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PCE
Classes
Macrolide Antibiotics
Ophthalmological Anti-infectives
Topical Antiinfectives for Acne
Administration
Most formulations are well absorbed and can be given without regard to meals. However, optimal absorption is achieved in the fasting state (1/2 hour before meals or 2 hours after meals). If GI irritation occurs, may be administered with food.
Erythromycin ethylsuccinate film-coated tablets: Swallow whole; do not crush, break, or chew. May be administered without regard to meals.
Erythromycin stearate: Swallow whole; do not crush, break, or chew. Administer in the fasting state or immediately prior to meals.
Erythromycin base, delayed-release tablets or capsules (enteric coated): Swallow whole; do not crush, chew, or open. May be given without regard to meals.
Erythromycin ethylsuccinate suspension: FDA-approved labeling states that may be given without regard to meals ; however, studies have shown better absorption when given with milk or food.
Shake well before administration. Administer using a calibrated measuring device.
Reconstitution
Review the manufacturer’s reconstitution instructions for the particular product and package size; the amount of water to be used for reconstitution may vary between manufacturers.
Prior to constitution, tap the bottle several times to loosen the powder.
Add approximately half of the total amount of water needed and shake well. Add the remaining water and shake well. Resultant concentration will be 40 or 80 mg/mL.
Storage: The prepared oral suspension should be refrigerated and used within 10 days.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Powder Vials for Injection
Reconstitution
Reconstitute each 500 mg vial with 10 mL of Sterile Water for Injection to yield 50 mg/mL.
Do not use diluents containing preservatives or inorganic salts. Other diluents may cause precipitation during reconstitution.
Storage: Reconstituted solutions are stable for 24 hours at room temperature or 14 days under refrigeration.
Dilution
Dilute appropriate dose in at least 100 mL of 0.9% Sodium Chloride for Injection, Lactated Ringer's Injection, or Normosol-R.
Do not use other diluents as acidic solution are unstable and lose their potency.
For intermittent infusion, dilute to a final concentration of 1 to 5 mg/mL.
For continuous infusion, dilute to a final concentration of 1 mg/mL.
Storage: The final diluted solution should be completely administered within 8 hours.
ADD-Vantage Vials
Reconstitution
Reconstitute only in 100 mL flexible container with 0.9% Sodium Chloride for Injection or 5% Dextrose for Injection.
Storage: Reconstitute immediately before administration. The diluted solution should be completely administered within 8 hours when reconstituted in 0.9% Sodium Chloride for Injection and 2 hours when reconstituted in 5% Dextrose for Injection.
Intermittent IV Infusion
Administer IV over 20 to 60 minutes.
Continuous IV infusion
Completely administer each infusion bag within 8 hours of dilution.
Do not use topical preparations near the eyes, nose, mouth, or other mucous membranes.
Cleanse and pat dry the affected area prior to application.
Wash hand after use.
Topical Gel and Solution
Apply a thin film to the cleansed affected area as prescribed.
Saturated Erythromycin Pledgets
Apply solution to cleansed affected area by gently rubbing pledgets over affected skin. Several pledgets may be required per application.
Apply topically to the eye taking care to avoid contamination.
Instruct patient on proper instillation of eye ointment.
Do not touch the tip of the tube to the eye, fingertips, or other surface.
Adverse Reactions
erythema multiforme / Delayed / 0-1.0
Stevens-Johnson syndrome / Delayed / 0-1.0
toxic epidermal necrolysis / Delayed / 0-1.0
pancreatitis / Delayed / 0-1.0
cardiac arrest / Early / 0-1.0
torsade de pointes / Rapid / 0-1.0
seizures / Delayed / 0-1.0
hearing loss / Delayed / 0-1.0
interstitial nephritis / Delayed / Incidence not known
acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
C. difficile-associated diarrhea / Delayed / Incidence not known
pyloric stenosis / Delayed / Incidence not known
phlebitis / Rapid / 19.0-19.0
erythema / Early / 1.0-10.0
jaundice / Delayed / 0-10.0
elevated hepatic enzymes / Delayed / 0-10.0
hepatitis / Delayed / 0-1.0
QT prolongation / Rapid / 0-1.0
superinfection / Delayed / Incidence not known
pseudomembranous colitis / Delayed / Incidence not known
skin irritation / Early / 0-25.0
xerosis / Delayed / 1.0-10.0
pruritus / Rapid / 1.0-10.0
vomiting / Early / 10.0
diarrhea / Early / 10.0
nausea / Early / 10.0
anorexia / Delayed / 10.0
abdominal pain / Early / 10.0
rash / Early / Incidence not known
urticaria / Rapid / Incidence not known
injection site reaction / Rapid / Incidence not known
ocular irritation / Rapid / Incidence not known
Jarisch-Herxheimer reaction / Early / Incidence not known
Common Brand Names
A/T/S, E-Mycin, E.E.S., Emcin Clear, EMGEL, Ery-Tab, ERYC, Erycette, Eryderm, Erygel, Erymax, EryPed, Erythra Derm, Erythrocin Lactobionate, Erythrocin Stearate, Ilotycin, Romycin, T-Stat
Dea Class
Rx
Description
Oral/parenteral/topical macrolide antibiotic. Active against many microbes, but clinical applications are relatively few. Used for Legionnaire's disease and Mycoplasma pneumoniae pneumonia, and as an alternative to beta-lactam antibiotics in allergic patients. May have benefits in hypomotility conditions, such as diabetic gastroparesis.
Dosage And Indications
250 to 500 mg PO twice daily initially, followed by 250 to 500 mg once daily for maintenance. The use of erythromycin for acne has decreased due to the high rates of resistance to P. acnes.
Apply a thin layer of a 1.5% or 2% topical preparation (i.e., pledget, solution, gel, or ointment) to the affected area twice daily. Due to a slow onset of action and the increased risk of the development of bacterial resistance, topical antibiotic monotherapy is not recommended. If topical antibiotic therapy is continued longer than a few weeks, the addition of topical benzoyl peroxide is recommended.
250 mg PO every 6 hours or 333 mg PO every 8 hours or 500 mg PO every 12 hours. Doses up to 4 g/day may be used for severe infections. Twice-daily dosing is not recommended with doses more than 1 g/day.[28251]
30 to 50 mg/kg/day PO in 3 to 4 divided doses (Usual Max: 2 g/day).[48677] [63245] The FDA-approved dose is up to 100 mg/kg/day (Max: 4 g/day) for more severe infections.[50528] However, this is rarely done in clinical practice.
10 mg/kg/dose PO every 6 hours.
1.6 g/day PO divided every 6 to 12 hours. Doses up to 4 g/day may be used for severe infections. Usual dose: 400 mg PO every 6 hours.[48677]
30 to 50 mg/kg/day PO in 3 to 4 divided doses (Usual Max: 2 g/day).[48677] [63245] The FDA-approved dose is up to 100 mg/kg/day (Max: 4 g/day) for more severe infections.[50528] However, this is rarely done in clinical practice.
10 mg/kg/dose PO every 6 hours.
250 mg PO every 6 hours or 500 mg PO every 12 hours. Doses up to 4 g/day may be used for severe infections. Twice-daily dosing is not recommended with doses more than 1 g/day.
30 to 50 mg/kg/day PO in 3 to 4 divided doses (Usual Max: 2 g/day).[48677] [63245] The FDA-approved dose is up to 100 mg/kg/day (Max: 4 g/day) for more severe infections.[50528] However, this is rarely done in clinical practice.
10 mg/kg/dose PO every 6 hours.
15 to 20 mg/kg/day IV divided every 6 hours (Max: 4 g/day).
15 to 20 mg/kg/day IV divided every 6 hours (Max: 4 g/day).
10 mg/kg/dose IV every 6 hours.
40 mg/kg/day PO in 4 divided doses (Usual Max: 2 g/day) for 10 days in patients with presumed/confirmed atypical pathogens as an alternative therapy to azithromycin.[46963] [63245]
20 mg/kg/day IV divided every 6 hours (Max: 4 g/day) for 10 days in patients with presumed/confirmed atypical pathogens as an alternative therapy to azithromycin.[46963] [63245]
500 mg to 1 g PO (of base, estolate, or stearate) or 400 mg to 1 g PO (of ethylsuccinate) every 6 hours.
500 mg to 1 g IV every 6 hours.
250 mg PO every 6 hours or 333 mg PO every 8 hours or 500 mg PO every 12 hours for 10 days. For the treatment of group A streptococcal pharyngitis, guidelines recommend erythromycin as an alternative for patients allergic to penicillin.
30 to 50 mg/kg/day PO in 3 to 4 divided doses (Max: 1 g/day) for 10 days. For the treatment of group A streptococcal pharyngitis, guidelines recommend erythromycin as an alternative for patients allergic to penicillin.
10 mg/kg/dose PO every 6 hours for 10 days.
400 mg PO every 6 hours for 10 days. May divide total daily dose every 8 or 12 hours. For the treatment of group A streptococcal pharyngitis, guidelines recommend erythromycin as an alternative for patients allergic to penicillin.
30 to 50 mg/kg/day PO in 3 to 4 divided doses (Max: 1.6 g/day) for 10 days. For the treatment of group A streptococcal pharyngitis, guidelines recommend erythromycin as an alternative for patients allergic to penicillin.
10 mg/kg/dose PO every 6 hours for 10 days.
250 mg PO every 6 hours or 500 mg PO every 12 hours for 10 days. For the treatment of group A streptococcal pharyngitis, guidelines recommend erythromycin as an alternative for patients allergic to penicillin.
30 to 50 mg/kg/day PO in 3 to 4 divided doses (Max: 1 g/day) for 10 days. For the treatment of group A streptococcal pharyngitis, guidelines recommend erythromycin as an alternative for patients allergic to penicillin.
10 mg/kg/dose PO every 6 hours for 10 days.
250 mg PO every 12 hours.[48678] [50528] A macrolide is recommended for secondary prevention of rheumatic fever in patients allergic to both penicillin and sulfisoxazole. Guidelines recommend secondary prophylaxis for 10 years or until age 40 years (whichever is longer) for patients who have experienced rheumatic fever with carditis and have residual heart disease (persistent valvular disease). For patients who have experienced rheumatic fever with carditis but have no residual heart disease, prophylaxis is recommended for 10 years or until age 21 years (whichever is longer). For patients who have experienced rheumatic fever without carditis, prophylaxis is recommended for 5 years or until age 21 years (whichever is longer).[35507]
30 to 50 mg/kg/day PO in 3 to 4 divided doses (Max: 500 mg/day). A macrolide is recommended for secondary prevention of rheumatic fever in patients allergic to both penicillin and sulfisoxazole. Guidelines recommend secondary prophylaxis for 10 years or until age 40 years (whichever is longer) for patients who have experienced rheumatic fever with carditis and have residual heart disease (persistent valvular disease). For patients who have experienced rheumatic fever with carditis but have no residual heart disease, prophylaxis is recommended for 10 years or until age 21 years (whichever is longer). For patients who have experienced rheumatic fever without carditis, prophylaxis is recommended for 5 years or until age 21 years (whichever is longer).[35507]
400 mg PO every 12 hours.[43258] A macrolide is recommended for secondary prevention of rheumatic fever in patients allergic to both penicillin and sulfisoxazole. Guidelines recommend secondary prophylaxis for 10 years or until age 40 years (whichever is longer) for patients who have experienced rheumatic fever with carditis and have residual heart disease (persistent valvular disease). For patients who have experienced rheumatic fever with carditis but have no residual heart disease, prophylaxis is recommended for 10 years or until age 21 years (whichever is longer). For patients who have experienced rheumatic fever without carditis, prophylaxis is recommended for 5 years or until age 21 years (whichever is longer).[35507]
30 to 50 mg/kg/day PO in 2 to 4 divided doses (Max: 800 mg/day).[43258] A macrolide is recommended for secondary prevention of rheumatic fever in patients allergic to both penicillin and sulfisoxazole. Guidelines recommend secondary prophylaxis for 10 years or until age 40 years (whichever is longer) for patients who have experienced rheumatic fever with carditis and have residual heart disease (persistent valvular disease). For patients who have experienced rheumatic fever with carditis but have no residual heart disease, prophylaxis is recommended for 10 years or until age 21 years (whichever is longer). For patients who have experienced rheumatic fever without carditis, prophylaxis is recommended for 5 years or until age 21 years (whichever is longer).[35507]
250 mg PO every 6 hours or 333 mg PO every 8 hours or 500 mg PO every 12 hours. Up to 4 g/day may be used. Twice-daily dosing is not recommended with doses more than 1 g/day.
30 to 50 mg/kg/day PO in 3 to 4 divided doses. Up to 100 mg/kg/day (Max: 4 g/day) may be used.
10 mg/kg/dose PO every 6 hours.
400 mg PO every 6 hours. May divide total daily dose every 8 or 12 hours. Up to 4 g/day may be used.
30 to 50 mg/kg/day PO in 3 to 4 divided doses. Up to 100 mg/kg/day (Max: 4 g/day) may be used.
10 mg/kg/dose PO every 6 hours.
250 mg PO every 6 hours or 500 mg PO every 12 hours. Up to 4 g/day may be used. Twice-daily dosing is not recommended with doses more than 1 g/day.
30 to 50 mg/kg/day PO in 3 to 4 divided doses. Up to 100 mg/kg/day (Max: 4 g/day) may be used.
10 mg/kg/dose PO every 6 hours.
15 to 20 mg/kg/day IV divided every 6 hours (Max: 4 g/day).
15 to 20 mg/kg/day IV divided every 6 hours (Max: 4 g/day).
10 mg/kg/dose IV every 6 hours.
250 to 500 mg (of base, estolate or stearate) PO every 6 hours or 400 to 800 mg (ethylsuccinate) PO every 6 hours. Up to 4 g/day PO may be used for severe infections.
30 to 50 mg/kg/day (Usual Max: 2 g/day) PO in 3 to 4 divided doses. The FDA-approved labeling states that up to 100 mg/kg/day (Max: 4 g/day) may be given for more severe infections; however, this is rarely done in clinical practice.
Not recommended by guidelines. The FDA-approved dosage is 500 mg PO 4 times daily (base or stearate), 666 mg PO every 8 hours (stearate), or 800 mg PO 3 times daily (ethylsuccinate) for 7 days.
Not recommended by guidelines.
50 mg/kg/day (base or ethylsuccinate) PO in 4 divided doses (Max: 2 g/day) for 14 days for chlamydial infections.
50 mg/kg/day PO in 4 divided doses for 14 days; a second course may be required. The FDA-approved duration is for at least 3 weeks.
50 mg/kg/day PO in 4 divided doses for 14 days; a second course may be required. The FDA-approved duration is for at least 3 weeks.
40 to 50 mg/kg/day (Max: 2 g/day) PO divided every 6 to 12 hours for 14 days as an adjunct to diphtheria antitoxin.
30 to 50 mg/kg/day (Max: 2 g/day) PO divided every 6 to 8 hours for 14 days as an adjunct to diphtheria antitoxin.
40 to 50 mg/kg/day (Max: 2 g/day) IV divided every 6 hours for 14 days as an adjunct to diphtheria antitoxin.
20 to 50 mg/kg/day (Max: 2 g/day) IV divided every 6 hours for 14 days as an adjunct to diphtheria antitoxin.
Not recommended by guidelines. The FDA-approved dosage is 500 mg IV every 6 hours for 3 days, followed by oral therapy for 7 days.
Not recommended by guidelines. The FDA-approved dosage is 250 mg PO every 6 hours for 7 days following initial IV therapy.
Not recommended by guidelines. The FDA-approved dosage is 400 mg PO every 6 hours for 7 days following initial IV therapy.
NOTE: For postexposure prophylaxis, administer to close contacts within 3 weeks of exposure, especially in high-risk patients (e.g., women in third trimester, infants < 12 months).
Oral dosage Adults
500 mg PO 4 times per day (2 g total) for 14 days.
40—50 mg/kg/day PO (maximum 2 g/day) in 4 divided doses for 14 days.
Azithromycin is the preferred agent. If azithromycin unavailable, erythromycin 40—50 mg/kg/day PO in 4 divided doses may be used. Monitor for infantile hypertrophic pyloric stenosis (IHPS) (see Adverse Reactions).
Not recommended by guidelines. The FDA-approved dosage is 48 to 64 g PO of erythromycin ethylsuccinate or 30 to 40 g PO of erythromycin base or erythromycin stearate in divided doses over 10 to 15 days.[28251] [48677] [50528]
1 g PO in combination with neomycin 1 g PO. Give as 3 doses over 10 hours the day before surgery (i.e., 1 pm, 2 pm, and 11 pm on the day before 8 am surgery). Appropriate IV antibmicrobial prophylaxis should also be given.
20 mg/kg/dose (Max: 1 g/dose) PO in combination with neomycin 15 mg/kg/dose (Max: 1 g/dose) PO. Give as 3 doses over 10 hours the day before surgery (i.e., 1 pm, 2 pm, and 11 pm on the day before 8 am surgery). Appropriate IV antibmicrobial prophylaxis should also be given. Data for antimicrobial prophylaxis in colorectal surgery in pediatric patients are lacking; however, it is suggested that prophylactic regimens that have been studied in adults would have similar efficacy in children.
1 centimeter ribbon in the affected eye(s) up to 6 times daily.
1 centimeter ribbon in the affected eye(s) up to 6 times daily.
50 mg/kg/day PO in 4 divided doses for 14 days. A second course of treatment may be necessary.
Apply a ribbon (approximately 1 cm) of 0.5% ophthalmic ointment into each lower conjunctival sac immediately after birth (i.e., within 1 hour). Do not flush eyes after instillation.
250 to 500 mg PO every 6 hours for 7 to 14 days.
30 to 50 mg/kg/day (Max: 1 g/day) PO divided every 6 hours for 7 to 14 days.
15 to 20 mg/kg/day IV divided every 6 hours for 7 to 14 days.
15 to 20 mg/kg/day IV divided every 6 hours for 7 to 14 days.
500 mg PO 3 times daily for 7 days as an alternative. A longer course of therapy may be required in HIV-infected patients and uncircumcised males.
500 mg PO 3 times daily for 7 days as an alternative. A longer course of therapy may be required in HIV-infected patients and uncircumcised males.
250 to 500 mg PO 3 times daily, 30 minutes before meals. Guidelines recommend a short course of therapy in patients with persistent symptoms after trials of standard prokinetic therapy (e.g., metoclopramide). A systematic review of studies showed a 43% improvement of symptoms with oral erythromycin. The oral suspension is often utilized due to rapid absorption and to facilitate dose modifications. Although dosage can be titrated to effect, side effects often limit the dose tolerated for gastroparesis. The effectiveness of chronic therapy may be limited due to the development of tachyphylaxis as a result of motilin receptor downregulation. Clinical responsiveness to oral erythromycin declines after 4 weeks.
3 mg/kg/dose PO 4 times daily; up to 10 mg/kg/dose (Max: 250 mg/dose) PO 4 times daily has been used; however, data are limited. Guidelines for the treatment of gastroparesis state that oral erythromycin improves gastric emptying; however, long-term use (e.g., more than 4 weeks) is limited by tachyphylaxis.
