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Clarithromycin

Medically reviewed by Drugs.com. Last updated on Jul 22, 2020.

Pronunciation

(kla RITH roe mye sin)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Suspension Reconstituted, Oral:

Biaxin: 250 mg/5 mL (100 mL [DSC])

Generic: 125 mg/5 mL (50 mL, 100 mL); 250 mg/5 mL (50 mL, 100 mL)

Tablet, Oral:

Biaxin: 250 mg [DSC] [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow)]

Biaxin: 500 mg [DSC] [contains fd&c yellow #10 (quinoline yellow)]

Generic: 250 mg, 500 mg

Tablet Extended Release 24 Hour, Oral:

Generic: 500 mg

Brand Names: U.S.

  • Biaxin [DSC]

Pharmacologic Category

  • Antibiotic, Macrolide

Pharmacology

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 distributes into most body tissues; manufacturer reports no data in regards to CNS penetration

Metabolism

Partially hepatic via CYP3A4; converted to 14-OH clarithromycin (active metabolite); undergoes extensive first-pass metabolism

Excretion

Primarily 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

Time to Peak

Immediate release: 2-3 hours; Extended release: 5-8 hours

Half-Life Elimination

Immediate release: Clarithromycin: 3-7 hours; 14-OH-clarithromycin: 5-9 hours

Protein Binding

42% to 70% (Peters, 1992)

Special Populations: Renal Function Impairment

The pharmacokinetics of clarithromycin were altered in subjects with impaired renal function.

Special Populations: 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.

Use: Labeled Indications

Chronic obstructive pulmonary disease, acute exacerbation: Treatment of acute bacterial exacerbation of chronic bronchitis in adults due to susceptible Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, or Streptococcus pneumoniae.

Helicobacter pylori eradication: Eradication of Helicobacter pylori to reduce the risk of duodenal ulcer recurrence as a component of combination therapy (triple therapy) in adults with H. pylori infection and duodenal ulcer disease (active or 5-year history of duodenal ulcer).

Limitations of use: Regimens that contain clarithromycin as the single antibacterial agent are more likely to be associated with the development of clarithromycin resistance. Clarithromycin-containing regimens should not be used in patients with known or suspected clarithromycin-resistant isolates (efficacy is reduced).

Mycobacterial (nontuberculous) infection: Prophylaxis and treatment of disseminated mycobacterial infections due to Mycobacterium avium complex (MAC) in patients with advanced HIV infection.

Otitis media: Treatment of acute otitis media in pediatric patients due to susceptible H. influenzae, M. catarrhalis, or S. pneumoniae.

Pneumonia, community-acquired: Treatment of community-acquired pneumonia due to susceptible Mycoplasma pneumoniae, S. pneumoniae, or Chlamydophila pneumoniae (adult and pediatric patients) and H. influenzae, H. parainfluenzae, or M. catarrhalis (adults).

Skin/skin structure infection: Treatment of uncomplicated skin/skin structure infection due to susceptible Staphylococcus aureus or Streptococcus pyogenes.

Streptococcal pharyngitis: Treatment of pharyngitis/tonsillitis due to susceptible S. pyogenes (alternative agent for patients with severe penicillin allergy).

Off Label Uses

Bartonella spp. infection

Based on the US Department of Health and Human Services guidelines for prevention and treatment of opportunistic infections in adults and adolescents with HIV, clarithromycin is an effective and recommended alternative agent for treatment or long-term suppression of bartonellosis infection.

Clinical experience also suggests the utility of clarithromycin for the treatment of cat scratch disease [Spach 2020].

Bronchiolitis obliterans, including diffuse panbronchiolitis and symptomatic cryptogenic bronchiolitis obliterans

Data from a limited number of patients studied in an open-label, nonrandomized, long-term trial suggest clarithromycin may be beneficial for the treatment of diffuse panbronchiolitis [Kadota 2003].

Clinical experience suggests the utility of clarithromycin in managing symptomatic cryptogenic bronchiolitis obliterans [Callahan 2019], [King 2020].

Endocarditis, prophylaxis, dental or invasive respiratory tract procedure

Based on the American Heart Association guidelines for the prevention of infective endocarditis, clarithromycin is an effective and recommended alternative antibiotic for prophylaxis of infective endocarditis in patients with certain cardiac conditions who are allergic to penicillins or ampicillin and undergoing dental or respiratory tract procedures.

Mycobacterium abscessus infection

Based on the American Thoracic Society/Infectious Diseases Society of America guideline on the diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases, the British Thoracic Society guidelines for the management of nontuberculous mycobacterial pulmonary disease, and the US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of nontuberculous mycobacteria in individuals with cystic fibrosis, clarithromycin (in combination with other antimicrobials) is effective and recommended for the treatment of M. abscessus pulmonary, skin, soft tissue, and bone infections [ATS/IDSA [Griffith 2007]], [BTS [Haworth 2017]], [CFF/ECFS [Floto 2016]].

