Ketoconazole Topical and Crizotinib: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Crizotinib
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 crizotinib exposure, increased ketoconazole exposure and an increased risk of QT interval prolongation
Interaction Deep Dive
Concomitant use of ketoconazole together with a CYP3A4 substrate known to prolong the QT interval (eg, crizotinib) is contraindicated. Concomitant use may result in elevated crizotinib exposure, increasing the risk for QT prolongation and life-threatening ventricular tachyarrhythmias, including torsades de pointes1. If concomitant use cannot be avoided, monitor ECG and electrolytes and dosage reductions of crizotinib are required. In patients with non-small cell lung cancer (NSCLC) or inflammatory myofibroblastic tumor (IMT), decrease the dose of crizotinib to 250 mg once daily. Permanently discontinue crizotinib if unable to tolerate 250 mg taken once daily. In pediatric patients with anaplastic large cell lymphoma (ALCL) or IMT and young adults with ALCL, and body surface area (BSA) 1.7 m(2) or greater, reduce crizotinib to 250 mg twice daily; BSA 1.17 to 1.69 m(2), reduce to 200 mg twice daily; BSA 0.98 to 1.16 m(2), reduce to 170 mg once daily; BSA 0.81 to 0.97 m(2), reduce to 150 mg once daily; BSA 0.62 to 0.80 m(2), reduce to 120 mg once daily; BSA 0.52 to 0.61 m(2), reduce to 90 mg once daily; BSA 0.47 to 0.51 m(2), reduce to 80 mg once daily; BSA 0.38 to 0.46 m(2), reduce to 70 mg once daily. Once ketoconazole is discontinued, resume the prior dose of crizotinib 2.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism of crizotinib; inhibition of CYP3A-mediated metabolism of ketoconazole; additive QT interval prolongation
Literature reports
3 reports — tap to read
a) Coadministration of ketoconazole 200 mg twice daily, a strong CYP3A inhibitor, with a single 150-mg dose of crizotinib (CYP3A substrate) increased the AUC and Cmax of crizotinib by 216% and 44%, respectively 2.
b) Coadministration of itraconazole 200 mg once daily, a strong CYP3A inhibitor, with crizotinib 250 mg once daily (CYP3A substrate) increased the steady-state AUC and Cmax of crizotinib by 57% and 33%, respectively 2.
c) In a pharmacokinetic study, coadministration of crizotinib 250 mg twice daily for 28 days (CYP3A inhibitor) with oral midazolam (CYP3A substrate) resulted in a 3.7-fold increase in the geometric mean midazolam AUC compared with midazolam administered alone 2.
Common questions
Can I take Ketoconazole Topical and Crizotinib together?
Increased crizotinib exposure, increased ketoconazole exposure and an increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Crizotinib 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 "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Ketoconazole Topical or Crizotinib 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: XALKORI(R) oral pellets, oral capsules, crizotinib oral pellets, oral capsules. Pfizer Labs (per FDA), New York, NY, 2023. DailyMed
Keep reading about Crizotinib
Keep reading about Ketoconazole Topical
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