Digoxin and Erythromycin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Erythromycin
Digoxin
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased digoxin exposure and digoxin toxicity (nausea, vomiting, arrhythmias)
Interaction Deep Dive
Concomitant use of digoxin and erythromycin (P-gp inhibitor) results in increased digoxin exposure. Measure the digoxin serum level prior to erythromycin initiation and reduce the digoxin dose by 30% to 50%. Alternatively, change the frequency of digoxin administration. Monitor digoxin levels throughout the coadministration period12. Also, monitor potential signs and symptoms of clinical toxicity is necessary when initiating, adjusting, or discontinuing erythromycin 3.
Why it happens (mechanism)
Inhibition of P-gp mediated efflux transport of digoxin
Literature reports
5 reports — tap to read
a) During pharmacokinetic studies, coadministration of erythromycin and oral digoxin resulted in a 100% increase in digoxin serum concentrations 12.
b) An in vitro study evaluated the impact of macrolide antibiotics on the P-gp mediated efflux of digoxin. Erythromycin had no effect on the P-gp transport of digoxin, although it did reduce the efflux ratio of dihydrodigoxin and digoxigenin (relatively inactive metabolites) by 34% and 43%. Erythromycin demonstrated only partial P-gp inhibition with the use of a known P-gp substrate. In comparison, clarithromycin almost completely inhibited P-gp efflux of digoxin and azithromycin had minimal influence on P-gp mediated digoxin transport. The authors concluded the mechanism behind the clinical cases of erythromycin-induced digoxin toxicity is multifactorial 5.
c) A 15 year case-control study revealed a strong association between digoxin toxicity and recent treatment with macrolides (clarithromycin, erythromycin and azithromycin), with clarithromycin imparting the highest risk. Patients who received at least 1 prescription a macrolide antibiotic during digoxin treatment and who were hospitalized for digoxin toxicity within 14 days of starting the antibiotic (n=1659) were matched with controls (n=6439). Analysis revealed a strong correlation between digoxin toxicity and recent treatment with clarithromycin (14.8-fold increase in risk of toxicity), as well as erythromycin (3.7-fold increase in risk of toxicity) and azithromycin (3.7-fold increase in risk of toxicity) compared with no antibiotic treatment. The risk of digoxin toxicity was 4 times greater following treatment with clarithromycin compared with erythromycin and azithromycin. No difference in risk of digoxin toxicity was observed between erythromycin and azithromycin 4.
d) Digoxin toxicity, presumably induced by erythromycin, was described in an 86-year-old woman. The patient had been receiving oral digoxin 0.25 mg daily and was given erythromycin 250 mg orally 4 times a day for 10 days for the treatment of pharyngitis and otitis media. The digoxin serum levels increased from a trough of 1.9 nmol/L to 5.1 nmol/L six days after initiation of erythromycin therapy. The only sign of toxicity was persistent lethargy. Digoxin was discontinued, resulting in improvement over a period of 1 week. Six weeks later, digoxin 0.125 mg/day was reinstituted, resulting in steady-state trough serum levels of 1.2 to 1.4 nmol/L over the ensuing year 6.
e) The effects of erythromycin and clarithromycin on pharmacokinetics of IV administered digoxin (0.5 mg) were studied in 9 healthy male volunteers. Subjects were randomly assigned to the following treatments: 1) digoxin only 2) digoxin plus erythromycin 3) digoxin plus clarithromycin. Subjects took erythromycin or clarithromycin on the day before digoxin dosing and during the following 4 days. Erythromycin 200 mg was given 4 times a day and clarithromycin 200 mg was given twice daily. Neither erythromycin nor clarithromycin caused significant changes in AUC, clearance, volume of distribution and half-life of digoxin. There was a significant increase in urinary digoxin excretion when erythromycin and clarithromycin were coadministered (digoxin alone: 98.4 mL/min; digoxin with erythromycin: 137.3 mL/min; digoxin and clarithromycin: 133.6 mL/min) 7.
Common questions
Can I take Digoxin and Erythromycin together?
Increased digoxin exposure and digoxin toxicity (nausea, vomiting, arrhythmias) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Digoxin and Erythromycin interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Digoxin or Erythromycin need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (7)
- Product Information: LANOXIN(R) oral tablets, digoxin oral tablets. Concordia Pharmaceuticals Inc (per FDA), Kansas City, MO, 2019. DailyMed
- Product Information: DIGOXIN oral tablets, digoxin oral tablets. Aurobindo Pharma USA, Inc. (per Dailymed), East Windsor, NJ, May. DailyMed
- Product Information: DIGOXIN intravenous injection, digoxin intravenous injection. Hikma Pharmaceuticals USA Inc. (per Dailymed), Berkeley Heights, NJ, 2023. DailyMed
- Gomes T, Mamdani MM, Juurlink DN, et al: Macrolide-induced digoxin toxicity: a population-based study. Clin Pharmacol Ther 2009; 86(4):383-386. PubMed
- Hughes J & Crowe A: Inhibition of P-glycoprotein-mediated efflux of digoxin and its metabolites by macrolide antibiotics. J Pharmacol Sci 2010; 113(4):315-324. PubMed
- Morton MR & Cooper JW: Erythromycin-induced digoxin toxicity. Drug Intell Clin Pharm 1989; 23:668-670. DOI
- Tsutsumi K, Kotegawa T, Kuranari M, et al: The effect of erythromycin and clarithromycin on the pharmacokinetics of intravenous digoxin in healthy volunteers. J Clin Pharmacol 2002; 42:115-1164. PubMed
Keep reading about Erythromycin
Keep reading about Digoxin
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