Ketoconazole Topical and Orforglipron: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole Topical
Orforglipron
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 orforglipron exposure and an increased risk of orforglipron-related adverse reactions
Interaction Deep Dive
Avoid concomitant use of orforglipron with strong CYP3A4 inhibitors as it may increase orforglipron exposure, which could increase orforglipron-related adverse reactions. In drug interaction studies, concomitant use of orforglipron with clarithromycin (strong CYP3A4 inhibitor) (500 mg twice daily) increased the orforglipron AUC by 3.5-fold, and Cmax by 1.9-fold. The maximum dosage of orforglipron is 9 mg once daily when used concomitantly with a strong CYP3A4 inhibitor1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of orforglipron
Literature reports
1 report — tap to read
a) In drug interaction studies, concomitant use of orforglipron with clarithromycin (strong CYP3A4 inhibitor) (500 mg twice daily) increased the orforglipron AUC by 3.5-fold, and Cmax by 1.9-fold 1.
Common questions
Can I take Ketoconazole Topical and Orforglipron together?
Increased orforglipron exposure and an increased risk of orforglipron-related adverse reactions Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Orforglipron 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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Ketoconazole Topical or Orforglipron 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: FOUNDAYO™ oral tablet, orforglipron oral tablet. Lilly USA LLC, Indianapolis, IN, 2026. DailyMed
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