Posaconazole 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
Posaconazole
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.
These two medicines can interact. Apixaban (Eliquis) is a blood thinner that helps prevent dangerous clots. Posaconazole (Noxafil) is an antifungal that slows down the way your body breaks down and clears apixaban. When they are taken together, more apixaban can build up in your blood.
That extra amount can raise your risk of bleeding, such as easy bruising, nosebleeds, or bleeding that is hard to stop. This combination is generally not recommended, but the good news is your care team can manage it. Please do not stop either drug on your own. Talk with your pharmacist or doctor so they can watch you closely and tailor your plan.
Effect: Increased apixaban exposure (higher AUC/Cmax), raising bleeding risk. Combination is not recommended.
Mechanism: Apixaban is a CYP3A4 and P-gp substrate; posaconazole is a strong CYP3A4 inhibitor and possible P-gp inhibitor, reducing apixaban metabolism and efflux. Neither is a prodrug, so inhibition potentiates the active anticoagulant.
- Direction: Increased apixaban effect
- Evidence: Established
- Onset: Unspecified
Management: Avoid if possible. If coadministration is necessary, monitor closely for bleeding; apixaban therapeutic drug monitoring is encouraged for individualized dosing. Dose may need adjustment by the care team.
What happens
Increased exposure of apixaban
Interaction Deep Dive
Taking apixaban together with posaconazole can raise apixaban levels, so this combination is not advised. As a substrate of both CYP3A4 and P-glycoprotein (P-gp), apixaban is affected by posaconazole, which acts as a strong CYP3A4 inhibitor and may also inhibit P-gp1. When the two must be given together, careful monitoring is warranted 2. Using therapeutic drug monitoring for apixaban is recommended to individualize dosing when it is combined with posaconazole 3.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of apixaban; possible inhibition of P-gp-mediated efflux transport of apixaban
How to manage this interaction
What your care team may do:
- Consider whether this combination can be avoided, since it is generally not recommended.
- If you do need both, individualize your apixaban dose and monitor you more closely, including possible apixaban therapeutic drug monitoring.
- Watch for signs of bleeding.
What you should do: Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Let your pharmacist or doctor know you are on both, and report any unusual bruising, blood in urine or stool, prolonged bleeding, or dizziness right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In an analysis drawing on data from the Food and Drug Administration Adverse Event Reporting System (FAERS), adverse events linked to direct oral anticoagulants (DOACs) taken together with CYP3A4 inhibitors (including macrolide antibiotics and azole antimycotics) were combined to detect signals of hemorrhages. Between 2010 and 2021, 1128 bleeding cases tied to concurrent use of CYP3A4 inhibitors and DOACs were found, comprising cases involving rivaroxaban (529 events), apixaban (315 events), dabigatran (296 events), and edoxaban (19 events); no cases involving betrixaban were reported. The patients had a median age of 73 years (range, 61 to 81 years). Hemorrhagic signals were represented by reporting odds ratios (RORs) with 95% confidence intervals and were regarded as significant when the lower boundary of the 95% CI exceeded 1 and the interaction group contained 3 or more cases. Subgroup analyses and logistic regression were performed by adjusting for factors associated with hemorrhagic events. The hemorrhagic signal reached significance for apixaban when given with posaconazole in comparison with apixaban used alone (ROR, 2.69; 95% CI, 1.37 to 5.28) 2.
b) 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 included fifteen cardiothoracic transplant recipients (CTRs) with 18 matched itraconazole levels and 13 CTRs with 15 matched posaconazole levels. Baseline characteristics were comparable across the groups. Apixaban was given for atrial fibrillation in 15 patients and for venous thromboembolism (VTE) in 19 patients, with 6 having dual anticoagulation indications. The majority (27 patients) received azole therapy as prophylaxis and 1 received posaconazole as treatment for Aspergillus fumigatus. Among patients on itraconazole, 83% of apixaban levels fell within the anticipated trough range of 34 to 230 nanograms(ng)/mL, 17% exceeded 230 ng/mL, and none were below 34 ng/mL, with a median itraconazole level of 0.4 mcg/mL (interquartile range [IQR], 0.2 to 0.9) based on the parent compound alone. With posaconazole, 100% of apixaban levels were within the anticipated 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 bleeding events, 3 VTEs, and 2 strokes; notably, both strokes occurred after apixaban had been withheld for 72 and 96 hours. Of the 19 patients receiving apixaban for VTE, clot resolution was seen in 8 of 9 patients who had a documented follow up ultrasound 3.
Common questions
Can I take Posaconazole and Apixaban together?
Posaconazole can raise apixaban levels and increase bleeding risk, so this combination is generally avoided; if you must take both, your care team will monitor you closely and tailor your dose. Report any unusual bleeding to your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Posaconazole 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 Posaconazole and Apixaban interaction managed?
What your care team may do: Consider whether this combination can be avoided, since it is generally not recommended. If you do need both, individualize your apixaban dose and monitor you more closely, including possible apixaban therapeutic drug monitoring. Watch for signs of bleeding. What you should do: Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Let your p… 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 Posaconazole 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)
- 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.
- Li D, Yan C, Guo M, et al: Evidence of potential pro-haemorrhagic drug interactions between CYP3A4 inhibitors and direct oral anticoagulants: analysis of the FAERS database. Br J Clin Pharmacol 2023; 89(8):2423-2429. PubMed
- 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
Keep reading about Posaconazole
Keep reading about Apixaban
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