Apixaban and Simeprevir: 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
Simeprevir
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 simeprevir (Olysio) is a medicine used for hepatitis C. When taken together, simeprevir can slow down how your body clears apixaban a little. That means the level of apixaban in your blood could go up somewhat, which could raise the chance of bleeding, such as easy bruising, nosebleeds, or bleeding that takes longer to stop.
The good news is this is something your care team can manage. This concern is based mostly on how the drugs work in theory, not on strong real-world evidence. Keep taking both exactly as prescribed, and let your doctor or pharmacist know if you notice any unusual bleeding.
Effect: Simeprevir may increase apixaban exposure. Apixaban is a substrate of CYP3A4 and P-gp; simeprevir mildly inhibits intestinal CYP3A4 (not hepatic) and inhibits P-gp-mediated efflux, potentially raising apixaban AUC/Cmax and bleeding risk.
- Direction: Increased anticoagulant exposure/effect.
- Onset: Unspecified.
- Evidence: Theoretical.
- Magnitude: Likely modest given intestinal-only CYP3A4 inhibition.
Management: Use caution. Monitor for signs of bleeding; dose may need to be individualized by the care team. Neither drug is a prodrug, so the interaction magnifies apixaban's effect rather than reducing it.
What happens
Increased exposure of the CYP3A4 and P-gp substrate
Interaction Deep Dive
Exercise caution when combining simeprevir with this drug, which serves as both a P-gp substrate and a CYP3A4 substrate, because simeprevir produces mild inhibition of intestinal CYP3A4 (though not hepatic CYP3A4) along with inhibition of P-gp-mediated efflux transport, potentially raising exposure to this drug1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism and P-gp-mediated efflux transport by simeprevir
How to manage this interaction
What your care team may do:
- Use extra caution when these two are combined.
- Monitor you more closely for signs of bleeding.
- Individualize your apixaban dose if they judge it necessary.
What you should do:
- Keep taking both medicines exactly as prescribed unless told otherwise.
- Watch for unusual bruising, blood in urine or stool, prolonged bleeding, or nosebleeds, and report these promptly.
- Tell your pharmacist and prescriber you are on both drugs so they can plan monitoring together.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Apixaban and Simeprevir together?
Simeprevir can modestly raise apixaban levels and bleeding risk, so keep taking both as prescribed but watch for unusual bleeding and let your care team monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Apixaban and Simeprevir 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 Simeprevir interaction managed?
What your care team may do: Use extra caution when these two are combined. Monitor you more closely for signs of bleeding. Individualize your apixaban dose if they judge it necessary. What you should do: Keep taking both medicines exactly as prescribed unless told otherwise. Watch for unusual bruising, blood in urine or stool, prolonged bleeding, or nosebleeds, and report these promptly. Tell your… 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 Simeprevir 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: OLYSIO(R) oral capsules, simeprevir oral capsules. Janssen Therapeutics (per manufacturer), Titusville, NJ, 2014.
Keep reading about Apixaban
Keep reading about Simeprevir
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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