Omeprazole and Sotorasib: 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
Sotorasib
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.
Here's what's going on. Sotorasib (Lumakras) is a cancer medicine that needs a bit of stomach acid to dissolve and get absorbed properly. Omeprazole (Prilosec) lowers stomach acid. When you take them together, your body may absorb less of the sotorasib, so it may not fight the cancer as well as it should.
This matters because we want the full benefit of your cancer treatment. The good news is your care team knows about this and can plan around it, sometimes by using a different type of stomach medicine or by adjusting timing. Please don't stop either drug on your own. Just talk with your oncologist or pharmacist so they can guide you.
Effect: Reduced sotorasib exposure and potentially diminished anti-tumor activity when coadministered with omeprazole.
Mechanism: Sotorasib absorption is pH-dependent; acid suppression by a PPI raises gastric pH and lowers sotorasib solubility and AUC/Cmax. It is not a prodrug issue, this is a solubility/absorption effect.
- Direction: reduced sotorasib effect (efficacy risk)
- Magnitude: significant reduction in exposure seen in PK study, with and without food
- Evidence: theoretical/PK-based; severity rated major
- Management: avoid coadministration with PPIs and H2-antagonists; even H2RA separated by 10 h before or 2 h after still reduced exposure. Consider alternative acid strategies with the oncology team.
What happens
Reduced sotorasib exposure and anti-tumor activity
Interaction Deep Dive
Sotorasib should not be given together with proton pump inhibitors or H2-antagonists, since lower sotorasib exposure could translate into weakened anti-tumor effect. A pharmacokinetic study demonstrated that combining sotorasib with the proton pump inhibitor omeprazole markedly lowered sotorasib exposure under both fed and fasted conditions. A separate study found that pairing sotorasib with the H2-antagonist famotidine, dosed 10 hours before or 2 hours after sotorasib, likewise decreased sotorasib exposure1.
Why it happens (mechanism)
Unknown
How to manage this interaction
What your care team may do:
- Reassess whether you still need a proton pump inhibitor while on sotorasib, since combining them can lower the amount of cancer drug your body absorbs.
- Consider a different approach for stomach symptoms, chosen by your oncology team.
- Note that simply spacing the two apart may not be enough to fix this, so this is best decided by your team rather than by adjusting timing yourself.
What you should do: Keep taking both exactly as prescribed for now, and let your oncologist or pharmacist know you are on both. Also mention any over-the-counter heartburn medicines, since Prilosec is available without a prescription.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a pharmacokinetic study, giving sotorasib together with multiple daily doses of omeprazole (a proton pump inhibitor) under fed conditions lowered sotorasib Cmax by 65% and AUC by 57%, whereas under fasted conditions these values were reduced by 57% and 42%, respectively 1.
b) In a pharmacokinetic study, administering a single dose of famotidine (an H2-antagonist) 10 hours before and 2 hours after a single dose of sotorasib under fed conditions lowered sotorasib Cmax by 35% and AUC by 38% 1.
Common questions
Can I take Omeprazole and Sotorasib together?
Omeprazole can lower how much sotorasib your body absorbs, which may weaken its cancer-fighting effect, so this combination is generally avoided. Talk to your oncology team before making any changes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Sotorasib 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 Sotorasib interaction managed?
What your care team may do: Reassess whether you still need a proton pump inhibitor while on sotorasib, since combining them can lower the amount of cancer drug your body absorbs. Consider a different approach for stomach symptoms, chosen by your oncology team. Note that simply spacing the two apart may not be enough to fix this, so this is best decided by your team rather than by adjusting timing… 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 Sotorasib 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: LUMAKRAS(TM) oral tablets, sotorasib oral tablets. Amgen Inc (per FDA), Thousand Oaks, CA, 2021. DailyMed
Keep reading about Sotorasib
Keep reading about Omeprazole
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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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