Sirolimus and Ketoconazole Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Sirolimus
Ketoconazole Topical
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 sirolimus exposure and an increased risk of sirolimus-related adverse reactions
Interaction Deep Dive
Avoid coadministration of sirolimus (CYP3A4/P-gp substrate) and ketoconazole (potent CYP3A4/P-gp inhibitor. Consider an alternative agents with lesser interaction potential with sirolimus2. Concomitant use may increase sirolimus exposure. If coadministration cannot be avoided, clinical monitoring for signs or symptoms of increased or prolonged effects or side effects of sirolimus is recommended, and reduce or interrupt sirolimus dosage as deemed necessary 1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of sirolimus; inhibition of P-gp-mediated metabolism of sirolimus
Literature reports
1 report — tap to read
a) A study of the administration of two 5 mg doses of sirolimus, the first alone, the second with concomitant oral ketoconazole 200 mg daily for 10 days at steady-state, resulted in a significant increase sirolimus whole blood concentrations. The study included 23 healthy volunteers, 8 women and 15 men. The sirolimus Cmax, tmax increased 4.3-fold and 1.4-fold, respectively. AUC (0-144 h) increased 11-fold (297 +/- 93 vs. 3319 +/- 1048 ng/h/mL). The terminal half-life of sirolimus was not changed. Single doses of sirolimus had no effect on the steady-state 12-hour ketoconazole exposure 3.
Common questions
Can I take Sirolimus and Ketoconazole Topical together?
Increased sirolimus exposure and an increased risk of sirolimus-related adverse reactions Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sirolimus and Ketoconazole Topical interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Sirolimus 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 a safer alternative to one of these medications for me?
References (3)
- Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
- Product Information: RAPAMUNE(R) oral solution, tablets, sirolimus oral solution, tablets. Wyeth Pharmaceuticals Inc (per FDA), Philadelphia, PA, 2022.
- Floren LC, Christians U, Zimmerman JJ, et al: PII-49 Sirolimus oral bioavailability increases ten-fold with concomitant ketoconazole (abstract). Clin Pharmacol Ther 1999; 65(2):159. DOI
Keep reading about Sirolimus
Keep reading about Ketoconazole Topical
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