Omeprazole and Rilzabrutinib: 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
Rilzabrutinib
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 medicines can work against each other in two ways. Rilzabrutinib (Wayrilz) needs an acidic stomach to dissolve properly. Omeprazole (Prilosec) lowers stomach acid, so it can keep your body from absorbing enough rilzabrutinib. That may make the rilzabrutinib work less well.
At the same time, rilzabrutinib can slow down how your body clears omeprazole, so the omeprazole may build up and cause more of its usual side effects. This is based on how the drugs are expected to behave, not on lots of patient data. The good news is your care team can manage this, often by avoiding the combination or watching you more closely. Please talk with your pharmacist or doctor before changing anything.
Direction: Dual, bidirectional interaction (theoretical).
- Rilzabrutinib (victim): Exhibits pH-dependent solubility. Omeprazole-induced gastric pH elevation reduces rilzabrutinib dissolution and absorption, lowering exposure and potentially reducing efficacy.
- Omeprazole (victim): Rilzabrutinib is a CYP3A inhibitor; omeprazole is partly a CYP3A substrate, so inhibition may increase omeprazole exposure and PPI-related adverse effects.
Onset: unspecified. Evidence: theoretical. Management: Avoid coadministration where possible. If combined, monitor for omeprazole-related adverse reactions more frequently and consider omeprazole dose adjustment. Neither is a prodrug requiring activation.
What happens
Reduced rilzabrutinib exposure, reduced efficacy of rilzabrutinib, an increased omeprazole exposure and an increased risk of omeprazole-related adverse reactions
Interaction Deep Dive
Do not give rilzabrutinib together with omeprazole (a proton pump inhibitor), because doing so can lower rilzabrutinib exposure and thereby diminish its efficacy. The solubility of rilzabrutinib depends on pH. In addition, giving rilzabrutinib (a CYP3A inhibitor) alongside omeprazole (a CYP3A substrate) can raise omeprazole exposure, potentially increasing adverse reactions associated with omeprazole. Watch more closely for omeprazole-related adverse reactions and consider adjusting the dose1.
Why it happens (mechanism)
Changes in gastric pH; inhibition of CYP3A-mediated metabolism of omeprazole
How to manage this interaction
Both directions of this interaction can usually be managed by your care team.
- Best option: Your prescriber may avoid using these together, since the acid-reducing effect of omeprazole can lower how well rilzabrutinib works.
- If they are used together: Your team may monitor you more closely for omeprazole side effects, and the omeprazole dose may need to be adjusted and individualized.
- What you should do: Keep taking both exactly as prescribed, and do not stop or change either drug on your own. Ask your pharmacist or prescriber whether a different stomach medicine or a timing plan would be better for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a drug interaction study, giving rilzabrutinib together with esomeprazole (a proton pump inhibitor) reduced rilzabrutinib Cmax by 55% and AUC by 51% 1.
b) In a drug interaction study involving healthy participants, taking a single 400 mg dose of rilzabrutinib along with midazolam (a sensitive CYP3A substrate) raised midazolam Cmax and AUC by 2.2-fold. Midazolam AUC is projected to rise as much as 3.0-fold in patients with immune thrombocytopenia when combined with 400 mg rilzabrutinib twice daily 1.
Common questions
Can I take Omeprazole and Rilzabrutinib together?
Omeprazole can reduce how well rilzabrutinib is absorbed and works, while rilzabrutinib may raise omeprazole levels and side effects, so this combination is best avoided; check with your pharmacist or doctor before making any changes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Rilzabrutinib 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 Rilzabrutinib interaction managed?
Both directions of this interaction can usually be managed by your care team. Best option: Your prescriber may avoid using these together, since the acid-reducing effect of omeprazole can lower how well rilzabrutinib works. If they are used together: Your team may monitor you more closely for omeprazole side effects, and the omeprazole dose may need to be adjusted and individualized. What you shou… 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 Rilzabrutinib 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: WAYRILZ™ oral tablets, rilzabrutinib oral tablets. Genzyme Corporation (per FDA), Cambridge, MA, 2025. DailyMed
Keep reading about Rilzabrutinib
Keep reading about Omeprazole
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