Tolfenamic Acid 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
Apixaban
Tolfenamic Acid
No brand names on record
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.
Taking these two together can make bleeding more likely. Apixaban (Eliquis) is a blood thinner that slows down how your blood clots. Tolfenamic acid is an anti-inflammatory pain reliever (an NSAID), and this type of drug can irritate the stomach lining and also affect the tiny cells (platelets) that help stop bleeding. When you combine them, those effects can add up, so bruises, nosebleeds, or stomach bleeding may happen more easily.
The good news is that your care team can manage this. Watch for unusual bruising, blood in your stool or urine, or bleeding that won't stop, and tell your pharmacist or doctor. Please don't stop either medicine on your own before checking with them.
Effect: Additive increase in bleeding risk when apixaban (a direct factor Xa inhibitor anticoagulant) is combined with the NSAID tolfenamic acid.
Mechanism: Pharmacodynamic, not pharmacokinetic. Apixaban impairs coagulation; NSAIDs impair platelet aggregation and cause GI mucosal injury. Effects on hemostasis are additive. Neither agent requires metabolic activation, so direction is straightforward.
- Direction: Increased bleeding risk vs either agent alone.
- Severity/Evidence: Major; theoretical basis.
- Special risk: Neuraxial anesthesia/spinal puncture raises risk of epidural or spinal hematoma.
- Management: Avoid if possible; if used together, monitor for overt and occult bleeding, hemoglobin, and GI symptoms.
What happens
An increased risk of bleeding
Interaction Deep Dive
Taking an anticoagulant together with an NSAID can raise the likelihood of serious bleeding compared with taking either agent by itself1234, and in patients receiving neuraxial anesthesia or having a spinal puncture, this combination can heighten the chance of epidural or spinal hematomas, which may lead to long-term or permanent paralysis 5. When the two are given together, watch for signs of bleeding 124.
Why it happens (mechanism)
Additive effect on hemostasis
How to manage this interaction
This combination can usually be managed with awareness and monitoring. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your care team may monitor you more closely for bleeding, and they may consider whether a different pain reliever is a better fit for you.
- Watch for warning signs: unusual bruising, nosebleeds, pink or red urine, black or bloody stools, coughing or vomiting blood, or severe headache.
- If you have any spinal procedure or epidural planned, make sure that team knows you take apixaban.
Report any bleeding signs promptly to your pharmacist or doctor.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Tolfenamic Acid and Apixaban together?
Combining apixaban with the NSAID tolfenamic acid adds up to a higher bleeding risk, so watch closely for any signs of bleeding and check with your pharmacist or doctor about the safest pain-relief plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tolfenamic Acid 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 Tolfenamic Acid and Apixaban interaction managed?
This combination can usually be managed with awareness and monitoring. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your care team may monitor you more closely for bleeding, and they may consider whether a different pain reliever is a better fit for you. Watch for warning signs: unusual bruising, nosebleeds, pink or red urine, black or bloody stools,… 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 Tolfenamic Acid 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)
- 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 Tolfenamic Acid
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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