Summary

Esomeprazole may increase phenytoin plasma concentrations by inhibiting CYP2C19-mediated metabolism, potentially leading to phenytoin toxicity. This interaction requires careful monitoring of phenytoin levels and clinical signs of toxicity when these medications are used together.

Introduction

Esomeprazole is a proton pump inhibitor (PPI) commonly prescribed for gastroesophageal reflux disease (GERD), peptic ulcers, and Helicobacter pylori eradication. It works by irreversibly blocking the H+/K+-ATPase enzyme in gastric parietal cells, reducing stomach acid production. Phenytoin is an anticonvulsant medication primarily used to treat and prevent seizures, including tonic-clonic and focal seizures. It belongs to the hydantoin class of antiepileptic drugs and works by blocking voltage-gated sodium channels in neurons, stabilizing neuronal membranes and preventing abnormal electrical activity.

Mechanism of Interaction

The interaction between esomeprazole and phenytoin occurs through cytochrome P450 enzyme inhibition. Esomeprazole is a moderate inhibitor of CYP2C19, the primary enzyme responsible for phenytoin metabolism. When esomeprazole inhibits CYP2C19, it reduces the clearance of phenytoin, leading to increased plasma concentrations and prolonged half-life of the anticonvulsant. This pharmacokinetic interaction can result in elevated phenytoin levels, potentially reaching toxic concentrations. The extent of this interaction may vary among individuals due to genetic polymorphisms in CYP2C19, with poor metabolizers being at higher risk for significant interactions.

Risks and Symptoms

The primary clinical risk of this interaction is phenytoin toxicity, which can manifest as neurological symptoms including ataxia, diplopia, nystagmus, confusion, slurred speech, and drowsiness. In severe cases, phenytoin toxicity can lead to coma, respiratory depression, and cardiovascular complications. The interaction is considered clinically significant because phenytoin has a narrow therapeutic index, meaning small increases in plasma concentrations can lead to toxicity. Patients may experience breakthrough seizures if phenytoin levels become subtherapeutic after discontinuing esomeprazole, or conversely, develop toxicity symptoms when starting esomeprazole therapy. The onset of this interaction typically occurs within days to weeks of concurrent therapy initiation.

Management and Precautions

Esomeprazole interactions with food and lifestyle

Esomeprazole should be taken at least one hour before meals for optimal absorption and effectiveness. Food can reduce the bioavailability of esomeprazole, particularly when taken with high-fat meals. While moderate alcohol consumption is generally not contraindicated with esomeprazole, chronic alcohol use may increase the risk of gastrointestinal bleeding and reduce the medication's protective effects on the stomach lining. Patients should avoid smoking as it can reduce esomeprazole's effectiveness in healing peptic ulcers and may increase gastric acid production.

Phenytoin interactions with food and lifestyle

Phenytoin has several important food and lifestyle interactions that patients should be aware of. Alcohol consumption can significantly affect phenytoin levels - chronic alcohol use may decrease phenytoin effectiveness by increasing metabolism, while acute alcohol intoxication can increase phenytoin levels and toxicity risk. Patients should discuss alcohol use with their healthcare provider. Enteral nutrition (tube feeding) can significantly reduce phenytoin absorption, requiring dosing adjustments and timing considerations. Folic acid supplementation may decrease phenytoin levels, as phenytoin can cause folate deficiency but supplementation can reduce drug effectiveness. Vitamin D supplementation may be necessary as phenytoin can cause vitamin D deficiency and bone problems. Smoking may increase phenytoin metabolism, potentially requiring dose adjustments. Patients should maintain consistent dietary habits and discuss any significant dietary changes with their healthcare provider, as phenytoin levels can be affected by nutritional status.