Divalproex Sodium in Children with Partial Seizures: 12-Month Safety Study

Abstract

This phase III, open-label, multicenter, outpatient study evaluated the 12-month safety of valproate using divalproex sodium sprinkle capsules for partial seizures, with or without secondary generalization, in children aged 3-10 years (n = 169). Laboratory parameters and vital signs were assessed, and the Wechsler Scales of Intelligence, the Developmental Profile-II, movement-related items from the Udvalg for Kliniske Undersøgelser, and the Behavior Assessment System for Children were administered. Efficacy was measured by the 4-week seizure rate. The most common treatment-emergent adverse events in the 169 study patients were typical childhood illnesses: pyrexia (18%), cough (17%), and nasopharyngitis (14%). The most common adverse events not considered typical childhood illnesses were vomiting (14%), tremor (9%), somnolence (8%), and diarrhea (8%). Of the 169 patients, 11 (6.5%) were hospitalized with serious treatment-emergent adverse events. Although elevated ammonia levels were observed in 31 treated patients, and mean increases in uric acid concentrations and decreases in platelets were observed, the majority of patients were asymptomatic. Except for tremor, no increases in movement-related adverse effects were observed. Small numeric improvements were reported in the Wechsler Scales and the Behavior Assessment System for Children. The safety findings in this 12-month study are generally consistent with previous reports of valproate in adult and pediatric epilepsy patients.