3 mg/kg/dose IV every 8 hours has been studied in hospitalized patients with diabetic gastroparesis. Although dosage can be titrated to effect, side effects often limit the dosage tolerated for gastroparesis. The effectiveness of chronic therapy may be limited due to the development of tachyphylaxis as a result of motilin receptor downregulation.
3 mg/kg/dose (Max: 250 mg/dose) IV every 6 to 8 hours; however, data are limited in children. 3 mg/kg/dose every 8 hours is recommended by clinical guidelines if an IV prokinetic agent is needed. However, metoclopramide is considered the first-line agent.
Doses of 70 or 200 mg IV as single dose, 200 mg IV every 12 hours for 7 days, or 250 mg IV every 6 hours for at least 24 to 48 hours have been used. In placebo-controlled studies that evaluated single doses of erythromycin (70 mg or 200 mg IV), patients treated with erythromycin demonstrated statistically significantly improved gastric emptying volumes and half-emptying volumes , had increased frequency and amplitude of gastric antrum contractions , and had a higher gastric emptying coefficient (GEC) as compared to placebo . In another placebo-controlled trial, trauma patients treated with erythromycin 250 mg IV every 6 hours reached a higher percentage of target enteral nutrition volume at 48 hours compared to those that received placebo (58% vs. 44%, p = 0.011); however, there was no difference in the amount of feeding tolerated over the course of the entire study. In 2 studies comparing erythromycin (250 mg IV every 6 hours or 200 mg IV every 12 hours) to metoclopramide (10 mg IV every 6 hours), gastric residual volumes were reduced and feeding rates increased similarly in both patient groups. However, another study showed that erythromycin 200 mg IV every 12 hours provided a greater percentage of gastric residual volume reduction (59 +/- 4% vs. 35 +/- 6%, p < 0.001), and the percentage of patients successfully fed with enteral nutrition was higher with erythromycin as compared to metoclopramide (87% vs. 62%, p = 0.02).
3 mg/kg/dose (Max: 250 mg/dose) IV every 6 to 8 hours; however, data are limited in children. 3 mg/kg/dose every 8 hours is recommended by clinical guidelines if an IV prokinetic agent is needed. However, metoclopramide is considered the first-line agent.
3 mg/kg/dose PO 4 times daily; up to 10 mg/kg/dose (Max: 250 mg/dose) PO 4 times daily has been used; however, data are limited. Guidelines for the treatment of gastroparesis state that oral erythromycin improves gastric emptying; however, long-term use (e.g., more than 4 weeks) is limited by tachyphylaxis.
10 to 12.5 mg/kg/dose PO every 6 hours given 30 minutes before feedings; however optimal dose has not been established and efficacy outcomes have differed in various studies. Most studies have used a treatment duration of 10 to 14 days. Studies of erythromycin for 'rescue therapy' (treatment of gastrointestinal dysmotility) in neonates (mainly premature neonates) have shown that high-dose erythromycin (50 mg/kg/day) is necessary to achieve significant prokinetic effects from erythromycin. In clinical studies, high-dose erythromycin has improved feeding tolerance, shortened the time that parenteral nutrition is required, and decreased the incidence of parenteral nutrition-associated cholestasis. Prophylactic therapy with erythromycin has not shown clinical efficacy in most studies. Intermediate-dose erythromycin (20 mg/kg/day PO divided every 6 hours) was also shown to improve feeding tolerance, and shorten parenteral nutrition duration and time to achieve body weight of 2500 g or more compared with placebo in a study of 45 very low birthweight infants. Low-dose erythromycin (less than 15 mg/kg/day) has been used in studies, but conflicting results have been reported. Some studies have shown a benefit while others have not. There have also been conflicting results with regards to efficacy for gestational age (GA) in studies that stratified results by GA. Some studies have only seen benefit in neonates older than 32 weeks , while others have reported benefit only in infants younger than 32 weeks.
For the treatment of intestinal amebiasis. Oral dosage (erythromycin base or stearate) Adults
250 mg PO every 6 hours or 333 mg PO every 8 hours or 500 mg PO every 12 hours for 10 to 14 days.
30 to 50 mg/kg/day (Max: 1 g/day) PO in 3 to 4 divided doses for 10 to 14 days.
400 mg PO every 6 hours for 10 to 14 days.
30 to 50 mg/kg/day (Max: 1.6 g/day) PO in 3 to 4 divided doses for 10 to 14 days.
250 to 500 mg PO every 6 hours for 3 days.
12.5 mg/kg/dose (Max: 500 mg/dose) PO every 6 hours for 3 days.
500 mg PO every 6 hours for 14 days. Due to lower efficacy, reserve macrolides for patients in whom other antibiotic classes are contraindicated.
12.5 mg/kg/dose (Max: 500 mg/dose) PO every 6 hours for 14 days. Due to lower efficacy, reserve macrolides for patients in whom other antibiotic classes are contraindicated.
250 mg PO every 6 hours for 14 days.
400 mg PO every 6 hours for 14 days.
250 to 500 mg PO every 6 hours for 5 to 7 days.
40 mg/kg/day PO in 3 to 4 divided doses (Max: 2 g/day) for 5 to 7 days.
10 mg/kg/dose PO every 6 hours for 5 to 7 days.
400 mg PO every 6 hours for 5 to 7 days.
40 mg/kg/day PO in 3 to 4 divided doses (Max: 1.6 g/day) for 5 to 7 days.
10 mg/kg/dose PO every 6 hours for 5 to 7 days.
250 mg PO every 6 hours or 333 mg PO every 8 hours or 500 mg PO every 12 hours. Up to 4 g/day may be used. Twice-daily dosing is not recommended with doses more than 1 g/day.[28251]
30 to 50 mg/kg/day PO in 3 to 4 divided doses. Up to 100 mg/kg/day (Max: 4 g/day) may be used.
10 mg/kg/dose PO every 6 hours.
400 mg PO every 6 hours. May divide total daily dose every 8 or 12 hours. Up to 4 g/day may be used.
30 to 50 mg/kg/day PO in 3 to 4 divided doses. Up to 100 mg/kg/day (Max: 4 g/day) may be used.
10 mg/kg/dose PO every 6 hours.
250 mg PO every 6 hours or 500 mg PO every 12 hours. Up to 4 g/day may be used. Twice-daily dosing is not recommended with doses more than 1 g/day.
30 to 50 mg/kg/day PO in 3 to 4 divided doses. Up to 100 mg/kg/day (Max: 4 g/day) may be used.
10 mg/kg/dose PO every 6 hours.
15 to 20 mg/kg/day IV divided every 6 hours (Max: 4 g/day).
15 to 20 mg/kg/day IV divided every 6 hours (Max: 4 g/day).
10 mg/kg/dose IV every 6 hours.
500 mg PO every 6 hours for 5 to 14 days.
30 to 50 mg/kg/day PO in 3 to 4 divided doses (Max: 2 g/day) for 5 to 14 days.
10 mg/kg/dose PO every 6 hours for 5 to 14 days.
400 mg PO every 6 hours for 5 to 14 days. [48677]
30 to 50 mg/kg/day PO in 3 to 4 divided doses (Max: 1.6 g/day) for 5 to 14 days.
10 mg/kg/dose PO every 6 hours for 5 to 14 days.
500 mg PO every 6 hours for 7 days.
400 mg PO every 6 hours for 7 days. [48677]
500 mg PO every 6 hours for 7 to 14 days for mild infections in patients allergic or intolerant to beta-lactams or at high risk for methicillin-resistant S. aureus. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.
400 mg PO every 6 hours 7 to 14 days for mild infections in patients allergic or intolerant to beta-lactams or at high risk for methicillin-resistant S. aureus. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease. [48677]
500 mg PO every 6 hours for 10 days has been used.
500 mg PO 4 times daily as an alternative for at least 3 weeks and until all lesions have completely healed. Consider adding a second antibiotic if lesions do not respond within the first few days of therapy. Erythromycin is recommended for pregnant and lactating patients.
500 mg PO 4 times daily as an alternative for at least 3 weeks and until all lesions have completely healed. Consider adding a second antibiotic if lesions do not respond within the first few days of therapy.
500 mg PO every 6 hours for at least 3 months.
40 mg/kg/day PO in 4 divided doses (Max: 2 g/day) for at least 3 months.
500 mg IV every 6 hours for at least 3 months.
20 mg/kg/day IV in 4 divided doses (Max: 2 g/day) for at least 3 months.
500 mg PO every 6 hours for 2 weeks to 3 months for uncomplicated infections. Add rifampin and treat complicated infections for 3 months. Treat relapses for 4 to 6 months.
40 mg/kg/day PO in 4 divided doses (Max: 2 g/day) for 2 weeks to 3 months for uncomplicated infections. Add rifampin and treat complicated infections for 3 months. Treat relapses for 4 to 6 months.
500 mg IV every 6 hours 2 weeks to 3 months for uncomplicated infections. Add rifampin and treat complicated infections for 3 months. Treat relapses for 4 to 6 months.
20 mg/kg/day IV in 4 divided doses (Max: 2 g/day) for 2 weeks to 3 months for uncomplicated infections. Add rifampin and treat complicated infections for 3 months. Treat relapses for 4 to 6 months.
500 mg PO every 6 hours for 3 to 4 months. Add rifampin for complicated infections. Treat relapses for 4 to 6 months.
40 mg/kg/day PO in 4 divided doses (Max: 2 g/day) for 3 to 4 months. Add rifampin for complicated infections. Treat relapses for 4 to 6 months.
500 mg IV every 6 hours for 3 to 4 months. Add rifampin for complicated infections. Treat relapses for 4 to 6 months.
20 mg/kg/day IV in 4 divided doses (Max: 2 g/day) for 3 to 4 months. Add rifampin for complicated infections. Treat relapses for 4 to 6 months.
500 mg PO every 6 hours for at least 3 months plus rifampin.
500 mg PO every 6 hours for at least 3 months plus rifampin.
500 mg IV every 6 hours for at least 3 months plus rifampin.
500 mg IV every 6 hours for at least 3 months plus rifampin.
500 mg PO every 6 hours for 14 days as second-line therapy.
7.5 to 12.5 mg/kg/dose (Max: 500 mg/dose) PO every 6 hours for 14 days as second-line therapy.
10 mg/kg/dose (Max: 250 mg/dose) PO twice daily until at least age 5 years.
10 mg/kg/dose (Max: 125 mg/dose) PO twice daily. Continue prophylaxis until at least age 5 years.
125 to 375 mg PO twice daily (approximately 30 to 40 mg/kg/day PO in 2 divided doses). 125 mg PO twice daily was successfully used in patients with moderate acne (n = 18) in a case series of 29 infants and children 6 to 16 months of age with infantile acne. Higher doses (250 or 375 mg twice daily) were necessary in patients with severe acne.
Apply a thin layer of a 2% topical preparation to the affected area twice daily. Due to a slow onset of action and the increased risk of the development of bacterial resistance, topical antibiotic monotherapy is not recommended. If topical antibiotic therapy is continued longer than a few weeks, the addition of topical benzoyl peroxide is recommended.
500 mg PO 4 times daily for 21 days is recommended as an alternative.
500 mg PO 4 times daily for 21 days is recommended as an alternative.
250 mg IV every 6 hours in combination with IV ampicillin for 48 hours followed by oral step-down therapy for 5 days. A 7-day course of therapy with broad-spectrum antibiotics is recommended for pregnant persons with preterm PROM who are less than 34 0/7 weeks gestation. Persons with preterm PROM who are candidates for Group B streptococcal (GBS) intrapartum prophylaxis should receive GBS prophylaxis to prevent vertical transmission regardless of earlier treatments.
250 mg IV every 6 hours in combination with IV ampicillin for 48 hours followed by oral step-down therapy for 5 days. A 7-day course of therapy with broad-spectrum antibiotics is recommended for pregnant persons with preterm PROM who are less than 34 0/7 weeks gestation. Persons with preterm PROM who are candidates for Group B streptococcal (GBS) intrapartum prophylaxis should receive GBS prophylaxis to prevent vertical transmission regardless of earlier treatments.
333 mg PO every 8 hours in combination with oral amoxicillin for 5 days as step-down therapy after 48 hours of IV therapy. A 7-day course of therapy with broad-spectrum antibiotics is recommended for pregnant persons with preterm PROM who are less than 34 0/7 weeks gestation. Alternatively, 250 mg PO every 6 hours for 10 days as monotherapy has been recommended. Persons with preterm PROM who are candidates for Group B streptococcal (GBS) intrapartum prophylaxis should receive GBS prophylaxis to prevent vertical transmission regardless of earlier treatments.
333 mg PO every 8 hours in combination with oral amoxicillin for 5 days as step-down therapy after 48 hours of IV therapy. A 7-day course of therapy with broad-spectrum antibiotics is recommended for pregnant persons with preterm PROM who are less than 34 0/7 weeks gestation. Alternatively, 250 mg PO every 6 hours for 10 days as monotherapy has been recommended. Persons with preterm PROM who are candidates for Group B streptococcal (GBS) intrapartum pr
ophylaxis should receive GBS prophylaxis to prevent vertical transmission regardless of earlier treatments.For the treatment of bronchiectasis† to reduce exacerbations in patients with high exacerbation rates. Oral dosage (Erythromycin ethylsuccinate) Adults
400 mg PO twice daily has been recommended to reduce exacerbation rates. Consider treatment for a minimum of 6 to 12 months to assess efficacy in reducing exacerbations; stop if no symptomatic improvement. Breaks in therapy may be considered to reduce treatment burden.
250 mg PO every 6 hours or 1 g PO every 12 hours for 7 to 10 days.
30 to 50 mg/kg/day (Max: 1 g/day) PO divided every 6 to 8 hours for 7 to 10 days.
250 mg PO every 6 hours for at least 14 days to 21 days.
30 to 50 mg/kg/day (as base) PO divided every 6 to 8 hours (Max: 500 mg/dose) for at least 14 to 28 days.
500 mg PO every 6 hours if a relapse occurs after at least 3 months of treatment. For persons living with HIV, discontinuation may be considered after 3 to 4 months of treatment and CD4 count more than 200 cells/mm3 for at least 6 months. Some experts suggest that Bartonella titers also decrease by 4-fold before discontinuing suppressive therapy.[34362]
500 mg PO every 6 hours if a relapse occurs after at least 3 months of treatment. For persons living with HIV, discontinuation may be considered after 3 to 4 months of treatment and CD4 count more than 200 cells/mm3 for at least 6 months. Some experts suggest that Bartonella titers also decrease by 4-fold before discontinuing suppressive therapy.[34362]
500 mg to 1 g IV every 6 hours for 2 to 6 weeks, followed by oral therapy for 6 to 12 months. Shorter courses may be appropriate for less extensive infections.
500 mg PO every 6 hours for 6 to 12 months after IV therapy. Shorter courses may be appropriate for less extensive infections.
†Indicates off-label use
Dosing Considerations
Erythromycin should be used with caution in patients with impaired hepatic function. Although specific dosage guidelines are not available, a reduced dosage may be necessary.
Renal ImpairmentNo dosage adjustment needed.
Drug Interactions
Abarelix: (Major) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation, such as erythromycin.
Abemaciclib: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with erythromycin is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Acalabrutinib: (Major) Decrease the acalabrutinib dose to 100 mg PO once daily if coadministered with erythromycin. Coadministration may result in increased acalabrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Acalabrutinib is a CYP3A4 substrate; erythromycin is a moderate CYP3A4 inhibitor. In physiologically based pharmacokinetic (PBPK) simulations, the Cmax and AUC values of acalabrutinib were increased by 2- to almost 3-fold when acalabrutinib was coadministered with moderate CYP3A inhibitors.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Inhibitors of the hepatic CYP4501A2, such as erythromycin, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine related side effects. In such patients, the dosage of caffeine containing medications or the ingestion of caffeine containing products may need to be reduced.
Acetaminophen; Caffeine: (Moderate) Inhibitors of the hepatic CYP4501A2, such as erythromycin, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine related side effects. In such patients, the dosage of caffeine containing medications or the ingestion of caffeine containing products may need to be reduced.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with erythromycin may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of erythromycin could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If erythromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Erythromycin is a moderate inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. (Moderate) Inhibitors of the hepatic CYP4501A2, such as erythromycin, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine related side effects. In such patients, the dosage of caffeine containing medications or the ingestion of caffeine containing products may need to be reduced.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Inhibitors of the hepatic CYP4501A2, such as erythromycin, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine related side effects. In such patients, the dosage of caffeine containing medications or the ingestion of caffeine containing products may need to be reduced.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with erythromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of erythromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If erythromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Erythromycin is a moderate inhibitor of CYP3A4.
Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of erythromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like erythromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If erythromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of erythromycin is necessary. If erythromycin is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like erythromycin can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If erythromycin is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Adagrasib: (Major) Concomitant use of adagrasib and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Afatinib: (Moderate) If the concomitant use of erythromycin and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of erythromycin. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-glycoprotein (P-gp) substrate and erythromycin is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib.
Albuterol; Budesonide: (Moderate) Avoid coadministration of oral budesonide with erythromycin due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Alfentanil: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of erythromycin is necessary. If erythromycin is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A substrate, and coadministration with CYP3A inhibitors like erythromycin can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If erythromycin is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Alfuzosin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), alfuzosin and erythromycin should be used together cautiously. Based on electrophysiology studies performed by the manufacturer, alfuzosin may prolong the QT interval in a dose-dependent manner. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known to prolong the QT interval. Erythromycin administration is associated with QT prolongation and TdP. In addition, coadministration of erythromycin, a CYP3A4 inhibitor, with alfuzosin, a CYP3A4 substrate, may result in elevated alfuzosin plasma concentrations.
Alosetron: (Moderate) Pharmacodynamic interactions between alosetron and drugs that enhance peristalsis are theoretically possible, based on opposing pharmacologic outcomes. It may be prudent to avoid use of erythromycin (when used to enhance GI motility) during alosetron treatment. Although a potential interaction has not been studied, erythromycin might negate the effect of alosetron. Caution and close monitoring are advised if these drugs are used together.
Alprazolam: (Major) Avoid coadministration of alprazolam and erythromycin due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with erythromycin, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. Coadministration with erythromycin increased alprazolam exposure by 1.61-fold.
Amiodarone: (Major) Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. In addition to potential pharmacokinetic interactions, erythromycin may cause QT prolongation and exhibit additive electrophysiologic effects with Class III antiarrhythmics. Concurrent use of erythromycin with amiodarone should be avoided. In addition, erythromycin may theoretically increase plasma concentrations of amiodarone via inhibition of CYP3A4. Higher antiarrhythmic plasma concentrations increase the potential risk of QT prolongation, TdP or other proarrhythmias.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with erythromycin. Amisulpride causes dose- and concentration- dependent QT prolongation. Erythromycin is associated with QT prolongation and TdP.
Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with erythromycin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Atorvastatin: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with erythromycin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure. (Moderate) Use caution and the lowest atorvastatin dose necessary if coadministration with erythromycin is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Use the lowest possible atorvastatin dose. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Atorvastatin is a CYP3A and OATP1B1/3 substrate; erythromycin is a moderate CYP3A and OATP1B1/3 inhibitor.
