phenytoin

Phenytoin is a hydantoin anticonvulsant used to control certain seizure types. Its primary mechanism is the stabilization of neuronal membranes by prolonging the inactivated state of voltage-gated sodium channels, which reduces repetitive firing. It may also modulate calcium channels and receptor signaling to a lesser extent.

Phenytoin is indicated for generalized tonic-clonic seizures and complex partial seizures, and is used for seizure prevention after neurosurgery. It is also employed in the management of status epilepticus after benzodiazepines in some protocols. Available oral formulations include tablets, chewables, and suspension; intravenous administration is possible but typically via the prodrug fosphenytoin to reduce local irritation. IV phenytoin should be given slowly (not exceeding about 50 mg per minute), diluted in normal saline, and never mixed with dextrose-containing solutions.

Pharmacokinetics are nonlinear due to saturable hepatic metabolism and high protein binding (about 90-95% to albumin). Small changes in dose can cause large changes in serum concentration. Therapeutic levels are commonly cited as total phenytoin 10–20 µg/mL; free phenytoin is 1–2 µg/mL. Many factors influence levels, including albumin status and interactions with other drugs. Monitoring trough levels, liver function, and hematologic parameters is recommended.

Adverse effects range from dose-related ataxia, diplopia, and nystagmus to long-term effects such as gingival hyperplasia, hirsutism, acne, and rash including Stevens–Johnson syndrome. Phenytoin can cause hepatotoxicity and teratogenic effects (fetal hydantoin syndrome). It is contraindicated in hypersensitivity to hydantoins, certain cardiac conditions, and should be used with caution in pregnancy (category D) and in hypersensitive or unstable patients.

Drug interactions are common: phenytoin induces many cytochrome P450 enzymes, lowering levels of warfarin, oral contraceptives, and other drugs; valproate can displace phenytoin from albumin and alter metabolism; rifampin and others can increase clearance.