Amiodarone with Apixaban Interaction Details

Brand Names Associated with Amiodarone

Brand Names Associated with Apixaban

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 04, 2024

Interaction Effect

Increased apixaban exposure and increased risk of bleeding

Interaction Summary

Concurrent use of apixaban, a substrate of both P-gp and CYP3A4[1], and a dual P-gp and CYP3A4 inhibitor, including amiodarone, may increase the risk of bleeding [2], especially in older patients. Bleeding risk may be increased for up to 60 days after amiodarone use [3].

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concurrent use of apixaban with a dual P-gp and CYP3A4 inhibitor, including amiodarone, may increase the risk of bleeding[2] especially in older patients. Bleeding risk may be increased for up to 60 days after amiodarone use [3].

Mechanism Of Interaction

Inhibition of CYP3A4-mediated apixaban metabolism; inhibition of P-gp-mediated efflux transport of apixaban

Literature Reports

A) Patients older than 66 years (median age, 80 years) with atrial fibrillation receiving a direct oral anticoagulant (DOAC) concomitantly with amiodarone therapy had an increased risk of major bleeding compared with unexposed controls (OR, 1.53; 95% CI, 1.24 to 1.89) in a retrospective case control analysis (N=86,679; 2766 cases of major bleeding [3.2% of surveyed population] matched with 5532 controls). This association was significant with current use (within 60 days) of amiodarone, but not with past use (61 to 140 days). Results were adjusted for patient demographics (eg, age, gender (female, 48.3%), and geography), comorbidities (eg, hypertension, 89.9%; congestive heart failure, 36.6%; diabetes 37%), and concomitant medications (eg, lipid lowering medications, 52.2%; beta-blockers, 47.8%). Apixaban was the most commonly used DOAC (53.8%) [3].

B) Treatment with a combined P-gp and moderate CYP3A4 inhibitor significantly increased risk of bleeding in patients taking apixaban or rivaroxaban for atrial fibrillation in a retrospective observational analysis (N=426). Bleeding, defined as the composite of major, clinically relevant non-major, and minor bleeding, occurred in 26.4% of the interacting agent group vs 18.4% in the propensity-matched control group (HR, 1.8; 95% CI, 1.19 to 2.73). Interacting agents consisted of diltiazem (68.1%), amiodarone (26.8%), verapamil (5.7%), dronedarone (2.3%), and multiple agents (2.8%); no patients received concomitant erythromycin. No significant differences in bleeding rates were identified when individual drug interactions were evaluated, and the impact of renal dysfunction, specific inhibitor, or specific anticoagulant were not evaluated [2].

References

1 ) Product Information: ELIQUIS(R) oral tablets, apixaban oral tablets. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2019.

2 ) Hanigan S, Das J, Pogue K, et al: The real world use of combined P-glycoprotein and moderate CYP3A4 inhibitors with rivaroxaban or apixaban increases bleeding. J Thromb Thrombolysis 2020; 49(4):636-643.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

3 ) Shurrab M, Jackevicius CA, Austin PC, et al: Association between concurrent use of amiodarone and DOACs and risk of bleeding in patients with atrial fibrillation. Am J Cardiol 2023; 186:58-65.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

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.

Apixaban Overview

• Apixaban is used help prevent strokes or blood clots in people who have atrial fibrillation (a condition in which the heart beats irregularly, increasing the chance of clots forming in the body and possibly causing strokes) that is not caused by heart valve disease. Apixaban is also used to prevent deep vein thrombosis (DVT; a blood clot, usually in the leg) and pulmonary embolism (PE; a blood clot in the lung) in people who are having hip replacement or knee replacement surgery. Apixaban is also used to treat DVT and PE and may be continued to prevent DVT and PE from happening again after the initial treatment is completed. Apixaban is in a class of medications called factor Xa inhibitors. It works by blocking the action of a certain natural substance that helps blood clots to form.

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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.