Omeprazole with Phenytoin Interaction Details

Brand Names Associated with Omeprazole

Brand Names Associated with Phenytoin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 05, 2023

Interaction Effect

Increased phenytoin exposure and an increased risk of phenytoin toxicity (ataxia, hyperreflexia, nystagmus, tremor)

Interaction Summary

A 5-year-old with homozygous CYP2C9*3 variant experienced phenytoin intoxication after being treated with phenytoin and omeprazole for a severe head trauma. Coadministration of omeprazole with phenytoin may increase the exposure of phenytoin . Monitor serum phenytoin levels, phenytoin dose adjustment may be necessary ; consider using an histamine-2 (H2) receptor antagonist instead of a proton pump inhibitor for gastrointestinal protection if CYP2C9 polymorphisms are unknown .

Severity

Major

Onset

Delayed

Evidence

Theoretical

How To Manage Interaction

Coadministration of omeprazole with phenytoin may increase the exposure of phenytoin. Monitor serum phenytoin levels, phenytoin dose adjustment may be necessary ; consider using an histamine-2 (H2) receptor antagonist instead of a proton pump inhibitor for gastrointestinal protection if CYP2C9 polymorphisms are unknown .

Mechanism Of Interaction

Inhibition of CYP2C19-mediated phenytoin metabolism by omeprazole

Literature Reports

A) A 5-year-old with homozygous CYP2C9*3 variant experienced phenytoin intoxication after being treated with phenytoin and omeprazole following severe head trauma. Phenytoin 5 mg/kg twice daily and omeprazole 0.8 mg/kg daily were initiated upon admission and normal intracranial pressure without neurological deficits was observed for the first 3 days. On day 3, an MRI revealed multiple small hemorrhagic contusions in the white matter of the frontal, parietal, and temporal lobes. Phenytoin was discontinued on day 8 after the patient experienced 2 failed extubations related to progressive respiratory distress with psychomotor agitation and tachypnea. By day 10, the patient was awake, but with loss of awareness, horizontal nystagmus, central neurological hyperventilation, positive bilateral Babinski signs, and increased I to V interpeak latency of the brainstem auditory evoked potentials. EEG analysis revealed frontal intermittent rhythmic delta activity. Phenytoin levels remained abnormally high (greater than 35 mcg/mL) 5 days after medication withdrawal. Omeprazole was discontinued and phenytoin levels decreased significantly over the following 3 days. The patients neurological signs and breathing normalized. Sequencing analysis revealed defective CYP2C9 metabolism leading to phenytoin intoxication .

Omeprazole Overview

• Prescription omeprazole is used alone or with other medications to treat the symptoms of gastroesophageal reflux disease (GERD), a condition in which backward flow of acid from the stomach causes heartburn and possible injury of the esophagus (the tube between the throat and stomach) in adults and children 1 year of age and older. Prescription omeprazole is used to treat damage from GERD in adults and children 1 month of age and older. Prescription omeprazole is used to allow the esophagus to heal and prevent further damage to the esophagus in adults and children 1 year of age and older with GERD. Prescription omeprazole is also used to treat conditions in which the stomach produces too much acid such as Zollinger-Ellison syndrome in adults. Prescription omeprazole is also used to treat ulcers (sores in the lining of the stomach or intestine) and it is also used with other medications to treat and prevent the return of ulcers caused by a certain type of bacteria (H. pylori) in adults. Nonprescription (over-the-counter) omeprazole is used to treat frequent heartburn (heartburn that occurs at least 2 or more days a week) in adults. Omeprazole is in a class of medications called proton-pump inhibitors. It works by decreasing the amount of acid made in the stomach.

Phenytoin Overview

• Phenytoin is used to control certain type of seizures, and to treat and prevent seizures that may begin during or after surgery to the brain or nervous system. Phenytoin is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in the brain.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.