Pertussis

Based on the Centers for Disease Control and Prevention (CDC) guidelines for treatment and postexposure prophylaxis of pertussis, clarithromycin is effective and recommended in the management of pertussis.

Q fever (Coxiella burnetii), acute symptomatic

Data from a limited number of patients studied suggest clarithromycin may be beneficial as an alternative treatment for symptomatic Q fever [Gikas 2001].

Based on the CDC recommendations for the diagnosis and management of Q fever, clarithromycin may be used as an alternative agent in the management of Q fever [CDC [Anderson 2013]].

Contraindications

Hypersensitivity to clarithromycin, erythromycin, any of the macrolide antibiotics, or any component of the formulation; history of cholestatic jaundice/hepatic dysfunction associated with prior use of clarithromycin; concomitant use with cisapride, pimozide, ergot alkaloids (eg, ergotamine, dihydroergotamine), lomitapide, or HMG-CoA reductase inhibitors extensively metabolized by CYP3A4 (eg, lovastatin, simvastatin); concomitant use with colchicine in patients with renal or hepatic impairment

Canadian labeling: Additional contraindications (not in US labeling): Severe hepatic failure in combination with renal impairment; history of QT prolongation (congenital or documented acquired QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes; hypokalemia; concomitant use with saquinavir, midazolam (oral), colchicine (regardless of hepatic/renal impairment), ticagrelor; concomitant use with astemizole, domperidone, terfenadine, or ranolazine (not available in Canada)

Dosing: Adult

General dosing note: IR and ER formulations are available; 500 mg every 12 hours of immediate release is equivalent to 1 g of extended release (two 500 mg ER tablets) once daily.

Bartonella spp. infection (off-label use):

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

Note: Not to be used for endocarditis or CNS infections (HHS [OI adult] 2019).

Primary treatment (alternative agent): Oral: Immediate release: 500 mg twice daily for at least 3 to 4 months (HHS [OI adult] 2019).

Long-term suppression for patients with relapse after ≥3 months of primary treatment: Oral: Immediate release: 500 mg twice daily; may discontinue if completed 3 to 4 months of therapy and CD4 >200 cells/mm3 for ≥6 months. Note: Some experts discontinue only if Bartonella titers have also decreased 4-fold (HHS [OI adult] 2019).

Cat scratch disease, lymphadenitis (alternative agent): Oral: Immediate release: 500 mg twice daily for 7 to 10 days (Spach 2020).

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 2020).

Oral: Immediate release: 500 mg every 12 hours for 3 to 7 days (Falagas 2008; GOLD 2019; Hunter 2001; Sethi 2020).

Endocarditis prophylaxis, dental or invasive respiratory tract procedure (alternative agent for patients with penicillin allergy) (off-label use): Oral: Immediate release: 500 mg administered 30 to 60 minutes prior to procedure. Note: Reserve for select situations (cardiac condition with the highest risk of adverse endocarditis outcomes and procedure likely to result in bacteremia with an organism that can cause endocarditis) (AHA [Wilson 2007]).

Helicobacter pylori eradication: Note: Avoid clarithromycin-based therapy in patients with risk factors for macrolide resistance (eg, prior macrolide exposure, local clarithromycin resistance rates ≥15% [which is assumed in the United States] or eradication rates with clarithromycin triple therapy ≤85%) (ACG [Chey 2017]; Crowe 2020; Fallone 2016).

Oral: Immediate release: 500 mg twice daily for 7 to 14 days as part of an appropriate combination regimen (ACG [Chey 2017]; Crowe 2020; Fallone 2016; McNicholl 2020).

Mycobacterial (nontuberculous) infection:

Mycobacterium avium complex infection:

Disseminated disease in patients with HIV:

Treatment: Oral: Immediate release: 500 mg twice daily as part of an appropriate combination regimen for a minimum of 12 months; subsequently may discontinue once there are no signs/symptoms of Mycobacterium avium complex disease and the CD4 count has exceeded 100 cells/mm3 for >6 months in response to antiretroviral therapy (ART) (HHS [OI adult] 2019).

Primary prophylaxis: Note: Not routinely recommended; reserve for patients with CD4 count <50 cells/mm3 who are not initiated on fully suppressive ART.

Oral: Immediate release: 500 mg twice daily; may discontinue prophylaxis when patient is initiated on effective ART (HHS [OI adult] 2019; IAS-USA [Saag 2018]).

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

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

Mycobacterium abscessus infection (off-label use): Note: Perform susceptibility testing before and after ≥14 days of clarithromycin incubation to evaluate for the presence of an inducible erm gene, which can result in decreased macrolide susceptibility even with a “susceptible” MIC result and may preclude use of clarithromycin (CFF/ECFS [Floto 2016]; Griffith 2020).

Pulmonary, skin, soft tissue, or bone infection: Oral: Immediate release: 500 mg twice daily as part of an appropriate combination regimen and continued for ≥6 to 12 months (ATS/IDSA [Griffith 2007]; CFF/ECFS [Floto 2016]; Griffith 2020). Note: Patients should be under the care of a clinician with expertise in managing mycobacterial infection.

Pertussis (off-label use):

Treatment: Note: Treatment should be initiated within 21 days of cough onset. After this interval, some experts reserve treatment for pregnant women, patients >65 years of age, and those with asthma, chronic obstructive pulmonary disease, or immunocompromising conditions (Cornia 2020).

Oral: Immediate release: 500 mg twice daily for 7 days (CDC [Tiwari 2005]).

Postexposure prophylaxis: Note: Postexposure prophylaxis should be administered, regardless of vaccination history, to close contacts of persons with pertussis during the first 21 days of cough.

Oral: Immediate release: 500 mg twice daily for 7 days (CDC [Tiwari 2005]).

Pneumonia, community-acquired:

Inpatient: Oral: Immediate release: 500 mg twice daily as part of an appropriate combination regimen (ATS/IDSA [Metlay 2019]).

Outpatient: Oral: 500 mg (immediate release) twice daily (ATS/IDSA [Metlay 2019]) or 1 g (two 500 mg ER tablets) once daily. Note: Use as part of an appropriate combination regimen; if local pneumococcal macrolide resistance is <25%, monotherapy is an alternative approach for outpatients without comorbidities or risk factors for antibiotic-resistant pathogens (ATS/IDSA [Metlay 2019]).

Duration of therapy: Minimum of 5 days; patients should be clinically stable with normal vital signs before therapy is discontinued (ATS/IDSA [Metlay 2019]).

Q fever (Coxiella burnetii), acute symptomatic (alternative agent) (off-label use): Note: Reserved for nonpregnant patients who are not at risk for complications (eg, no endocarditis or underlying valvular disease) (Raoult 2020). Treatment is most effective if given within the first 3 days of symptoms (CDC [Anderson 2013]).

Oral: Immediate release: 500 mg twice daily for 14 days (Gikas 2001; Raoult 2020).

Streptococcal pharyngitis (group A) (alternative agent for patients with severe penicillin allergy): Oral: Immediate release: 250 mg every 12 hours for 10 days (IDSA [Shulman 2012]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: All pediatric dosing recommendations based on immediate release product formulations (tablet and oral suspension):

General dosing, susceptible infection, mild to moderate infection: Infants, Children, and Adolescents: Oral: 15 mg/kg/day divided every 12 hours; maximum single dose: 500 mg (Red Book [AAP 2012])

Bartonellosis, treatment and secondary prophylaxis in HIV-exposed/-positive patients (excluding CNS infections and endocarditis): Limited data available: Oral:

Infants and Children: 15 mg/kg/day divided every 12 hours for at least 3 months; maximum single dose: 500 mg (CDC 2009)

Adolescents: 500 mg twice daily administered for at least 3 months (DHHS [adult] 2013)

Endocarditis, prophylaxis: Note: AHA guidelines (Baltimore 2015) limit the use of prophylactic antibiotics to patients at the highest risk for infective endocarditis (IE) or adverse outcomes (eg, prosthetic heart valves, patients with previous IE, unrepaired cyanotic congenital heart disease, repaired congenital heart disease with prosthetic material or device during first 6 months after procedure, repaired congenital heart disease with residual defects at the site or adjacent to site of prosthetic patch or device, heart transplant recipients with cardiac valvulopathy):

Dental procedures in patients allergic to penicillins: Limited data available: Infants, Children, and Adolescents: Oral: 15 mg/kg; maximum single dose: 500 mg; administer 30 to 60 minutes before procedure (AHA [Wilson 2007]).

