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Erythromycin (Systemic)

Medically reviewed by Drugs.com. Last updated on Jul 19, 2020.

Pronunciation

(er ith roe MYE sin)

Index Terms

  • Eryc
  • Erythromycin Base
  • Erythromycin Ethylsuccinate
  • Erythromycin Lactobionate
  • Erythromycin Stearate

Dosage Forms

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

Capsule Delayed Release Particles, Oral, as base:

Generic: 250 mg

Solution Reconstituted, Intravenous, as lactobionate [preservative free]:

Erythrocin Lactobionate: 500 mg (1 ea)

Suspension Reconstituted, Oral, as ethylsuccinate:

E.E.S. Granules: 200 mg/5 mL (100 mL, 200 mL) [cherry flavor]

EryPed 200: 200 mg/5 mL (100 mL) [fruit flavor]

EryPed 400: 400 mg/5 mL (100 mL) [banana flavor]

Generic: 200 mg/5 mL (100 mL, 200 mL); 400 mg/5 mL (100 mL)

Suspension Reconstituted, Oral, as ethylsuccinate [preservative free]:

Generic: 200 mg/5 mL (100 mL)

Tablet, Oral, as base:

Generic: 250 mg, 500 mg

Tablet, Oral, as ethylsuccinate:

E.E.S. 400: 400 mg [DSC] [contains fd&c red #40, fd&c yellow #10 (quinoline yellow)]

Generic: 400 mg

Tablet, Oral, as stearate:

Erythrocin Stearate: 250 mg [contains corn starch]

Tablet Delayed Release, Oral, as base:

Ery-Tab: 250 mg, 333 mg, 500 mg

PCE: 333 mg [DSC]

PCE: 500 mg [DSC] [dye free, no artificial color(s)]

Generic: 250 mg, 333 mg, 500 mg

Brand Names: U.S.

  • E.E.S. 400 [DSC]
  • E.E.S. Granules
  • Ery-Tab
  • EryPed 200
  • EryPed 400
  • Erythrocin Lactobionate
  • Erythrocin Stearate
  • PCE [DSC]

Pharmacologic Category

  • Antibiotic, Macrolide

Pharmacology

Inhibits RNA-dependent protein synthesis at the chain elongation step; binds to the 50S ribosomal subunit resulting in blockage of transpeptidation

Absorption

Oral: Variable but better with salt forms than with base form; 18% to 45%; ethylsuccinate may be better absorbed with food (Thompson 1980).

Distribution

Vd: 0.64 L/kg

Relative diffusion from blood into CSF: Minimal even with inflammation

CSF:blood level ratio: Normal meninges: 2% to 13%; Inflamed meninges: 7% to 25%

Metabolism

Demethylation primarily via hepatic CYP3A4

Excretion

Primarily feces; urine (2% to 15% as unchanged drug)

Time to Peak

Serum: Base: 4 hours; Ethylsuccinate: 0.5 to 2.5 hours; Stearate: 3 hours (Steigbigel 2000); delayed with food due to differences in absorption

Half-Life Elimination

Neonates (≤15 days of age): 2.1 hours; Adults: Peak: 1.5-2 hours; End-stage renal disease: 5-6 hours

Protein Binding

Base: 73% to 81%

Use: Labeled Indications

Bacterial infections: Treatment of susceptible bacterial infections, including S. pyogenes, some S. pneumoniae, some S. aureus, M. pneumoniae, Legionella pneumophila, diphtheria, pertussis, Chlamydia, erythrasma, N. gonorrhoeae, E. histolytica, syphilis and nongonococcal urethritis, and Campylobacter gastroenteritis; used in conjunction with neomycin for decontaminating the bowel

Surgical (preoperative) prophylaxis (colorectal): Colorectal decontamination, in conjunction with other agents, prior to surgical intervention

Off Label Uses

Acne vulgaris

Based on the American Academy of Dermatology guidelines of care for the management of acne vulgaris, oral erythromycin, in combination with topical therapy, may be considered as a treatment option for moderate and severe acne and forms of inflammatory acne that are resistant to topical treatments. However, its use should be restricted due to an increased risk of bacterial resistance and limited to patients who cannot receive a tetracycline (ie, pregnant women). Concomitant topical therapy with benzoyl peroxide or a retinoid should be administered with systemic antibiotic therapy (eg, oral erythromycin) and continued for maintenance after the oral antibiotic course is completed [AAD [Zaenglein 2016]].

Bartonella spp. infections (treatment)

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), erythromycin may be considered for the treatment of cutaneous bacillary angiomatosis. Guidelines state that therapy has not been systematically examined and erythromycin appears effective based on case reports and small series [IDSA [Stevens 2014]].

Data from a study with a limited number of patients suggest that erythromycin may be beneficial for the treatment of Bartonella spp infections [Koehler 1992], [Tappero 1993]. Expert opinion recommendations based upon clinical experience also suggests the utility of erythromycin in the treatment of this condition [Rolain 2004].

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV, erythromycin is a recommended and effective agent for treatment of bacillary angiomatosis, peliosis hepatis, bacteremia, osteomyelitis, and other severe infections (excluding CNS infections or endocarditis) due to Bartonella in adolescent and adult patients with HIV [HHS [OI adult 2020]].

Chancroid

Based on Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, erythromycin (base) is effective and recommended for the treatment of chancroid due to H. ducreyi. However, intermediate resistance to erythromycin has been reported in several isolates. Potential resistance issues should be considered when initiating therapy for the treatment of chancroid [CDC [Workowski 2015]].

Chronic obstructive pulmonary disease, prevention of exacerbations

Data from 2 randomized, double-blind, placebo-controlled trials and a prospective, randomized, controlled, but not blinded, trial support the use of erythromycin in prevention of exacerbations of chronic obstructive pulmonary disease (COPD) [He 2010], [Seemungal 2008], [Suzuki 2001]. In addition, data from a meta-analysis support the prophylactic use of erythromycin in prevention of COPD exacerbations [Donath 2013].

Based on the European Respiratory Society and American Thoracic Society Guideline for the Prevention of COPD exacerbations and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease guidelines, erythromycin is effective and recommended to prevent exacerbations in patients with moderate to severe COPD despite optimal maintenance inhaler therapy [GOLD 2019], [Wedzicha 2017].

Endoscopy/esophagogastroduodenoscopy, adjunctive prokinetic agent

Data from 4 small randomized, controlled studies support the use of IV erythromycin as a prokinetic agent to improve quality of examination by reducing the amount of blood in the stomach prior to endoscopy in patients with acute upper GI bleeding [Altraif 2011], [Carbonell 2006], [Coffin 2002], [Frossard 2002]. Two meta-analyses also support the use of IV erythromycin as a prokinetic agent prior to esophagogastroduodenoscopy (EGD) to reduce the need for second endoscopy in patients with acute upper GI bleeding [Bai 2011], [Barkun 2010].

Gastroparesis (management)

Based on the American College of Gastroenterology guidelines for the management of gastroparesis, erythromycin is effective and recommended for the management of gastroparesis [ACG [Camilleri 2013]].

Granuloma inguinale (donovanosis)

Based on CDC sexually transmitted diseases treatment guidelines, erythromycin (base) is effective and recommended for the treatment of granuloma inguinale when azithromycin is not appropriate [CDC [Workowski 2015]].

Contraindications

Hypersensitivity to erythromycin, any macrolide antibiotics, or any component of the formulation

Concomitant use with pimozide, cisapride, ergotamine or dihydroergotamine, terfenadine, astemizole, lovastatin, or simvastatin

Dosing: Adult

Note: PCE tablets have been discontinued in the US for more than 1 year.

Note: Due to differences in absorption, 400 mg erythromycin ethylsuccinate produces the same serum levels as 250 mg erythromycin base or stearate.

Usual dosage range:

Oral:

Base: 250 to 500 mg every 6 to 12 hours; maximum: 4 g daily.

Ethylsuccinate: 400 to 800 mg every 6 to 12 hours; maximum: 4 g daily.

IV: Lactobionate: 15 to 20 mg/kg/day divided every 6 hours or 500 mg to 1 g every 6 hours; maximum: 4 g daily.

Indication-specific dosing:

Acne vulgaris (alternative therapy) (off-label use): Oral: Initial: 250 to 500 mg (base) twice daily, followed by 250 to 500 mg (base) once daily (Tan 2003; Tan 2005). The shortest possible duration should be used to minimize development of bacterial resistance; re-evaluate at 3 to 4 months (AAD [Zaenglein 2016]).

Bartonella spp infections (off-label use):

Patients with HIV:

Note: Duration of therapy is at least 3 months; continuation of therapy depends on relapse occurrence and clinical condition.

Bacillary angiomatosis, peliosis hepatis, bacteremia, and osteomyelitis: Oral, IV: 500 mg every 6 hours (HHS [OI adult 2020]).

Other severe infections (excluding CNS infections or endocarditis): Oral, IV: 500 mg every 6 hours with rifampin (HHS [OI adult 2020]).

Patients without HIV:

Bacillary angiomatosis (BA), peliosis hepatitis (PH): Oral: 500 mg (base) 4 times daily for 3 months (BA) or 4 months (PH) (Koehler 1992; Rolain 2004; Stevens 2014; Tappero 1993). Note: IDSA skin and soft tissue infection guidelines recommend a duration of initial therapy of 2 weeks to 2 months for cutaneous BA, although treatment durations are not standardized (IDSA [Stevens 2014]).

Chancroid (off-label use): Oral: 500 mg (base) 3 times daily for 7 days; Note: Isolates with intermediate resistance have been documented (CDC [Workowski 2015]).

Chlamydia trachomatis infection, uncomplicated: Oral:

Urogenital infections (off-label): 500 mg (base) four times daily or 800 mg (ethylsuccinate) four times daily for 7 days (CDC [Workowski 2015]).

Lymphogranuloma venereum (off-label; alternative therapy to doxycycline): Oral: 500 mg (base) 4 times daily for 21 days (CDC [Workowski 2015]).

