history, to close contacts of persons with pertussis during the
first 21 days of cough.
Oral: Immediate release: 500 mg twice daily for 7 days (CDC [Tiwari 2005]).
Pneumonia, community-acquired:
Inpatient: Oral: Immediate release: 500 mg twice daily as part of an appropriate

combination regimen (ATS/IDSA [Metlay 2019]).
Outpatient: Oral: 500 mg (immediate release) twice daily (ATS/IDSA [Metlay 2019]) or 1
g (two 500 mg ER tablets) once daily. Note: Use as part of an appropriate combination
regimen; if local pneumococcal macrolide resistance is <25%, monotherapy is an
alternative approach for outpatients without comorbidities or risk factors for antibiotic-
resistant pathogens (ATS/IDSA [Metlay 2019]).
Duration of therapy: Minimum of 5 days; patients should be clinically stable with normal
vital signs before therapy is discontinued (ATS/IDSA [Metlay 2019]).
Q fever (Coxiella burnetii), acute symptomatic (alternative agent) (off-label use): Note:
Reserved for nonpregnant patients who are not at risk for complications (eg, no endocarditis
or underlying valvular disease) (Raoult 2020). Treatment is most effective if given within the
first 3 days of symptoms (CDC [Anderson 2013]).
Oral: Immediate release: 500 mg twice daily for 14 days (Gikas 2001; Raoult 2020).
Streptococcal pharyngitis (group A) (alternative agent for patients with severe

penicillin allergy): Oral: Immediate release: 250 mg every 12 hours for 10 days (IDSA
[Shulman 2012]).
Dosing: Renal Impairment: Adult
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: Decrease clarithromycin dose by 50%
Hemodialysis: Administer after HD session is completed (Aronoff 2007).
In combination with atazanavir or ritonavir:
CrCl 30 to 60 mL/minute: Decrease clarithromycin dose by 50%.
CrCl <30 mL/minute: Decrease clarithromycin dose by 75%.
Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary if renal function is normal; however, in patients with hepatic
impairment and concomitant severe renal impairment, a dosage reduction or prolonged dosing
intervals may be appropriate.
Dosing: Pediatric
(For additional information see "Clarithromycin: Pediatric drug information")
Note: All pediatric dosing recommendations based on immediate release product

formulations (tablet and oral suspension):
General dosing, susceptible infection, mild to moderate infection: Infants,

Children, and Adolescents: Oral: 15 mg/kg/day divided every 12 hours; maximum single
dose: 500 mg (Red Book [AAP 2012])
Bartonellosis, treatment and secondary prophylaxis in HIV-exposed/-positive

patients (excluding CNS infections and endocarditis): Limited data available: Oral:
Infants and Children: 15 mg/kg/day divided every 12 hours for at least 3 months;
maximum single dose: 500 mg (CDC 2009)
Adolescents: 500 mg twice daily administered for at least 3 months (DHHS [adult]
2013)
Endocarditis, prophylaxis: Note: AHA guidelines (Baltimore 2015) limit the use of
prophylactic antibiotics to patients at the highest risk for infective endocarditis (IE) or
adverse outcomes (eg, prosthetic heart valves, patients with previous IE, unrepaired
cyanotic congenital heart disease, repaired congenital heart disease with prosthetic
material or device during first 6 months after procedure, repaired congenital heart
disease with residual defects at the site or adjacent to site of prosthetic patch or device,
heart transplant recipients with cardiac valvulopathy):
Dental procedures in patients allergic to penicillins: Limited data available: Infants,

Children, and Adolescents: Oral: 15 mg/kg; maximum single dose: 500 mg;
administer 30 to 60 minutes before procedure (AHA [Wilson 2007]).
Group A streptococcal infection; rheumatic fever, primary prevention and

treatment of streptococcal tonsillopharyngitis: Infants, Children, and Adolescents:
Oral: 15 mg/kg/day divided every 12 hours for 10 days; maximum single dose: 250 mg
(Gerber 2009; IDSA [Shulman 2012])
Helicobacter pylori eradication: Children and Adolescents: Oral: 20 mg/kg/day

divided every 12 hours for 7 to 14 days. Note: Duration dependent on regimen used;
maximum single dose: 500 mg. Administer as part of triple or quadruple combination
regimens with amoxicillin and proton pump inhibitor with or without metronidazole
(Koletzko 2011)
Lyme disease: Limited data available: Infants, Children, and Adolescents: Oral: 7.5
mg/kg twice daily for 14 to 21 days; maximum single dose: 500 mg (IDSA [Wormser
2006])
Mycobacterium avium complex infection (MAC) (HIV-exposed/-positive):
Infants and Children (DHHS [pediatric] 2013):
Prophylaxis:
Primary prophylaxis: Oral: 15 mg/kg/day divided every 12 hours;

maximum single dose: 500 mg; to prevent first episode begin therapy at
the following CD4+ T-lymphocyte counts (see below):
Infants <12 months: <750 cells/mm3
Children 1 to <2 years: <500 cells/mm3
Children 2 to 5 years: <75 cells/mm3
Children ≥6 years: <50 cells/mm3
Secondary prophylaxis: Oral: 15 mg/kg/day divided every 12 hours;

maximum single dose: 500 mg; use in combination with ethambutol with
or without rifabutin
Treatment: Oral: 15 to 30 mg/kg/day divided every 12 hours; maximum single

dose: 500 mg; use in combination with ethambutol and if severe infection,
rifabutin; follow with chronic suppressive therapy
Adolescents (DHHS [adult] 2013):
Prophylaxis:
Primary prophylaxis: Oral: 500 mg twice daily
Secondary prophylaxis: Oral: 500 mg twice daily plus ethambutol;

consider additional agents (eg, rifabutin, aminoglycoside, fluoroquinolone)
for CD4 <50 cells/mm3, high mycobacterial load, or ineffective
antiretroviral therapy.
Treatment: Oral: 500 mg twice daily in combination with ethambutol: Consider

additional agents (eg, rifabutin, aminoglycoside, fluoroquinolone) for CD4 <50
cells/mm3, high mycobacterial load, or ineffective antiretroviral therapy.
Otitis media, acute (AOM): Infants ≥6 months and Children: Oral: 15 mg/kg/day
divided every 12 hours for 10 days; maximum single dose: 500 mg; Note: Due to
increased S. pneumoniae and H. influenzae resistance, clarithromycin is not routinely
recommended as a treatment option (AAP [Lieberthal 2013])
Peritonitis (peritoneal dialysis), prophylaxis for patients requiring invasive dental

procedures: Infants, Children, and Adolescents: Oral: 15 mg/kg 30 to 60 minutes
before dental procedure; maximum single dose: 500 mg (Warady [ISPD 2012])
Pertussis: Infants, Children, and Adolescents: Oral: 15 mg/kg/day divided every 12

hours for 7 days; maximum single dose: 500 mg (CDC [Tiwari 2005])
Pneumonia, community-acquired (CAP); presumed atypical pneumonia (M.

pneumoniae, C. pneumoniae, C. trachomatis); mild infection or step-down
therapy: Infants >3 months, Children, and Adolescents: Oral: 15 mg/kg/day every 12
hours for 10 days; shorter courses may be appropriate for mild disease; maximum
single dose: 500 mg; Note: A beta-lactam antibiotic should be added if typical bacterial
pneumonia cannot be ruled out (Bradley 2011).
Dosing: Renal Impairment: Pediatric
Infants, Children, and Adolescents: The following adjustments have been

recommended (Aronoff 2007). Note: Renally adjusted dose recommendations are
based on a dose 15 mg/kg/day divided twice daily.
GFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary
GFR 10 to 29 mL/minute/1.73 m2: 4 mg/kg/dose every 12 hours
GFR <10 mL/minute/1.73 m2: 4 mg/kg/dose once daily
Hemodialysis: Administer after HD session is completed: 4 mg/kg/dose once daily
Peritoneal dialysis: 4 mg/kg/dose once daily
Dosing: Hepatic Impairment: Pediatric

Infants, Children, and Adolescents: No dosage adjustment necessary if renal function is normal;
however, in patients with hepatic impairment and concomitant severe renal impairment, a
dosage reduction or prolonged dosing intervals may be appropriate.
Dosing: Geriatric
Refer to adult dosing.
Dosage Forms: US
Excipient information presented when available (limited, particularly for generics); consult
specific product labeling. [DSC] = Discontinued product
Suspension Reconstituted, Oral:
Biaxin: 250 mg/5 mL (100 mL [DSC])
Generic: 125 mg/5 mL (50 mL, 100 mL); 250 mg/5 mL (50 mL, 100 mL)
Tablet, Oral:
Biaxin: 250 mg [DSC] [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10
(quinoline yellow)]
Biaxin: 500 mg [DSC] [contains fd&c yellow #10 (quinoline yellow)]
Generic: 250 mg, 500 mg
Tablet Extended Release 24 Hour, Oral:
Generic: 500 mg
Generic Equivalent Available: US

Yes
Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult
specific product labeling.
Suspension Reconstituted, Oral:
Biaxin: 125 mg/5 mL (55 mL, 105 mL); 250 mg/5 mL (105 mL)
Generic: 125 mg/5 mL (55 mL, 105 mL, 150 mL); 250 mg/5 mL (55 mL, 105 mL, 150
mL)
Tablet, Oral:
Biaxin: 250 mg, 500 mg [contains fd&c yellow #10 (quinoline yellow)]
Generic: 250 mg, 500 mg
Tablet Extended Release 24 Hour, Oral:
Biaxin XL: 500 mg [contains fd&c yellow #10 aluminum lake]
Generic: 500 mg
Administration: Adult
Oral:
IR tablets and granules for suspension: Administer with or without meals. Administer
every 12 hours rather than twice daily to avoid peak and trough variation. Shake
suspension well before each use.
ER tablets: Administer with food. Do not break, crush, or chew.
Bariatric surgery: Some institutions may have specific protocols that conflict with
these recommendations; refer to institutional protocols as appropriate. Switch to IR
formulation (tablet or oral solution).
Administration: Pediatric
Oral:
Immediate-release tablets and oral suspension: May be administered with or without meals;
give every 12 hours rather than twice daily to avoid peak and trough variation. Shake
suspension well before each use.
Extended-release tablets: Should be given with food. Do not crush or chew extended-
release tablet.
Use: Labeled Indications
Chronic obstructive pulmonary disease, acute exacerbation: Treatment of acute

bacterial exacerbation of chronic bronchitis in adults due to susceptible Haemophilus
influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, or Streptococcus
pneumoniae.
Helicobacter pylori eradication: Eradication of Helicobacter pylori to reduce the risk of

duodenal ulcer recurrence as a component of combination therapy (triple therapy) in adults
with H. pylori infection and duodenal ulcer disease (active or 5-year history of duodenal
ulcer).
Limitations of use: Regimens that contain clarithromycin as the single antibacterial

agent are more likely to be associated with the development of clarithromycin
resistance. Clarithromycin-containing regimens should not be used in patients with
known or suspected clarithromycin-resistant isolates (efficacy is reduced).
Mycobacterial (nontuberculous) infection: Prophylaxis and treatment of disseminated

mycobacterial infections due to Mycobacterium avium complex (MAC) in patients with
advanced HIV infection.
Otitis media: Treatment of acute otitis media in pediatric patients due to susceptible H.
influenzae, M. catarrhalis, or S. pneumoniae.
Pneumonia, community-acquired: Treatment of community-acquired pneumonia due to

susceptible Mycoplasma pneumoniae, S. pneumoniae, or Chlamydophila pneumoniae
(adult and pediatric patients) and H. influenzae, H. parainfluenzae, or M. catarrhalis (adults).
Skin/skin structure infection: Treatment of uncomplicated skin/skin structure infection due

to susceptible Staphylococcus aureus or Streptococcus pyogenes.
Streptococcal pharyngitis: Treatment of pharyngitis/tonsillitis due to susceptible S.

pyogenes (alternative agent for patients with severe penicillin allergy).
Use: Off-Label: Adult
Bartonella spp. infection; Bronchiolitis obliterans; Endocarditis, prophylaxis, dental or invasive

respiratory tract procedure; Mycobacterium abscessus infection; Pertussis; Q fever (Coxiella
burnetii), acute symptomatic
Medication Safety Issues

Sound-alike/look-alike issues:
Clarithromycin may be confused with Claritin, clindamycin, erythromycin
Adverse Reactions
1% to 10%:
Central nervous system: Headache (2%), insomnia
Dermatologic: Skin rash (children 3%)
Gastrointestinal: Dysgeusia (adults 3% to 7%), vomiting (children 6%), diarrhea (3% to

6%), nausea (adults 3%), abdominal pain (2% to 3%), dyspepsia (adults 2%)
Hematologic & oncologic: Prolonged prothrombin time (adults 1%)
Hepatic: Abnormal hepatic function tests
Hypersensitivity: Anaphylactoid reaction
Infection: Candidiasis (including oral)
Renal: Increased blood urea nitrogen (4%)
<1%, postmarketing, and/or case reports: Abdominal distension, abnormal albumin-globulin

ratio, acne vulgaris, acute generalized exanthematous pustulosis, ageusia, agranulocytosis,
altered sense of smell, anaphylaxis, angioedema, anorexia, anosmia, anxiety, asthma, atrial
fibrillation, behavioral changes, bullous dermatitis, cellulitis, chest pain, chills, cholestasis,
cholestatic hepatitis, Clostridioides (formerly Clostridium) difficile-associated diarrhea,
Clostridioides (formerly Clostridium) difficile (colitis), confusion, constipation, dark urine
(abnormal urine color associated with liver injury), decreased appetite, decreased white
blood cell count, dental discoloration (reversible with dental cleaning), depersonalization,
depression, disorientation, dizziness, DRESS syndrome, drowsiness, dyskinesia,
eosinophilia, epistaxis, eructation, esophagitis, extrasystoles, fatigue, fever, flatulence,
gastritis, gastroenteritis, gastroesophageal reflux disease, glossitis, hallucination, hearing
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loss (reversible), hemorrhage, hepatic failure, hepatic insufficiency, hepatitis, hepatotoxicity

(idiosyncratic) (Chalasani 2014), hyperhidrosis, hypersensitivity reaction, hypoglycemia, IgA
vasculitis, increased gamma-glutamyl transferase, increased INR, increased lactate
dehydrogenase, increased serum alkaline phosphatase, increased serum ALT, increased
serum AST, increased serum bilirubin, increased serum creatinine, infection, interstitial
nephritis, jaundice, leukopenia, loss of consciousness, maculopapular rash, malaise, manic
behavior, muscle spasm, myalgia, myopathy, neck stiffness, nervousness, neutropenia,
nightmares, palpitations, pancreatitis, parasomnias, paresthesia, prolonged QT interval on
ECG, pruritus, pseudomembranous colitis, psychosis, pulmonary embolism, rectal pain,
renal failure, rhabdomyolysis, seizure, Stevens-Johnson syndrome, stomatitis,
thrombocytopenia, tinnitus, tongue discoloration, torsades de pointes, toxic epidermal
necrolysis, tremor, urticaria, vaginal infection, ventricular arrhythmia, ventricular tachycardia,
vertigo, weakness, xerostomia
Contraindications
Hypersensitivity to clarithromycin, erythromycin, any of the macrolide antibiotics, or any

component of the formulation; history of cholestatic jaundice/hepatic dysfunction associated
with prior use of clarithromycin; concomitant use with cisapride, pimozide, ergot alkaloids
(eg, ergotamine, dihydroergotamine), lomitapide, or HMG-CoA reductase inhibitors
extensively metabolized by CYP3A4 (eg, lovastatin, simvastatin); concomitant use with
colchicine in patients with renal or hepatic impairment
Canadian labeling: Additional contraindications (not in US labeling): Severe hepatic failure in

combination with renal impairment; history of QT prolongation (congenital or documented
acquired QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes;
hypokalemia; concomitant use with saquinavir, midazolam (oral), colchicine (regardless of
hepatic/renal impairment), ticagrelor; concomitant use with astemizole, domperidone,
terfenadine, or ranolazine (not available in Canada)
Warnings/Precautions
Concerns related to adverse effects:
• Altered cardiac conduction: Use has been associated with QT prolongation and
infrequent cases of arrhythmias, including torsades de pointes (may be fatal); avoid use
in patients with known prolongation of the QT interval, ventricular cardiac arrhythmia
(including torsades de pointes), uncorrected hypokalemia or hypomagnesemia,
clinically significant bradycardia, and patients receiving Class IA (eg, quinidine,
procainamide) or Class III (eg, amiodarone, dofetilide, sotalol) antiarrhythmic agents or
other drugs known to prolong the QT interval.
• Hepatic effects: Elevated liver function tests and hepatitis (hepatocellular and/or
cholestatic with or without jaundice) have been reported; usually reversible after
discontinuation of clarithromycin. May lead to hepatic failure or death (rarely), especially
in the presence of preexisting diseases and/or concomitant use of medications.
Discontinue immediately if symptoms of hepatitis (eg, anorexia, jaundice, abdominal
tenderness, pruritus, dark urine) occur.
• Hypersensitivity reactions: Severe acute reactions have been reported, including

anaphylaxis, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug
rash with eosinophilia and systemic symptoms (DRESS), Henoch-Schönlein purpura
(IgA vasculitis), and acute generalized exanthematous pustulosis; discontinue therapy
and initiate treatment immediately for severe acute hypersensitivity reactions.
• Superinfection: Use may result in fungal or bacterial superinfection, including C.

difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been
observed >2 months postantibiotic treatment.
Disease-related concerns:
• CAD: Use with caution in patients with CAD. A clinical trial in patients with CAD
demonstrated an increase in risk of all-cause mortality ≥1 year after the end of
treatment in patients randomized to receive clarithromycin. Other epidemiologic studies
evaluating this risk have variable results.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; exacerbation
of symptoms and new onset of symptoms has occurred.
• Renal impairment: Use with caution in severe renal impairment; dosage adjustment
required.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or

frequency adjustment, additional monitoring, and/or selection of alternative therapy.
Consult drug interactions database for more detailed information.
Special populations:
• Elderly: Use with caution; elderly patients may be at increased risk of torsades de
pointes.
• HIV patients: Decreased survival has been observed in HIV patients with
Mycobacterium avium complex (MAC) receiving clarithromycin doses above the
maximum recommended dose; maximum recommended dosing should not be
exceeded in this population. Development of resistance to clarithromycin has been
observed when used as prophylaxis and treatment of MAC infection (Biaxin Canadian
product labeling).
Dosage form specific issues:
• Extended release formulation: The presence of extended release tablets in the stool
has been reported, particularly in patients with anatomic (eg, ileostomy, colostomy) or
functional GI disorders with decreased transit times. Consider alternative dosage forms
(eg, suspension) or an alternative antimicrobial for patients with tablet residue in the
stool and no signs of clinical improvement.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts
are potentially toxic and have been associated hyperosmolality, lactic acidosis,
seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).
Other warnings/precautions:
• Appropriate use: Helicobacter pylori eradication: Short-term combination therapy (≤7

days) has been associated with a higher incidence of treatment failure. Current
guidelines recommend 10 to 14 days of therapy (triple or quadruple) for eradication of
H. pylori in pediatric and adult patients (Chey 2007; NASPHGAN [Koletzko 2011]).
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on
clinically relevant drug interaction potential; Inhibits CYP3A4 (strong), OATP1B1/1B3
(SLCO1B1/1B3), P-glycoprotein/ABCB1
Drug Interactions
(For additional information: Launch drug interactions program)
Abemaciclib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Abemaciclib. Management: In patients taking abemaciclib at a dose of 200 mg or 150 mg
twice daily, reduce the dose to 100 mg twice daily when combined with strong CYP3A4
inhibitors. In patients taking abemaciclib 100 mg twice daily, decrease the dose to 50 mg
twice daily. Risk D: Consider therapy modification
Acalabrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Acalabrutinib. Risk X: Avoid combination
Ado-Trastuzumab Emtansine: CYP3A4 Inhibitors (Strong) may increase serum

concentrations of the active metabolite(s) of Ado-Trastuzumab Emtansine. Specifically,
strong CYP3A4 inhibitors may increase concentrations of the cytotoxic DM1 component.
Risk X: Avoid combination
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib.

