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):
Patients with HIV:
Treatment:
Bacillary angiomatosis, cat scratch disease, peliosis hepatitis, bacteremia, or osteomyelitis (alternative agent): Note: Not to be used for endocarditis or CNS infections.
Oral: Immediate release: 500 mg twice daily for ≥3 months (HHS [OI adult] 2022).
Suppressive therapy: Note: For patients who experience a relapse after receiving a ≥3-month course of primary treatment.
Oral: Immediate release: 500 mg twice daily. Continue until patient has received ≥3 months of therapy and CD4 count is >200 cells/mm3 for ≥6 months; some experts discontinue only if Bartonella titers have also decreased 4-fold (HHS [OI adult] 2022; Spach 2022a).
Patients without HIV:
Cat scratch disease, lymphadenitis (alternative agent): Oral: Immediate release: 500 mg twice daily for 7 to 10 days (Spach 2022b).
Bronchiolitis obliterans, including diffuse panbronchiolitis and symptomatic cryptogenic bronchiolitis obliterans (off-label use): Oral: Immediate release: 250 to 500 mg once daily (Kadota 2003; King 2020). After a 3- to 6-month trial, long-term therapy may be continued based on response (King 2020).
Chronic obstructive pulmonary disease, acute exacerbation: Note: Avoid use in patients with risk factors for Pseudomonas infection or poor outcomes (eg, ≥65 years of age with major comorbidities, FEV1 <50% predicted, frequent exacerbations) (Sethi 2022).
Oral: Immediate release: 500 mg every 12 hours for 5 to 7 days (Falagas 2008; GOLD 2022; Hunter 2001).
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; if inadvertently not given prior to the procedure, may be administered up to 2 hours after the 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]; AHA [Wilson 2021]).
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] 2020).
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] 2020; IAS-USA [Saag 2018]).
Pulmonary disease, nonsevere noncavitary nodular/bronchiectatic disease in patients without cystic fibrosis (alternative agent) (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/ERS/ESCMID/IDSA [Daley 2020]; BTS [Haworth 2017]).
Pulmonary disease, severe nodular/bronchiectatic disease, cavitary disease, or disease in patients with cystic fibrosis (alternative agent) (off-label use): Oral: Immediate release: 500 mg twice daily as part of an appropriate combination regimen. Continue treatment until patient is culture negative on therapy for ≥1 year (ATS/ERS/ESCMID/IDSA [Daley 2020]; BTS [Haworth 2017]; CFF/ECFS [Floto 2016]).
Rapidly growing nontuberculous mycobacterial (eg, M. 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 (ATS/ERS/ESCMID/IDSA [Daley 2020]; 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 for pulmonary and bone infections and ≥4 months for skin/soft tissue infections (ATS/ERS/ESCMID/IDSA [Daley 2020]; CFF/ECFS [Floto 2016]; Griffith 2020). Note: Patients should be under the care of a clinician with expertise in managing mycobacterial infection (ATS/ERS/ESCMID/IDSA [Daley 2020]).
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 2021).
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, underlying valvular disease, or antiphospholipid antibodies) (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 twice daily for 10 days (IDSA [Shulman 2012]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
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a Davey 1991; Fraschini 1993; Hardy 1992; manufacturer’s labeling | |||
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b CrCl determined using Cockcroft-Gault formula. | |||
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c IR = immediate release | |||
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d ER = extended release | |||
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e IR product would be equally effective (expert opinion). | |||
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f No pharmacokinetic data in hemodialysis/peritoneal dialysis patients; recommendations are based on expert opinion only. | |||
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g Although unlikely to be significantly dialyzed (manufacturer’s labeling), because no data on degree of dialyzability are available, consider administering after dialysis when scheduled dose falls on dialysis days. | |||
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CrClb |
If the usual recommended dose is IRc 250 mg twice daily |
If the usual recommended dose is IR 500 mg twice daily |
If the usual recommended dose is ERd 1 g once daily |
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≥30 mL/minute |
No dosage adjustment necessary. |
No dosage adjustment necessary. |
No dosage adjustment necessary. |
|
<30 mL/minute |
IR: 250 mg once daily |
IR: 250 mg twice daily or 500 mg once daily |
ER: 500 mg once dailye |
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Intermittent hemodialysis, thrice weeklyf,g |
IR: 250 mg once daily |
IR: 250 mg twice daily or 500 mg once daily |
ER: 500 mg once dailye |
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Peritoneal dialysisf |
IR: 250 mg once daily |
IR: 250 mg twice daily or 500 mg once daily |
ER: 500 mg once dailye |
CRRT: Unlikely to be significantly dialyzed (large Vd) (expert opinion):
Oral: Follow dosing recommendations for patients with CrCl <30 mL/minute. Note: In general, use of IV antimicrobial therapy may be preferred in patients receiving CRRT (expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): Unlikely to be significantly dialyzed (large Vd) (expert opinion):
Oral: Follow dosing recommendations for patients with CrCl <30 mL/minute.Note: In general, use of IV antimicrobial therapy may be preferred in patients receiving PIRRT (expert opinion).
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.
