Apixaban and Nefazodone: 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
Nefazodone
No brand names on recordApixaban
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.
Let's talk about taking these two together. Apixaban (Eliquis) is a blood thinner that helps prevent dangerous clots. Nefazodone is an antidepressant. The issue is that nefazodone slows down how your body clears apixaban, so more of the blood thinner can build up in your system. That can raise your chance of serious bleeding.
The good news is your care team can manage this. They may adjust your apixaban dose or watch you more closely. Please don't change anything on your own. Tell your doctor or pharmacist you take both, and call right away if you notice unusual bruising, pink or dark urine, black stools, or bleeding that won't stop.
Effect: Nefazodone (strong CYP3A4 and P-gp inhibitor with effects on hemostasis) increases apixaban exposure, raising bleeding risk (potentially serious/fatal).
Mechanism: Inhibition of CYP3A4-mediated metabolism and P-gp-mediated efflux of apixaban, plus additive hemostatic effects. Direction: increased apixaban AUC/Cmax (neither drug is a prodrug).
- Evidence: theoretical; severity: major; onset: unspecified.
- Management: Avoid combination at apixaban 2.5 mg BID. For 5 or 10 mg BID, reduce dose by 50%. Discontinue apixaban with active pathological bleeding; andexanet or PCC/rFVIIa available for reversal. PD effect persists >=24 h after last dose. Clotting/anti-FXa assays not useful to guide PCC therapy.
What happens
Increased apixaban exposure and an increased risk of bleeding and can cause serious, potentially fatal bleeding
Interaction Deep Dive
Do not give apixaban (which is a substrate of both CYP3A4 and P-gp and acts as a factor Xa inhibitor) at oral doses of 2.5 mg twice daily together with nefazodone (an inhibitor of P-gp and a strong CYP3A4 inhibitor that also functions as a serotonin norepinephrine reuptake inhibitor (SNRI) and influences hemostasis). For the higher apixaban doses (namely 5 or 10 mg twice daily), cut the dose by 50% when nefazodone is used concurrently. Taking apixaban alongside nefazodone can raise apixaban exposure and may heighten bleeding risk1. Should active pathological bleeding develop, stop apixaban. There is an agent available to reverse the anti-factor Xa activity of apixaban. Apixaban's pharmacodynamic effect can be anticipated to last for a minimum of 24 hours following the final dose. Options that may be considered include prothrombin complex concentrate (PCC), activated prothrombin complex concentrate, or recombinant factor VIIa. If PCCs are administered, using a clotting test (PT, INR, or aPTT) or anti-factor Xa (FXa) activity to monitor apixaban's anticoagulation effect provides no benefit and is not recommended12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of apixaban; inhibition of P-gp-mediated efflux transport of apixaban; additive effects on hemostasis
How to manage this interaction
This combination can raise apixaban levels and bleeding risk, but your care team has clear ways to handle it. Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Your team may avoid this combination at the lower apixaban dose (2.5 mg twice daily) or choose a different antidepressant.
- If you take a higher apixaban dose (5 or 10 mg twice daily), your dose may be reduced by half and individualized by your care team.
- They may monitor you more closely for signs of bleeding.
Call your doctor or pharmacist right away about unusual bruising, blood in urine or stool, or bleeding that won't stop.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
Common questions
Can I take Apixaban and Nefazodone together?
Nefazodone can make apixaban build up and increase serious bleeding risk, so your care team may avoid the combination, cut the apixaban dose in half, or watch you closely. Don't change either medicine on your own, and report any unusual bleeding. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Apixaban and Nefazodone 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 Nefazodone interaction managed?
This combination can raise apixaban levels and bleeding risk, but your care team has clear ways to handle it. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Your team may avoid this combination at the lower apixaban dose (2.5 mg twice daily) or choose a different antidepressant. If you take a higher apixaban dose (5 or 10 mg twice daily), your dose may be reduce… 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 Nefazodone 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)
- 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
Keep reading about Nefazodone
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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