Group A streptococcal infection; rheumatic fever, primary prevention and treatment of streptococcal tonsillopharyngitis: Infants, Children, and Adolescents: Oral: 15 mg/kg/day divided every 12 hours for 10 days; maximum single dose: 250 mg (Gerber 2009; IDSA [Shulman 2012])

Helicobacter pylori eradication: Children and Adolescents: Oral: 20 mg/kg/day divided every 12 hours for 7 to 14 days. Note: Duration dependent on regimen used; maximum single dose: 500 mg. Administer as part of triple or quadruple combination regimens with amoxicillin and proton pump inhibitor with or without metronidazole (Koletzko 2011)

Lyme disease: Limited data available: Infants, Children, and Adolescents: Oral: 7.5 mg/kg twice daily for 14 to 21 days; maximum single dose: 500 mg (IDSA [Wormser 2006])

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

Infants and Children (DHHS [pediatric] 2013):

Prophylaxis:

Primary prophylaxis: Oral: 15 mg/kg/day divided every 12 hours; maximum single dose: 500 mg; to prevent first episode begin therapy at the following CD4+ T-lymphocyte counts (see below):

Infants <12 months: <750 cells/mm3

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

Children 2 to 5 years: <75 cells/mm3

Children ≥6 years: <50 cells/mm3

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

Treatment: Oral: 15 to 30 mg/kg/day divided every 12 hours; maximum single dose: 500 mg; use in combination with ethambutol and if severe infection, rifabutin; follow with chronic suppressive therapy

Adolescents (DHHS [adult] 2013):

Prophylaxis:

Primary prophylaxis: Oral: 500 mg twice daily

Secondary prophylaxis: Oral: 500 mg twice daily plus ethambutol; consider additional agents (eg, rifabutin, aminoglycoside, fluoroquinolone) for CD4 <50 cells/mm3, high mycobacterial load, or ineffective antiretroviral therapy.

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

Otitis media, acute (AOM): Infants ≥6 months and Children: Oral: 15 mg/kg/day divided every 12 hours for 10 days; maximum single dose: 500 mg; Note: Due to increased S. pneumoniae and H. influenzae resistance, clarithromycin is not routinely recommended as a treatment option (AAP [Lieberthal 2013])

Peritonitis (peritoneal dialysis), prophylaxis for patients requiring invasive dental procedures: Infants, Children, and Adolescents: Oral: 15 mg/kg 30 to 60 minutes before dental procedure; maximum single dose: 500 mg (Warady [ISPD 2012])

Pertussis: Infants, Children, and Adolescents: Oral: 15 mg/kg/day divided every 12 hours for 7 days; maximum single dose: 500 mg (CDC [Tiwari 2005])

Pneumonia, community-acquired (CAP); presumed atypical pneumonia (M. pneumoniae, C. pneumoniae, C. trachomatis); mild infection or step-down therapy: Infants >3 months, Children, and Adolescents: Oral: 15 mg/kg/day every 12 hours for 10 days; shorter courses may be appropriate for mild disease; maximum single dose: 500 mg; Note: A beta-lactam antibiotic should be added if typical bacterial pneumonia cannot be ruled out (Bradley 2011).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Reconstitution

Granules for suspension: Refer to manufacturer's product labeling for reconstitution instructions. Shake well.

Administration

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).

Storage

Extended release tablets: Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Immediate release tablets:

250 mg: Store at 15°C to 30°C (59°F to 86°F). Protect from light.

500 mg: Store at 20°C to 25°C (68°F to 77°F).

Granules for suspension: Store at 25°C (77°F) prior to and following reconstitution. Do not refrigerate. Use within 14 days of reconstitution.

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

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. Consider therapy modification

Acalabrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Acalabrutinib. 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. 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. 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. Consider therapy modification

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

Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. 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. 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. Consider therapy modification

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

ALPRAZolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ALPRAZolam. Management: Consider using an alternative agent that is less likely to interact. If combined, monitor for increased therapeutic/toxic effects of alprazolam if combined with a strong CYP3A4 inhibitor. Consider therapy modification

Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Monitor therapy

Antihepaciviral Combination Products: May increase the serum concentration of Clarithromycin. Management: Avoid clarithromycin doses greater than 1000 mg/day when used with an antihepaciviral combination product. Further dose reductions may be needed in patients with impaired renal function. Consider an alternative antimicrobial for any non-MAC infection. Consider therapy modification

Apixaban: Clarithromycin may increase the serum concentration of Apixaban. Monitor therapy

Aprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Aprepitant. 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. 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. Consider therapy modification

Astemizole: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Astemizole. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Astemizole. Avoid combination

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

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

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

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

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

Avapritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avapritinib. 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. Consider therapy modification

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

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

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

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

Betamethasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Ophthalmic). Monitor therapy

Betamethasone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Systemic). Monitor therapy

Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease adult betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-gp inhibitor. Avoid concomitant use of betrixaban and P-gp inhibitors in patients with severe renal impairment (CrCL less than 30 mL/min). Consider therapy modification

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

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

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

Bortezomib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib. 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. Consider therapy modification

Bosutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib. 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. 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. 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). Consider therapy modification