Amlodipine; Benazepril: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with erythromycin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Celecoxib: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with erythromycin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Olmesartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with erythromycin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Valsartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with erythromycin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with erythromycin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amoxapine: (Moderate) Erythromycin may be used to stimulate GI motility, such as in patients with diabetic gastroparesis. Some cyclic antidepressants with substantial antimuscarinic properties, such as amoxapine, may counteract erythromycin's effectiveness in enhancing GI motility.
Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include erythromycin.
Apomorphine: (Major) Concomitant use of apomorphine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Aprepitant, Fosaprepitant: (Major) Avoid coadministration of erythromycin and aprepitant due to substantially increased exposure of aprepitant. Fosaprepitant is rapidly converted to aprepitant; therefore, a similar interaction is likely. If coadministration cannot be avoided, use caution, and monitor for an increase in aprepitant-related adverse effects for several days after administration of a multi-day aprepitant regimen. Erythromycin is a moderate CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of daily oral aprepitant (230 mg, or 1.8 times the recommended single dose) with another moderate CYP3A4 inhibitor increased the aprepitant AUC 2-fold.
Aripiprazole: (Major) Avoid concomitant use aripiprazole and erythromycin, if possible, especially in patients with risk factors for torsade de pointes (TdP). If concomitant use is necessary, patients receiving both a CYP2D6 inhibitor plus erythromycin may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. Additionally, consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Concomitant use increases the risk for QT/QTc prolongation and TdP and may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate, erythromycin is a moderate CYP3A inhibitor, and both medications have been associated with QT interval prolongation.
Armodafinil: (Moderate) Armodafinil is partially metabolized by CYP3A4/5 isoenzymes. Interactions with potent inhibitors of CYP3A4 such as erythromycin are possible. However, because armodafinil is itself an inducer of the CYP3A4 isoenzyme, drug interactions due to CYP3A4 inhibition by other medications may be complex and difficult to predict. Observation of the patient for increased effects from armodafinil may be needed.
Arsenic Trioxide: (Major) Concurrent use of arsenic trioxide and erythromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, erythromycin should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported. Erythromycin is also associated with QT prolongation and TdP.
Artemether; Lumefantrine: (Major) Avoid coadministration of artemether and erythromycin due to the increased potential of QT prolongation. Consider ECG monitoring if erythromycin must be used with or after artemether treatment. Additionally, erythromycin is an inhibitor of CYP3A4 and artemether is a substrate of CYP3A4; therefore, coadministration may lead to increased concentrations of artemether. (Major) Avoid coadministration of lumefantrine and erythromycin due to the increased potential of QT prolongation. Consider ECG monitoring if erythromycin must be used with or after lumefantrine treatment. Additionally, erythromycin is an inhibitor of CYP3A4 and lumefantrine is a substrate of CYP3A4; therefore, coadministration may lead to increased concentrations of lumefantrine.
Asenapine: (Major) Concomitant use of asenapine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Inhibitors of the hepatic CYP4501A2, such as erythromycin, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine related side effects. In such patients, the dosage of caffeine containing medications or the ingestion of caffeine containing products may need to be reduced.
Aspirin, ASA; Caffeine: (Moderate) Inhibitors of the hepatic CYP4501A2, such as erythromycin, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine related side effects. In such patients, the dosage of caffeine containing medications or the ingestion of caffeine containing products may need to be reduced.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Inhibitors of the hepatic CYP4501A2, such as erythromycin, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine related side effects. In such patients, the dosage of caffeine containing medications or the ingestion of caffeine containing products may need to be reduced.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with erythromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of erythromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If erythromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Erythromycin is a moderate inhibitor of CYP3A4.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of erythromycin is necessary. If erythromycin is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like erythromycin can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If erythromycin is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Atazanavir; Cobicistat: (Major) Avoid concurrent use of erythromycin with regimens containing cobicistat and atazanavir or darunavir; use of an alternative antibiotic is recommended. Taking these drugs together may result in elevated concentrations of erythromycin, cobicistat, atazanavir and darunavir. Erythromycin is a CYP3A4 inhibitor and a P-glycoprotein (P-gp) substrate. Cobicistat is a substrate of CYP3A4 and a P-gp inhibitor, while both atazanavir and darunavir are CYP3A4 substrates.
Atogepant: (Major) Limit the dose of atogepant to 10 or 30 mg PO once daily for episodic migraine or 30 mg PO once daily for chronic migraine if coadministered with erythromycin. Concurrent use may increase atogepant exposure and the risk of adverse effects. Atogepant is a substrate of OATP1B1 and OATP1B3 and erythromycin is an OATP inhibitor. Coadministration with an OATP1B1/3 inhibitor resulted in a 2.85-fold increase in atogepant overall exposure and a 2.23-fold increase in atogepant peak concentration.
Atomoxetine: (Major) Concomitant use of atomoxetine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Atorvastatin: (Moderate) Use caution and the lowest atorvastatin dose necessary if coadministration with erythromycin is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Use the lowest possible atorvastatin dose. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Atorvastatin is a CYP3A and OATP1B1/3 substrate; erythromycin is a moderate CYP3A and OATP1B1/3 inhibitor.
Atorvastatin; Ezetimibe: (Moderate) Use caution and the lowest atorvastatin dose necessary if coadministration with erythromycin is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Use the lowest possible atorvastatin dose. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Atorvastatin is a CYP3A and OATP1B1/3 substrate; erythromycin is a moderate CYP3A and OATP1B1/3 inhibitor.
Atropine; Difenoxin: (Minor) Diphenoxylate/difenoxin decreases GI motility. It may antagonize the muscarinic and/or prokinetic effects of erythromycin (when used for GI motility). Use these drugs in combination should be avoided.
Avanafil: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving erythromycin. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. Coadministration with erythromycin increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Avapritinib: (Major) Avoid coadministration of avapritinib with erythromycin due to the risk of increased avapritinib-related adverse reactions. If concurrent use is unavoidable, reduce the starting dose of avapritinib from 300 mg PO once daily to 100 mg PO once daily in patients with gastrointestinal stromal tumor or from 200 mg PO once daily to 50 mg PO once daily in patients with advanced systemic mastocytosis. Avapritinib is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. Coadministration of avapritinib 300 mg PO once daily with a moderate CYP3A4 inhibitor is predicted to increase the AUC of avapritinib by 210% at steady-state.
Azelastine: (Minor) Coadministration of orally administered azelastine (4 mg twice daily) with erythromycin (500 mg three times daily for 7 days) resulted in a slightly lower Cmax and a slightly higher AUC for azelastine compared to azelastine alone. The clinical relevance is unknown.
Azelastine; Fluticasone: (Minor) Coadministration of orally administered azelastine (4 mg twice daily) with erythromycin (500 mg three times daily for 7 days) resulted in a slightly lower Cmax and a slightly higher AUC for azelastine compared to azelastine alone. The clinical relevance is unknown.
Bedaquiline: (Major) Concurrent use of bedaquiline and a strong CYP3A4 inhibitor, such as erythromycin, for more than 14 days should be avoided unless the benefits justify the risks. When administered together, erythromycin may inhibit the metabolism of bedaquiline resulting in increased systemic exposure (AUC) and potentially more adverse reactions. Furthermore, since both drugs are associated with QT prolongation, coadministration may result in additive prolongation of the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. An interaction with topically applied erythromycin is not expected.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with erythromycin may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of erythromycin in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If erythromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4. Erythromycin is a moderate inhibitor of CYP3A4.
Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking erythromycin. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Berotralstat is a P-gp substrate and erythromycin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased berotralstat exposure by 69%.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving erythromycin. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving erythromycin. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; erythromycin inhibits P-gp.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bortezomib: (Minor) Erythromycin can inhibit the hepatic metabolism of other drugs, such as borezomib, increasing their serum concentrations and potentially causing toxicity. If therapy with erythromycin is necessary, a reduction in the dose of bortezomib may be required. Such patients should be monitored carefully and lower doses should be used.
Bosentan: (Moderate) Co-administration of bosentan with erythromycin, a CYP3A4 inhibitor, may increase the plasma concentrations of bosentan. The potential for increased bosentan effects should be monitored. The severity of this interaction is increased when erythromycin is combined with a potent CYP 2C9 inhibitor, like sulfisoxazole.
Bosutinib: (Major) Avoid concomitant use of bosutinib and erythromycin as bosutinib plasma exposure may be significantly increased resulting in an increased risk of bosutinib adverse events (e.g., myelosuppression, GI toxicity). Bosutinib is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. In a cross-over trial in 18 healthy volunteers, the Cmax and AUC values of bosutinib were increased 1.5-fold and 2-fold, respectively, when bosutinib 500 mg PO was administered with a single dose of a moderate CYP3A4 inhibitor.
Brexpiprazole: (Moderate) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Erythromycin is a moderate inhibitor of CYP3A4. If erythromycin is used in combination with brexpiprazole and a moderate to strong CYP2D6 inhibitor, the brexpiprazole dose should be adjusted and the patient should be carefully monitored for brexpiprazole-related adverse reactions. A reduction of the brexpiprazole dose to 25% of the usual dose is also recommended in patients who are poor metabolizers of CYP2D6 and are receiving a moderate CYP3A4 inhibitor.
Brigatinib: (Major) Avoid coadministration of brigatinib with erythromycin if possible due to increased plasma exposure of brigatinib; an increase in brigatinib-related adverse reactions may occur. If concomitant use is unavoidable, reduce the dose of brigatinib by approximately 40% without breaking tablets (i.e., from 180 mg to 120 mg; from 120 mg to 90 mg; from 90 mg to 60 mg); after discontinuation of erythromycin, resume the brigatinib dose that was tolerated prior to initiation of erythromycin. Brigatinib is a CYP3A4 substrate; erythromycin is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor is predicted to increase the AUC of brigatinib by approximately 40%.
Brincidofovir: (Moderate) Postpone the administration of erythromycin for at least three hours after brincidofovir administration and increase monitoring for brincidofovir-related adverse reactions (i.e., elevated hepatic enzymes and bilirubin, diarrhea, other gastrointestinal adverse events) if concomitant use of brincidofovir and erythromycin is necessary. Brincidofovir is an OATP1B1/3 substrate and erythromycin is an OATP1B1/3 inhibitor. In a drug interaction study, the mean AUC and Cmax of brincidofovir increased by 374% and 269%, respectively, when administered with another OATP1B1/3 inhibitor.
Bromocriptine: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of erythromycin. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; erythromycin is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Budesonide: (Moderate) Avoid coadministration of oral budesonide with erythromycin due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Budesonide; Formoterol: (Moderate) Avoid coadministration of oral budesonide with erythromycin due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Avoid coadministration of oral budesonide with erythromycin due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Buprenorphine: (Major) Concomitant use of buprenorphine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use can also increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when erythromycin is added after a stable buprenorphine dose is achieved. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, consider dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping erythromycin, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If erythromycin is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Buprenorphine is a CYP3A4 substrate and erythromycin is a CYP3A4 inhibitor.
Buprenorphine; Naloxone: (Major) Concomitant use of buprenorphine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use can also increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when erythromycin is added after a stable buprenorphine dose is achieved. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, consider dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping erythromycin, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If erythromycin is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Buprenorphine is a CYP3A4 substrate and erythromycin is a CYP3A4 inhibitor.
Buspirone: (Moderate) Monitor for an increase in buspirone-related adverse reactions if coadministration with erythromycin is necessary; the effect may be more pronounced if the patient has been titrated to a stable dose of buspirone and erythromycin is added or removed from therapy. Buspirone is a sensitive CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with other moderate CYP3A inhibitors increased buspirone exposure by 3.4 to 6-fold and was accompanied by increased buspirone-related adverse reactions.
Butalbital; Acetaminophen; Caffeine: (Moderate) Inhibitors of the hepatic CYP4501A2, such as erythromycin, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine related side effects. In such patients, the dosage of caffeine containing medications or the ingestion of caffeine containing products may need to be reduced.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with erythromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of erythromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If erythromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Erythromycin is a moderate inhibitor of CYP3A4. (Moderate) Inhibitors of the hepatic CYP4501A2, such as erythromycin, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine related side effects. In such patients, the dosage of caffeine containing medications or the ingestion of caffeine containing products may need to be reduced.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with erythromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of erythromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If erythromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Erythromycin is a moderate inhibitor of CYP3A4. (Moderate) Inhibitors of the hepatic CYP4501A2, such as erythromycin, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine related side effects. In such patients, the dosage of caffeine containing medications or the ingestion of caffeine containing products may need to be reduced.
Cabotegravir; Rilpivirine: (Major) Close clinical monitoring is advised when administering erythromycin with rilpivirine due to an increased potential for rilpivirine-related adverse events, including QT prolongation. When possible, alternative antibiotics should be considered. Predictions about the interaction can be made based on metabolic pathways. Erythromycin is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations. Also, supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval, such as erythromycin.
Cabozantinib: (Minor) Monitor for an increase in erythromycin-related adverse reactions if coadministration with cabozantinib is necessary. Erythromycin is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Caffeine: (Moderate) Inhibitors of the hepatic CYP4501A2, such as erythromycin, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine related side effects. In such patients, the dosage of caffeine containing medications or the ingestion of caffeine containing products may need to be reduced. (Moderate) Inhibitors of the hepatic CYP4501A2, such as erythromycin, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine related side effects. In such patients, the dosage of caffeine containing medications or the ingestion of caffeine containing products may need to be reduced.
Caffeine; Sodium Benzoate: (Moderate) Inhibitors of the hepatic CYP4501A2, such as erythromycin, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine related side effects. In such patients, the dosage of caffeine containing medications or the ingestion of caffeine containing products may need to be reduced.
Carbamazepine: (Moderate) Monitor carbamazepine concentrations closely during coadministration of erythromycin; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and erythromycin is a CYP3A inhibitor.
Carbidopa; Levodopa; Entacapone: (Moderate) Entacapone should be given cautiously with drugs known to interfere with biliary excretion, glucuronidation or intestinal beta-glucuronidation such as erythromycin. Decreased biliary excretion of entacapone may occur if these agents are given concurrently.
Cariprazine: (Moderate) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Erythromycin is a moderate inhibitor of CYP3A4 and may reduce the hepatic metabolism of CYP3A4 substrates, although the impact of moderate CYP3A4 inhibitors on cariprazine metabolism has not been studied. Monitoring for adverse effects, such as CNS effects and extrapyramidal symptoms, is advisable during coadministration.
Celecoxib; Tramadol: (Moderate) Administration of CYP3A4 inhibitors such as erythromycin with tramadol may affect the metabolism of tramadol leading to altered tramadol exposure. Increased serum tramadol concentrations may occur.
Ceritinib: (Major) Avoid coadministration of ceritinib with erythromycin if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Erythromycin is associated with QT prolongation and torsade de pointes (TdP).
Chloroquine: (Major) Concomitant use of chloroquine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with erythromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of erythromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If erythromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Erythromycin is a moderate inhibitor of CYP3A4.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with erythromycin may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of erythromycin could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If erythromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Erythromycin is a moderate inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of erythromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like erythromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If erythromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Chlorpromazine: (Major) Concurrent use of chlorpromazine and erythromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Erythromycin is associated with QT prolongation and TdP. Phenothiazines have also been associated with a risk of QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine.
Cholera Vaccine: (Major) Avoid the live cholera vaccine in patients that have received erythromycin within 14 days prior to vaccination. Concurrent administration of the live cholera vaccine with antibiotics active against cholera, such as erythromycin, may diminish vaccine efficacy and result in suboptimal immune response. A duration of fewer than 14 days between stopping antibiotics and vaccination might also be acceptable in some clinical settings if travel cannot be avoided before 14 days have elapsed after stopping antibiotics.
Cilostazol: (Major) Erythromycin can inhibit the hepatic metabolism of cilostazol, increasing it's serum concentrations and potentially causing toxicity. When erythromycin or other significant CYP3A4 inhibitors are coadministered with cilostazol, the manufacturer recommends that the cilostazol dosage be reduced by 50%.
Ciprofloxacin: (Major) Concomitant use of ciprofloxacin and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cisapride: (Contraindicated) Avoid concomitant use of erythromycin and cisapride due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Citalopram: (Major) Concomitant use of citalopram and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clofazimine: (Major) Concomitant use of clofazimine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clonazepam: (Moderate) Monitor for increased sedation and respiratory depression if clonazepam is coadministered with erythromycin; adjust the dose of clonazepam if necessary. The systemic exposure of clonazepam may be increased resulting in an increase in treatment-related adverse reactions. Clonazepam is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Clorazepate: (Moderate) CYP3A4 inhibitors, such as erythromycin, may reduce the metabolism of clorazepate and increase the potential for benzodiazepine toxicity.
Clozapine: (Major) Concurrent use of erythromycin and clozapine should be avoided if possible. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death and erythromycin has an established risk of QT prolongation and TdP. A case report has documented increased serum clozapine concentrations and the occurrence of a seizure when erythromycin was added to a stable dose of clozapine. Erythromycin is an inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of clozapine. Elevated plasma concentrations of clozapine occurring through CYP inhibition may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. According to the manufacturer, patients receiving clozapine in combination with an inhibitor of CYP3A4 should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. If the inhibitor is discontinued after dose adjustments are made, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary.
Cobicistat: (Major) Avoid concurrent use of erythromycin with regimens containing cobicistat and atazanavir or darunavir; use of an alternative antibiotic is recommended. Taking these drugs together may result in elevated concentrations of erythromycin, cobicistat, atazanavir and darunavir. Erythromycin is a CYP3A4 inhibitor and a P-glycoprotein (P-gp) substrate. Cobicistat is a substrate of CYP3A4 and a P-gp inhibitor, while both atazanavir and darunavir are CYP3A4 substrates.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with chronic erythromycin therapy due to the risk of cobimetinib toxicity. If concurrent short-term (14 days or less) use of erythromycin is unavoidable, reduce the dose of cobimetinib to 20 mg once daily for patients normally taking 60 mg daily; after discontinuation of erythromycin, resume cobimetinib at the previous dose. Use an alternative to erythromycin in patients who are already taking a reduced dose of cobimetinib (40 or 20 mg daily). Cobimetinib is a P-glycoprotein (P-gp) substrate as well as a CYP3A substrate in vitro; erythromycin is a moderate inhibitor of both CYP3A and P-gp. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), a strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7).
Codeine: (Moderate) Concomitant use of codeine with erythromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of erythromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If erythromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Erythromycin is a moderate inhibitor of CYP3A4.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with erythromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of erythromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If erythromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Erythromycin is a moderate inhibitor of CYP3A4.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with erythromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of erythromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If erythromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Erythromycin is a moderate inhibitor of CYP3A4.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of promethazine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Moderate) Concomitant use of codeine with erythromycin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of erythromycin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If erythromycin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Erythromycin is a moderate inhibitor of CYP3A4.
Codeine; Promethazine: (Major) Concomitant use of promethazine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in pati
Colchicine: (Major) Avoid concomitant use of colchicine and erythromycin due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and erythromycin is a dual moderate CYP3A and P-gp inhibitor. Concomitant use with other dual moderate CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 2- to 3.6-fold.
Conivaptan: (Moderate) Caution is warranted with concomitant use of conivaptan, a CYP3A4 substrate, and erythromycin, a moderate CYP3A4 inhibitor. Coadministration may result in elevated concentrations of conivaptan.
