Drug Interaction Report

Sibutramine and Ketoconazole Topical: Interaction Details

A pharmacist-reviewed analysis of the Sibutramine 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

Sibutramine

No brand names on record
+

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
Major
Potentially serious — often needs a change or close monitoring.
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 51 documented Sibutramine interactions, 46 are rated major — 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
delayed
Evidence
theoretical
Severity
Major

What happens

Increased sibutramine exposure

Interaction Deep Dive

Sibutramine inhibits the reuptake of norepinephrine, dopamine, and serotonin. In addition, the two major metabolites of sibutramine, M1 and M2, also inhibit the reuptake of these neurotransmitters. Ketoconazole 200 mg twice daily and sibutramine 20 mg once daily were coadministered for seven days to 12 uncomplicated obese subjects. The AUC and Cmax were increased by 58% and 36%, respectively, for the M1 metabolite and were increased by 20% and 19%, respectively, for the M2 metabolite. Ketoconazole is CYP3A4 inhibitor and sibutramine is metabolized to M1 and M2 principally by CYP3A4. However, the magnitude of this interaction appears small, and currently no dosing adjustments are recommended2. Concomitant use of ketoconazole with a CYP3A4 substrate such as sibutramine may result in elevated sibutramine exposure resulting in increased or prolonged therapeutic and adverse effects 1.

Why it happens (mechanism)

Inhibition of CYP3A4-mediated metabolism of sibutramine

Literature reports

1 report — tap to read

a) Ketoconazole 200 mg twice daily and sibutramine 20 mg once daily were coadministered for seven days to 12 uncomplicated obese subjects. The AUC and Cmax were increased by 58% and 36%, respectively, for the M1 metabolite and were increased by 20% and 19%, respectively, for the M2 metabolite 2.

Common questions

Can I take Sibutramine and Ketoconazole Topical together?

Increased sibutramine exposure Always confirm with your pharmacist or prescriber before making any change.

How serious is the Sibutramine and Ketoconazole Topical interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "delayed". Effects tend to build up gradually over days to weeks.

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 Sibutramine 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: Meridia(R), sibutramine hydrochloride monohydrate. Knoll Pharmaceutical Company, Mount Olive, NJ, 1997. DailyMed
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Sibutramine

Keep reading about Sibutramine

All Sibutramine interactions (51)
Also serious with: Metoclopramide Injection Linezolid Injection Diethylpropion Metoclopramide Nasal Spray
Ketoconazole Topical

Keep reading about Ketoconazole Topical

All Ketoconazole Topical interactions (546) Ketoconazole Topical drug information
Also serious with: Colchicine Conivaptan Crizotinib Dabrafenib
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:

Sibutramine + Activated Charcoal American Hellebore Arsenic Cesium Ephedra Grapefruit Lithium Peyote + 183 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.