Weekly methotrexate may reduce valproate levels causing relapse of genetic generalized epilepsy

• Seizures have been observed in epilepsy patients receiving high dose intravenous or intrathecal Methotrexate (Mtx) therapy for the treatment of leukemias, due to reduction in valproic acid (VPA) levels. • Prolonged low dose weekly Mtx exposure can also produce reduction in VPA levels causing seizure relapse as reported in this case. • Mtx competes with VPA for binding to albumin as a result of which a larger proportion of VPA become unbound and is rapidly metabolized by the liver causing decline in VPA levels. • Awareness about pharmacological interactions of anti-epileptic drugs (AEDs) is essential in epilepsy management.