Chronic obstructive pulmonary disease (COPD), prevention of exacerbations (off-label use): Oral: 200 to 400 mg/day (formulation not specified) (Suzuki 2001) or 250 mg (stearate) twice daily (Seemungal 2008).

Endoscopy/esophagogastroduodenoscopy, adjunctive prokinetic agent (off-label use): IV: 3 mg/kg as a single dose over 30 minutes administered 30 to 90 minutes prior to endoscopy (Coffin 2002; Saltzman 2019) or 250 mg as a single dose over 5 to 30 minutes administered 20 to 30 minutes prior to endoscopy (Carbonell 2006; Frossard 2002).

Gastroparesis (off-label use):

IV: 3 mg/kg administered over 45 minutes every 8 hours (Camilleri 2013)

Oral: Patients refractory/intolerant to other prokinetic agents (eg, metoclopramide, domperidone): 250 to 500 mg (base) 3 times daily before meals. Limit duration of therapy, tachyphylaxis may occur after 4 weeks (Camilleri 2013).

Granuloma inguinale (donovanosis) (off-label use): Oral: 500 mg (base) 4 times daily for at least 21 days and resolution of lesions (CDC [Workowski 2015]). Note: If symptoms do not improve within the first few days of therapy, the addition of gentamicin may be considered (CDC [Workowski 2015]).

Impetigo (IDSA [Stevens 2014]): Oral:

Base: 250 mg 4 times daily for 7 days, depending on response.

Ethylsuccinate: 400 mg 4 times daily for 7 days, depending on response.

Legionnaire disease: Oral: 1.6 to 4 g (ethylsuccinate) daily or 1 to 4 g (base) daily in divided doses for 21 days. Note: No longer preferred therapy and only used in nonhospitalized patients.

Nongonococcal urethritis: Oral:

500 mg (base) 4 times daily or 800 mg (ethylsuccinate) 4 times daily for 7 days (CDC [Workowski 2015]).

Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice.

Base: 500 mg (base) 4 times daily or two 333 mg (base) tablets every 8 hours.

Ethylsuccinate: 800 mg (ethylsuccinate) 3 times daily. Note: May use 250 mg (base) or 400 mg (ethylsuccinate) 4 times daily.

Pertussis: Oral: 500 mg (base) every 6 hours for 14 days.

Surgical (preoperative) prophylaxis (colorectal) (off-label dose): Oral: 1 g erythromycin base per dose at 1 PM, 2 PM, and 11 PM on the day before 8 AM surgery combined with mechanical cleansing of the large intestine, oral neomycin. Perioperative IV antibiotics are also given on the day of surgery (Bratzler 2013).

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

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

General dosing, susceptible infection: Infants, Children, and Adolescents:

Manufacturer's labeling:

Oral: Base, ethylsuccinate, stearate: 30 to 50 mg/kg/day divided every 6 to 8 hours usually; for severe infection may double dose; maximum daily dose: Mild to moderate infection: 2,000 mg/day; severe infection: 4,000 mg/day

IV: Lactobionate: 15 to 20 mg/kg/day divided every 6 hours; maximum daily dose: 4,000 mg/day

Alternate dosing (Red Book 2012):

Mild to moderate infection: Oral: 50 mg/kg/day divided every 6 to 8 hours; maximum daily dose: 2,000 mg/day

Severe infection: IV: Lactobionate: 5 mg/kg/dose every 6 hours, maximum daily dose: 4,000 mg/day

Acne, moderate to severe; treatment: Children and Adolescents: Oral: 250 to 500 mg 1 to 2 times daily in conjunction with topical therapy (eg, benzoyl peroxide); maximum daily dose: 50 mg/kg/day; duration of 4 to 8 weeks of therapy usually necessary to evaluate initial clinical response with a longer duration for a maximum effect (3 to 6 months); resistance problematic with therapy, use typically reserved for patients <8 years who cannot receive tetracycline derivatives (Eichenfield 2013)

Anthrax, cutaneous, community-acquired (Stevens 2005): Infants, Children, and Adolescents:

Oral: 10 mg/kg/dose every 6 hours; treatment duration of 5 to 9 days usually adequate in most cases

IV: 20 to 40 mg/kg/day divided every 6 hours; maximum daily dose: 4,000 mg; treatment duration of 5 to 9 days usually adequate in most cases

Bartonella sp infections [bacillary angiomatosis (BA), peliosis hepatis (PH)]:

Non-HIV-exposed/-positive; treatment: Infants, Children, and Adolescents: Oral: Ethylsuccinate: 10 mg/kg/ dose 4 times daily; maximum daily dose: 2,000 mg/day; treatment duration: BA: 3 months; PH: 4 months (Rolain 2004)

HIV-exposed/-positive:

Prophylaxis: Infants and Children (CDC 2009): Oral: 30 to 50 mg/kg/day divided into 2 to 4 doses daily; maximum daily dose: 2,000 mg/day

Treatment: Duration of therapy: ≥3 months (of sufficient duration to prevent relapse)

Infants and Children (CDC 2009):

Oral: 30 to 50 mg/kg/day divided into 2 to 4 doses daily; maximum daily dose: 2,000 mg/day

