Apixaban and Dronedarone: 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
Dronedarone
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.
Here's what's going on. Apixaban (Eliquis) is a blood thinner that helps prevent clots. Dronedarone (Multaq) helps steady your heart rhythm, but it also slows down how your body clears apixaban. That means more apixaban can build up in your blood, which raises your chance of bleeding, like easy bruising, nosebleeds, or bleeding that is hard to stop.
The good news is this is very manageable. Your care team may lower your apixaban dose and keep a closer eye on you. Please keep taking both medicines exactly as prescribed, and ask your pharmacist or doctor before making any changes.
Effect: Increased apixaban exposure and elevated bleeding risk.
Mechanism: Dronedarone is a dual P-gp inhibitor and moderate CYP3A4 inhibitor. It reduces both CYP3A4-mediated metabolism and P-gp-mediated efflux of apixaban, increasing apixaban AUC and Cmax. Neither agent is a prodrug, so the effect is a straightforward increase in active anticoagulant exposure.
- Severity: Major; evidence probable.
- Management: If coadministration is required in AF, a reduced apixaban regimen (3.75 mg every 12 hours, normal or reduced renal function) is recommended.
- Monitor: Signs of bleeding; use added caution with other agents raising apixaban levels.
What happens
Increased apixaban exposure and increased risk of bleeding
Interaction Deep Dive
Taking apixaban together with dronedarone (which inhibits both P-gp and CYP3A4 to a moderate degree) can raise apixaban exposure and heighten the likelihood of bleeding4. When patients with atrial fibrillation must receive dronedarone alongside apixaban, a lowered apixaban dose is advised (3.75 mg every 12 hours whether renal function is normal or reduced)4. Exercise caution during coadministration1, particularly when other agents that may elevate apixaban concentrations are also present2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated apixaban metabolism; inhibition of P-gp-mediated efflux transport of apixaban
How to manage this interaction
This can be managed safely. When these two are used together for atrial fibrillation, the guidance is a reduced apixaban dose (3.75 mg every 12 hours), which your care team will set and individualize for you.
- Keep taking both medicines exactly as prescribed unless your doctor tells you otherwise.
- Your team may monitor you more closely for bleeding.
- Watch for unusual bruising, nosebleeds, pink or red urine, black stools, or bleeding that won't stop, and report these promptly.
- Tell your pharmacist about any new medicines or supplements, since some can raise apixaban levels further.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a pharmacokinetic/pharmacodynamic modeling analysis, giving dronedarone 400 mg every 12 hours together with apixaban 5 mg every 12 hours for 14 days in geriatric patients (over 65 years) with atrial fibrillation was projected to raise apixaban Cmax by 1.41-fold (90% CI, 1.2 to 1.91) and apixaban AUC by 1.33-fold (90% CI, 1.15 to 1.68). Among geriatric patients with moderate renal impairment (estimated GFR 30 to 60 mL/min) taking apixaban 5 mg every 12 hours, Cmax rose 1.39-fold (90% CI, 1.21 to 1.97) and AUC rose 1.38-fold (90% CI, 1.17 to 1.83); in those with severe renal impairment (eGFR under 30), Cmax rose 1.44-fold (90% CI, 1.21 to 1.93) and AUC rose 1.46-fold (90% CI, 1.24 to 1.92). Relative to patients taking apixaban alone, combining apixaban 5 mg every 12 hours with dronedarone raised bleeding risk by 1.45-fold (90% CI, 0.92 to 2.57) in those with normal renal function, 1.79-fold (90% CI, 1.07 to 3.31) in those with moderate renal impairment, and 1.95-fold (90% CI, 0.93 to 3.27) in those with severe impairment 4.
b) In a retrospective observational analysis (N=426), use of an agent that is both a P-gp inhibitor and a moderate CYP3A4 inhibitor markedly raised bleeding risk in patients receiving apixaban or rivaroxaban for atrial fibrillation. Bleeding, defined as the composite of major, clinically relevant non-major, and minor bleeding, was seen in 26.4% of the interacting agent group compared with 18.4% in the propensity-matched control group (HR, 1.8; 95% CI, 1.19 to 2.73). The interacting agents were diltiazem (68.1%), amiodarone (26.8%), verapamil (5.7%), dronedarone (2.3%), and multiple agents (2.8%); no patients were given concomitant erythromycin. When individual drug interactions were assessed, no significant differences in bleeding rates were found, and the effects of renal dysfunction, the specific inhibitor, or the specific anticoagulant were not assessed 3.
Common questions
Can I take Apixaban and Dronedarone together?
Dronedarone raises apixaban levels and bleeding risk, so your care team may lower your apixaban dose and watch you more closely. Keep taking both as prescribed and report any signs of bleeding. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Apixaban and Dronedarone interaction?
It is rated major. Potentially serious — often needs a change or close 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 Dronedarone interaction managed?
This can be managed safely. When these two are used together for atrial fibrillation, the guidance is a reduced apixaban dose (3.75 mg every 12 hours), which your care team will set and individualize for you. Keep taking both medicines exactly as prescribed unless your doctor tells you otherwise. Your team may monitor you more closely for bleeding. Watch for unusual bruising, nosebleeds, pink or r… 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 Dronedarone 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 a safer alternative to one of these medications for me?
References (4)
- Burnett AE, Mahan CE, Vazquez SR, et al: Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. J Thromb Thrombolysis 2016; 41(1):206-232. PubMed
- 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
- Wen H-N, He Q-F, Xiang X-Q, et al: Predicting drug-drug interactions with physiologically based pharmacokinetic/pharmacodynamic modelling and optimal dosing of apixaban and rivaroxaban with dronedarone co-administration. Thromb Res 2022; 218:24-34. DOI
Keep reading about Dronedarone
Keep reading about Apixaban
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