Vorapaxar 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
Vorapaxar
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 vorapaxar exposure
Interaction Deep Dive
Concomitant use of vorapaxar (a CYP3A4 substrate) with a strong CYP3A4 inhibitor may result in an increase in vorapaxar exposure and a greater risk of related adverse events. During drug interaction studies, coadministration of ketoconazole (a strong CYP3A4 inhibitor) and vorapaxar (a CYP3A4 substrate) resulted in an approximately 2-fold increase in both vorapaxar AUC and Cmax. Avoid coadministration of vorapaxar with a strong CYP3A4 inhibitor1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated vorapaxar metabolism
Literature reports
1 report — tap to read
a) During drug interaction studies, coadministration of ketoconazole and vorapaxar resulted in an approximately 2-fold increase in both vorapaxar AUC and Cmax 1.
Common questions
Can I take Vorapaxar and Ketoconazole Topical together?
Increased vorapaxar exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Vorapaxar 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 Vorapaxar 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: ZONTIVITY(R) oral tablets, vorapaxar oral tablets. Merck Sharp & Dohme Corp. (per FDA), Whitehouse Station, NJ, 2015. DailyMed
Keep reading about Ketoconazole Topical
Keep reading about Vorapaxar
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