Summary

Cimetidine significantly inhibits the metabolism of phenytoin, leading to increased phenytoin blood levels and potential toxicity. This clinically significant interaction requires careful monitoring and possible dose adjustments when these medications are used together.

Introduction

Cimetidine is an H2 receptor antagonist commonly used to treat peptic ulcers, gastroesophageal reflux disease (GERD), and other acid-related disorders by reducing stomach acid production. Phenytoin is a first-generation anticonvulsant medication primarily used to treat and prevent seizures, including tonic-clonic and focal seizures. Both medications are frequently prescribed, making their potential interaction clinically relevant for healthcare providers and patients.

Mechanism of Interaction

The interaction between cimetidine and phenytoin occurs through hepatic enzyme inhibition. Cimetidine is a potent inhibitor of several cytochrome P450 enzymes, particularly CYP2C9 and CYP2C19, which are responsible for phenytoin metabolism. When cimetidine inhibits these enzymes, phenytoin clearance is significantly reduced, leading to increased plasma concentrations and prolonged half-life. This pharmacokinetic interaction can result in phenytoin levels rising to potentially toxic ranges, even with standard dosing.

Risks and Symptoms

The primary risk of this interaction is phenytoin toxicity, which can manifest as neurological symptoms including ataxia, diplopia, nystagmus, confusion, and drowsiness. Severe toxicity may lead to seizures, coma, or cardiovascular complications. Studies have shown that cimetidine can increase phenytoin plasma levels by 20-40%, with effects becoming apparent within 24-48 hours of concurrent administration. Patients with pre-existing high-normal phenytoin levels are at particular risk for developing toxicity. The interaction is dose-dependent and more pronounced with higher cimetidine doses.

Management and Precautions

When concurrent use is necessary, close monitoring of phenytoin serum levels is essential, with baseline levels obtained before starting cimetidine. Phenytoin levels should be checked within 3-5 days of initiating cimetidine and weekly thereafter until stable. Consider reducing phenytoin dose by 20-25% when starting cimetidine, with further adjustments based on serum levels and clinical response. Alternative H2 blockers like ranitidine or famotidine may be preferred as they have minimal effects on hepatic enzymes. If cimetidine is discontinued, phenytoin levels may decrease, requiring dose increases to maintain therapeutic levels. Patients should be educated about signs of phenytoin toxicity and advised to report symptoms promptly.

Cimetidine interactions with food and lifestyle

Cimetidine should be taken with food or immediately after meals to reduce stomach upset and improve absorption. Alcohol consumption should be limited or avoided while taking cimetidine, as both substances can affect liver metabolism and may increase the risk of side effects. Smoking may reduce the effectiveness of cimetidine in treating ulcers and should be avoided or minimized during treatment. Caffeine intake should be moderated as cimetidine can increase caffeine levels in the blood, potentially leading to increased caffeine-related side effects such as jitteriness or insomnia.

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.