Moderate
Established
Descripción
Valproic acid displaces phenytoin from protein binding and inhibits its metabolism, leading to increased free phenytoin levels despite total levels that may appear unchanged or decreased.
Mecanismo
Valproate displaces phenytoin from albumin (protein binding competition) and inhibits its CYP2C9-mediated metabolism; free phenytoin fraction increases.
Relevancia clínica
Standard total phenytoin levels may be misleadingly normal while free levels are toxic; nystagmus, ataxia, and mental status changes may develop.
Manejo clínico
Monitor free (unbound) phenytoin levels rather than total levels; watch for phenytoin toxicity signs and adjust dose accordingly.