Rilpivirine 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
Rilpivirine
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 rilpivirine exposure, increased risk of fungal infection and an increased risk of QT interval prolongation
Interaction Deep Dive
Concomitant use of rilpivirine (CYP3A substrate) with ketoconazole (azole antifungal agent and moderate CYP3A inhibitor) is contraindicated because it may result in additive QT interval prolongation1. Additionally, it may cause increased rilpivirine exposure 12. In a pharmacokinetic study using higher than recommended doses of rilpivirine, the mean AUC of rilpivirine significantly increased and the mean AUC of ketoconazole significantly decreased when coadministered with ketoconazole. Consider alternatives to rilpivirine when coadministered with a drug with a known risk of torsade de pointes. Clinically monitor for breakthrough fungal infections when ketoconazole is coadministered with rilpivirine 32.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism of rilpivirine; additive QT interval prolongation
Literature reports
1 report — tap to read
a) In drug interaction studies, the concomitant administration of ketoconazole and rilpivirine in healthy subjects or in patients with antiretroviral treatment-naive HIV-1 resulted in increased rilpivirine and decreased ketoconazole plasma concentrations. Patients (n=15) received once daily doses of ketoconazole 400 mg and rilpivirine 150 mg. The rilpivirine dose was higher than recommended to assess the maximal effect. The mean AUC ratio of rilpivirine (with/without ketoconazole) was 1.49 (90% confidence interval (CI), 1.31 to 1.7) , the Cmax was 1.3 (90% CI, 1.13 to 1.48), and Cmin was 1.76 (90% CI, 1.57 to 1.97). In another study (n=14), when the 2 drugs were coadministered with the same dosage, the mean AUC ratio of ketoconazole (with/without rilpivirine) was 0.76 (90% CI, 0.7 to 0.82), the Cmax was 0.85 (90% CI, 0.8 to 0.9), and the Cmin was 0.34 (90% CI, 0.25 to 0.46) 32.
Common questions
Can I take Rilpivirine and Ketoconazole Topical together?
Increased rilpivirine exposure, increased risk of fungal infection and an increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.
How serious is the Rilpivirine 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 Rilpivirine 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 (3)
- Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
- Product Information: EDURANT(R) PED oral tablets for suspension, rilpivirine oral tablets for suspension. Janssen Therapeutics (per FDA), Horsham, Pa, 2024. DailyMed
- Product Information: EDURANT(R) oral tablets, rilpivirine oral tablets. Janssen Therapeutics (per FDA), Horsham, Pa, 2024. DailyMed
Keep reading about Ketoconazole Topical
Keep reading about Rilpivirine
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