Ketoconazole Topical and Pralsetinib: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole Topical
Pralsetinib
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 pralsetinib exposure and an increased risk of pralsetinib-related adverse events
Interaction Deep Dive
Concomitant use of pralsetinib (P-gp and a CYP3A substrate) and a combined P-gp and strong CYP3A inhibitor may increase pralsetinib exposure, which may increase the incidence and severity of adverse reactions. Coadministration of itraconazole (a combined P-gp and strong CYP3A inhibitor) with pralsetinib increased pralsetinib Cmax by 84% and AUC by 251%. Coadministration of cycloSPORINE with pralsetinib in healthy subjects increased pralsetinib AUC(0 to inf) by 81% and Cmax by 48%, relative to pralsetinib administered alone. Avoid concomitant use. If concomitant use cannot be avoided, reduce the dose of pralsetinib (from 400 mg or 300 mg once daily to 200 mg once daily or from 200 mg once daily to 100 mg once daily). After the combined P-gp and strong CYP3A inhibitor has been discontinued for 3 to 5 elimination half-lives, resume pralsetinib at the dose taken prior to initiating the combined P-gp and strong CYP3A inhibitor1.
Why it happens (mechanism)
Inhibition of P-gp mediated efflux transport of pralsetinib; inhibition of CYP3A-mediated metabolism of pralsetinib
Literature reports
3 reports — tap to read
a) In the clinical studies, coadministration of itraconazole (a combined P-gp and strong CYP3A inhibitor) 200 mg twice daily on Day 1 followed by 200 mg once daily with pralsetinib increased pralsetinib Cmax by 84% and AUC(0 to infinity) by 251% 1.
b) In a model-informed approach, coadministration of voriconazole (a strong CYP3A inhibitor) 400 mg twice daily on Day 1 followed by 200 mg twice daily with pralsetinib is predicted to increase pralsetinib Cmax by 20% and AUC by 122% 1.
c) Coadministration of cycloSPORINE (single 600 mg dose) with a single 200 mg dose of pralsetinib in healthy subjects increased pralsetinib AUC(0 to inf) by 81% and Cmax by 48%, relative to a 200 mg dose of pralsetinib administered alone 1.
Common questions
Can I take Ketoconazole Topical and Pralsetinib together?
Increased pralsetinib exposure and an increased risk of pralsetinib-related adverse events Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Pralsetinib 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 "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Ketoconazole Topical or Pralsetinib 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 (1)
- Product Information: GAVRETO(TM) oral capsules, pralsetinib oral capsules. Genentech USA Inc (per FDA), South San Fransisco, CA, 2023. DailyMed
Keep reading about Ketoconazole Topical
Keep reading about Pralsetinib
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