ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Clarithromycin: Pediatric drug information

Clarithromycin: Pediatric drug information
(For additional information see "Clarithromycin: Drug information" and see "Clarithromycin: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: Canada
  • ACT Clarithromycin XL;
  • APO-Clarithromycin;
  • APO-Clarithromycin XL;
  • Biaxin;
  • Biaxin XL [DSC];
  • DOM-Clarithromycin;
  • GEN-Clarithromycin;
  • M-Clarithromycin;
  • PMS-Clarithromycin;
  • RIVA-Clarithromycin;
  • SANDOZ Clarithromycin;
  • TARO-Clarithromycin;
  • TEVA-Clarithromycin [DSC]
Therapeutic Category
  • Antibiotic, Macrolide
Dosing: Pediatric

General dosing: Infants, Children, and Adolescents: Immediate release: Oral: 7.5 mg/kg/dose every 12 hours; maximum dose: 500 mg/dose (Red Book [AAP 2021]).

Bartonellosis

Bartonellosis: Limited data available:

Primary treatment (alternative agent): Adolescents, HIV-infected: Immediate release: Oral: 500 mg twice daily for ≥3 months. After completion of therapy, closely monitor for relapse; if relapse occurs, an additional course of treatment followed by long-term suppression is recommended. Note: Should not be used for endocarditis or CNS infections (HHS [OI adult 2021]).

Endocarditis, prophylaxis before invasive dental or respiratory tract procedures

Endocarditis, prophylaxis before invasive dental or respiratory tract procedures (alternative agent for patients with penicillin allergy): Limited data available:

Note: Recommended only in patients who are at highest risk for infective endocarditis (IE) or adverse outcomes (eg, history of IE, prosthetic heart valves or prosthetic material used to repair valves, unrepaired cyanotic congenital heart disease, repaired congenital heart disease with prosthetic material or device during first 6 months after procedure, repaired congenital heart disease with residual defects at the site or adjacent to site of prosthetic patch or device, heart transplant recipients with cardiac valvulopathy) (AHA [Baltimore 2015]; AHA [Wilson 2021]; AHA/ACC [Nishimura 2017]).

Infants, Children, and Adolescents: Immediate release: Oral: 15 mg/kg as a single dose administered 30 to 60 minutes prior to procedure; maximum dose: 500 mg/dose (AHA [Wilson 2021]).

Helicobacter pylori eradication

Helicobacter pylori eradication : Limited data available: Note: Use as part of an appropriate combination regimen; usual duration of therapy is 14 days (NASPGHAN/ESPGHAN [Jones 2017]).

Weight-directed dosing: Children and Adolescents: Immediate release: Oral: 7.5 to 10 mg/kg/dose twice daily; maximum dose: 500 mg/dose (Bontems 2011; Butenko 2017; Huang 2013; Koletzko 2011; Kutluk 2014; Szajewska 2009).

Fixed dosing (NASPGHAN/ESPGHAN [Jones 2017]): Children and Adolescents: Immediate release:

15 to <25 kg: Oral: 250 mg twice daily.

25 to <35 kg: Oral: 500 mg in the morning and 250 mg in the evening.

≥35 kg: Oral: 500 mg twice daily.

Lyme disease, erythema migrans

Lyme disease (Borrelia spp. infection), erythema migrans (alternative agent): Limited data available: Note: Current guidelines recommend macrolides (azithromycin) only when first-line agents cannot be used due to lower efficacy (IDSA/AAN/ACR [Lantos 2021]).

Infants, Children, and Adolescents: Immediate release: Oral: 7.5 mg/kg twice daily for 14 days; maximum dose: 500 mg/dose (Nizič 2012; IDSA [Wormser 2006]).

Mycobacterial infection

Mycobacterial (nontuberculous) infection:

Mycobacterium avium complex infection in patients that are HIV-exposed/-infected: (HHS [pediatric OI 2021]; HHS [adult OI 2021]):

Infants, Children, and Adolescents: Limited data available in Infants and Children <20 months:

Primary prophylaxis (patients who meet age-specific CD4 count thresholds): Immediate release: Oral: 7.5 mg/kg/dose every 12 hours; maximum dose: 500 mg/dose.

Treatment: Immediate release: Oral: 7.5 to 15 mg/kg/dose every 12 hours as part of an appropriate combination regimen for ≥12 months; maximum dose: 500 mg/dose; follow with chronic maintenance therapy (secondary prophylaxis).

Chronic maintenance therapy (secondary prophylaxis): Immediate release: Oral: 7.5 mg/kg/dose every 12 hours as part of an appropriate combination regimen; maximum dose: 500 mg/dose. May be discontinued once there are no signs/symptoms of M. avium complex disease, and the CD4 count has exceeded age-specific thresholds for ≥6 months in response to stable antiretroviral therapy.

Pulmonary infection in patients with or without cystic fibrosis (eg, M. avium complex, Mycobacterium abscessus): Limited data available: Infants, Children, and Adolescents: Immediate release: Oral: 7.5 mg/kg/dose every 12 hours for ≥12 months after culture conversion; maximum dose: 500 mg/dose (BTS [Haworth 2017]; CFF/ECFS [Floto 2016]).

Otitis media, acute

Otitis media, acute (AOM): Note: Not recommended for routine empiric use due to limited efficacy against Streptococcus pneumoniae and Haemophilus influenzae (AAP [Lieberthal 2013]).

Infants ≥6 months and Children: Immediate release: Oral: 7.5 mg/kg/dose every 12 hours for 10 days; maximum dose: 500 mg/dose (manufacturer's labeling).

Peritonitis, prophylaxis for patients requiring invasive dental procedures

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

Infants, Children, and Adolescents: Immediate release: Oral: 15 mg/kg as a single dose 30 to 60 minutes prior to dental procedure; maximum dose: 500 mg/dose (ISPD [Warady 2012]).

Pertussis; treatment or postexposure prophylaxis

Pertussis; treatment or postexposure prophylaxis: Infants, Children, and Adolescents: Immediate release: Oral: 7.5 mg/kg/dose every 12 hours for 7 days; maximum dose: 500 mg/dose (CDC [Tiwari 2005]).

Pneumonia, community-acquired; mild infection or step-down therapy

Pneumonia, community-acquired (presumed or proven atypical pneumonia); mild infection or step-down therapy:

Infants >3 months, Children, and Adolescents: Immediate release: Oral: 7.5 mg/kg/dose every 12 hours for 10 days; shorter courses may be appropriate for mild disease; maximum dose: 500 mg/dose (PIDS/IDSA [Bradley 2011]; manufacturer's labeling).

Streptococcus, group A; pharyngitis/tonsillitis

Streptococcus, group A; pharyngitis/tonsillitis (alternative agent for severe penicillin allergy):

Infants ≥6 months, Children, and Adolescents: Immediate release: Oral: 7.5 mg/kg/dose every 12 hours for 10 days; maximum dose: 250 mg/dose (IDSA [Shulman 2012]; manufacturer's labeling).

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

Dosing: Kidney Impairment: Pediatric

Infants, Children, and Adolescents: The following adjustments have been recommended (Aronoff 2007). Note: Renally adjusted dose recommendations are based on a dose of 7.5 mg/kg/dose every 12 hours.

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

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

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

Hemodialysis: Administer after hemodialysis session is completed: Immediate release: 4 mg/kg/dose once daily.

Peritoneal dialysis: Immediate release: 4 mg/kg/dose once daily.

Dosing: Hepatic Impairment: Pediatric

Infants ≥6 months, Children, and Adolescents: No dosage adjustment necessary if renal function is normal; however, in patients with hepatic impairment and concomitant severe renal impairment, a dosage reduction or prolonged dosing intervals may be appropriate.

Dosing: Adult

(For additional information see "Clarithromycin: Drug information")

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

Bartonella spp. infection (off-label use):

Patients with HIV:

Treatment:

Bacillary angiomatosis, cat scratch disease, peliosis hepatitis, bacteremia, or osteomyelitis (alternative agent): Note: Not to be used for endocarditis or CNS infections.

Oral: Immediate release: 500 mg twice daily for ≥3 months (HHS [OI adult] 2022).

Suppressive therapy: Note: For patients who experience a relapse after receiving a ≥3-month course of primary treatment.

Oral: Immediate release: 500 mg twice daily. Continue until patient has received ≥3 months of therapy and CD4 count is >200 cells/mm3 for ≥6 months; some experts discontinue only if Bartonella titers have also decreased 4-fold (HHS [OI adult] 2022; Spach 2022a).

Patients without HIV:

Cat scratch disease, lymphadenitis (alternative agent): Oral: Immediate release: 500 mg twice daily for 7 to 10 days (Spach 2022b).

Bronchiolitis obliterans, including diffuse panbronchiolitis and symptomatic cryptogenic bronchiolitis obliterans

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

Chronic obstructive pulmonary disease, acute exacerbation: Note: Avoid use in patients with risk factors for Pseudomonas infection or poor outcomes (eg, ≥65 years of age with major comorbidities, FEV1 <50% predicted, frequent exacerbations) (Sethi 2022).

Oral: Immediate release: 500 mg every 12 hours for 5 to 7 days (Falagas 2008; GOLD 2021; Hunter 2001).

