Moderate
Established
Deskripsi
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.
Mekanisme
Valproate displaces phenytoin from albumin (protein binding competition) and inhibits its CYP2C9-mediated metabolism; free phenytoin fraction increases.
Signifikansi Klinis
Standard total phenytoin levels may be misleadingly normal while free levels are toxic; nystagmus, ataxia, and mental status changes may develop.
Penatalaksanaan
Monitor free (unbound) phenytoin levels rather than total levels; watch for phenytoin toxicity signs and adjust dose accordingly.