IV: 15 to 50 mg/kg/day divided into 4 doses daily; maximum daily dose: 2,000 mg/day

Adolescents: IV, Oral: 500 mg every 6 hours with or without rifampin (DHHS [adult] 2013)

Catheter (peritoneal dialysis); exit-site or tunnel infection: Infants, Children, and Adolescents: Oral (base): 30 to 50 mg/kg/day divided 3 to 4 times daily; maximum dose: 500 mg/dose (Warady [ISPD 2012])

Chlamydia trachomatis infection (CDC 2010; Red Book 2012):

Conjunctivitis or pneumonia: Infants, Children, and Adolescents: Oral (base or ethylsuccinate): 50 mg/kg/day divided every 6 hours for 14 days; maximum daily dose: 2,000 mg/day; a repeat course may be necessary; for severe trachoma, longer durations may be necessary (40 days)

Anogenital tract infection:

Children and Adolescents <45 kg: Oral (base or ethylsuccinate): 50 mg/kg/day divided every 6 hours for 14 days; maximum daily dose: 2,000 mg/day

Adolescents ≥45 kg: Oral:

Base: 500 mg 4 times daily for 7 days

Ethylsuccinate: 800 mg 4 times daily for 7 days

Lymphogranuloma venereum (LGV): Adolescents ≥45 kg: Oral (base): 500 mg 4 times daily for 21 days

Impetigo: Infants, Children, and Adolescents: Oral: 10 mg/kg/dose 4 times daily (Stevens 2005)

Lyme Disease: Infants, Children, and Adolescents: Oral: 50 mg/kg/day divided every 6 hours for 14 to 21 days; maximum dose: 500 mg (Wormser 2006)

Pertussis (CDC 2005; Red Book 2012):

Infants 1 to 5 months: Oral: 10 mg/kg/dose 4 times daily for 14 days

Infants ≥6 months and Children: Oral: 10 mg/kg/dose 4 times daily for 7 to 14 days; maximum daily dose: 2,000 mg/day

Adolescents: Oral: 500 mg 4 times daily for 7 to 14 days

Pneumonia, community-acquired (CAP) (Bradley 2011): Infants >3 months, Children, and Adolescents: Note: A beta-lactam antibiotic should be added if typical bacterial pneumonia cannot be ruled out.

Presumed atypical (M. pneumoniae, C. pneumoniae, C. trachomatis); mild infection or step-down therapy: Oral: 10 mg/kg/dose every 6 hours; maximum daily dose: 2,000 mg/day

Moderate to severe atypical infection: IV: Lactobionate: 5 mg/kg/dose every 6 hours; maximum daily dose: 4,000 mg/day

Preoperative bowel preparation: Children and Adolescents: Oral: Base: 20 mg/kg; maximum dose: 1,000 mg administered at 1, 2, and 11 PM on the day before surgery combined with mechanical cleansing of the large intestine and oral neomycin (Bratzler 2013)

Prokinetic (GI motility) agent: Limited data available: Infants, Children, and Adolescents:

Diagnosis; gastric emptying study (provocative testing): IV: 2.8 mg/kg infused over 20 minutes was reported from one center's experience; maximum dose: 250 mg (Waseem 2012)

Treatment: Oral: 3 mg/kg/dose 4 times daily; may increase as needed to effect; maximum dose: 10 mg/kg or 250 mg (Rodriguez 2012)

Pneumococcal, prophylaxis in penicillin-allergic patients with sickle cell disease (SCD) and functional or anatomic asplenia (Knight-Madden 2001): Oral:

Infants and Children: 4 months to <3 years: 125 mg twice daily; salt not specified

Children 3 to 4 years: 250 mg twice daily; salt not specified

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

Reconstitution

Erythromycin lactobionate should be reconstituted with sterile water for injection without preservatives to a concentration of 50 mg/mL. No less than 100 mL of IV diluent should be used for an infusion bag. The final diluted solution should be 1 to 5 mg/mL.

Administration

Oral: Administer base, PCE, or stearate dosage forms on an empty stomach (2 hours before or after a meal); administer ethylsuccinate (EES) or delayed release (ERY-TAB) without regard to meals; may consider administering after food to decrease GI discomfort. Swallow delayed-release capsule or enteric-coated tablets whole; do not chew or break.

Bariatric surgery: Capsule and tablet, delayed release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Delayed-release capsule and tablet cannot be opened. Switch to IR tablet or oral suspension.

IV: Infuse 1 g over 20 to 60 minutes. IV infusion may be very irritating to the vein; infusion should be sufficiently slow to minimize pain along the vein. Do not administer IV push or bolus.

Dietary Considerations

Some products may contain sodium.

Base, PCE or stearate dosage forms should be taken on an empty stomach (2 hours before or after a meal).

Ethylsuccinate (EES) or delayed-release (ERY-TAB) dosage forms may be administered without regards to meals.

May consider administering after food to decrease GI discomfort.