Endocarditis prophylaxis, dental or invasive respiratory tract procedure

Endocarditis prophylaxis, dental or invasive respiratory tract procedure (alternative agent for patients with penicillin allergy) (off-label use): Oral: Immediate release: 500 mg administered 30 to 60 minutes prior to procedure; if inadvertently not given prior to the procedure, may be administered up to 2 hours after the procedure. Note: Reserve for select situations (cardiac condition with the highest risk of adverse endocarditis outcomes and procedure likely to result in bacteremia with an organism that can cause endocarditis) (AHA [Wilson 2007]; AHA [Wilson 2021]).

Helicobacter pylori eradication

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 infection

Mycobacterial (nontuberculous) infection:

Mycobacterium avium complex infection:

Disseminated disease in patients with HIV:

Treatment: Oral: Immediate release: 500 mg twice daily as part of an appropriate combination regimen for a minimum of 12 months; subsequently may discontinue once there are no signs/symptoms of Mycobacterium avium complex disease and the CD4 count has exceeded 100 cells/mm3 for >6 months in response to antiretroviral therapy (ART) (HHS [OI adult] 2020).

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

Oral: Immediate release: 500 mg twice daily; may discontinue prophylaxis when patient is initiated on effective ART (HHS [OI adult] 2020; IAS-USA [Saag 2018]).

Pulmonary disease, nonsevere noncavitary nodular/bronchiectatic disease in patients without cystic fibrosis (alternative agent) (off-label use): Oral: Immediate release: 500 mg twice daily 3 times weekly as part of an appropriate combination regimen; continue treatment until patient is culture negative on therapy for ≥1 year (ATS/ERS/ESCMID/IDSA [Daley 2020]; BTS [Haworth 2017]).

Pulmonary disease, severe nodular/bronchiectatic disease, cavitary disease, or disease in patients with cystic fibrosis (alternative agent) (off-label use): Oral: Immediate release: 500 mg twice daily as part of an appropriate combination regimen. Continue treatment until patient is culture negative on therapy for ≥1 year (ATS/ERS/ESCMID/IDSA [Daley 2020]; BTS [Haworth 2017]; CFF/ECFS [Floto 2016]).

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

Pulmonary, skin, soft tissue, or bone infection: Oral: Immediate release: 500 mg twice daily as part of an appropriate combination regimen and continued for ≥6 to 12 months for pulmonary and bone infections and ≥4 months for skin/soft tissue infections (ATS/ERS/ESCMID/IDSA [Daley 2020]; CFF/ECFS [Floto 2016]; Griffith 2020). Note: Patients should be under the care of a clinician with expertise in managing mycobacterial infection (ATS/ERS/ESCMID/IDSA [Daley 2020]).

Pertussis

Pertussis (off-label use):

Treatment: Note: Treatment should be initiated within 21 days of cough onset. After this interval, some experts reserve treatment for pregnant women, patients >65 years of age, and those with asthma, chronic obstructive pulmonary disease, or immunocompromising conditions (Cornia 2021).

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

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

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

Pneumonia, community-acquired

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, acute symptomatic

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

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

Streptococcal pharyngitis, group A

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

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

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function:

Clarithromycin Dosage Adjustments in Altered Kidney Functiona: Oral

a Davey 1991; Fraschini 1993; Hardy 1992; manufacturer’s labeling

b CrCl determined using Cockcroft-Gault formula.

c IR = immediate release

d ER = extended release

e IR product would be equally effective (expert opinion).

f No pharmacokinetic data in hemodialysis/peritoneal dialysis patients; recommendations are based on expert opinion only.

g Although unlikely to be significantly dialyzed (manufacturer’s labeling), because no data on degree of dialyzability are available, consider administering after dialysis when scheduled dose falls on dialysis days.

CrClb

If the usual recommended dose is IRc 250 mg twice daily

If the usual recommended dose is IR 500 mg twice daily

If the usual recommended dose is ERd 1 g once daily

≥30 mL/minute

No dosage adjustment necessary.

No dosage adjustment necessary.

No dosage adjustment necessary.

<30 mL/minute

IR: 250 mg once daily

IR: 250 mg twice daily or 500 mg once daily

ER: 500 mg once dailye

Intermittent hemodialysis, thrice weeklyf,g

IR: 250 mg once daily

IR: 250 mg twice daily or 500 mg once daily

ER: 500 mg once dailye

Peritoneal dialysisf

IR: 250 mg once daily

IR: 250 mg twice daily or 500 mg once daily

ER: 500 mg once dailye

CRRT: Unlikely to be significantly dialyzed (large Vd) (expert opinion):

Oral: Follow dosing recommendations for patients with CrCl <30 mL/minute. Note: In general, use of IV antimicrobial therapy may be preferred in patients receiving CRRT (expert opinion).

PIRRT (eg, sustained, low-efficiency diafiltration): Unlikely to be significantly dialyzed (large Vd) (expert opinion):

Oral: Follow dosing recommendations for patients with CrCl <30 mL/minute.Note: In general, use of IV antimicrobial therapy may be preferred in patients receiving PIRRT (expert opinion).

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary if renal function is normal; however, in patients with hepatic impairment and concomitant severe renal impairment, a dosage reduction or prolonged dosing intervals may be appropriate.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension Reconstituted, Oral:

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

Tablet, Oral:

Generic: 250 mg, 500 mg

Tablet Extended Release 24 Hour, Oral:

Generic: 500 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

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

Suspension Reconstituted, Oral:

Biaxin: 125 mg/5 mL (55 mL, 105 mL); 250 mg/5 mL (105 mL)

Generic: 125 mg/5 mL (55 mL, 105 mL, 150 mL); 250 mg/5 mL (55 mL, 105 mL, 150 mL)

Tablet, Oral:

Biaxin: 250 mg, 500 mg [contains quinoline yellow (d&c yellow #10)]

Generic: 250 mg, 500 mg

Tablet Extended Release 24 Hour, Oral:

Biaxin XL: 500 mg [DSC] [contains quinoline (d&c yellow #10) aluminum lake]

Generic: 500 mg

Administration: Pediatric

Oral:

Immediate-release tablets and oral suspension: May be administered with or without meals. Shake suspension well before each use.

Extended-release tablets: Administer with food. Do not break, crush, or chew.

Administration: Adult

Oral:

IR tablets and granules for suspension: Administer with or without meals. Administer every 12 hours rather than twice daily to avoid peak and trough variation. Shake suspension well before each use.

ER tablets: Administer with food. Do not break, crush, or chew.

Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Switch to IR formulation (tablet or oral solution).

Storage/Stability

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

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

Use

Immediate-release formulations: Treatment of community-acquired pneumonia, acute otitis media, acute maxillary sinusitis, pharyngitis/tonsillitis, and skin and soft tissue infections due to susceptible bacteria (FDA approved in ages ≥6 months and adults); prophylaxis and treatment of Mycobacterium avium complex (MAC) disease in patients with advanced HIV infection (FDA approved in ages ≥20 months and adults); eradication of Helicobacter pylori (FDA approved in adults); acute exacerbation of chronic obstructive pulmonary disease (FDA approved in adults); has also been used for prophylaxis of endocarditis before invasive dental or respiratory tract procedures; prophylaxis of peritonitis in patients with peritoneal dialysis catheters undergoing invasive dental procedures; treatment of bartonellosis; treatment of Lyme disease; treatment and postexposure prophylaxis of pertussis; and treatment of pulmonary nontuberculous mycobacterial infections.

Extended-release tablets: Treatment of acute maxillary sinusitis, acute exacerbation of chronic obstructive pulmonary disease, and community-acquired pneumonia due to susceptible bacteria (FDA approved in adults).

Medication Safety Issues
Sound-alike/look-alike issues:

Clarithromycin may be confused with Claritin, clindamycin, erythromycin

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Central nervous system: Headache (2%), insomnia

Dermatologic: Skin rash (children 3%)

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

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

Hepatic: Abnormal hepatic function tests

Hypersensitivity: Anaphylactoid reaction

Infection: Candidiasis (including oral)

Renal: Increased blood urea nitrogen (4%)

<1%, postmarketing, and/or case reports: Abdominal distension, abnormal albumin-globulin ratio, acne vulgaris, acute generalized exanthematous pustulosis, ageusia, agranulocytosis, altered sense of smell, anaphylaxis, angioedema, anorexia, anosmia, anxiety, asthma, atrial fibrillation, behavioral changes, bullous dermatitis, cellulitis, chest pain, chills, cholestasis, cholestatic hepatitis, Clostridioides difficile-associated diarrhea, Clostridioides difficile (colitis), confusion, constipation, dark urine (abnormal urine color associated with liver injury), decreased appetite, decreased white blood cell count, dental discoloration (reversible with dental cleaning), depersonalization, depression, disorientation, dizziness, DRESS syndrome, drowsiness, dyskinesia, eosinophilia, epistaxis, eructation, esophagitis, extrasystoles, fatigue, fever, flatulence, gastritis, gastroenteritis, gastroesophageal reflux disease, glossitis, hallucination, hearing loss (reversible), hemorrhage, hepatic failure, hepatic insufficiency, hepatitis, hepatotoxicity (idiosyncratic) (Chalasani 2014), hyperhidrosis, hypersensitivity reaction, hypoglycemia, IgA vasculitis, increased gamma-glutamyl transferase, increased INR, increased lactate dehydrogenase, increased serum alkaline phosphatase, increased serum ALT, increased serum AST, increased serum bilirubin, increased serum creatinine, infection, interstitial nephritis, jaundice, leukopenia, loss of consciousness, maculopapular rash, malaise, manic behavior, muscle spasm, myalgia, myopathy, neck stiffness, nervousness, neutropenia, nightmares, palpitations, pancreatitis, parasomnias, paresthesia, prolonged QT interval on ECG, pruritus, pseudomembranous colitis, psychosis, pulmonary embolism, rectal pain, renal failure, rhabdomyolysis, seizure, Stevens-Johnson syndrome, stomatitis, thrombocytopenia, tinnitus, tongue discoloration, torsades de pointes, toxic epidermal necrolysis, tremor, urticaria, vaginal infection, ventricular arrhythmia, ventricular tachycardia, vertigo, weakness, xerostomia

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, ergot alkaloids (eg, ergotamine, dihydroergotamine), HMG-CoA reductase inhibitors extensively metabolized by CYP3A4 (eg, lovastatin, simvastatin), lomitapide, or pimozide; concomitant use with colchicine in patients with renal or hepatic impairment.

