Drug Interaction Report

Omeprazole and Posaconazole: 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

Posaconazole

Noxafil
+

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
Updated Jul 2, 2026
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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 142 documented Omeprazole interactions, 114 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.
At a glance Theoretical Effects may be weaker Effects may be stronger
The Bottom Line
Omeprazole can lower posaconazole absorption (risking a weaker antifungal effect) while posaconazole can raise omeprazole levels; keep taking both as prescribed and let your care team monitor levels and adjust as needed.

Here's what's going on. Posaconazole (Noxafil) is an antifungal that your body needs to absorb well from your stomach to work. Omeprazole (Prilosec) lowers stomach acid. When acid drops, your body may absorb less posaconazole, so the antifungal may not work as well against a serious infection. At the same time, posaconazole can slow how your body clears omeprazole, so omeprazole levels may go up a bit.

The good news is your care team can manage this easily. They may check your posaconazole levels, adjust your doses, or choose a different acid medicine. Please don't stop either drug on your own, just talk with your pharmacist or doctor first.

Bidirectional interaction. Two mechanisms operate here:

  • Reduced posaconazole exposure: omeprazole raises gastric pH, decreasing posaconazole (oral suspension) bioavailability. This risks subtherapeutic antifungal troughs and treatment failure.
  • Increased omeprazole exposure: posaconazole inhibits CYP3A4, reducing omeprazole clearance and raising its AUC/Cmax.

Onset: delayed. Evidence: theoretical, though a case report showed a posaconazole trough drop that reversed after omeprazole discontinuation. Severity: major, driven by antifungal efficacy loss.

Management: monitor posaconazole trough levels; individualize dosing; consider an alternative acid-suppression strategy or the delayed-release tablet/IV formulation (less pH-dependent) if clinically appropriate.

Onset
delayed
Evidence
theoretical
Severity
Major

What happens

Increased omeprazole exposure and reduced posaconazole exposure

Interaction Deep Dive

Taking posaconazole together with omeprazole (a CYP3A4 substrate) can raise omeprazole exposure12. This combination may likewise lower exposure to posaconazole. In one case, a 58-year-old man receiving posaconazole for invasive aspergillosis showed a marked drop in his serum trough level after omeprazole was added. The omeprazole, dosed at 40 mg daily to guard against corticosteroid induced gastrointestinal hemorrhage, was stopped after 3 days of use. Monitoring of posaconazole concentrations demonstrated that serum trough levels returned to baseline once omeprazole was discontinued3.

Why it happens (mechanism)

Inhibition of CYP3A4-mediated metabolism by posaconazole; decreased bioavailability of posaconazole with increase in gastric pH

How to manage this interaction

Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This is manageable with the right monitoring.

  • Your team may check your posaconazole blood levels (troughs) to make sure the antifungal is still working.
  • Your doses may need to be adjusted and individualized by your care team.
  • They may consider a different acid-reducing option or a posaconazole formulation less affected by stomach acid.

What to raise: tell your pharmacist or doctor you take both, and mention any signs your infection isn't improving. Don't start or stop either drug on your own.

Management is individual — confirm any change with your pharmacist or prescriber.

Literature reports

1 report — tap to read

a) A 58-year-old man receiving posaconazole for invasive aspergillosis had a marked drop in his serum trough concentration when omeprazole was given concurrently. Omeprazole 40 mg once daily had been started to prevent corticosteroid induced gastrointestinal bleeding but was stopped after 3 days of treatment. Monitoring of posaconazole concentrations demonstrated a return to baseline serum trough levels once omeprazole was discontinued 3.

Common questions

Can I take Omeprazole and Posaconazole together?

Omeprazole can lower posaconazole absorption (risking a weaker antifungal effect) while posaconazole can raise omeprazole levels; keep taking both as prescribed and let your care team monitor levels and adjust as needed. Always confirm with your pharmacist or prescriber before making any change.

How serious is the Omeprazole and Posaconazole 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 is the Omeprazole and Posaconazole interaction managed?

Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This is manageable with the right monitoring. Your team may check your posaconazole blood levels (troughs) to make sure the antifungal is still working. Your doses may need to be adjusted and individualized by your care team. They may consider a different acid-reducing option or a posaconazole formulation less aff… 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 Posaconazole 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: NOXAFIL(R) PowderMix delayed-release oral suspension, posaconazole delayed-release oral suspension. Merck Sharp & Dohme LLC (per FDA), Rahway, NJ, 2024. DailyMed
  2. Product Information: Posaconazole oral delayed-release tablets, posaconazole oral delayed-release tablets. SpecGx LLC (per DailyMed), Webster Groves, MO, 2024. DailyMed
  3. Alffenaar JW, vanAssen S, vanderWerf TS, et al: Omeprazole Significantly Reduces Posaconazole Serum Trough Level. Clin Infect Dis 2009; 48(6):839-839. PubMed
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Beyond drug–drug

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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.