Storage

Injection: Store unreconstituted vials at 20°C to 25°C (68°F to 77°F). Reconstituted solution (50 mg/mL) is stable for 2 weeks when refrigerated or for 24 hours at room temperature. Erythromycin IV infusion solution is stable at pH 6 to 8; stability of lactobionate is pH dependent; IV form has longest stability in NS. Parenteral admixture in NS is stable for 24 hours at 4°C. Admixtures in NS (including Add-Vantage containers) should be infused within 8 hours of preparation.

Oral suspension:

Granules: Prior to mixing, store at 20°C to 25°C (68°F to 77°F). After mixing, store under refrigeration and use within 10 days.

Powder: Prior to mixing, store at <30°C (86°F). After mixing, store at ≤25°C (77°F) and use within 35 days.

Tablet and capsule formulations: Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

Abemaciclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Abemaciclib. Management: Monitor for increased abemaciclib toxicities if combined with moderate CYP3A4 inhibitors. Consider reducing the abemaciclib dose in 50 mg decrements if necessary. Monitor therapy

Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use. Consider therapy modification

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

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

Alfuzosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Alfuzosin. Monitor therapy

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

Alitretinoin (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Alitretinoin (Systemic). Monitor therapy

ALPRAZolam: Erythromycin (Systemic) may increase the serum concentration of ALPRAZolam. Monitor therapy

Amiodarone: Erythromycin (Systemic) may enhance the QTc-prolonging effect of Amiodarone. Amiodarone may enhance the QTc-prolonging effect of Erythromycin (Systemic). Erythromycin (Systemic) may increase the serum concentration of Amiodarone. Avoid combination

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

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

Aprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Aprepitant. Avoid combination

ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Monitor therapy

ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole Lauroxil. Monitor therapy

Astemizole: Erythromycin (Systemic) may enhance the QTc-prolonging effect of Astemizole. Astemizole may enhance the QTc-prolonging effect of Erythromycin (Systemic). Erythromycin (Systemic) may increase the serum concentration of Astemizole. Avoid combination

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

AtorvaSTATin: Erythromycin (Systemic) may increase the serum concentration of AtorvaSTATin. Monitor therapy

Avanafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil. Management: The maximum avanafil dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects (eg, hypotension, syncope, priapism). Consider therapy modification

Avapritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avapritinib. Management: Avoid use of moderate CYP3A4 inhibitors with avapritinib. If this combination cannot be avoided, reduce the avapritinib dose from 300 mg once daily to 100 mg once daily. Consider therapy modification

Axitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Axitinib. Monitor therapy

Barnidipine: Erythromycin (Systemic) may increase the serum concentration of Barnidipine. Avoid combination

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

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

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

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

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

Blonanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin. Monitor therapy

Bortezomib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bortezomib. Monitor therapy

Bosutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib. Avoid combination

Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Monitor therapy

Brigatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inhibitors when possible. If such a combination cannot be avoided, reduce the dose of brigatinib by approximately 40% (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg). Consider therapy modification

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

Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) 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 CYP3A4 inhibitors, they should be closely monitored for signs and symptoms of corticosteroid excess. Consider therapy modification

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

BusPIRone: Erythromycin (Systemic) may increase the serum concentration of BusPIRone. Management: Limit the buspirone dose to 2.5 mg twice daily and monitor for increased buspirone effects/toxicities if combined with erythromycin. Consider therapy modification

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

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

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

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

CarBAMazepine: Erythromycin (Systemic) may increase the serum concentration of CarBAMazepine. Management: Consider alternative antimicrobial therapy in combination with carbamazepine. If combined, monitor for increased carbamazepine effects/toxicities. Consider therapy modification

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

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

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

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

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

Cisapride: Erythromycin (Systemic) may enhance the QTc-prolonging effect of Cisapride. Cisapride may enhance the QTc-prolonging effect of Erythromycin (Systemic). Erythromycin (Systemic) may increase the serum concentration of Cisapride. Avoid combination

Citalopram: May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Citalopram. Monitor therapy

Clindamycin (Topical): Erythromycin (Systemic) may diminish the therapeutic effect of Clindamycin (Topical). Avoid combination

Clopidogrel: Erythromycin (Systemic) may diminish the antiplatelet effect of Clopidogrel. Monitor therapy

Cobicistat: May increase the serum concentration of Erythromycin (Systemic). Management: Consider alternatives to this combination when cobicistat is combined with atazanavir or darunavir. If combined, monitor for increased erythromycin and cobicistat effects/toxicities. Consider therapy modification

Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cobimetinib. Management: Avoid this combination when possible. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose from 60 mg to 20 mg daily. Avoid concomitant use in patients already receiving reduced cobimetinib doses. Consider therapy modification

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

Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. See interaction monograph for details. Use extra caution in patients with impaired renal and/or hepatic function. Consider therapy modification

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

Copanlisib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Copanlisib. Monitor therapy

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

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

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

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Substrates (High risk with Inhibitors): CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Exceptions: Alitretinoin (Systemic); Bromperidol; Copanlisib; Praziquantel; Ripretinib; Trabectedin; Vinorelbine. Monitor therapy

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

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4. Consider therapy modification

Darifenacin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Darifenacin. Monitor therapy

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

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

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

Doxofylline: Erythromycin (Systemic) may increase the serum concentration of Doxofylline. Monitor therapy

