Apixaban and Cobicistat: 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
Cobicistat
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.
Cobicistat (Tybost) is a booster drug that blocks two systems your body uses to break down and clear apixaban (Eliquis), a blood thinner. When those systems are blocked, more apixaban stays in your body. That means the blood thinner can act more strongly, which raises your chance of bleeding, like easy bruising, nosebleeds, or blood in your urine or stool.
The good news is this is very manageable. Your care team may adjust your apixaban dose or choose a different plan depending on the dose you take. Please don't change anything on your own. Just check in with your pharmacist or doctor so they can set you up safely.
Effect: Cobicistat, a combined strong CYP3A4 and P-gp inhibitor, increases apixaban exposure (apixaban is a substrate of both), raising bleeding risk. Apixaban is active as given (not a prodrug), so inhibition increases its anticoagulant effect.
- Magnitude: analogous strong dual inhibitor (ketoconazole) raised apixaban Cmax ~62% and AUC ~97%.
- Evidence/severity: probable; major.
- Management: Avoid coadministration when apixaban is dosed 2.5 mg PO BID. For 5 or 10 mg BID regimens, reduce apixaban dose by 50%. Monitor for signs/symptoms of bleeding.
What happens
Increased apixaban exposure and an increased risk of bleeding
Interaction Deep Dive
In patients taking apixaban at 2.5 mg orally twice daily, steer clear of concurrent administration. When apixaban is given at higher doses (that is, 5 or 10 mg twice daily) together with an agent that inhibits both P-gp and strong CYP3A4, cut the apixaban dose by 50%. Because apixaban is a substrate for both CYP3A4 and P-gp, combining it with a drug that inhibits both P-gp and strong CYP3A4 can raise apixaban exposure and heighten the likelihood of bleeding12. A pharmacokinetic study demonstrated that coadministration with ketoconazole (an agent that inhibits both P-gp and strong CYP3A4) produced a 62% rise in apixaban Cmax and a 97% rise in AUC3.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism; inhibition of P-gp-mediated efflux transport of apixaban
How to manage this interaction
This combination can raise apixaban levels and increase bleeding risk, but your care team can manage it by tailoring your dose.
- If you take apixaban 2.5 mg twice daily, this combination is generally avoided, so your team may choose a different approach.
- If you take 5 mg or 10 mg twice daily, your dose may be reduced by half while on cobicistat.
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Watch for unusual bruising, nosebleeds, pink or red urine, black stools, or bleeding that won't stop, and report these promptly.
Ask your pharmacist or doctor to confirm the right plan for your specific dose.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) When apixaban was given together with ketoconazole, apixaban Cmax rose by 62% and apixaban AUC rose by 97% relative to apixaban given by itself. In 18 subjects, a 10 mg oral dose of apixaban was given 4 days after ketoconazole 400 mg once daily was started 3.
b) In a study of drug interactions, giving apixaban together with ketoconazole 400 mg raised apixaban Cmax and AUC by roughly 1.6-fold and 2-fold, respectively 2.
Common questions
Can I take Apixaban and Cobicistat together?
Cobicistat can boost apixaban levels and raise bleeding risk; your care team may avoid the combo at low apixaban doses or cut higher doses in half, so confirm your plan with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Apixaban and Cobicistat 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 Cobicistat interaction managed?
This combination can raise apixaban levels and increase bleeding risk, but your care team can manage it by tailoring your dose. If you take apixaban 2.5 mg twice daily, this combination is generally avoided, so your team may choose a different approach. If you take 5 mg or 10 mg twice daily, your dose may be reduced by half while on cobicistat. Keep taking both exactly as prescribed unless your pr… 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:
Questions for your pharmacist
- Does my dose of Apixaban or Cobicistat 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 (3)
- Product Information: ELIQUIS(R) oral tablets, tablets for suspension, apixaban oral tablets, tablets for suspension. Bristol-Myers Squibb Company (per Manufacturer), Princeton, NJ, 2025. DailyMed
- Product Information: ELIQUIS(R) oral film coated tablets, apixaban oral film coated tablets. Bristol-Myers Squibb Company (per Dailymed), Princeton, NJ, 2024. DailyMed
- Frost CE, Byon W, Song Y, et al: Effect of ketoconazole and diltiazem on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor. Br J Clin Pharmacol 2015; 79(5):838-846.
Keep reading about Cobicistat
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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