(For additional information see "Clarithromycin: Pediatric drug information")
General dosing: Infants, Children, and Adolescents: Immediate release: Oral: 7.5 mg/kg/dose every 12 hours; maximum dose: 500 mg/dose (Red Book [AAP 2021]).
Bartonellosis: Limited data available:
Primary treatment (alternative agent): Adolescents, HIV-infected: Immediate release: Oral: 500 mg twice daily for ≥3 months. After completion of therapy, closely monitor for relapse; if relapse occurs, an additional course of treatment followed by long-term suppression is recommended. Note: Should not be used for endocarditis or CNS infections (HHS [OI adult 2021]).
Endocarditis, prophylaxis before invasive dental or respiratory tract procedures (alternative agent for patients with penicillin allergy): Limited data available:
Note: Recommended only in patients who are at highest risk for infective endocarditis (IE) or adverse outcomes (eg, history of IE, prosthetic heart valves or prosthetic material used to repair valves, 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) (AHA [Baltimore 2015]; AHA [Wilson 2021]; AHA/ACC [Nishimura 2017]).
Infants, Children, and Adolescents: Immediate release: Oral: 15 mg/kg as a single dose administered 30 to 60 minutes prior to procedure; maximum dose: 500 mg/dose (AHA [Wilson 2021]).
Helicobacter pylori eradication : Limited data available: Note: Use as part of an appropriate combination regimen; usual duration of therapy is 14 days (NASPGHAN/ESPGHAN [Jones 2017]).
Weight-directed dosing: Children and Adolescents: Immediate release: Oral: 7.5 to 10 mg/kg/dose twice daily; maximum dose: 500 mg/dose (Bontems 2011; Butenko 2017; Huang 2013; Koletzko 2011; Kutluk 2014; Szajewska 2009).
Fixed dosing (NASPGHAN/ESPGHAN [Jones 2017]): Children and Adolescents: Immediate release:
15 to <25 kg: Oral: 250 mg twice daily.
25 to <35 kg: Oral: 500 mg in the morning and 250 mg in the evening.
≥35 kg: Oral: 500 mg twice daily.
Lyme disease (Borrelia spp. infection), erythema migrans (alternative agent): Limited data available: Note: Current guidelines recommend macrolides (azithromycin) only when first-line agents cannot be used due to lower efficacy (IDSA/AAN/ACR [Lantos 2021]).
Infants, Children, and Adolescents: Immediate release: Oral: 7.5 mg/kg twice daily for 14 days; maximum dose: 500 mg/dose (Nizič 2012; IDSA [Wormser 2006]).
Mycobacterial infection, nontuberculous:
Mycobacterium avium complex infection in patients that are HIV-exposed/-infected: (HHS [pediatric OI 2021]; HHS [adult OI 2021]):
Infants, Children, and Adolescents: Limited data available in Infants and Children <20 months:
Primary prophylaxis (patients who meet age-specific CD4 count thresholds): Immediate release: Oral: 7.5 mg/kg/dose every 12 hours; maximum dose: 500 mg/dose.
Treatment: Immediate release: Oral: 7.5 to 15 mg/kg/dose every 12 hours as part of an appropriate combination regimen for ≥12 months; maximum dose: 500 mg/dose; follow with chronic maintenance therapy (secondary prophylaxis).
Chronic maintenance therapy (secondary prophylaxis): Immediate release: Oral: 7.5 mg/kg/dose every 12 hours as part of an appropriate combination regimen; maximum dose: 500 mg/dose. May be discontinued once there are no signs/symptoms of M. avium complex disease, and the CD4 count has exceeded age-specific thresholds for ≥6 months in response to stable antiretroviral therapy.
Pulmonary infection in patients with or without cystic fibrosis (eg, M. avium complex, Mycobacterium abscessus): Limited data available: Infants, Children, and Adolescents: Immediate release: Oral: 7.5 mg/kg/dose every 12 hours for ≥12 months after culture conversion; maximum dose: 500 mg/dose (BTS [Haworth 2017]; CFF/ECFS [Floto 2016]).
Otitis media, acute (AOM) (alternative agent for patients who cannot tolerate beta-lactam antibiotics): Note: Not recommended for routine empiric use due to limited efficacy against Streptococcus pneumoniae and Haemophilus influenzae (AAP [Lieberthal 2013]).
Infants ≥6 months and Children: Immediate release: Oral: 7.5 mg/kg/dose every 12 hours; maximum dose: 500 mg/dose (manufacturer's labeling). For patients with severe or recurrent AOM, tympanic membrane perforation, or who are <2 years of age, treat for 10 days; for patients ≥2 years of age with mild to moderate, nonrecurrent disease without tympanic membrane perforation, shorter durations of 5 to 7 days may be sufficient (AAP [Lieberthal 2013]; Hoberman 2016; Kozyrskyj 2010; Marchisio 2019; NICE 2018).
Peritonitis (peritoneal dialysis), prophylaxis for patients requiring invasive dental procedures:
Infants, Children, and Adolescents: Immediate release: Oral: 15 mg/kg as a single dose 30 to 60 minutes prior to dental procedure; maximum dose: 500 mg/dose (ISPD [Warady 2012]).
