Ketoconazole Topical and Venlafaxine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Venlafaxine
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
Increased venlafaxine exposure and its active metabolite and an increased risk for QT interval prolongation
Interaction Deep Dive
Coadministering oral ketoconazole and a CYP3A4 substrate that are known to prolong the QT interval, such as venlafaxine is contraindicated as it may increase venlafaxine exposure and may also increase the risk of QT interval prolongation1. In addition, coadministration of venlafaxine with CYP3A4 inhibitors increases the exposure of O-desmethylvenlafaxine which may increase the risk of toxicity of venlafaxine. Consider reducing the dose of venlafaxine. A pharmacokinetic study demonstrated an increase in Cmax and AUC of both venlafaxine and the O-desvenlafaxine active metabolite with concomitant use 2.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism of venlafaxine and its active metabolite; reduced venlafaxine clearance; additive QT interval prolongation
Literature reports
1 report — tap to read
a) Higher plasma concentrations of both venlafaxine and the active metabolite O-desvenlafaxine (ODV) occurred during a pharmacokinetic study of ketoconazole 100 mg twice daily plus a single dose of venlafaxine (50 mg to 14 extensive metabolizers (EM) and 25 mg to 6 poor metabolizers (PM)). The Cmax of venlafaxine increased by 48% in PM and 26% in EM. Cmax of ODV increased by 29% in PM and 14% in EM subjects. Venlafaxine AUC increased by 70% (range, -2% to 206%) and 21% in PM and EM subjects, respectively. The ODV metabolite AUC increased by 33% (range, -38% to 105%) and 23% in PM and EM subjects, respectively, and the combined AUCs of venlafaxine plus ODV increased an average of 53% (range, 4% to 134%) and 23%, respectively 2.
Common questions
Can I take Ketoconazole Topical and Venlafaxine together?
Increased venlafaxine exposure and its active metabolite and an increased risk for QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Venlafaxine 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Ketoconazole Topical or Venlafaxine 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: EFFEXOR XR(R) oral extended-release capsules, venlafaxine oral extended-release capsules. Viatris Specialty (per FDA), Morgantown, WV, 2023. DailyMed
Keep reading about Venlafaxine
Keep reading about Ketoconazole Topical
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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