Management: Reduce afatinib by 10 mg if not tolerated. Some non-US labeling
recommends avoiding combination if possible. If used, administer the P-gp inhibitor
simultaneously with or after the dose of afatinib. Risk D: Consider therapy modification
Alfuzosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin.
Alitretinoin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of
Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when
used together with strong CYP3A4 inhibitors. Monitor for increased alitretinoin
effects/toxicities if combined with a strong CYP3A4 inhibitor. Risk D: Consider therapy
modification
Almotriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Almotriptan. Management: Limit initial almotriptan dose to 6.25 mg and maximum dose to
12.5 mg in any 24-period when used with a strong CYP3A4 inhibitor. Avoid concurrent use
in patients with impaired hepatic or renal function. Risk D: Consider therapy modification
Alosetron: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron.
Risk C: Monitor therapy
ALPRAZolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

ALPRAZolam. Management: Consider using an alternative agent that is less likely to
interact. If combined, monitor for increased therapeutic/toxic effects of alprazolam if
combined with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents

(Moderate Risk). Risk C: Monitor therapy
Antihepaciviral Combination Products: May increase the serum concentration of

Clarithromycin. Management: Avoid clarithromycin doses greater than 1000 mg/day when
used with an antihepaciviral combination product. Further dose reductions may be needed
in patients with impaired renal function. Consider an alternative antimicrobial for any non-
MAC infection. Risk D: Consider therapy modification
Antineoplastic Agents (Vinca Alkaloids): Macrolide Antibiotics may increase the serum
concentration of Antineoplastic Agents (Vinca Alkaloids). Macrolides may also increase the
distribution of Vinca Alkaloids into certain cells and/or tissues. Management: Consider an
alternative to using a macrolide antibiotic when possible in order to avoid the potential for
increased vinca alkaloid toxicity. Risk D: Consider therapy modification
Apixaban: Clarithromycin may increase the serum concentration of Apixaban. Risk C:

Monitor therapy
Aprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Aprepitant.
ARIPiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

ARIPiprazole. Management: Aripiprazole dose reductions are required for indications other
than major depressive disorder. Dose reductions vary based on formulation, CYP2D6
genotype, and use of CYP2D6 inhibitors. See full interaction monograph for details. Risk D:
Consider therapy modification
ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Strong) may increase serum concentrations of

the active metabolite(s) of ARIPiprazole Lauroxil. Management: Decrease aripiprazole
lauroxil dose to next lower strength if used with strong CYP3A4 inhibitors for over 14 days.
No dose adjustment needed if using the lowest dose (441 mg). Max dose is 441 mg in
CYP2D6 PMs or if also taking strong CYP2D6 inhibitors. Risk D: Consider therapy
modification
Astemizole: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the
QTc-prolonging effect of Astemizole. QT-prolonging Strong CYP3A4 Inhibitors (Moderate
Risk) may increase the serum concentration of Astemizole. Risk X: Avoid combination
Asunaprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Asunaprevir. Risk X: Avoid combination
Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum

concentration of Asunaprevir. Risk X: Avoid combination
Atazanavir: May decrease serum concentrations of the active metabolite(s) of

Clarithromycin. Atazanavir may increase the serum concentration of Clarithromycin.
Management: Decrease clarithromycin dose 50% and do not exceed 1,000 mg per day.
Decrease clarithromycin dose 75% in patients with CrCL less than 30 mL/min. Use
alternative antimicrobial therapy if treating infections other than Mycobacterium avium
complex. Risk D: Consider therapy modification
AtorvaSTATin: Clarithromycin may increase the serum concentration of AtorvaSTATin.

Management: Limit atorvastatin to a maximum dose of 20 mg/day (for adults) when used
with clarithromycin. If this combination is used, monitor patients more closely for evidence of
atorvastatin toxicity. Risk D: Consider therapy modification
Avanafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avanafil.
Avapritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Avapritinib. Risk X: Avoid combination
Axitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
Management: Avoid concurrent use of axitinib with any strong CYP3A inhibitor whenever
possible. If a strong CYP3A inhibitor must be used with axitinib, a 50% axitinib dose
reduction is recommended. Risk D: Consider therapy modification
Barnidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Barnidipine. Risk X: Avoid combination
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical).
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG
Vaccine (Immunization). Risk C: Monitor therapy
Benperidol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Benperidol. Risk C: Monitor therapy
Benzhydrocodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk
C: Monitor therapy
Betamethasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum

concentration of Betamethasone (Ophthalmic). Risk C: Monitor therapy
Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of

Betrixaban. Management: Decrease adult betrixaban dose to an initial single dose of 80 mg
followed by 40 mg once daily if combined with a P-gp inhibitor. Avoid concomitant use of
betrixaban and P-gp inhibitors in patients with severe renal impairment (CrCL less than 30
mL/min). Risk D: Consider therapy modification
Bictegravir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Bictegravir. Risk C: Monitor therapy
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of

Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in
patients with moderate to severe renal insufficiency who are receiving p-glycoprotein
inhibitors. Risk D: Consider therapy modification
Blonanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Blonanserin. Risk X: Avoid combination
Bortezomib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Bortezomib. Risk C: Monitor therapy
Bosentan: May increase serum concentrations of the active metabolite(s) of Clarithromycin.

Specifically, bosentan may increase concentrations of 14-hydroxyclarithromycin. Bosentan
may decrease the serum concentration of Clarithromycin. Clarithromycin may increase the
serum concentration of Bosentan. Management: Consider alternative antimicrobial if
possible. The clinical activity of clarithromycin may be altered, and increased bosentan
toxicity may be expected. Risk D: Consider therapy modification
Bosutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib.
Brentuximab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E
(MMAE) component may be increased. Risk C: Monitor therapy
Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum

concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl
auristatin E (MMAE) component may be increased. Risk C: Monitor therapy
Brexpiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Brexpiprazole. Management: Reduce brexpiprazole dose 50% with strong CYP3A4
inhibitors; reduce to 25% of usual if used with both a strong CYP3A4 inhibitor and a
CYP2D6 inhibitor in patients not being treated for MDD, or strong CYP3A4 inhibitor used in
a CYP2D6 poor metabolizer. Risk D: Consider therapy modification
Brigatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brigatinib.
Management: Avoid concurrent use of brigatinib with strong CYP3A4 inhibitors when
possible. If combination cannot be avoided, reduce the brigatinib dose by approximately
50%, rounding to the nearest tablet strength (ie, from 180 mg to 90 mg, or from 90 mg to 60
mg). Risk D: Consider therapy modification
Brinzolamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Brinzolamide. Risk C: Monitor therapy
Bromocriptine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Bromocriptine. Risk X: Avoid combination
Budesonide (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of
Budesonide (Nasal). Risk C: Monitor therapy
Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum
concentration of Budesonide (Oral Inhalation). Risk C: Monitor therapy
Budesonide (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration
of Budesonide (Systemic). Risk X: Avoid combination
Budesonide (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of
Budesonide (Topical). Management: Per US prescribing information, avoid this combination.
Canadian product labeling does not recommend strict avoidance. If combined, monitor for
excessive glucocorticoid effects as budesonide exposure may be increased. Risk D:
Buprenorphine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Buprenorphine. Risk C: Monitor therapy
BusPIRone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

BusPIRone. Management: Limit the buspirone dose to 2.5 mg daily and monitor patients for
increased buspirone effects/toxicities if combined with strong CYP3A4 inhibitors. Risk D:
Cabazitaxel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Cabazitaxel. Management: Concurrent use of cabazitaxel with strong inhibitors of CYP3A4
should be avoided when possible. If such a combination must be used, consider a 25%
reduction in the cabazitaxel dose. Risk D: Consider therapy modification
Cabergoline: Clarithromycin may increase the serum concentration of Cabergoline. Risk C:

Monitor therapy
Cabozantinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Cabozantinib. Management: Avoid use of a strong CYP3A4 inhibitor with cabozantinib if
possible. If combined, decrease cabozantinib capsules (Cometriq) by 40 mg from previous
dose or decrease cabozantinib tablets (Cabometyx) by 20 mg from previous dose. Risk D:
Calcifediol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcifediol.
Calcium Channel Blockers: Macrolide Antibiotics may decrease the metabolism of Calcium
Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine
Canadian labeling specifically recommends avoiding its use in combination with
clarithromycin. Exceptions: Clevidipine. Risk D: Consider therapy modification
Cannabidiol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Cannabidiol. Risk C: Monitor therapy
Cannabis: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabis.
More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be
increased. Risk C: Monitor therapy
Capmatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Capmatinib. Risk C: Monitor therapy
CarBAMazepine: May increase serum concentrations of the active metabolite(s) of

Clarithromycin. Clarithromycin may increase the serum concentration of CarBAMazepine.
CarBAMazepine may decrease the serum concentration of Clarithromycin. Management:
Consider alternatives to this combination when possible. If combined, monitor for increased
carbamazepine effects/toxicities and for reduced clarithromycin efficacy. Risk D: Consider
therapy modification
Cardiac Glycosides: Macrolide Antibiotics may increase the serum concentration of Cardiac
Glycosides. Risk C: Monitor therapy
Cariprazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Cariprazine. Management: Decrease cariprazine dose 50% (4.5 mg to 1.5 mg or 3 mg; 1.5
mg to 1.5 mg every other day) if starting a strong CYP3A4 inhibitor. If on a strong CYP3A4
inhibitor, start cariprazine at 1.5 mg day 1, 0 mg day 2, then 1.5 mg daily. May increase to 3
mg daily Risk D: Consider therapy modification
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of

Celiprolol. Risk C: Monitor therapy
Ceritinib: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4

Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may
increase the serum concentration of Ceritinib. Management: Avoid use of ceritinib and
strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If combined,
decrease ceritinib dose by one-third (to the nearest 150 mg) and monitor patients for
ceritinib toxicities including QTc prolongation. Risk D: Consider therapy modification
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine.
Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14
days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Cilostazol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilostazol.
Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients
who are also receiving strong inhibitors of CYP3A4. Risk D: Consider therapy modification
Cinacalcet: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Cinacalcet. Risk C: Monitor therapy
Cisapride: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-
prolonging effect of Cisapride. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk)
may increase the serum concentration of Cisapride. Risk X: Avoid combination
Citalopram: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4

increase the serum concentration of Citalopram. Risk C: Monitor therapy
Cobicistat: Clarithromycin may increase the serum concentration of Cobicistat. Cobicistat

may increase the serum concentration of Clarithromycin. Management: Consider alternative
antibiotics. Reduce clarithromycin dose by 50% in patients receiving
elvitegravir/cobicistat/emtricitabine/tenofovir with estimated creatinine clearance 50 to 60
mL/min. Closely monitor for clarithromycin toxicity. Risk D: Consider therapy modification
Cobimetinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Cobimetinib. Risk X: Avoid combination
Codeine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active
metabolite(s) of Codeine. Risk C: Monitor therapy
Colchicine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine.
Management: Colchicine is contraindicated in patients with impaired renal or hepatic
function who are also receiving a strong CYP3A4 inhibitor. In those with normal renal and
hepatic function, reduce colchicine dose as directed. See interaction monograph for details.
Risk D: Consider therapy modification
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of

Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased.
Management: Colchicine is contraindicated in patients with impaired renal or hepatic
function who are also receiving a P-gp inhibitor. In those with normal renal and hepatic
function, reduce colchicine dose as directed. See interaction monograph for details. Risk D:
Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Conivaptan. Risk X: Avoid combination
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with
Inhibitors). Risk X: Avoid combination
Copanlisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Copanlisib. Management: If concomitant use of copanlisib and strong CYP3A4 inhibitors
cannot be avoided, reduce the copanlisib dose to 45 mg. Monitor patients for increased
copanlisib effects/toxicities. Risk D: Consider therapy modification
Corticosteroids (Orally Inhaled): CYP3A4 Inhibitors (Strong) may increase the serum
concentration of Corticosteroids (Orally Inhaled). Management: Orally inhaled fluticasone
propionate with a strong CYP3A4 inhibitor is not recommended. Exceptions:
Beclomethasone (Oral Inhalation); Triamcinolone (Systemic). Risk C: Monitor therapy
Corticosteroids (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum

concentration of Corticosteroids (Systemic). Exceptions: MethylPREDNISolone;
PrednisoLONE (Systemic); PredniSONE. Risk C: Monitor therapy
Crizotinib: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4

increase the serum concentration of Crizotinib. Management: Avoid concomitant use of
crizotinib and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If
combined, decrease crizotinib dose to 250 mg daily. Monitor patients for crizotinib toxicities
including QTc prolongation and arrhythmias. Risk D: Consider therapy modification
CycloSPORINE (Systemic): Clarithromycin may increase the serum concentration of

CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May increase serum concentrations of the active

metabolite(s) of Clarithromycin. CYP3A4 Inducers (Moderate) may decrease the serum
concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for
patients receiving a CYP3A inducer. Drugs that enhance the metabolism of clarithromycin
into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and impair its
efficacy. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase serum concentrations of the active metabolite(s)
of Clarithromycin. Clarithromycin may increase the serum concentration of CYP3A4
Inducers (Strong). CYP3A4 Inducers (Strong) may decrease the serum concentration of
Clarithromycin. Management: Consider alternative antimicrobial therapy for patients
receiving a CYP3A inducer. Drugs that enhance the metabolism of clarithromycin into 14-
hydroxyclarithromycin may alter the clinical activity of clarithromycin and may impair
clarithromycin efficacy. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High
risk with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk
with Inhibitors). Management: Consider avoiding this combination. Some combinations are
specifically contraindicated by manufacturers; others may have recommended dose
adjustments. If combined, monitor for increased substrate effects. Risk D: Consider therapy
modification
CYP3A4 Substrates (High risk with Inhibitors): CYP3A4 Inhibitors (Strong) may decrease
the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider
avoiding this combination. Some combinations are specifically contraindicated by
manufacturers; others may have recommended dose adjustments. If combined, monitor for
increased substrate effects. Exceptions: Alitretinoin (Systemic); AmLODIPine;
Benzhydrocodone; Buprenorphine; Gefitinib; HYDROcodone; Mirtazapine; Praziquantel;

Ripretinib; Telithromycin; Vinorelbine. Risk D: Consider therapy modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations

of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy
Dabrafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Dabrafenib. Risk X: Avoid combination
Daclatasvir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Daclatasvir. Management: Decrease the daclatasvir dose to 30 mg once daily if combined
with a strong CYP3A4 inhibitor. No dose adjustment is needed when daclatasvir is used with
darunavir/cobicistat. Risk D: Consider therapy modification
Dapoxetine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Dapoxetine. Risk X: Avoid combination
Darifenacin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Darifenacin. Management: Limit the darifenacin dose to no more than 7.5 mg daily if
combined with strong CYP3A4 inhibitors. Monitor patients for increased darifenacin
toxicities (eg, dry mouth, constipation, headache, CNS effects) when these agents are
combined. Risk D: Consider therapy modification
Darolutamide: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum
concentration of Darolutamide. Risk C: Monitor therapy
Dasatinib: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4

increase the serum concentration of Dasatinib. Management: Avoid this combination if
possible. If combined, decrease dasatinib dose from 140 mg to 40 mg, 100 mg to 20 mg, or
70 mg to 20 mg. If taking 60 mg or 40 mg daily, stop dasatinib until the CYP3A4 inhibitor is
discontinued. Monitor for prolonged QT interval Risk D: Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with
Inducers). Risk C: Monitor therapy
Deflazacort: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active
metabolite(s) of Deflazacort. Management: Administer one third of the recommended
deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Risk D:
DexAMETHasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum

concentration of DexAMETHasone (Ophthalmic). Risk C: Monitor therapy
Dienogest: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dienogest.
Dihydroergotamine: Clarithromycin may increase the serum concentration of

Dihydroergotamine. Risk X: Avoid combination
DOCEtaxel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

DOCEtaxel. Management: Avoid the concomitant use of docetaxel and strong CYP3A4
inhibitors when possible. If combined use is unavoidable, consider a 50% docetaxel dose
reduction and monitor for increased docetaxel toxicities. Risk D: Consider therapy
modification
Domperidone: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the
QTc-prolonging effect of Domperidone. QT-prolonging Strong CYP3A4 Inhibitors (Moderate
Risk) may increase the serum concentration of Domperidone. Risk X: Avoid combination
Doxercalciferol: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the

active metabolite(s) of Doxercalciferol. Risk C: Monitor therapy
DOXOrubicin (Conventional): CYP3A4 Inhibitors (Strong) may increase the serum

concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong
CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S.
manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Risk D:
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum

concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-
glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S.
manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Risk D:
Dronabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Dronabinol. Risk C: Monitor therapy
Dronedarone: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the
QTc-prolonging effect of Dronedarone. QT-prolonging Strong CYP3A4 Inhibitors (Moderate
Risk) may increase the serum concentration of Dronedarone. Risk X: Avoid combination
Drospirenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Drospirenone. Management: Drospirenone use is contraindicated specifically when the
strong CYP3A4 inhibitors atazanavir and cobicistat are administered concurrently. Caution
should be used when drospirenone is coadministered with other strong CYP3A4 inhibitors.
Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Dutasteride. Risk C: Monitor therapy
Duvelisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Duvelisib.
Management: Reduce the dose of duvelisib to 15 mg twice a day when used together with a
strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Edoxaban: Clarithromycin may increase the serum concentration of Edoxaban.

Management: In patients treated for DVT/PE, reduce edoxaban dose to 30 mg daily when
combined with clarithromycin. No dose adjustment is recommended for patients treated for
atrial fibrillation. Monitor for increased edoxaban toxicities (ie, bleeding) when combined.
Efavirenz: May enhance the QTc-prolonging effect of Clarithromycin. Efavirenz may

decrease the serum concentration of Clarithromycin. Additionally, efavirenz may increase
the active metabolite of clarithromycin Management: Consider using an alternative antibiotic
in patients taking efavirenz. If concomitant therapy cannot be avoided, monitor for
decreased therapeutic effect of clarithromycin and for QT interval prolongation. Risk D:
Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of

Elagolix. Risk X: Avoid combination
Eletriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eletriptan.
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum
concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with
strong CYP3A4 inhibitors, administer two elexacaftor/tezacaftor/ivacaftor tablets (100 mg/50
mg/75 mg) in the morning, twice a week, approximately 3 to 4 days apart. No evening doses
of ivacaftor (150 mg) alone should be administered. Risk D: Consider therapy modification
Eliglustat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eliglustat.
Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with strong
CYP3A4 inhibitors. Use of strong CYP3A4 inhibitors is contraindicated in CYP2D6 IMs,
PMs, or in CYP2D6 EMs who are also taking strong or moderate CYP2D6 inhibitors. Risk D:
Eluxadoline: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum

concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice
daily if combined with OATP1B1/1B3 inhibitors and monitor patients for increased
eluxadoline effects/toxicities. Risk D: Consider therapy modification
Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4

increase the serum concentration of Encorafenib. Management: Avoid use of encorafenib
and strong CYP3A4 inhibitors when possible. If combined, decrease encorafenib dose from
450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Monitor closely for QT
interval prolongation. Risk D: Consider therapy modification
Enfortumab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E
(MMAE) component may be increased. Risk C: Monitor therapy
Entrectinib: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4

increase the serum concentration of Entrectinib. Risk X: Avoid combination
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with
Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have
a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4
substrate should be performed with caution and close monitoring. Risk D: Consider therapy
modification
Eplerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Eplerenone. Risk X: Avoid combination
Erdafitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erdafitinib.
Management: Avoid concomitant use of erdafitinib and strong CYP3A4 inhibitors when
possible. If combined, monitor closely for erdafitinib adverse reactions and consider dose
modifications accordingly. Risk D: Consider therapy modification
Ergot Derivatives: Macrolide Antibiotics may increase the serum concentration of Ergot
Derivatives. Cabergoline and Clarithromycin may interact, see specific monograph for full
details. Exceptions: Cabergoline; Lisuride; Nicergoline; Pergolide. Risk X: Avoid
combination
Ergotamine: Clarithromycin may increase the serum concentration of Ergotamine. Risk X:

Avoid combination
Erlotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erlotinib.
Management: Avoid use of this combination when possible. When the combination must be
used, monitor the patient closely for the development of severe adverse reactions, and if
such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Risk D:
Erythromycin (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Strong

CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and
ventricular arrhythmias when these agents are combined. Patients with additional risk
factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Estrogen Derivatives: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
Estrogen Derivatives. Risk C: Monitor therapy
Eszopiclone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Eszopiclone. Management: Limit the eszopiclone dose to 2 mg daily when combined with
strong CYP3A4 inhibitors and monitor for increased eszopiclone effects and toxicities (eg,
somnolence, drowsiness, CNS depression). Risk D: Consider therapy modification
Etizolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Etizolam.
Management: Consider use of lower etizolam doses when using this combination; specific
recommendations concerning dose adjustment are not available. Monitor clinical response
to the combination closely. Risk D: Consider therapy modification
Everolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Everolimus. Risk X: Avoid combination
Evogliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Evogliptin.
Fedratinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fedratinib.
Management: Consider alternatives when possible. If used together, decrease fedratinib
dose to 200 mg/day. After the inhibitor is stopped, increase fedratinib to 300 mg/day for the
first 2 weeks and then to 400 mg/day as tolerated. Risk D: Consider therapy modification
FentaNYL: CYP3A4 Inhibitors (Strong) may increase the serum concentration of FentaNYL.
Management: Monitor patients closely for several days following initiation of this
combination, and adjust fentanyl dose as necessary. Risk D: Consider therapy modification
Fesoterodine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active
metabolite(s) of Fesoterodine. Management: Limit fesoterodine doses to 4 mg daily in
patients who are also receiving strong CYP3A4 inhibitors. Risk D: Consider therapy
modification
Fexinidazole [INT]: May enhance the QTc-prolonging effect of QT-prolonging Agents

