Moderate
Probable
Descrição
Phenytoin induces hepatic CYP enzymes that increase the formation of acetaminophen's toxic metabolite NAPQI, raising hepatotoxicity risk; conversely, large doses of acetaminophen may transiently reduce phenytoin levels.
Mecanismo
Phenytoin induces CYP2E1 and CYP3A4, augmenting toxic NAPQI production from acetaminophen while reducing glucuronidation; high-dose acetaminophen may also compete for CYP2C9 sites involved in phenytoin hydroxylation.
Significância Clínica
Chronic phenytoin therapy significantly increases acetaminophen hepatotoxicity risk; acute phenytoin changes in patients receiving analgesic doses are less predictable.
Conduta
Limit acetaminophen dose and duration in patients on phenytoin; monitor liver function tests if prolonged co-administration is unavoidable.