Omeprazole and Pirtobrutinib: 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
Omeprazole
Pirtobrutinib
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. Pirtobrutinib (Jaypirca) mildly slows down a liver enzyme called CYP2C19, which is the same enzyme your body uses to break down omeprazole (Prilosec). When that enzyme is slowed, omeprazole isn't cleared as fast, so more of it can build up in your blood. In a study, omeprazole levels went up by about half when the two were taken together.
For most people this means a bit more stomach-acid suppression than expected. The good news is this is very manageable. Please don't stop or change either medicine on your own. Just let your pharmacist or doctor know you take both so they can keep an eye on things and adjust if needed.
Mechanism: Pirtobrutinib is a weak CYP2C19 inhibitor; omeprazole is a sensitive CYP2C19 substrate. Coadministration reduces omeprazole clearance, raising exposure. Neither is a prodrug here, so this is a straightforward exposure increase.
- Magnitude: Omeprazole AUC increased 56%, Cmax 49% in a DDI study.
- Direction: Increased omeprazole exposure and increased risk of substrate-related adverse effects.
- Evidence: Probable; severity rated major.
- Onset: Unspecified.
- Management: Monitor for enhanced/prolonged acid suppression or GI adverse effects; individualize omeprazole dosing. Apply greater caution with narrow-therapeutic-index CYP2C19 substrates.
What happens
Increased sensitive CYP2C19 substrate exposure and an increased risk of sensitive CYP2C19 substrate-related adverse effects
Interaction Deep Dive
When pirtobrutinib is given together with a sensitive CYP2C19 substrate, exposure to that substrate can rise, potentially heightening the likelihood of adverse reactions tied to CYP2C19 substrates in the case of drugs sensitive to small changes in concentration. A drug interaction study showed that pirtobrutinib raised omeprazole's AUC by 56% and its Cmax by 49%1.
Why it happens (mechanism)
Inhibition of CYP2C19-mediated metabolism of omeprazole
How to manage this interaction
This is manageable with your care team's help. Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise.
- Your team may monitor you more closely for signs of increased omeprazole effect (extra acid suppression, digestive changes).
- The omeprazole dose may need to be adjusted and individualized by your care team.
- Tell your pharmacist and doctor you take both so they can review the combination.
- Report any new or bothersome stomach or digestive symptoms.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a drug interaction study, pirtobrutinib raised the AUC of omeprazole (a sensitive CYP2C19 substrate) by 56% and its Cmax by 49% 1.
Common questions
Can I take Omeprazole and Pirtobrutinib together?
Pirtobrutinib can raise omeprazole levels by about half by slowing its breakdown, so keep taking both as prescribed and let your care team monitor you or adjust the omeprazole dose if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Pirtobrutinib 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 Pirtobrutinib interaction managed?
This is manageable with your care team's help. Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise. Your team may monitor you more closely for signs of increased omeprazole effect (extra acid suppression, digestive changes). The omeprazole dose may need to be adjusted and individualized by your care team. Tell your pharmacist and doctor you take both so th… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
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 Pirtobrutinib 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 (1)
- Product Information: JAYPIRCA(TM) oral tablets, pirtobrutinib oral tablets. Lilly USA LLC (per FDA), Indianapolis, IN, 2023. DailyMed
Keep reading about Omeprazole
Keep reading about Pirtobrutinib
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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