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

Budesonide (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Nasal). Monitor therapy

Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Oral Inhalation). Monitor therapy

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. Consider therapy modification

Budesonide (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Topical). Avoid combination

Buprenorphine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Buprenorphine. 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. Consider therapy modification

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. Consider therapy modification

Cabergoline: Clarithromycin may increase the serum concentration of Cabergoline. 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. Consider therapy modification

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

Calcium Channel Blockers: Macrolide Antibiotics may decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Exceptions: Clevidipine. Consider therapy modification

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

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

Capmatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Capmatinib. 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. Consider therapy modification

Cardiac Glycosides: Macrolide Antibiotics may increase the serum concentration of Cardiac Glycosides. Monitor therapy

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

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. 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. Consider therapy modification

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination

Ciclesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ciclesonide (Oral Inhalation). Monitor therapy

Cilostazol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving strong inhibitors of CYP3A4. Consider therapy modification

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

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

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

Codeine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Codeine. 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. 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. Consider therapy modification

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

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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. Consider therapy modification

Corticosteroids (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Systemic). Exceptions: MethylPREDNISolone; PrednisoLONE (Systemic); PredniSONE. 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, decrease crizotinib dose to 250 mg daily. Monitor patients for crizotinib toxicities including QTc prolongation and arrhythmias. Consider therapy modification

CycloSPORINE (Systemic): Clarithromycin may increase the serum concentration of CycloSPORINE (Systemic). Monitor therapy

CYP3A4 Inducers (Moderate): May increase serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and impair its efficacy. Consider therapy modification

CYP3A4 Inducers (Strong): May increase serum concentrations of the active metabolite(s) of Clarithromycin. Clarithromycin may increase the serum concentration of CYP3A4 Inducers (Strong). CYP3A4 Inducers (Strong) may decrease the serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and may impair clarithromycin efficacy. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination. Some combinations are specifically contraindicated by manufacturers; others may have recommended dose adjustments. If combined, monitor for increased substrate effects. Consider therapy modification

CYP3A4 Substrates (High risk with Inhibitors): CYP3A4 Inhibitors (Strong) may decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination. Some combinations are specifically contraindicated by manufacturers; others may have recommended dose adjustments. If combined, monitor for increased substrate effects. Exceptions: Alitretinoin (Systemic); AmLODIPine; Benzhydrocodone; Bromperidol; Buprenorphine; Gefitinib; HYDROcodone; Mirtazapine; Oliceridine; Praziquantel; Ripretinib; Telithromycin; VinBLAStine; Vinorelbine. Consider therapy modification

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Monitor therapy

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

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

Dapoxetine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dapoxetine. 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. Consider therapy modification

Darolutamide: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Darolutamide. 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 Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Deflazacort: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Consider therapy modification

DexAMETHasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of DexAMETHasone (Ophthalmic). Monitor therapy

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

Dihydroergotamine: Clarithromycin may increase the serum concentration of Dihydroergotamine. Avoid combination

DOCEtaxel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of DOCEtaxel. Management: Avoid the concomitant use of docetaxel and strong CYP3A4 inhibitors when possible. If combined use is unavoidable, consider a 50% docetaxel dose reduction and monitor for increased docetaxel toxicities. 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. Avoid combination

Doxercalciferol: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Doxercalciferol. Monitor therapy

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Avoid combination

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

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

Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. 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. Consider therapy modification

Edoxaban: Clarithromycin may increase the serum concentration of Edoxaban. Management: In patients treated for DVT/PE, reduce edoxaban dose to 30 mg daily when combined with clarithromycin. No dose adjustment is recommended for patients treated for atrial fibrillation. Monitor for increased edoxaban toxicities (ie, bleeding) when combined. Consider therapy modification

Efavirenz: May enhance the QTc-prolonging effect of Clarithromycin. Efavirenz may decrease the serum concentration of Clarithromycin. Additionally, efavirenz may increase the active metabolite of clarithromycin Management: Consider using an alternative antibiotic in patients taking efavirenz. If concomitant therapy cannot be avoided, monitor for decreased therapeutic effect of clarithromycin and for QT interval prolongation. Consider therapy modification

Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. 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. Avoid combination

Elagolix, Estradiol, and Norethindrone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Avoid combination

Eletriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eletriptan. 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. 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. 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. 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. Consider therapy modification

Enfortumab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. 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. Avoid combination

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Eplerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. 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. Consider therapy modification

Ergot Derivatives: Macrolide Antibiotics may increase the serum concentration of Ergot Derivatives. Cabergoline and Clarithromycin may interact, see specific monograph for full details. Exceptions: Cabergoline; Lisuride; Nicergoline; Pergolide. Avoid combination

