Defactinib 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
Omeprazole
Defactinib
No brand names on record
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 don't mix well. Omeprazole (Prilosec) works by lowering the acid in your stomach. That's great for heartburn, but it turns out defactinib, your cancer medicine, needs an acidic stomach to dissolve and get absorbed properly.
When they're taken together, your body absorbs a lot less defactinib (studies showed a drop of around 80%). That means defactinib may not work as well as it should, which is a big deal for a cancer treatment. The good news is your care team can plan around this by choosing a different acid remedy or spacing out the timing. Please talk with your doctor or pharmacist before making any changes.
Interaction: Omeprazole markedly reduces defactinib exposure via a pH-dependent absorption mechanism (defactinib has pH-dependent aqueous solubility). This is a PK interaction, not enzyme-mediated; neither drug is a prodrug in the relevant sense here.
- Direction/magnitude: Defactinib AUC decreased 79%, Cmax decreased 85% with omeprazole 40 mg daily; active M4 metabolite AUC decreased 83%, Cmax decreased 88%.
- Consequence: Reduced defactinib efficacy.
- Evidence: Probable. Severity major.
- Management: Avoid concomitant PPI use. If an acid-reducing agent is unavoidable, use a locally acting antacid and give defactinib 2 hours before or 2 hours after the antacid.
What happens
Reduced defactinib exposure and an reduced efficacy of defactinib
Interaction Deep Dive
Do not combine defactinib with proton pump inhibitors (PPIs), because doing so can lower defactinib exposure and thereby diminish its efficacy. When use of an acid-reducing medication is unavoidable, give defactinib either 2 hours prior to or 2 hours after a locally acting antacid. The aqueous solubility of defactinib is pH-dependent. With repeated dosing of the PPI omeprazole at 40 mg once daily, defactinib AUC fell by 79% and Cmax fell by 85%, while M4 AUC dropped by 83% and Cmax by 88%1.
Why it happens (mechanism)
Changes in gastric pH
How to manage this interaction
What your care team may do:
- Prefer to avoid using omeprazole (a proton pump inhibitor) together with defactinib, since it can lower how much defactinib you absorb.
- If an acid-reducing medicine cannot be avoided, they may switch you to a locally acting antacid and have you take defactinib 2 hours before or 2 hours after that antacid.
What you should do: Keep taking both exactly as prescribed for now, and do not stop anything on your own. Let your pharmacist or prescriber know you are on both so they can adjust the plan and monitor how well your defactinib is working.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Defactinib exhibited aqueous solubility that depended on pH. When co-administered with multiple 40 mg daily doses of omeprazole (a PPI), the AUC of defactinib fell by 79% and its Cmax fell by 85%. For the principal metabolite of defactinib, N-desmethyl amide (M4), the AUC dropped by 83% and the Cmax dropped by 88% 1.
Common questions
Can I take Defactinib and Omeprazole together?
Omeprazole can cut defactinib absorption by roughly 80%, which may make the cancer medicine less effective, so this combination should generally be avoided. Talk with your care team about a safer acid remedy or proper timing before changing anything. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Defactinib 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 Defactinib and Omeprazole interaction managed?
What your care team may do: Prefer to avoid using omeprazole (a proton pump inhibitor) together with defactinib, since it can lower how much defactinib you absorb. If an acid-reducing medicine cannot be avoided, they may switch you to a locally acting antacid and have you take defactinib 2 hours before or 2 hours after that antacid. What you should do: Keep taking both exactly as prescribed for no… 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 Defactinib 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: AVMAPKI(TM) FAKZYNJA(TM) CO-PACK oral capsules, tablets, avutometinib oral capsules, defactinib oral tablets. Verastem, Inc (per manufacturer), Needham, MA, 2025. DailyMed
Keep reading about Omeprazole
Keep reading about Defactinib
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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