Pertussis; treatment or postexposure prophylaxis: Infants, Children, and Adolescents: Immediate release: Oral: 7.5 mg/kg/dose every 12 hours for 7 days; maximum dose: 500 mg/dose (CDC [Tiwari 2005]).
Pneumonia, community-acquired (presumed or proven atypical pneumonia); mild infection or step-down therapy:
Infants >3 months, Children, and Adolescents: Immediate release: Oral: 7.5 mg/kg/dose every 12 hours for 10 days; shorter courses may be appropriate for mild disease; maximum dose: 500 mg/dose (PIDS/IDSA [Bradley 2011]; manufacturer's labeling).
Streptococcus, group A; pharyngitis/tonsillitis (alternative agent for severe penicillin allergy):
Infants ≥6 months, Children, and Adolescents: Immediate release: Oral: 7.5 mg/kg/dose every 12 hours for 10 days; maximum dose: 250 mg/dose (IDSA [Shulman 2012]; manufacturer's labeling).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents: The following adjustments have been recommended (Aronoff 2007). Note: Renally adjusted dose recommendations are based on a dose of 7.5 mg/kg/dose every 12 hours.
GFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
GFR 10 to 29 mL/minute/1.73 m2: Immediate release: 4 mg/kg/dose every 12 hours.
GFR <10 mL/minute/1.73 m2: Immediate release: 4 mg/kg/dose once daily.
Hemodialysis: Administer after hemodialysis session is completed: Immediate release: 4 mg/kg/dose once daily.
Peritoneal dialysis: Immediate release: 4 mg/kg/dose once daily.
Infants ≥6 months, 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.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension Reconstituted, Oral:
Generic: 125 mg/5 mL (50 mL, 100 mL); 250 mg/5 mL (50 mL, 100 mL)
Tablet, Oral:
Generic: 250 mg, 500 mg
Tablet Extended Release 24 Hour, Oral:
Generic: 500 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
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 quinoline yellow (d&c yellow #10)]
Generic: 250 mg, 500 mg
Tablet Extended Release 24 Hour, Oral:
Biaxin XL: 500 mg [DSC] [contains quinoline (d&c yellow #10) aluminum lake]
Generic: 500 mg
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).
Oral:
Immediate-release tablets and oral suspension: May be administered with or without meals. Shake suspension well before each use.
Extended-release tablets: Administer with food. Do not break, crush, or chew.
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, group A: Treatment of pharyngitis/tonsillitis due to susceptible S. pyogenes (alternative agent for patients with severe penicillin allergy).
Bartonella spp. infection; Bronchiolitis obliterans, including diffuse panbronchiolitis and symptomatic cryptogenic bronchiolitis obliterans; Endocarditis, prophylaxis; Mycobacterial (nontuberculous, rapidly growing) infection; Pertussis; Q fever (Coxiella burnetii), acute symptomatic
Clarithromycin may be confused with Claritin, clindamycin, erythromycin
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
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 difficile-associated diarrhea, Clostridioides 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 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
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, ergot alkaloids (eg, ergotamine, dihydroergotamine), HMG-CoA reductase inhibitors extensively metabolized by CYP3A4 (eg, lovastatin, simvastatin), lomitapide, or pimozide; 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; hypomagnesemia; concomitant use with astemizole, colchicine (regardless of hepatic/renal impairment), domperidone, midazolam (oral), ranolazine (not available in Canada), saquinavir, terfenadine, or ticagrelor.
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.
Special populations:
• Older adult: Use with caution; elderly patients may be at increased risk of torsades de pointes.
• Patients with HIV: Decreased survival has been observed in patients with HIV 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]).
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
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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. Management: Avoid concomitant use of ado-trastuzumab emtansine and strong CYP3A4 inhibitors when possible. Consider alternatives that do not inhibit CYP3A4 or consider administering after CYP3A4 inhibitor discontinuation. Monitor for toxicities if combined. Risk D: Consider therapy modification
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider therapy modification
Alfentanil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfentanil. Management: If use of alfentanil and strong CYP3A4 inhibitors is necessary, consider dosage reduction of alfentanil until stable drug effects are achieved. Frequently monitor patients for respiratory depression and sedation when these agents are combined. Risk D: Consider therapy modification
Alfuzosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. Risk X: Avoid combination
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: Monitor therapy
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. Risk X: Avoid combination
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
AmLODIPine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of AmLODIPine. Risk C: Monitor therapy
Antihepaciviral Combination Products: May increase the serum concentration of Clarithromycin. Management: Avoid clarithromycin doses greater than 1,000 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
Apixaban: Clarithromycin may increase the serum concentration of Apixaban. Risk C: Monitor therapy
Aprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Aprepitant. Risk X: Avoid combination
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
Artemether and Lumefantrine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Artemether and Lumefantrine. Risk C: Monitor therapy
Asciminib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Asciminib. Risk C: Monitor therapy
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. Clarithromycin may increase the serum concentration of Atazanavir. 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
Atogepant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Atogepant. Management: The recommended dose of atogepant is 10 mg once daily when coadministered with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Atogepant. Management: The recommended dose of atogepant when coadministered with OATP1B1/1B3 inhibitors is 10 mg once daily or 30 mg once daily. 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 when used with clarithromycin. If this combination is used, monitor patients more closely for evidence of atorvastatin toxicity. Risk D: Consider therapy modification
Avacopan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avacopan. Management: Decrease the avacopan dose to 30 mg once daily during coadministration with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Avanafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avanafil. Risk X: Avoid combination
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
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. 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). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Benidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benidipine. 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
Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification
Betamethasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Nasal). Risk C: Monitor therapy
Betamethasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Ophthalmic). Risk C: Monitor therapy
Betamethasone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Systemic). Risk C: Monitor therapy
Betamethasone (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Topical). Risk C: Monitor therapy
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination
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. Risk X: Avoid combination
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
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
Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Brincidofovir. Management: Consider alternatives to OATP1B/1B3 inhibitors in patients treated with brincidofovir. If coadministration is required, administer OATP1B1/1B3 inhibitors at least 3 hours after brincidofovir and increase monitoring for brincidofovir adverse reactions. Risk D: Consider therapy modification
Bromocriptine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bromocriptine. Management: Consider alternatives to the use of bromocriptine with strong CYP3A4 inhibitors. If combined, monitor closely for increased bromocriptine toxicities and consider bromocriptine dose reductions. Risk D: Consider therapy modification
Bromperidol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bromperidol. Risk C: Monitor therapy
Brotizolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brotizolam. Risk C: Monitor therapy
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). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of inhaled budesonide and strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Budesonide (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic). Management: Avoid the concomitant use of CYP3A4 inhibitors and oral budesonide. If patients receive both budesonide and a strong CYP3A4 inhibitor, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider therapy modification
Budesonide (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Topical). Risk X: Avoid combination
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. Dose adjustments of buspirone or a strong CYP3A4 inhibitor should be based on clinical assessment. Risk D: Consider therapy modification
Butorphanol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Butorphanol. Risk C: Monitor therapy
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: Consider therapy modification
Calcifediol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcifediol. Risk C: Monitor therapy
Calcitriol (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcitriol (Systemic). Risk C: Monitor therapy
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 serum concentrations of the active metabolite(s) of Cariprazine. Specifically, concentrations of didesmethylcariprazine (DDCAR), the primary active metabolite of cariprazine, may increase. 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
ChlordiazePOXIDE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ChlordiazePOXIDE. Risk C: Monitor therapy
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
Ciclesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ciclesonide (Oral Inhalation). Risk C: Monitor therapy
Cilnidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilnidipine. Risk C: Monitor therapy
Cilostazol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with strong CYP3A4 inhibitors. 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 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Citalopram. 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
Clindamycin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Clindamycin (Systemic). Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
ClonazePAM: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ClonazePAM. Risk C: Monitor therapy
Cobicistat: May decrease serum concentrations of the active metabolite(s) of Clarithromycin. 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: Consider therapy modification
Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan. 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
Cortisone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cortisone. Risk C: Monitor therapy
Crizotinib: 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 Crizotinib. Management: Avoid concomitant use of crizotinib and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If combined, crizotinib dose adjustments are required, which vary according to indication. See full interaction monograph for details. Risk D: Consider therapy modification
CycloSPORINE (Systemic): Clarithromycin may increase the serum concentration of CycloSPORINE (Systemic). Management: Monitor for increased serum concentrations/toxic effects of cyclosporine if combined with clarithromycin. Cyclosporine dose reductions and/or prolongation of the dosing interval will likely be required. Risk D: Consider therapy modification