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

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:

• Older adult: Use with caution; elderly patients may be at increased risk of torsades de pointes.

• Patients with HIV: Decreased survival has been observed in patients with HIV with Mycobacterium avium complex (MAC) receiving clarithromycin doses above the maximum recommended dose; maximum recommended dosing should not be exceeded in this population. Development of resistance to clarithromycin has been observed when used as prophylaxis and treatment of MAC infection (Biaxin Canadian product labeling).

Dosage form specific issues:

• Extended release formulation: The presence of extended release tablets in the stool has been reported, particularly in patients with anatomic (eg, ileostomy, colostomy) or functional GI disorders with decreased transit times. Consider alternative dosage forms (eg, suspension) or an alternative antimicrobial for patients with tablet residue in the stool and no signs of clinical improvement.

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

Other warnings/precautions:

• Appropriate use: Helicobacter pylori eradication: Short-term combination therapy (≤7 days) has been associated with a higher incidence of treatment failure. Current guidelines recommend 10 to 14 days of therapy (triple or quadruple) for eradication of H. pylori in pediatric and adult patients (Chey 2007; NASPHGAN [Koletzko 2011]).

Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (strong), OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program

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

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

Ado-Trastuzumab Emtansine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ado-Trastuzumab Emtansine. Specifically, strong CYP3A4 inhibitors may increase concentrations of the cytotoxic DM1 component. Management: Avoid concomitant use of ado-trastuzumab emtansine and strong CYP3A4 inhibitors when possible. Consider alternatives that do not inhibit CYP3A4 or consider administering after CYP3A4 inhibitor discontinuation. Monitor for toxicities if combined. Risk D: Consider therapy modification

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider therapy modification

Alfentanil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfentanil. Management: If use of alfentanil and strong CYP3A4 inhibitors is necessary, consider dosage reduction of alfentanil until stable drug effects are achieved. Frequently monitor patients for respiratory depression and sedation when these agents are combined. Risk D: Consider therapy modification

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

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

Alitretinoin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when used together with strong CYP3A4 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP3A4 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg). Max dose is 441 mg in CYP2D6 PMs or if also taking strong CYP2D6 inhibitors. Risk D: Consider therapy modification

Artemether and Lumefantrine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Artemether and Lumefantrine. Risk C: Monitor therapy

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

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

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

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

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

Atogepant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Atogepant. Management: The recommended dose of atogepant is 10 mg once daily when coadministered with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Atogepant. Management: The recommended dose of atogepant when coadministered with OATP1B1/1B3 inhibitors is 10 mg once daily or 30 mg once daily. Risk D: Consider therapy modification

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

Avacopan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avacopan. Management: Decrease the avacopan dose to 30 mg once daily during coadministration with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

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

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

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

Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification

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

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

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

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

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

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

Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification

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

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

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

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

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

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

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

Bosentan: May increase serum concentrations of the active metabolite(s) of Clarithromycin. Specifically, bosentan may increase concentrations of 14-hydroxyclarithromycin. Bosentan may decrease the serum concentration of Clarithromycin. Clarithromycin may increase the serum concentration of Bosentan. Management: Consider alternative antimicrobial if possible. The clinical activity of clarithromycin may be altered, and increased bosentan toxicity may be expected. Risk D: Consider therapy modification

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

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

Brexpiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose 50% with strong CYP3A4 inhibitors; reduce to 25% of usual if used with both a strong CYP3A4 inhibitor and a CYP2D6 inhibitor in patients not being treated for MDD, or strong CYP3A4 inhibitor used in a CYP2D6 poor metabolizer. Risk D: Consider therapy modification

Brigatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with strong CYP3A4 inhibitors when possible. If combination cannot be avoided, reduce the brigatinib dose by approximately 50%, rounding to the nearest tablet strength (ie, from 180 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider therapy modification

Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Brincidofovir. Management: Consider alternatives to OATP1B/1B3 inhibitors in patients treated with brincidofovir. If coadministration is required, administer OATP1B1/1B3 inhibitors at least 3 hours after brincidofovir and increase monitoring for brincidofovir adverse reactions. Risk D: Consider therapy modification

Bromocriptine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bromocriptine. Management: Consider alternatives to the use of bromocriptine with strong CYP3A4 inhibitors. If combined, monitor closely for increased bromocriptine toxicities and consider bromocriptine dose reductions. Risk D: Consider therapy modification

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

Brotizolam [INT]: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brotizolam [INT]. Risk C: Monitor therapy

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

Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Oral Inhalation). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of inhaled budesonide and strong CYP3A4 inhibitors. Risk D: Consider therapy modification

Budesonide (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic). Management: Avoid the concomitant use of CYP3A4 inhibitors and oral budesonide. If patients receive both budesonide and a strong CYP3A4 inhibitor, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider therapy modification

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

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

BusPIRone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of BusPIRone. Management: Limit the buspirone dose to 2.5 mg daily and monitor patients for increased buspirone effects/toxicities if combined with strong CYP3A4 inhibitors. Dose adjustments of buspirone or a strong CYP3A4 inhibitor should be based on clinical assessment. Risk D: Consider therapy modification

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

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

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

Cabozantinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabozantinib. Management: Avoid use of a strong CYP3A4 inhibitor with cabozantinib if possible. If combined, decrease cabozantinib capsules (Cometriq) by 40 mg from previous dose or decrease cabozantinib tablets (Cabometyx) by 20 mg from previous dose. Risk D: Consider therapy modification

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

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

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

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

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

CarBAMazepine: May increase serum concentrations of the active metabolite(s) of Clarithromycin. Clarithromycin may increase the serum concentration of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Clarithromycin. Management: Consider alternatives to this combination when possible. If combined, monitor for increased carbamazepine effects/toxicities and for reduced clarithromycin efficacy. Risk D: Consider therapy modification

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

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

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

Ceritinib: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Ceritinib. Management: Avoid use of ceritinib and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If combined, decrease ceritinib dose by one-third (to the nearest 150 mg) and monitor patients for ceritinib toxicities including QTc prolongation. Risk D: Consider therapy modification

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

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

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

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

Cilostazol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

Colchicine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a strong CYP3A4 inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See interaction monograph for details. Risk D: Consider therapy modification

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a P-gp inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See interaction monograph for details. Risk D: Consider therapy modification

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

Copanlisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Copanlisib. Management: If concomitant use of copanlisib and strong CYP3A4 inhibitors cannot be avoided, reduce the copanlisib dose to 45 mg. Monitor patients for increased copanlisib effects/toxicities. Risk D: Consider therapy modification

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

Crizotinib: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Crizotinib. Management: Avoid concomitant use of crizotinib and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If combined, crizotinib dose adjustments are required, which vary according to indication. See full interaction monograph for details. Risk D: Consider therapy modification

CycloSPORINE (Systemic): Clarithromycin may increase the serum concentration of CycloSPORINE (Systemic). Management: Monitor for increased serum concentrations/toxic effects of cyclosporine if combined with clarithromycin. Cyclosporine dose reductions and/or prolongation of the dosing interval will likely be required. Risk D: Consider therapy modification

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

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

CYP3A4 Inhibitors (Strong): May decrease serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Clarithromycin. Risk C: Monitor therapy

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

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

Dabrafenib: May enhance the QTc-prolonging effect of Clarithromycin. Dabrafenib may increase serum concentrations of the active metabolite(s) of Clarithromycin. Clarithromycin may increase serum concentrations of the active metabolite(s) of Dabrafenib. Clarithromycin may increase the serum concentration of Dabrafenib. Dabrafenib may increase the serum concentration of Clarithromycin. Management: If coadministration is unavoidable, monitor for decreased clarithromycin efficacy, increased dabrafenib adverse effects, and QTc interval prolongation and ventricular arrhythmias when these agents are combined. Risk D: Consider therapy modification

Daclatasvir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Daclatasvir. Management: Decrease the daclatasvir dose to 30 mg once daily if combined with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification

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

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

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

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

Dasatinib: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Dasatinib. Management: Avoid this combination if possible. If combined, decrease dasatinib dose from 140 mg to 40 mg, 100 mg to 20 mg, or 70 mg to 20 mg. If taking 60 mg or 40 mg daily, stop dasatinib until the CYP3A4 inhibitor is discontinued. Monitor for prolonged QT interval Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Duvelisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Duvelisib. Management: Reduce the dose of duvelisib to 15 mg twice a day when used together with a strong CYP3A4 inhibitor. Monitor closely for evidence of altered response to treatment. Risk D: Consider therapy modification

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

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

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

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

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

Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Risk X: Avoid combination

Elagolix, Estradiol, and Norethindrone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Elagolix, Estradiol, and Norethindrone may decrease the serum concentration of CYP3A4 Inhibitors (Strong). Specifically, concentrations of strong CYP3A4 inhibitors that are also CYP3A4 substrates may be decreased. Risk X: Avoid combination

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

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

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with strong CYP3A4 inhibitors, administer two elexacaftor/tezacaftor/ivacaftor tablets (100 mg/50 mg/75 mg) in the morning, twice a week, approximately 3 to 4 days apart. No evening doses of ivacaftor (150 mg) alone should be administered. Risk D: Consider therapy modification

Eliglustat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with strong CYP3A4 inhibitors. Use of strong CYP3A4 inhibitors is contraindicated in CYP2D6 IMs, PMs, or in CYP2D6 EMs who are also taking strong or moderate CYP2D6 inhibitors. Risk D: Consider therapy modification

Eluxadoline: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with OATP1B1/1B3 inhibitors and monitor patients for increased eluxadoline effects/toxicities. Risk D: Consider therapy modification

Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Encorafenib. Management: Avoid use of encorafenib and strong CYP3A4 inhibitors when possible. If combined, decrease encorafenib dose from 450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Monitor closely for QT interval prolongation. Risk D: Consider therapy modification

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

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

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

Erdafitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erdafitinib. Management: Avoid concomitant use of erdafitinib and strong CYP3A4 inhibitors when possible. If combined, monitor closely for erdafitinib adverse reactions and consider dose modifications accordingly. Risk D: Consider therapy modification

Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination

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

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

Escitalopram: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). Risk C: Monitor therapy

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

Eszopiclone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eszopiclone. Management: Limit the eszopiclone dose to 2 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased eszopiclone effects and toxicities (eg, somnolence, drowsiness, CNS depression). Risk D: Consider therapy modification

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

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

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

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

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

Fedratinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fedratinib. Management: Consider alternatives when possible. If used together, decrease fedratinib dose to 200 mg/day. After the inhibitor is stopped, increase fedratinib to 300 mg/day for the first 2 weeks and then to 400 mg/day as tolerated. Risk D: Consider therapy modification

Felodipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Felodipine. Management: Consider using lower felodipine doses when combined with strong CYP3A4 inhibitors. Monitor patients for increased felodipine effects and toxicities (eg, hypotension, edema) when combined. Risk D: Consider therapy modification

FentaNYL: CYP3A4 Inhibitors (Strong) may increase the serum concentration of FentaNYL. Management: Consider fentanyl dose reductions when combined with a strong CYP3A4 inhibitor. Monitor for respiratory depression and sedation. Upon discontinuation of a CYP3A4 inhibitor, consider a fentanyl dose increase; monitor for signs and symptoms of withdrawal. Risk D: Consider therapy modification

Fesoterodine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Management: Limit fesoterodine doses to 4 mg daily in patients who are also receiving strong CYP3A4 inhibitors. This combination is not recommended in pediatric patients weighing 25 kg up to 35 kg. Risk D: Consider therapy modification

Fexinidazole: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Fexinidazole. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may decrease serum concentrations of the active metabolite(s) of Fexinidazole. Management: Consider alternatives to this combination. If combined, monitor for QT interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QT prolongation may be at even higher risk. Also monitor for reduced fexinidazole efficacy. Risk D: Consider therapy modification

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

Flibanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Flibanserin. Management: Use of flibanserin with strong CYP3A4 inhibitors is contraindicated. If starting flibanserin, start 2 weeks after the last dose of the CYP3A4 inhibitor. If starting a CYP3A4 inhibitor, start 2 days after the last dose of flibanserin. Risk X: Avoid combination

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

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

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

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

Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Management: Consider alternatives to this combination if possible. Coadministration of fluticasone propionate and strong CYP3A4 inhibitors is not recommended. If combined, monitor patients for systemic corticosteroid adverse effects (eg, adrenal suppression). Risk D: Consider therapy modification

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

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

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

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

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

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

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

Gilteritinib: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Gilteritinib. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Gilteritinib. Management: Consider alternatives to the use of gilteritinib with strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. Risk D: Consider therapy modification

Glasdegib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Glasdegib. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor closely for evidence of QT interval prolongation and other adverse reactions to glasdegib. Risk D: Consider therapy modification

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

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

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

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

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

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

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

Ibrexafungerp: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrexafungerp. Management: Decrease the ibrexafungerp dose to 150 mg every 12 hours for 2 doses in patients receiving strong CYP3A4 inhibitors. Risk D: Consider therapy modification

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

Idelalisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Idelalisib. Management: Use alternative therapies that are not strong CYP3A4 inhibitors whenever possible. If unable to use alternative drugs, monitor patients more frequently for idelalisib toxicities. Risk D: Consider therapy modification

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

Iloperidone: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification

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

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

Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy

Infigratinib: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Infigratinib. Risk X: Avoid combination

Irinotecan Products: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. Management: Avoid administration of strong CYP3A4 inhibitors during and within 1 week prior to irinotecan administration, unless no therapeutic alternatives to these agents exist. If combined, monitor closely for increased irinotecan toxicities. Risk D: Consider therapy modification

Isavuconazonium Sulfate: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Strong) may increase isavuconazole serum concentrations. Risk X: Avoid combination

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

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

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

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

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

Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. Management: Avoid use of ixabepilone and strong CYP3A4 inhibitors when possible. If combined, reduce the ixabepilone dose to 20 mg/m2. The previous ixabepilone dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification

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

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

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

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

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

Larotrectinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Larotrectinib. Management: Avoid use of strong CYP3A4 inhibitors with larotrectinib. If this combination cannot be avoided, reduce the larotrectinib dose by 50%. Increase to previous dose after stopping the inhibitor after a period of 3 to 5 times the inhibitor's half-life. Risk D: Consider therapy modification

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

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

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

Leuprolide and Norethindrone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Leuprolide and Norethindrone. Specifically, concentrations of norethindrone may increase. Risk C: Monitor therapy

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

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

Levoketoconazole: QT-prolonging CYP3A4 Substrates may enhance the QTc-prolonging effect of Levoketoconazole. Levoketoconazole may increase the serum concentration of QT-prolonging CYP3A4 Substrates. Risk X: Avoid combination

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

Levomilnacipran: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levomilnacipran. Management: The dose of levomilnacipran should not exceed 80 mg once daily when used with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

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

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

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

Lorlatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with strong CYP3A4 inhibitors. If the combination cannot be avoided, reduce the lorlatinib dose from 100 mg once daily to 75 mg once daily, or from 75 mg once daily to 50 mg once daily. Risk D: Consider therapy modification

Lovastatin: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Lovastatin. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin. Risk X: Avoid combination

Lumateperone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumateperone. Management: Limit the lumateperone dose to 10.5 mg once daily when used with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification

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

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

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

Manidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inhibitors. If combined, monitor closely for increased manidipine effects and toxicities. Manidipine dose reductions may be required. Risk D: Consider therapy modification

Maraviroc: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Management: Reduce maraviroc to 150mg twice/day in adult and pediatrics weighing 40kg or more. See full interaction monograph for dose adjustments in pediatrics weighing 10 to less than 40kg. Do not use if CrCl less than 30mL/min or in those weighing less than 10 kg. Risk D: Consider therapy modification

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

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

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

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

Midazolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Midazolam. Management: Avoid use of nasal midazolam and strong CYP3A4 inhibitors whenever possible, and consider alternatives to use with other routes of midazolam (oral, IV, IM). If combined, consider lower midazolam doses and monitor for increased midazolam toxicities. Risk D: Consider therapy modification

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

MiFEPRIStone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MiFEPRIStone. Management: For treatment of hyperglycemia in Cushing's syndrome, start mifepristone at 300 mg/day, may titrate to a maximum of 900 mg/day. If starting a strong CYP3A4 inhibitor and taking > 300 mg/day mifepristone, decrease the mifepristone dose by 300 mg/day. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

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

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

Nevirapine: May increase serum concentrations of the active metabolite(s) of Clarithromycin. Nevirapine may decrease the serum concentration of Clarithromycin. Management: Consider alternatives to clarithromycin, such as azithromycin, for the treatment of Mycobacterium avium-intracellulare complex in patients taking nevirapine. Risk D: Consider therapy modification

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

NIFEdipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NIFEdipine. Management: Consider alternatives to this combination when possible. If combined, initiate nifedipine at the lowest dose available and monitor patients closely for increased nifedipine effects and toxicities (eg, hypotension, edema). Risk D: Consider therapy modification