(Moderate Risk). Risk X: Avoid combination
Flibanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Flibanserin. Management: Use of flibanserin with strong CYP3A4 inhibitors is
contraindicated. If starting flibanserin, start 2 weeks after the last dose of the CYP3A4
inhibitor. If starting a CYP3A4 inhibitor, start 2 days after the last dose of flibanserin. Risk X:
Avoid combination
Fluconazole: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4

Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and
FLUoxetine: May enhance the QTc-prolonging effect of Clarithromycin. Clarithromycin may

increase the serum concentration of FLUoxetine. Risk C: Monitor therapy
Fluticasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of
Fluticasone (Nasal). Risk X: Avoid combination
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum
concentration of Fluticasone (Oral Inhalation). Management: Use of orally inhaled
fluticasone propionate with strong CYP3A4 inhibitors is not recommended. Use of orally
inhaled fluticasone furoate with strong CYP3A4 inhibitors should be done with caution.
Monitor patients using such a combination more closely. Risk D: Consider therapy
modification
Fosaprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Fosaprepitant. Risk X: Avoid combination
Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with
Inhibitors). Risk C: Monitor therapy
Fostamatinib: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active
metabolite(s) of Fostamatinib. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates
(High risk with Inhibitors). Risk X: Avoid combination
Galantamine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Galantamine. Risk C: Monitor therapy
Gefitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gefitinib.
Gilteritinib: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-
prolonging effect of Gilteritinib. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk)
may increase the serum concentration of Gilteritinib. Management: Consider alternatives to
the use of gilteritinib with strong CYP3A4 inhibitors that prolong the QTc interval whenever
possible Risk D: Consider therapy modification
Glasdegib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Glasdegib.
Management: Consider alternatives to this combination when possible. If the combination
must be used, monitor closely for evidence of QT interval prolongation and other adverse
reactions to glasdegib. Risk D: Consider therapy modification
GlipiZIDE: Clarithromycin may increase the serum concentration of GlipiZIDE. Risk C:

Monitor therapy
GlyBURIDE: Clarithromycin may increase the serum concentration of GlyBURIDE. Risk C:

Monitor therapy
Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum

concentration of Grazoprevir. Risk X: Avoid combination
GuanFACINE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when
combined with a strong CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when
these agents are combined. Risk D: Consider therapy modification
Halofantrine: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the
QTc-prolonging effect of Halofantrine. QT-prolonging Strong CYP3A4 Inhibitors (Moderate
Risk) may increase the serum concentration of Halofantrine. Risk X: Avoid combination
HYDROcodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

HYDROcodone. Risk C: Monitor therapy
Ibrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrutinib.
Management: Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong
CYP3A4 inhibitor must be used short-term (eg, anti-infectives for 7 days or less), interrupt
ibrutinib therapy until the strong CYP3A4 inhibitor is discontinued. Risk X: Avoid
combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with
Inhibitors). Risk X: Avoid combination
Ifosfamide: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active
metabolite(s) of Ifosfamide. Risk C: Monitor therapy
Iloperidone: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active
metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95
may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of
Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong
CYP3A4 inhibitor. Risk D: Consider therapy modification
Imatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imatinib. Risk
C: Monitor therapy
Imidafenacin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Imidafenacin. Risk C: Monitor therapy
Irinotecan Products: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the
active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may
be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of
Irinotecan Products. Risk X: Avoid combination
Isavuconazonium Sulfate: CYP3A4 Inhibitors (Strong) may increase serum concentrations

of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors
(Strong) may increase isavuconazole serum concentrations. Management: Combined use is
considered contraindicated per US labeling. Lopinavir/ritonavir (and possibly other uses of
ritonavir doses less than 400 mg every 12 hours) is treated as a possible exception to this
contraindication despite strongly inhibiting CYP3A4. Risk X: Avoid combination
Istradefylline: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Istradefylline. Management: Limit the maximum istradefylline dose to 20 mg daily when
combined with strong CYP3A4 inhibitors and monitor for increased istradefylline
effects/toxicities. Risk D: Consider therapy modification
Ivabradine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Ivabradine. Risk X: Avoid combination
Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivacaftor.
Management: Ivacaftor dose reductions are required; consult full drug interaction
monograph content for age- and weight-specific recommendations. Risk D: Consider
Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Ixabepilone. Management: Avoid use of ixabepilone and strong CYP3A4 inhibitors when
possible. If combined, reduce the ixabepilone dose to 20 mg/m2. The previous ixabepilone
dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D:
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and
Estriol. Risk C: Monitor therapy
Lapatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib.
Management: Avoid use of lapatinib and strong CYP3A4 inhibitors when possible. If
combined, reduce lapatinib dose to 500 mg daily. The previous lapatinib dose can be
resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider
Larotrectinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Larotrectinib. Management: Avoid use of strong CYP3A4 inhibitors with larotrectinib. If this
combination cannot be avoided, reduce the larotrectinib dose by 50%. Increase to previous
dose after stopping the inhibitor after a period of 3 to 5 times the inhibitor half-life. Risk D:
Lefamulin: May enhance the QTc-prolonging effect of QT-prolonging CYP3A4 Substrates.

Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates.
Lefamulin prescribing information lists this combination as contraindicated. Risk X: Avoid
combination
Lefamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lefamulin.
Management: Avoid concomitant use of lefamulin tablets and strong inhibitors of CYP3A4.
Lemborexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Lemborexant. Risk X: Avoid combination
Lercanidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Lercanidipine. Risk X: Avoid combination
Levobupivacaine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Levobupivacaine. Risk C: Monitor therapy
Levomilnacipran: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Levomilnacipran. Management: Do not exceed a maximum adult levomilnacipran dose of 80
mg/day in patients also receiving strong CYP3A4 inhibitors. Risk D: Consider therapy
modification
Lomitapide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Lomitapide. Risk X: Avoid combination
Lopinavir: Clarithromycin may enhance the QTc-prolonging effect of Lopinavir. Lopinavir

may diminish the therapeutic effect of Clarithromycin. Specifically, lopinavir may decrease
the formation of the active 14-hydroxy-clarithromycin metabolite, which may negatively
impact clarithromycin effectiveness. Lopinavir may increase the serum concentration of
Clarithromycin. Clarithromycin may increase the serum concentration of Lopinavir. Risk X:
Avoid combination
Lorlatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lorlatinib.
Management: Avoid use of lorlatinib with strong CYP3A4 inhibitors. If the combination
cannot be avoided, reduce the lorlatinib dose from 100 mg once daily to 75 mg once daily,
or from 75 mg once daily to 50 mg once daily. Risk D: Consider therapy modification
Lovastatin: Clarithromycin may increase the serum concentration of Lovastatin. Risk X:

Avoid combination
Lumateperone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Lumateperone. Risk X: Avoid combination
Lumefantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Lumefantrine. Risk C: Monitor therapy
Lurasidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Lurasidone. Risk X: Avoid combination
Macitentan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Macitentan. Risk X: Avoid combination
Manidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Manidipine. Management: Consider avoiding concomitant use of manidipine and strong
CYP3A4 inhibitors. If combined, monitor closely for increased manidipine effects and
toxicities. Manidipine dose reductions may be required. Risk D: Consider therapy
modification
Maraviroc: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
Management: Reduce maraviroc to 150mg twice/day in adult and pediatric patients
weighing 40kg or more. See full interaction monograph or maraviroc labeling for dose
adjustments in pediatric patients less than 40kg. Do not use in patients with CrCl less than
30mL/min. Risk D: Consider therapy modification
MedroxyPROGESTERone: CYP3A4 Inhibitors (Strong) may increase the serum

concentration of MedroxyPROGESTERone. Risk C: Monitor therapy
Meperidine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Meperidine. Risk C: Monitor therapy
MethylPREDNISolone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

MethylPREDNISolone. Management: Consider methylprednisolone dose reduction in
patients receiving strong CYP3A4 inhibitors and monitor for increased steroid related
adverse effects. Risk D: Consider therapy modification
Midazolam: Macrolide Antibiotics may increase the serum concentration of Midazolam.

Management: Consider an alternative less likely to interact. Azithromycin is likely a lower-
risk macrolide, and benzodiazepines less dependent on CYP3A metabolism (e.g.,
lorazepam, oxazepam) are similarly less likely to interact. Risk D: Consider therapy
modification
Midostaurin: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the
QTc-prolonging effect of Midostaurin. QT-prolonging Strong CYP3A4 Inhibitors (Moderate
Risk) may increase the serum concentration of Midostaurin. Management: Consider
alternatives to this drug combination. If combined, monitor for QTc interval prolongation and
ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at
even higher risk. Risk D: Consider therapy modification
MiFEPRIStone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

MiFEPRIStone. Management: Limit mifepristone adult dose, when used for treatment of
hyperglycemia in Cushing's syndrome, to a maximum of 900 mg/day when combined with a
strong CYP3A4 inhibitor. Monitor for increased mifepristone toxicity regardless of dose or
indication. Risk D: Consider therapy modification
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk
with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for
increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone.
Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus,
and tacrolimus. Risk D: Consider therapy modification
Mirodenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Mirodenafil. Management: Consider using a lower dose of mirodenafil when used with
strong CYP3A4 inhibitors. Monitor for increased mirodenafil effects/toxicities with the use of
this combination. Risk D: Consider therapy modification
Mirtazapine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Mirtazapine. Risk C: Monitor therapy
Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with
Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted
substantially when used in patients being treated with mitotane. Risk D: Consider therapy
modification
Mizolastine: Macrolide Antibiotics may increase the serum concentration of Mizolastine.