Ergotamine: Clarithromycin may increase the serum concentration of Ergotamine. Avoid combination

Erlotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erlotinib. Management: Avoid use of this combination when possible. When the combination must be used, monitor the patient closely for the development of severe adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Consider therapy modification

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

Estrogen Derivatives: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estrogen Derivatives. 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). Consider therapy modification

Etizolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Etizolam. Management: Consider use of lower etizolam doses when using this combination; specific recommendations concerning dose adjustment are not available. Monitor clinical response to the combination closely. Consider therapy modification

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

Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Monitor therapy

Everolimus: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Everolimus. Avoid combination

Evogliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Evogliptin. 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. 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. 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. Consider therapy modification

Fexinidazole [INT]: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). 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. 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. Monitor therapy

FLUoxetine: May enhance the QTc-prolonging effect of Clarithromycin. Clarithromycin may increase the serum concentration of FLUoxetine. Monitor therapy

Fluticasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Nasal). Avoid combination

Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Consider therapy modification

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

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fostamatinib: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fostamatinib. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

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

Gefitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gefitinib. 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 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. Consider therapy modification

Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy

GlipiZIDE: Clarithromycin may increase the serum concentration of GlipiZIDE. Monitor therapy

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

Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Grazoprevir. Avoid combination

GuanFACINE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when combined with a strong CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. 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. Avoid combination

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

Ibrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrutinib. Management: Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for 7 days or less), interrupt ibrutinib therapy until the strong CYP3A4 inhibitor is discontinued. Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Ifosfamide: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. 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. Consider therapy modification

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

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

Irinotecan Products: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan Products. Avoid combination

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

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

Ivabradine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine. 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. 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. Consider therapy modification

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Lapatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib. Management: Avoid use of lapatinib and strong CYP3A4 inhibitors when possible. If combined, reduce lapatinib dose to 500 mg daily. The previous lapatinib dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. 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. Consider therapy modification

Lefamulin: May enhance the QTc-prolonging effect of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Avoid combination

Lefamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets and strong inhibitors of CYP3A4. Avoid combination

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

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

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

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

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

Lopinavir: Clarithromycin may enhance the QTc-prolonging effect of Lopinavir. Lopinavir may diminish the therapeutic effect of Clarithromycin. Specifically, lopinavir may decrease the formation of the active 14-hydroxy-clarithromycin metabolite, which may negatively impact clarithromycin effectiveness. Lopinavir may increase the serum concentration of Clarithromycin. Clarithromycin may increase the serum concentration of Lopinavir. 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. Consider therapy modification

Lovastatin: Clarithromycin may increase the serum concentration of Lovastatin. Avoid combination

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

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

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

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

Macitentan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Macitentan. 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. Consider therapy modification

Maraviroc: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Management: Reduce maraviroc to 150mg twice/day in adult and pediatric patients weighing 40kg or more. See full interaction monograph or maraviroc labeling for dose adjustments in pediatric patients less than 40kg. Do not use in patients with CrCl less than 30mL/min. Consider therapy modification

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

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

MethylPREDNISolone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose reduction in patients receiving strong CYP3A4 inhibitors and monitor for increased steroid related adverse effects. Consider therapy modification

Midazolam: Macrolide Antibiotics may increase the serum concentration of Midazolam. Management: Consider an alternative less likely to interact. Azithromycin is likely a lower-risk macrolide, and benzodiazepines less dependent on CYP3A metabolism (e.g., lorazepam, oxazepam) are similarly less likely to interact. 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. 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. Consider therapy modification

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. 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. Consider therapy modification

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

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

Mizolastine: Macrolide Antibiotics may increase the serum concentration of Mizolastine. Avoid combination

Mometasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mometasone (Oral Inhalation). Monitor therapy

Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Monitor therapy

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

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

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

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

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

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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. Consider therapy modification

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

Nintedanib: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Nintedanib. Monitor therapy

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

Olaparib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Olaparib. Management: Avoid use of strong CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 100 mg twice daily and the dose of olaparib capsules should be reduced to 150 mg twice daily. Consider therapy modification

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

Osilodrostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Osilodrostat. Management: Reduce osilodrostat dose by 50% during coadministration with a strong CYP3A4 inhibitor. 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. Consider therapy modification

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

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

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. Consider therapy modification

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. 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. Monitor therapy

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

PARoxetine: Clarithromycin may enhance the adverse/toxic effect of PARoxetine. Clarithromycin may enhance the QTc-prolonging effect of PARoxetine. Monitor therapy

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. 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. 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. 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 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. Consider therapy modification

Pimecrolimus: CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus. Monitor therapy

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

Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). 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. Consider therapy modification

