Ketoconazole Topical and Triazolam: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Triazolam
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
Increased triazolam exposure and potential triazolam toxicity (excessive sedation and prolonged hypnotic effects)
Interaction Deep Dive
Concomitant use of ketoconazole and oral triazolam is contraindicated as it may cause several-fold increase in triazolam exposure. This may potentiate and prolong hypnotic and sedative effects, especially with repeated dosing or chronic administration of these agents1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of triazolam
Literature reports
3 reports — tap to read
a) Seven healthy male volunteers participated in a double-blind, single-dose, 5-way crossover study to determine the magnitude and clinical consequence of the interaction of ketoconazole with triazolam and ALPRAZolam. The five treatment phases consisted of placebo and ALPRAZolam 1 mg, ketoconazole 200 mg and ALPRAZolam 1 mg, placebo and triazolam 0.25 mg, ketoconazole 200 mg and triazolam 0.25 mg, and ketoconazole 200 mg and placebo. The elimination half-life of ALPRAZolam increased from 15.2 hours to 59 hours during ketoconazole coadministration, while the total area under the concentration-time curve (AUC) of ALPRAZolam rose from 237 ng/mL/hr to 944 ng/mL/hr. The oral clearance of ALPRAZolam decreased from 86 mL/min to 27 mL/min. However, the peak plasma concentrations were not significantly altered by the presence of ketoconazole. Pharmacodynamically, ketoconazole enhanced the benzodiazepine effects of ALPRAZolam but statistical significance was not always achieved due to the degree of variability and the small sample size. Overall, ketoconazole had a much more profound clinical effect on the pharmacokinetic and pharmacodynamic parameters of triazolam than on ALPRAZolam 4.
b) Azole antifungals, including ketoconazole are thought to inhibit the metabolism of drugs cleared by the cytochrome P450 3A subfamily of enzymes and, possibly, the P450 2C subfamily 23.
c) An interim report of a controlled study observed a marked pharmacokinetic interaction between triazolam and ketoconazole. The study results indicated that triazolam half-life increased, and triazolam clearance was reduced, by approximately 9-fold 5.
Common questions
Can I take Ketoconazole Topical and Triazolam together?
Increased triazolam exposure and potential triazolam 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 Triazolam interaction?
It is rated contraindicated. These should generally not be used together.
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 "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Ketoconazole Topical or Triazolam 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 (5)
- Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
- Slaughter RL & Edwards DJ: Recent advances: the cytochrome P450 enzymes. Ann Pharmacother 1995; 29:619-624. PubMed
- Shen WW: Cytochrome P450 monooxygenases and interactions of psychotropic drugs: a five-year update. Int J Psychiatry Med 1995; 25:277-290. DOI
- Greenblatt DJ, Wright CE, von Moltke LL, et al: Ketoconazole inhibition of triazolam and alprazolam clearance: differential kinetic and dynamic consequences. Clin Pharmacol Ther 1998; 64:237-247. DOI
- Greenblatt DJ, Von Moltke LL, Harmatz JS, et al: Interaction of triazolam and ketoconazole (letter). Lancet 1995; 345:191. PubMed
Keep reading about Triazolam
Keep reading about Ketoconazole Topical
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