Apixaban and Indomethacin: 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
Apixaban
Indomethacin
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.
Apixaban (Eliquis) is a blood thinner that helps prevent dangerous clots. Indomethacin (Indocin) is an anti-inflammatory pain reliever (an NSAID). Both of these can make bleeding more likely, and taking them together can add up, so your risk of bleeding goes higher than with either one alone.
Watch for things like unusual bruising, nosebleeds, pink or red urine, black or bloody stools, or bleeding that won't stop. The good news is your care team can manage this. Don't stop either medicine on your own. Just check in with your pharmacist or doctor so they can keep an eye on you and make sure this combination is right for you.
Effect: Additive bleeding risk when combining apixaban (a direct factor Xa inhibitor) with indomethacin (a nonselective NSAID).
- Mechanism: Additive effect on hemostasis. Apixaban inhibits clot formation; NSAIDs impair platelet function and can cause GI mucosal injury. Neither is a prodrug here; this is pharmacodynamic, not PK-mediated.
- Direction/magnitude: Increased bleeding risk vs either agent alone; magnitude not quantified.
- Evidence: Theoretical; severity rated major.
- Management: Monitor for bleeding (GI, mucocutaneous, anemia). Heightened concern for spinal/epidural hematoma with neuraxial anesthesia or spinal puncture. Consider gastroprotection and alternative analgesics where appropriate.
What happens
An increased risk of bleeding
Interaction Deep Dive
When an anticoagulant is given together with an NSAID, the likelihood of serious bleeding may rise compared with taking either agent by itself1234. In addition, for patients receiving neuraxial anesthesia or undergoing spinal puncture, this combination may heighten the chance of epidural or spinal hematomas, which can lead to long-term or permanent paralysis5. Should the two be used at the same time, watch for indications of bleeding124.
Why it happens (mechanism)
Additive effect on hemostasis
How to manage this interaction
Both drugs raise bleeding risk, so together they need a little extra care. Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Watch for bleeding: unexpected bruising, nosebleeds, bleeding gums, pink/red urine, black or bloody stools, or coughing/vomiting blood. Report these promptly.
- Ask your team whether a different pain reliever might be safer for you, and whether you need any extra monitoring.
- Important: if you have any spinal procedure, epidural, or spinal puncture planned, tell that provider you take both, because the combination raises the risk of a spinal blood clot.
Your care team can individualize and monitor this safely.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Apixaban and Indomethacin together?
Apixaban and indomethacin both increase bleeding risk, and using them together adds up, so watch closely for any signs of bleeding and talk with your pharmacist or doctor about whether this combination is right for you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Apixaban and Indomethacin 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 Indomethacin interaction managed?
Both drugs raise bleeding risk, so together they need a little extra care. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Watch for bleeding: unexpected bruising, nosebleeds, bleeding gums, pink/red urine, black or bloody stools, or coughing/vomiting blood. Report these promptly. Ask your team whether a different pain reliever might be safer for you, and whether… 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 Apixaban or Indomethacin 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)
- Product Information: CALDOLOR(R) intravenous injection, ibuprofen intravenous injection. Cumberland Pharmaceuticals Inc. (per FDA), Nashville, TN, 2016. DailyMed
- Product Information: CELEBREX(R) oral capsules, celecoxib oral capsules. GD Searle LLC (per FDA), New York, NY, 2016. DailyMed
- Product Information: COUMADIN(R) oral tablets, intravenous injection powder for solution, warfarin sodium oral tablets, intravenous injection powder for solution. Bristol-Myers Squibb Company (per manufacturer), Princeton, NJ, 2015. DailyMed
- Product Information: COMBOGESIC(R) oral tablets, acetaminophen ibuprofen oral tablets. AFT Pharmaceuticals Inc (per FDA), Highland, MD, 2023. DailyMed
- Product Information: PRADAXA(R) oral capsules, dabigatran etexilate oral capsules. Boehringer Ingelheim Pharmaceuticals Inc (per FDA), Ridgefield, CT, 2023. DailyMed
Keep reading about Apixaban
Keep reading about Indomethacin
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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