FDA Approves Valproic Acid Oral Solution (valproic acid) for Complex Partial and Absence Seizures.

Not reported in label.

Valproic acid is indicated as monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizures. It is indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types which include absence seizures. It is approved for adults and pediatric patients down to the age of 10 years. The label states it should not be used to treat women with epilepsy who are pregnant or who plan to become pregnant unless other medications have failed to provide adequate symptom control or are otherwise unacceptable. It should not be administered to a woman of childbearing potential unless other medications have failed.

Valproic Acid Oral Solution is for oral administration. For complex partial seizures (monotherapy initial therapy, conversion to monotherapy, and adjunctive therapy): Initiate at 10 to 15 mg/kg/day. Increase by 5 to 10 mg/kg/week to achieve optimal clinical response, typically at doses below 60 mg/kg/day. If response is unsatisfactory, check plasma levels (therapeutic range 50 to 100 mcg/mL). No safety recommendation can be made for doses above 60 mg/kg/day. For adjunctive therapy, if the total daily dose exceeds 250 mg, it should be given in divided doses. For simple and complex absence seizures: The recommended initial dose is 15 mg/kg/day, increasing at one week intervals by 5 to 10 mg/kg/day until seizures are controlled or side effects preclude further increases. The maximum recommended dosage is 60 mg/kg/day. When converting to monotherapy, concomitant antiepilepsy drug (AED) dosage can be reduced by approximately 25% every 2 weeks.

Trial data not available in label.

The label contains a warning regarding fatal hepatic dysfunction. Because of the risk to the fetus of decreased IQ, neurodevelopmental disorders, neural tube defects, and other major congenital malformations, valproate is contraindicated for prophylaxis of migraine headaches in women who are pregnant and in women of childbearing potential who are not using effective contraception. For epilepsy or bipolar disorder, it should not be used in women who are pregnant or plan to become pregnant, or in women of childbearing potential, unless other medications have failed to provide adequate symptom control or are otherwise unacceptable. The probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations above 110 mcg/mL in females and 135 mcg/mL in males.

Valproic acid is indicated as monotherapy and adjunctive therapy for specific seizure types (complex partial, simple absence, complex absence). Its use is limited by significant teratogenic risks and boxed warnings for hepatic failure, restricting its use in women of childbearing potential to situations where other treatments have failed. It is an option for seizure control in approved populations when the benefit-risk profile is carefully considered.