Omeprazole and Fedratinib: 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
Fedratinib
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. Fedratinib (Inrebic) slows down two of the liver's cleanup enzymes (called CYP3A4 and CYP2C19). Omeprazole (Prilosec) is broken down by those same enzymes. So when you take them together, your body clears the omeprazole more slowly and its levels can rise. In studies, fedratinib raised omeprazole levels about 3-fold.
In everyday terms, that means more omeprazole effect and a higher chance of side effects like headache, stomach upset, or diarrhea. The good news is this is very manageable. Your care team can adjust your dose and keep an eye on how you feel, so please don't change anything on your own. Just talk with your pharmacist or doctor.
Mechanism: Fedratinib inhibits both CYP3A4 and CYP2C19. Omeprazole is a substrate of both (primarily CYP2C19), so concurrent use reduces its metabolism and increases exposure. Neither drug is a prodrug here, so the effect is increased omeprazole exposure and effect.
- Magnitude: Single-dose PK studies showed fedratinib increased omeprazole AUC ~3-fold (and midazolam AUC ~4-fold).
- Direction: Increased omeprazole concentration and adverse-reaction risk.
- Evidence: Probable. Severity major.
- Management: If coadministration is necessary, monitor for omeprazole-related adverse effects and adjust the omeprazole dose, individualized by the care team.
What happens
Increased CYP3A4/CYP2C19 substrate exposure
Interaction Deep Dive
When fedratinib, which inhibits both CYP3A4 and CYP2C19, is taken together with agents that are substrates of both CYP3A4 and CYP2C19, the levels of those substrates can rise, raising the likelihood of adverse reactions from them. Single-dose pharmacokinetic investigations showed that fedratinib raised the AUC of midazolam (a CYP3A4 substrate) 4-fold and that of omeprazole (a CYP2C19 substrate) 3-fold. Should coadministration be required, watch for adverse reactions and modify the dose of medications that serve as dual CYP3A4 and CYP2C19 substrates1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated substrate metabolism by fedratinib; inhibition of CYP2C19-mediated substrate metabolism by fedratinib
How to manage this interaction
The takeaway: this combination can be used together safely when your team keeps an eye on it. Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise.
- Your care team may adjust the omeprazole dose, individualized to you.
- They may monitor you more closely for omeprazole-related side effects such as headache, nausea, stomach upset, or diarrhea.
- Tell your pharmacist or doctor if you notice new or worsening side effects, or before starting any new medicine.
This is a well-recognized interaction, and your team can manage it by tailoring your dose and watching how you respond.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
Common questions
Can I take Omeprazole and Fedratinib together?
Fedratinib can raise omeprazole levels about 3-fold by slowing its breakdown, which increases the chance of omeprazole side effects. Keep taking both as prescribed and let your care team adjust the dose and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Fedratinib 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 Fedratinib interaction managed?
The takeaway: this combination can be used together safely when your team keeps an eye on it. Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise. Your care team may adjust the omeprazole dose, individualized to you. They may monitor you more closely for omeprazole-related side effects such as headache, nausea, stomach upset, or diarrhea. Tell your pharmac… 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 Omeprazole or Fedratinib 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: INREBIC(R) oral capsules, fedratinib oral capsules. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2023. DailyMed
Keep reading about Fedratinib
Keep reading about Omeprazole
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist