Lorlatinib and Ketoconazole Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Lorlatinib
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 lorlatinib exposure and an increased risk of lorlatinib-related adverse reactions
Interaction Deep Dive
Avoid the concomitant use of lorlatinib (CYP3A substrate) with a strong CYP3A inhibitor as it may lead to an increase in lorlatinib exposure, which may increase the incidence and severity of adverse reactions of lorlatinib. Lorlatinib AUC and Cmax was increased by 1.4-fold and 1.2-fold, respectively, with concomitant itraconazole (strong CYP3A inhibitor). If concomitant use cannot be avoided, reduce the starting dose of lorlatinib to 75 mg orally once daily. In patients who have had a dose reduction to 75 mg orally once daily due to adverse reactions and who initiate a strong CYP3A inhibitor, reduce the lorlatinib dose to 50 mg orally once daily. If concomitant use of a strong CYP3A inhibitor is discontinued, increase the lorlatinib dose (after 3 plasma half-lives of the strong CYP3A inhibitor) to the dose that was used before starting the strong inhibitor1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism of lorlatinib
Literature reports
1 report — tap to read
a) Coadministration of a single 100 mg dose of lorlatinib with itraconazole (a strong CYP3A inhibitor) resulted in an increase in lorlatinib AUC(inf) by 1.4-fold and Cmax by 1.2-fold 1.
Common questions
Can I take Lorlatinib and Ketoconazole Topical together?
Increased lorlatinib exposure and an increased risk of lorlatinib-related adverse reactions Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lorlatinib 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 "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 Lorlatinib 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 (1)
- Product Information: LORBRENA® oral tablets, lorlatinib oral tablets. Pfizer Labs (per FDA), New York, NY, 2026. DailyMed
Keep reading about Lorlatinib
Keep reading about Ketoconazole Topical
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