phenytoin and isoniazid

Isoniazid inhibits the hepatic metabolism of phenytoin, primarily by inhibiting cytochrome P450 enzyme CYP2C9. This reduces the clearance of phenytoin, leading to increased plasma concentrations and potential toxicity.

Phenytoin toxicity can occur, manifesting as nystagmus, ataxia, slurred speech, confusion, and in severe cases, seizures or coma. The interaction is more pronounced in slow acetylators of isoniazid, who have higher isoniazid levels and greater enzyme inhibition.

Monitor plasma phenytoin concentrations closely, especially within the first two weeks of concurrent therapy. Reduce the phenytoin dose as needed to maintain therapeutic levels. Advise patients to report symptoms of toxicity. If isoniazid is stopped, monitor for decreased phenytoin levels and increase the dose if required.

This interaction is well documented in clinical literature and standard drug interaction references. It is based on case reports, pharmacokinetic studies, and clinical observations. The magnitude of effect varies among individuals, particularly with isoniazid acetylator status.