Nilotinib: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Nilotinib. Management: Avoid concomitant use of nilotinib and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If combined, nilotinib dose reductions are required. Monitor patients for nilotinib toxicities including QTc prolongation and arrhythmias. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

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

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

OxyCODONE: CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased. Risk C: Monitor therapy

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

PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy

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

Palbociclib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palbociclib. Management: Avoid concurrent use of strong CYP3A4 inhibitors with palbociclib when possible. If the use of a strong CYP3A4 inhibitor cannot be avoided, decrease the palbociclib dose to 75 mg/day. Risk D: Consider therapy modification

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

Panobinostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Panobinostat. Management: Reduce the panobinostat dose to 10 mg when it must be used with a strong CYP3A4 inhibitor. Monitor patient response to therapy closely for evidence of more severe adverse effects related to panobinostat therapy. Risk D: Consider therapy modification

Parecoxib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Parecoxib. Specifically, serum concentrations of the active moiety valdecoxib may be increased. Risk C: Monitor therapy

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

PAZOPanib: Clarithromycin may enhance the QTc-prolonging effect of PAZOPanib. Clarithromycin may increase the serum concentration of PAZOPanib. Risk X: Avoid combination

Pemigatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pemigatinib. Management: If combined use cannot be avoided, reduce the pemigatinib dose from 13.5 mg daily to 9 mg daily, or from 9 mg daily to 4.5 mg daily. Resume prior pemigatinib dose after stopping the strong inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider therapy modification

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

Pexidartinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pexidartinib. Management: Avoid use of pexidartinib with strong CYP3A4 inhibitors if possible. If combined use cannot be avoided, pexidartinib dose should be reduced. Decrease 800 mg or 600 mg daily doses to 200 mg twice daily. Decrease doses of 400 mg per day to 200 mg once daily Risk D: Consider therapy modification

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

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

Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination

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

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

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

PONATinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PONATinib. Management: Avoid concomitant use if possible. If combined, reduce ponatinib dose as follows: If taking 45 mg, reduce to 30 mg; if taking 30 mg, reduce to 15 mg; if taking 15 mg, reduce to 10 mg. If taking 10 mg, avoid concomitant use with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

Posaconazole: May increase the serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. Risk X: Avoid combination

Pralsetinib: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Pralsetinib. Management: Avoid concomitant use if possible. If combined, reduce the pralsetinib dose. If taking 400 mg or 300 mg once daily, reduce to 200 mg once daily. If taking 200 mg once daily, reduce to 100 mg once daily. Risk D: Consider therapy modification

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

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

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

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

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

Protease Inhibitors: May decrease serum concentrations of the active metabolite(s) of Clarithromycin. Protease Inhibitors may increase the serum concentration of Clarithromycin. Management: Do not exceed clarithromycin doses greater than 1,000 mg/day in patients taking protease inhibitors. If CrCL is 30 to 60 mL/min, reduced clarithromycin dose 50%. If CrCL is less than 30 mL/min, reduced clarithromycin dose 75%. Risk D: Consider therapy modification

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

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

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

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

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

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

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

QUEtiapine: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QUEtiapine. Management: Reduce the quetiapine dose to one-sixth of the regular dose when initiating these strong CYP3A4 inhibitors. In patients already receiving these strong CYP3A4 inhibitors, initiate quetiapine at the lowest dose and titrate cautiously as needed. Risk D: Consider therapy modification

Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor therapy

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

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

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

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

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

Regorafenib: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib. Risk X: Avoid combination

Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification

Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification

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

Retapamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Retapamulin. Management: The use of retapamulin with strong CYP3A4 inhibitors is not recommended in patients less than 2 years old. No action is required in other populations. Risk C: Monitor therapy

Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Risk X: Avoid combination

Ribociclib: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Ribociclib. Management: Avoid concomitant use of ribociclib and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If combined, decrease the ribociclib dose to 400 mg daily. Monitor for ribociclib toxicities including QTc prolongation and arrhythmias. Risk D: Consider therapy modification

Rifabutin: May increase serum concentrations of the active metabolite(s) of Clarithromycin. Rifabutin may decrease the serum concentration of Clarithromycin. Clarithromycin may increase the serum concentration of Rifabutin. Management: Consider alternatives to this combination when possible. If combined, consider use of lower rifabutin doses and monitor patients for increased rifabutin toxicities. Additionally, monitor for reduced clarithromycin efficacy when these agents are combined. Risk D: Consider therapy modification

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

Rilpivirine: Macrolide Antibiotics may increase the serum concentration of Rilpivirine. Management: Consider the use of azithromycin or another non-macrolide alternative when appropriate to avoid this potential interaction. Risk D: Consider therapy modification

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

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

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

RisperiDONE: May enhance the QTc-prolonging effect of Clarithromycin. Clarithromycin may increase the serum concentration of RisperiDONE. Management: Monitor for increased risperidone toxicities, including QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

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

Roflumilast-Containing Products: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy

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

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

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

Ruxolitinib (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib (Systemic). Management: This combination should be avoided under some circumstances; dose adjustments may be required in some circumstances and depend on the indication for ruxolitinib. See monograph for details. Risk D: Consider therapy modification

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

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

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

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

Selumetinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Selumetinib. Management: Avoid concomitant use when possible. If combined, selumetinib dose reductions are recommended and vary based on body surface area and selumetinib dose. For details, see the full drug interaction monograph or selumetinib prescribing information. Risk D: Consider therapy modification

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

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

Sildenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sildenafil. Management: Use of sildenafil for pulmonary arterial hypertension (PAH) should be avoided with strong CYP3A4 inhibitors. When used for erectile dysfunction, consider using a lower starting dose of 25 mg and monitor patients for sildenafil toxicities. Risk D: Consider therapy modification

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

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

Simvastatin: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simvastatin. Risk X: Avoid combination

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification

Sirolimus (Conventional): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with strong CYP3A4 inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Concomitant use of sirolimus and voriconazole or posaconazole is contraindicated. Risk D: Consider therapy modification

Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider therapy modification

Sirolimus (Protein Bound): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination

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

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

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

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

SUFentanil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SUFentanil. Management: If a strong CYP3A4 inhibitor is initiated in a patient on sufentanil, consider a sufentanil dose reduction and monitor for increased sufentanil effects and toxicities (eg, respiratory depression). Risk D: Consider therapy modification

Sulfonylureas: Clarithromycin may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

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

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

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

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

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

Talazoparib: Clarithromycin may increase the serum concentration of Talazoparib. Management: If concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg once daily. When clarithromycin is discontinued, increase the talazoparib dose to the dose used before initiation of clarithromycin after 3 to 5 times the half-life of clarithromycin. Risk D: Consider therapy modification

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

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

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

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

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

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

Temsirolimus: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inhibitors. If coadministration is unavoidable, decrease temsirolimus dose to 12.5 mg per week. Resume previous temsirolimus dose 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

Thiotepa: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Thiotepa. Management: Avoid coadministration of thiotepa and strong CYP3A4 inhibitors. If concomitant use cannot be avoided, monitor for thiotepa adverse effects and decreased efficacy. Risk D: Consider therapy modification

Ticagrelor: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. Risk X: Avoid combination

Tipranavir: Clarithromycin may increase the serum concentration of Tipranavir. Tipranavir may increase the serum concentration of Clarithromycin. Management: Limit adult clarithromycin doses to 1,000 mg/day if combined with tipranavir. Consider reducing the clarithromycin dose by 50% for patients with CrCl 30 to 60 mL/min, and for patients with CrCl <30 mL/min consider reducing the clarithromycin dose by 75%. Risk D: Consider therapy modification

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

Tofacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tofacitinib. Management: Tofacitinib dose reductions are recommended when combined with strong CYP3A4 inhibitors. Recommended dose adjustments vary by tofacitinib formulation and therapeutic indication. See full Lexi Interact monograph for details. Risk D: Consider therapy modification

Tolterodine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolterodine. Management: The maximum recommended dose of tolterodine is 2 mg per day (1 mg twice daily for immediate-release tablets or 2 mg daily for extended-release capsules) when used together with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification

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

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

Toremifene: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Toremifene. Management: Avoid concomitant use of toremifene and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If combined, monitor patients for toremifene toxicities including QTc prolongation and TdP. Risk D: Consider therapy modification

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

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

TraZODone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraZODone. Management: Consider the use of a lower trazodone dose and monitor for increased trazodone effects (eg, sedation, QTc prolongation) if combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

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

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

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

Triamcinolone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triamcinolone (Systemic). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of triamcinolone and strong CYP3A4 inhibitors. Risk D: Consider therapy modification

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

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

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification

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

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

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

Upadacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Upadacitinib. Management: For ulcerative colitis use upadacitinib 30 mg/day for 8 weeks for induction, then 15 mg/day for maintenance. For rheumatoid arthritis, psoriatic arthritis, or atopic dermatitis use upadacitinib 15 mg/day. Monitor for upadacitinib toxicities. Risk D: Consider therapy modification

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

Vardenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 2.5 mg dose within a 24-hour period if combined with strong CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and strong CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D: Consider therapy modification

