Valproic Acid Serum Concentration and Incidence of Toxicity in Pediatric Patients

In certain pediatric patients on valproic acid, therapeutic range (50-100 μg/mL) is maximized or exceeded to achieve better seizure control. This study compared incidence of common valproic acid adverse effects (thrombocytopenia, hepatotoxicity, and hyperammonemia) across maintenance concentration and age group. One hundred twenty-four children on maintenance valproic acid between January 2013 and January 2021 were eligible for inclusion. Fifty-six patients were maintained in concentration range 50 to 80 μg/mL, an additional 44 between 80 and 100 μg/mL and 24 between 100 and 120 μg/mL. Forty-one patients were prepubescent, 57 pubescent, and 26 postpubescent. There were no statistically significant differences observed in the primary endpoint of thrombocytopenia across serum concentration range (P = .093) or age group (P = .628). No significant differences in hepatic dysfunction (P = .099) or hyperammonemia (P = .548) were observed in serum concentration groups. Similarly, age group analysis observed no difference in hepatic dysfunction (P = .615) or hyperammonemia (P = .369). Serum valproic acid levels >100 μg/mL can be considered in select pediatric patients based on this study.