Drug Interaction Report

Ketoconazole Topical and Omeprazole: Interaction Details

A pharmacist-reviewed analysis of the Ketoconazole Topical and Omeprazole 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

Ketoconazole Topical

Extina® Foam Ketozole® Cream Kuric Nizoral AD® Shampoo Nizoral® Cream Nizoral® Shampoo Xolegel®
+

Omeprazole

Gastrobim Prilosec Prilosec® Prilosec® OTC Primeguard Talicia (as a combination product containing Amoxicillin, Omeprazole, Rifabutin) UlcerGard
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
LinkedIn
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 546 documented Ketoconazole Topical interactions, 380 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
unspecified
Evidence
theoretical
Severity
Major

What happens

Reduced ketoconazole exposure, reduced efficacy of ketoconazole, increased omeprazole exposure and an increased risk of omeprazole-related adverse reactions

Interaction Deep Dive

Caution is advised when using ketoconazole together with a proton pump inhibitor such as omeprazole as coadministration may impair the gastrointestinal absorption of ketoconazole leading to a loss of therapeutic effect. If concomitant use is required, administer ketoconazole with an acidic beverage such as non-diet cola and monitor antifungal activity closely. An increase in ketoconazole dose may be indicated. Administer acid neutralizing medicines at least 1 hour before or 2 hours after the intake of oral ketoconazole. Concomitant use of ketoconazole (strong CYP3A4 inhibitor) with omeprazole (CYP3A4 substrate) may also increase omeprazole exposure and may increase omeprazole-related adverse reactions1.

Why it happens (mechanism)

Inhibition of CYP3A4-mediated metabolism of omeprazole; changes in gastric pH

Literature reports

1 report — tap to read

a) When ketoconazole 400 mg daily was coadministered with rabeprazole (proton pump inhibitor) 20 mg daily, the absorption of ketoconazole was reduced by 30%, although this decrease was not considered clinically significant 23.

Common questions

Can I take Ketoconazole Topical and Omeprazole together?

Reduced ketoconazole exposure, reduced efficacy of ketoconazole, increased omeprazole exposure and an increased risk of omeprazole-related adverse reactions Always confirm with your pharmacist or prescriber before making any change.

How serious is the Ketoconazole Topical and Omeprazole 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.

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 Omeprazole 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)

  1. Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
  2. Humphries TJHumphries TJ: A review of the drug-drug interaction potential of rabeprazole sodium based on CYP-450 interference or absorption effects, World Congress, Vienna, Austria, 1999.
  3. Product Information: Aciphex(R), rabeprazole sodium. Eisai Co. Ltd. Tokyo, Japan, 2002. DailyMed
Was this write-up helpful?
Ketoconazole Topical

Keep reading about Ketoconazole Topical

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

Keep reading about Omeprazole

All Omeprazole interactions (142) Omeprazole drug information
Also serious with: Ensitrelvir Rilpivirine Octreotide Injection Diazepam Rectal
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:

Omeprazole + Activated Charcoal Grapefruit St. John's Wort Acacia Rigidula Adrafinil African Wild Potato American Elder Artichoke + 166 more

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

Check another combination

Our instant two-drug interaction checker is almost here.

Coming soon

The instant two-drug checker is on its way.

In the meantime, browse the directory below to look up any drug and see its documented interactions.

Still have questions about this combination?

Every question gets a real answer from a licensed pharmacist — free, and usually within a day.

Ask the pharmacist
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.