Digoxin with Erythromycin Interaction Details

Brand Names Associated with Digoxin

Brand Names Associated with Erythromycin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Jan 08, 2024

Interaction Effect

Increased digoxin levels and digoxin toxicity (nausea, vomiting, arrhythmias)

Interaction Summary

The coadministration of digoxin and erythromycin results in elevated digoxin serum levels. The mechanism behind the interaction is not completely understood . 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 period .

Severity

Major

Onset

Delayed

Evidence

Established

How To Manage Interaction

Concomitant use of digoxin and erythromycin results in elevated digoxin serum levels. 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 period.

Mechanism Of Interaction

Unknown

Literature Reports

A) 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 .

B) 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 .

C) 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 .

D) 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) .

Digoxin Overview

• Digoxin is used to treat heart failure and abnormal heart rhythms (arrhythmias). It helps the heart work better and it helps control your heart rate.

Erythromycin Overview

• Erythromycin is used to treat certain infections caused by bacteria, such as infections of the respiratory tract, including bronchitis, pneumonia, Legionnaires' disease (a type of lung infection), and pertussis (whooping cough; a serious infection that can cause severe coughing); diphtheria (a serious infection in the throat); sexually transmitted diseases (STD), including syphilis; and ear, intestine, gynecological, urinary tract, and skin infections. It also is used to prevent recurrent rheumatic fever. Erythromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as erythromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.