Ketoconazole Topical and Larotrectinib: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Larotrectinib
No brand names on recordKetoconazole 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 larotrectinib exposure
Interaction Deep Dive
Avoid concomitant use of larotrectinib (a CYP3A4 substrate) with a strong CYP3A4 inhibitor as it may increase larotrectinib exposure, which may result in a higher incidence of adverse reactions. Coadministration of a single larotrectinib 100 mg dose with itraconazole, a strong CYP3A inhibitor, increased the AUC(0 to infinity) and the Cmax of larotrectinib. If use cannot be avoided, reduce the larotrectinib dose by 50%. After the strong CYP3A4 inhibitor has been discontinued for 3 to 5 elimination half-lives, resume the larotrectinib dose taken prior to initiating the CYP3A4 inhibitor1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of larotrectinib
Literature reports
1 report — tap to read
a) Coadministration of a single larotrectinib 100 mg dose with itraconazole, a strong CYP3A inhibitor, increased the AUC(0 to infinity) of larotrectinib by 4.3-fold and the Cmax by 2.8-fold compared with larotrectinib administered alone 1.
Common questions
Can I take Ketoconazole Topical and Larotrectinib together?
Increased larotrectinib exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Larotrectinib 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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Ketoconazole Topical or Larotrectinib 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: VITRAKVI(R) oral capsules, oral solution, larotrectinib oral capsules, oral solution. Bayer HealthCare Pharmaceuticals Inc (per FDA), Whippany, NJ, 2022. DailyMed
Keep reading about Larotrectinib
Keep reading about Ketoconazole Topical
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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