Daily dosage should be established according to age and body weight; nevertheless, the wide individual sensitivity to valproate should also be considered.
Optimum dosage should be determined essentially according to the clinical response; the determination of valproic acid plasma levels may be considered in addition to clinical monitoring when adequate seizure control is not achieved or when adverse effects are suspected. The reported effective range is usually between 40-100 mg/L (300-700 micromole/L).
Initiation of Depakine Therapy (Oral Administration): In patients without other antiepileptic drugs, the dosage should be preferably increased by successive dose levels at 2- to 3- day intervals in order to reach the optimum dosage in about 1 week.
In patients previously receiving antiepileptic agents, substitution with Depakine should be progressive, the optimum dosage being reached in about 2 weeks and other treatments being tapered then stopped.
Addition of another antiepileptic agent should be done progressively where it is necessary (see Interactions).
Dosage: Epilepsy: Initial daily dosage is usually 10-15 mg/kg then doses are titrated up to the optimum dosage (see Initiation of Depakine Therapy in previous text).
This is generally within the range 20-30 mg/kg. Nevertheless, where seizure control is not achieved within this range, the dose may be further increased adequately; patients should be carefully monitored when receiving daily doses >50 mg/kg. (See Precautions.)
Adults: Usual dosage is within the range 20-30 mg/kg/day.
Children: Usual dosage is about 30 mg/kg/day.
Elderly: Although the pharmacokinetics of Depakine is modified, they have limited clinical significance and dosage should be determined by seizure control.
Mania: Initial Dose: 1000 mg/day. The recommended maintenance dosage is 1000-2000 mg daily. The dose may be increased to not more than 3000 mg daily. Doses should be adjusted according to individual clinical response.
Administration: Tablets, liquid and syrup may be given twice daily.
The use of a sustained-release form (Depakine Chrono) allows the drug to be given once daily.
Depakine Chrono may be used in children provided that they are able to take such a form.
Depakine IV Administration: Patients being treated satisfactorily with oral Depakine may be continued at their current dosage using continuous or repeated infusion ie, a patient stabilized on 25 mg/kg administered daily should be continued with an infusion at the rate of 1 mg/kg/hr.
Other patients may initially be given a slow IV injection (>3 min), usually 15 mg/kg followed by an infusion at the usual rate of 1-2 mg/kg/hr and adjusted on the clinical response.