Isoniazid and Ketoconazole Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Isoniazid
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
Reduced ketoconazole exposure, reduced efficacy of ketoconazole and an increased risk of ketoconazole toxicity
Interaction Deep Dive
Concomitant use of isoniazid and ketoconazole is not recommended as this may cause reduced ketoconazole exposure resulting in reduced ketoconazole efficacy and avoid within 2 weeks of initiating ketoconazole therapy, unless benefits outweigh potential risks associated with concomitant use. If concomitant use is required, monitor antifungal response as an increase in ketoconazole dosage may be necessary1. Additionally, concomitant use of isoniazid and ketoconazole (CYP3A4 substrate) may reduce elimination of ketoconazole, which may increase the risk of toxicities of ketoconazole. Adjust dosage of ketoconazole and monitor patients closely for adverse reactions 2.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of ketoconazole; inhibition of CYP3A4-mediated metabolism of ketoconazole
Literature reports
2 reports — tap to read
a) In one case report, a 55-year-old woman who was taking isoniazid, rifAMPin and ketoconazole experienced treatment failure after 9 months. Serum levels of all 3 drugs were undetectable, suggesting a drug interaction as the primary cause 4.
b) A study evaluated the serum concentrations of ketoconazole given alone or with rifAMPin, isoniazid or both. Concentrations were also measured when ketoconazole was administered 12 hours after rifAMPin or isoniazid. Serum concentrations of rifAMPin and ketoconazole were undetectable when all 3 drugs were administered together. When the patient took only isoniazid, the ketoconazole concentration was much lower than when ketoconazole was given alone. No difference was noted when the antimicrobials were given concurrently or 12 hours apart. These results imply that isoniazid interferes with ketoconazole metabolism rather than interacting through gastrointestinal absorption 3.
Common questions
Can I take Isoniazid and Ketoconazole Topical together?
Reduced ketoconazole exposure, reduced efficacy of ketoconazole and an increased risk of ketoconazole toxicity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Isoniazid 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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Isoniazid 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 (4)
- Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
- Product Information: RIFATER(R) oral tablets, rifampin, isoniazid, pyrazinamide oral tablets. sanofi-aventis US LLC (per FDA), Bridgewater, NJ, 2023. DailyMed
- Engelhard D, Stutman HR, & Marks MI: Interaction of ketoconazole with rifampin and isoniazid. N Engl J Med 1984; 311:1681-1683. PubMed
- Abadie-Kemmerly S, Pankey GA, & Dalovisio JR: Failure of ketoconazole treatment of blastomyces dermatidis due to interaction of isoniazid and rifampin (letter). Ann Intern Med 1988; 109:844-845.
Keep reading about Isoniazid
Keep reading about Ketoconazole Topical
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