Amiodarone with Digoxin Interaction Details

Brand Names Associated with Amiodarone

Brand Names Associated with Digoxin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Feb 27, 2024

Interaction Effect

Digoxin toxicity (nausea, vomiting, cardiac arrhythmias) and potentiated effects of amiodarone

Interaction Summary

Coadministration with amiodarone increased digoxin serum levels by 70% (oral digoxin)[1] and 17% (IV digoxin) [2]. Effects of amiodarone may be potentiated by digoxin, causing bradycardia, sinus arrest, and AV block [3]. Measure digoxin levels prior to starting concurrent use and reduce IV or IM digoxin dose by 15% to 30% [2] and oral digoxin dose by 30% to 50% [1], or modify dosing frequency. Monitor digoxin plasma levels [2][1], heart rate, and for evidence of digoxin toxicity. Drug interactions may persist for weeks to months after amiodarone discontinuation of amiodarone [3].

Severity

Major

Onset

Unspecified

Evidence

Established

How To Manage Interaction

Coadministration of amiodarone and digoxin may increase digoxin serum levels. Measure digoxin levels prior to initiation of concurrent use[2][1]. Reduce oral digoxin dose by about 30% to 50% [1][4] or the IV or IM digoxin dose by about 15% to 30% [2], or modify dosing frequency. Monitor digoxin plasma levels [2][1] and for digoxin toxicity. Concomitant use can potentiate effects of amiodarone and cause bradycardia, sinus arrest, and atrioventricular block. Monitor heart rate. Drug interactions may persist for weeks to months after discontinuation of amiodarone [3].

Mechanism Of Interaction

Inhibition of p-glycoprotein by amiodarone, and reduction of digoxin clearance; interference with amiodarone by digoxin

Literature Reports

A) During pharmacokinetic studies, coadministration of amiodarone and oral digoxin resulted in a 70% increase in digoxin serum concentrations [1][4]. Coadministration of amiodarone and IV digoxin resulted in a 17% increase in digoxin serum concentrations and a 40% increase in digoxin AUC [2].

B) Digoxin serum concentrations were increased significantly following the addition of amiodarone to oral and intravenous digoxin in patients receiving long term digoxin therapy. In patients taking oral digoxin, digoxin levels increased from 0.97 to 1.98 nanogram/mL (1.24 to 2.535 nanomol/L) in 28 patients. Gastrointestinal toxicity occurred in nine patients, central nervous system toxicity in five patients, and cardiovascular reactions in four patients. Increases in digoxin serum levels were produced one to three weeks after amiodarone administration. Kinetic studies in six patients receiving digoxin 1 mg IV prior to and during amiodarone administration resulted in increased serum digoxin levels at 30 minutes (from 8.6 to 10 nanogram/mL or 11.01 nanomol/L to 13 nanomol/L); digoxin half-life was prolonged by 31%. The total body clearance and nonrenal clearance of digoxin was reduced significantly. Renal clearance of digoxin decreased by 22% [5].

C) Oral amiodarone increased the bioavailability of digoxin in healthy subjects. Subjects received a single oral dose of digoxin 0.5 mg prior to and at the end of a 7-day treatment course with amiodarone (200 mg orally three times daily). In four of six subjects, significant increases in serum digoxin levels and AUC were observed while renal clearance was unaltered. Recovery of digoxin in the urine was increased. The authors suggested that amiodarone increases the bioavailability of digoxin by a mechanism independent of changes in was suspected [6].

D) Oral amiodarone administered concomitantly with oral digoxin (0.5 milligrams as a single dose) significantly increased digoxin serum concentrations and area-under-the-curve. With intravenous digoxin, changes were marginal and not statistically significant. The bioavailability of digoxin was 33% greater with amiodarone as determined from the mean values of oral and intravenous AUC. These data suggest that the most relevant aspect of the amiodarone-digoxin interaction is the enhancement of oral digoxin bioavailability. The authors suggested that amiodarone may inhibit p-glycoprotein in the gastrointestinal tract [7].

E) Serious cardiac arrhythmias have been reported, in 2 case studies, in patients treated with amiodarone and digoxin, possibly because of a pharmacodynamic interaction. In one case a 8-second episode of asystole was observed in a 52-year-old man with severe angina and congestive heart failure treated with amiodarone and digoxin [8]. In the other case, concurrent use of amiodarone and digoxin was associated with torsades de pointes in a 74-year-old female [9].

F) In patients receiving digoxin therapy, administration of oral amiodarone regularly results in an increase in serum digoxin concentration that may reach toxic levels with resultant clinical toxicity. Amiodarone taken concomitantly with digoxin increases the serum digoxin concentration by 70% after one day. On administration of oral amiodarone, the need for digitalis therapy should be reviewed and the dose reduced by approximately 50% or discontinued. If digitalis treatment is continued, serum levels should be closely monitored and patients observed for clinical evidence of toxicity. These precautions probably should apply to digitoxin administration as well [10].

References

1 ) Product Information: LANOXIN(R) oral tablets, digoxin oral tablets. Covis Pharmaceuticals, Inc. (per FDA), Cary, NC, 2013.

2 ) Product Information: LANOXIN(R) intravenous injection, intramuscular injection, digoxin intravenous injection, intramuscular injection. Covis Pharmaceuticals, Inc. (per FDA), Cary, NC, 2015.

3 ) Product Information: CORDARONE(R) oral tablets, amiodarone oral tablets. Wyeth Pharmaceuticals Inc (per FDA), Philadephia, PA, 2018.

4 ) Product Information: digoxin oral solution, digoxin oral solution. Roxane Laboratories, Inc. (per manufacturer), Columbus, OH, 2012.

5 ) Nademanee K, Kannan R, Hendrickson J, et al: Amiodarone-digoxin interaction: clinical significance, time course of development, potential pharmacokinetic mechanisms and therapeutic implications. J Am Coll Cardiol 1984; 4:111-116.

6 ) Maragno I, Santostasi G, Gaion RM, et al: Influence of amiodarone on oral digoxin bioavailability in healthy volunteers. Int J Clin Pharm Res 1984; 4:149-153.

7 ) Santostasi G, Fantin M, Maragno I, et al: Effects of amiodarone on oral and intravenous digoxin kinetics in healthy subjects. J Cardiovasc Pharmacol 1987; 9:385-390.

8 ) Klein HO, Beker B, DiSegni E, et al: Asystole produced by the combination of amiodarone and digoxin. Am Heart J 1987; 113:399-400.

9 ) Bajaj BP, Baig MW, & Perrins EJ: Amiodarone-induced torsades de pointes: the possible role of digoxin. Int J Cardiol 1991; 33:335-337.

10 ) Product Information: Cordarone(R) IV, amiodarone. Wyeth Laboratories, Philadelphia, PA, 2002.

Amiodarone Overview

• Amiodarone is used to treat and prevent certain types of serious, life-threatening ventricular arrhythmias (a certain type of abnormal heart rhythm when other medications did not help or could not be tolerated. Amiodarone is in a class of medications called antiarrhythmics. It works by relaxing overactive heart muscles.

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.

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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.