Letrozole and Ketoconazole Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole Topical
Letrozole
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 letrozole plasma concentrations
Interaction Deep Dive
Caution is advised when using ketoconazole, a strong CYP3A4 inhibitor, together with a CYP3A4 substrate such as letrozole, as concomitant use may result in elevated plasma concentrations of letrozole resulting in increased or prolonged therapeutic and adverse effects1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of letrozole
Common questions
Can I take Letrozole and Ketoconazole Topical together?
Increased letrozole plasma concentrations Always confirm with your pharmacist or prescriber before making any change.
How serious is the Letrozole and Ketoconazole Topical interaction?
It is rated moderate. Can be significant — usually manageable with 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 Letrozole or Ketoconazole Topical 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 anything you'd monitor while I'm on both?
References (1)
- Product Information: NIZORAL(R) oral tablets, ketoconazole oral tablets. Janssen Pharmaceuticals, Inc (per FDA), Titusville, NJ, 2014. DailyMed
Keep reading about Ketoconazole Topical
Keep reading about Letrozole
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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