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

Dronabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Monitor therapy

Dronedarone: May enhance the QTc-prolonging effect of Erythromycin (Systemic). Erythromycin (Systemic) may increase the serum concentration of Dronedarone. Avoid combination

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

Eletriptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eletriptan. Management: The use of eletriptan within 72 hours of a moderate CYP3A4 inhibitor should be avoided. Consider therapy modification

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, two elexacaftor/tezacaftor/ivacaftor (100 mg/50 mg/75 mg) tablets should be given in the morning, every other day. Ivacaftor (150 mg) should be given in the morning, every other day on alternate days. Consider therapy modification

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

Encorafenib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Encorafenib. Management: Avoid use of encorafenib and moderate CYP3A4 inhibitors when possible. If combined, decrease the encorafenib dose from 450 mg to 225 mg; 300 mg to 150 mg; and 225 mg or 150 mg to 75 mg. Resume prior dose once inhibitor discontinued for 3 to 5 half-lives. Consider therapy modification

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

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

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

Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: When used concomitantly with moderate inhibitors of CYP3A4, eplerenone dosing recommendations vary by indication and international labeling. See full drug interaction monograph for details. Consider therapy modification

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

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

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

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

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

Everolimus: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase the serum concentration of Everolimus. Management: Afinitor: For TSC-associated SEGA or TSC-associated seizures reduce everolimus dose 50%. For other Afinitor indications, reduce everolimus dose to 2.5 mg/day, increase to 5 mg/day if tolerated. Zortress: Monitor for increased everolimus concentrations. Consider therapy modification

Fedratinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fedratinib. Monitor therapy

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

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

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

Fluconazole: May enhance the QTc-prolonging effect of Erythromycin (Systemic). Fluconazole may increase the serum concentration of Erythromycin (Systemic). Avoid combination

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

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

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

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

Haloperidol: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect 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. Monitor therapy

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

Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib. Management: When treating B-cell malignancies, decrease ibrutinib to 280 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions. Consider therapy modification

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

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

Ivabradine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine. Avoid combination

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

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

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

Lapatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lapatinib. Monitor therapy

Larotrectinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Larotrectinib. Monitor therapy

Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Consider therapy modification

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

Lincomycin: Erythromycin (Systemic) may diminish the therapeutic effect of Lincomycin. Avoid combination

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

Lorlatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lorlatinib. Monitor therapy

Lovastatin: Erythromycin (Systemic) may increase the serum concentration of Lovastatin. Avoid combination

Lumacaftor and Ivacaftor: May decrease the serum concentration of Erythromycin (Systemic). Avoid combination

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

Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: US labeling recommends reducing lurasidone dose by 50% with a moderate CYP3A4 inhibitor and initiating 20 mg/day, max 80 mg/day. Some non-US labels recommend initiating lurasidone 20 mg/day, max 40 mg/day. Avoid concurrent use of grapefruit products. Consider therapy modification

Lurbinectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and moderate CYP3A4 inhibitors when possible. If combined, consider a lurbinectedin dose reduction as clinically indicated. Consider therapy modification

Macitentan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Macitentan. Monitor therapy

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

Mequitazine: Erythromycin (Systemic) may enhance the arrhythmogenic effect of Mequitazine. Management: Concurrent administration of intravenous erythromycin with mequitazine is contraindicated. Avoid combination

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

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

Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil. Monitor therapy

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

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

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

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

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

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

Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol. Management: The use of naloxegol and moderate CYP3A4 inhibitors should be avoided. If concurrent use is unavoidable, reduce naloxegol dose to 12.5 mg once daily and monitor for signs of opiate withdrawal (eg, hyperhidrosis, chills, diarrhea, anxiety, irritability). Consider therapy modification

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

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

Olaparib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 150 mg twice daily and the dose of olaparib capsules should be reduced to 200 mg twice daily. Consider therapy modification

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

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

Oxybutynin: Erythromycin (Systemic) may increase the serum concentration of Oxybutynin. Monitor therapy

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

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

Pemigatinib: CYP3A4 Inhibitors (Moderate) 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 moderate inhibitor once 3 half-lives of the inhibitor has passed. Consider therapy modification

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

Pexidartinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pexidartinib. Management: Avoid use of pexidartinib with moderate CYP3A4 inhibitors if possible. If combined, the pexidartinib dose should be reduced. Decrease 800 mg or 600 mg daily doses to 200 mg twice daily. Decrease doses of 400 mg per day to 200 mg once daily. Consider therapy modification

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

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

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

Pitavastatin: Erythromycin (Systemic) may increase the serum concentration of Pitavastatin. Management: Limit pitavastatin to a maximum of 1 mg/day when used in combination with erythromycin. If this combination is used, monitor patients more closely for evidence of pitavastatin toxicity. Consider therapy modification

Pivmecillinam: Erythromycin (Systemic) may diminish the therapeutic effect of Pivmecillinam. Monitor therapy

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

Pravastatin: Erythromycin (Systemic) may increase the serum concentration of Pravastatin. Monitor therapy

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

QT-prolonging Antipsychotics (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (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. Exceptions: Pimozide; QUEtiapine. Monitor therapy

