Apixaban and Rivaroxaban: 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
Rivaroxaban
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.
Rivaroxaban (Xarelto) and apixaban (Eliquis) are both blood thinners. They work in the same way, by blocking a clotting protein called factor Xa. Taking both at once means your blood is being thinned twice over, which greatly raises your risk of serious bleeding.
Warning signs to watch for include unusual bruising, pink or red urine, black or bloody stools, coughing or vomiting blood, or bleeding that will not stop. If any of these happen, get emergency help right away. The good news is your care team usually would not have you on both together on purpose, and they can manage your anticoagulation safely. Always check with your pharmacist or doctor before combining these.
Mechanism: additive anticoagulation. Both rivaroxaban and apixaban are direct factor Xa inhibitors (neither is a prodrug), so concurrent use produces additive anti-Xa activity and a markedly increased bleeding risk.
- Direction: increased anticoagulant effect / bleeding risk.
- Magnitude: pharmacodynamic studies with apixaban plus enoxaparin showed a 50 to 60 percent rise in anti-Xa activity; expect a comparable additive effect here.
- Evidence: probable; severity: major.
- Management: avoid overlapping factor Xa inhibitors except during a supervised transition. Discontinue if active pathological bleeding occurs; anti-Xa effect persists at least 24 hours after the last dose. Specific reversal agents (andexanet alfa) and PCC/aPCC/rFVIIa are options. Counsel on bleeding signs.
What happens
An increased risk of bleeding and can cause serious, potentially fatal bleeding
Interaction Deep Dive
Giving apixaban, a factor Xa inhibitor, together with another anticoagulant raises the likelihood of bleeding. Pharmacodynamic drug interaction studies of apixaban demonstrated a 50% to 60% rise in anti-factor Xa activity when apixaban was administered alongside enoxaparin. Should active pathological bleeding develop, apixaban should be stopped. A product capable of reversing apixaban's anti-factor Xa activity exists. Apixaban's pharmacodynamic effect is anticipated to remain for a minimum of 24 hours following the final dose. Patients should be counseled about the signs and symptoms of blood loss and instructed to report these right away or proceed to an emergency room. Options that may be contemplated include prothrombin complex concentrate (PCC), activated prothrombin complex concentrate, or recombinant factor VIIa. If PCCs are administered, assessing apixaban's anticoagulant effect via a clotting assay (PT, INR, or aPTT) or anti-factor Xa (FXa) activity provides no benefit and is not advised. Activated oral charcoal decreases apixaban absorption and consequently reduces apixaban exposure1.
Why it happens (mechanism)
Additive anticoagulation
How to manage this interaction
These two drugs are not normally taken together because they do the same job and stacking them can cause dangerous bleeding. If you have been prescribed both, contact your pharmacist or prescriber promptly to confirm this is intended. Your care team manages this by:
- Generally using only one factor Xa inhibitor, and only overlapping briefly under supervision when switching.
- Watching closely for bleeding and stopping treatment if serious bleeding occurs.
- Keeping in mind the effect lasts at least 24 hours after the last dose.
Do not stop or change either drug on your own. Report bruising, blood in urine or stool, or bleeding that will not stop, and go to an emergency room for major bleeding.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In investigations of pharmacodynamic drug interactions involving apixaban, a 50% to 60% rise in anti-factor Xa activity was seen when apixaban and enoxaparin were given together 1.
Common questions
Can I take Apixaban and Rivaroxaban together?
Rivaroxaban and apixaban are both factor Xa blood thinners, so taking them together doubles up the effect and can cause serious bleeding. Confirm with your pharmacist or doctor, do not stop either on your own, and get emergency care for any major bleeding. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Apixaban and Rivaroxaban 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 Rivaroxaban interaction managed?
These two drugs are not normally taken together because they do the same job and stacking them can cause dangerous bleeding. If you have been prescribed both, contact your pharmacist or prescriber promptly to confirm this is intended. Your care team manages this by: Generally using only one factor Xa inhibitor, and only overlapping briefly under supervision when switching. Watching closely for ble… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
- Can You Take Cod Liver Oil With Rivaroxaban (Xarelto)?
- Can You Take NAC With Xarelto (Rivaroxaban)?
- Does Astaxanthin Interact With Xarelto (Rivaroxaban)?
- Can You Take Baobab Fiber With Eliquis (Apixaban)?
- Can You Replace an Evening Apixaban Dose With Berberine?
- Can I Take Ginkgo With Apixaban (Eliquis) and Atorvastatin?
Questions for your pharmacist
- Does my dose of Apixaban or Rivaroxaban 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 Rivaroxaban
Keep reading about Apixaban
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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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