Salsalate 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
Salsalate
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, and salsalate (Disalcid) is an anti-inflammatory pain reliever in the NSAID family. Taken together, both can make it harder for your blood to clot, so the concern is a higher chance of bleeding. In some cases that bleeding can be serious.
Watch for warning signs like unusual bruising, pink or red urine, black or bloody stools, nosebleeds that won't stop, or vomit that looks like coffee grounds. If any of these happen, get medical help right away. The good news is your care team can manage this by watching you more closely and adjusting your plan, so please don't stop either medicine on your own. Just talk with your pharmacist or doctor.
Effect: Additive risk of bleeding when apixaban (a direct factor Xa inhibitor) is combined with salsalate, a nonacetylated salicylate NSAID.
Mechanism: Pharmacodynamic (additive effects on hemostasis); NSAIDs can also impair platelet function and irritate GI mucosa. Neither agent's interaction here is PK-based, and neither is a prodrug relevant to this effect.
- Direction: Increased bleeding risk, potentially serious/fatal.
- Evidence: Theoretical; severity major; onset unspecified.
- Management: Assess bleeding risk, use lowest effective NSAID dose/duration or an alternative analgesic, counsel on blood-loss signs. Apixaban's PD effect persists >=24 h; andexanet or PCC/rFVIIa for reversal. Discontinue apixaban if active pathological hemorrhage.
What happens
An increased risk of bleeding and can cause serious, potentially fatal bleeding
Interaction Deep Dive
Taking apixaban together with medications that influence hemostasis, including NSAIDs, can heighten the likelihood of bleeding. If active pathological bleeding develops, apixaban should be stopped. A reversal agent for the anti-factor Xa activity of apixaban is on the market. Apixaban's pharmacodynamic effect can be anticipated to remain for a minimum of 24 hours following the final dose. Patients should be counseled about the warning signs and symptoms of blood loss and instructed to report these right away or present to an emergency room. In cases of active pathological hemorrhage, discontinue apixaban. A reversal agent for the anti-factor Xa activity of apixaban is available. The pharmacodynamic effect of apixaban is expected to last for at least 24 hours after the last dose. Options that may be considered include prothrombin complex concentrate (PCC), activated prothrombin complex concentrate, or recombinant factor VIIa. If PCCs are administered, it is not helpful and not advised to assess apixaban's anticoagulant effect through a clotting test (PT, INR, or aPTT) or anti-factor Xa (FXa) activity. Absorption of apixaban is decreased by activated oral charcoal, which in turn reduces the plasma concentration of apixaban1.
Why it happens (mechanism)
Additive effects on hemostasis
How to manage this interaction
Both drugs can raise bleeding risk, so your care team will weigh whether the combination is appropriate and how to keep you safe.
- Keep taking both as prescribed unless your prescriber tells you otherwise.
- Your team may use the lowest effective dose and shortest duration of the NSAID, monitor you more closely, or consider a different pain reliever. Any changes should be individualized by them.
- Learn the signs of bleeding (unusual bruising, blood in urine or stool, black stools, prolonged nosebleeds, coffee-ground vomit) and report them right away or go to the ER.
- Ask your pharmacist before adding any other NSAID or aspirin product.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) A clinical study involving high-risk patients following acute coronary syndrome who were treated with aspirin or with aspirin combined with clopidogrel (APPRAISE-2) was stopped early because apixaban produced a greater incidence of bleeding than placebo. Among patients on single antiplatelet therapy, the rate of ISTH major bleeding was 2.8% per year with apixaban compared with 0.6% per year with placebo, and among patients on dual antiplatelet therapy it was 5.9% per year with apixaban compared with 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); the use of dual antiplatelet therapy alongside apixaban in this trial was limited (2.3%) 1.
Common questions
Can I take Salsalate and Apixaban together?
Combining apixaban (Eliquis) with salsalate adds to bleeding risk, so watch closely for signs of bleeding and check with your pharmacist or doctor before continuing or adding NSAIDs. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Salsalate 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 Salsalate and Apixaban interaction managed?
Both drugs can raise bleeding risk, so your care team will weigh whether the combination is appropriate and how to keep you safe. Keep taking both as prescribed unless your prescriber tells you otherwise. Your team may use the lowest effective dose and shortest duration of the NSAID, monitor you more closely, or consider a different pain reliever. Any changes should be individualized by them. Lear… 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 Salsalate 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 (1)
- Product Information: ELIQUIS(R) oral film coated tablets, apixaban oral film coated tablets. Bristol-Myers Squibb Company (per Dailymed), Princeton, NJ, 2024. DailyMed
Keep reading about Apixaban
Keep reading about Salsalate
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