Conjugated Estrogens: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as erythromycin may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea, breast tenderness, and endometrial hyperplasia. Patients receiving estrogens should be monitored for an increase in adverse events. In addition, when chronically coadministering erythromycin ( > 30 days) with conjugated estrogens; bazedoxifene, adequate diagnostic measures, including directed or random endometrial sampling when indicated by signs and symptoms of endometrial hyperplasia, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.
Conjugated Estrogens; Bazedoxifene: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as erythromycin may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea, breast tenderness, and endometrial hyperplasia. Patients receiving estrogens should be monitored for an increase in adverse events. In addition, when chronically coadministering erythromycin ( > 30 days) with conjugated estrogens; bazedoxifene, adequate diagnostic measures, including directed or random endometrial sampling when indicated by signs and symptoms of endometrial hyperplasia, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.
Conjugated Estrogens; Medroxyprogesterone: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as erythromycin may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea, breast tenderness, and endometrial hyperplasia. Patients receiving estrogens should be monitored for an increase in adverse events. In addition, when chronically coadministering erythromycin ( > 30 days) with conjugated estrogens; bazedoxifene, adequate diagnostic measures, including directed or random endometrial sampling when indicated by signs and symptoms of endometrial hyperplasia, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.
Crizotinib: (Major) Avoid coadministration of crizotinib with erythromycin due to the risk of QT prolongation; crizotinib exposure may also increase. If concomitant use is unavoidable, monitor for an increase in crizotinib-related adverse reactions, monitor ECGs for QT prolongation, and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib is a CYP3A substrate that has been associated with concentration-dependent QT prolongation. Erythromycin is a moderate CYP3A4 inhibitor that is also associated with QT prolongation and torsade de pointes (TdP).
Cyclosporine: (Major) Erythromycin may inhibit the metabolism of cyclosporine via inhibition of the CYP3A4 isoenzyme, thus increasing cyclosporine's effects and the potential for toxicity. Additionally, erythromycin has been associated with inhibition of P-glycoprotein, which leads to decreased intestinal metabolism and increased oral absorption of cyclosporine. It has been recommend to avoid cyclosporine in combination with macrolide agents or reduce the cyclosporine dosage by 50% when it is necessary to give any macrolide concurrently. Increased cyclosporine concentrations may be seen with 2 days of beginning combination therapy. In managing potential interactions between macrolides and cyclosporine, appropriate monitoring of cyclosporine concentrations is critical to help avoid graft failure or drug-related toxicity.
Dabigatran: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with erythromycin, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE), or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like erythromycin in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with erythromycin, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Daclatasvir: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with erythromycin, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. In addition, the therapeutic effects of erythromycin, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Dapagliflozin; Saxagliptin: (Minor) Saxagliptin plasma concentrations are expected to increase in the presence of moderate CYP 3A4/5 inhibitors such as erythromycin, but saxagliptin dose adjustment is not advised.
Daridorexant: (Major) Limit the daridorexant dose to 25 mg if coadministered with erythromycin. Concomitant use may increase daridorexant exposure and the risk for daridorexant-related adverse effects. Daridorexant is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Concomitant use of another moderate CYP3A inhibitor increased daridorexant overall exposure 2.4-fold.
Darunavir: (Moderate) Concentrations of darunavir may be increased with coadministration, as erythromycin is a CYP3A4 inhibitor and darunavir is a CYP3A4 substrate. Patients should be monitored for increased side effects.
Darunavir; Cobicistat: (Major) Avoid concurrent use of erythromycin with regimens containing cobicistat and atazanavir or darunavir; use of an alternative antibiotic is recommended. Taking these drugs together may result in elevated concentrations of erythromycin, cobicistat, atazanavir and darunavir. Erythromycin is a CYP3A4 inhibitor and a P-glycoprotein (P-gp) substrate. Cobicistat is a substrate of CYP3A4 and a P-gp inhibitor, while both atazanavir and darunavir are CYP3A4 substrates. (Moderate) Concentrations of darunavir may be increased with coadministration, as erythromycin is a CYP3A4 inhibitor and darunavir is a CYP3A4 substrate. Patients should be monitored for increased side effects.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concurrent use of erythromycin with regimens containing cobicistat and atazanavir or darunavir; use of an alternative antibiotic is recommended. Taking these drugs together may result in elevated concentrations of erythromycin, cobicistat, atazanavir and darunavir. Erythromycin is a CYP3A4 inhibitor and a P-glycoprotein (P-gp) substrate. Cobicistat is a substrate of CYP3A4 and a P-gp inhibitor, while both atazanavir and darunavir are CYP3A4 substrates. (Moderate) Concentrations of darunavir may be increased with coadministration, as erythromycin is a CYP3A4 inhibitor and darunavir is a CYP3A4 substrate. Patients should be monitored for increased side effects.
Dasatinib: (Major) Concomitant use of dasatinib and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Deflazacort: (Major) Decrease deflazacort dose to one third of the recommended dosage when coadministered with erythromycin. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Deflazacort is a CYP3A4 substrate; erythromycin is a moderate inhibitor of CYP3A4. Administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold.
Degarelix: (Major) Concomitant use of degarelix and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Deutetrabenazine: (Major) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and erythromycin. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Erythromycin is associated with QT prolongation and torsade de pointes (TdP).
Dexamethasone: (Moderate) Monitor for steroid-related adverse reactions if concomitant use of erythromycin with dexamethasone is necessary. Concomitant use may increase dexamethasone exposure. Dexamethasone is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dextromethorphan; Quinidine: (Major) Concomitant use of quinidine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and may result in increased plasma concentrations of quinidine. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Quinidine is a CYP3A substrate, and erythromycin is a moderate CYP3A inhibitor.
Diazepam: (Moderate) Monitor for an increase in diazepam-related adverse reactions, including sedation and respiratory depression, if coadministration with erythromycin is necessary. Concurrent use may increase diazepam exposure. Diazepam is a CYP3A substrate and erythromycin is a CYP3A inhibitor.
Dienogest; Estradiol valerate: (Minor) As erythromycin inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Digoxin: (Moderate) Monitor digoxin concentrations as appropriate and watch for digoxin-related adverse reactions if coadministration with erythromycin is necessary. The dose of digoxin may need to be adjusted. Concurrent use may increase digoxin exposure by 100%. Digoxin is a P-gp substrate and erythromycin is a P-gp inhibitor.
Diltiazem: (Moderate) Monitor blood pressure and heart rate if coadministration of diltiazem with erythromycin is necessary. Concurrent use may result in elevated diltiazem concentrations. Diltiazem is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Diphenoxylate; Atropine: (Minor) Diphenoxylate/difenoxin decreases GI motility. It may antagonize the muscarinic and/or prokinetic effects of erythromycin (when used for GI motility). Use these drugs in combination should be avoided.
Disopyramide: (Major) Cases of life-threatening interactions have been reported for disopyramide when given with erythromycin. In vitro studies have shown that erythromycin inhibits the metabolism of disopyramide. Avoid the coadministration of disopyramide with agents that are associated with QT interval prolongation, including erythromycin. Additionally, erythromycin may inhibit the CYP3A4 metabolism of disopyramide (CYP3A4 substrate). Disopyramide and erythromycin interact both pharmacokinetically and pharmacodynamically. In two patients, erythromycin caused disopyramide serum concentrations to rise significantly, which was associated with development of QT prolongation and tachyarrhythmias. Also, the antimuscarinic actions of disopyramide can interfere with the motility-enhancing properties of erythromycin in patients receiving erythromycin for this purpose.
Docetaxel: (Minor) Docetaxel is metabolized by cytochrome P450 3A (CYP3A4 and CYP3A5) enzymes. Erythromycin is a CYP3A4 inhibitor. In vitro studies have shown drugs that inhibit, induce, or are also metabolized by CYP3A enzymes can significantly affect the metabolism of docetaxel. In a small pharmacokinetic study, 7 patients received 2 courses of docetaxel, one with concurrent ketoconazole (docetaxel 10 mg/m2) and one without ketoconazole (docetaxel 100mg/m2). The ketoconazole dosage was 200 mg once daily for 3 days. Concurrent administration of ketoconazole decreased the clearance of docetaxel by 49% as compared to giving docetaxel alone. However, there was large interpatient variability in the reduction in clearance. Use docetaxel cautiously when administered concurrently with inducers or inhibitors of CYP3A enzymes.
Dofetilide: (Major) Coadministration of dofetilide and erythromycin is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Erythromycin is associated with QT prolongation and TdP. In addition, erythromycin may theoretically increase plasma concentrations of dofetilide via inhibition of CYP3A4. Higher antiarrhythmic plasma concentrations increase the potential risk of QT prolongation, TdP, or other proarrhythmias.
Dolasetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dolasetron and erythromycin should be used together cautiously. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Erythromycin is associated with QT prolongation and TdP. Concurrent use may increase the risk of QT prolongation.
Dolutegravir; Rilpivirine: (Major) Close clinical monitoring is advised when administering erythromycin with rilpivirine due to an increased potential for rilpivirine-related adverse events, including QT prolongation. When possible, alternative antibiotics should be considered. Predictions about the interaction can be made based on metabolic pathways. Erythromycin is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations. Also, supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval, such as erythromycin.
Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Erythromycin has a possible risk for QT prolongation and TdP and use of erythromycin should be used cautiously and with close monitoring with donepezil. In addition, donepezil is partially metabolized by CYP3A4 and coadministration with CYP3A4 inhibitors, such as erythromycin, may increase donepezil concentrations, potentially resulting in dose-related toxicity. However, the clinical effect of such an interaction on the response to donepezil has not been determined.
Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Erythromycin has a possible risk for QT prolongation and TdP and use of erythromycin should be used cautiously and with close monitoring with donepezil. In addition, donepezil is partially metabolized by CYP3A4 and coadministration with CYP3A4 inhibitors, such as erythromycin, may increase donepezil concentrations, potentially resulting in dose-related toxicity. However, the clinical effect of such an interaction on the response to donepezil has not been determined.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with erythromycin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erythromycin is a P-gp inhibitor.
Doxercalciferol: (Moderate) CYP450 enzyme inhibitors, like erythromycin, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
Doxorubicin Liposomal: (Major) Avoid coadministration of erythromycin with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Erythromycin is a CYP3A4 and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of CYP3A4 and P-gp. Concurrent use of CYP3A4 or P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of erythromycin with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Erythromycin is a CYP3A4 and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of CYP3A4 and P-gp. Concurrent use of CYP3A4 or P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Dronabinol: (Major) Use caution if coadministration of dronabinol with erythromycin is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; erythromycin is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Dronedarone: (Contraindicated) Avoid concomitant use of erythromycin and dronedarone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include erythromycin.
Drospirenone; Estradiol: (Minor) As erythromycin inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Dutasteride: (Moderate) Dutasteride is metabolized by CYP3A4 enzyme and CYP3A5 isoenzymes. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors, such as erythromycin.
Dutasteride; Tamsulosin: (Moderate) Dutasteride is metabolized by CYP3A4 enzyme and CYP3A5 isoenzymes. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors, such as erythromycin. (Moderate) Use caution if coadministration of erythromycin with tamsulosin is necessary, especially at a tamsulosin dose higher than 0.4 mg, as the systemic exposure of tamsulosin may be increased resulting in increased treatment-related adverse reactions including hypotension, dizziness, and vertigo. Tamsulosin is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Duvelisib: (Moderate) Monitor for increased toxicity of duvelisib if coadministered with erythromycin. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; erythromycin is a moderate CYP3A inhibitor.
Edoxaban: (Major) Reduce the dose of edoxaban to 30 mg/day PO in patients being treated for deep venous thrombosis (DVT) or pulmonary embolism and receiving concomitant therapy with erythromycin. No dosage adjustment is required in patients with atrial fibrillation. Edoxaban is a P-glycoprotein (P-gp) substrate and erythromycin is a P-gp inhibitor. Increased concentrations of edoxaban may occur during concomitant use of erythromycin; monitor for increased adverse effects of edoxaban.
Efavirenz: (Major) Consider alternative therapy as the coadministration of efavirenz and erythromycin may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Erythromycin is associated with QT prolongation and TdP. In addition, concurrent use may increase the systemic concentration of efavirenz as efavirenz is a CYP3A4 substrate, while erythromycin is a CYP3A4 inhibitor.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Consider alternative therapy as the coadministration of efavirenz and erythromycin may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Erythromycin is associated with QT prolongation and TdP. In addition, concurrent use may increase the systemic concentration of efavirenz as efavirenz is a CYP3A4 substrate, while erythromycin is a CYP3A4 inhibitor. (Moderate) Coadministration of tenofovir disoproxil fumarate with erythromycin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erythromycin is a P-gp inhibitor.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Consider alternative therapy as the coadministration of efavirenz and erythromycin may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Erythromycin is associated with QT prolongation and TdP. In addition, concurrent use may increase the systemic concentration of efavirenz as efavirenz is a CYP3A4 substrate, while erythromycin is a CYP3A4 inhibitor. (Moderate) Coadministration of tenofovir disoproxil fumarate with erythromycin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erythromycin is a P-gp inhibitor.
Elacestrant: (Major) Avoid concomitant use of elacestrant and erythromycin due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Elagolix: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as erythromycin is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Erythromycin significantly inhibits OATP1B1, and also inhibits CYP3A and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. Consider an alternative to erythromycin in a patient receiving elagolix.
Elagolix; Estradiol; Norethindrone acetate: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as erythromycin is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Erythromycin significantly inhibits OATP1B1, and also inhibits CYP3A and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. Consider an alternative to erythromycin in a patient receiving elagolix. (Minor) As erythromycin inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with erythromycin may cause the plasma concentrations of all three drugs to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Erythromycin is a substrate and moderate inhibitor of CYP3A. Both elbasvir and grazoprevir are metabolized by CYP3A, and grazoprevir is also a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of hepatotoxicity.
Eletriptan: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with erythromycin. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A, and erythromycin is a moderate CYP3A inhibitor. Coadministration of other moderate CYP3A inhibitors increased the eletriptan AUC by 2 to 4-fold.
Elexacaftor; tezacaftor; ivacaftor: (Major) Adjust the tezacaftor; ivacaftor dosing schedule when coadministered with erythromycin; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days (i.e., tezacaftor/ivacaftor tablet on Day 1 and ivacaftor tablet on Day 2). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); erythromycin is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure 3-fold. Simulation suggests a moderate inhibitor may increase tezacaftor exposure 2-fold. (Major) If erythromycin and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold. (Major) Reduce the dosing frequency of elexacaftor; tezacaftor; ivacaftor to every other day in the morning when coadministered with erythromycin; omit the ivacaftor evening dose and administer in the morning every other day alternating with elexacaftor; tezacaftor; ivacaftor (i.e., recommended dose of elexacaftor; tezacaftor; ivacaftor on day 1 in the morning and recommended dose of ivacaftor on day 2 in the morning). Coadministration may increase elexacaftor; tezacaftor; ivacaftor exposure and adverse reactions. Elexacaftor, tezacaftor, and ivacaftor are CYP3A substrates; erythromycin is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure by 2.9-fold. Simulation suggests a moderate inhibitor may increase elexacaftor and tezacaftor exposure by 2.3-fold and 2.1-fold, respectively.
Eliglustat: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of erythromycin (including erythromycin; sulfisoxazole) and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EMs), coadministration of erythromycin and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both erythromycin and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Both eliglustat and erythromycin can independently prolong the QT interval, and coadministration increases this risk. Erythromycin is a moderate CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors, such as erythromycin, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A.
Eluxadoline: (Major) Consider reduction of the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity) if coadministered with erythromycin. Coadministration may increase exposure of eluxadoline. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. Eluxadoline is an OATP1B1 substrate and erythromycin is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concurrent use of erythromycin with regimens containing cobicistat and atazanavir or darunavir; use of an alternative antibiotic is recommended. Taking these drugs together may result in elevated concentrations of erythromycin, cobicistat, atazanavir and darunavir. Erythromycin is a CYP3A4 inhibitor and a P-glycoprotein (P-gp) substrate. Cobicistat is a substrate of CYP3A4 and a P-gp inhibitor, while both atazanavir and darunavir are CYP3A4 substrates.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent use of erythromycin with regimens containing cobicistat and atazanavir or darunavir; use of an alternative antibiotic is recommended. Taking these drugs together may result in elevated concentrations of erythromycin, cobicistat, atazanavir and darunavir. Erythromycin is a CYP3A4 inhibitor and a P-glycoprotein (P-gp) substrate. Cobicistat is a substrate of CYP3A4 and a P-gp inhibitor, while both atazanavir and darunavir are CYP3A4 substrates. (Moderate) Coadministration of tenofovir disoproxil fumarate with erythromycin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erythromycin is a P-gp inhibitor.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Close clinical monitoring is advised when administering erythromycin with rilpivirine due to an increased potential for rilpivirine-related adverse events, including QT prolongation. When possible, alternative antibiotics should be considered. Predictions about the interaction can be made based on metabolic pathways. Erythromycin is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations. Also, supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval, such as erythromycin.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Close clinical monitoring is advised when administering erythromycin with rilpivirine due to an increased potential for rilpivirine-related adverse events, including QT prolongation. When possible, alternative antibiotics should be considered. Predictions about the interaction can be made based on metabolic pathways. Erythromycin is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations. Also, supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval, such as erythromycin. (Moderate) Coadministration of tenofovir disoproxil fumarate with erythromycin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erythromycin is a P-gp inhibitor.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with erythromycin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erythromycin is a P-gp inhibitor.
Encorafenib: (Major) Avoid coadministration of encorafenib and erythromycin due to increased encorafenib exposure and QT prolongation. If concurrent use cannot be avoided, reduce the encorafenib dose to one-half of the dose used prior to the addition of erythromycin. Monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. If erythromycin is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of erythromycin. Encorafenib is a CYP3A4 substrate that has been associated with dose-dependent QT prolongation; erythromycin is a moderate CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Coadministration of a moderate CYP3A4 inhibitor with a single 50 mg dose of encorafenib (0.1 times the recommended dose) increased the encorafenib AUC and Cmax by 2-fold and 45%, respectively.
Entacapone: (Moderate) Entacapone should be given cautiously with drugs known to interfere with biliary excretion, glucuronidation or intestinal beta-glucuronidation such as erythromycin. Decreased biliary excretion of entacapone may occur if these agents are given concurrently.
Entrectinib: (Major) Avoid coadministration of entrectinib with erythromycin due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If erythromycin is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of erythromycin. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; erythromycin is a moderate CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Eplerenone: (Major) Do not exceed an eplerenone dose of 25 mg PO once daily if given concurrently with a CYP3A4 inhibitor in a post-myocardial infarction patient with heart failure. In patients with hypertension receiving a concurrent CYP3A4 inhibitor, initiate eplerenone at 25 mg PO once daily; the dose may be increased to a maximum of 25 mg PO twice daily for inadequate blood pressure response. In addition, measure serum creatinine and serum potassium within 3 to 7 days of initiating a CYP3A4 inhibitor and periodically thereafter. Eplerenone is a CYP3A4 substrate. Erythromycin is a CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors increased eplerenone exposure by 100% to 190%. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
Ergot alkaloids: (Contraindicated) Coadministration of ergot alkaloids and erythromycin is contraindicated due to the potential for increased ergot exposure. Increased plasma concentrations of ergot alkaloids are associated with risk of acute ergot toxicity which is characterized by peripheral vasospasm and ischemia of the extremities and other tissues. Ergot alkaloids are CYP3A substrates and erythromycin is a CYP3A inhibitor.
