Apixaban and Verapamil: 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
Verapamil
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.
Verapamil can raise the level of apixaban (Eliquis) in your blood. Apixaban is a blood thinner, and verapamil slows down how your body clears it out. That means more of the blood thinner can build up, which can raise your chance of bleeding or bruising more easily.
The good news is that this is very manageable. Your care team knows about this combination and can watch you a bit more closely and adjust doses if needed. Keep taking both exactly as prescribed, and let your doctor or pharmacist know if you notice unusual bruising, nosebleeds, blood in your urine or stool, or bleeding that won't stop.
Effect: Increased apixaban exposure and elevated bleeding risk.
Mechanism: Apixaban is a substrate of both CYP3A4 and P-gp. Verapamil is a dual P-gp and moderate CYP3A4 inhibitor, reducing apixaban metabolism and efflux, raising AUC and Cmax. Neither drug is a prodrug; the effect is a straightforward increase in active apixaban.
- Magnitude: Analogous diltiazem PK study showed apixaban Cmax +31%, AUC +39%.
- Evidence: Probable; severity major; onset unspecified.
- Management: Use with caution. Monitor for signs of bleeding; dose may be individualized by the care team, especially with additional bleeding risk factors.
What happens
Increased apixaban exposure and increased risk of bleeding
Interaction Deep Dive
Because apixaban is a substrate for both P-gp and CYP3A42, taking it alongside an agent that inhibits both P-gp and moderately inhibits CYP3A4 can raise apixaban serum levels 5 and heighten the likelihood of bleeding 4. One pharmacokinetic study found that when apixaban was given together with diltiazem, an inhibitor of both P-gp and moderately of CYP3A4, its Cmax rose by 31% and its AUC by 39% 5. When the two must be given together, caution is advised 31.
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 medicines as prescribed unless your prescriber tells you otherwise. This combination can be managed with care.
- Your care team may monitor you more closely for signs of bleeding.
- Your apixaban dose may need to be adjusted and individualized by your doctor, especially if you have other bleeding risk factors.
- Watch for and report unusual bruising, nosebleeds, pink or red urine, black or bloody stools, or bleeding that does not stop.
Bring this up at your next visit or call your pharmacist if you have questions or notice anything concerning.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a retrospective observational analysis (N=426), the use of an agent that inhibits both P-gp and CYP3A4 moderately was associated with a markedly higher bleeding risk in patients receiving apixaban or rivaroxaban for atrial fibrillation. Bleeding, defined as the combination of major, clinically relevant non-major, and minor bleeding, was seen in 26.4% of those taking an interacting agent 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%); none of the patients were given concurrent erythromycin. When the individual drug interactions were assessed separately, no significant differences in bleeding rates emerged, and the effects of renal impairment, the particular inhibitor, or the particular anticoagulant were not assessed 4.
b) Giving diltiazem, an inhibitor of both P-gp and CYP3A4 at a moderate level, together with apixaban raised apixaban Cmax by 31% and AUC by 39% relative to apixaban given alone. In 18 subjects, a 10 mg oral dose of apixaban was given 8 days after starting diltiazem 360 mg once daily 5.
Common questions
Can I take Apixaban and Verapamil together?
Verapamil can increase apixaban (Eliquis) levels and raise bleeding risk, so use both with caution, keep taking them as prescribed, and report any unusual bleeding to your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Apixaban and Verapamil 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 Verapamil interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This combination can be managed with care. Your care team may monitor you more closely for signs of bleeding. Your apixaban dose may need to be adjusted and individualized by your doctor, especially if you have other bleeding risk factors. Watch for and report unusual bruising, nosebleeds, pink or red urine, black… 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 Verapamil 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 (5)
- 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
- 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
- Frost CE, Byon W, Song Y, et al: Effect of ketoconazole and diltiazem on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor. Br J Clin Pharmacol 2015; 79(5):838-846.
Keep reading about Verapamil
Keep reading about Apixaban
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