Purpose: To determine whether valproic acid [divalproex (DVP)] extended-release, administered at a higher proportionate once-daily dosage, can be safely substituted for delayed-release or sprinkle in pediatric patients with epilepsy.
Methods: Patients between ages 6 and 17 years with stable epilepsy taking DVP were randomized to 7 days of either DVP delayed-release/sprinkle (at the usual daily dose taken before study entry) or extended-release DVP (daily dose, 8% to 25% higher than their usual dose), and then (crossed over to) 7 days of the comparator formulation. Patient's clinical status was evaluated at a screening visit and on days 8 and 15, and with telephone follow-up 1 month after study completion.
Results: No statistically significant difference in mean plasma VPA levels measured at the end of treatment was observed: 99, 92, and 103 mug/ml with the delayed-release tablets (n = 4), the sprinkle formulation (n = 11), and the extended-release tablets (n = 16), respectively. Seizure-control rates were stable during patients' use of the extended-release formulation. None of the study patients experienced a treatment-related adverse event.
Conclusions: The total daily dose for patients taking the delayed-formulation may need to be increased by < or = 20% when they are switched to the extended-release formulation. When switching from sprinkles to the extended-release formulation, individual variability must be considered. In patients who have VPA levels near the very high end of the therapeutic range (>100 microg/ml), it may be more prudent to make only minor modifications to the total daily dose during conversion and then to individualize the DVP extended-release dose based on plasma levels.