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

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

QT-prolonging Class III Antiarrhythmics (Highest Risk): Erythromycin (Systemic) may enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). QT-prolonging Class III Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Erythromycin (Systemic). Management: Avoid concomitant use of erythromycin and class III antiarrhythmic agents. Use of erythromycin with dronedarone is specifically contraindicated. Exceptions: Dronedarone. Avoid combination

QT-prolonging Kinase Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Kinase Inhibitors (Highest 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. Exceptions: Ivosidenib; Selpercatinib. Consider therapy modification

QT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Kinase Inhibitors (Moderate Risk). Exceptions: Encorafenib; Entrectinib. Monitor therapy

QT-prolonging Miscellaneous Agents (Highest Risk): Erythromycin (Systemic) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect 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. Exceptions: Astemizole; Cisapride; Terfenadine. Consider therapy modification

QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration 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. Exceptions: Domperidone. Monitor therapy

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): Erythromycin (Systemic) may enhance the QTc-prolonging effect of QT-prolonging Moderate 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. Exceptions: Crizotinib; Fluconazole. Monitor therapy

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

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

QUEtiapine: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QUEtiapine. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QUEtiapine. Management: Monitor for increased quetiapine 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. Monitor therapy

QuiNIDine: Erythromycin (Systemic) may enhance the QTc-prolonging effect of QuiNIDine. Erythromycin (Systemic) may increase the serum concentration of QuiNIDine. Avoid combination

Ranolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors. Monitor for increased ranolazine effects and toxicities during concomitant use. Consider therapy modification

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

Rifamycin Derivatives: Macrolide Antibiotics may decrease the metabolism of Rifamycin Derivatives. Exceptions: Rifapentine. Monitor therapy

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

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

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

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

Rivaroxaban: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase the serum concentration of Rivaroxaban. Management: No action is needed in patients with normal renal function. Do not use this combination in patients with estimated creatinine clearance 15 to 80 mL/min unless prospective benefits outweigh the risks. Consider therapy modification

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

Rupatadine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rupatadine. Monitor therapy

Ruxolitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ruxolitinib. Monitor therapy

Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Monitor therapy

Saquinavir: Erythromycin (Systemic) may enhance the QTc-prolonging effect of Saquinavir. Erythromycin (Systemic) may increase the serum concentration of Saquinavir. Avoid combination

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

SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SAXagliptin. Monitor therapy

Selpercatinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Selpercatinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Selpercatinib. Management: Avoid combination if possible. If use is necessary, reduce selpercatinib dose as follows: from 120mg twice/day to 80mg twice/day, or from 160mg twice/day to 120mg twice/day. Monitor QT interval more closely for QTc interval prolongation and arrhythmias. Consider therapy modification

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

Sertraline: Erythromycin (Systemic) may enhance the adverse/toxic effect of Sertraline. Monitor therapy

Sildenafil: Erythromycin (Systemic) may increase the serum concentration of Sildenafil. Management: For pulmonary arterial hypertension, no dose adjustment required. For erectile dysfunction, consider using a lower starting dose of 25 mg in patients who are also taking erythromycin. Consider therapy modification

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

Silodosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Silodosin. Monitor therapy

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

Simeprevir: May increase the serum concentration of Erythromycin (Systemic). Erythromycin (Systemic) may increase the serum concentration of Simeprevir. Avoid combination

Simvastatin: Erythromycin (Systemic) may increase the serum concentration of Simvastatin. Avoid combination

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

Sirolimus: Erythromycin (Systemic) may increase the serum concentration of Sirolimus. Sirolimus may increase the serum concentration of Erythromycin (Systemic). Management: Monitor for increased serum concentrations of sirolimus if combined with erythromycin. Lower initial sirolimus doses or sirolimus dose reductions will likely be required. Consider therapy modification

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

Sonidegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Consider therapy modification

SUNItinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SUNItinib. Monitor therapy

Suvorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy. Consider therapy modification

Tacrolimus (Systemic): Erythromycin (Systemic) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy

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

Tadalafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tadalafil. Monitor therapy

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

Tamsulosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. Monitor therapy

Tazemetostat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tazemetostat. Management: Avoid when possible. If combined, reduce tazemetostat dose from 800 mg twice daily to 400 mg twice daily, from 600 mg twice daily to 400 mg in AM and 200 mg in PM, or from 400 mg twice daily to 200 mg twice daily. Consider therapy modification

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

Telithromycin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Telithromycin. Monitor therapy

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

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

Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tezacaftor and Ivacaftor. Management: If combined with moderate CYP3A4 inhibitors, give tezacaftor/ivacaftor in the morning, every other day; give ivacaftor in the morning, every other day on alternate days. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact monograph Consider therapy modification

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

Ticagrelor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor. Monitor therapy

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

Tofacitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tofacitinib. Monitor therapy

Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Management: Avoid this combination with Samsca brand of tolvaptan. Reduce dose for Jynarque brand: 90 mg AM and 30 mg PM, reduce to 45 mg AM and 15 mg PM; 60 mg AM and 30 mg PM, reduce to 30 mg AM and 15 mg PM; 45 mg AM and 15 mg PM, reduce to 15 mg AM and PM. Consider therapy modification

