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Extended‐release Divalproex in Child and Adolescent Outpatients with Epilepsy
Author(s) -
Kernitsky Lydia,
O'Hara Kathryn A.,
Jiang Ping,
Pellock John M.
Publication year - 2005
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.0013-9580.2005.39804.x
Subject(s) - valproic acid , epilepsy , anticonvulsant , adverse effect , extended release , medicine , anesthesia , divalproex , randomized controlled trial , pediatrics , pharmacology , bipolar disorder , psychiatry , cognition , mania
Summary: 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 μg/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 ≤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 μg/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.