Recommended Dosing for Depakote (Valproate)
For adults with epilepsy, the recommended initial dosage of Depakote (valproate) is 10-15 mg/kg/day, with weekly increases of 5-10 mg/kg until optimal clinical response is achieved, typically at doses below 60 mg/kg/day. 1
Dosing Guidelines by Indication
Epilepsy (Oral Administration)
- Initial therapy: 10-15 mg/kg/day divided into 2-3 doses 1
- Titration: Increase by 5-10 mg/kg/week to achieve optimal clinical response 1
- Maximum recommended dose: 60 mg/kg/day 1
- Therapeutic plasma concentration range: 50-100 μg/mL 1
- Risk of thrombocytopenia increases significantly at trough plasma concentrations above 110 μg/mL in females and 135 μg/mL in males 1
Mood Stabilization (for agitation, combativeness)
- Initial dosage: 125 mg twice daily 2
- Titration: Increase to therapeutic blood level (40-90 μg/mL) 2
- Monitor liver enzyme levels, platelets, prothrombin time, and partial thromboplastin time as indicated 2
- Generally better tolerated than other mood stabilizers 2
Status Epilepticus (IV Administration)
- Loading dose: 20-30 mg/kg IV 2
- Infusion rate: Up to 6 mg/kg/min is considered safe 3
- Efficacy in status epilepticus: 63-88% of patients respond 2
- IV valproate can safely achieve therapeutic levels (>100 μg/mL) with rapid infusion 3
Formulation Considerations
- Extended-release formulation (Depakote ER) is appropriate for once-daily dosing across a wide dose range 4
- Enteric-coated, delayed-release formulation (standard Depakote) should not be given once-daily at high doses (≥2000 mg) due to risk of excessive peak concentrations 4
- Sprinkle formulation has equal bioavailability to syrup formulation (relative bioavailability = 1.02) but with slower absorption (time to maximum concentration = 4.2 vs 0.9 hours) 5
- Sprinkle formulation results in less fluctuation in serum concentrations (34.8% vs 62.3%) compared to syrup 5
Monitoring Parameters
- Plasma valproate concentrations should be measured if satisfactory clinical response is not achieved 1
- Monitor liver enzyme levels regularly 2
- Monitor complete blood count, especially platelets 2
- Monitor prothrombin time and partial thromboplastin time as indicated 2
Special Considerations
- Missed doses: If doses are missed for 12-24 hours, plasma concentrations can fall below therapeutic range (50 mg/kg) 6
- When replacing missed doses, be cautious in patients taking enzyme-inducing antiepileptic drugs as this may result in transiently high valproate levels 6
- Valproate, divalproex, and valpromide all deliver the same active substance (valproate ion) despite having different labeled indications in some countries 7
- Abrupt discontinuation should be avoided due to risk of precipitating status epilepticus 1