Omeprazole and Ketoconazole: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole
Omeprazole
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.
These two can work against each other. Oral ketoconazole (an antifungal pill) needs an acidic stomach to dissolve and get absorbed. Omeprazole (Prilosec) lowers stomach acid, so it can make ketoconazole less able to soak in. That may mean the antifungal doesn't work as well as it should.
At the same time, ketoconazole can slow down how your body clears omeprazole, so omeprazole levels may rise a bit and cause more side effects like headache or stomach upset. The good news: your care team can manage this by adjusting timing, doses, and watching how you respond. Please don't change either medicine on your own, just check with your pharmacist or doctor.
Bidirectional interaction. Two mechanisms:
- PK/absorption: Omeprazole raises gastric pH, reducing dissolution and GI absorption of oral ketoconazole, lowering ketoconazole exposure and antifungal efficacy.
- CYP3A4: Ketoconazole is a strong CYP3A4 inhibitor and omeprazole is a partial CYP3A4 substrate, so omeprazole exposure may increase, raising adverse-effect risk.
Evidence: theoretical. Severity: major. Onset: unspecified.
Management: If coadministration is required, give oral ketoconazole with an acidic beverage (e.g., non-diet cola), monitor antifungal response, and consider a ketoconazole dose increase. Separate acid-neutralizing agents by 1 hour before or 2 hours after ketoconazole. Watch for omeprazole-related adverse effects.
What happens
Reduced ketoconazole exposure, reduced efficacy of ketoconazole, increased omeprazole exposure and an increased risk of omeprazole-related adverse reactions
Interaction Deep Dive
When ketoconazole is combined with a proton pump inhibitor like omeprazole, caution is warranted because giving them together can reduce ketoconazole's absorption from the gastrointestinal tract, potentially causing a loss of therapeutic effect. Should concurrent therapy be necessary, ketoconazole should be taken with an acidic drink such as non-diet cola, and antifungal activity should be watched closely. Raising the ketoconazole dose may be warranted. Medicines that neutralize acid should be given no sooner than 1 hour before, or at least 2 hours after, oral ketoconazole is taken. In addition, using ketoconazole (a strong CYP3A4 inhibitor) alongside omeprazole (a CYP3A4 substrate) may raise omeprazole exposure and could heighten adverse reactions linked to omeprazole1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of omeprazole; changes in gastric pH
How to manage this interaction
If you need both, your care team can manage this. Keep taking them as prescribed unless told otherwise.
- Boost absorption: Oral ketoconazole may be taken with an acidic drink such as non-diet cola to help it absorb.
- Timing: Acid-neutralizing medicines should be spaced at least 1 hour before or 2 hours after oral ketoconazole.
- Dose: Your ketoconazole dose may need to be adjusted and individualized by your care team.
- Monitoring: Your team may check that the antifungal is still working and watch for omeprazole side effects.
Ask your pharmacist or prescriber before changing anything, and report new or worsening symptoms.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
Common questions
Can I take Omeprazole and Ketoconazole together?
Omeprazole can lower stomach acid and reduce absorption of oral ketoconazole (making it less effective), while ketoconazole may raise omeprazole levels; keep taking both as prescribed and ask your care team about timing, dosing, and monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Ketoconazole 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 is the Omeprazole and Ketoconazole interaction managed?
If you need both, your care team can manage this. Keep taking them as prescribed unless told otherwise. Boost absorption: Oral ketoconazole may be taken with an acidic drink such as non-diet cola to help it absorb. Timing: Acid-neutralizing medicines should be spaced at least 1 hour before or 2 hours after oral ketoconazole. Dose: Your ketoconazole dose may need to be adjusted and individualized b… Management is individual — always follow your own care team's guidance.
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 Omeprazole or Ketoconazole 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)
- Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
- 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.
- Product Information: Aciphex(R), rabeprazole sodium. Eisai Co. Ltd. Tokyo, Japan, 2002. DailyMed
Keep reading about Ketoconazole
Keep reading about Omeprazole
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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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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