Naldemedine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Naldemedine. Risk C: Monitor therapy
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of

Naldemedine. Risk C: Monitor therapy
Nalfurafine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Nalfurafine. Risk C: Monitor therapy
Naloxegol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naloxegol.
Neratinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Neratinib.
Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with
Inhibitors). Risk C: Monitor therapy
Nilotinib: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4

increase the serum concentration of Nilotinib. Management: Avoid concomitant use of
nilotinib and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If
combined, nilotinib dose reductions are required. Monitor patients for nilotinib toxicities
NiMODipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

NiMODipine. Risk X: Avoid combination
Nintedanib: Combined Inhibitors of CYP3A4 and P-glycoprotein may increase the serum
concentration of Nintedanib. Risk C: Monitor therapy
Nisoldipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Nisoldipine. Risk X: Avoid combination
Olaparib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Olaparib.
Management: Avoid use of strong CYP3A4 inhibitors with olaparib, if possible. If such
concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 100
mg twice daily and the dose of olaparib capsules should be reduced to 150 mg twice daily.
Ondansetron: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the
QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation
and ventricular arrhythmias when these agents are combined. Patients with additional risk
Osilodrostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Osilodrostat. Management: Reduce osilodrostat dose by 50% during coadministration with a
strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Osimertinib: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4

Inhibitors (Moderate Risk). Management: Consider alternatives to this drug combination. If
combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with
additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider
Ospemifene: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Ospemifene. Risk C: Monitor therapy
Oxybutynin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Oxybutynin. Risk C: Monitor therapy
Palbociclib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Palbociclib. Risk X: Avoid combination
Panobinostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Panobinostat. Management: Reduce the panobinostat dose to 10 mg when it must be used
with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Parecoxib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Parecoxib.
Specifically, serum concentrations of the active moiety valdecoxib may be increased. Risk
C: Monitor therapy
Paricalcitol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Paricalcitol. Risk C: Monitor therapy
PARoxetine: Clarithromycin may enhance the adverse/toxic effect of PARoxetine.

Clarithromycin may enhance the QTc-prolonging effect of PARoxetine. Risk C: Monitor
therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of

PAZOPanib. Risk X: Avoid combination
Pemigatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Pemigatinib. Management: If combined use cannot be avoided, reduce the pemigatinib dose
from 13.5 mg daily to 9 mg daily, or from 9 mg daily to 4.5 mg daily. Resume prior
pemigatinib dose after stopping the strong inhibitor once 3 half-lives of the inhibitor has
passed. Risk D: Consider therapy modification
Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Strong

CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and
Pexidartinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Pexidartinib. Management: Avoid use of pexidartinib with strong CYP3A4 inhibitors if
possible. If combined use cannot be avoided, the pexidartinib dose should be reduced.
Decrease 800 mg or 600 mg daily doses to 200 mg twice daily. Decrease doses of 400
mg/day to 200 mg/day. Risk D: Consider therapy modification
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum

concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also
enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where
p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.).
Exceptions: Loperamide. Risk C: Monitor therapy
Pimavanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Pimavanserin. Management: Decrease the pimavanserin dose to 10 mg daily when
combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Pimecrolimus: CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus.

Pimozide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimozide.
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate

Risk). Risk X: Avoid combination
Piperaquine: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the
QTc-prolonging effect of Piperaquine. QT-prolonging Strong CYP3A4 Inhibitors (Moderate
Risk) may increase the serum concentration of Piperaquine. Management: Consider
alternatives to this drug combination. If combined, monitor for QTc interval prolongation and
ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at
even higher risk. Risk D: Consider therapy modification
Pitavastatin: Clarithromycin may increase the serum concentration of Pitavastatin. Risk C:

Monitor therapy
Polatuzumab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule
component of polatuzumab vedotin, may be increased. Risk C: Monitor therapy
PONATinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

PONATinib. Management: Per ponatinib U.S. prescribing information, the adult starting dose
of ponatinib should be reduced to 30 mg daily during treatment with any strong CYP3A4
inhibitor. Risk D: Consider therapy modification
Posaconazole: May increase the serum concentration of QT-prolonging CYP3A4

Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other
similar toxicities. Risk X: Avoid combination
Pranlukast: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Pranlukast. Risk C: Monitor therapy
Pravastatin: Clarithromycin may increase the serum concentration of Pravastatin.

Management: Limit pravastatin to a maximum of 40 mg/day (for adults) when used in
combination with clarithromycin. If this combination is used, monitor patients more closely
for evidence of pravastatin toxicity. Risk D: Consider therapy modification
Praziquantel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Praziquantel. Risk C: Monitor therapy
PrednisoLONE (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum

concentration of PrednisoLONE (Systemic). Risk C: Monitor therapy
PredniSONE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

PredniSONE. Risk C: Monitor therapy
Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of

Prucalopride. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of

Clarithromycin. Risk X: Avoid combination
QT-prolonging Antidepressants (Moderate Risk): QT-prolonging Strong CYP3A4 Inhibitors

(Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antidepressants
(Moderate Risk). Exceptions: Citalopram. Risk C: Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): May enhance the QTc-prolonging effect of

Clarithromycin. Management: Monitor for QTc interval prolongation and ventricular
arrhythmias when these agents are combined. Patients with additional risk factors for QTc
prolongation may be at even higher risk. Exceptions: Pimozide; QUEtiapine. Risk C:
Monitor therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging

effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). Management: Monitor
for QTc interval prolongation and ventricular arrhythmias when these agents are combined.
Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C:
Monitor therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Strong CYP3A4

Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging
Miscellaneous Agents (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate
Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents
(Moderate Risk). Exceptions: Domperidone; Halofantrine; Midostaurin; Piperaquine;

Toremifene. Risk X: Avoid combination
QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging

effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). Management: Monitor
for QTc interval prolongation and ventricular arrhythmias when these agents are combined.
Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C:
Monitor therapy
QUEtiapine: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4

increase the serum concentration of QUEtiapine. Management: Reduce the quetiapine dose
to one-sixth of the regular dose when combined with strong CYP3A4 inhibitors. Monitor
patients for quetiapine toxicities, including QTc prolongation and torsades de pointes. Risk
D: Consider therapy modification
Radotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Radotinib.
Ramelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Ramelteon. Risk C: Monitor therapy
Ranolazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Ranolazine. Risk X: Avoid combination
Red Yeast Rice: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Red
Yeast Rice. Specifically, concentrations of lovastatin and related compounds found in Red
Yeast Rice may be increased. Risk X: Avoid combination
Regorafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Regorafenib. Risk X: Avoid combination
Repaglinide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Repaglinide. Management: The addition of a CYP2C8 inhibitor to this drug combination may
substantially increase the magnitude of increase in repaglinide exposure. Risk C: Monitor
therapy
Retapamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Retapamulin. Management: Avoid this combination in patients less than 2 years old. No
action is required in other populations. Risk C: Monitor therapy
Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations

of the active metabolite(s) of Revefenacin. Risk X: Avoid combination
Ribociclib: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4

increase the serum concentration of Ribociclib. Management: Avoid concomitant use of
ribociclib and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If
combined, decrease the ribociclib dose to 400 mg daily. Monitor for ribociclib toxicities
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of

RifAXIMin. Risk C: Monitor therapy
Rilpivirine: Macrolide Antibiotics may increase the serum concentration of Rilpivirine.

Management: Consider the use of azithromycin or another non-macrolide alternative when
appropriate to avoid this potential interaction. Risk D: Consider therapy modification
Rimegepant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Rimegepant. Risk X: Avoid combination
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of

Rimegepant. Risk X: Avoid combination
Ripretinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ripretinib.
Ritonavir: May decrease serum concentrations of the active metabolite(s) of Clarithromycin.

Ritonavir may increase the serum concentration of Clarithromycin. Management: Decrease
clarithromycin dose 50% and do not exceed 1,000 mg per day. Decrease clarithromycin
dose 75% in patients with CrCL less than 30 mL/min. Use alternative antimicrobial therapy if
treating infections other than Mycobacterium avium complex. Risk D: Consider therapy
modification
Rivaroxaban: Clarithromycin may increase the serum concentration of Rivaroxaban.

Management: In patients with impaired renal function, clarithromycin should not be used
unless the potential benefits outweigh the potential risks. This interaction is unlikely clinically
significant in patients with normal renal function. Risk D: Consider therapy modification
RomiDEPsin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

RomiDEPsin. Risk C: Monitor therapy
Rupatadine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Rupatadine. Risk X: Avoid combination
Ruxolitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib.
Management: This combination should be avoided under some circumstances. See
monograph for details. Risk D: Consider therapy modification
Salmeterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Salmeterol. Risk X: Avoid combination
Saquinavir: May enhance the QTc-prolonging effect of Clarithromycin. Clarithromycin may

increase the serum concentration of Saquinavir. Risk X: Avoid combination
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with
SAXagliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

SAXagliptin. Management: Limit the saxagliptin dose to 2.5 mg daily when combined with
strong CYP3A4 inhibitors. When using the saxagliptin combination products
saxagliptin/dapagliflozin or saxagliptin/dapagliflozin/metformin, avoid use with strong
CYP3A4 inhibitors. Risk D: Consider therapy modification
Selumetinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Selumetinib. Management: Avoid concomitant use when possible. If combined, selumetinib
dose reductions are recommended and vary based on body surface area and selumetinib
dose. For details, see the Pediatric and Neonatal Lexi-Drugs monograph or the full drug
interaction monograph Risk D: Consider therapy modification
Sibutramine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active
metabolite(s) of Sibutramine. CYP3A4 Inhibitors (Strong) may increase the serum
concentration of Sibutramine. Risk C: Monitor therapy
Sildenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sildenafil.
Management: Use of sildenafil for pulmonary hypertension should be avoided with strong
CYP3A4 inhibitors. When used for erectile dysfunction, starting adult dose should be
reduced to 25 mg. Maximum adult dose with ritonavir or cobicistat is 25 mg per 48 hours.
Silodosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin.
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with
Simeprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Simeprevir. Risk X: Avoid combination
Simvastatin: Clarithromycin may increase the serum concentration of Simvastatin. Risk X:

Avoid combination
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of
Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility
prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy
modification
Sirolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus.
Management: Consider avoiding concurrent use of sirolimus with strong CYP3A4 inhibitors
in order to minimize the risk for sirolimus toxicity. Concomitant use of sirolimus and
voriconazole or posaconazole is contraindicated. Risk D: Consider therapy modification
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate.
Management: Consider using an alternative product for bowel cleansing prior to a
colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk
Solifenacin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Solifenacin. Management: Limit adult solifenacin doses to 5 mg daily and limit doses in
pediatric patients to the recommended weight-based starting dose (and do not increase the
dose) when combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Sonidegib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sonidegib.
SORAfenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

SORAfenib. Risk C: Monitor therapy
Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with
Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to
have a narrow therapeutic index should be avoided due to the increased risk for adverse
effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring.
SUFentanil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

SUFentanil. Management: If a strong CYP3A4 inhibitor is initiated in a patient on sufentanil,
consider a sufentanil dose reduction and monitor for increased sufentanil effects and
toxicities (eg, respiratory depression). Risk D: Consider therapy modification
SUNItinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SUNItinib.
Management: Avoid when possible. If combined, decrease sunitinib dose to a minimum of
37.5 mg daily when treating GIST or RCC. Decrease sunitinib dose to a minimum of 25 mg
daily when treating pNET. Monitor patients for both reduced efficacy and increased
toxicities. Risk D: Consider therapy modification
Suvorexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Suvorexant. Risk X: Avoid combination
Tacrolimus (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of
Tacrolimus (Systemic). Management: Reduce tacrolimus dose to one-third of the original
dose if starting posaconazole or voriconazole. Coadministration with nelfinavir is not
generally recommended. Tacrolimus dose reductions or prolongation of dosing interval will
likely be required. Risk D: Consider therapy modification
Tacrolimus (Topical): Macrolide Antibiotics may increase the serum concentration of

Tacrolimus (Topical). Risk C: Monitor therapy
Tadalafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tadalafil.
Management: Avoid this combination in patients taking tadalafil for pulmonary arterial
hypertension. In patients taking tadalafil for ED or BPH, max tadalafil dose is 2.5 mg if
taking daily or 10 mg no more frequently than every 72 hours if used as needed. Risk D:
Talazoparib: Clarithromycin may increase the serum concentration of Talazoparib.