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 CYP3A4 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. CYP3A4 Inducers (Strong) may decrease the serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A4 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 (Strong): May decrease serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Clarithromycin. Risk C: Monitor therapy
Cyproterone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cyproterone. Risk C: Monitor therapy
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy
Dabrafenib: May enhance the QTc-prolonging effect of Clarithromycin. Dabrafenib may increase serum concentrations of the active metabolite(s) of Clarithromycin. Clarithromycin may increase serum concentrations of the active metabolite(s) of Dabrafenib. Clarithromycin may increase the serum concentration of Dabrafenib. Dabrafenib may increase the serum concentration of Clarithromycin. Management: If coadministration is unavoidable, monitor for decreased clarithromycin efficacy, increased dabrafenib adverse effects, and QTc interval prolongation and ventricular arrhythmias when these agents are combined. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Dapoxetine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dapoxetine. Risk X: Avoid combination
Daridorexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Daridorexant. 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 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may 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
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: Consider therapy modification
DexAMETHasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of DexAMETHasone (Ophthalmic). Risk C: Monitor therapy
DexAMETHasone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapy
DiazePAM: CYP3A4 Inhibitors (Strong) may increase the serum concentration of DiazePAM. Risk C: Monitor therapy
DilTIAZem: CYP3A4 Inhibitors (Strong) may increase the serum concentration of DilTIAZem. Risk C: Monitor therapy
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
Doxazosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Doxazosin. Risk C: Monitor therapy
Doxercalciferol: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Doxercalciferol. Risk C: Monitor therapy
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy
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
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. Monitor closely for evidence of altered response to treatment. Risk D: Consider therapy modification
Dydrogesterone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dydrogesterone. Risk C: Monitor therapy
Ebastine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ebastine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ebastine. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Efonidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Efonidipine. Risk C: Monitor therapy
Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Risk X: Avoid combination
Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Risk X: Avoid combination
Elagolix, Estradiol, and Norethindrone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Elagolix, Estradiol, and Norethindrone may decrease the serum concentration of CYP3A4 Inhibitors (Strong). Specifically, concentrations of strong CYP3A4 inhibitors that are also CYP3A4 substrates may be decreased. Risk X: Avoid combination
Elbasvir and Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Eletriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eletriptan. Risk X: Avoid combination
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: Consider therapy modification
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 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may 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: Inhibitors of CYP3A4 (Strong) and P-glycoprotein 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 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Entrectinib. Risk X: Avoid combination
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 (Vasoconstrictive CYP3A4 Substrates): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). 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 erlotinib-associated adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Risk D: Consider therapy modification
Erythromycin (Systemic): 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 Erythromycin (Systemic). 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
Escitalopram: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate 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. Risk C: Monitor therapy
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy
Everolimus: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Everolimus. Risk X: Avoid combination
Evogliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Evogliptin. Risk C: Monitor therapy
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
Felodipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Felodipine. Management: Consider using lower felodipine doses when combined with strong CYP3A4 inhibitors. Monitor patients for increased felodipine effects and toxicities (eg, hypotension, edema) when combined. Risk D: Consider therapy modification
FentaNYL: CYP3A4 Inhibitors (Strong) may increase the serum concentration of FentaNYL. Management: Consider fentanyl dose reductions when combined with a strong CYP3A4 inhibitor. Monitor for respiratory depression and sedation. Upon discontinuation of a CYP3A4 inhibitor, consider a fentanyl dose increase; monitor for signs and symptoms of withdrawal. 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. This combination is not recommended in pediatric patients weighing 25 kg up to 35 kg. Risk D: Consider therapy modification
Fexinidazole: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Fexinidazole. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may decrease serum concentrations of the active metabolite(s) of Fexinidazole. Management: Consider alternatives to this combination. If combined, monitor for QT interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QT prolongation may be at even higher risk. Also monitor for reduced fexinidazole efficacy. Risk D: Consider therapy modification
Finerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Finerenone. 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 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
Fluorouracil Products: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. 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
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: Consider alternatives to this combination if possible. Coadministration of fluticasone propionate and strong CYP3A4 inhibitors is not recommended. If combined, monitor patients for systemic corticosteroid adverse effects (eg, adrenal suppression). Risk D: Consider therapy modification
Fluticasone (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Topical). Risk C: Monitor therapy
Fosaprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fosaprepitant. Risk X: Avoid combination
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
Futibatinib: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Futibatinib. 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. Risk C: Monitor therapy
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
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
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. Management: Consider alternatives to this 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
Haloperidol: 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 Haloperidol. 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
Hormonal Contraceptives: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Hormonal Contraceptives. Risk C: Monitor therapy
HYDROcodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of HYDROcodone. Risk C: Monitor therapy
Hydrocortisone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy
Ibrexafungerp: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrexafungerp. Management: Decrease the ibrexafungerp dose to 150 mg every 12 hours for 2 doses in patients receiving strong CYP3A4 inhibitors. Risk D: Consider therapy modification
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: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Idelalisib. Management: Use alternative therapies that are not strong CYP3A4 inhibitors whenever possible. If unable to use alternative drugs, monitor patients more frequently for idelalisib toxicities. Risk D: Consider therapy modification
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
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Infigratinib: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Infigratinib. Risk X: Avoid combination
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. Management: Avoid administration of strong CYP3A4 inhibitors during and within 1 week prior to irinotecan administration, unless no therapeutic alternatives to these agents exist. If combined, monitor closely for increased irinotecan toxicities. Risk D: Consider therapy modification
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. Risk X: Avoid combination
Isradipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Isradipine. Risk C: Monitor therapy
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
Itraconazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Itraconazole. Risk C: Monitor therapy
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 therapy modification
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: Consider therapy modification
Ketamine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ketamine. Risk C: Monitor therapy
Ketoconazole (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ketoconazole (Systemic). Risk C: Monitor therapy
Lacidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lacidipine. Risk C: Monitor therapy
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, a reduced lapatinib dose of 500 mg daily should be considered. The previous lapatinib dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
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's half-life. Risk D: Consider therapy modification
Lefamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets and strong inhibitors of CYP3A4. Risk X: Avoid combination
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
Leuprolide and Norethindrone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Leuprolide and Norethindrone. Specifically, concentrations of norethindrone may increase. Risk C: Monitor therapy
Levamlodipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levamlodipine. Risk C: Monitor therapy
Levobupivacaine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. Risk C: Monitor therapy
Levoketoconazole: QT-prolonging CYP3A4 Substrates may enhance the QTc-prolonging effect of Levoketoconazole. Levoketoconazole may increase the serum concentration of QT-prolonging CYP3A4 Substrates. Risk X: Avoid combination
Levomethadone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levomethadone. Risk C: Monitor therapy
Levomilnacipran: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levomilnacipran. Management: The dose of levomilnacipran should not exceed 80 mg once daily when used with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Lidocaine (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy
Lomitapide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lomitapide. Risk X: Avoid combination
Lonafarnib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lonafarnib. 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: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Lovastatin. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin. Risk X: Avoid combination
Lumateperone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumateperone. Management: Limit the lumateperone dose to 10.5 mg once daily when used with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Lurasidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone. Risk X: Avoid combination
Lurbinectedin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurbinectedin. 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 pediatrics weighing 40kg or more. See full interaction monograph for dose adjustments in pediatrics weighing 10 to less than 40kg. Do not use if CrCl less than 30mL/min or in those weighing less than 10 kg. Risk D: Consider therapy modification
Mavacamten: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mavacamten. Risk X: Avoid combination
Mefloquine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mefloquine. 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. Risk C: Monitor therapy
Midazolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Midazolam. Management: Avoid use of nasal midazolam and strong CYP3A4 inhibitors whenever possible, and consider alternatives to use with other routes of midazolam (oral, IV, IM). If combined, consider lower midazolam doses and monitor for increased midazolam toxicities. 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: For treatment of hyperglycemia in Cushing's syndrome, start mifepristone at 300 mg/day, may titrate to a maximum of 900 mg/day. If starting a strong CYP3A4 inhibitor and taking > 300 mg/day mifepristone, decrease the mifepristone dose by 300 mg/day. 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
Mirvetuximab Soravtansine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirvetuximab Soravtansine. Risk C: Monitor therapy
Mitapivat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mitapivat. Risk X: Avoid combination
Mizolastine: Macrolide Antibiotics may increase the serum concentration of Mizolastine. Risk X: Avoid combination
Mometasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mometasone (Nasal). Risk C: Monitor therapy
Mometasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mometasone (Oral Inhalation). Risk C: Monitor therapy
Mometasone (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mometasone (Topical). Risk C: Monitor therapy
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy
Naldemedine: CYP3A4 Inhibitors (Strong) 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. Risk X: Avoid combination
Neratinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Neratinib. Risk X: Avoid combination
Nevirapine: May increase serum concentrations of the active metabolite(s) of Clarithromycin. Nevirapine may decrease the serum concentration of Clarithromycin. Management: Consider alternatives to clarithromycin, such as azithromycin, for the treatment of Mycobacterium avium-intracellulare complex in patients taking nevirapine. Risk D: Consider therapy modification
NiCARdipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiCARdipine. Risk C: Monitor therapy
NIFEdipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NIFEdipine. Management: Consider alternatives to this combination when possible. If combined, initiate nifedipine at the lowest dose available and monitor patients closely for increased nifedipine effects and toxicities (eg, hypotension, edema). Risk D: Consider therapy modification
Nilotinib: 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 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 including QTc prolongation and arrhythmias. Risk D: Consider therapy modification
Nilvadipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilvadipine. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiMODipine. Risk X: Avoid combination
Nintedanib: Inhibitors of CYP3A4 (Strong) 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
Nitrendipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nitrendipine. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Oliceridine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oliceridine. Risk C: Monitor therapy
Olmutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Olmutinib. Risk C: Monitor therapy
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 factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Orelabrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Orelabrutinib. Risk X: Avoid combination
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 therapy modification
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
OxyCODONE: CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased. Risk C: Monitor therapy
PACLitaxel (Conventional): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy
Pacritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pacritinib. Risk X: Avoid combination
Palbociclib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palbociclib. Management: Avoid concurrent use of strong CYP3A4 inhibitors with palbociclib when possible. If the use of a strong CYP3A4 inhibitor cannot be avoided, decrease the palbociclib dose to 75 mg/day. Risk D: Consider therapy modification
