Drug Interaction Report

Nelfinavir and Avanafil: Interaction Details

A pharmacist-reviewed analysis of the Nelfinavir 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

Nelfinavir

Viracept
+

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 171 documented Nelfinavir interactions, 143 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

Decreased avanafil clearance and increased avanafil plasma concentration

Interaction Deep Dive

Concomitant administration of nelfinavir (a strong CYP3A4 inhibitor)2 and avanafil (a CYP3A4 substrate) may result in increased avanafil exposure and toxicity. Compared with the pharmacokinetics of avanafil alone, the administration of a single dose of avanafil 50 mg with ketoconazole 400 mg/day (a 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. Although not specifically studied with nelfinavir, other strong CYP3A4 inhibitors would be expected to have similar effects. Nelfinavir and avanafil should not be used concomitantly 1.

Why it happens (mechanism)

Inhibition of CYP3A4-mediated metabolism of avanafil by nelfinavir

Literature reports

1 report — tap to read

a) Compared with the pharmacokinetics of avanafil alone, the administration of a single dose of avanafil 50 mg with ketoconazole 400 mg/day (a 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. Although not specifically studied with nelfinavir, other strong CYP3A4 inhibitors would be expected to have similar effects 1.

Common questions

Can I take Nelfinavir and Avanafil together?

Decreased avanafil clearance and increased avanafil plasma concentration Always confirm with your pharmacist or prescriber before making any change.

How serious is the Nelfinavir 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 Nelfinavir 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: VIRACEPT(R) oral tablets, oral powder, nelfinavir mesylate oral tablets, oral powder. ViiV Healthcare Company (Per FDA), Research Triangle Park, NC, 2012. DailyMed
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Nelfinavir

Keep reading about Nelfinavir

All Nelfinavir interactions (171)
Also serious with: Dihydroergotamine Injection Lovastatin Finerenone Midazolam Injection
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:

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.