Warfarin with Amiodarone Interaction Details

Brand Names Associated with Warfarin

  • Coumadin®
  • Jantoven®
  • Warfarin

Brand Names Associated with Amiodarone

  • Amiodarone
  • Cordarone®
  • Pacerone®

Medical Content Editor
Last updated Feb 27, 2024

Curious for more information about this interaction?

Ask our pharmacists directly!

Reach out to us

Interaction Effect

Increased warfarin exposure, INR, and risk of bleeding

Interaction Summary

Concurrent use of amiodarone (CYP2C9 and CYP3A4 inhibitor) and warfarin (CYP2C9 and CYP3A4 substrate) increases warfarin exposure[1] and increases prothrombin time by 100% after 3 to 4 days, which may result in serious or fatal bleeding. If concurrent use is required, decrease the warfarin dose by one-third to one-half [2]. In a study, the combination was found to have a higher risk of achieving INR greater than 5 when compared to warfarin alone. This occurred most commonly during the first 12 weeks of concomitant warfarin and amiodarone therapy, therefore monitor intensively during this period [3]. Consider the drug interaction potential when starting, stopping, or changing dosages of concomitant medications [1]. Due to the long half-life of amiodarone (15 to 142 days), drug interaction effects can persist for weeks to months after amiodarone discontinuation [4].

Severity

Major

Onset

Delayed

Evidence

Established

How To Manage Interaction

Concurrent use of amiodarone and warfarin increases warfarin exposure[1] and increases prothrombin time by 100% after 3 to 4 days, which may result in serious or fatal bleeding. If concurrent use is required, decrease the warfarin dose by one-third to one-half and monitor INR closely [2] especially during the first 12 weeks of concomitant use [3]. Consider the drug interaction potential when starting, stopping, or changing dosages of concomitant medications [1]. Due to the long half-life of amiodarone (15 to 142 days), drug interaction effects can persist for weeks to months after amiodarone discontinuation [4].

Mechanism Of Interaction

Inhibition of CYP2C9- and CYP3A4-mediated metabolism of warfarin by amiodarone

Literature Reports

A) A retrospective, cohort study of 70 patients (mean age, 61 +/- 15 years) concurrently taking warfarin and amiodarone found that amiodarone significantly increased the effect of warfarin, as indicated by supratherapeutic INR values. Most of the patients in the study were taking warfarin for atrial fibrillation/flutter (80%) and/or valve replacement (34%). The majority of the patients in the study were initiated on amiodarone for nonvalvular atrial arrhythmias (77%). Patient data was collected retrospectively from an anticoagulation clinic database, pharmacy records, and patient records. Sixty-three patients were actively receiving warfarin therapy before amiodarone was initiated. Study subjects had concurrent warfarin and amiodarone use data for a mean of 632 +/- 519 days. The study found that the relative risk (RR) of an INR greater than 5 for patients taking both amiodarone and warfarin was 1.366 (95% CI, 1.101 to 1.695) compared to patients on warfarin alone. For patients receiving both amiodarone and warfarin, the RR of an INR greater than 5 was 2.306 (95% CI, 0.996 to 5.339) after initiating amiodarone when compared to before the addition of amiodarone. INR values greater than 5 were most common during the first 12 weeks while on concomitant warfarin and amiodarone therapy. Intensive monitoring during this period and empiric 35 to 65% warfarin dosage reduction are recommended [3].

References

    1 ) Product Information: COUMADIN(R) oral tablets, warfarin sodium oral tablets. Bristol-Myers Squibb Company (per manufacturer), Princeton, NJ, 2019.

    2 ) Product Information: NEXTERONE intravenous injection, amiodarone HCl intravenous injection. Baxter Healthcare Corporation (per FDA), Deerfield, IL, 2021.

    3 ) Lu Y, Won KA, Nelson BJ, et al: Characteristics of the amiodarone-warfarin interaction during long-term follow-up. Am J Health Syst Pharm 2008; 65(10):947-952.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

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

Warfarin Overview

  • Warfarin is used to prevent blood clots from forming or growing larger in your blood and blood vessels. It is prescribed for people with certain types of irregular heartbeat, people with prosthetic (replacement or mechanical) heart valves, and people who have suffered a heart attack. Warfarin is also used to treat or prevent venous thrombosis (swelling and blood clot in a vein) and pulmonary embolism (a blood clot in the lung). Warfarin is in a class of medications called anticoagulants ('blood thinners'). It works by decreasing the clotting ability of the blood.

See More information Regarding Warfarin

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.

See More information Regarding Amiodarone

Return To Our Drug Interaction Homepage

Feedback, Question Or Comment About This Information?

Ask , our medical editor, directly! He's always more than happy to assist.

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:

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.