Ergotamine; Caffeine: (Moderate) Inhibitors of the hepatic CYP4501A2, such as erythromycin, may inhibit the hepatic oxidative metabolism of caffeine. No specific management is recommended except in patients who complain of caffeine related side effects. In such patients, the dosage of caffeine containing medications or the ingestion of caffeine containing products may need to be reduced.
Eribulin: (Major) Concomitant use of eribulin and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Escitalopram: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as erythromycin, should be done with caution and close monitoring. In addition, escitalopram is metabolized by CYP3A4. Theoretically, erythromycin may inhibit this enzyme and lead to elevated plasma levels of this SSRI. However, because escitalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease its clearance.
Estazolam: (Moderate) Erythromycin is a CYP3A4 inhibitor and may reduce the metabolism of estazolam and increase the potential for benzodiazepine toxicity.
Esterified Estrogens: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as erythromycin may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Esterified Estrogens; Methyltestosterone: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as erythromycin may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Estradiol: (Minor) As erythromycin inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Estradiol; Levonorgestrel: (Minor) As erythromycin inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Estradiol; Norethindrone: (Minor) As erythromycin inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Estradiol; Norgestimate: (Minor) As erythromycin inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Estradiol; Progesterone: (Minor) As erythromycin inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives. (Minor) The metabolism of progesterone may be inhibited by erythromycin, an inhibitor of cytochrome P450 3A4 hepatic enzymes.
Estropipate: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4, such as erythromycin, may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Etonogestrel: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as erythromycin may increase the serum concentration of etonogestrel.
Etonogestrel; Ethinyl Estradiol: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as erythromycin may increase the serum concentration of etonogestrel.
Etravirine: (Moderate) Use caution with the coadministration of etravirine and erythromycin as serum concentrations of both drugs may be increased. Etravirine is a CYP3A4 substrate and a P-glycoprotein (P-gp) inhibitor, while erythromycin is a CYP3A4 inhibitor and P-gp substrate.
Everolimus: (Major) Coadministration of everolimus with erythromycin requires a dose reduction for some indications and close monitoring for others. For patients with oncology indications and tuberous sclerosis complex (TSC)-associated renal angiomyolipoma, reduce the initial dose of everolimus to 2.5 mg PO once daily; the dose may be increased to 5 mg PO once daily if the 2.5 mg dose is tolerated. For patients with TSC-associated subependymal giant cell astrocytoma (SEGA) and TSC-associated partial-onset seizures, reduce the daily dose of everolimus by 50%, changing to every-other-day dosing if the reduced dose is lower than the lowest available strength; assess the everolimus whole blood trough concentration 2 weeks after initiation of erythromycin and adjust the dose as necessary to remain in the recommended therapeutic range. Also monitor everolimus whole blood trough concentrations for patients receiving everolimus for either kidney or liver transplant and adjust the dose as necessary to remain in the recommended therapeutic range. Everolimus is a sensitive CYP3A4 substrate and a P-glycoprotein (P-gp) substrate. Erythromycin is a moderate CYP3A4 and P-gp inhibitor. Coadministration with erythromycin increased the Cmax, AUC, and half-life of everolimus by 2-fold, 4.4-fold, and 39%, respectively.
Ezetimibe; Simvastatin: (Contraindicated) Erythromycin is contraindicated during simvastatin therapy. Erythromycin potently inhibits the metabolism of simvastatin via the CYP3A4 isoenzyme and increases the risk of myopathy and rhabdomyolysis. According to the manufacturer, if no alternative to a short course of erythromycin therapy is available, therapy with simvastatin must be suspended during the course of erythromycin treatment. There are no known adverse effects with short-term discontinuation of simvastatin.
Felodipine: (Major) Avoid administration of erythromycin and felodipine, particularly in geriatric patients. Coadministration has been associated with an increased risk of hypotension and shock. Azithromycin may be preferred if the use of a macrolide antibiotic is necessary in a patient receiving felodipine therapy. If coadministration is unavoidable, monitor blood pressure and heart rate. Felodipine is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of erythromycin is necessary. If erythromycin is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like erythromycin can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If erythromycin is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
Finasteride; Tadalafil: (Moderate) Monitor for an increase in tadalafil-related adverse reactions if coadministration with erythromycin is necessary. Tadalafil is a CYP3A4 substrate and erythromycin is a moderate CYP3A inhibitor. Although specific interactions have not been studied, moderate CYP3A4 inhibitors would likely increase tadalafil exposure.
Finerenone: (Moderate) Monitor serum potassium during initiation or dose adjustment of either finerenone or erythromycin; a finerenone dosage reduction may be necessary. Concomitant use may increase finerenone exposure and the risk of hyperkalemia. Finerenone is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with erythromycin increased overall exposure to finerenone by 248%.
Fingolimod: (Major) Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsades de pointes (TdP). Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with fingolimod include erythromycin.
Flecainide: (Major) Concurrent use of flecainide and erythromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Erythromycin administration is associated with QT prolongation and TdP. In addition, erythromycin may theoretically increase plasma concentrations of flecainide via inhibition of CYP3A4. Higher antiarrhythmic plasma concentrations increases the potential risk of QT prolongation, TdP or other proarrhythmias.
Flibanserin: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as erythromycin, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Fluconazole: (Major) Concomitant use of fluconazole and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluoxetine: (Major) Concomitant use of erythromycin and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluphenazine: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with fluphenazine. Erythromycin is associated with prolongation of the QT interval and TdP. Fluphenazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
Flurazepam: (Moderate) Erythromycin may inhibit the CYP3A4-mediated metabolism of flurazepam, Monitor patient clinically for enhanced benzodiazepine response.
Fluvastatin: (Major) The risk of developing myopathy and/or rhabdomyolysis with HMG-CoA reductase inhibitors, such as fluvastatin, is increased if coadministered with erythromycin. Fluvastatin is partially metabolized by CYP3A4, and erythromycin is a potent CYP3A4 inhibitor. However, according to the manufacturer, coadministration of erythromycin did not significantly alter the pharmacokinetic disposition of fluvastatin.
Fluvoxamine: (Major) Concomitant use of erythromycin and fluvoxamine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fosamprenavir: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with erythromycin. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Foscarnet: (Major) Concomitant use of erythromycin and foscarnet increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fostemsavir: (Major) Use erythromycin and fostemsavir together with caution. Erythromycin is associated with QT prolongation and torsade de pointes (TdP). Supratherapeutic doses of fostemsavir (2,400 mg twice daily, 4 times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Gemifloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with gemifloxacin. Erythromycin is associated with QT prolongation and TdP, and gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Major) Use gemtuzumab ozogamicin and erythromycin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Cases ofTdP have been spontaneously reported during postmarketing surveillance in patients receiving erythromycin. Fatalities have been reported.
Gilteritinib: (Major) Use caution and monitor for evidence of QT prolongation if concurrent use of gilteritinib and erythromcyin is necessary. Gilteritinib has been associated with QT prolongation. Erythromycin is associated with QT prolongation and torsade de pointes (TdP). Coadministration has the potential for additive cardiotoxicity.
Glasdegib: (Major) Avoid coadministration of glasdegib with erythromycin due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Erythromycin is associated with QT prolongation and torsade de pointes (TdP).
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and erythromycin as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and erythromycin are both substrates and inhibitors of P-glycoprotein (P-gp). Additionally, glecaprevir is a substrate of organic anion transporting polypeptide (OATP) 1B1/3 and erythromycin is an inhibitor of OATP1B1/3. (Moderate) Caution is advised with the coadministration of pibrentasvir and erythromycin as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Both pibrentasvir and erythromycin are substrates and inhibitors of P-glycoprotein (P-gp).
Goserelin: (Major) Concomitant use of erythromycin and goserelin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Granisetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and erythromycin should be used together cautiously. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron with drugs known to prolong the QT interval or are arrhythmogenic, may result in clinical consequences. Erythromycin administration is associated with QT prolongation and TdP.
Green Tea: (Moderate) Some, but not all, green tea products contain caffeine. Inhibitors of the hepatic CYP450 isoenzyme CYP1A2, such as erythromycin, may inhibit the hepatic oxidative metabolism of caffeine. In patients who complain of caffeine related side effects, the dosage of caffeine containing products may need to be reduced.
Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of erythromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like erythromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If erythromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Guanfacine: (Major) Erythromycin may significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available. Monitor patients closely for alpha-adrenergic effects including hypotension, drowsiness, lethargy, and bradycardia. Upon erythromycin discontinuation, the guanfacine ER dosage should be increased back to the recommended dose. Guanfacine is primarily metabolized by CYP3A4, and erythromycin is a moderate CYP3A4 inhibitor.
Halogenated Anesthetics: (Major) Concomitant use of erythromycin and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Haloperidol: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with haloperidol. It is prudent to use caution and carefully weighing the risks and benefits of these agents versus alternative treatment options. Erythromycin has an established risk for QT prolongation and TdP. QT prolongation and TdP have also been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) of haloperidol may be associated with a higher risk of QT prolongation. In addition, inhibition of CYP3A4 by eythromycin may result in elevated haloperidol concentrations, thereby increasing the risk of adverse effects, including QT prolongation.
Histrelin: (Major) Concomitant use of histrelin and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of erythromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like erythromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If erythromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of erythromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like erythromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If erythromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of erythromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like erythromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If erythromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of erythromycin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like erythromycin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If erythromycin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocortisone: (Moderate) Monitor for corticosteroid-related adverse events if hydrocortisone is used with erythromycin. Concurrent use may increase hydrocortisone exposure. Hydrocortisone is a CYP3A substrate and erythromycin is a CYP3A inhibitor.
Hydroxychloroquine: (Major) Concomitant use of hydroxychloroquine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Major) Concomitant use of hydroxyzine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ibrutinib: (Major) If ibrutinib is coadministered with erythromycin, reduce the initial ibrutinib dosage to 280 mg/day PO in patients receiving ibrutinib for B-cell malignancy. Resume ibrutinib at the previous dosage if erythromycin is discontinued. No initial ibrutinib dosage adjustment is necessary in patients receiving ibrutinib for chronic graft-versus-host disease. Monitor patients for ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection); modify the ibrutinib dosage as recommended if toxicity occurs. Ibrutinib is a CYP3A4 substrate; erythromycin is a moderate CYP3A4 inhibitor. When ibrutinib was administered with multiple doses of erythromycin, the AUC value of ibrutinib increased by 3-fold.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of erythromycin is necessary. If erythromycin is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like erythromycin can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If erythromycin is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Ibutilide: (Major) Concurrent use of erythromycin with Class III antiarrhythmic agents should be avoided. Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). In addition to potential pharmacokinetic interactions, erythromycin may cause QT prolongation and exhibit additive electrophysiologic effects with Class III antiarrhythmics. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with erythromycin, a CYP3A substrate, as erythromycin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Ifosfamide: (Moderate) Monitor for a decrease in the efficacy of ifosfamide if coadministration with erythromycin is necessary. Ifosfamide is metabolized by CYP3A4 to its active alkylating metabolites. Erythromycin is a moderate CYP3A4 inhibitor. Coadministration may decrease plasma concentrations of these active metabolites, decreasing the effectiveness of ifosfamide treatment.
Iloperidone: (Major) Concomitant use of iloperidone and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Imatinib: (Moderate) Any agent that inhibits cytochrome P450 3A4, such as erythromycin, may decrease the metabolism of imatinib and increase imatinib concentrations leading to an increased incidence of adverse reactions.
Infigratinib: (Major) Avoid concomitant use of infigratinib and erythromycin. Coadministration may increase infigratinib exposure, increasing the risk of adverse effects. Infigratinib is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with erythromycin due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Erythromycin is associated with QT prolongation and TdP.
Isavuconazonium: (Moderate) Caution is warranted as concomitant use of isavuconazonium and erythromycin may result in increased isavuconazonium serum concentrations. Erythromycin is an inhibitor of CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of CYP3A4.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Caution is warranted with the concomitant use of erythromycin and rifampin as this may result in reduced erythromycin Cmax and increased clearance. Coadministration of oral erythromycin 500 mg and rifampin 600 mg to healthy patients led to a reduced erythromycin maximum serum concentration (Cmax) and an increased clearance. Specifically, as monotherapy, the median erythromycin Cmax was 1.34 mg/L (range, 0.4 to 3.16), and the median apparent oral clearance was 96 L/hour (range, 37 to 250). In combination with rifampin, the median erythromycin Cmax was 0.72 mg/L (range, 0.06 to 1.66), and the median apparent oral clearance was 197 L/hour (range, 102 to 2015).
Isoniazid, INH; Rifampin: (Major) Caution is warranted with the concomitant use of erythromycin and rifampin as this may result in reduced erythromycin Cmax and increased clearance. Coadministration of oral erythromycin 500 mg and rifampin 600 mg to healthy patients led to a reduced erythromycin maximum serum concentration (Cmax) and an increased clearance. Specifically, as monotherapy, the median erythromycin Cmax was 1.34 mg/L (range, 0.4 to 3.16), and the median apparent oral clearance was 96 L/hour (range, 37 to 250). In combination with rifampin, the median erythromycin Cmax was 0.72 mg/L (range, 0.06 to 1.66), and the median apparent oral clearance was 197 L/hour (range, 102 to 2015).
Isradipine: (Major) Avoid administration of erythromycin and isradipine, particularly in geriatric patients. Coadministration has been associated with an increased risk of hypotension and shock. Azithromycin may be preferred if the use of a macrolide antibiotic is necessary in a patient receiving isradipine therapy. If coadministration is unavoidable, monitor blood pressure and heart rate. Isradipine is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Itraconazole: (Major) Caution is advised when administering itraconazole with drugs that are known to prolong that QT interval, such as erythromycin. Both erythromycin and itraconazole are associated with QT prolongation; coadministration may increase this risk. In addition, itraconazole is a substrate of CYP3A4 and erythromycin is an inhibitor of CYP3A4. Coadministration may result in increased plasma concentrations of itraconazole, thereby further increasing the risk for adverse events.
Ivabradine: (Major) Avoid coadministration of ivabradine and erythromycin as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; erythromycin inhibits CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Ivacaftor: (Major) If erythromycin and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with erythromycin due to increased plasma concentrations of ivosidenib, which increases the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. Ivosidenib is a CYP3A4 substrate that has been associated with QTc prolongation and ventricular arrhythmias. Erythromycin is a moderate CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Coadministration with another moderate CYP3A4 inhibitor is predicted to increase the ivosidenib single-dose AUC to 173% of control based on physiologically-based pharmacokinetic modeling, with no change in Cmax. Multiple doses of the moderate CYP3A4 inhibitor are predicted to increase the ivosidenib steady-state AUC to 152% of control and AUC to 190% of control.
Ixabepilone: (Moderate) Monitor for ixabepilone toxicity and reduce the ixabepilone dose as needed if concurrent use of erythromycin is necessary. Concomitant use may increase ixabepilone exposure and the risk of adverse reactions. Ixabepilone is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and erythromycin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. In addition, ketoconazole is a strong CYP3A4 inhibitor, and may increase exposure to erythromycin, a CYP3A4 substrate.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with erythromycin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erythromycin is a P-gp inhibitor.
Lapatinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of lapatinib with erythromycin is necessary; correct electrolyte abnormalities prior to treatment. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Erythromycin is also associated with QT prolongation and TdP.
Larotrectinib: (Moderate) Monitor for an increase in larotrectinib-related adverse reactions if concomitant use with erythromycin is necessary. Concomitant use may increase larotrectinib exposure. Larotrectinib is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase larotrectinib exposure by 2.7-fold.
Ledipasvir; Sofosbuvir: (Moderate) Caution and close monitoring of adverse reactions is advised with concomitant administration of erythromycin and ledipasvir; sofosbuvir. Both ledipasvir and erythromycin are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp); sofosbuvir is a P-gp substrate. Taking these drugs together may increase plasma concentrations of all three drugs. According to the manufacturer, no dosage adjustments are required when ledipasvir; sofosbuvir is administered concurrently with P-gp inhibitors.
Lefamulin: (Major) Avoid coadministration of lefamulin with erythromycin as concurrent use may increase the risk of QT prolongation; concurrent use may also increase exposure from lefamulin tablets which may increase the risk of adverse effects. If coadministration cannot be avoided, monitor ECG during treatment; additionally, monitor for lefamulin-related adverse effects if oral lefamulin is administered. Lefamulin is a CYP3A4 and P-gp substrate that has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Erythromycin is a P-gp and moderate CYP3A4 that is associated with QT prolongation and torsade de pointes (TdP). The effect of moderate inhibitors on lefamulin has not been studied; however, coadministration of a combined P-gp and strong CYP3A4 inhibitor increased the exposure of oral and intravenous lefamulin by 165% and 31%, respectively.
Lemborexant: (Major) Avoid coadministration of lemborexant and erythromycin as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; erythromycin is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Lenvatinib: (Major) Concomitant use of lenvatinib and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Letermovir: (Moderate) Caution is warranted with the concurrent administration of erythromycin and letermovir, as this may result in increased concentrations of letermovir. Closely monitor for adverse events, including gastrointestinal events. Erythromycin is an inhibitor of the organic anion-transporting polypeptides (OATP1B1/3). Letermovir is an OATP1B1/3 substrate.
Leuprolide: (Major) Concomitant use of leuprolide and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Leuprolide; Norethindrone: (Major) Concomitant use of leuprolide and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levamlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with erythromycin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Levofloxacin: (Major) Concomitant use of levofloxacin and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and erythromycin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. In addition, ketoconazole is a strong CYP3A4 inhibitor, and may increase exposure to erythromycin, a CYP3A4 substrate.
Lithium: (Major) Concomitant use of erythromycin and lithium increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lofexidine: (Major) Concomitant use of lofexidine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lomitapide: (Contraindicated) Concomitant use of erythromycin and lomitapide is contraindicated. If treatment with erythromycin is unavoidable, lomitapide should be stopped during the course of treatment. Erythromycin is a moderate CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use.
Lonafarnib: (Contraindicated) Coadministration of lonafarnib and erythromycin is contraindicated; concurrent use may increase the exposure of lonafarnib and the risk of adverse effects. Lonafarnib is a sensitive CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Loperamide: (Major) Concomitant use of loperamide and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a P-gp substrate and erythromycin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Major) Concomitant use of loperamide and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a P-gp substrate and erythromycin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Major) Concomitant use of lopinavir and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Moderate) Caution is warranted with the use of erythromycin and ritonavir as erythromycin may increase ritonavir serum concentrations resulting in increased treatment-related adverse effects. Erythromycin inhibits CYP3A4 and P-glycoprotein (P-gp), while ritonavir is a substrate of both CYP3A4 and P-gp.
Losartan: (Minor) Losartan is metabolized to an active metabolite E-3174. The AUC of this active metabolite of oral losartan is not affected by erythromycin, a CYP3A4 inhibitor; however, the AUC of losartan is increased by 30%.
