Clopidogrel and Apixaban: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Clopidogrel
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.
What happens
Increased risk of bleeding and can cause serious, potentially fatal bleeding
Interaction Deep Dive
Coadministration of apixaban and antiplatelet agents increases the risk of bleeding2. Promptly evaluate any signs or symptoms of blood loss that occur in a patient treated concomitantly with anticoagulants and antiplatelet drugs 3. Discontinue apixaban in patients with active pathological hemorrhage. Advise patients of signs and symptoms of blood loss and to report them immediately or go to an emergency room. Discontinue apixaban in patients with active pathological hemorrhage. An agent to reverse the anti-factor Xa activity of apixaban is available. The pharmacodynamic effect of apixaban can be expected to persist for at least 24 hours after the last dose. Prothrombin complex concentrate (PCC), activated prothrombin complex concentrate or recombinant factor VIIa may be considered. When PCCs are used, monitoring for the anticoagulation effect of apixaban using a clotting test (PT, INR, or aPTT) or anti-factor Xa (FXa) activity is not useful and is not recommended. Activated oral charcoal reduces absorption of apixaban, thereby lowering apixaban plasma concentration 2.
Why it happens (mechanism)
Additive effects on hemostasis
Literature reports
3 reports — tap to read
a) A clinical trial of high-risk, post-acute coronary syndrome patients treated with aspirin or the combination of aspirin and clopidogrel (APPRAISE-2) was terminated early due to a higher rate of bleeding with apixaban compared to placebo. The rate of ISTH major bleeding was 2.8% per year with apixaban vs 0.6% per year with placebo in patients receiving single antiplatelet therapy, and was 5.9% per year with apixaban vs 2.5% per year with placebo in those receiving dual antiplatelet therapy 2.
b) In patients receiving apixaban, concomitant use of aspirin increased the bleeding risk from 1.8% per year to 3.4% per year, and concomitant use of aspirin and warfarin increased the bleeding risk from 2.7% per year to 4.6% per year in a clinical trial (ARISTOTLE); there was limited (2.3%) use of dual antiplatelet therapy with apixaban in this trial 2.
c) Concomitant use of direct oral anticoagulant (DOAC) and antiplatelet therapy (APT; n=78) compared to DOAC therapy alone (n=329) did not significantly alter the incidence of major bleeding (1.3% vs 1.2%) or clinically relevant non-major bleeding (10.2% vs 6.4%) over 6 months of treatment in a retrospective study. Patients were primarily Caucasian men with a mean age of 63.7 years. Patients receiving concurrent APT had significantly higher mean body mass index (30.7 vs 28.4), mean CHA2DS2-VASc score (4.28 vs 3.85), and were more likely to have diabetes (26.9% vs 17.3%) compared with those prescribed DOAC monotherapy. DOACs were prescribed for VTE treatment or atrial fibrillation, and included apixaban (58.5%), rivaroxaban (38.1%), and dabigatran (3.4%). Single antiplatelet therapy was utilized in 94.9% (74 patients), with aspirin 81 mg once daily as the most common regimen (69 patients). Other APT regimens included aspirin 81 mg twice daily (3 patients), aspirin 325 mg daily (1 patient), clopidogrel 75 mg daily (1 patient), and dual APT with aspirin 81 mg and clopidogrel 75 mg daily (4 patients) 1.
Common questions
Can I take Clopidogrel and Apixaban together?
Increased risk of bleeding and can cause serious, potentially fatal bleeding Always confirm with your pharmacist or prescriber before making any change.
How serious is the Clopidogrel 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 strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Clopidogrel 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 (3)
- Tinkham TT, Vazquez SR, Jones AE, et al: Direct oral anticoagulant plus antiplatelet therapy: prescribing practices and bleeding outcomes. J Thromb Thrombolysis 2020; 49(3):492-496. PubMed
- Product Information: ELIQUIS(R) oral film coated tablets, apixaban oral film coated tablets. Bristol-Myers Squibb Company (per Dailymed), Princeton, NJ, 2024. DailyMed
- Product Information: SAVAYSA(R) oral tablets, edoxaban oral tablets. Daiichi Sankyo Inc (per FDA), Basking Ridge, NJ, 2023. DailyMed
Keep reading about Clopidogrel
Keep reading about Apixaban
These medications also interact with supplements
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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