Ribociclib and Ketoconazole Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ribociclib
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 ribociclib exposure, an increased risk of ribociclib-related adverse reaction, an increased ketoconazole exposure, an increased risk of ketoconazole-related adverse reaction and an increased risk of QT interval prolongation
Interaction Deep Dive
Coadministration of ketoconazole with ribociclib (QT prolonging CYP3A4 substrate) is contraindicated, as it may increase ribociclib exposure and cause additive QT effects. Concomitant use with ribociclib (a strong CYP3A4 inhibitor) with ketoconazole (a CYP3A4 substrate) may also increase ketoconazole exposure1. Monitor ECG when initiating, during concomitant use, and as needed. Consider an alternative drug with less potential for CYP3A4 inhibition. In early breast cancer, interrupt ribociclib. Wait until QTcF resolves to less than 480 ms, and resume at the same dose, In advanced or metastatic breast cancer, interrupt ribociclib. Wait until QTcF resolves to less than 480 ms, and reduce to the next lower dose level; if QTcF prolongation of more than 480 ms recurs, interrupt ribociclib treatment and wait until QTcF resolves to less than 480 ms, then resume at next lower dose level. When QTcF prolongation is more than 500 ms: Interrupt ribociclib treatment and wait until QTcF resolves to less than 480 ms, then resume at next lower dose level. If QTcF more than 500 ms recurs, discontinue ribociclib. Permanently discontinue ribociclib if QTcF interval prolongation is either more than 500 ms or more than 60 ms change from baseline and associated with any of the following: Torsade's de pointes, polymorphic ventricular tachycardia, syncope, or signs/symptoms of serious arrhythmia. If dose reduction below 200 mg/day is required, discontinue ribociclib 2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of ribociclib; inhibition of CYP3A4-mediated metabolism of ketoconazole; additive QT interval prolongation
Literature reports
3 reports — tap to read
a) Coadministration of a single ribociclib 400 mg dose with ritonavir 100 mg twice a day for 14 days (a strong CYP3A4 inhibitor) resulted in an increase in ribociclib Cmax by 1.7-fold and AUC(inf) by 3.2-fold compared with ribociclib alone in a drug interaction study in health subjects 2.
b) A moderate CYP3A4 inhibitor (erythromycin) is predicted to increase ribociclib steady-state Cmax and AUC by 1.1-fold and 1.2-fold, respectively, following ribociclib 400 mg once daily, and 1.1-fold and 1.1-fold respectively, following ribociclib 600 mg once daily 2.
c) Coadministration of ribociclib 400 mg once daily for 8 days with midazolam increased midazolam Cmax by 2.1-fold and AUC(inf) by 3.8-fold in a drug interaction study in healthy subjects. Administration of ribociclib at 600 mg once daily is predicted to increase midazolam Cmax by 2.4-fold and AUC by 5.2-fold 2.
Common questions
Can I take Ribociclib and Ketoconazole Topical together?
Increased ribociclib exposure, an increased risk of ribociclib-related adverse reaction, an increased ketoconazole exposure, an increased risk of ketoconazole-related adverse reaction and an increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ribociclib 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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Ribociclib 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: KISQALI(R) oral tablets, ribociclib oral tablets. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2025. DailyMed
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