What is the IV form of Depakote (valproate)?

Intravenous Valproate (Depakote)

The intravenous form of Depakote is valproate sodium injection, available as a clear, colorless solution containing 100 mg of valproic acid equivalent per mL in single-dose vials for intravenous administration. 1

Formulation and Administration

• IV valproate sodium is available in 5 mL single-dose vials (100 mg/mL)
• Each mL contains valproate sodium equivalent to 100 mg valproic acid, edetate disodium 0.40 mg, and water for injection 1
• The solution has a pH of approximately 7.6, adjusted with sodium hydroxide and/or hydrochloric acid 1
• Administered as an intravenous infusion, typically over 60 minutes for standard dosing 1

Pharmacokinetics

• Equivalent doses of IV valproate and oral valproate products result in equivalent maximum concentration (Cmax), minimum concentration (Cmin), and total systemic exposure when administered as a 60-minute infusion 1
• The time to maximum concentration (Tmax) occurs at the end of the one-hour infusion for IV valproate, compared to approximately 4 hours for oral divalproex sodium 1
• IV administration allows for rapid achievement of therapeutic serum levels, which is particularly beneficial in acute situations 2
• Mean terminal half-life is approximately 16 ± 3.0 hours after an intravenous infusion of 1,000 mg 1

Safety and Efficacy

• IV valproate has been shown to be safe when administered at rates up to 10 mg/kg/min and doses up to 30 mg/kg 3
• Studies have demonstrated that loading doses of IV valproate (21-28 mg/kg) can be administered safely and rapidly at infusion rates of 3-6 mg/kg per minute 2
• In a study comparing IV valproate (30 mg/kg) with IV phenytoin (18 mg/kg) for convulsive status epilepticus, valproate was more effective (66% vs. 42%) and had fewer adverse effects like respiratory depression and hypotension 3

Clinical Applications

Status Epilepticus

• IV valproate is effective for status epilepticus with a success rate of approximately 88% 4
• Dosing for status epilepticus is typically 20-30 mg/kg IV 4
• Compared to phenytoin, IV valproate has fewer adverse effects such as hypotension and respiratory depression 3

Other Applications

• Can be used in patients unable to take oral medications 2
• Has been used successfully as an adjunctive treatment for delirium and psychotic agitation in hospitalized patients who are NPO (nothing by mouth) 5
• May provide more rapid symptom improvement in acute psychiatric settings compared to oral formulations 6

Adverse Effects and Monitoring

• Most common adverse effects include gastrointestinal disturbances, tremor, and weight gain 7
• Local irritation at the injection site may occur but is typically transient 3, 2
• No significant changes in blood pressure or ECG abnormalities have been observed with rapid infusion 2
• Monitoring of hemodynamic parameters is recommended due to potential adverse effects 4

Practical Considerations

• IV valproate can be administered more rapidly than previously thought, which enables its use in emergency situations like status epilepticus 2
• When transitioning from oral to IV administration, comparable plasma levels are maintained when equivalent doses are used 1
• For patients on established oral valproic acid therapy (750-4250 mg daily), switching to IV valproate as a 1-hour infusion results in comparable plasma levels 1

IV valproate provides a valuable alternative to oral formulations when rapid achievement of therapeutic levels is necessary or when oral administration is not possible, with a favorable safety and efficacy profile compared to other intravenous antiepileptic medications.