Palovarotene: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palovarotene. 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. Monitor patient response to therapy closely for evidence of more severe adverse effects related to panobinostat therapy. 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
PAZOPanib: Clarithromycin may enhance the QTc-prolonging effect of PAZOPanib. Clarithromycin 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 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
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, pexidartinib dose should be reduced. Decrease 800 mg or 600 mg daily doses to 200 mg twice daily. Decrease doses of 400 mg per day to 200 mg once daily Risk D: Consider therapy modification
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. Risk C: Monitor therapy
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: Avoid concomitant use if possible. If combined, reduce ponatinib dose as follows: If taking 45 mg, reduce to 30 mg; if taking 30 mg, reduce to 15 mg; if taking 15 mg, reduce to 10 mg. If taking 10 mg, avoid concomitant use with strong CYP3A4 inhibitors. 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
Pralsetinib: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Pralsetinib. Management: Avoid concomitant use if possible. If combined, reduce the pralsetinib dose. If taking 400 mg or 300 mg once daily, reduce to 200 mg once daily. If taking 200 mg once daily, reduce to 100 mg once daily. Risk D: Consider therapy modification
Pravastatin: Clarithromycin may increase the serum concentration of Pravastatin. Management: Limit pravastatin to a maximum of 40 mg/day 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
Prazepam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Prazepam. Risk C: Monitor therapy
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
Propofol: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Propofol. 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
Protease Inhibitors: May decrease serum concentrations of the active metabolite(s) of Clarithromycin. Protease Inhibitors may increase the serum concentration of Clarithromycin. Management: Do not exceed clarithromycin doses greater than 1,000 mg/day in patients taking protease inhibitors. If CrCL is 30 to 60 mL/min, reduced clarithromycin dose 50%. If CrCL is less than 30 mL/min, reduced clarithromycin dose 75%. Risk D: Consider therapy modification
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). 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. 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 Inhalational Anesthetics (Moderate Risk): QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (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). 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 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 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QUEtiapine. Management: Reduce the quetiapine dose to one-sixth of the regular dose when initiating these strong CYP3A4 inhibitors. In patients already receiving these strong CYP3A4 inhibitors, initiate quetiapine at the lowest dose and titrate cautiously as needed. Risk D: Consider therapy modification
Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor therapy
Radotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Radotinib. Risk X: Avoid combination
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
Reboxetine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Reboxetine. Risk C: Monitor therapy
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 decrease serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib. Risk X: Avoid combination
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification
Repaglinide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy
Retapamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Retapamulin. Management: The use of retapamulin with strong CYP3A4 inhibitors is not recommended 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 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may 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 including QTc prolongation and arrhythmias. Risk D: Consider therapy modification
Rifabutin: May increase serum concentrations of the active metabolite(s) of Clarithromycin. Rifabutin may decrease the serum concentration of Clarithromycin. Clarithromycin may increase the serum concentration of Rifabutin. Management: Consider alternatives to this combination when possible. If combined, consider use of lower rifabutin doses and monitor patients for increased rifabutin toxicities. Additionally, monitor for reduced clarithromycin efficacy when these agents are combined. Risk D: Consider therapy modification
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
Riociguat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Riociguat. Risk C: Monitor therapy
Ripretinib: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ripretinib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ripretinib. Risk C: Monitor therapy
RisperiDONE: May enhance the QTc-prolonging effect of Clarithromycin. Clarithromycin may increase the serum concentration of RisperiDONE. Management: Monitor for increased risperidone toxicities, including 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
Rivaroxaban: Clarithromycin may increase the serum concentration of Rivaroxaban. Risk C: Monitor therapy
Roflumilast-Containing Products: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
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 (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib (Systemic). Management: This combination should be avoided under some circumstances; dose adjustments may be required in some circumstances and depend on the indication for ruxolitinib. See monograph for details. Risk D: Consider therapy modification
Ruxolitinib (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib (Topical). Risk X: Avoid combination
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
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 full drug interaction monograph or selumetinib prescribing information. Risk D: Consider therapy modification
Sertindole: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Sertindole. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Sertindole. Risk X: Avoid combination
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 arterial hypertension (PAH) should be avoided with strong CYP3A4 inhibitors. When used for erectile dysfunction, consider using a lower starting dose of 25 mg and monitor patients for sildenafil toxicities. Risk D: Consider therapy modification
Silodosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. Risk X: Avoid combination
Simeprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir. Risk X: Avoid combination
Simvastatin: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Strong) 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 (Conventional): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with strong CYP3A4 inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Concomitant use of sirolimus and voriconazole or posaconazole is contraindicated. Risk D: Consider therapy modification
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider therapy modification
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Sirolimus (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus (Topical). Risk C: Monitor therapy
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 D: Consider therapy modification
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. Risk X: Avoid combination
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
Sulfonylureas: Clarithromycin may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
SUNItinib: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of SUNItinib. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) 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): CYP3A4 Inhibitors (Strong) 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: Consider therapy modification
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 D: Consider therapy modification
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
Taurursodiol: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Taurursodiol. Risk X: Avoid combination
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
Telithromycin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Telithromycin. Risk C: Monitor therapy
Temsirolimus: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be increased. 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