Management: If concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg
once daily. When clarithromycin is discontinued, increase the talazoparib dose to the dose
used before initiation of clarithromycin after 3 to 5 times the half-life of clarithromycin. Risk
Tamsulosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Tamsulosin. Risk X: Avoid combination
Tasimelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Tasimelteon. Risk C: Monitor therapy
Tazemetostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Tazemetostat. Risk X: Avoid combination
Tegaserod: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of

Tegaserod. Risk C: Monitor therapy
Temsirolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Temsirolimus. Management: Avoid concomitant use of temsirolimus and strong CYP3A4
inhibitors. If coadministration is unavoidable, decrease temsirolimus dose to 12.5 mg per
week. Resume previous temsirolimus dose 1 week after discontinuation of the strong
CYP3A4 inhibitor. Risk D: Consider therapy modification
Terfenadine: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the
QTc-prolonging effect of Terfenadine. QT-prolonging Strong CYP3A4 Inhibitors (Moderate
Risk) may increase the serum concentration of Terfenadine. Risk X: Avoid combination
Tetrahydrocannabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Tetrahydrocannabinol. Risk C: Monitor therapy
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Strong) may increase the serum
concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor therapy
Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration
of Tezacaftor and Ivacaftor. Management: If combined with strong CYP3A4 inhibitors,
tezacaftor/ivacaftor should be administered in the morning, twice a week, approximately 3 to
4 days apart. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact
monograph for details. Risk D: Consider therapy modification
Theophylline Derivatives: Macrolide Antibiotics may decrease the metabolism of

Theophylline Derivatives. Management: Consider avoiding erythromycin and
troleandomycin in patients receiving theophylline derivatives. Monitor for toxic effects of
theophylline derivatives if a macrolide is initiated/dose increased. Other macrolides appear
to have little to no effect. Exceptions: Dyphylline. Risk D: Consider therapy modification
Thiotepa: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active
metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Strong) may increase the serum
concentration of Thiotepa. Management: Thiotepa prescribing information recommends
avoiding concomitant use of thiotepa and strong CYP3A4 inhibitors. If concomitant use is
unavoidable, monitor for adverse effects and decreased efficacy. Risk D: Consider therapy
modification
Ticagrelor: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active
metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum
concentration of Ticagrelor. Risk X: Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with
Tofacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tofacitinib.
Management: Tofacitinib dose reductions are recommended when combined with strong
CYP3A4 inhibitors. Recommended dose adjustments vary by tofacitinib formulation and
therapeutic indication. See full Lexi Interact monograph for details. Risk D: Consider therapy
modification
Tolterodine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Tolterodine. Management: The maximum recommended adult dose of tolterodine is 2
mg/day when used together with a strong CYP3A4 inhibitor. Risk D: Consider therapy
modification
Tolvaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan.
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of

Topotecan. Risk X: Avoid combination
Toremifene: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4

increase the serum concentration of Toremifene. Management: Avoid concomitant use of
toremifene and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If
combined, monitor patients for toremifene toxicities including QTc prolongation and TdP.
Trabectedin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Trabectedin. Risk X: Avoid combination
TraMADol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraMADol.
TraZODone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

TraZODone. Management: Consider the use of a lower trazodone dose and monitor for
increased trazodone effects (eg, sedation, QTc prolongation) if combined with strong
CYP3A4 inhibitors. Risk D: Consider therapy modification
Triazolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triazolam.
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only
the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated
typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic
antibacterial agents. Use of this vaccine should be postponed until at least 3 days after
cessation of antibacterial agents. Risk D: Consider therapy modification
Ubrogepant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Ubrogepant. Risk X: Avoid combination
Udenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Udenafil.
Ulipristal: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ulipristal.
Management: This is specific for when ulipristal is being used for signs/symptoms of uterine
fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive,
patients receiving this combo should be monitored for ulipristal toxicity. Risk X: Avoid
combination
Upadacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Upadacitinib. Risk C: Monitor therapy
Valbenazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Valbenazine. Management: Reduce the valbenazine dose to 40 mg daily when combined
with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Vardenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vardenafil.
Management: Limit Levitra (vardenafil) dose to a single 2.5 mg dose within a 24-hour period
if combined with strong CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil)
and strong CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D:
Vemurafenib: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4

increase the serum concentration of Vemurafenib. Management: Avoid concomitant use of
vemurafenib and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible.
If combined monitor patients for vemurafenib toxicities including QTc prolongation and TdP.
Venetoclax: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Venetoclax. Management: Coadministration is contraindicated during venetoclax initiation
and ramp-up in CLL/SLL patients. Reduced venetoclax doses are required during ramp-up
for patients with AML, and all maintenance therapy. See full Lexi Interact monograph for
details. Risk D: Consider therapy modification
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of

Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring
concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous
venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider
Vilanterol: May increase the serum concentration of CYP3A4 Inhibitors (Strong). Risk C:
Monitor therapy
Vilazodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Vilazodone. Management: Limit maximum adult vilazodone dose to 20 mg daily in patients
receiving strong CYP3A4 inhibitors. The original vilazodone dose can be resumed following
discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
VinCRIStine (Liposomal): CYP3A4 Inhibitors (Strong) may increase the serum concentration
of VinCRIStine (Liposomal). Risk X: Avoid combination
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum

concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
Vinflunine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinflunine.
Vitamin K Antagonists (eg, warfarin): Macrolide Antibiotics may increase the serum
concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Vorapaxar: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vorapaxar.
Voriconazole: Clarithromycin may enhance the QTc-prolonging effect of Voriconazole.

Voriconazole may increase the serum concentration of Clarithromycin. Management:
Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are
combined. Patients with additional risk factors for QTc prolongation may be at even higher
risk. Risk C: Monitor therapy
Voxelotor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Voxelotor.
Management: Avoid concomitant use of voxelotor and strong CYP3A4 inhibitors. If
concomitant use is unavoidable, reduce the voxelotor dose to 1,000 mg once daily. Risk D:
Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum

concentration of Voxilaprevir. Risk X: Avoid combination
Zanubrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg once daily during
coadministration with a strong CYP3A4 inhibitor. Further dose adjustments may be required
for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider
Zidovudine: Clarithromycin may enhance the myelosuppressive effect of Zidovudine.

Clarithromycin may decrease the serum concentration of Zidovudine. Management: Monitor
response to zidovudine closely when used with clarithromycin, and consider staggering
zidovudine and clarithromycin doses when possible in order to minimize the potential for
interaction. Risk D: Consider therapy modification
Zopiclone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zopiclone.
Management: If coadministered with strong CYP3A4 inhibitors, initiate zopiclone at 3.75 mg
in adults, with a maximum dose of 5 mg. Monitor for zopiclone toxicity (eg, drowsiness,
confusion, lethargy, ataxia, respiratory depression). Risk D: Consider therapy modification
Zuclopenthixol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of

Zuclopenthixol. Management: Consider zuclopenthixol dosage reduction with concomitant
use of a strong CYP3A4 inhibitor (eg, ketoconazole) in poor CYP2D6 metabolizers or with
strong CYP2D6 inhibitors (eg, paroxetine). Monitor for increased zuclopenthixol
levels/toxicity. Risk D: Consider therapy modification
Food Interactions
Immediate release: Food delays rate, but not extent of absorption; Extended release: Food
increases clarithromycin AUC by ~30% relative to fasting conditions. Management: Administer
immediate release products without regard to meals. Administer extended release products with
food.
Pregnancy Considerations
Clarithromycin crosses the placenta (Witt 2003).
The manufacturer recommends that clarithromycin not be used in a pregnant woman unless
there are no alternative therapies. Clarithromycin is not recommended as a first-line agent for the
treatment or prophylaxis of Mycobacterium avium complex or for treatment of bacterial
respiratory disease in HIV-infected pregnant patients (HHS [OI adult] 2019]).
Breast-Feeding Considerations
Clarithromycin and its active metabolite (14-hydroxy clarithromycin) are present in breast
milk.
The relative infant dose (RID) of clarithromycin is <1% when calculated using the highest
mean breast milk concentration located and compared to an infant therapeutic dose of 15
mg/kg/day.
In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016;
Ito 2000).
Using the highest mean milk concentrations (clarithromycin: 0.85 mg/L; 14-hydroxy
clarithromycin: 0.63 mg/L), the estimated daily infant dose via breast milk was calculated to
be 136 mcg/kg/day. This milk concentration was obtained following maternal administration
of oral clarithromycin 250 mg twice daily; the half-lives of clarithromycin and 14-hydroxy
clarithromycin in breast milk were 4.3 ± 0.3 hours and 9 ± 1.2 hours, respectively (Sedlmayr
1993).
Decreased appetite, diarrhea, rash, and somnolence have been reported in breastfed
infants exposed to macrolide antibiotics (Goldstein 2009). In general, antibiotics that are
present in breast milk may cause non-dose-related modification of bowel flora. Monitor
infants for GI disturbances, such as thrush and diarrhea (WHO 2002). In addition, an
increased risk for infantile hypertrophic pyloric stenosis (IHPS) may be present in infants
who are exposed to macrolides via breast milk, especially during the first two weeks of life
(Lund 2014); however, data are conflicting (Goldstein 2009). According to the manufacturer,
the decision to breastfeed during therapy should consider the risk of infant exposure, the
benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Monitoring Parameters
BUN, creatinine; perform culture and sensitivity studies prior to initiating drug therapy as
appropriate
Mechanism of Action
Exerts its antibacterial action by binding to 50S ribosomal subunit resulting in inhibition of protein
synthesis. The 14-OH metabolite of clarithromycin is twice as active as the parent compound
against certain organisms.
Pharmacodynamics and Pharmacokinetics
Absorption:
Immediate release: Rapid; food delays rate, but not extent of absorption
Extended-release: Fasting is associated with ~30% lower AUC relative to

administration with food
Distribution: Widely into most body tissues; manufacturer reports no data in regards to CNS
penetration
Protein binding: 42% to 70% (Peters, 1992)
Metabolism: Partially hepatic via CYP3A4; converted to 14-OH clarithromycin (active

metabolite); undergoes extensive first-pass metabolism
Bioavailability: ~50%
Half-life elimination: Immediate release: Clarithromycin: 3-7 hours; 14-OH-clarithromycin: 5-

