Omeprazole and Netupitant: 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
Netupitant
No brand names on recordOmeprazole
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.
Netupitant is a medicine used to help prevent nausea and vomiting from chemotherapy. It gently slows down an enzyme in your liver called CYP3A4, which is one of the ways your body breaks down certain drugs. Omeprazole (Prilosec) is handled in part by that same enzyme, so netupitant could cause a bit more omeprazole to build up in your body while the enzyme is slowed.
The good news is this is based on theory (how the drugs work on paper) rather than reports of harm. This effect can last up to about a week after a netupitant dose. Please don't change anything on your own. Your care team can easily manage this by adjusting your dose if needed or keeping a closer eye on you.
Mechanism: Netupitant (and its prodrug fosnetupitant) is a moderate CYP3A4 inhibitor. Omeprazole is partly a CYP3A4 substrate, so inhibition may reduce its metabolism and increase exposure (AUC/Cmax).
- Direction: Increased omeprazole exposure and effect.
- Onset: Rapid; inhibition may persist up to ~1 week (dexamethasone AUC elevated up to 8 days after a single netupitant dose).
- Evidence: Theoretical; supported by PK data with other CYP3A4 substrates (erythromycin, dexamethasone).
- Management: Avoid concomitant use for 1 week where feasible. If co-administration is needed, consider reducing the CYP3A4 substrate dose and monitor clinically.
What happens
Increased exposure of CYP3A4 substrate
Interaction Deep Dive
For a period of one week, do not use CYP3A4 substrates together with netupitant or with fosnetupitant (the prodrug form of netupitant), which acts as a moderate CYP3A4 inhibitor. Giving netupitant or fosnetupitant alongside CYP3A4 substrates can raise the exposure to those substrates. In a pharmacokinetic study, the mean AUC and Cmax of erythromycin, a CYP3A4 substrate, rose when netupitant was coadministered. Elevated AUC of dexAMETHasone, a CYP3A4 probe substrate, persisted for as long as 8 days after a single netupitant dose. CYP3A4 substrates should therefore not be given together with netupitant for one week. Should a CYP3A4 substrate need to be given within one week of netupitant, consider lowering the dose of that CYP3A4 substrate1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism by netupitant
How to manage this interaction
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Because netupitant can slow how your body clears omeprazole for about a week, here is how a care team typically handles this:
- They may avoid using them together during that roughly one-week window when possible.
- If both are needed, the omeprazole dose may be adjusted and individualized by your team.
- Your team may monitor you more closely for stronger or extra side effects.
Let your pharmacist or prescriber know you take omeprazole before starting netupitant, and report any new or unusual symptoms.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In one study that evaluated how long CYP3A4 inhibition persisted by using dexAMETHasone as a CYP3A4 probe substrate, the mean AUC of dexAMETHasone rose by 1.6-fold on day 1, 2.4-fold on day 4, 1.5-fold on day 6, and 1.2-fold on day 8 following a single dose of the combination netupitant 300 mg/palonosetron 0.5 mg given to participants on day 1. These participants had received a dexAMETHasone regimen consisting of 12 mg on day 1 and then 8 mg on days 2, 3, 4, 6, 8, and 10 1.
b) A pharmacokinetic study showed that coadministration of erythromycin 500 mg with netupitant 300 mg produced a 56% increase in the mean AUC of erythromycin and a 92% increase in the Cmax 1.
Common questions
Can I take Omeprazole and Netupitant together?
Netupitant can raise omeprazole levels for about a week by slowing the CYP3A4 enzyme, so your care team may space the drugs apart, adjust your omeprazole dose, or monitor you more closely. Do not change either medicine on your own; check with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Netupitant interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How is the Omeprazole and Netupitant interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Because netupitant can slow how your body clears omeprazole for about a week, here is how a care team typically handles this: They may avoid using them together during that roughly one-week window when possible. If both are needed, the omeprazole dose may be adjusted and individualized by your team. Your te… 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 Netupitant 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: AKYNZEO(R) oral capsules, netupitant palonosetron oral capsules. Helsinn Therapeutics (US), Inc (per FDA), Iselin, NJ, 2018. DailyMed
Keep reading about Netupitant
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