Omeprazole and Fluconazole: 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
Fluconazole
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.
Here's what's going on. Fluconazole (Diflucan) is an antifungal that slows down two liver enzymes your body uses to break down omeprazole (Prilosec). When those enzymes are slowed, omeprazole clears out of your body more slowly and builds up to higher levels than usual.
For most people this just means you may notice more of omeprazole's usual side effects, like headache, diarrhea, or stomach pain. It starts quickly and can linger for a few days after you finish the fluconazole. The good news is your care team knows how to handle this, so keep taking both as prescribed and let them know if you feel off.
Mechanism: Fluconazole inhibits CYP2C19 and CYP3A4, the enzymes responsible for omeprazole metabolism. Omeprazole is an active drug (not a prodrug), so inhibited clearance raises its exposure.
- Direction: Increased omeprazole AUC and Cmax.
- Onset: Rapid; inhibition may persist 4 to 5 days after fluconazole discontinuation.
- Evidence: Established. Fluconazole PK is not meaningfully altered by omeprazole.
- Management: Routine omeprazole dose adjustment usually unnecessary. Consider adjustment in Zollinger-Ellison syndrome on high doses (up to 240 mg/day). Monitor for elevated LFTs, headache, diarrhea, abdominal pain.
What happens
Increased omeprazole exposure
Interaction Deep Dive
When omeprazole, which is a substrate of both CYP2C19 and CYP3A41, is given together with fluconazole, an agent that inhibits CYP2C19 as well as CYP3A4, notable rises in omeprazole AUC and Cmax have been observed, an effect most likely attributable to fluconazole suppressing omeprazole metabolism 3. A different pharmacokinetic evaluation found that fluconazole pharmacokinetics were not meaningfully changed by the coadministration of omeprazole 4. Dosage changes for omeprazole are generally unnecessary during coadministration of these drugs; however, in patients with Zollinger-Ellison's syndrome receiving elevated omeprazole doses (up to 240 mg/day), a dosage adjustment might be considered. Patients should also be watched for heightened omeprazole adverse effects, for instance elevated liver enzymes, headache, diarrhea, and abdominal pain 1. The enzyme inhibition caused by fluconazole can last for 4 to 5 days following its discontinuation. When these agents must be used together, monitor carefully for adverse effects 2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated omeprazole metabolism by fluconazole; inhibition of CYP2C19-mediated omeprazole metabolism by fluconazole
How to manage this interaction
Keep taking both medications as prescribed unless your prescriber tells you otherwise. This combination is commonly used and manageable.
- A routine omeprazole dose change usually isn't needed, but your dose may be adjusted and individualized by your care team, especially if you take high doses for Zollinger-Ellison syndrome.
- Watch for and report signs of more omeprazole effect: headache, diarrhea, stomach pain, or symptoms that could suggest liver strain.
- Remember the effect can linger about 4 to 5 days after you stop fluconazole.
Bring any new or worsening symptoms to your pharmacist or doctor.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a pharmacokinetic study conducted in healthy male volunteers, giving omeprazole together with fluconazole raised omeprazole Cmax and AUC concentrations by 2.4 and 6.3 times, respectively, relative to omeprazole given alone. On day 1, participants (n=18; mean age, 25 years) took a single oral dose of omeprazole 20 mg. After a 10-day washout interval, oral fluconazole 100 mg once daily was administered on days 12 through 16. On day 16, subjects received omeprazole 20 mg together with fluconazole 100 mg. Combining omeprazole with fluconazole produced an omeprazole AUC rise from 491 to 3090 nanogram (ng) x hr/mL and a Cmax rise from 311 to 746 ng/mL (900 to 2160 nanomol/L) compared with omeprazole administered alone. The omeprazole half-life increased from 0.85 to 2.59 hours when coadministered with fluconazole. No adverse events were noted throughout the study 3. In a different pharmacokinetic study (n=12) evaluating the effect of gastric pH on fluconazole, omeprazole treatment showed no significant impact on fluconazole pharmacokinetics 4.
Common questions
Can I take Omeprazole and Fluconazole together?
Fluconazole can raise omeprazole levels in your body, so watch for more omeprazole side effects like headache, diarrhea, or stomach pain and tell your care team. Most people don't need a dose change, but your team can adjust and monitor if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Fluconazole interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How is the Omeprazole and Fluconazole interaction managed?
Keep taking both medications as prescribed unless your prescriber tells you otherwise. This combination is commonly used and manageable. A routine omeprazole dose change usually isn't needed, but your dose may be adjusted and individualized by your care team, especially if you take high doses for Zollinger-Ellison syndrome. Watch for and report signs of more omeprazole effect: headache, diarrhea,… Management is individual — always follow your own care team's guidance.
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 Omeprazole or Fluconazole 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 (4)
- Product Information: PRILOSEC(R) oral delayed-release capsules, oral delayed-release suspension, omeprazole oral delayed-release capsules, omeprazole magnesium oral delayed-release suspension. AstraZeneca, Wilmington, PA, 2010. DailyMed
- Product Information: DIFLUCAN(R) oral tablets, suspension, fluconazole oral tablets, suspension. Roerig (per FDA), New York, NY, 2023. DailyMed
- Kang BC, Yang CQ, Cho HK, et al: Influence of fluconazole on the pharmacokinetics of omeprazole in healthy volunteers. Biopharm Drug Dispos 2002; 23(2):77-81. DOI
- Zimmermann T, Yeates RA, Riedel KD, et al: The influence of gastric pH on the pharmacokinetics of fluconazole: the effect of omeprazole. Int J Clin Pharmacol Ther 1994; 32(9):491-496.
Keep reading about Fluconazole
Keep reading about Omeprazole
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