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

Trabectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin. Monitor therapy

Triazolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant moderate CYP3A4 inhibitors. Consider therapy modification

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

Ubrogepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and avoid a second dose for 24 hours when used with moderate CYP3A4 inhibitors. Consider therapy modification

Udenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Udenafil. Monitor therapy

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

Vardenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 5 mg dose within a 24-hour period if combined with moderate CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and moderate CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Consider therapy modification

Venetoclax: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with moderate CYP3A4 inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of moderate CYP3A4 inhibitors. Consider therapy modification

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

Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Monitor therapy

VinBLAStine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinBLAStine. Monitor therapy

VinCRIStine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of VinCRIStine. Monitor therapy

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

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

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

Zafirlukast: Erythromycin (Systemic) may decrease the serum concentration of Zafirlukast. Monitor therapy

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

Zopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone. Management: The starting adult dose of zopiclone should not exceed 3.75 mg if combined with a moderate CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined. Consider therapy modification

Test Interactions

False-positive urinary catecholamines (fluorometric assay), 17-hydroxycorticosteroids and 17-ketosteroids

Adverse Reactions

Frequency not defined. Incidence may vary with formulation.

Cardiovascular: QTc prolongation, torsade de pointes, ventricular arrhythmia, ventricular tachycardia

Central nervous system: Seizure

Dermatologic: Erythema multiforme, pruritus, skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria

Gastrointestinal: Abdominal pain, anorexia, diarrhea, nausea, oral candidiasis, pancreatitis, pseudomembranous colitis, pyloric stenosis (infantile hypertrophic), vomiting

Hepatic: Abnormal hepatic function tests, cholestatic jaundice (most common with estolate), hepatitis

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

Local: Injection site phlebitis

Neuromuscular & skeletal: Weakness

Otic: Hearing loss

Renal: Interstitial nephritis

Postmarketing and/or case reports: Hepatotoxicity (idiosyncratic) (Chalasani 2014)

Warnings/Precautions

Concerns related to adverse effects:

• Altered cardiac conduction: Macrolides have been associated with rare QTc prolongation and ventricular arrhythmias, including torsade de pointes; use with caution in patients at risk of prolonged cardiac repolarization; avoid use in patients with prolonged QT interval, uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, or concurrent use of Class IA (eg, quinidine, procainamide) or Class III (eg, amiodarone, dofetilide, sotalol) antiarrhythmic agents.

• Superinfection: Prolonged 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:

• Hepatic impairment: Use with caution in patients with preexisting liver disease; hepatic impairment, including hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been observed. Discontinue if symptoms of malaise, nausea, vomiting, abdominal colic, and fever.

• Myasthenia gravis: Exacerbation of and new onset of myasthenia gravis symptoms have been reported.

Concurrent drug therapy issues:

• Major inhibitor of CYP3A4: Use caution with any agents with substantial metabolism through the CYP3A4 pathway; high potential for drug interactions exists. Avoid concurrent use with strong CYP3A4 inhibitors; may increase the risk of sudden cardiac death (Ray 2004).

Special populations:

• Infants: Use of erythromycin has been associated with infantile hypertrophic pyloric stenosis (IHPS); observe for non-bilious vomiting or irritability with feeding.

• Elderly: May be at increased risk of adverse events, including hearing loss and/or torsade de pointes, particularly if concurrent renal/hepatic impairment.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.

Pregnancy Considerations

Erythromycin crosses the placenta.

Cardiovascular anomalies following exposure in early pregnancy have been reported in some observational studies.

Serum concentrations of erythromycin may be variable in pregnant women (Kiefer 1955; Philipson 1976).

Erythromycin is the antibiotic of choice for preterm prelabor rupture of membranes <34 0/7 weeks' gestation) (ACOG 188 2018), the treatment of lymphogranuloma venereum in pregnancy, and the treatment of or long-term suppression of Bartonella infection in HIV-infected pregnant patients. Erythromycin is one of the antibiotics that may be used for the treatment of chancroid or granuloma inguinale during pregnancy, and may be appropriate as an alternative agent for the treatment of chlamydial infections in pregnant women (consult current guidelines) (CDC [Workowski 2015]; HHS [OI adult 2020]). Agents other than systemic erythromycin are preferred for the treatment of acne during pregnancy (AAD [Zaenglein 2016]).

Patient Education

What is this drug used for?

• It is used to treat or prevent bacterial infections.

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

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

• Abdominal pain

• Nausea

• Vomiting

• Diarrhea

• Lack of appetite

• Injection site irritation

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

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

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

• Not able to pass urine

• Change in amount of urine passed

• Severe dizziness

• Passing out

• Fast heartbeat

• Hearing loss

• Muscle weakness

• Trouble chewing or swallowing

• Trouble breathing

• Droopy eyelids

• Vision changes

• Blurred vision

• Double vision

• Irritability (newborns)

• Vomiting (newborns)

• Abnormal heartbeat

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

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

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

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

Further information

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

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