Drug Interaction Report

Avanafil and Fluconazole: Interaction Details

A pharmacist-reviewed analysis of the Avanafil and Fluconazole interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Fluconazole

Diflucan
+

Avanafil

Stendra Stendra®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 113 documented Avanafil interactions, 60 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

Increased avanafil exposure

Interaction Deep Dive

Use caution when using avanafil, a CYP3A4 substrate, together with a moderate CYP3A4 inhibitor, such as fluconazole, as concomitant use may result in increased avanafil exposure and an increased risk for toxicity. Carefully monitor if coadministered. Fluconazole-mediated CYP3A4 inhibition may persist for 4 to 5 days after discontinuation2. Although coadministration of avanafil and fluconazole has not been studied, avanafil Cmax and AUC increased 2-fold and 3.6-fold, respectively, when a single 200-mg dose of avanafil was coadministered with erythromycin 500 mg twice daily (also a moderate CYP3A4 inhibitor) in a study of 15 healthy volunteers. Avanafil doses should not exceed 50 mg once every 24 hours in patients taking fluconazole 1.

Why it happens (mechanism)

Inhibition of CYP3A4-mediated avanafil metabolism by fluconazole

Literature reports

1 report — tap to read

a) Although coadministration of avanafil and fluconazole has not been studied, avanafil Cmax and AUC increased 2-fold and 3.6-fold, respectively, when a single 200 mg dose of avanafil was coadministered with erythromycin 500 mg twice daily (also a moderate CYP3A4 inhibitor) in a study of 15 healthy volunteers 1.

Common questions

Can I take Avanafil and Fluconazole together?

Increased avanafil exposure Always confirm with your pharmacist or prescriber before making any change.

How serious is the Avanafil and Fluconazole 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 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 Avanafil or Fluconazole 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)

  1. Product Information: STENDRA(R) oral tablets, avanafil oral tablets. Metuchen Pharmaceuticals LLC (per FDA), Freehold, NJ, 2022. DailyMed
  2. Product Information: DIFLUCAN(R) oral tablets, suspension, fluconazole oral tablets, suspension. Roerig (per FDA), New York, NY, 2023. DailyMed
Was this write-up helpful?
Fluconazole

Keep reading about Fluconazole

All Fluconazole interactions (166)
Also serious with: Buprenorphine Glasdegib Bedaquiline Sertraline
Avanafil

Keep reading about Avanafil

All Avanafil interactions (113) Avanafil drug information
Also serious with: Nitroglycerin Transdermal Patch Isosorbide Amyl Nitrite Erythrityl Tetranitrate
Beyond drug–drug

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:

Fluconazole + Activated Charcoal Beer Siberian Cocklebur Wine Adrafinil Ashwagandha Black Cohosh Boldo + 73 more
Avanafil + Activated Charcoal American Mistletoe Grapefruit Hawthorn St. John's Wort Acacia Rigidula Adrafinil African Wild Potato + 136 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.