Rifampin and Ketoconazole Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Rifampin
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
Reduced ketoconazole exposure and reduce efficacy of ketoconazole
Interaction Deep Dive
Concomitant use of rifAMPin with ketoconazole may reduce ketoconazole exposure and may also reduce efficacy of ketoconazole341. Coadministration of oral ketoconazole and rifAMPin is not recommended as it may reduce ketoconazole exposure to such an extent that efficacy may be reduced. Avoid the use of these drugs from 2 weeks before and during treatment with oral ketoconazole, unless the benefits outweigh the risk of potentially reduced ketoconazole efficacy. Upon coadministration, the antifungal activity should be monitored and the oral ketoconazole dose increased as deemed necessary 2. The addition of rifAMPin to ketoconazole therapy decreased the ketoconazole levels by up to 50%. The peak concentration of rifAMPin was reduced 40% to 50% if ketoconazole was administered at the same time as rifAMPin 67.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of ketoconazole
Literature reports
2 reports — tap to read
a) One study reported significantly diminished AUC and peak plasma levels of ketoconazole in 6 subjects when ketoconazole 200 mg was administered with rifAMPin 600 mg. RifAMPin peak plasma concentrations were unaltered by ketoconazole 5.
b) The addition of rifAMPin to ketoconazole therapy decreased the ketoconazole levels by up to 50%. The peak concentration of rifAMPin was reduced 40% to 50% if ketoconazole was administered at the same time as rifAMPin 67.
Common questions
Can I take Rifampin and Ketoconazole Topical together?
Reduced ketoconazole exposure and reduce efficacy of ketoconazole Always confirm with your pharmacist or prescriber before making any change.
How serious is the Rifampin 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 "delayed". Effects tend to build up gradually over days to weeks.
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 Rifampin 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 (7)
- Product Information: NIZORAL(R) oral tablets, ketoconazole oral tablets. Janssen Pharmaceuticals, Inc (per FDA), Titusville, NJ, 2014. DailyMed
- Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
- Product Information: RIFADIN(R) oral capsules, rifampin oral capsules. sanofi-aventis US LLC (per FDA), Bridgewater, NJ, 2023. DailyMed
- Product Information: RIFATER(R) oral tablets, rifampin, isoniazid, pyrazinamide oral tablets. sanofi-aventis US LLC (per FDA), Bridgewater, NJ, 2023. DailyMed
- Doble N, Shaw R, Rowland-Hill C, et al: Pharmacokinetic study of the interaction between rifampicin and ketoconazole. J Antimicrob Chemother 1988; 21:633-635. PubMed
- Meunier F: Serum fungistatic and fungicidal activity in volunteers receiving antifungal agents. Eur J Clin Microbiol Infect Dis 1986; 5:103-109. DOI
- Engelhard D, Stutman HR, & Marks MI: Interaction of ketoconazole with rifampin and isoniazid. N Engl J Med 1984; 311:1681-1683. PubMed
Keep reading about Rifampin
Keep reading about Ketoconazole Topical
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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