Intravenous Valproate: The IV Equivalent of Depakote

Yes, there is an FDA-approved intravenous (IV) formulation of valproate, which is the IV equivalent of oral Depakote. 1

IV Valproate Overview

IV valproate is indicated as an intravenous alternative in patients for whom oral administration of valproate products is temporarily not feasible 1
It is approved for monotherapy and adjunctive therapy of complex partial seizures, simple and complex absence seizures, and as adjunctive therapy in patients with multiple seizure types that include absence seizures 1
IV valproate has demonstrated efficacy in 77-88% of status epilepticus cases 2

IV valproate can be administered at up to 30 mg/kg at a maximum rate of 10 mg/kg/min 3, 4
Rapid administration of undiluted valproate has been shown to be safe and well tolerated at infusion rates up to 10 mg/kg/min and doses up to 30 mg/kg 5
Equivalent doses of IV valproate and oral valproate products result in equivalent maximum concentration (Cmax), minimum concentration (Cmin), and total systemic exposure to the valproate ion when administered as a 60-minute infusion 1

IV valproate has been shown to be effective in the treatment of status epilepticus, with seizure termination achieved within 20 minutes of infusion for 83% of patients in one study 3
In refractory status epilepticus, IV valproate is recommended as one of the agents that can be administered after failed treatment with benzodiazepines (Level B recommendation) 3
Limdi and Faught reported that 16 of 20 patients (80%) with intractable seizures were effectively treated with a rapid infusion of IV valproate 3

IV valproate has fewer cardiovascular side effects compared to phenytoin/fosphenytoin, with minimal risk of hypotension 2
Sinha and Naritoku reported that IV valproate did not exacerbate hypotension in 13 hypotensive geriatric patients 3
The most common adverse effects include transient pain at the injection site, which appears to be related to the concentration of valproic acid in the infusion fluid 6
No significant changes in blood pressure or ECG abnormalities were observed in studies of rapid IV valproate infusion 6, 5

The maximum concentration (Tmax) after IV valproate occurs at the end of the infusion, while Tmax after oral dosing with divalproex sodium occurs at approximately 4 hours 1
The bioavailability and tolerance of IV valproate, when administered in infusion for 60 minutes every 6 hours, are similar to those of oral valproate 7
Patients maintained on oral divalproex sodium show comparable plasma levels when switching to IV valproate 1

IV valproate is particularly useful in situations where rapid elevation of serum valproate levels is needed or for patients unable to take oral medication 6
It can be used in emergency situations including status epilepticus that is refractory to initial treatments 8
IV valproate offers an alternative to phenobarbital and other CNS depressants in the treatment of status epilepticus that is partially resistant to diazepam and phenytoin 7

Delaying administration of IV antiepileptic drugs in patients with known epilepsy who have had multiple seizures 2
Inadequate dosing of IV valproate when treating seizure emergencies 2
Failing to monitor for potential adverse effects, although they are relatively uncommon compared to other IV antiepileptic medications 8