Ketoconazole Topical and Sufentanil: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Sufentanil
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 SUFentanil exposure and an increased risk of respiratory depression
Interaction Deep Dive
Concomitant use of SUFentanil and any CYP3A4 inhibitor may increase plasma concentrations of SUFentanil, and may lead to prolonged opioid effects, including respiratory depression. If use of a CYP3A4 inhibitor is necessary in a patient receiving SUFentanil, consider reducing the dose of SUFentanil and frequently monitor for respiratory depression or sedation. When discontinuing a CYP3A4 inhibitor in a patient receiving SUFentanil therapy, consider a SUFentanil dose increase and monitor for signs of opioid withdrawal12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated SUFentanil metabolism
Literature reports
1 report — tap to read
a) In a randomized, 3-phase, crossover study, coadministration of ALfentanil and voriconazole led to increased exposure, decreased plasma clearance, and prolonged half-life of ALfentanil. Healthy volunteers (n=20) were administered either no pretreatment (control phase), oral voriconazole for 2 days (400 mg twice on day 1, then 200 mg twice on day 2; voriconazole phase), or oral terbinafine 250 mg once daily for 3 days (terbinafine phase) in a randomized order. Following the last voriconazole or terbinafine dose, all subjects received intravenous (IV) ALfentanil 20 micrograms/kilogram over a period of 2 minutes. Additionally, IV naloxone 0.1 mg was administered prior to and following the ALfentanil injection to prevent ALfentanil's sedative and respiratory depressant effects. While terbinafine had no statistically significant effects on ALfentanil's pharmacokinetics, voriconazole decreased the mean ALfentanil plasma clearance by 85% (p less than 0.001) and prolonged its half-life from 1.5 +/- 0.49 hours to 6.6 +/- 1.8 hours (p less than 0.001). Voriconazole also increased the mean AUC of ALfentanil by 6-fold (p less than 0.001), with the greatest increase being 8.5-fold. In addition to visual adverse events reported during the voriconazole phase, nausea (n=5) and vomiting (n=4) occurred in the voriconazole phase, 4 hours after ALfentanil injection. No adverse events were noted during the control and terbinafine phases. Inhibition of CYP3A4-mediated ALfentanil metabolism by voriconazole was postulated to be the responsible mechanism. The study investigators recommend that caution be used if ALfentanil and voriconazole are coadministered and ALfentanil doses may need to be reduced by 70% to 90% when given concomitantly with voriconazole 3.
Common questions
Can I take Ketoconazole Topical and Sufentanil together?
Increased SUFentanil exposure and an increased risk of respiratory depression Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Sufentanil 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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Ketoconazole Topical or Sufentanil 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 (3)
- Product Information: Sufentanil citrate injection, sufentanil citrate r intravenous and epidural injection. Akron Inc (per FDA), Lake Forest, IL, 2023. DailyMed
- Product Information: DSUVIA(TM) sublingual tablets, sufentanil sublingual tablets. AcelRx Pharmaceuticals Inc (per FDA), Hayward, CA, 2023. DailyMed
- Saari TI, Laine K, Leino K, et al: Voriconazole, but not terbinafine, markedly reduces alfentanil clearance and prolongs its half-life. Clin Pharmacol Ther 2006; 80(5):502-508. PubMed
Keep reading about Sufentanil
Keep reading about Ketoconazole Topical
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