Phenytoin in Epilepsy Management: Efficacy, Safety, and Drug Interactions

Phenytoin is a widely used antiepileptic drug that has played a significant role in the management of seizure disorders for several decades. It is primarily indicated for the treatment of focal (partial) seizures and generalized tonic–clonic seizures. Phenytoin exerts its antiepileptic effect mainly by stabilizing neuronal membranes through selective inhibition of voltagegated sodium channels, thereby reducing repetitive neuronal firing and seizure propagation. Despite its proven efficacy, phenytoin exhibits complex pharmacokinetics characterized by nonlinear (zero-order)metabolism, narrow therapeutic index, and high plasma protein binding, which necessitate careful therapeutic drug monitoring. The drug is extensively metabolized in the liver by cytochrome P450 enzymes, making it susceptible to numerous drug–drug interactions. Long-term use of phenytoin is associated with several adverse effects, including gingival hyperplasia, hirsutism, osteomalacia, peripheral neuropathy, and hematological abnormalities. Recent studies have focused on improving phenytoin delivery systems, minimizing toxicity, and understanding pharmacogenetic influences on its metabolism and response. This review summarizes the pharmacology, mechanism of action, pharmacokinetics, clinical applications, adverse effects,