Ketoconazole Topical and Voriconazole: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Voriconazole
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 risk of QT interval prolongation, an increased ketoconazole exposure, an increased risk of ketoconazole-related adverse reactions, an increased voriconazole exposure and an increased risk of voriconazole-related adverse reactions
Interaction Deep Dive
Coadministration of ketoconazole (strong CYP3A4 inhibitor that may prolong the QT interval) with voriconazole (CYP3A4 substrates that are known to prolong the QT interval) is contraindicated as it may cause voriconazole exposure, increasing the risk for QT interval prolongation and result in life-threatening ventricular tachyarrhythmias such as torsade de pointes1. Adjust voriconazole dosage and monitor for adverse reactions when coadministered with ketoconazole (CYP2C9 inhibitor) 2. Coadministration of ketoconazole with voriconazole (strong CYP3A4 inhibitor), may increase ketoconazole exposure and may also increase ketoconazole-related adverse reactions. If coadministered, monitor closely for signs or symptoms of increased or prolonged pharmacologic effects of ketoconazole, and reduce the oral ketoconazole dose as deemed necessary. When appropriate, measure ketoconazole exposure 1.
Why it happens (mechanism)
Additive QT interval prolongation; inhibition of CYP3A4-mediated metabolism of ketoconazole; inhibition of CYP3A4-mediated metabolism of voriconazole; inhibition of CYP2C9-mediated metabolism of voriconazole
Literature reports
4 reports — tap to read
a) In an independent published study, concomitant use of voriconazole (400 mg every 12 hours on Day 1, then 200 mg every 12 hours on Day 2) with a single intravenous dose of fentaNYL (CYP3A4 substrate) (5 microgram/kg) resulted in an increase in the mean AUC (0 to inf) of fentaNYL by 1.4-fold (range 0.81- to 2.04-fold) 2.
b) In another independent published study, coadministration of multiple doses of oral voriconazole (400 mg every 12 hours, on Day 1 followed by five doses of 200 mg every 12 hours on Days 2 to 4) with a single 10 mg oral dose of oxyCODONE (CYP3A4 substrate) on Day 3 resulted in an increase in the mean Cmax and AUC (0 to inf) of oxyCODONE by 1.7-fold (range 1.4- to 2.2-fold) and 3.6- fold (range 2.7- to 5.6-fold), respectively. The mean elimination half-life of oxyCODONE was also increased by 2.0-fold (range 1.4- to 2.5-fold) 2.
c) In stable renal transplant recipients receiving chronic cycloSPORINE (CYP3A4 substrate) therapy, concomitant administration of oral voriconazole (200 mg every 12 hours for 8 days) increased cycloSPORINE Cmax and AUC (tau) an average of 1.1 times (90% CI: 0.9, 1.41) and 1.7 times (90% CI: 1.5, 2.0), respectively, as compared to when cycloSPORINE was administered without voriconazole 2.
d) In a drug interaction study, concurrent administration of oral voriconazole (400 mg every 12 hours for 1 day, then 200 mg every 12 hours for 2.5 days) and oral fluconazole (CYP3A4/CYP2C9 inhibitor) (400 mg on day 1, then 200 mg every 24 hours for 4 days) to 6 healthy male subjects resulted in an increase in Cmax and AUC(tau) of voriconazole by an average of 57% (90% CI: 20%, 107%) and 79% (90% CI: 40%, 128%), respectively 2.
Common questions
Can I take Ketoconazole Topical and Voriconazole together?
Increased risk of QT interval prolongation, an increased ketoconazole exposure, an increased risk of ketoconazole-related adverse reactions, an increased voriconazole exposure and an increased risk of voriconazole-related adverse reactions Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Voriconazole 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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Ketoconazole Topical or Voriconazole 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 (2)
- Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
- Product Information: VFEND(R) oral tablets, oral suspension, intravenous injection, voriconazole oral tablets, oral suspension, intravenous injection. Roerig (per FDA), New York, NY, 2025. DailyMed
Keep reading about Voriconazole
Keep reading about Ketoconazole Topical
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