Apixaban and Amiodarone: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Aug 8, 2026 · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Amiodarone
Apixaban
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.
Amiodarone can raise the level of apixaban (Eliquis) in your blood. Apixaban is a blood thinner, and amiodarone slows down how your body clears it. When more apixaban stays in your system, its blood-thinning effect gets stronger, which means a higher chance of bleeding or bruising.
Watch for signs like unusual bruising, nosebleeds, pink or red urine, black stools, or bleeding that won't stop. This matters more for older adults. One thing to know: amiodarone leaves the body very slowly, so this effect can linger for weeks. The good news is your care team can manage this by adjusting your dose and keeping a closer eye on you. Please don't stop either drug on your own, just talk with your pharmacist or doctor.
Effect: Increased apixaban exposure and elevated bleeding risk.
Mechanism: Amiodarone is a dual inhibitor of CYP3A4 and P-glycoprotein; apixaban is a substrate of both. Inhibition reduces metabolism and efflux, increasing apixaban AUC/Cmax and anticoagulant PD effect. Neither drug is a prodrug.
- Direction: Increased apixaban effect (bleeding).
- Onset: Unspecified; note amiodarone's long half-life means risk may persist up to 60 days after discontinuation.
- Evidence: Probable.
- Management: Use with caution, especially in elderly or with other bleeding risk factors/interacting drugs. Monitor for bleeding; dose may need individualization per guidelines.
What happens
Increased apixaban exposure and increased risk of bleeding
Interaction Deep Dive
Because apixaban is a substrate for both P-gp and CYP3A41, taking it together with an agent that inhibits both P-gp and CYP3A4, such as amiodarone, may raise the likelihood of bleeding 3, particularly among elderly patients. This elevated bleeding risk can persist for as long as 60 days following amiodarone administration 4. When the two must be given together, exercise caution, especially when additional bleeding risk factors are present or when other medications that can raise apixaban concentrations are also being used 2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated apixaban metabolism; inhibition of P-gp-mediated efflux transport of apixaban
How to manage this interaction
Keep taking both medications exactly as prescribed unless your care team tells you otherwise. This combination is used when needed, with some extra caution.
- Your team may adjust and individualize your apixaban dose and monitor you more closely, especially if you are older or have other bleeding risk factors.
- Tell your prescriber about all other medicines you take, since some can further raise apixaban levels.
- Because amiodarone leaves the body slowly, this caution can apply for up to about 60 days after stopping it.
- Report any unusual bleeding or bruising to your pharmacist or doctor right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) A metaanalysis of 9 studies, comprising 118,037 patients taking amiodarone together with a direct oral anticoagulant (DOAC) and 224,539 patients receiving a DOAC alone, found that combining amiodarone with DOAC therapy did not meaningfully raise bleeding risk or lower the risk of stroke or systemic embolism relative to DOAC monotherapy. The studies analyzed were cohort studies (n=6) and post-hoc analyses of randomized controlled trials (n=3), all conducted in heart failure populations. Comparing the amiodarone plus DOAC group with the DOAC only group, no significant difference was seen in the primary outcome of major bleeding (OR, 1.12; 95% CI, 0.98 to 1.27); likewise, no significant difference was found between groups for any secondary outcome, including any bleeding (OR, 1.18; 95% CI, 0.88 to 1.57), gastrointestinal bleeding (OR, 0.97; 95% CI, 0.84 to 1.11), intracranial bleeding (OR, 1.14; 95% CI, 1 to 1.3), stroke or systemic embolism (OR, 0.86; 95% CI, 0.74 to 1), or all-cause mortality (OR, 1.58; 95% CI, 0.72 to 3.46). The analysis lacked sufficient power to evaluate clinical outcomes according to the particular DOAC used, and most of the studies employed apixaban or rivaroxaban. In addition, dosing regimens reported were not standardized across the studies, and some of the included studies failed to provide dosing regimen details. Meaningful differences among the studies included may affect the validity of these findings 5.
b) In a retrospective case control analysis (N=86,679; 2766 cases of major bleeding [3.2% of surveyed population] matched with 5532 controls), patients over 66 years of age (median age, 80 years) with atrial fibrillation who received a direct oral anticoagulant (DOAC) together with amiodarone had a higher risk of major bleeding than unexposed controls (OR, 1.53; 95% CI, 1.24 to 1.89). This relationship was significant for current amiodarone use (within 60 days), but not for past use (61 to 140 days). The findings 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 DOAC used most frequently (53.8%) 4.
c) In a retrospective observational analysis (N=426), treatment with an agent that combined P-gp and moderate CYP3A4 inhibition markedly raised the risk of bleeding in patients using apixaban or rivaroxaban for atrial fibrillation. Bleeding, defined as the composite of major, clinically relevant non-major, and minor bleeding, was observed in 26.4% of the interacting agent group versus 18.4% in the propensity-matched control group (HR, 1.8; 95% CI, 1.19 to 2.73). The interacting agents included diltiazem (68.1%), amiodarone (26.8%), verapamil (5.7%), dronedarone (2.3%), and multiple agents (2.8%); none of the patients received concurrent erythromycin. No significant differences in bleeding rates emerged when individual drug interactions were assessed, and the influence of renal dysfunction, the specific inhibitor, or the specific anticoagulant was not assessed 3.
Common questions
Can I take Apixaban and Amiodarone together?
Amiodarone can increase apixaban levels and your bleeding risk, so take both as prescribed and watch for unusual bruising or bleeding, especially if you are older. Your care team can manage this with dosing and monitoring, and the effect can last weeks after amiodarone is stopped. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Apixaban and Amiodarone interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Apixaban and Amiodarone interaction managed?
Keep taking both medications exactly as prescribed unless your care team tells you otherwise. This combination is used when needed, with some extra caution. Your team may adjust and individualize your apixaban dose and monitor you more closely, especially if you are older or have other bleeding risk factors. Tell your prescriber about all other medicines you take, since some can further raise apix… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Apixaban or Amiodarone 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 anything you'd monitor while I'm on both?
References (5)
- Product Information: ELIQUIS(R) oral tablets, apixaban oral tablets. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2019. DailyMed
- Steffel J, Collins R, Antz M, et al: 2021 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Europace 2021; 23(10):1612-1676.
- 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
- 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. DOI
- Kido K, Shimizu M, Shiga T, et al: The concomitant therapy of direct oral anticoagulants with amiodarone in atrial fibrillation: a meta-analysis. J Cardiovasc Pharmacol Ther 2025; 30:1-8. PubMed
Keep reading about Amiodarone
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