Losartan; Hydrochlorothiazide, HCTZ: (Minor) Losartan is metabolized to an active metabolite E-3174. The AUC of this active metabolite of oral losartan is not affected by erythromycin, a CYP3A4 inhibitor; however, the AUC of losartan is increased by 30%.
Lovastatin: (Contraindicated) Concurrent use of lovastatin and erythromycin is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with strong CYP3A4 inhibitors including erythromycin. If no alternative to a short course of treatment with erythromycin is available, a brief suspension of lovastatin therapy during such treatment can be considered as there are no known adverse consequences to brief interruptions of long-term cholesterol-lowering therapy.
Lumacaftor; Ivacaftor: (Major) If erythromycin and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may decrease the therapeutic efficacy of erythromycin; avoid concurrent use if possible. If concomitant use of erythromycin is necessary, monitor for microbiological activity and signs and symptoms of lumacaftor; ivacaftor toxicity. Erythromycin is a substrate and inhibitor of CYP3A. Ivacaftor is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer. The enzyme induction effects of lumacaftor may decrease the systemic exposure of erythromycin and decrease its therapeutic efficacy. In addition, the inhibitory effects of erythromycin may increase the systemic exposure of ivacaftor, although no dosage adjustment is recommended for moderate CYP3A inhibition.
Lumateperone: (Major) Reduce the dose of lumateperone to 21 mg once daily if concomitant use of erythromycin is necessary. Concurrent use may increase lumateperone exposure and the risk of adverse effects. Lumateperone is a CYP3A4 substrate; erythromycin is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased lumateperone exposure by approximately 2-fold.
Lurasidone: (Major) Erythromycin is a moderate inhibitor of CYP3A4 and has the potential for interactions with substrates of CYP3A4 such as lurasidone. Concurrent use of these medications may lead to an increased risk of lurasidone-related adverse reactions. If a moderate inhibitor of CYP3A4 is being prescribed and lurasidone is added in an adult patient, the recommended starting dose of lurasidone is 20 mg/day and the maximum recommended daily dose of lurasidone is 80 mg/day. If a moderate CYP3A4 inhibitor is added to an existing lurasidone regimen, reduce the lurasidone dose to one-half of the original dose. Patients should be monitored for efficacy and toxicity.
Lurbinectedin: (Major) Avoid coadministration of lurbinectedin and erythromycin due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as erythromycin. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Erythromycin is associated with QT prolongation and torsade de pointes (TdP).
Maprotiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with maprotiline. Erythromycin is associated with prolongation of the QT interval and TdP. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. In addition, erythromycin is sometimes used to stimulate GI motility, for example, in patients with diabetic gastroparesis. In patients requiring erythromycin to enhance GI motility, some cyclic antidepressants with substantial antimuscarinic properties may counteract erythromycin's effectiveness.
Maraviroc: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and eythromycin as increased maraviroc concentrations may occur. Maraviroc is a substrate of CYP3A, P-glycoprotein (P-gp), and organic anion-transporting polypeptide (OATP1B). Erythromycin is a CYP3A4, P-gp, and OATP1B1 inhibitor. Monitor for an increase in adverse effects with concomitant use.
Mavacamten: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting erythromycin therapy. Avoid initiation of erythromycin in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable erythromycin therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Mefloquine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with mefloquine. Erythromycin is associated with prolongation of the QT interval and TdP. There is also evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. In addition, mefloquine is metabolized by CYP3A4 and P-glycoprotein (P-gp) and erythromycin is a CYP3A4 and P-gp inhibitor. Coadministration may decrease the clearance of mefloquine and increase mefloquine systemic exposure further increasing the risk for QT prolongation.
Metformin; Repaglinide: (Moderate) Repaglinide is metabolized in the liver by cytochrome P450 isoenzyme CYP3A4. Clarithromycin inhibits this enzyme and has been found to produce a greater hypoglycemic effect from repaglinide. These are clinically significant increases in repaglinide plasma levels which may necessitate a repaglinide dose adjustment. Erythromycin is likely to interact in a similar fashion.
Metformin; Saxagliptin: (Minor) Saxagliptin plasma concentrations are expected to increase in the presence of moderate CYP 3A4/5 inhibitors such as erythromycin, but saxagliptin dose adjustment is not advised.
Methadone: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with methadone. The need to coadminister these drugs should be done with careful assessment of treatment risks versus benefits. Erythromycin is associated with prolongation of the QT interval and TdP. Methadone is also considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses averaging approximately 400 mg/day in adult patients. In addition, methadone is a substrate for CYP3A4 and P-glycoprotein (P-gp), while erythromycin is a CYP3A4 and P-gp inhibitor. Concurrent use may result in increased serum concentrations of methadone.
Methylprednisolone: (Minor) Erythromycin decreases the clearance of methylprednisolone. The clinical implications of these pharmacokinetic interactions are uncertain, but some studies have used the interaction to dose-reduce methylprednisolone in acutely asthmatic patients without compromising steroid efficacy.
Metronidazole: (Major) Concomitant use of metronidazole and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Midazolam: (Major) Midazolam is metabolized by hepatic isozyme CYP3A4. Inhibitors of this pathway, such as erythromycin, can potentiate the clinical effects of midazolam. Use this combination with caution.
Midostaurin: (Major) Concomitant use of erythromycin and midostaurin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mifepristone: (Major) Concomitant use of mifepristone and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase mifepristone concentrations. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Mifepristone is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Mirtazapine: (Major) Concomitant use of erythromycin and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mitapivat: (Moderate) Do not exceed mitapivat 20 mg PO twice daily during coadministration with erythromycin and monitor hemoglobin and for adverse reactions from mitapivat. Coadministration increases mitapivat concentrations. Mitapivat is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased mitapivat overall exposure by 2.6-fold.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and erythromycin; reduce the dose of mobocertinib by approximately 50% and monitor the QT interval more frequently if use is necessary. Concomitant use increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and may increase mobocertinib exposure and the risk for mobocertinib-related adverse reactions. Mobocertinib is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Use of a moderate CYP3A inhibitor is predicted to increase the overall exposure of mobocertinib and its active metabolites by 100% to 200%.
Modafinil: (Moderate) Erythromycin can inhibit the hepatic metabolism of other drugs, such as modafinil, increasing their serum concentrations and potentially causing toxicity.
Moxifloxacin: (Major) Concomitant use of erythromycin and moxifloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions if coadministered with erythromycin. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a substrate of CYP3A4 and P-gp; erythromycin is a moderate P-gp inhibitor and a moderate CYP3A4 inhibitor.
Naloxegol: (Major) Avoid concomitant administration of naloxegol and erythromycin due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; erythromycin is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with erythromycin is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and erythromycin. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and erythromycin is a moderate CYP3A and P-gp inhibitor.
Neratinib: (Major) Avoid concomitant use of erythromycin with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and erythromycin is a dual moderate CYP3A4/P-glycoprotein (P-gp) inhibitor. Simulations using physiologically based pharmacokinetic (PBPK) models suggest that another dual moderate CYP3A4/P-gp inhibitor may increase neratinib exposure by 299%.
Nevirapine: (Moderate) Monitor for nevirapine-related side effects and decreased erythromycin efficacy if nevirapine and erythromycin are coadministered. Concomitant use may increase nevirapine exposure and decrease erythromycin exposure. Nevirapine is a CYP3A substrate and weak CYP3A inducer; erythromycin is a moderate CYP3A inhibitor.
Niacin; Simvastatin: (Contraindicated) Erythromycin is contraindicated during simvastatin therapy. Erythromycin potently inhibits the metabolism of simvastatin via the CYP3A4 isoenzyme and increases the risk of myopathy and rhabdomyolysis. According to the manufacturer, if no alternative to a short course of erythromycin therapy is available, therapy with simvastatin must be suspended during the course of erythromycin treatment. There are no known adverse effects with short-term discontinuation of simvastatin.
Nicardipine: (Major) Avoid administration of erythromycin and nicardipine, particularly in geriatric patients. Coadministration has been associated with an increased risk of hypotension and shock. Azithromycin may be preferred if the use of a macrolide antibiotic is necessary in a patient receiving nicardipine therapy. If coadministration is unavoidable, monitor blood pressure and heart rate. Nicardipine is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Nifedipine: (Major) Avoid administration of erythromycin and nifedipine, particularly in geriatric patients. Coadministration has been associated with an increased risk of hypotension and shock. Azithromycin may be preferred if the use of a macrolide antibiotic is necessary in a patient receiving nifedipine therapy. If coadministration is unavoidable, monitor blood pressure and heart rate. Nifedipine is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Nilotinib: (Major) Concomitant use of nilotinib and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Nimodipine: (Major) Avoid administration of erythromycin and nimodipine, particularly in geriatric patients. Coadministration has been associated with an increased risk of hypotension and shock. Azithromycin may be preferred if the use of a macrolide antibiotic is necessary in a patient receiving nimodipine therapy. If coadministration is unavoidable, monitor blood pressure and heart rate. Nimodipine is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Nintedanib: (Moderate) Dual inhibitors of P-glycoprotein (P-gp) and CYP3A4, such as erythromycin, are expected to increase the exposure and clinical effect of nintedanib. If use together is necessary, closely monitor for increased nintedanib side effects including gastrointestinal toxicity (nausea, vomiting, diarrhea, abdominal pain, loss of appetite), headache, elevated liver enzymes, and hypertension. A dose reduction, interruption of therapy, or discontinuation of nintedanib therapy may be necessary. Erythromycin is a moderate inhibitor of P-gp and CYP3A4; nintedanib is a P-gp substrate and a minor CYP3A4 substrate. In drug interactions studies, administration of nintedanib with a dual P-gp and CYP3A4 inhibitor increased nintedanib AUC by 60%.
Nirmatrelvir; Ritonavir: (Major) Consider temporary discontinuation of erythromycin during treatment with ritonavir-boosted nirmatrelvir and for at least 2 to 3 days after treatment completion; if not feasible, consider alternative COVID-19 therapy. Coadministration may increase nirmatrelvir exposure resulting in increased toxicity. Erythromycin inhibits CYP3A4 and P-glycoprotein (P-gp), while nirmatrelvir is a substrate for CYP3A4 and P-gp. (Moderate) Caution is warranted with the use of erythromycin and ritonavir as erythromycin may increase ritonavir serum concentrations resulting in increased treatment-related adverse effects. Erythromycin inhibits CYP3A4 and P-glycoprotein (P-gp), while ritonavir is a substrate of both CYP3A4 and P-gp.
Nisoldipine: (Major) Avoid administration of erythromycin and nisoldipine, particularly in geriatric patients. Coadministration has been associated with an increased risk of hypotension and shock. Azithromycin may be preferred if the use of a macrolide antibiotic is necessary in a patient receiving nisoldipine therapy. If coadministration is unavoidable, monitor blood pressure and heart rate. Nisoldipine is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Ofloxacin: (Major) Concomitant use of ofloxacin and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine: (Major) Concomitant use of olanzapine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine; Fluoxetine: (Major) Concomitant use of erythromycin and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Major) Concomitant use of olanzapine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine; Samidorphan: (Major) Concomitant use of olanzapine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olaparib: (Major) Avoid coadministration of olaparib with erythromycin due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after erythromycin is discontinued. Olaparib is a CYP3A substrate and erythromycin is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and erythromycin is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and erythromycin may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If erythromycin is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with erythromycin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Omaveloxolone: (Major) Avoid concomitant use of omaveloxolone and erythromycin. If concomitant use is necessary, decrease omaveloxolone dose to 100 mg once daily; additional dosage reductions may be necessary. Concomitant use may increase omaveloxolone exposure and the risk for omaveloxolone-related adverse effects. Omaveloxolone is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased omaveloxolone overall exposure by 1.25-fold.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Caution is warranted when erythromycin is administered with rifabutin as rifabutin concentrations may be elevated. Monitor for adverse events of rifabutin, such as neutropenia and rash. Erythromycin is an inhibitor of CYP3A4, and rifabutin is a substrate of CYP3A4.
Ondansetron: (Major) Concomitant use of ondansetron and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Osilodrostat: (Major) Concomitant use of osilodrostat and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Osimertinib: (Major) Concomitant use of osimertinib and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oxaliplatin: (Major) Concomitant use of oxaliplatin and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oxybutynin: (Moderate) Monitor for oxybutynin-related adverse reactions if coadministration with erythromycin is necessary. Oxybutynin is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Concomitant use with moderate CYP3A inhibitors may alter the mean pharmacokinetic parameters of oxybutynin, although the clinical relevance of these potential interactions is unknown.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of erythromycin is necessary. If erythromycin is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like erythromycin can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If erythromycin is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking erythromycin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Erythromycin is associated with QT prolongation and TdP.
Paclitaxel: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 (CYP) isoenzymes 2C8 and 3A4. Erythromycin is a CYP3A4 inhibitor. In vitro, the metabolism of paclitaxel is inhibited by various agents (e.g., ketoconazole, verapamil, diazepam, quinidine, dexamethasone, tenopiside, etoposide, and vincristine) but concentrations used exceeded those found in vivo following normal therapeutic doses. Closely monitor patients for toxicity when administering paclitaxel with any of these agents.
Pacritinib: (Major) Avoid concurrent use of pacritinib with erythromycin due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Paliperidone: (Major) Concomitant use of paliperidone and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Palovarotene: (Major) Avoid concomitant use of palovarotene and erythromycin due to the risk for increased palovarotene exposure which may increase the risk for adverse effects. If concomitant use is necessary, decrease the palovarotene dose by half. Palovarotene is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Concomitant use increased palovarotene overall exposure by 2.5-fold.
Panobinostat: (Major) The co-administration of panobinostat with erythromycin or erythromycin; sulfisoxazole is not recommended; QT prolongation has been reported with panobinostat and erythromycin and the levels of panobinostat may increase. Although an initial panobinostat dose reduction is recommended in patients taking concomitant strong CYP3A4 inhibitors, no dose recommendations with mild or moderate CYP3A4 inhibitors are provided by the manufacturer. If concomitant use of erythromycin and panobinostat cannot be avoided, closely monitor electrocardiograms and for signs and symptoms of panobinostat toxicity such as cardiac arrhythmias, diarrhea, bleeding, infection, and hepatotoxicity. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Erythromycin is a CYP3A4 inhibitor and panobinostat is a CYP3A4 substrate. The panobinostat Cmax and AUC (0-48hr) values were increased by 62% and 73%, respectively, in patients with advanced cancer who received a single 20 mg-dose of panobinostat after taking 14 days of a strong CYP3A4 inhibitor.
Paricalcitol: (Moderate) Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as erythromycin. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
Pasireotide: (Major) Concomitant use of pasireotide and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pazopanib: (Major) Concomitant use of pazopanib and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and erythromycin due to the risk of increased pemigatinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of pemigatinib to 9 mg PO once daily if original dose was 13.5 mg per day and to 4.5 mg PO once daily if original dose was 9 mg per day. If erythromycin is discontinued, resume the original pemigatinib dose after 3 elimination half-lives of erythromycin. Pemigatinib is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor is predicted to increase pemigatinib exposure by approximately 50% to 80%.
Pentamidine: (Major) Concomitant use of pentamidine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Perindopril; Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with erythromycin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Perphenazine: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with perphenazine. Erythromycin is associated with prolongation of the QT interval and TdP. Perphenazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
Perphenazine; Amitriptyline: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with perphenazine. Erythromycin is associated with prolongation of the QT interval and TdP. Perphenazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
Pexidartinib: (Major) Avoid concomitant use of pexidartinib and erythromycin due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If erythromycin is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of erythromycin. Additionally, monitor for evidence of hepatotoxicity if coadministration is necessary and avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Pexidartinib is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor, and both medications have been associated with hepatotoxicity. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%.
Pimavanserin: (Major) Concomitant use of pimavanserin and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of macrolide antibiotics with pimozide is contraindicated.
Pitavastatin: (Major) Do not exceed a daily dose of 1 mg PO for pitavastatin if used concomitantly with erythromycin due to increased pitavastatin exposure and risk for myopathy or rhabdomyolysis. When coadministered with erythromycin 500 mg 4 times daily for 6 days, the pitavastatin AUC increased by 2.8-fold and the Cmax increased by 3.6-fold.
Pitolisant: (Major) Concomitant use of pitolisant and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking erythromycin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Erythromycin is associated with QT prolongation and TdP.
Posaconazole: (Major) Caution is advised when administering posaconazole with drugs that are known to prolong that QT interval, such as erythromycin. Both erythromycin and posaconazole are associated with QT prolongation and torsade de pointes (TdP); coadministration may increase this risk. Both posaconazole and erythromycin are inhibitors and substrates of the drug efflux protein, P-glycoprotein (P-gp), which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and erythromycin and an increased risk for serious adverse events.
Pralsetinib: (Major) Avoid concomitant use of erythromycin with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A and P-gp substrate and erythromycin is a combined moder ate CYP3A and P-gp inhibitor. Coadministration with another combined moderate CYP3A and P-gp inhibitor increased the overall exposure of pralsetinib by 108%.
Pravastatin: (Moderate) Monitor for evidence of myopathy during coadministration of pravastatin and erythromycin. With concurrent therapy of erythromycin, the risk of myopathy increases. The pravastatin labeling recommends caution during concurrent use.
Praziquantel: (Moderate) Erythromycin is a significant CYP3A4 inhibitor and may reduce metabolism of praziquantel. This interaction may be beneficial. The combination may prolong the exposure of the parasites to praziquantel and may not result in an increased risk of side effects.
Pretomanid: (Major) Avoid coadministration of pretomanid with erythromycin, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Primaquine: (Major) Concomitant use of primaquine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and erythromycin due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and erythromycin is a dual moderate CYP3A and P-gp inhibitor. Concomitant use with other dual moderate CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 2- to 3.6-fold.
Procainamide: (Major) Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). In addition to potential pharmacokinetic interactions, erythromycin may cause QT prolongation and exhibit additive electrophysiologic effects with procainamide. Concurrent use of erythromycin with procainamide should be avoided.
Prochlorperazine: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with prochlorperazine. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Erythromycin is associated with prolongation of the QT interval and TdP. Phenothiazines, such as prochlorperazine, have also been reported to prolong the QT interval.
Progesterone: (Minor) The metabolism of progesterone may be inhibited by erythromycin, an inhibitor of cytochrome P450 3A4 hepatic enzymes.
Promethazine: (Major) Concomitant use of promethazine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Dextromethorphan: (Major) Concomitant use of promethazine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Phenylephrine: (Major) Concomitant use of promethazine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propafenone: (Major) Concomitant use of propafenone and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). In addition, concurrent use may increase propafenone exposure and therefore increase the risk of proarrhythmias. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Avoid simultaneous use of propafenone and erythromycin with a CYP2D6 inhibitor or in patients with CYP2D6 deficiency. Propafenone is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Quazepam: (Moderate) Erythromycin can decrease the hepatic metabolism of quazepam if administered concomitantly. Patients receiving quazepam should be monitored for signs of an exaggerated response if erythromycin is used concomitantly.
Quetiapine: (Major) Concomitant use of quetiapine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase quetiapine concentrations. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Quetiapine is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. Coadministration of with erythromycin resulted in decreased quetiapine clearance, increased quetiapine plasma concentrations, and prolonged quetiapine half-life. Nineteen patients received quetiapine (200 mg PO twice a day) for roughly 7 days, then erythromycin (500 mg PO 3 times a day) was added for 5 days. Mean quetiapine AUC increased 129% (range 15 to 300%) and the half-life was elevated from 7 to 16 hours.
Quinidine: (Major) Concomitant use of quinidine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and may result in increased plasma concentrations of quinidine. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Quinidine is a CYP3A substrate, and erythromycin is a moderate CYP3A inhibitor.
Quinine: (Major) Concurrent use of quinine with erythromycin should be avoided due to the risk for QT prolongation and torsade de pointes (TdP). Both quinine and erythromycin have been associated with prolongation of the QT interval. In addition, because quinine is a substrate of CYP3A4 and erythromycin is an inhibitor of CYP3A4; coadministration may result in elevated quinine serum concentrations, causing an increased risk for adverse events.
Quizartinib: (Major) Concomitant use of quizartinib and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ramelteon: (Moderate) Coadministration of ramelteon with inhibitors of CYP3A4, such as erythromycin, may lead to increases in the serum concentrations of ramelteon.
Ranolazine: (Major) Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. The mean increase in QTc is about 6 milliseconds, measured at the tmax of the maximum dosage (1000 mg PO twice daily). However, in 5% of the population studied, increases in the QTc of at least 15 milliseconds have been reported. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Ranolazine should be used cautiously with drugs that prolong the QT interval, such as erythromycin. Furthermore, the dose of ranolazine, a CYP3A4 and P-glycoprotein substrate, should be limited to 500 mg PO twice daily when coadministered with erythromycin, a moderate CYP3A inhibitor. Furthermore, erythromycin may decrease the absorption of ranolazine via inhibition of P-glycoprotein transport.
Red Yeast Rice: (Contraindicated) The concurrent use of erythromycin is not recommended during lovastatin therapy. Erythromycin potently inhibits the metabolism of certain statins via the CYP3A4 isoenzyme and increase the risk of myopathy and rhabdomyolysis. Several case reports have described the development of rhabdomyolysis after erythromycin was added to a drug regimen containing lovastatin. Symptoms improved after erythromycin was discontinued. According to the manufacturer, if no alternative to a short course of erythromycin therapy is available, brief interruption of lovastatin therapy should be considered. There are no known adverse effects with short-term discontinuation of statins. Other HMG-CoA reductase inhibitors which are significant CYP3A4 substrates include atorvastatin and cerivastatin. Coadministration of atorvastatin with erythromycin increases atorvastatin plasma concentrations by about 40%. Since pravastatin and rosuvastatin are not substantially metabolized and fluvastatin is a minor CYP3A4 substrate (20%), these statins are less likely to be significantly affected by CYP3A4 inhibitors such as erythromycin. Coadministration of a single dose of rosuvastatin (80 mg) with erythromycin results in a 20% decrease in the AUC of rosuvastatin. Erythromycin (500 mg, single dose) does not affect steady state plasma levels of fluvastatin when administered 40 mg once daily. Since compounds in red yeast rice claim to have HMG-CoA reductase inhibitor activity, red yeast rice should not be used in combination with erythromycin. In general, erythromycin should be used with caution in patients receiving HMG CoA-reductase inhibitors; patients should be monitored closely for signs and symptoms of myopathy and/or rhabdomyolysis.
Relugolix: (Major) Avoid concomitant use of relugolix and oral erythromycin. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer erythromycin at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of erythromycin is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Erythromycin is associated with QT prolongation and torsade de pointes (TdP). Relugolix is a P-gp substrate and erythromycin is a P-gp inhibitor. Coadministration with erythromycin increased the AUC and Cmax of relugolix by 6.2-fold.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral erythromycin. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer erythromycin at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of erythromycin is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Erythromycin is associated with QT prolongation and torsade de pointes (TdP). Relugolix is a P-gp substrate and erythromycin is a P-gp inhibitor. Coadministration with erythromycin increased the AUC and Cmax of relugolix by 6.2-fold. (Minor) As erythromycin inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives.
Repaglinide: (Moderate) Repaglinide is metabolized in the liver by cytochrome P450 isoenzyme CYP3A4. Clarithromycin inhibits this enzyme and has been found to produce a greater hypoglycemic effect from repaglinide. These are clinically significant increases in repaglinide plasma levels which may necessitate a repaglinide dose adjustment. Erythromycin is likely to interact in a similar fashion.
Revefenacin: (Major) Coadministration of revefenacin is not recommended with erythromycin because it could lead to an increase in systemic exposure of the active metabolite of revefenacin and an increased potential for anticholinergic adverse effects. The active metabolite of revefenacin is a substrate of OATP1B1 and OATP1B3; erythromycin is an inhibitor of OATP1B1 and OATP1B3.
Ribociclib: (Major) Concomitant use of ribociclib and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ribociclib; Letrozole: (Major) Concomitant use of ribociclib and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Rifabutin: (Moderate) Caution is warranted when erythromycin is administered with rifabutin as rifabutin concentrations may be elevated. Monitor for adverse events of rifabutin, such as neutropenia and rash. Erythromycin is an inhibitor of CYP3A4, and rifabutin is a substrate of CYP3A4.
Rifampin: (Major) Caution is warranted with the concomitant use of erythromycin and rifampin as this may result in reduced erythromycin Cmax and increased clearance. Coadministration of oral erythromycin 500 mg and rifampin 600 mg to healthy patients led to a reduced erythromycin maximum serum concentration (Cmax) and an increased clearance. Specifically, as monotherapy, the median erythromycin Cmax was 1.34 mg/L (range, 0.4 to 3.16), and the median apparent oral clearance was 96 L/hour (range, 37 to 250). In combination with rifampin, the median erythromycin Cmax was 0.72 mg/L (range, 0.06 to 1.66), and the median apparent oral clearance was 197 L/hour (range, 102 to 2015).
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with erythromycin is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and erythromycin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rilpivirine: (Major) Close clinical monitoring is advised when administering erythromycin with rilpivirine due to an increased potential for rilpivirine-related adverse events, including QT prolongation. When possible, alternative antibiotics should be considered. Predictions about the interaction can be made based on metabolic pathways. Erythromycin is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations. Also, supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval, such as erythromycin.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and erythromycin. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with erythromycin; concurrent use may increase rimegepant exposure. Rimegepant is a CYP3A4 and P-gp substrate; erythromycin is a moderate CYP3A4 inhibitor and a P-gp inhibitor.
Risperidone: (Major) Concomitant use of risperidone and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ritonavir: (Moderate) Caution is warranted with the use of erythromycin and ritonavir as erythromycin may increase ritonavir serum concentrations resulting in increased treatment-related adverse effects. Erythromycin inhibits CYP3A4 and P-glycoprotein (P-gp), while ritonavir is a substrate of both CYP3A4 and P-gp.
Rivaroxaban: (Moderate) Avoid coadministration of rivaroxaban and erythromycin in patients with renal impairment (CrCL 15 to 79 mL/minute) unless the potential benefit justifies the potential risk. Rivaroxaban is a CYP3A4 and P-glycoprotein (P-gp) inhibitor and erythromycin is a P-gp and moderate CYP3A4 inhibitor. In a pharmacokinetic trial, coadministration with erythromycin increased the AUC of rivaroxaban by 76% in patients with mild renal impairment (CrCL 50 to 79 mL/minute) and by 99% in patients with moderate renal impairment (CrCL 30 to 49 mL/minute) compared to patients with normal renal function (CrCL greater than 80 mL/minute); similar trends in pharmacodynamic effects were also observed.
Roflumilast: (Moderate) Monitor for an increase in roflumilast-related adverse reactions if concomitant use with erythromycin is necessary. Concurrent use may increase roflumilast exposure and the risk for roflumilast-related adverse reactions. Roflumilast is a CYP3A4 and CYP1A2 substrate. Erythromycin is a dual inhibitor of both CYP3A4 (moderate) and CYP1A2 (weak). Coadministration with erythromycin increased the exposure of roflumilast by 70%.
Romidepsin: (Major) Romidepsin is a substrate for CYP3A4 and P-glycoprotein (P-gp). Erythromycin is an inhibitor of CYP3A4 and P-gp. Concurrent administration of romidepsin with an inhibitor of CYP3A4 and P-gp may cause an increase in systemic romidepsin concentrations. Use caution when concomitant administration of these agents is necessary. In addition, romidepsin has been reported to prolong the QT interval. Erythromycin may also prolong the QT interval. If romidepsin and erythromycin must be continued, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.
Rosuvastatin: (Minor) Erythromycin is generally associated with an increased risk of myopathy with HMG-CoA reductase inhibitors. This interaction is likely due to CYP3A4 inhibition of statins which are CYP3A4 substrates; however, rosuvastatin is not substantially metabolized, and is less likely to be significantly affected by CYP3A4 inhibitors such as erythromycin. However, other mechanisms, such as an effect on OATP1B1, may be involved. Rosuvastatin is an OATP1B1 substrate. Coadministration of a single dose of rosuvastatin (80 mg) with erythromycin results in 31% and 20% decrease in Cmax and AUC of rosuvastatin, respectively. The clinical significance of this interaction has not been established, monitor for effectiveness of rosuvastatin and for myopathy and adjust treatment as clinically indicated.
Rosuvastatin; Ezetimibe: (Minor) Erythromycin is generally associated with an increased risk of myopathy with HMG-CoA reductase inhibitors. This interaction is likely due to CYP3A4 inhibition of statins which are CYP3A4 substrates; however, rosuvastatin is not substantially metabolized, and is less likely to be significantly affected by CYP3A4 inhibitors such as erythromycin. However, other mechanisms, such as an effect on OATP1B1, may be involved. Rosuvastatin is an OATP1B1 substrate. Coadministration of a single dose of rosuvastatin (80 mg) with erythromycin results in 31% and 20% decrease in Cmax and AUC of rosuvastatin, respectively. The clinical significance of this interaction has not been established, monitor for effectiveness of rosuvastatin and for myopathy and adjust treatment as clinically indicated.
Ruxolitinib: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as erythromycin, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure.
Saquinavir: (Contraindicated) Concurrent use of erythromycin and saquinavir boosted with ritonavir is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Saquinavir boosted with ritonavir causes dose-dependent QT and PR prolongation. Saquinavir boosted with ritonavir is a substrate of CYP3A4. Erythromycin is a CYP3A4. Elevated concentrations of saquinavir may further increase the risk of QT prolongation.
Saxagliptin: (Minor) Saxagliptin plasma concentrations are expected to increase in the presence of moderate CYP 3A4/5 inhibitors such as erythromycin, but saxagliptin dose adjustment is not advised.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Coadministration of segesterone, a CYP3A4 substrate and a moderate CYP3A4 inhibitor, such as erythromycin may increase the serum concentration of segesterone.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and erythromycin due to the risk of additive QT prolongation and increased selpercatinib exposure resulting in increased treatment-related adverse effects. If coadministration is unavoidable, reduce the dose of selpercatinib to 80 mg PO twice daily if original dose was 120 mg twice daily, and to 120 mg PO twice daily if original dose was 160 mg twice daily. Monitor ECGs for QT prolongation more frequently. If erythromycin is discontinued, resume the original selpercatinib dose after 3 to 5 elimination half-lives of erythromycin. Selpercatinib is a CYP3A4 substrate that has been associated with concentration-dependent QT prolongation; erythromycin is a moderate CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Coadministration with other moderate CYP3A4 inhibitors is predicted to increase selpercatinib exposure by 60% to 99%.
Selumetinib: (Major) Avoid coadministration of selumetinib and erythromycin due to the risk of increased selumetinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of selumetinib to 20 mg/m2 PO twice daily if original dose was 25 mg/m2 twice daily and 15 mg/m2 PO twice daily if original dose was 20 mg/m2 twice daily. If erythromycin is discontinued, resume the original selumetinib dose after 3 elimination half-lives of erythromycin. Selumetinib is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. Coadministration with erythromycin is predicted to increase selumetinib exposure by 41%.
Sertraline: (Major) Concomitant use of sertraline and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sildenafil: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with erythromycin is necessary; consider a starting dose of 25 mg of sildenafil when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. In a drug interaction study, coadministration with erythromycin increased the Cmax and AUC of sildenafil by 160% and 182%, respectively. Predictions based on a pharmacokinetic model suggest that drug-drug interactions with CYP3A inhibitors will be less for sildenafil injection than those observed after oral sildenafil administration.
Silodosin: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, drugs that inhibit CYP3A4 and P-gp such as erythromycin may cause significant increases in silodosin plasma concentrations.
Simvastatin: (Contraindicated) Erythromycin is contraindicated during simvastatin therapy. Erythromycin potently inhibits the metabolism of simvastatin via the CYP3A4 isoenzyme and increases the risk of myopathy and rhabdomyolysis. According to the manufacturer, if no alternative to a short course of erythromycin therapy is available, therapy with simvastatin must be suspended during the course of erythromycin treatment. There are no known adverse effects with short-term discontinuation of simvastatin.
Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by erythromycin. False study results are possible in patients with drug-induced hyper- or hypo-responsiveness; thorough patient history is important in the interpretation of results.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving erythromycin due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Erythromycin has also been associated with prolongation of the QT interval. Additionally, concomitant use of siponimod and erythromycin may increase siponimod exposure. If the patient is also receiving a drug regimen containing a moderate CYP2C9 inhibitor, use of siponimod is not recommended due to a significant increase in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; erythromycin is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP2C9/CYP3A4 dual inhibitor led to a 2-fold increase in the exposure of siponimod.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of erythromycin. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and erythromycin is a moderate CYP3A and P-gp inhibitor. Concomitant use increased sirolimus overall exposure by 4.2-fold in a drug interaction study.
Sodium Phenylbutyrate; Taurursodiol: (Major) Avoid coadministration of sodium phenylbutyrate; taurursodiol and erythromycin. Concomitant use may increase plasma concentrations of sodium phenylbutyrate; taurursodiol. Sodium phenylbutyrate; taurursodiol is an OATP1B3 substrate and erythromycin is an OATP1B3 inhibitor.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with erythromycin. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). In addition, erythromycin is an inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concurrent administration of voxilaprevir and erythromycin. Taking these medications together may increase plasma concentrations of both drugs, potentially increasing the risk for adverse events. Voxilaprevir is a substrate for the drug transporter Organic Anion Transporting Polypeptides 1B1/1B3 (OATP1B1/1B3); erythromycin is an OATP1B1/1B3 inhibitor. In addition, voxilaprevir is an inhibitor of P-glycoprotein, while erythromycin is a P-gp substrate. (Moderate) Use caution when administering velpatasvir with erythromycin. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). In addition, erythromycin is an inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Solifenacin: (Major) Consider the potential risk for additive QT prolongation if solifenacin is administered with erythromycin. Erythromycin is associated with QT prolongation and torsade de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined. Also solifenacin may antagonize the stimulatory effects of erythromycin on the GI tract when erythromycin is used therapeutically for improving GI motility. If erythromycin is not being used to enhance GI motility, then these potential interactions are of little clinical significance.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and erythromycin; sonidegib exposure may be significantly increased resulting in increased risk of adverse events, particularly musculoskeletal toxicity. If concomitant use cannot be avoided, administer erythromycin for less than 14 days; monitor patients closely for adverse reactions (e.g., elevated serum creatine kinase and serum creatinine levels). Sonidegib is a CYP3A substrate and erythromycin is a moderate CYP3A4 inhibitor. Physiologic-based pharmacokinetic (PBPK) simulations indicate a moderate 3A4 inhibitor would increase the sonidegib AUC by 1.8-fold if administered for 14 days and by 2.8-fold if the moderate CYP3A inhibitor is administered with sonidegib for more than 14 days.
Sorafenib: (Major) Concomitant use of sorafenib and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sotalol: (Major) Concomitant use of sotalol and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sparsentan: (Moderate) Monitor for an increase in sparsentan-related adverse effects if concomitant use with erythromycin is necessary. Concomitant use may increase sparsentan exposure. Sparsentan is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased sparsentan overall exposure by 70%.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if erythromycin must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of erythromycin is necessary. If erythromycin is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like erythromycin can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If erythromycin is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Sunitinib: (Major) Concomitant use of sunitinib and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Suvorexant: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with erythromycin. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
Tacrolimus: (Major) When possible avoid concurrent erythromycin and tacrolimus therapy. However, if concomitant therapy is necessary, close monitoring of tacrolimus blood concentrations and of the QT interval is warranted. Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP such as tacrolimus should be used cautiously with erythromycin. In addition, the concurrent administration of erythromycin and tacrolimus may result in elevated tacrolimus levels resulting in nephrotoxicity. In one case, the whole blood tacrolimus concentration was > 60 ng/ml following 3 days of therapy with erythromycin (prior tacrolimus level 9.8 ng/ml).
Tadalafil: (Moderate) Monitor for an increase in tadalafil-related adverse reactions if coadministration with erythromycin is necessary. Tadalafil is a CYP3A4 substrate and erythromycin is a moderate CYP3A inhibitor. Although specific interactions have not been studied, moderate CYP3A4 inhibitors would likely increase tadalafil exposure.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with erythromycin is necessary. Talazoparib is a P-gp substrate and erythromycin is a P-gp inhibitor.
Tamoxifen: (Major) Concomitant use of tamoxifen and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tamsulosin: (Moderate) Use caution if coadministration of erythromycin with tamsulosin is necessary, especially at a tamsulosin dose higher than 0.4 mg, as the systemic exposure of tamsulosin may be increased resulting in increased treatment-related adverse reactions including hypotension, dizziness, and vertigo. Tamsulosin is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Tasimelteon: (Moderate) Caution is recommended during concurrent use of tasimelteon and erythromycin. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as erythromycin, may increase exposure to tasimelteon with the potential for adverse reactions.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with erythromycin as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If erythromycin is discontinued, wait at least 3 half-lives of erythromycin before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Telavancin: (Major) Concomitant use of telavancin and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Telmisartan; Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with erythromycin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Temsirolimus: (Moderate) Monitor for an increase in adverse reactions of both temsirolimus and erythromycin if coadministration is necessary. Both drugs are P-glycoprotein (P-gp) substrates and inhibitors. Concomitant use may lead to increased concentrations of both drugs.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with erythromycin may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and erythromycin is a P-gp inhibitor.
Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with erythromycin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and erythromycin is a P-gp inhibitor.
Terbinafine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering erythromycin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; erythromycin is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
Tetrabenazine: (Major) Concomitant use of tetrabenazine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tezacaftor; Ivacaftor: (Major) Adjust the tezacaftor; ivacaftor dosing schedule when coadministered with erythromycin; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days (i.e., tezacaftor/ivacaftor tablet on Day 1 and ivacaftor tablet on Day 2). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); erythromycin is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure 3-fold. Simulation suggests a moderate inhibitor may increase tezacaftor exposure 2-fold. (Major) If erythromycin and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Theophylline, Aminophylline: (Major) Erythromycin can inhibit aminophylline clearance by inhibiting the cytochrome P450 CYP3A isoenzymes. If erythromycin is used with aminophylline therapy, patients should be monitored for elevated theophylline levels and/or toxicity. (Major) Erythromycin can inhibit theophylline clearance by inhibiting the cytochrome P450 CYP3A isoenzymes. If erythromycin is used with theophylline therapy, patients should be monitored for elevated theophylline levels and/or theophylline toxicity.
