Ketoconazole Topical and Sildenafil: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole Topical
Sildenafil
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.
What happens
Increased sildenafil exposure and an increased risk of prolonged sildenafil adverse effects (headache, flushing, priapism)
Interaction Deep Dive
Concomitant use of ketoconazole (a strong CYP3A4 inhibitor) with sildenafil (for pulmonary arterial hypertension) is not recommended1. Sildenafil is metabolized by CYP3A4 enzymes, and the administration of erythromycin, a CYP3A4 inhibitor, has increased the sildenafil systemic exposure by 182%. Ketoconazole is a more potent CYP3A4 inhibitor than erythromycin, so it would be expected to have greater effects on sildenafil metabolism. Due to the significant increase in sildenafil plasma concentrations patients should be monitored for increased sildenafil adverse effects. For erectile dysfunction a starting sildenafil dose of 25 mg should be considered in patients also receiving ketoconazole 2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of sildenafil
Literature reports
2 reports — tap to read
a) In clinical studies, sildenafil Cmax was increased 140% and sildenafil AUC increased 210% when administered with saquinavir, a strong CYP3A4 inhibitor. Ketoconazole is a stronger CYP3A4 inhibitor than saquinavir, and therefore may produce greater increases in sildenafil exposure 2.
b) In clinical studies, sildenafil Cmax was increased 160% and sildenafil AUC increased 182% when administered with erythromycin, a moderate CYP3A4 inhibitor. Ketoconazole is a stronger CYP3A4 inhibitor than erythromycin, and therefore may produce greater increases in sildenafil exposure 2.
Common questions
Can I take Ketoconazole Topical and Sildenafil together?
Increased sildenafil exposure and an increased risk of prolonged sildenafil adverse effects (headache, flushing, priapism) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Sildenafil 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 "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Ketoconazole Topical or Sildenafil 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: REVATIO(R) oral tablets, oral suspension, intravenous injection, sildenafil oral tablets, oral suspension, intravenous injection. Pfizer Labs (per FDA), New York, NY, 2023. DailyMed
- Product Information: VIAGRA(R) oral tablets, sildenafil citrate oral tablets. Pfizer Labs (per FDA), New York, NY, 2015. DailyMed
Keep reading about Ketoconazole Topical
Keep reading about Sildenafil
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist