Ketoconazole Topical and Roflumilast: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole Topical
Roflumilast
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 roflumilast exposure and an increased risk of roflumilast-related adverse events
Interaction Deep Dive
Coadministration of roflumilast with CYP3A4 inhibitors like ketoconazole may increase roflumilast systemic exposure and may result in increased adverse reactions. The risk of such concurrent use should be weighed carefully against benefit. In an open-label crossover study of 16 healthy volunteers, concomitant oral administration of ketoconazole 200 mg twice daily for 13 days and a single dose of roflumilast 500 mcg resulted in increased roflumilast Cmax and AUC values of 23% and 99%, respectively, and a 38% reduction and 3% increase in the Cmax and AUC of roflumilast N-oxide (active metabolite), respectively12.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism of roflumilast
Literature reports
1 report — tap to read
a) In an open-label crossover study of 16 healthy volunteers, concomitant oral administration of ketoconazole 200 mg twice daily for 13 days and a single dose of roflumilast 500 mcg resulted in increased roflumilast Cmax and AUC values of 23% and 99%, respectively, and a 38% reduction and 3% increase in the Cmax and AUC of roflumilast N-oxide (active metabolite), respectively 12.
Common questions
Can I take Ketoconazole Topical and Roflumilast together?
Increased roflumilast exposure and an increased risk of roflumilast-related adverse events Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Roflumilast 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.
Questions for your pharmacist
- Does my dose of Ketoconazole Topical or Roflumilast 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)
Keep reading about Ketoconazole Topical
Keep reading about Roflumilast
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.
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