Summary

Isoniazid 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

Phenytoin is an anticonvulsant medication primarily used to treat epilepsy and prevent seizures. It belongs to the hydantoin class of antiepileptic drugs and works by stabilizing neuronal membranes. Isoniazid is a first-line antituberculosis antibiotic used to treat and prevent tuberculosis infections. It belongs to the class of antimycobacterial agents and works by inhibiting mycolic acid synthesis in mycobacteria.

Mechanism of Interaction

The interaction between phenytoin and isoniazid occurs through metabolic inhibition. Isoniazid inhibits cytochrome P450 enzymes, particularly CYP2C9 and CYP2C19, which are responsible for phenytoin metabolism. This inhibition reduces phenytoin clearance, leading to increased plasma concentrations and prolonged half-life. The effect is dose-dependent and can result in phenytoin accumulation over time.

Risks and Symptoms

The primary risk of this interaction is phenytoin toxicity due to elevated blood levels. Signs of phenytoin toxicity include ataxia, nystagmus, diplopia, slurred speech, confusion, and in severe cases, coma. Patients may also experience nausea, vomiting, and drowsiness. The interaction can develop gradually over days to weeks, making it particularly dangerous as symptoms may not be immediately apparent. Elderly patients and those with liver impairment are at higher risk for developing toxicity.

Management and Precautions

When co-administering phenytoin and isoniazid, close monitoring is essential. Baseline phenytoin levels should be obtained before starting isoniazid. Monitor phenytoin serum concentrations regularly, especially during the first few weeks of concurrent therapy. Consider reducing the phenytoin dose by 25-30% when initiating isoniazid therapy. Watch for signs and symptoms of phenytoin toxicity and adjust doses accordingly. Alternative antituberculosis agents may be considered if the interaction cannot be adequately managed. Patients should be educated about toxicity symptoms and advised to report any concerning signs immediately.

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.

Isoniazid interactions with food and lifestyle

Alcohol: Avoid alcohol consumption while taking isoniazid as it significantly increases the risk of hepatotoxicity (liver damage). The combination can lead to severe liver injury and potentially fatal hepatitis. Food interactions: Take isoniazid on an empty stomach (1 hour before or 2 hours after meals) for optimal absorption. Foods high in tyramine (aged cheeses, cured meats, fermented foods) should be avoided as isoniazid has mild MAO inhibitor properties and may cause hypertensive reactions. Histamine-rich foods (tuna, skipjack fish) should also be avoided as isoniazid can inhibit histamine metabolism, potentially causing flushing, headache, and palpitations.