Ketoconazole 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
Ketoconazole
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.
Taking these two together can raise the amount of apixaban (Eliquis) in your body. Ketoconazole slows down the pathways your body uses to clear apixaban, so the blood thinner builds up and works more strongly than intended. That means a higher chance of bleeding, such as easy bruising, nosebleeds, or bleeding that is hard to stop.
The good news is that this is manageable. Your care team may lower your apixaban dose or avoid using the two together, depending on your situation. Please don't change anything on your own. Just check in with your pharmacist or doctor so they can pick the safest plan for you.
Effect: Ketoconazole (combined strong CYP3A4 and P-gp inhibitor) increases apixaban exposure, raising bleeding risk. Apixaban is a substrate of both CYP3A4 and P-gp; neither is a prodrug, so inhibition increases active anticoagulant exposure.
- Magnitude: PK study showed apixaban Cmax +62%, AUC +97%.
- Evidence/onset: Probable; onset unspecified.
- Management: Avoid coadministration if apixaban dose is 2.5 mg PO BID. For 5 or 10 mg BID, reduce apixaban by 50% during concomitant use. Monitor for bleeding signs.
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 the higher apixaban regimens (that is, 5 or 10 mg twice daily) are used alongside an agent that inhibits both P-gp and CYP3A4 strongly, cut the dose in half. Because apixaban is a substrate of both CYP3A4 and P-gp, giving it together with a combined P-gp and strong CYP3A4 inhibitor can raise apixaban levels and heighten the potential for bleeding12. A pharmacokinetic study demonstrated that when apixaban was given with ketoconazole (an inhibitor of both P-gp and CYP3A4 that is strong), apixaban Cmax rose by 62% and AUC rose by 97%3.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism; inhibition of P-gp-mediated efflux transport of apixaban
How to manage this interaction
This interaction is manageable with the right plan from your care team. Depending on your apixaban dose, they may:
- Avoid using the two together if you take the lower 2.5 mg twice-daily dose.
- Reduce higher apixaban doses (5 or 10 mg twice daily) by 50% while you are on ketoconazole.
- Watch you more closely for signs of bleeding.
What you should do: Keep taking both exactly as prescribed and do not adjust anything yourself. Tell your pharmacist or prescriber you are taking both, and report any unusual bruising, bleeding, dark stools, or pink/red urine right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) Giving apixaban together with ketoconazole produced a 62% rise in apixaban Cmax and a 97% rise in apixaban AUC relative to apixaban given by itself. In 18 subjects, oral apixaban 10 mg was given 4 days after starting ketoconazole 400 mg once daily 3.
b) In a drug interaction study, giving apixaban together with ketoconazole 400 mg increased apixaban Cmax and AUC by roughly 1.6-fold and 2-fold, respectively 2.
Common questions
Can I take Ketoconazole and Apixaban together?
Ketoconazole can nearly double apixaban levels and raise bleeding risk, so your care team may lower your apixaban dose or avoid the combination. Don't stop or change either drug on your own; talk with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole 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 Ketoconazole and Apixaban interaction managed?
This interaction is manageable with the right plan from your care team. Depending on your apixaban dose, they may: Avoid using the two together if you take the lower 2.5 mg twice-daily dose. Reduce higher apixaban doses (5 or 10 mg twice daily) by 50% while you are on ketoconazole. Watch you more closely for signs of bleeding. What you should do: Keep taking both exactly as prescribed and do not a… 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 Ketoconazole 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 (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 Ketoconazole
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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