Selpercatinib and Esomeprazole: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Selpercatinib
Esomeprazole
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.
What happens
Reduced selpercatinib exposure and reduced anti-tumor activity
Interaction Deep Dive
Avoid coadministration of selpercatinib with proton pump inhibitors because reduced selpercatinib exposure may result in diminished anti-tumor activity. In a pharmacokinetic study coadministration with omeprazole (a proton pump inhibitor) in the fasted state significantly reduced selpercatinib exposure. However, coadministration with omeprazole and food did not significantly effect exposure. If coadministration is necessary, take each selpercatinib dose with food to improve exposure. In a pharmacokinetic study, coadministration of selpercatinib with multiple daily doses of omeprazole in the fasting state decreased selpercatinib AUC(0 to infinity) by 69% and Cmax by 88%. However, when selpercatinib was coadministered with omeprazole and a meal, AUC(0 to infinity) was unchanged (low-fat meal) or increased 2% (high-fat meal) and Cmax was reduced by 22% and 49%, respectively1.
Why it happens (mechanism)
Changes in gastric pH
Literature reports
1 report — tap to read
a) In a pharmacokinetic study, coadministration of selpercatinib with multiple daily doses of omeprazole in the fasting state decreased selpercatinib AUC(0 to infinity) by 69% and Cmax by 88%. However, when selpercatinib was coadministered with omeprazole and a meal, AUC(0 to infinity) was unchanged (low-fat meal) or increased 2% (high-fat meal) and Cmax was reduced by 22% and 49%, respectively 1.
Common questions
Can I take Selpercatinib and Esomeprazole together?
Reduced selpercatinib exposure and reduced anti-tumor activity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Selpercatinib and Esomeprazole 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 strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Selpercatinib or Esomeprazole 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 Esomeprazole
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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