Selpercatinib 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
Selpercatinib
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 selpercatinib exposure and an increased risk of QT interval prolongation
Interaction Deep Dive
Coadministration of ketoconazole (a strong CYP3A4 inhibitor that may prolong the QT interval) with CYP3A4 substrates that are known to prolong the QT interval, such as selpercatinib is contraindicated1, as it may increase selpercatinib exposure, increasing the risk for QT prolongation. Assess QT interval, electrolytes and TSH at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating selpercatinib and during treatment. Withhold and reduce the dose or permanently discontinue selpercatinib based on severity 2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of selpercatinib; additive QT interval prolongation
Literature reports
2 reports — tap to read
a) In a pharmacokinetic study, coadministration of selpercatinib with multiple doses of itraconazole (a strong CYP3A inhibitor) increased selpercatinib AUC(0 to infinity) by 133% and Cmax by 30% 2.
b) Simulated coadministration of multiple doses of dilTIAZem, fluconazole, or verapamil (moderate CYP3A inhibitors) is predicted to increase selpercatinib AUC(0 to infinity) by 60% to 99% and Cmax by 46% to 76% 2.
Common questions
Can I take Selpercatinib and Ketoconazole Topical together?
Increased selpercatinib exposure and an increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.
How serious is the Selpercatinib and Ketoconazole Topical interaction?
It is rated contraindicated. These should generally not be used together.
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.
Questions for your pharmacist
- Does my dose of Selpercatinib 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 (2)
- Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
- Product Information: RETEVMO(R) oral capsules, tablets, selpercatinib oral capsules, tablets. Lilly USA LLC (per FDA), Indianapolis, IN, 2024. DailyMed
Keep reading about Ketoconazole Topical
Keep reading about Selpercatinib
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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