Recommended Dosing for Depakote (Valproate)
For adults with epilepsy, the recommended initial dose of Depakote is 10-15 mg/kg/day, with titration by 5-10 mg/kg/week to achieve optimal clinical response, typically at doses below 60 mg/kg/day and serum levels of 50-100 μg/mL. 1
Dosing by Indication
Epilepsy
- Initial dose: 10-15 mg/kg/day 1
- Titration: Increase by 5-10 mg/kg/week to achieve optimal clinical response 1
- Target serum level: 50-100 μg/mL 1
- Maximum recommended dose: 60 mg/kg/day 1
- For status epilepticus: Loading dose of 20-30 mg/kg IV, with efficacy in 63-88% of patients 2
Mood Disorders
- Initial dose: 125 mg twice daily 3
- Target serum level: 40-90 μg/mL 3
- For cyclothymia and milder bipolar disorders: Lower doses (125-500 mg/day) may be effective with mean serum levels around 32.5 μg/mL 4
- For acute mania: Serum levels ≥45 μg/mL are associated with 2-7 times greater likelihood of clinical improvement 5
Administration Guidelines
Oral Administration
- If total daily dose exceeds 250 mg, it should be given in divided doses 1
- Weight-based dosing guide for oral solution 1:
- 10-24.9 kg: 250 mg/day (5 mL/day)
- 25-39.9 kg: 500 mg/day (10 mL/day)
- 40-59.9 kg: 750 mg/day (15 mL/day)
- 60-74.9 kg: 1,000 mg/day (20 mL/day)
- 75-89.9 kg: 1,250 mg/day (25 mL/day)
Extended-Release Formulation
- Extended-release divalproex is appropriate for once-daily dosing across a wide dose range 6
- Enteric-coated, delayed-release divalproex should not be administered once-daily at high doses (≥2000 mg) due to risk of toxicity from high peak concentrations 6
Monitoring and Safety
- Regular monitoring of serum levels is essential 1
- Thrombocytopenia risk increases significantly at trough levels above 110 μg/mL in females and 135 μg/mL in males 1
- Adverse effects are disproportionately associated with serum levels ≥125 μg/mL 5
- Monitor liver enzyme levels, platelets, prothrombin time, and partial thromboplastin time 3
Special Populations
Elderly Patients
- Use reduced starting doses due to decreased unbound clearance and potentially greater sensitivity to side effects 1
- Increase dose more slowly with regular monitoring for fluid/nutritional intake, dehydration, and adverse events 1
- Consider dose reductions or discontinuation in patients with decreased food/fluid intake or excessive somnolence 1
Drug Interactions
- Valproate may increase amitriptyline levels by approximately 31% through decreased first-pass metabolism and inhibition of systemic metabolism 7
- May affect blood concentrations of phenobarbital, carbamazepine, and/or phenytoin when used concomitantly 1