Drug Interaction Report

Cobicistat and Avanafil: Interaction Details

A pharmacist-reviewed analysis of the Cobicistat and Avanafil 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

Cobicistat

Tybost
+

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 129 documented Cobicistat interactions, 103 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 and increased risk of avanafil-related adverse events

Interaction Deep Dive

Coadministration of avanafil (a CYP3A4 substrate and phosphodiesterase-5 [PDE-5] inhibitor) with cobicistat (a CYP3A4 inhibitor) is not recommended as it may increase avanafil exposure and the risk of PDE-5 inhibitor adverse events21, including hypotension, syncope, visual disturbances, and priapism. Because a safe and effective dosing regimen has not been determined, concurrent use of avanafil and cobicistat is not recommended 2.

Why it happens (mechanism)

Inhibition of CYP3A4-mediated metabolism of avanafil

Literature reports

1 report — tap to read

a) Compared with the pharmacokinetics of avanafil alone, administration of a single avanafil 50 mg dose with ketoconazole 400 mg/day (strong CYP3A4 inhibitor) resulted in a 13-fold increase in AUC, 3.1-fold increase in Cmax, and a prolonged half-life of 9 hours for avanafil 1.

Common questions

Can I take Cobicistat and Avanafil together?

Increased avanafil exposure and increased risk of avanafil-related adverse events Always confirm with your pharmacist or prescriber before making any change.

How serious is the Cobicistat and Avanafil 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.

Questions for your pharmacist

  • Does my dose of Cobicistat or Avanafil 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: TYBOST(R) oral tablets, cobicistat oral tablets. Gilead Sciences Inc (per FDA), Foster City, CA, 2025. DailyMed
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Cobicistat

Keep reading about Cobicistat

All Cobicistat interactions (129)
Also serious with: Lovastatin Ivabradine Lurasidone Colchicine
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:

Cobicistat + Activated Charcoal Adrafinil Cannabidiol (cbd) Cannabinol (cbn) Cannabis Coffee Charcoal Delta-9-tetrahydrocannabinol (thc) Ergot + 22 more
Avanafil + Activated Charcoal American Mistletoe Grapefruit Hawthorn St. John's Wort Acacia Rigidula Adrafinil African Wild Potato + 136 more

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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.