9 hours
Time to peak: Immediate release: 2-3 hours; Extended release: 5-8 hours
Excretion: Urine (20% to 40% as unchanged drug; additional 10% to 15% as metabolite);
feces (29% to 40% mostly as metabolites) (Ferrero 1990)
Clearance: Approximates normal GFR
Pharmacodynamics and Pharmacokinetics: Additional Considerations

Renal function impairment: The pharmacokinetics of clarithromycin were altered in subjects

with impaired renal function.
Hepatic function impairment: The 14-OH clarithromycin concentrations were lower in

subjects with hepatic impairment but may be partially offset by an increase in renal
clearance of clarithromycin.
Pricing: US
Suspension (reconstituted) (Clarithromycin Oral)
125 mg/5 mL (per mL): $1.47
250 mg/5 mL (per mL): $2.14
Tablet, 24-hour (Clarithromycin ER Oral)
500 mg (per each): $8.95
Tablets (Clarithromycin Oral)
250 mg (per each): $4.52 - $6.02
500 mg (per each): $4.52 - $6.02
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided
as reference price only. A range is provided when more than one manufacturer's AWP price is
available and uses the low and high price reported by the manufacturers to determine the range.
The pricing data should be used for benchmarking purposes only, and as such should not be
used alone to set or adjudicate any prices for reimbursement or purchasing functions or
considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly
disclaims all warranties of any kind or nature, whether express or implied, and assumes no
liability with respect to accuracy of price or price range data published in its solutions. In no
event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising
from use of price or price range data. Pricing data is updated monthly.
Brand Names: International

Abbotic (ID); Abbotic Granule (ID); Abbotic XL (ID); Adel (MX); Aeroxina (AR); Avexus (HK, MY);
Aziclar (ET, UA); Baclecin (HK); Bacterfin (EC); Bedrevida (EG); Biaxin HP (DE); Biclar (BE, LU);
Bicrolid (ID, LK, SG); Binoclar (CR, DO, GT, HN, NI, PA, SV, VN); Bysclas (PH); C-Clarin (KR);
Carimycin (TW); Clabax (UA); Clabet (PH); Clacee (ZW); Clacina (TH); Clafax (LK); Clamise
(VN); Clamisin (KR); Clamycin (AE, BH, LB, PH, QA, SA); Clarac (AU, NZ); Claranta (PH, ZW);
Clarem (ET); Clarexid (HR); Clari (SG); Claribax (PH); Claribid (IN); Claricide (ET); Claricin (BD);
Claricin-P (TH); Claridar (AE, BH, CY, IQ, IR, JO, LY, OM, QA, SA, SY, YE); Clarikan (EG);
Clarimac (IN, QA); Clarimax (CL, CU); Clarimed (PE); Clarimin (LK); Clarin (BD); Clarion (LK);
Claripen (SG); Clariston (EC); Claritek (VN); Clarith (JP, TH); Clarithro (AU); Claritrox (MY);
Clariva (QA); Clariwin (SG); Clarix (AE, BH, CY, ET, IQ, IR, JO, LY, OM, SA, SY, YE); Clarocin
(EG); Claroma (KR); Claron (TH); Clarosin (KR); Clasine (PE); Claxin (KR); Cleron (SG, TR);
Clonocid (IE); Clormicin (CO); Clorom (IE); Crixan OD (PH); Fascar (TH); Fevaxid DS (PH);
Fromilid (HR, HU, MT, RO, TR); Gervaken (MX); Hecobac (ID); Heliclar (BE, LU); Heliclo (KR);
Immaculate XL (EG); Kalixocin (AU); Karin (IL); Klabax (ZW); Klacid (AE, AT, AU, BG, BH, CH,
CN, CY, CZ, DE, DK, EE, EG, ES, FI, HK, HU, IE, IL, IQ, IR, IS, IT, JO, KR, KW, LB, LT, LV, LY,
MT, MY, NO, NZ, OM, PL, PT, QA, RO, RU, SA, SE, SG, SI, SK, SY, TH, TR, UA, VN, YE, ZW);
Klacid Forte (VN); Klacid MR (MY, VN); Klacid XL (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM,
QA, SA, SY, YE, ZW); Klaribac (AE, BH, CY, IQ, IR, JO, LY, OM, SA, SY, YE); Klaricid (AR, BB,
BM, BR, BS, BZ, CL, CO, CR, DO, EC, GB, GR, GT, GY, HN, JM, KR, LK, MT, MX, NI, NL, PA,
PE, PH, PK, PR, PY, SR, SV, TT, TW, UY, VE); Klaricid Pediatric (PH); Klaricid XL (KR); Klarid
(PH); Klaridex (IL); Klariger (IE); Klaris (KR); Klarith (TW); Klarithan (ZA); Klarix (BD); Klarmyn
(MX, PH); Klerimed (AE, BH, CY, ET, IQ, IR, JO, LB, LY, MY, OM, QA, SA, SG, SY, YE); Klerimid
(AE, BH, CY, IQ, IR, JO, LY, OM, SA, SY, YE); Kofron (ES); Krobicin (MX); Macladin (IT); Maclar
(BE, LU); Macrodin (PH); Mavid (DE); Minatev (IE); Monoclarium (SG); Mononaxy (FR); Naxy
(FR); Neo-Clarosip (MX); Orixal (ID); Orokin (VN); Resclar (ET); Rolicytin (MX); Suclari (KR);
Synclar (HK); Veclam (IT); Zeclar (FR, LB); Zix (PY)
For country abbreviations used in Lexicomp (show table)
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Brand Names: Canada

Bartonella spp. infection (off-label use):

Bacillary angiomatosis, peliosis hepatitis, bacteremia, or osteomyelitis in patients with

Primary treatment (alternative agent): Oral: Immediate release: 500 mg twice

Long-term suppression for patients with relapse after ≥3 months of primary

Chronic obstructive pulmonary disease, acute exacerbation: Oral: Immediate release:

Endocarditis prophylaxis, dental or invasive respiratory tract procedure (alternative

Helicobacter pylori eradication : Note: Avoid clarithromycin-based therapy in patients

Mycobacterial (nontuberculous) infection:

Mycobacterium avium complex infection:

Disseminated disease in patients with HIV:

Treatment: Oral: Immediate release: 500 mg twice daily as part of an

Primary prophylaxis: Note: Not routinely recommended; reserve for patients

Oral: Immediate release: 500 mg twice daily; may discontinue prophylaxis

Pulmonary disease, nonsevere noncavitary nodular/bronchiectatic disease in

Pulmonary disease, severe nodular/bronchiectatic disease, cavitary disease, or

Mycobacterium abscessus infection (off-label use): Note: Perform susceptibility testing

Pertussis (off-label use):

Postexposure prophylaxis: Note: Postexposure prophylaxis should be administered,

Inpatient: Oral: Immediate release: 500 mg twice daily as part of an appropriate

Streptococcal pharyngitis (group A) (alternative agent for patients with severe

Dosing: Renal Impairment: Adult

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: Decrease clarithromycin dose by 50%

Hemodialysis: Administer after HD session is completed (Aronoff 2007).

In combination with atazanavir or ritonavir:

CrCl 30 to 60 mL/minute: Decrease clarithromycin dose by 50%.

CrCl <30 mL/minute: Decrease clarithromycin dose by 75%.

Dosing: Hepatic Impairment: Adult

(For additional information see "Clarithromycin: Pediatric drug information")

Note: All pediatric dosing recommendations based on immediate release product

General dosing, susceptible infection, mild to moderate infection: Infants,

Bartonellosis, treatment and secondary prophylaxis in HIV-exposed/-positive

Dental procedures in patients allergic to penicillins: Limited data available: Infants,

Group A streptococcal infection; rheumatic fever, primary prevention and

Helicobacter pylori eradication: Children and Adolescents: Oral: 20 mg/kg/day

Mycobacterium avium complex infection (MAC) (HIV-exposed/-positive):

Infants and Children (DHHS [pediatric] 2013):

Primary prophylaxis: Oral: 15 mg/kg/day divided every 12 hours;

Infants <12 months: <750 cells/mm3

Children 1 to <2 years: <500 cells/mm3

Children 2 to 5 years: <75 cells/mm3

Children ≥6 years: <50 cells/mm3

Secondary prophylaxis: Oral: 15 mg/kg/day divided every 12 hours;

Treatment: Oral: 15 to 30 mg/kg/day divided every 12 hours; maximum single

Adolescents (DHHS [adult] 2013):

Primary prophylaxis: Oral: 500 mg twice daily

Secondary prophylaxis: Oral: 500 mg twice daily plus ethambutol;

Treatment: Oral: 500 mg twice daily in combination with ethambutol: Consider

Peritonitis (peritoneal dialysis), prophylaxis for patients requiring invasive dental

Pertussis: Infants, Children, and Adolescents: Oral: 15 mg/kg/day divided every 12

Pneumonia, community-acquired (CAP); presumed atypical pneumonia (M.

Dosing: Renal Impairment: Pediatric

Infants, Children, and Adolescents: The following adjustments have been

GFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary

GFR 10 to 29 mL/minute/1.73 m2: 4 mg/kg/dose every 12 hours

GFR <10 mL/minute/1.73 m2: 4 mg/kg/dose once daily