Drug Interaction Report

Darifenacin and Ketoconazole Topical: Interaction Details

A pharmacist-reviewed analysis of the Darifenacin 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

Darifenacin

Enablex
+

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 23 documented Darifenacin interactions, 22 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
established
Severity
Major

What happens

Increased darifenacin exposure and increased darifenacin-related adverse reactions

Interaction Deep Dive

Concomitant use of ketoconazole, a strong CYP3A4 inhibitor with darifenacin, a CYP3A4 substrate may increase darifenacin exposure and may also increase darifenacin-related adverse reactions1. When used concomitantly with potent CYP3A4 inhibitors such as ketoconazole, limit the dose of darifenacin to no more than 7.5 mg 2.

Why it happens (mechanism)

Inhibition of CYP3A4-mediated metabolism of darifenacin

Literature reports

1 report — tap to read

a) When darifenacin 7.5 mg once daily was coadministered with ketoconazole 400 mg, the mean maximum concentration (Cmax) and mean area under the concentration-time curve (AUC) both increased for extensive metabolizers (EM) and poor metabolizers (PM), alike. The observed mean Cmax and AUC increased to 11.2 ng/mL and 143 ng.h/mL , respectively, for EMs. The mean Cmax and AUC for PMs increased to 55.4 ng/ML and 939 ng.h/mL, respectively. Compare to an unrelated study of healthy volunteers, the mean Cmax and mean AUC of EMs were reported to be 2.01 ng/mL and 29.24 ng.h/mL, respectively. The mean Cmax and AUC values for PMs were reported to be 2.81 ng/mL and 67.56 ng.h/mL, respectively. Similar increases were seen with a dose of 15 mg darifenacin once daily coadministered with 400 mg ketoconazole 2.

Common questions

Can I take Darifenacin and Ketoconazole Topical together?

Increased darifenacin exposure and increased darifenacin-related adverse reactions Always confirm with your pharmacist or prescriber before making any change.

How serious is the Darifenacin 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 "established". Well documented — supported by controlled studies or strong clinical data.

Questions for your pharmacist

  • Does my dose of Darifenacin 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: Enablex, darifenacin. Pfizer Inc. Brooklyn, New york, USA, 2004. DailyMed
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Darifenacin

Keep reading about Darifenacin

All Darifenacin interactions (23)
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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:

Darifenacin + Activated Charcoal Henbane Scopolia Angel's Trumpet Bacopa Belladonna Betel Nut Boxwood + 38 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.