Drug Interaction Report

Trazodone and Ketoconazole Topical: Interaction Details

A pharmacist-reviewed analysis of the Trazodone and Ketoconazole Topical interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Trazodone

Raldesy
+

Ketoconazole Topical

Extina® Foam Ketozole® Cream Kuric Nizoral AD® Shampoo Nizoral® Cream Nizoral® Shampoo Xolegel®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Contraindicated
These should generally not be used together.
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.

Of 124 documented Trazodone interactions, 2 are rated contraindicated — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
probable
Severity
Contraindicated

What happens

Increased traZODone exposure and increased risk for QT interval prolongation

Interaction Deep Dive

Concomitant use of ketoconazole with a CYP3A4 substrate known to prolong the QT interval, such as traZODone, is contraindicated. Concomitant use may also increase traZODone exposure, increasing the risk for QT prolongation and life-threatening ventricular tachyarrhythmias, including torsades de pointes1. If used concomitantly, start traZODone at a low dose and monitor patient closely 2.

Why it happens (mechanism)

Inhibition of CYP3A4-mediated metabolism of traZODone; additive QT interval prolongation

Literature reports

1 report — tap to read

a) In vitro drug metabolism studies suggest that there is a potential for drug interactions when traZODone is given with CYP3A4 inhibitors. Ritonavir, a potent CYP3A4 inhibitor, increased the Cmax, AUC, and elimination half-life, and decreased clearance of trazodone after administration of ritonavir twice daily for 2 days. Adverse effects including nausea, hypotension, and syncope were observed when ritonavir and traZODone were coadministered 2.

Common questions

Can I take Trazodone and Ketoconazole Topical together?

Increased traZODone exposure and increased risk for QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.

How serious is the Trazodone and Ketoconazole Topical 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 "probable". Good supporting evidence, though not definitively proven.

From our Q&A

Real reader questions about these medications, each personally answered by our pharmacist:

Questions for your pharmacist

  • Does my dose of Trazodone 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 (2)

  1. Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
  2. Product Information: OLEPTRO(TM) oral extended-release tablets, trazodone HCl oral extended-release tablets. Angelini Pharma Inc. (per DailyMed), Gaithersburg, MD, 2014. DailyMed
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Trazodone

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Ketoconazole Topical

Keep reading about Ketoconazole Topical

All Ketoconazole Topical interactions (546) Ketoconazole Topical drug information
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Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Trazodone + Activated Charcoal Beer Grapefruit Lithium Siberian Cocklebur St. John's Wort Wine 1,3-dmaa + 189 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.