From the FDA Drug Label
DOSAGE AND ADMINISTRATION Valproic acid is administered orally. Valproic acid is indicated as monotherapy and adjunctive therapy in complex partial seizures in adults and pediatric patients down to the age of 10 years, and in simple and complex absence seizures. Complex Partial Seizures: For adults and children 10 years of age or older. Monotherapy (Initial Therapy): Valproic acid has not been systematically studied as initial therapy. Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. 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.
The pediatric dosing for Depakote (Valproate) is as follows:
- For children 10 years of age or older with complex partial seizures: 10 to 15 mg/kg/day, increasing by 5 to 10 mg/kg/week to achieve optimal clinical response, with a maximum recommended dosage of 60 mg/kg/day.
- For simple and complex absence seizures: 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, with a maximum recommended dosage of 60 mg/kg/day. 1
From the Research
Pediatric Dosing for Depakote (Valproate)
The pediatric dosing for Depakote (Valproate) can be summarized as follows:
- Initial dosage: 20 to 30 mg/kg per day in two or three divided doses 2
- Mean dose in seizure-free children: 15.7 mg/kg/day, with over 95% of patients responding below 25 mg/kg/day 3
- Intravenous administration: 15-20 mg/kg, followed by 6 mg/kg every 6 hours 4
Key Considerations
- Plasma levels may be useful in adjusting the dosage after several days of treatment 2
- The risk of fatal hepatotoxicity is lower with valproate monotherapy (one per 10,000 patients) than with polytherapy 2
- Valproate is a preferred drug for primary generalized seizures, which are common in pediatric epilepsies 2
- The volume of distribution of 0.20 L/kg can be applied for initial intravenous administration with a favorable efficacy 4
Pharmacokinetics
- Oral forms of valproate are almost completely bioavailable, but the rate of absorption varies between formulations 5
- Plasma protein binding is 80-94% and tends to decrease with increasing drug concentration 5
- Valproate elimination is markedly decreased in newborns compared with older children and adults 5
- Clearance rates are 2.5 times higher in patients on hepatic inducers than in children receiving oral anticonvulsant polytherapy 6