Apixaban and Voriconazole: 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
Voriconazole
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.
You've been prescribed apixaban (Eliquis), a blood thinner, along with voriconazole (Vfend), an antifungal medicine. Your body normally uses an enzyme called CYP3A4 to break down apixaban. Voriconazole slows that enzyme down, so more apixaban can build up in your blood.
More apixaban means stronger blood-thinning, which can raise your risk of bruising or bleeding, like nosebleeds, bleeding gums, or blood in your urine or stool. The good news is your care team can manage this by adjusting your dose and watching you more closely. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor, and let them know right away if you notice unusual bleeding.
Effect: Increased apixaban exposure with heightened anticoagulant effect and bleeding risk.
Mechanism: Apixaban is a CYP3A4 (and P-gp) substrate; voriconazole is a strong CYP3A4 inhibitor. Inhibition reduces apixaban clearance, raising AUC/Cmax. Apixaban is not a prodrug, so inhibition amplifies its effect.
- Direction: Increased apixaban levels/effect
- Severity: Major; combination not recommended
- Onset: Unspecified
- Evidence: Theoretical
Management: Avoid concomitant use if possible. If co-administered, consider dose reduction and monitor closely for bleeding (Hgb/Hct, clinical signs). Individualize per care team.
What happens
Increased apixaban exposure and an increased efficacy of apixaban-related adverse effects
Interaction Deep Dive
Taking apixaban together with voriconazole is not advised. Apixaban serves as a CYP3A4 substrate, whereas voriconazole acts as a potent CYP3A4 inhibitor1. When used together, apixaban exposure may rise, potentially heightening the effectiveness of apixaban. The dosage of these substrates should be lowered and patients monitored for adverse reactions2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of apixaban
How to manage this interaction
This combination is generally not recommended, but your care team can manage it safely if both are needed.
- Keep taking both exactly as prescribed unless your doctor or pharmacist tells you otherwise.
- Your apixaban dose may need to be adjusted and individualized by your care team, and they may monitor you more closely for signs of bleeding.
- Watch for unusual bruising, nosebleeds, bleeding gums, pink or red urine, black or bloody stools, or unusual tiredness, and report these promptly.
- Ask your pharmacist or prescriber whether a different antifungal or a dose change is right for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) In a separately published trial, giving voriconazole (400 mg every 12 hours on Day 1, followed by 200 mg every 12 hours on Day 2) together with a single intravenous fentaNYL dose (5 microgram/kg) produced a 1.4-fold rise in the mean AUC (0 to inf) of fentaNYL (range 0.81- to 2.04-fold) 2.
b) In a different independently published trial, administering multiple oral voriconazole doses (400 mg every 12 hours on Day 1, then five doses of 200 mg every 12 hours across Days 2 to 4) alongside a single 10 mg oral dose of oxyCODONE on Day 3 led to increases in the mean Cmax and AUC (0 to inf) of oxyCODONE of 1.7-fold (range 1.4- to 2.2-fold) and 3.6-fold (range 2.7- to 5.6-fold), respectively. The mean elimination half-life of oxyCODONE likewise rose by 2.0-fold (range 1.4- to 2.5-fold) 2.
c) Among stable renal transplant patients on ongoing cycloSPORINE therapy, giving oral voriconazole (200 mg every 12 hours for 8 days) at the same time raised cycloSPORINE Cmax and AUC (tau) by an average of 1.1 times (90% CI: 0.9, 1.41) and 1.7 times (90% CI: 1.5, 2.0), respectively, compared with cycloSPORINE given without voriconazole 2.
Common questions
Can I take Apixaban and Voriconazole together?
Voriconazole can raise apixaban levels and increase bleeding risk, so this combination is generally avoided; if used together, your care team will tailor the dose and monitor you closely. Report any unusual bleeding right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Apixaban and Voriconazole 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 Voriconazole interaction managed?
This combination is generally not recommended, but your care team can manage it safely if both are needed. Keep taking both exactly as prescribed unless your doctor or pharmacist tells you otherwise. Your apixaban dose may need to be adjusted and individualized by your care team, and they may monitor you more closely for signs of bleeding. Watch for unusual bruising, nosebleeds, bleeding gums, pin… 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 Voriconazole 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 (2)
- Steffel J, Collins R, Antz M, et al: 2021 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Europace 2021; 23(10):1612-1676.
- Product Information: VFEND(R) oral tablets, oral suspension, intravenous injection, voriconazole oral tablets, oral suspension, intravenous injection. Roerig (per FDA), New York, NY, 2025. DailyMed
Keep reading about Voriconazole
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:
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