Vemurafenib: May enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Vemurafenib. Management: Avoid concomitant use of vemurafenib and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If combined monitor patients for vemurafenib toxicities including QTc prolongation and TdP, and consider a vemurafenib dose reduction. Risk D: Consider therapy modification

Venetoclax: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Venetoclax. Management: Coadministration is contraindicated during venetoclax initiation and ramp-up in CLL/SLL patients. Reduced venetoclax doses are required during ramp-up for patients with AML, and all maintenance therapy. See full Lexi Interact monograph for details. Risk D: Consider therapy modification

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

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

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

Vilazodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. Management: Limit the maximum vilazodone dose to 20 mg daily in patients receiving strong CYP3A4 inhibitors. The original vilazodone dose can be resumed following discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification

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

VinCRIStine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine. Management: Seek alternatives to this combination when possible. If combined, monitor closely for vincristine toxicities (eg, neurotoxicity, gastrointestinal toxicity, myelosuppression). Risk D: Consider therapy modification

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

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

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

Vinflunine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Vinflunine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinflunine. Risk X: Avoid combination

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

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

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

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

Voriconazole: Clarithromycin may enhance the QTc-prolonging effect of Voriconazole. Voriconazole may increase the serum concentration of Clarithromycin. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

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

Zanubrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg once daily during coadministration with a strong CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider therapy modification

Zidovudine: Clarithromycin may enhance the myelosuppressive effect of Zidovudine. Clarithromycin may decrease the serum concentration of Zidovudine. Management: Monitor response to zidovudine closely when used with clarithromycin, and consider staggering zidovudine and clarithromycin doses when possible in order to minimize the potential for interaction. Risk D: Consider therapy modification

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

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

Food Interactions

Immediate release: Food delays rate, but not extent of absorption; Extended release: Food increases clarithromycin AUC by ~30% relative to fasting conditions. Management: Administer immediate release products without regard to meals. Administer extended release products with food.

Pregnancy Considerations

Clarithromycin crosses the placenta (Witt 2003).

The manufacturer recommends that clarithromycin not be used in pregnant patients unless there are no alternative therapies. Clarithromycin is not recommended as a first-line agent for the treatment or prophylaxis of Mycobacterium avium complex in pregnant patients living with HIV (HHS [OI adult] 2022).

Monitoring Parameters

BUN, creatinine, liver function tests; observe for changes in bowel frequency.

Mechanism of Action

Exerts its antibacterial action by binding to 50S ribosomal subunit resulting in inhibition of protein synthesis. The 14-OH metabolite of clarithromycin is twice as active as the parent compound against certain organisms.

Pharmacokinetics (Adult data unless noted)

Absorption:

Immediate release: Rapid; food delays rate, but not extent of absorption

Extended-release: Fasting is associated with ~30% lower AUC relative to administration with food

Distribution: Widely into most body tissues; manufacturer reports no data in regards to CNS penetration

Protein binding: 42% to 70% (Peters, 1992)

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

Bioavailability: ~50%

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

Time to peak: Immediate release: 2-3 hours; Extended release: 5-8 hours

Excretion: Urine (20% to 40% as unchanged drug; additional 10% to 15% as metabolite); feces (29% to 40% mostly as metabolites) (Ferrero 1990)

Clearance: Approximates normal GFR

Pharmacokinetics: Additional Considerations

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

Hepatic function impairment: The 14-OH clarithromycin concentrations were lower in subjects with hepatic impairment but may be partially offset by an increase in renal clearance of clarithromycin.

Anti-infective considerations:

Parameters associated with efficacy: Concentration (AUC/minimum inhibitory concentration [MIC]) and time (time/MIC) dependent (Bauernfeind 1995; Craig 2001a; Craig 2001b; Periti 1999).

Expected drug exposure in normal renal function:

Cmax (peak):

Children ≤7 years of age: Multiple doses (steady state): 7.5 mg/kg/dose every 12 hours: 4.6 ± 2.08 mg/L (Gan 1992).

Adults, multiple doses (steady state):

IR tablet: 250 mg every 12 hours: 1 to 2 mg/L; 500 mg every 8 to 12 hours: 3 to 4 mg/L.

ER tablet: 500 mg once daily: 1 to 2 mg/L; 1 g once daily: 2 to 3 mg/L.

AUC:

Children ≤7 years of age: Multiple doses (steady state): 7.5 mg/kg/dose every 12 hours: AUC0-6: 15.7 ± 6.72 mg•hour/L (Gan 1992).

Adults, multiple doses (steady state): IR tablet: 250 mg every 12 hours: AUC24 7.85 ± 2 mg•hour/L (Kees 1995).

Postantibiotic effect: Varies based on organism:

Gram-positive/gram-negative respiratory pathogens: 1.7 to 3.8 hours (Ferrara 1996).

Mycobacterium avium complex: 5.5 to 18 hours (Ellis 1995; Horgen 1999).

Pricing: US

Suspension (reconstituted) (Clarithromycin Oral)

125 mg/5 mL (per mL): $1.47

250 mg/5 mL (per mL): $2.14

Tablet, 24-hour (Clarithromycin ER Oral)

500 mg (per each): $8.95

Tablets (Clarithromycin Oral)

250 mg (per each): $4.52 - $6.02

500 mg (per each): $4.52 - $6.02

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

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


For country code abbreviations (show table)
  1. ADA Division of Legal Affairs, “A Legal Perspective on Antibiotic Prophylaxis,” J Am Dent Assoc, 2003, 134(9):1260. [PubMed 14529001]
  2. American Academy of Pediatrics (AAP). In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021-2024 Report of the Committee on Infectious Diseases. 32nd ed. American Academy of Pediatrics; 2021.
  3. American Dental Association Council on Scientific Affairs, “Combating Antibiotic Resistance,” J Am Dent Assoc, 2004, 135(4):484-7. [PubMed 15127872]
  4. Amsden GW, “Erythromycin, Clarithromycin, and Azithromycin: Are the Differences Real?” Clin Ther, 1996, 18(1):56-72. [PubMed 8851453]
  5. Anderson A, Bijlmer H, Fournier PE, et al. Diagnosis and management of Q fever--United States, 2013: recommendations from CDC and the Q Fever Working Group [published correction appears in MMWR Recomm Rep. 2013;62(35):730]. MMWR Recomm Rep. 2013;62(RR-03):1-30. [PubMed 23535757]
  6. Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52. [PubMed 27060684]
  7. Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007.
  8. Aspin MM, Hoberman A, McCarty J, et al, “Comparative Study of the Safety and Efficacy of Clarithromycin and Amoxicillin-Clavulanate in the Treatment of Acute Otitis Media in Children,” J Pediatr, 1994, 125(1):136-41. [PubMed 8021763]
  9. Baltimore RS, Gewitz M, Baddour LM, et al. Infective endocarditis in childhood: 2015 update: a scientific statement from the American Heart Association. Circulation. 2015;132(15):1487-1515. [PubMed 26373317]
  10. Bauernfeind A, Jungwirth R, Eberlein E. Comparative pharmacodynamics of clarithromycin and azithromycin against respiratory pathogens. Infection. 1995;23(5):316-321. doi:10.1007/BF01716300 [PubMed 8557398]
  11. Biaxin (clarithromycin) [prescribing information]. North Chicago, IL: AbbVie; September 2019.
  12. Biaxin (clarithromycin) [product monograph]. Etobieoke, Ontario, Canada: BGP Pharma ULC; October 2021.
  13. Bonow RO, Carabello B, de Leon Jr, AC, et al, “ACC/AHA Guidelines for the Management of Patients with Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Valvular Heart Disease),” J Am Coll Cardiol, 1998, 32(5):1486-1588. [PubMed 9809971]
  14. Bontems P, Kalach N, Oderda G, et al. Sequential therapy versus tailored triple therapies for Helicobacter pylori infection in children. J Pediatr Gastroenterol Nutr. 2011;53(6):646-650. doi:10.1097/MPG.0b013e318229c769 [PubMed 21701406]
  15. Bradley JS, Byington CL, Shah SS, et al. “The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America”, Clin Infect Dis 2011, 53(7):e25-76. [PubMed 21880587]
  16. Butenko T, Jeverica S, Orel R, Homan M. Antibacterial resistance and the success of tailored triple therapy in Helicobacter pylori strains isolated from Slovenian children. Helicobacter. 2017;22(5):e12400. doi:10.1111/hel.12400 [PubMed 28653787]
  17. Callahan SJ, Vranic A, Flors L, Hanley M, Stoler MH, Mehrad B. Sporadic obliterative bronchiolitis: case series and systematic review of the literature. Mayo Clin Proc Innov Qual Outcomes. 2019;3(1):86-93. doi:10.1016/j.mayocpiqo.2018.10.003 [PubMed 30899912]
  18. Chalasani NP, Hayashi PH, Bonkovsky HL, et al. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2014;109(7):950-966. [PubMed 24935270]
  19. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017;112(2):212-239. doi: 10.1038/ajg.2016.563. [PubMed 28071659]
  20. Chey WD, Wong B, “American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection,” Am J Gastroenterol, 2007 102(8):1808-25. [PubMed 17608775]
  21. Chow AW, Benninger MS, Brook I, et al; Infectious Diseases Society of America. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012;54(8):e72-e112. doi: 10.1093/cid/cir1043. [PubMed 22438350]
  22. Chu SY, Wilson DS, Guay DR, et al, “Clarithromycin Pharmacokinetics in Healthy Young and Elderly Volunteers,” J Clin Pharmacol, 1992, 32(11):1045-9. [PubMed 1474166]
  23. Clarithromycin tablets [prescribing information]. Bedminster, NJ: Alembic Pharmaceuticals Inc; February 2022.
  24. Clarithromycin extended-release tablets [prescribing information]. Greenville, NC: Mayne Pharma; September 2019.
  25. Clarithromycin extended-release tablets [prescribing information]. Parsippany, NJ: Actavis Pharma; September 2020.
  26. Clarithromycin suspension [prescribing information]. Princeton, NJ: Sandoz; September 2019.
  27. Cornia P, Lipsky BA. Pertussis infection in adolescents and adults: treatment and prevention. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 1, 2021.
  28. Craig WA. Does the dose matter? Clin Infect Dis. 2001b;33(suppl 3):S233-S237. doi:10.1086/321854 [PubMed 11524724]
  29. Craig WA. The hidden impact of antibacterial resistance in respiratory tract infection. Re-evaluating current antibiotic therapy. Respir Med. 2001a;95(suppl A):S12-S19; discussion S26-S27. doi:10.1016/s0954-6111(01)90023-x [PubMed 11419669]
  30. Crowe SE. Treatment regimens for Helicobacter pylori. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 13, 2020.
  31. Daley CL, Iaccarino JM, Lange C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Clin Infect Dis. 2020;71(4):905-913. doi:10.1093/cid/ciaa1125 [PubMed 32797222]
  32. Dajani AS, Taubert KA, Wilson W, et al, “Prevention of Bacterial Endocarditis Recommendations by the American Heart Association,” JAMA 1997, 277(22):1794-801. [PubMed 9178793]
  33. Davey PG. The pharmacokinetics of clarithromycin and its 14-OH metabolite. J Hosp Infect. 1991;19(suppl A):S29-S37. doi:10.1016/0195-6701(91)90215-t [PubMed 1684980]
  34. Ellis LC, Benson CA, Koenig GI, Trenholme GM. Postantibiotic effect of clarithromycin alone and combined with ethambutol against Mycobacterium avium complex. Antimicrob Agents Chemother. 1995;39(12):2803-2806. doi:10.1128/AAC.39.12.2803 [PubMed 8593025]
  35. Falagas ME, Avgeri SG, Matthaiou DK, Dimopoulos G, Siempos II. Short- versus long-duration antimicrobial treatment for exacerbations of chronic bronchitis: a meta-analysis. J Antimicrob Chemother. 2008;62(3):442-450. doi: 10.1093/jac/dkn201. [PubMed 18467303]
  36. Fallone CA, Chiba N, van Zanten SV, et al. The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology. 2016;151(1):51-69.e14. [PubMed 27102658]
  37. Ferrara A, Dos Santos C, Cimbro M, Grassi GG. Comparative antimicrobial activity and post-antibiotic effect of azithromycin, clarithromycin and roxithromycin against some respiratory pathogens. Int J Antimicrob Agents. 1996;7(3):181-186. doi:10.1016/s0924-8579(96)00320-2 [PubMed 18611754]
  38. Ferrero JL, Bopp BA, Marsh KC, et al. Metabolism and Disposition of Clarithromycin in Man. Drug Metab Dispos. 1990;18(4):441-446. [PubMed 1976065]
  39. File TM Jr. Treatment of community-acquired pneumonia in adults who require hospitalization. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 28, 2021.
  40. Floto RA, Olivier KN, Saiman L, et al; US Cystic Fibrosis Foundation and European Cystic Fibrosis Society. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis. Thorax. 2016;71(suppl 1):i1-i22. doi: 10.1136/thoraxjnl-2015-207360. [PubMed 26666259]
  41. Fraschini F, Scaglione F, Demartini G. Clarithromycin clinical pharmacokinetics. Clin Pharmacokinet. 1993;25(3):189-204. doi:10.2165/00003088-199325030-00003 [PubMed 8222460]
  42. Gan VN, Chu SY, Kusmiesz HT, Craft JC. Pharmacokinetics of a clarithromycin suspension in infants and children. Antimicrob Agents Chemother. 1992;36(11):2478-2480. doi:10.1128/AAC.36.11.2478 [PubMed 1489191]
  43. Gerber MA, Baltimore RS, Eaton CB, et al, "Prevention of Rheumatic Fever and Diagnosis and Treatment of Acute Streptococcal pharyngitis: A Scientific Statement From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: Endorsed by the American Academy of Pediatrics," Circulation, 2009, 119(11):1541-51. [PubMed 19246689]
  44. Gikas A, Kofteridis DP, Manios A, Pediaditis J, Tselentis Y. Newer macrolides as empiric treatment for acute Q fever infection. Antimicrob Agents Chemother. 2001;45(12):3644-3646. doi: 10.1128/AAC.45.12.3644-3646.2001. [PubMed 11709360]
  45. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2021 report. https://goldcopd.org/wp-content/uploads/2020/11/GOLD-REPORT-2021-v1.1-25Nov20_WMV.pdf. Accessed July 16, 2021.
  46. Goldman MP and Longworth DL, “The Role of Azithromycin and Clarithromycin in Clinical Practice,” Cleve Clin J Med, 1993, 60(5):359-64. [PubMed 8403355]
  47. Goldstein LH, Berlin M, Tsur L, et al, "The Safety of Macrolides During Lactation," Breastfeed Med, 2009, 4(4):197-200. [PubMed 19366316]
  48. Griffith DE. Rapidly growing mycobacterial infections: Mycobacteria abscessus, chelonae, and fortuitum. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 25, 2020.
  49. Guay DR, “Pharmacokinetics of New Macrolides,” Infect Med, 1992, 9(Suppl A):9-13.
  50. Guay DR and Craft JC, “Overview of the Pharmacology of Clarithromycin Suspension in Children and a Comparison With That in Adults,” Pediatr Infect Dis J, 1993, 12(12 Suppl 3):106-11. [PubMed 8295810]
  51. Hardy DJ, Guay DR, Jones RN. Clarithromycin, a unique macrolide. A pharmacokinetic, microbiological, and clinical overview. Diagn Microbiol Infect Dis. 1992;15(1):39-53. doi:10.1016/0732-8893(92)90055-x [PubMed 1530914]
  52. Haworth CS, Banks J, Capstick T, et al. British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD). Thorax. 2017;72(suppl 2):ii1-ii64. doi: 10.1136/thoraxjnl-2017-210927. [PubMed 29054853]
  53. Horgen L, Legrand E, Rastogi N. Postantibiotic effects of rifampin, amikacin, clarithromycin and ethambutol used alone or in various two-, three- and four-drug combinations against Mycobacterium avium. FEMS Immunol Med Microbiol. 1999;23(1):37-44. doi:10.1111/j.1574-695X.1999.tb01714.x [PubMed 10030545]
  54. Huang J, Zhou L, Geng L, et al. Randomised controlled trial: sequential vs. standard triple therapy for Helicobacter pylori infection in Chinese children-a multicentre, open-labelled study. Aliment Pharmacol Ther. 2013;38(10):1230-1235. doi:10.1111/apt.12516 [PubMed 24117692]