Thioridazine: (Contraindicated) Avoid concomitant use of thioridazine and erythromycin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Ticagrelor: (Moderate) Coadministration of ticagrelor and erythromycin may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and erythromycin is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding.
Tolterodine: (Major) Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Tolterodine should be used cautiously and with close monitoring in patients taking erythromycin. Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). Furthermore, patients receiving strong CYP3A4 inhibitors, such as erythromycin, concomitantly with tolterodine should not receive > 2 mg/day of tolterodine. Because it is difficult to assess which patients will be poor metabolizers of tolterodine via CYP2D6, those patients receiving CYP3A4 inhibitors should not receive > 2 mg/day of tolterodine. In a small portion of patients who poorly metabolize tolterodine via CYP2D6, the CYP3A4 pathway becomes important in tolterodine elimination. Pharmacokinetic studies of the use of tolterodine concomitantly with CYP3A4 inhibitors have not been performed.
Tolvaptan: (Major) Avoid coadministration of erythromycin when tolvaptan is administered for hyponatremia. In patients with autosomal dominant polycystic kidney disease (ADPKD), reduce tolvaptan dosage if administered with erythromycin. In ADPKD patients receiving tolvaptan 90mg every morning and 30 mg every evening, reduce the dose to 45 mg every morning and 15 mg every evening; for those receiving tolvaptan 60 mg every morning and 30 mg every evening, reduce the dose to 30 mg every morning and 15 mg every evening; for those receiving tolvaptan 45 mg every morning and 15 mg every evening, reduce the dose to 15 mg every morning and 15 mg every evening. Consider additional dosage reduction if the reduced dose is not tolerated. Interrupt tolvaptan in ADPKD patients if the recommended reduced doses are not available in patients requiring short-term therapy of erythromycin. Tolvaptan is a sensitive CYP3A4 substrate; erythromycin is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased the tolvaptan AUC by 200%.
Topotecan: (Major) Avoid coadministration of erythromycin with oral topotecan due to increased topotecan exposure; erythromycin may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and erythromycin is a P-gp inhibitor. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
Toremifene: (Major) Concomitant use of toremifene and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tramadol: (Moderate) Administration of CYP3A4 inhibitors such as erythromycin with tramadol may affect the metabolism of tramadol leading to altered tramadol exposure. Increased serum tramadol concentrations may occur.
Tramadol; Acetaminophen: (Moderate) Administration of CYP3A4 inhibitors such as erythromycin with tramadol may affect the metabolism of tramadol leading to altered tramadol exposure. Increased serum tramadol concentrations may occur.
Trandolapril; Verapamil: (Moderate) Monitor blood pressure and heart rate during coadministration of verapamil with erythromycin. Coadministration may increase the exposure of verapamil. Erythromycin is a moderate inhibitor of CYP3A4; verapamil is a substrate of CYP3A4.
Trazodone: (Major) Concomitant use of trazodone and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase trazadone concentrations. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Trazadone is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Triazolam: (Moderate) Monitor for signs of triazolam toxicity during coadministration with erythromycin and consider appropriate dose reduction of triazolam if clinically indicated. Coadministration may increase triazolam exposure. Triazolam is a sensitive CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Triclabendazole: (Major) Concomitant use of triclabendazole and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tricyclic antidepressants: (Minor) The use of erythromycin with tricyclic antidepressants is rarely problematic. Tricyclic antidepressants may prolong the QT interval, particularly in overdose, and erythromycin has also been reported to have this effect in rare circumstances. Erythromycin is sometimes used to stimulate GI motility, for example, in patients with diabetic gastroparesis. In patients requiring erythromycin to enhance GI motility, some tricyclic antidepressants with substantial antimuscarinic properties may counteract erythromycin's effectiveness.
Trifluoperazine: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with trifluoperazine. Erythromycin is associated with prolongation of the QT interval and TdP. Trifluoperazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
Triptorelin: (Major) Concomitant use of triptorelin and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trospium: (Minor) The antimuscarinics can antagonize the stimulatory effects of erythromycin on the GI tract when erythromycin is used therapeutically for improving GI motility.
Ubrogepant: (Major) Limit the initial dose of ubrogepant to 50 mg and avoid a second dose within 24 hours if coadministered with erythromycin. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 and P-gp substrate; erythromycin is a moderate CYP3A4 inhibitor and a P-gp inhibitor. Coadministration with another moderate CYP3A4 inhibitor resulted in a 3.5-fold increase in the exposure of ubrogepant.
Vandetanib: (Major) Concomitant use of vandetanib and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vardenafil: (Major) Do not use vardenafil orally disintegrating tablets with erythromycin due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Concomitant use also increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Vardenafil is primarily metabolized by CYP3A and erythromycin is a moderate CYP3A inhibitor. Coadministration with erythromycin increased the AUC of vardenafil by 4-fold.
Vemurafenib: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with vemurafenib. If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Both erythromycin and vemurafenib have been associated with QT prolongation. Also, erythromycin is a CYP3A4 inhibitor and a P-glycoprotein (P-gp) substrate/inhibitor, while vemurafenib is a CYP3A4 substrate and a P-gp substrate/inhibitor. Concentrations of both erythromycin and vemurafenib may be altered with concomitant use.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with erythromycin due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of erythromycin. Venetoclax is a CYP3A4 and P-glycoprotein (P-gp) substrate; erythromycin is a CYP3A4 (moderate) and P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
Venlafaxine: (Major) Concomitant use of erythromycin and venlafaxine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Verapamil: (Moderate) Monitor blood pressure and heart rate during coadministration of verapamil with erythromycin. Coadministration may increase the exposure of verapamil. Erythromycin is a moderate inhibitor of CYP3A4; verapamil is a substrate of CYP3A4.
Vinblastine: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with erythromycin is necessary. Vinblastine is a CYP3A4 substrate and erythromycin is a CYP3A4 inhibitor. Enhanced toxicity has been reported in patients receiving concomitant erythromycin.
Vincristine Liposomal: (Major) Increased concentrations of vincristine are likely. Consider if alternative antibiotic therapy is appropriate. Monitor for vincristine-related side effects, including neurotoxicity, if these drugs must be used together. Erythromycin is an inhibitor of CYP3A4 and also inhibits P-gp. Vincristine is a CYP3A4 and P-gp substrate. Reports of interactions between erythromycin and vinca alkaloids have been noted.
Vincristine: (Major) Increased concentrations of vincristine are likely. Consider if alternative antibiotic therapy is appropriate. Monitor for vincristine-related side effects, including neurotoxicity, if these drugs must be used together. Erythromycin is an inhibitor of CYP3A4 and also inhibits P-gp. Vincristine is a CYP3A4 and P-gp substrate. Reports of interactions between erythromycin and vinca alkaloids have been noted.
Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with erythromycin is necessary. Vinorelbine is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Vitamin C: (Moderate) Monitor for decreased efficacy of erythromycin during coadministration; discontinue ascorbic acid therapy if decreased efficacy is suspected. Coadministration may result in decreased efficacy of erythromycin.
Voclosporin: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with erythromycin. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Additive QT prolongation may also occur. Voclosporin is a sensitive CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and erythromycin. Increased serum concentrations of vorapaxar are possible when vorapaxar, a CYP3A4 substrate, is coadministered with erythromycin, a CYP3A inhibitor. Increased exposure to vorapaxar may increase the risk of bleeding complications.
Voriconazole: (Major) Caution is advised when administering voriconazole with drugs that are known to prolong that QT interval, such as erythromycin. Both erythromycin and voriconazole are associated with QT prolongation; coadministration may increase this risk. Voriconazole has also been associated with rare cases of torsades de pointes, cardiac arrest, and sudden death. If these drugs are given together, closely monitor for prolongation of the QT interval. Rigorous attempts to correct any electrolyte abnormalities (i.e., potassium, magnesium, calcium) should be made before initiating concurrent therapy.
Vorinostat: (Major) Concomitant use of vorinostat and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with erythromycin is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Erythromycin is a moderate CYP3A4 inhibitor and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Zafirlukast: (Moderate) Erythromycin may decrease the bioavailability of zafirlukast. Be alert for decreased clinical response to zafirlukast when erythromycin is added concurrently.
Zaleplon: (Moderate) Monitor for an increase in zaleplon-related adverse effects if concomitant use with erythromycin is necessary. Concomitant use has been observed to increase zaleplon concentrations which may increase the risk for adverse effects. Coadministration of single oral doses of erythromycin 800 mg and zaleplon 10 mg resulted in a 34% increase in zaleplon peak concentrations and a 20% increase in zaleplon exposure. Zaleplon is a CYP3A substrate and erythromycin is a CYP3A inhibitor.
Zanubrutinib: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with erythromycin. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of erythromycin, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; erythromycin is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 317% when coadministered with erythromycin.
Zavegepant: (Major) Avoid concomitant use of zavegepant and erythromycin. Concomitant use may increase zavegepant exposure and the risk for zavegepant-related adverse effects. Zavegepant is an OATP1B3 substrate and erythromycin is an OATP1B3 inhibitor. Concomitant use with another OATP1B3 inhibitor increased zavegepant overall exposure by 2.3-fold.
Ziprasidone: (Major) Concomitant use of ziprasidone and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and erythromycin is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.
How Supplied
A/T/S/EMGEL/Erygel/Erythromycin Topical Gel: 2%
A/T/S/Eryderm/Erymax/Erythra Derm/Erythromycin/T-Stat Topical Sol: 2%
E.E.S./EryPed/Erythromycin/Erythromycin Ethylsuccinate Oral Gran F/Recon: 5mL, 200mg, 400mg
E.E.S./Erythrocin Stearate/Erythromycin/Erythromycin Ethylsuccinate Oral Tab: 250mg, 400mg, 500mg
Emcin Clear/Erycette/Erythromycin Topical Swab: 2%
E-Mycin/Ery-Tab/Erythromycin Oral Tab DR: 250mg, 333mg, 500mg
ERYC/Erythromycin Oral Cap DR Pellets: 250mg
Erythrocin Lactobionate Intravenous Inj Pwd F/Sol: 1g, 500mg
Erythromycin/Ilotycin/Romycin Ophthalmic Ointment: 0.5%
Maximum Dosage
4 g erythromycin base/day PO; 4 g/day IV.
Geriatric4 g erythromycin base/day PO; 4 g/day IV.
Adolescents50 mg/kg/day (Max: 2 g/day) PO is the common maximum dose used in clinical practice; however, up to 100 mg/kg/day PO (Max: 4 g/day) is FDA-approved for the treatment of severe infections. 20 mg/kg/day (Max: 4 g/day) is the FDA-approved IV maximum dose; however, doses up to 40 mg/kg/day (Max: 4 g/day) IV have been used off-label.
Children50 mg/kg/day (Max: 2 g/day) PO is the common maximum dose used in clinical practice; however, up to 100 mg/kg/day PO (Max: 4 g/day) is FDA-approved for the treatment of severe infections. 20 mg/kg/day (Max: 4 g/day) is the FDA-approved IV maximum dose; however, doses up to 40 mg/kg/day (Max: 4 g/day) IV have been used off-label.
Infants50 mg/kg/day PO is the common maximum dose used in clinical practice; however, up to 100 mg/kg/day PO is FDA-approved for the treatment of severe infections. 20 mg/kg/day is the FDA-approved maximum IV dose; however, doses up to 40 mg/kg/day IV have been used off-label.
Neonates50 mg/kg/day PO; safety and efficacy of IV use have not been established, however, doses up to 40 mg/kg/day IV have been used off-label.
Mechanism Of Action
Erythromycin binds to the 50S ribosomal subunit, inhibiting bacterial protein synthesis. It is effective against a wide range of microorganisms, and like other antibiotics that inhibit protein synthesis, erythromycin is mainly bacteriostatic. Activity of erythromycin against gram-positive organisms generally is greater than against gram-negative organisms due to its superior penetration into gram-positive organisms.
Erythromycin has actions that make it useful outside of the infectious disease field. Erythromycin mimics the effect of the gastrointestinal polypeptide motilin on gastrointestinal motility. This action is probably due to agonism at the motilin receptors. Motilin receptors are found mainly in the gastric antrum and proximal duodenum. The physiologic action produced is increased motility during the interdigestive (between-meal) period, without affecting postprandial motility. Erythromycin does not affect either dopamine receptors or increase acetylcholine concentrations in the gut. Tachyphylaxis can result from motilin receptor down regulation. Low-dose erythromycin (1 to 3 mg/kg/dose) has been shown to stimulate the neural motilin receptors, augmenting phase III migrating motor complexes, and thus peristalsis, whereas higher doses act on smooth muscle motilin receptors, producing sustained antral and antroduodenal contractions. With respect to feeding intolerance in neonates, erythromycin's prokinetic actions are likely to be both dose and gestational age-dependent, with better efficacy noted with higher doses and more mature neonates.
The susceptibility interpretive criteria for erythromycin are delineated by pathogen. The MICs are defined for Staphylococcus sp. and Enterococcus sp. as susceptible at 0.5 mcg/mL or less, intermediate at 1 to 4 mcg/mL, and resistant at 8 mcg/mL or more. The MICs are defined for S. pneumoniae, beta-hemolytic Streptococcus sp., and S. viridans group as susceptible at 0.25 mcg/mL or less, intermediate at 0.5 mcg/mL, and resistant at 1 mcg/mL or more.
The primary mechanisms for bacterial resistance to erythromycin include a modification of the 23S rRNA in the 50S ribosomal subunit to alter binding and active drug efflux.
Pharmacokinetics
Erythromycin is administered orally, intravenously, topically, and ophthalmically. Distribution of erythromycin is extensive following either oral or intravenous administration. Protein binding is extensive at 75% to 90%. Erythromycin is widely distributed into most body tissues except the brain and cerebrospinal fluid (CSF); in the presence of meningitis, penetration into the CSF increases. Tissue concentrations persist longer than do serum concentrations. Erythromycin concentrates in the bile and liver in patients with normal hepatic function. Because of erythromycin's relatively poor oral absorption, significant concentrations are achieved in the large intestine. Excretion of erythromycin is mainly via the bile, with some reabsorption. Only small amounts are found in the urine, with less than 5% excreted as unchanged drug. In adult patients with normal renal function, the serum half-life is about 1.5 hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-glycoprotein (P-gp)
Erythromycin is an inhibitor of the CYP3A4 enzyme system as well as a substrate and inhibitor of P-glycoprotein (P-gp). As a result, concurrent administration of erythromycin and drugs primarily metabolized by CYP3A4 may result in elevated serum concentrations of the concomitant drug and potentially significant drug interactions.
In general, oral bioavailability of erythromycin is poor. Erythromycin is readily inactivated by stomach acid, and several salts have been developed to overcome this drawback. Absorption takes place mainly in the duodenum. Gastric emptying time, the salt or formulation administered, and the presence of food in the stomach also affect bioavailability, especially for the unprotected base. Stearate preparations are susceptible to gastric acid destruction; however, dissociation in the duodenum yields free erythromycin, which is subsequently absorbed. Estolate preparations are more acid-stable and dissociate in the upper intestine to liberate an inactive propanoate ester, which is then absorbed and hydrolyzed in the blood to produce free erythromycin. Ethylsuccinate preparations are absorbed first and hydrolyzed in the blood to free erythromycin. The newest formulation of oral erythromycin is encapsulated pellets that are small enough to pass through the pyloric sphincter independent of gastric emptying and are absorbed as the base. None of the oral forms, however, allows complete absorption, although some evidence suggests oral bioavailability is greatest with the oral pellets.
All oral dosage forms produce relatively similar effective erythromycin base serum concentrations, although some data suggest the erythromycin base serum concentrations are somewhat higher after oral doses of the estolate salt compared to the ethylsuccinate. Following single oral doses, peak serum levels of free erythromycin are achieved in 1—4 hours and range from 0.1—2 mcg/mL.
Parenteral erythromycin is available as the gluceptate or lactobionate. Since administration of parenteral erythromycin is painful, these preparations are used when high serum levels of erythromycin are desirable. Serum levels of 8—12 mcg/mL are possible after IV doses of 500—1000 mg.
Pregnancy And Lactation
Observational studies in pregnant women have reported cardiovascular malformations after exposure to systemic erythromycin in early pregnancy.[43258] In a large population-based cohort study (n = 104,605 live births) assessing systemic macrolide (n = 8,632) or penicillin (n = 95,973) use during pregnancy and the risk of major malformations, macrolide use in the first trimester was associated with increased risk of any malformation (27.7 vs. 17.7 per 1,000 live births; adjusted risk ratio 1.55, 95% CI 1.19 to 2.03), and in particular, cardiovascular malformations (10.6 vs. 6.6 per 1,000 live births; adjusted risk ratio 1.62, 95% CI 1.05 to 2.51). Erythromycin use during the first trimester was associated with an increased risk of any major malformation compared to penicillins (adjusted risk ratio 1.5, 95% CI 1.13 to 1.99). Macrolide use during the second and third trimesters showed no increased risk of any major malformation (19.5 vs. 17.3 per 1,000 live births; adjusted risk ratio 1.13, 95% CI 0.94 to 1.36); however, a borderline association with gastrointestinal malformations was observed (adjusted risk ratio 1.89, 95% CI 1 to 3.58). Macrolide use in any trimester was associated with an increased risk of genital malformations (adjusted risk ratio 1.58, 95% CI 1.14 to 2.19), mainly hypospadias.[65012] Additionally, in another large population-based cohort study (n = 139,938 live births) assessing systemic antibiotic exposure during the first trimester of pregnancy (n = 15,469 exposures) and the risk of major birth defects, macrolide exposure was associated with an increased risk of digestive system malformations (adjusted odds ratio (aOR) 1.46, 95% CI 1.04 to 2.06, 35 exposed cases). Erythromycin use was also associated with an increased risk of urinary system malformations (aOR 2.12, 95% CI 1.08 to 4.17, 9 exposed cases).[62177] Systemic erythromycin has been reported to cross the placental barrier in humans, but fetal plasma concentrations are generally low. The effect of erythromycin on labor and obstetric delivery unknown.[43258] [48676]
According to the manufacturer, erythromycin should be used with caution in breast-feeding mothers because it is excreted into breast milk. A prospective observational study assessing the safety of macrolide antibiotics during lactation found that 12.7% (n = 55) of babies exposed to macrolides via breast milk experienced adverse events including rash, diarrhea, loss of appetite, and somnolence. The adverse event rate was similar to that seen in babies in a control group whose mothers were treated with amoxicillin (8.3%). Only 2 mothers in the study received erythromycin, 10 received azithromycin, 6 received clarithromycin, and the remainder were treated with roxythromycin. A population based cohort study found that babies diagnosed with infantile hypertrophic pyloric stenosis were 2.3—3 times more likely to have been exposed to a macrolide antibiotic through breast milk during the first 90 days of life than babies not exposed during that same time period. The study did not specify which antibiotic the mothers of affected babies were prescribed; however, the majority of macrolide prescriptions were for erythromycin (72%), with 7% for azithromycin and 1.7% for clarithromycin. The American Academy of Pediatrics (AAP) considers erythromycin to be a medication that is usually compatible with breast-feeding; azithromycin and clarithromycin have not been evaluated by the AAP. Consider the benefits of breast-feeding, the risk of potential drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding baby experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.