Epilepsan ECC Dosage/Direction for Use

General: Divalproex Sodium caplets are administered orally and should be swallowed whole, without chewing.
Epilepsy: Divalproex Sodium caplets are indicated as monotherapy and adjunctive therapy in complex partial seizure in adults and pediatric patients down to the age of ten years, and in simple and complex absence seizures in adults and adolescents. As the Divalproex Sodium dosage is titrated upward, concentrations of Phenobarbital, Carbamazepine, and/or Phenytoin may be affected [see INTERACTIONS].
Complex Partial Seizure (CPS): For adults and children ten years of age or older.
Monotherapy (Initial Therapy): Divalproex Sodium 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. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of Valproate for use at doses above 60 mg/kg/day can be made.
The probability of thrombocytopenia increases significantly at total trough Valproate plasma concentrations above 110 mcg/mL in females and 135 mcg/mL in males. The benefit of improved seizure control with higher doses should be weighed against the possibility of a greater incidence of adverse reactions [see Thrombocytopenia under PRECAUTIONS].
Conversion to Monotherapy: Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage 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. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of Valproate for use at doses above 60 mg/kg/day can be made. Concomitant anti-epilepsy drug (AED) dosage can ordinarily be reduced by approximately 25% every two weeks. This reduction may be started at initiation of Divalproex Sodium therapy, or delayed by one to two weeks if there is a concern that seizures are likely to occur with a reduction. The speed and duration of withdrawal of the concomitant AED can be highly variable, and patients should be monitored closely during this period for increased seizure frequency.
Adjunctive Therapy: Divalproex Sodium may be added to the patient's regimen at a dosage of 10 to 15 mg/kg/day. The dosage may 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. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. If the total daily dose exceeds 250 mg, it should be given in divided doses.
Adjunctive therapy for complex partial seizures in which patients were receiving either carbamazepine or phenytoin in addition to Divalproex Sodium, no adjustment of carbamazepine or phenytoin dosage was needed. However, since valproate may interact with these or other concurrently administered AEDs as well as other drugs, periodic plasma concentration determinations of concomitant AEDs are recommended during the early course of therapy [see INTERACTIONS].
Simple and Complex Absence Seizures: The recommended initial dose is 15 mg/kg/day, increasing a tone 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. If the total daily dose exceeds 250 mg, it should be given in divided doses. A good correlation has not been established between daily dose, serum concentrations, and therapeutic effect. However, therapeutic valproate serum concentrations for most patients with absence seizures will range from 50 to 100 mcg/mL. Some patients may be controlled with lower or higher serum concentrations.
As the Divalproex Sodium dosage is titrated upward, blood concentrations of phenobarbital and/or phenytoin may be affected [see INTERACTIONS].
Anti-epilepsy drugs should not be abruptly discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life.
Conversion from Valproic Acid to Divalproex Sodium: In patients previously receiving Valproic Acid therapy, Divalproex Sodium products should be initiated at the same daily dose and dosing schedule. After the patient is stabilized on a Divalproex sodium product, a dosing schedule of two or three times a day may be elected in selected patients.
General dosing advice: Dosing in Elderly Patients: Due to decrease in clearance of unbound Valproate and possibly a greater sensitivity to somnolence in the elderly, the starting dose should be reduced in these patients. Dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse events. Dose reductions or discontinuation of Valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence. The ultimate therapeutic dose should be achieved on the basis of clinical response [see Somnolence in the Elderly under PRECAUTIONS].
Dose-Related Adverse Events: The frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia) may be dose-related. The probability of thrombocytopenia appears to increase significantly at total Valproate concentrations of ≥ 110 mcg/mL (females) or ≥ 135 mcg/mL (males) [see Thrombocytopenia under PRECAUTIONS]. The benefit of improved therapeutic effect with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.
G.I Irritations: Patients who experience G.I irritation may benefit from administrations of the drug with food or by slowly building up the dose from an initial low level.