Ketoconazole Topical and Chlordiazepoxide: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Chlordiazepoxide
No brand names on recordKetoconazole 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
Decreased chlordiazepoxide clearance and potentially increased chlordiazepoxide toxicity (excessive sedation and prolonged hypnotic effects)
Interaction Deep Dive
Chlordiazepoxide clearance was reduced when administered with ketoconazole1. Potential exist for increased chlordiazepoxide concentrations and subsequent chlordiazepoxide toxicity (excessive sedation and prolonged hypnotic effects).
Why it happens (mechanism)
Unknown
Literature reports
1 report — tap to read
a) Chlordiazepoxide clearance was reduced in a study evaluating the pharmacokinetics of chlordiazepoxide after a single dose of ketoconazole and after a 5-day course of ketoconazole given to healthy subjects. Six subjects received oral ketoconazole 200 mg or 400 mg with chlordiazepoxide 0.6 mg/kg injected intravenously over 5 minutes. After the single dose of ketoconazole, chlordiazepoxide clearance decreased by 20% and volume of distribution by 26%. After 5 days of ketoconazole therapy in 5 subjects, chlordiazepoxide clearance was reduced by 38% and lower concentrations of its metabolite N-desmethylchloridazepoxide were found. Concentrations of the metabolite demoxepam were unchanged. The postulated mechanism of this interaction was partial inhibition by ketoconazole of hepatic oxidative metabolism of chlordiazepoxide and its metabolites 1.
Common questions
Can I take Ketoconazole Topical and Chlordiazepoxide together?
Decreased chlordiazepoxide clearance and potentially increased chlordiazepoxide toxicity (excessive sedation and prolonged hypnotic effects) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Chlordiazepoxide interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
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 Chlordiazepoxide 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 anything you'd monitor while I'm on both?
References (1)
- Brown MW, Maldonado AL, Meredith CG, et al: Effect of ketoconazole on hepatic oxidative drug metabolism. Clin Pharmacol Ther 1985; 37:290-297. DOI
Keep reading about Chlordiazepoxide
Keep reading about Ketoconazole Topical
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