Omeprazole and Phenytoin: 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
Phenytoin
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.
If you take phenytoin (Dilantin) for seizures and start taking omeprazole (Prilosec) for heartburn or acid reflux, the omeprazole can slow down how your body breaks down phenytoin. That means phenytoin can build up a little higher than usual.
Phenytoin is a medicine where even small changes in the blood level matter. Too much can cause things like unsteady walking, shaky hands, tremor, or jerky eye movements. At the same time, the phenytoin may make the omeprazole work a bit less well for your stomach.
This is mostly a theoretical concern, so please don't worry or change anything on your own. Your care team can easily manage this by checking your phenytoin levels and adjusting the dose if needed. Just let your pharmacist or doctor know you take both.
Effect: Omeprazole inhibits CYP2C19-mediated metabolism of phenytoin/fosphenytoin, increasing phenytoin exposure and risk of dose-related toxicity (ataxia, hyperreflexia, nystagmus, tremor). Reciprocally, phenytoin can induce CYP2C19, reducing omeprazole exposure and acid-suppression efficacy.
- Direction: Increased phenytoin effect; decreased omeprazole effect.
- Onset: Delayed.
- Evidence: Theoretical.
- NTI concern: Phenytoin has a narrow therapeutic index and nonlinear kinetics, so small exposure changes can be clinically significant.
Management: Monitor serum phenytoin levels and for toxicity; individualize/adjust phenytoin dose as needed. Consider an H2-receptor antagonist for GI protection instead of a PPI, particularly where CYP2C9/2C19 polymorphism status is unknown.
What happens
Increased phenytoin exposure or fosphenytoin (prodrug of phenytoin), an increased risk of phenytoin or fosphenytoin toxicity (ataxia, hyperreflexia, nystagmus, tremor) and reduced omeprazole exposure
Interaction Deep Dive
When omeprazole is given together with phenytoin or fosphenytoin (the prodrug of phenytoin), the exposure of phenytoin or fosphenytoin may rise2. In addition, giving phenytoin or fosphenytoin alongside omeprazole (a CYP2C19 substrate) may lower omeprazole exposure. In patients taking omeprazole at the same time, watch for indications of phenytoin or fosphenytoin toxicity, including ataxia, hyperreflexia, nystagmus, and tremor 34. Serum levels of phenytoin or fosphenytoin should be tracked, and adjustment of the phenytoin or fosphenytoin dose may be required 15; if CYP2C9 polymorphisms have not been determined, consider a histamine-2 (H2) receptor antagonist rather than a proton pump inhibitor for gastrointestinal protection 6.
Why it happens (mechanism)
Inhibition of CYP2C19-mediated metabolism of phenytoin; induction of CYP2C19-mediated metabolism of omeprazole
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. Because phenytoin needs careful control, your team can manage this easily.
- Your team may check your phenytoin blood levels and watch for signs of too much phenytoin, such as unsteadiness, tremor, or unusual eye movements.
- Your phenytoin dose may need to be adjusted and individualized by your care team.
- Your team may consider a different type of acid reducer (an H2 blocker) instead of omeprazole for stomach protection.
Tell your pharmacist or doctor that you take both, and report any new dizziness, shakiness, or vision changes.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A 5-year-old child carrying the homozygous CYP2C9*3 variant developed phenytoin toxicity after receiving phenytoin along with omeprazole following a severe head injury. On admission, phenytoin 5 mg/kg twice daily and omeprazole 0.8 mg/kg daily were started, and during the first 3 days intracranial pressure remained normal with no neurological deficits. On day 3, an MRI showed multiple small hemorrhagic contusions within the white matter of the frontal, parietal, and temporal lobes. Phenytoin was stopped on day 8 after the patient had 2 unsuccessful extubations associated with worsening respiratory distress accompanied by psychomotor agitation and tachypnea. By day 10, the patient was awake but showed loss of awareness, horizontal nystagmus, central neurological hyperventilation, positive bilateral Babinski signs, and prolonged I to V interpeak latency on brainstem auditory evoked potentials. EEG evaluation showed frontal intermittent rhythmic delta activity. Phenytoin concentrations stayed abnormally elevated (greater than 35 mcg/mL) 5 days after the drug was withdrawn. When omeprazole was discontinued, phenytoin levels fell substantially over the next 3 days. The patient's neurological signs and respiration returned to normal. Sequencing analysis identified impaired CYP2C9 metabolism as the cause of the phenytoin intoxication 6.
Common questions
Can I take Omeprazole and Phenytoin together?
Omeprazole can raise phenytoin levels and increase toxicity risk, while phenytoin may weaken omeprazole; keep taking both as prescribed and let your care team monitor levels and adjust the dose. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Phenytoin interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How is the Omeprazole and Phenytoin interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. Because phenytoin needs careful control, your team can manage this easily. Your team may check your phenytoin blood levels and watch for signs of too much phenytoin, such as unsteadiness, tremor, or unusual eye movements. Your phenytoin dose may need to be adjusted and individualized by your care team. Your team ma… 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 Phenytoin 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 (6)
- Product Information: PRILOSEC(R) oral delayed-release capsules, omeprazole oral delayed-release capsules. AstraZeneca Pharmaceuticals LP (per FDA), Wilmington, DE, 2018. DailyMed
- Product Information: KONVOMEP(TM) powder for oral suspension, omeprazole sodium bicarbonate powder for oral suspension. Azurity Pharmaceuticals Inc (per manufacturer), Woburn, MA, 2022. DailyMed
- Product Information: FOSPHENYTOIN SODIUM intravenous and intramuscular injection, fosphenytoin sodium intravenous and intramuscular injection. SAGENT Pharmaceuticals (per Dailymed), Schaumburg, IL, 2024. DailyMed
- Product Information: PHENYTOIN SODIUM intravenous and intramuscular injection, phenytoin sodium intravenous and intramuscular injection. Acella Pharmaceuticals, LLC (per Dailymed), Alpharetta, GA, 2024. DailyMed
- Product Information: PHENYTOIN SODIUM oral extended-release capsules, phenytoin sodium oral extended-release capsules. Sun Pharmaceutical Industries, Inc. (per Dailymed), Cranbury, NJ, 2023. DailyMed
- Marano M, Nicoletti F, Pro S, et al: Phenytoin intoxication associated with omeprazole administration in a child with defective CYP2C9. Eur J Clin Pharmacol 2020; 76(5):731-732. PubMed
Keep reading about Phenytoin
Keep reading about Omeprazole
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