Selpercatinib and Omeprazole: 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
Selpercatinib
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.
Selpercatinib (Retevmo) is a targeted cancer medicine, and omeprazole (Prilosec) is a common heartburn drug that lowers stomach acid. Here's the issue: selpercatinib needs a more acidic stomach to dissolve and absorb well. When omeprazole reduces that acid, your body can absorb much less of the cancer medicine, which could make it work less well against your tumor.
The good news is your care team can manage this. In studies, taking selpercatinib with food largely made up for the difference. Please don't stop or change either medicine on your own. Talk with your oncologist or pharmacist so they can guide the timing and choose the safest plan for you.
Mechanism: Omeprazole raises gastric pH, reducing the pH-dependent dissolution and absorption of selpercatinib (a kinase inhibitor, not a prodrug). Net effect is reduced selpercatinib exposure and potentially diminished anti-tumor activity.
- Magnitude (fasted): AUC(0-inf) down ~69%, Cmax down ~88% with multiple-dose omeprazole.
- With food: AUC unchanged (low-fat) or +2% (high-fat); Cmax reduced 22% and 49% respectively.
- Evidence: probable; PK study data. Severity: major.
Management: Avoid coadministration with PPIs where possible. If unavoidable, administer each selpercatinib dose with food to preserve exposure. Consider therapeutic response monitoring.
What happens
Reduced selpercatinib exposure and reduced anti-tumor activity
Interaction Deep Dive
Do not combine selpercatinib with proton pump inhibitors, since lower selpercatinib exposure could lead to reduced anti-tumor activity. A pharmacokinetic study showed that giving it together with omeprazole (a proton pump inhibitor) under fasted conditions markedly decreased selpercatinib exposure. In contrast, administering it with omeprazole alongside food had no significant impact on exposure. When coadministration cannot be avoided, each selpercatinib dose should be taken with food to enhance exposure. That pharmacokinetic study found that combining selpercatinib with multiple daily doses of omeprazole during fasting lowered selpercatinib AUC(0 to infinity) by 69% and Cmax by 88%. By comparison, when selpercatinib was given with omeprazole together with a meal, AUC(0 to infinity) remained unchanged (low-fat meal) or rose by 2% (high-fat meal), while Cmax fell by 22% and 49%, respectively1.
Why it happens (mechanism)
Changes in gastric pH
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction can often be handled by adjusting how you take selpercatinib.
- Your team may prefer to avoid combining selpercatinib with omeprazole or another acid-reducing drug when possible.
- If you do need both, taking each selpercatinib dose with food helps your body absorb it properly.
- Ask your pharmacist before starting any over-the-counter heartburn product, since many contain acid reducers.
Raise this with your oncologist or pharmacist so they can time your doses and monitor how well your treatment is working.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a pharmacokinetic study, giving selpercatinib together with multiple daily doses of omeprazole under fasting conditions reduced selpercatinib AUC(0 to infinity) by 69% and Cmax by 88%. In contrast, when selpercatinib was given with omeprazole and food, AUC(0 to infinity) remained unchanged (low-fat meal) or rose by 2% (high-fat meal), while Cmax dropped by 22% and 49%, respectively 1.
Common questions
Can I take Selpercatinib and Omeprazole together?
Omeprazole can significantly lower the amount of selpercatinib your body absorbs, which may weaken its anti-cancer effect; if both are needed, take selpercatinib with food and let your oncology team guide the plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Selpercatinib and Omeprazole 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 Selpercatinib and Omeprazole interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction can often be handled by adjusting how you take selpercatinib. Your team may prefer to avoid combining selpercatinib with omeprazole or another acid-reducing drug when possible. If you do need both, taking each selpercatinib dose with food helps your body absorb it properly. Ask your pharmacist befo… 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 Selpercatinib or Omeprazole 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: RETEVMO(R) oral capsules, tablets, selpercatinib oral capsules, tablets. Lilly USA LLC (per FDA), Indianapolis, IN, 2024. DailyMed
Keep reading about Selpercatinib
Keep reading about Omeprazole
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