Apixaban and Diflunisal: 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
Diflunisal
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.
Diflunisal (an anti-inflammatory pain reliever, like a stronger cousin of ibuprofen) and apixaban (Eliquis), a blood thinner, both make it harder for your blood to clot. When you take them together, that effect adds up, so your risk of bleeding goes up. This can show up as easy bruising, nosebleeds, bleeding gums, or, less often, more serious internal bleeding.
Please don't stop either medicine on your own. Many people do take a pain reliever alongside a blood thinner safely when their care team is watching. The key is to talk with your pharmacist or doctor so they can decide the safest plan and keep an eye on you.
Effect: Additive bleeding risk from combining an NSAID (diflunisal) with a factor Xa inhibitor (apixaban). This is a pharmacodynamic interaction on hemostasis, not a PK/enzyme effect. Neither drug is a prodrug, so direction is straightforward: both impair clotting, increasing bleeding risk versus either alone.
- Severity: Major; evidence: theoretical.
- Onset: unspecified.
- Concern: serious GI and other bleeding; risk of spinal/epidural hematoma with neuraxial anesthesia or spinal puncture.
- Management: avoid if feasible; if combined, monitor for bleeding (CBC/hemoglobin, signs/symptoms), consider gastroprotection, and reassess analgesic choice.
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, and there may be a heightened chance of epidural or spinal hematomas capable of causing lasting or permanent paralysis in individuals receiving neuraxial anesthesia or undergoing spinal puncture5. Should the two be taken at the same time, watch for indications of bleeding124.
Why it happens (mechanism)
Additive effect on hemostasis
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination is manageable with the right precautions.
- Your team may watch you more closely for signs of bleeding and may choose a different pain reliever if one is safer for you.
- Watch for and report: unusual bruising, black or bloody stools, pink or red urine, prolonged bleeding, severe headache, or coughing/vomiting blood.
- If you have any planned spinal procedure or epidural (including for surgery), make sure the team knows you take both drugs, because of a rare risk of a spinal blood clot.
- Ask your pharmacist before adding any new pain or anti-inflammatory product.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Apixaban and Diflunisal together?
Taking diflunisal with apixaban raises your bleeding risk because both affect clotting; keep taking them as prescribed but ask your pharmacist or doctor about the safest pain option and watch for any unusual bleeding. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Apixaban and Diflunisal 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 Diflunisal interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination is manageable with the right precautions. Your team may watch you more closely for signs of bleeding and may choose a different pain reliever if one is safer for you. Watch for and report: unusual bruising, black or bloody stools, pink or red urine, prolonged bleeding, severe headache, or coughing/vo… 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 Diflunisal 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 Diflunisal
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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