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Tepotinib: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Tepotinib. Risk X: Avoid combination
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: Clarithromycin may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
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: Avoid coadministration of thiotepa and strong CYP3A4 inhibitors. If concomitant use cannot be avoided, monitor for thiotepa 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
Tipranavir: Clarithromycin may increase the serum concentration of Tipranavir. Tipranavir may increase the serum concentration of Clarithromycin. Management: Limit adult clarithromycin doses to 1,000 mg/day if combined with tipranavir. Consider reducing the clarithromycin dose by 50% for patients with CrCl 30 to 60 mL/min, and for patients with CrCl <30 mL/min consider reducing the clarithromycin dose by 75%. Risk D: Consider therapy modification
Tisotumab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tisotumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor therapy
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 dose of tolterodine is 2 mg per day (1 mg twice daily for immediate-release tablets or 2 mg daily for extended-release capsules) when used together with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Tolvaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
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 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may 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. Risk D: Consider therapy modification
Trabectedin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Trabectedin. Risk X: Avoid combination
TraMADol: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of TraMADol. CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraMADol. Risk C: Monitor therapy
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
Tretinoin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tretinoin (Systemic). Risk C: Monitor therapy
Triamcinolone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triamcinolone (Nasal). Risk C: Monitor therapy
Triamcinolone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triamcinolone (Ophthalmic). Risk C: Monitor therapy
Triamcinolone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triamcinolone (Systemic). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of triamcinolone and strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Triamcinolone (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triamcinolone (Topical). Risk C: Monitor therapy
Triazolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triazolam. Risk X: Avoid combination
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. 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. Risk X: Avoid combination
Ulipristal: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ulipristal. Risk C: Monitor therapy
Upadacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Upadacitinib. Management: For ulcerative colitis use upadacitinib 30 mg/day for 8 weeks for induction, then 15 mg/day for maintenance. For rheumatoid arthritis, psoriatic arthritis, or atopic dermatitis use upadacitinib 15 mg/day. Monitor for upadacitinib toxicities. Risk D: Consider therapy modification
Valbenazine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of 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: Consider therapy modification
Vemurafenib: 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 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, and consider a vemurafenib dose reduction. Risk D: Consider therapy modification
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
Verapamil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Verapamil. Risk C: Monitor therapy
Vilanterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilanterol. Risk C: Monitor therapy
Vilazodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. Management: Limit the maximum 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
VinBLAStine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinBLAStine. Risk C: Monitor therapy
VinCRIStine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine. Management: Seek alternatives to this combination when possible. If combined, monitor closely for vincristine toxicities (eg, neurotoxicity, gastrointestinal toxicity, myelosuppression). Risk D: Consider therapy modification
VinCRIStine (Liposomal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
Vindesine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vindesine. Risk C: Monitor therapy
Vinflunine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Vinflunine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinflunine. Risk X: Avoid combination
Vinorelbine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinorelbine. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Macrolide Antibiotics may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Voclosporin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Voclosporin. Risk X: Avoid combination
Vorapaxar: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vorapaxar. Risk X: Avoid combination
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
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 therapy modification
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
Zolpidem: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zolpidem. Risk C: Monitor therapy
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
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.
Clarithromycin crosses the placenta (Witt 2003).
The manufacturer recommends that clarithromycin not be used in pregnant patients unless there are no alternative therapies. Clarithromycin is not recommended as a first-line agent for the treatment or prophylaxis of Mycobacterium avium complex in pregnant patients living with HIV (HHS [OI adult] 2022).
Clarithromycin and its active metabolite (14-hydroxyclarithromycin) are present in breast milk.
Data related to the presence of clarithromycin in breast milk is available from 12 breastfeeding women taking oral clarithromycin 250 mg twice daily for puerperal infections. Serial blood and milk samples were obtained at timed intervals. Both clarithromycin and its active metabolite, 14-hydroxyclarithromycin, were present in breast milk. The mean peak clarithromycin milk concentration was 0.85 mg/L ± 0.12 mg/L at 2.2 ± 0.2 hours after the dose; peak 14-hydroxyclarithromycin concentrations were 0.63 mg/L ± 0.08 mg/L at 2.8 ± 0.3 hours after the dose. The half-lives of clarithromycin and 14-hydroxyclarithromycin in breast milk were 4.3 ± 0.3 hours and 9 ± 1.2 hours, respectively (Sedlmayr 1993).
The manufacturer calculated the estimated daily infant dose of drug and active metabolite via breast milk to be 136 mcg/kg/day (relative infant dose [RID] <1% based on a therapeutic infant dose of 15 mg/kg/day). In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000).
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.
BUN, creatinine, LFTs, audiogram with prolonged use, ECG for QTc prolongation (ATS/ERS/ESCMID/IDSA [Daley 2020]).
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.
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
Altered kidney function: 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.
Anti-infective considerations:
Parameters associated with efficacy: Concentration (AUC/minimum inhibitory concentration [MIC]) and time (time/MIC) dependent (Bauernfeind 1995; Craig 2001a; Craig 2001b; Periti 1999).
Expected drug exposure in normal renal function:
Cmax (peak):
Children ≤7 years of age: Multiple doses (steady state): 7.5 mg/kg/dose every 12 hours: 4.6 ± 2.08 mg/L (Gan 1992).
Adults, multiple doses (steady state):
IR tablet: 250 mg every 12 hours: 1 to 2 mg/L; 500 mg every 8 to 12 hours: 3 to 4 mg/L.
ER tablet: 500 mg once daily: 1 to 2 mg/L; 1 g once daily: 2 to 3 mg/L.
AUC:
Children ≤7 years of age: Multiple doses (steady state): 7.5 mg/kg/dose every 12 hours: AUC0-6: 15.7 ± 6.72 mg•hour/L (Gan 1992).
Adults, multiple doses (steady state): IR tablet: 250 mg every 12 hours: AUC24 7.85 ± 2 mg•hour/L (Kees 1995).
Postantibiotic effect: Varies based on organism:
Gram-positive/gram-negative respiratory pathogens: 1.7 to 3.8 hours (Ferrara 1996).
Mycobacterium avium complex: 5.5 to 18 hours (Ellis 1995; Horgen 1999).
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
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