  55. Hunter MH, King DE. COPD: management of acute exacerbations and chronic stable disease. Am Fam Physician. 2001;64(4):603-612. [PubMed 11529259]
  56. Husson RN, Ross LA, Sandelli S, et al, “Orally Administered Clarithromycin for the Treatment of Systemic Mycobacterium avium Complex Infection in Children With Acquired Immunodeficiency Syndrome,” J Pediatr, 1994, 124(5 Pt 1):807-14. [PubMed 8176574]
  57. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs. Pediatrics. 1997;99(2):268-278. [PubMed 9024461]
  58. Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126. [PubMed 10891521]
  59. Jespersen CM, Als-Nielsen B, Damgaard M, et al, “Randomised Placebo Controlled Multicentre Trial to Assess Short Term Clarithromycin for Patients with Stable Coronary Heart Disease: CLARICOR Trial,” BMJ, 2006, 332(7532):22-7. [PubMed 16339220]
  60. Jones NL, Koletzko S, Goodman K, et al. Joint ESPGHAN/NASPGHAN Guidelines for the management of Helicobacter pylori in children and adolescents (update 2016). J Pediatr Gastroenterol Nutr. 2017;64(6):991-1003. doi:10.1097/MPG.0000000000001594 [PubMed 28541262]
  61. Kadota J, Mukae H, Ishii H, et al. Long-term efficacy and safety of clarithromycin treatment in patients with diffuse panbronchiolitis. Respir Med. 2003;97(7):844-850. doi: 10.1016/s0954-6111(03)00042-8. [PubMed 12854636]
  62. Kees F, Wellenhofer M, Grobecker H. Serum and cellular pharmacokinetics of clarithromycin 500 mg q.d. and 250 mg b.i.d. in volunteers. Infection. 1995;23(3):168-172. doi:10.1007/BF01793859 [PubMed 7499006]
  63. King TE. Overview of bronchiolar disorders in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 10, 2020.
  64. Koletzko S, Jones NL, Goodman KJ, et al. Evidence-Based Guidelines From ESPGHAN and NASPGHAN for Helicobacter pylori Infection in Children. J Pediatr Gastroenterol Nutr. 2011;53(2):230-243. [PubMed 21558964]
  65. Kutluk G, Tutar E, Bayrak A, et al. Sequential therapy versus standard triple therapy for Helicobacter pylori eradication in children: any advantage in clarithromycin-resistant strains?. Eur J Gastroenterol Hepatol. 2014;26(11):1202-1208. doi:10.1097/MEG.0000000000000190 [PubMed 25171023]
  66. Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis, and treatment of lyme disease. Arthritis Care Res (Hoboken). 2021;73(1):1-9. doi:10.1002/acr.24495 [PubMed 33251700]
  67. Lieberthal AS, Carroll AE, Chonmaitree T, et al. The Diagnosis and Management of Acute Otitis Media. Pediatrics. 2013;131(3):e964-999. [PubMed 23439909]
  68. Lund M, Pasternak B, Davidsen RB, et al. Use of macrolides in mother and child and risk of infantile hypertrophic pyloric stenosis: nationwide cohort study. BMJ. 2014;348:1908. [PubMed 21911976]
  69. McConnell SA and Amsden GW, “Review and Comparison of Advanced-Generation Macrolides Clarithromycin and Dirithromycin,” Pharmacotherapy, 1999, 19(4):404-15. [PubMed 10212011]
  70. McNicholl AG, Bordin DS, Lucendo A, et al. Combination of bismuth and standard triple therapy eradicates Helicobacter pylori infection in more than 90% of patients. Clin Gastroenterol Hepatol. 2020;18(1):89-98. doi: 10.1016/j.cgh.2019.03.048. [PubMed 30978536]
  71. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Resp Crit Care Med. 2019;200(7):e45-e67. doi:10.1164/rccm.201908-1581ST. [PubMed 31573350]
  72. Moayyedi PM, Lacy BE, Andrews CN, Enns RA, Howden CW, Vakil N. ACG and CAG clinical guideline: management of dyspepsia. Am J Gastroenterol. 2017;112(7):988-1013. doi: 10.1038/ajg.2017.154. [PubMed 28631728]
  73. Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-289. doi:10.1016/j.jacc.2017.03.011 [PubMed 28315732]
  74. Nizič T, Velikanje E, Ružić-Sabljić E, Arnež M. Solitary erythema migrans in children: comparison of treatment with clarithromycin and amoxicillin. Wien Klin Wochenschr. 2012;124(13-14):427-433. doi:10.1007/s00508-012-0194-1 [PubMed 22760494]
  75. Periti P, Mazzei T. Clarithromycin: pharmacokinetic and pharmacodynamic interrelationships and dosage regimen. J Chemother. 1999;11(1):11-27. doi:10.1179/joc.1999.11.1.11 [PubMed 10078776]
  76. Peters DH and Clissold SP, “Clarithromycin: A Review of its Antimicrobial Activity, Pharmacokinetic Properties, and Therapeutic Potential,” Drugs, 1992, 44(1):117-64. [PubMed 1379907]
  77. “Pimozide (Orap) Contraindicated With Clarithromycin (Biaxin) and Other Macrolide Antibiotics,” FDA Medical Bulletin, October 1996, 3.
  78. Raoult D. Treatment and prevention of Q fever. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 17, 2020.
  79. Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, et al. Clinical practice guideline (update): adult sinusitis. Otolaryngol Head Neck Surg. 2015;152(2)(suppl):S1-S39. doi: 10.1177/0194599815572097. [PubMed 25832968]
  80. Saag MS, Benson CA, Gandhi RT, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2018 recommendations of the International Antiviral Society-USA panel. JAMA. 2018;320(4):379-396. doi: 10.1001/jama.2018.8431. [PubMed 30043070]
  81. Sedlak T, Shufelt C, Iribarren C, et al, "Oral Contraceptive Use and the ECG: Evidence of an Adverse QT Effect on Corrected QT Interval," Ann Noninvasive Electrocardiol, 2013, 18(4):389-98. [PubMed 23879279]
  82. Sedlmayr T, Peters F, Raasch W, Kees F. Clarithromycin, a new macrolide antibiotic. Effectiveness in puerperal infections and pharmacokinetics in breast milk. Geburtshilfe Frauenheilkd. 1993;53(7):488-491. [PubMed 8370491]
  83. Sethi S, Murphy TF. Management of infection in exacerbations of chronic obstructive pulmonary disease. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 16, 2022.
  84. Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259. [PubMed 19188870]
  85. Shulman ST, Bisno AL, Clegg HW, et al; Infectious Diseases Society of America. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis. 2012;55(10):e86-e102. [PubMed 22965026]
  86. Spach DH. Diagnosis, treatment, and prevention of Bartonella infections in persons with HIV. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 2, 2022a.
  87. Spach DH, Kaplan SL. Treatment of cat scratch disease. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 20, 2022b.
  88. Stafstrom CE, Nohria V, Loganbill H, et al, “Erythromycin-induced Carbamazepine Toxicity: A Continuing Problem,” Arch Pediatr Adolesc Med, 1995, 149(1):99-101. [PubMed 7827672]
  89. Szajewska H, Albrecht P, Topczewska-Cabanek A. Randomized, double-blind, placebo-controlled trial: effect of lactobacillus GG supplementation on Helicobacter pylori eradication rates and side effects during treatment in children. J Pediatr Gastroenterol Nutr. 2009;48(4):431-436. doi:10.1097/mpg.0b013e318182e716 [PubMed 19330931]
  90. Talley NJ and Vakil N, “Practice Parameters Committee of the American College of Gastroenterology. Guidelines for the Management of Dyspepsia,” Am J Gastroenterol, 2005, 100(10):2324-37. [PubMed 16181387]
  91. Tiwari T, Murphy TV, Moran J; National Immunization Program, CDC. Recommended antimicrobial agents for the treatment and postexposure prophylaxis of pertussis: 2005 CDC guidelines. MMWR Recomm Rep. 2005;54(RR-14):1-16. [PubMed 16340941]
  92. US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed May 6, 2020.
  93. US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in Adults and Adolescents With HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic-infection/whats-new-guidelines. Updated August 18, 2021. Accessed October 5, 2021.
  94. US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in Adults and Adolescents With HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Adult_OI.pdf. Updated February 17, 2022. Accessed January 31, 2022.
  95. US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children. https://clinicalinfo.hiv.gov/en/guidelines/pediatric-opportunistic-infection/whats-new. Updated March 19, 2021. Accessed October 5, 2021.
  96. Wallace RJ Jr, Brown BA, and Griffith DE, “Drug Intolerance to High-Dose Clarithromycin Among Elderly Patients,” Diagn Microbiol Infect Dis, 1993, 16(3):215-21. [PubMed 8477575]
  97. Warady BA, Bakkaloglu S, Newland J, et al, "Consensus Guidelines for the Prevention and Treatment of Catheter-Related Infections and Peritonitis in Pediatric Patients Receiving Peritoneal Dialysis: 2012 Update," Perit Dial Int, 2012, 32(Suppl 2):S32-86. [PubMed 22851742]
  98. Wilson WR, Gewitz M, Lockhart PB, et al; American Heart Association Young Hearts Rheumatic Fever, Endocarditis and Kawasaki Disease Committee of the Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Council on Cardiovascular and Stroke Nursing; and the Council on Quality of Care and Outcomes Research. Prevention of viridans group streptococcal infective endocarditis: a scientific statement from the American Heart Association. Circulation. 2021;143(20):e963-e978. doi:10.1161/CIR.0000000000000969 [PubMed 33853363]
  99. Wilson W, Taubert KA, Gewitz M, et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; American Heart Association Council on Cardiovascular Disease in the Young; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Cardiovascular Surgery and Anesthesia; Quality of Care and Outcomes Research Interdisciplinary Working Group. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group [published correction appears in Circulation. 2007;116(15):e376-e377]. Circulation. 2007;116(15)1736-1754. [PubMed 17446442]
  100. Witt A, Sommer EM, Cichna M, et al, "Placental Passage of Clarithromycin Surpasses Other Macrolide Antibiotics," Am J Obstet Gynecol, 2003, 188(3):816-9. [PubMed 12634663]
  101. World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the Eleventh WHO Model List of Essential Drugs. 2002. Available at http://www.who.int/maternal_child_adolescent/documents/55732/en/ [PubMed 23215911]
  102. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America [published correction appears in Clin Infect Dis, 2007;45(7):941]. Clin Infect Dis. 2006;43(9):1089-1134. [PubMed 17029130]
  103. Wynn RL, Bergman SA, Meiller TF, et al, “Antibiotics in Treating Oral-Facial Infections of Odontogenic Origin: An Update,” Gen Dent, 2001, 49(3):238-40, 242, 244 passim. [PubMed 12004720]
  104. Zar T, Graeber C, Perazella MA. Recognition, treatment, and prevention of propylene glycol toxicity. Semin Dial. 2007;20(3):217-219. [PubMed 17555487]
Topic 13165 Version 511.0