Summary

Esomeprazole may increase phenytoin plasma concentrations through inhibition of CYP2C19 metabolism, potentially leading to phenytoin toxicity. This interaction requires careful monitoring of phenytoin levels and possible dose adjustments when these medications are used concurrently.

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 competitive inhibition of the cytochrome P450 enzyme CYP2C19. Esomeprazole is metabolized by CYP2C19 and also acts as an inhibitor of this enzyme. Phenytoin is primarily metabolized by CYP2C9, but CYP2C19 also contributes to its metabolism, particularly the formation of 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH). When esomeprazole inhibits CYP2C19, it reduces the clearance of phenytoin, leading to increased plasma concentrations. This effect is dose-dependent and may be more pronounced in patients who are extensive metabolizers of CYP2C19.

Risks and Symptoms

The primary clinical risk of this interaction is phenytoin toxicity due to elevated plasma concentrations. Signs and symptoms of phenytoin toxicity include ataxia, nystagmus, diplopia, slurred speech, confusion, drowsiness, and in severe cases, coma. Chronic phenytoin toxicity can lead to cerebellar dysfunction, peripheral neuropathy, and cognitive impairment. The interaction may be particularly significant in patients with narrow therapeutic windows, elderly patients, or those with compromised hepatic function. Additionally, the onset of toxicity may be delayed, as it can take several days to weeks for phenytoin levels to reach steady state after initiation or dose changes of esomeprazole.

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.