Apixaban and Itraconazole: 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
Itraconazole
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 your risk of bleeding. Apixaban (Eliquis) is a blood thinner. Itraconazole (Sporanox) is an antifungal that slows down the body systems that normally clear apixaban out of your blood. When apixaban builds up, its blood-thinning effect gets stronger, so you could bruise or bleed more easily.
Watch for warning signs like unusual bruising, nosebleeds, pink or red urine, black stools, or bleeding that won't stop. Please don't stop or change either medicine on your own. Your doctor or pharmacist can manage this safely, sometimes by adjusting your apixaban dose or watching you more closely. Give them a call to talk it through.
Effect: Itraconazole (strong CYP3A4 inhibitor and P-gp inhibitor) reduces metabolism and efflux of apixaban, a dual CYP3A4/P-gp substrate, increasing apixaban exposure (AUC/Cmax) and bleeding risk. Neither drug is a prodrug; this is a straightforward inhibition-driven exposure increase.
- Severity: Major; evidence: established.
- Management: Concurrent use generally not recommended during and for 2 weeks after stopping itraconazole. If unavoidable and apixaban dose is greater than 2.5 mg BID, reduce apixaban by 50%. If already on 2.5 mg BID, avoid the combination.
- Monitor for bleeding; therapeutic drug monitoring encouraged for individualized dosing.
What happens
Increased apixaban exposure and an increased risk of bleeding
Interaction Deep Dive
It is advised to avoid apixaban both while taking itraconazole and for a period of 2 weeks following its discontinuation 34. Because apixaban is a substrate of CYP3A4 as well as P-gp, giving it together with an agent that inhibits both P-gp and strongly inhibits CYP3A4 raises apixaban exposure. When such combined use cannot be avoided in a patient already taking apixaban at doses above 2.5 mg twice daily, the apixaban dose should be lowered by 50%. For patients on apixaban 2.5 mg twice daily, concurrent administration of a strong dual CYP3A4 and P-gp inhibitor should not be used 1. When apixaban is combined with itraconazole, therapeutic drug monitoring of apixaban is recommended to support individualized dosing 2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of apixaban; inhibition of P-gp-mediated efflux transport of apixaban
How to manage this interaction
This is manageable with the right plan from your care team. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your team may decide the combination is best avoided, or may adjust your apixaban dose and monitor you more closely.
- If you take more than 2.5 mg of apixaban twice daily, your dose may be lowered. If you take 2.5 mg twice daily, they may avoid using the two together.
- Your team can individualize your dose, sometimes with blood-level monitoring.
- Report any unusual bruising, bleeding, dark stools, or blood in urine right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a drug interaction study, apixaban 2.5 mg twice daily combined with itraconazole or posaconazole produced drug exposure comparable to apixaban 5 mg twice daily without any azole exposure. The study enrolled fifteen cardiothoracic transplant recipients (CTRs) with 18 matched itraconazole levels and 13 CTRs with 15 matched posaconazole levels. Baseline characteristics did not differ substantially between the groups. Apixaban was given for atrial fibrillation in 15 patients and venous thromboembolism (VTE) in 19 patients, with 6 patients having dual anticoagulation indications. The majority (27 patients) received azole therapy as prophylaxis, and 1 patient received posaconazole to treat Aspergillus fumigatus. Among patients on itraconazole, 83% of apixaban levels fell within the expected trough range of 34 to 230 nanograms(ng)/mL, 17% exceeded 230 ng/mL, and none fell below 34 ng/mL, with a median itraconazole level of 0.4 mcg/mL (interquartile range [IQR], 0.2 to 0.9) based on parent compound alone. With posaconazole, 100% of apixaban levels were within the expected trough range of 34 to 230 ng/mL, with a median posaconazole level of 1.46 mg/L (IQR, 0.88 to 2). During the study there were two major bleed events, 3 VTEs, and 2 strokes; notably, both strokes occurred after apixaban had been held for 72 and 96 hours. Of the 19 patients treated with apixaban for VTE, clot resolution was documented in 8 of 9 patients who had a follow up ultrasound 2.
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 1.
Common questions
Can I take Apixaban and Itraconazole together?
Itraconazole makes apixaban build up and raises bleeding risk, so this combination is usually avoided or requires a dose adjustment and closer monitoring. Do not change anything on your own; check with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Apixaban and Itraconazole 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 Itraconazole interaction managed?
This is manageable with the right plan from your care team. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your team may decide the combination is best avoided, or may adjust your apixaban dose and monitor you more closely. If you take more than 2.5 mg of apixaban twice daily, your dose may be lowered. If you take 2.5 mg twice daily, they may avoid usi… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
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 Itraconazole 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 (4)
- Product Information: ELIQUIS(R) oral film coated tablets, apixaban oral film coated tablets. Bristol-Myers Squibb Company (per Dailymed), Princeton, NJ, 2024. DailyMed
- Concannon K, Huntsman R, Cole K, et al: Concurrent apixaban with itraconazole or posaconazole pharmacokinetic and clinical outcome evaluation in cardiothoracic transplant recipients. Clin Transplant 2025; 39(5):e70165. DOI
- Product Information: SPORANOX(R) oral solution, itraconazole oral solution. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2024. DailyMed
- Product Information: SPORANOX(R) oral capsules, itraconazole oral capsules. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2024. DailyMed
Keep reading about Itraconazole
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist