Cilostazol 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
Cilostazol
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.
Both of these medicines affect how your blood clots. Apixaban (Eliquis) is a blood thinner, and cilostazol (Pletal) helps keep platelets from sticking together. When you take them together, their effects add up, so bleeding can happen more easily and may be harder to stop.
Watch for things like unusual bruising, nosebleeds, blood in your urine or stool, black stools, pink or brown urine, or bleeding that won't stop. If you notice any of these, or feel unusually weak or dizzy, get help right away. The good news is your care team can safely manage this combination with monitoring, so keep taking both exactly as prescribed and check in with them.
Mechanism: Additive pharmacodynamic effect on hemostasis. Apixaban is a direct factor Xa inhibitor; cilostazol has antiplatelet activity. Combined use amplifies bleeding risk. Neither drug meaningfully alters the other's metabolism here, so this is a PD, not PK, interaction. Direction: increased bleeding effect.
- Severity: Major; evidence: theoretical/additive.
- Onset: unspecified.
- Monitor: signs/symptoms of blood loss; hemoglobin/hematocrit as indicated.
- Management: Use lowest effective doses; individualize. Discontinue apixaban for active pathological hemorrhage. Andexanet alfa reverses anti-FXa activity; apixaban PD effect persists >=24 h. PCC, aPCC, or rFVIIa may be considered; clotting assays are not useful to monitor reversal after PCC.
What happens
Increased risk of bleeding and can cause serious, potentially fatal bleeding
Interaction Deep Dive
Taking apixaban together with antiplatelet drugs raises the likelihood of bleeding1. In any patient receiving both anticoagulants and antiplatelet agents, any indications or symptoms of blood loss should be assessed without delay 2. Apixaban should be stopped in patients experiencing active pathological hemorrhage. Patients should be counseled on the signs and symptoms of blood loss and instructed to report them right away or proceed to an emergency room. Apixaban should be stopped in patients experiencing active pathological hemorrhage. There is an available agent that reverses the anti-factor Xa activity of apixaban. Apixaban's pharmacodynamic effect can be anticipated to remain for a minimum of 24 hours following the final dose. Options that may be considered include prothrombin complex concentrate (PCC), activated prothrombin complex concentrate, or recombinant factor VIIa. In cases where PCCs are administered, using a clotting test (PT, INR, or aPTT) or anti-factor Xa (FXa) activity to monitor the anticoagulation effect of apixaban is not helpful and is therefore not recommended. Absorption of apixaban is reduced by activated oral charcoal, which consequently decreases apixaban plasma concentration 1.
Why it happens (mechanism)
Additive effects on hemostasis
How to manage this interaction
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Do not stop or change either one on your own.
- Your care team may adjust and individualize your doses and monitor you more closely while you take both.
- Learn the signs of bleeding: unusual bruising, nosebleeds, bleeding gums, blood in urine or stool, black stools, coughing or vomiting blood, or severe headache.
- Report any of these to your pharmacist or doctor promptly, and go to an emergency room for bleeding that won't stop or if you feel faint.
- Tell any new provider or dentist that you take both of these.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) A clinical study involving high-risk patients after acute coronary syndrome who were treated with aspirin or with aspirin plus clopidogrel (APPRAISE-2) was stopped ahead of schedule because bleeding occurred more often with apixaban than with placebo. Among patients on single antiplatelet therapy, the ISTH major bleeding rate was 2.8% per year with apixaban versus 0.6% per year with placebo, while among those on dual antiplatelet therapy it was 5.9% per year with apixaban versus 2.5% per year with placebo 1.
b) Among patients taking apixaban, adding aspirin raised the bleeding risk from 1.8% per year to 3.4% per year, and adding both aspirin and warfarin raised the bleeding risk from 2.7% per year to 4.6% per year in a clinical trial (ARISTOTLE); use of dual antiplatelet therapy alongside apixaban was limited (2.3%) in this trial 1.
c) In a retrospective study, combining direct oral anticoagulant (DOAC) therapy with antiplatelet therapy (APT; n=78) compared with DOAC therapy by itself (n=329) did not produce a significant change in the rate of major bleeding (1.3% vs 1.2%) or of clinically relevant non-major bleeding (10.2% vs 6.4%) across 6 months of treatment. The patients were predominantly Caucasian men with a mean age of 63.7 years. Those receiving concurrent APT had significantly higher mean body mass index (30.7 vs 28.4), higher mean CHA2DS2-VASc score (4.28 vs 3.85), and were more likely to have diabetes (26.9% vs 17.3%) than those on DOAC monotherapy. DOACs were prescribed for VTE treatment or atrial fibrillation and consisted of apixaban (58.5%), rivaroxaban (38.1%), and dabigatran (3.4%). Single antiplatelet therapy was used in 94.9% (74 patients), with aspirin 81 mg once daily being the most frequent regimen (69 patients). Additional APT regimens comprised 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) 3.
Common questions
Can I take Cilostazol and Apixaban together?
Taking cilostazol with apixaban adds up their blood-thinning effects and raises your bleeding risk, so keep taking both as prescribed, watch closely for any signs of bleeding, and get help immediately if bleeding won't stop. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cilostazol 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 Cilostazol and Apixaban interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Do not stop or change either one on your own. Your care team may adjust and individualize your doses and monitor you more closely while you take both. Learn the signs of bleeding: unusual bruising, nosebleeds, bleeding gums, blood in urine or stool, black stools, coughing or vomiting blood, or severe headache. Rep… Management is individual — always follow your own care team's guidance.
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 Cilostazol 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)
- 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
- 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
Keep reading about Cilostazol
Keep reading about Apixaban
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