Pitavastatin: Clarithromycin may increase the serum concentration of Pitavastatin. 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. Monitor therapy

PONATinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PONATinib. Management: Per ponatinib U.S. prescribing information, the adult starting dose of ponatinib should be reduced to 30 mg daily during treatment with any strong CYP3A4 inhibitor. 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. 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. Consider therapy modification

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

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. Consider therapy modification

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

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

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

QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Clarithromycin. Avoid combination

QT-prolonging Antidepressants (Moderate Risk): QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Exceptions: Citalopram. Monitor therapy

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

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

QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. 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 combined with strong CYP3A4 inhibitors. Monitor patients for quetiapine toxicities, including QTc prolongation and torsades de pointes. Consider therapy modification

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

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

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

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

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

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

Retapamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Retapamulin. Management: Avoid this combination in patients less than 2 years old. No action is required in other populations. Monitor therapy

Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. 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. Consider therapy modification

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. 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. Consider therapy modification

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

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

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

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

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

Rivaroxaban: Clarithromycin may increase the serum concentration of Rivaroxaban. Management: In patients with impaired renal function (ie, CrCl 15-80 mL/min), clarithromycin should not be used unless the potential benefits outweigh the potential risks. Monitor for bleeding in all patients using clarithromycin and rivaroxaban. Consider therapy modification

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

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

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

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

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

Saquinavir: May enhance the QTc-prolonging effect of Clarithromycin. Clarithromycin may increase the serum concentration of Saquinavir. Avoid combination

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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. 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. Consider therapy modification

Sibutramine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Sibutramine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sibutramine. Monitor therapy

Sildenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sildenafil. Management: Use of sildenafil for pulmonary hypertension should be avoided with strong CYP3A4 inhibitors. When used for erectile dysfunction, starting adult dose should be reduced to 25 mg. Maximum adult dose with ritonavir or cobicistat is 25 mg per 48 hours. Consider therapy modification

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

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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

Simvastatin: Clarithromycin may increase the serum concentration of Simvastatin. 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. Consider therapy modification

Sirolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus. 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. Consider therapy modification

Sirolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus. 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. Consider therapy modification

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. 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. Consider therapy modification

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

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

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

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). Consider therapy modification

SUNItinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SUNItinib. Management: Avoid when possible. If combined, decrease sunitinib dose to a minimum of 37.5 mg daily when treating GIST or RCC. Decrease sunitinib dose to a minimum of 25 mg daily when treating PNET. Monitor patients for both reduced efficacy and increased toxicities. Consider therapy modification

Suvorexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Suvorexant. 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. Consider therapy modification

Tacrolimus (Topical): Macrolide Antibiotics may increase the serum concentration of Tacrolimus (Topical). 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. 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. Consider therapy modification

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

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

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

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

Temsirolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Temsirolimus. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inhibitors. If coadministration is unavoidable, decrease temsirolimus dose to 12.5 mg per week. Resume previous temsirolimus dose 1 week after discontinuation of the strong CYP3A4 inhibitor. Consider therapy modification

Terfenadine: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Terfenadine. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Terfenadine. Avoid combination

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

Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. 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. Consider therapy modification

Theophylline Derivatives: Macrolide Antibiotics may decrease the metabolism of Theophylline Derivatives. Management: Consider avoiding erythromycin and troleandomycin in patients receiving theophylline derivatives. Monitor for toxic effects of theophylline derivatives if a macrolide is initiated/dose increased. Other macrolides appear to have little to no effect. Exceptions: Dyphylline. Consider therapy modification

Thiotepa: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Thiotepa. Management: Thiotepa prescribing information recommends avoiding concomitant use of thiotepa and strong CYP3A4 inhibitors. If concomitant use is unavoidable, monitor for adverse effects and decreased efficacy. 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. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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. Consider therapy modification

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

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

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. 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. Consider therapy modification

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

TraMADol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraMADol. 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. Consider therapy modification

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

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

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

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

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

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

Valbenazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Valbenazine. Management: Reduce the valbenazine dose to 40 mg daily when combined with strong CYP3A4 inhibitors. 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. 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. 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. Consider therapy modification

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Consider therapy modification

Vilanterol: May increase the serum concentration of CYP3A4 Inhibitors (Strong). 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. Consider therapy modification

VinBLAStine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinBLAStine. 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). Consider therapy modification

VinCRIStine (Liposomal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination

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

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

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

Vitamin K Antagonists (eg, warfarin): Macrolide Antibiotics may increase the serum concentration of Vitamin K Antagonists. Monitor therapy

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

Voxelotor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and strong CYP3A4 inhibitors. If concomitant use is unavoidable, reduce the voxelotor dose to 1,000 mg once daily. Consider therapy modification

Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. 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. 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. Consider therapy modification

Zopiclone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zopiclone. Management: If coadministered with strong CYP3A4 inhibitors, initiate zopiclone at 3.75 mg in adults, with a maximum dose of 5 mg. Monitor for zopiclone toxicity (eg, drowsiness, confusion, lethargy, ataxia, respiratory depression). Consider therapy modification

Adverse Reactions

1% to 10%:

Central nervous system: Headache (2%), insomnia

Dermatologic: Skin rash (children 3%)

Gastrointestinal: Dysgeusia (adults 3% to 7%), vomiting (children 6%), diarrhea (3% to 6%), nausea (adults 3%), abdominal pain (2% to 3%), dyspepsia (adults 2%)

Hematologic & oncologic: Prolonged prothrombin time (adults 1%)

Hepatic: Abnormal hepatic function tests

Hypersensitivity: Anaphylactoid reaction

Infection: Candidiasis (including oral)

Renal: Increased blood urea nitrogen (4%)

<1%, postmarketing, and/or case reports: Abdominal distension, abnormal albumin-globulin ratio, acne vulgaris, acute generalized exanthematous pustulosis, ageusia, agranulocytosis, altered sense of smell, anaphylaxis, angioedema, anorexia, anosmia, anxiety, asthma, atrial fibrillation, behavioral changes, bullous dermatitis, cellulitis, chest pain, chills, cholestasis, cholestatic hepatitis, Clostridioides (formerly Clostridium) difficile-associated diarrhea, Clostridioides (formerly Clostridium) difficile (colitis), confusion, constipation, dark urine (abnormal urine color associated with liver injury), decreased appetite, decreased white blood cell count, dental discoloration (reversible with dental cleaning), depersonalization, depression, disorientation, dizziness, DRESS syndrome, drowsiness, dyskinesia, eosinophilia, epistaxis, eructation, esophagitis, extrasystoles, fatigue, fever, flatulence, gastritis, gastroenteritis, gastroesophageal reflux disease, glossitis, hallucination, hearing 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

Warnings/Precautions

Concerns related to adverse effects:

• Altered cardiac conduction: Use has been associated with QT prolongation and infrequent cases of arrhythmias, including torsades de pointes (may be fatal); avoid use in patients with known prolongation of the QT interval, ventricular cardiac arrhythmia (including torsades de pointes), uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and patients receiving Class IA (eg, quinidine, procainamide) or Class III (eg, amiodarone, dofetilide, sotalol) antiarrhythmic agents or other drugs known to prolong the QT interval.

• Hepatic effects: Elevated liver function tests and hepatitis (hepatocellular and/or cholestatic with or without jaundice) have been reported; usually reversible after discontinuation of clarithromycin. May lead to hepatic failure or death (rarely), especially in the presence of preexisting diseases and/or concomitant use of medications. Discontinue immediately if symptoms of hepatitis (eg, anorexia, jaundice, abdominal tenderness, pruritus, dark urine) occur.

• Hypersensitivity reactions: Severe acute reactions have been reported, including anaphylaxis, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), Henoch-Schönlein purpura (IgA vasculitis), and acute generalized exanthematous pustulosis; discontinue therapy and initiate treatment immediately for severe acute hypersensitivity reactions.

• Superinfection: Use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• CAD: Use with caution in patients with CAD. A clinical trial in patients with CAD demonstrated an increase in risk of all-cause mortality ≥1 year after the end of treatment in patients randomized to receive clarithromycin. Other epidemiologic studies evaluating this risk have variable results.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis; exacerbation of symptoms and new onset of symptoms has occurred.

• Renal impairment: Use with caution in severe renal impairment; dosage adjustment required.

Special populations:

• Elderly: 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]).

Monitoring Parameters

BUN, creatinine; perform culture and sensitivity studies prior to initiating drug therapy as appropriate

Pregnancy Considerations

Clarithromycin crosses the placenta (Witt 2003).

The manufacturer recommends that clarithromycin not be used in a pregnant woman unless there are no alternative therapies. Clarithromycin is not recommended as a first-line agent for the treatment or prophylaxis of Mycobacterium avium complex or for treatment of bacterial respiratory disease in HIV-infected pregnant patients (HHS [OI adult] 2019]).

Patient Education

What is this drug used for?

• It is used to treat bacterial infections.

• It is used to prevent an infection in people with HIV.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Abdominal pain

• Change in taste

• Passing gas

• Headache

• Nausea

• Vomiting

• Diarrhea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Abnormal heartbeat

• Muscle pain

• Fast heartbeat

• Severe dizziness

• Passing out

• Muscle weakness

• Chest pain

• Shortness of breath

• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes

Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Tablet shell in stool

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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