FDA Approves Valproate Sodium Injection (valproate sodium) for IV Use in Complex Partial and Absence Seizures

Not reported in label.

Valproate Sodium Injection is indicated as an intravenous alternative in patients for whom oral administration of valproate products is temporarily not feasible. It is indicated for 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 also indicated for use as sole and adjunctive therapy in the treatment of patients with simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures. Because of the risk to the fetus, valproate 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. Valproate should not be administered to a woman of childbearing potential unless other medications have failed to provide adequate symptom control or are otherwise unacceptable.

Valproate Sodium Injection is for intravenous use only. Use for periods of more than 14 days has not been studied. Patients should be switched to oral valproate products as soon as clinically feasible. The injection should be administered as a 60-minute infusion (but not more than 20 mg/min) with the same frequency as oral products, although plasma concentration monitoring and dosage adjustments may be necessary. For complex partial seizures and simple and complex absence seizures in adults and children 10 years of age or older: The initial dose is 10 to 15 mg/kg/day, increasing at 1-week intervals by 5 to 10 mg/kg/day to achieve optimal clinical response. The maximum recommended dose is 60 mg/kg/day. No recommendation regarding safety at doses above 60 mg/kg/day can be made. The probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations above 110 mcg/mL in females and 135 mcg/mL in males.

Trial data not available in label. The label states that Valproate Sodium Injection has not been systematically studied as initial therapy. Dosage recommendations were obtained from studies utilizing oral divalproex sodium products. One clinical safety study in approximately 90 patients with epilepsy assessed tolerability of single rapid infusions (5-10 minutes) but was not designed to assess effectiveness.

Important limitations are stated due to the risk to the fetus of decreased IQ, neurodevelopmental disorders, neural tube defects, and other major congenital malformations. Valproate 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. Valproate should not be administered to a woman of childbearing potential unless other medications have failed to provide adequate symptom control or are otherwise unacceptable. For prophylaxis of migraine headaches, valproate is contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception. See WARNINGS AND PRECAUTIONS for statement regarding fatal hepatic dysfunction.

Valproate Sodium Injection serves as a temporary intravenous alternative for valproate therapy when the oral route is not feasible, such as in hospitalized patients. It is intended for short-term use (not studied beyond 14 days) to maintain seizure control in patients already established on or initiating valproate therapy for complex partial or absence seizures, with the goal of transitioning back to oral medication as soon as possible.