Diltiazem and Apixaban: 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
Diltiazem
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.
Diltiazem can raise the amount of apixaban (Eliquis) in your blood. Apixaban is a blood thinner, and diltiazem slows down how your body clears it. That means a little more of the blood thinner sticks around, which can raise your chance of bleeding or bruising.
The good news is this is very manageable. In studies the increase was modest (about a third more). Your care team knows about this combo and can watch you and adjust your dose if needed. Keep taking both exactly as prescribed, and let your doctor or pharmacist know if you notice unusual bruising, nosebleeds, pink or dark urine, or bleeding that won't stop.
Effect: Increased apixaban exposure and bleeding risk. Neither drug is a prodrug; apixaban is the affected substrate.
Mechanism: Diltiazem is a dual P-gp and moderate CYP3A4 inhibitor. It reduces CYP3A4-mediated metabolism and P-gp efflux of apixaban, increasing systemic exposure.
- Magnitude: Apixaban Cmax +31%, AUC +39% in a PK study.
- Onset: Unspecified.
- Evidence: Probable; severity major.
Management: Coadminister with caution. Monitor for signs/symptoms of bleeding; consider renal/hepatic function and overall bleeding risk. Dose may be individualized by the care team.
What happens
Increased apixaban exposure and increased risk of bleeding
Interaction Deep Dive
Apixaban is metabolized as a substrate of P-gp as well as CYP3A42, so taking it together with 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 combining apixaban with diltiazem, which acts as a dual P-gp and moderate CYP3A4 inhibitor, produced increases of 31% in Cmax and 39% in AUC 5. Should the two need to be used together, exercise caution 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
This combination can be used safely with attention from your care team.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise.
- Your team may monitor you more closely for bleeding, and your apixaban dose may be adjusted and individualized to your situation.
- Watch for warning signs: unusual bruising, nosebleeds, bleeding gums, pink/red/dark urine, black stools, or coughing/vomiting blood.
- Tell any provider you see that you take both medicines, and ask your pharmacist before starting new drugs or supplements.
If you notice bleeding that won't stop or feel dizzy or weak, seek care right away.
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), use of an agent that inhibits both P-gp and CYP3A4 to a moderate degree markedly raised bleeding risk among 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 those on 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 included diltiazem (68.1%), amiodarone (26.8%), verapamil (5.7%), dronedarone (2.3%), and multiple agents (2.8%); none of the patients were given concomitant erythromycin. When individual drug interactions were assessed, no significant differences in bleeding rates emerged, and the influence of renal dysfunction, the specific inhibitor, or the specific anticoagulant was not assessed 4.
b) Giving diltiazem, an agent that inhibits both P-gp and CYP3A4 moderately, together with apixaban raised apixaban Cmax by 31% and AUC by 39% relative to apixaban given alone. In 18 subjects, oral apixaban 10 mg was given 8 days after starting diltiazem 360 mg once daily 5.
Common questions
Can I take Diltiazem and Apixaban together?
Diltiazem modestly raises apixaban levels and bleeding risk, so keep taking both as prescribed while your care team monitors you and adjusts the dose if needed. Report any unusual bleeding or bruising promptly. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Diltiazem and Apixaban 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 Diltiazem and Apixaban interaction managed?
This combination can be used safely with attention from your care team. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Your team may monitor you more closely for bleeding, and your apixaban dose may be adjusted and individualized to your situation. Watch for warning signs: unusual bruising, nosebleeds, bleeding gums, pink/red/dark urine, black stools, or cough… 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 Diltiazem or Apixaban 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 Diltiazem
Keep reading about Apixaban
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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