Sign Out
Divalproex sodium/Valproate/Valproic Acid is prescribed and dispensed in accordance to the measures for prevention of pregnancy mentioned in Contraindications and Warnings.
After the treating physician determines the suitability of the patient (according to Dosage & Administration), Divalproex sodium/Valproate/Valproic Acid should preferably be prescribed as monotherapy and at the lowest effective dose, if possible as a prolonged release formulation. The daily dose should be divided into at least two single doses (see Use in Pregnancy & Lactation).
Prophylaxis of migraine attacks: Divalproex sodium/Valproate/Valproic Acid should only be initiated and supervised by a specialist experienced in the management of migraine. Treatment should only be initiated if other treatments are ineffective or not tolerated (see Contraindications, Precautions and Use in Pregnancy & Lactation) and the benefit and risk should be carefully reconsidered at regular treatment reviews.
Patients with renal insufficiency: It may be necessary in patients with renal insufficiency to decrease the dosage, or to increase the dosage in patients on hemodialysis. Divalproex sodium/Valproate/Valproic acid is dialysable (see Overdosage). Dosing should be modified according to the clinical monitoring of the patient.
General: A divalproex sodium extended-release tablet is an extended-release product intended for once-a-day administration.
Mania: Divalproex sodium extended-release tablets are administered orally. The recommended initial dose is 25 mg/kg/day given once daily. The dose should be increased as rapidly as possible to achieve the lowest therapeutic dose which produces the desired clinical effect or the desired range of plasma concentrations.
In a placebo-controlled clinical trial of acute mania or mixed type, patients were dosed to a clinical response with a trough plasma concentration between 85 and 125 mcg/mL. The maximum recommended dosage is 60 mg/kg/day.
There is no body of evidence available from controlled trials to guide a clinician in the longer term management of a patient who improves during divalproex sodium extended-release tablets treatment of an acute manic episode. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no data to support the benefits of divalproex sodium extended-release tablets in such longer-term treatment (i.e., beyond 3 weeks).
Epilepsy: Divalproex sodium is indicated as monotherapy and adjunctive therapy in complex partial seizures, and in simple and complex absence seizures in adult and pediatric patients 10 years of age or older. As the divalproex sodium dosage is titrated upward, concentrations of phenobarbital, carbamazepine, and/or phenytoin may be affected (see Interactions).
Complex Partial Seizures (CPS) for adults and children 10 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 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. Concomitant antiepilepsy 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.
In a study of 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 (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). 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 for adults and children 10 years of age and older: 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.
A good correlation has not been established between daily dose, serum concentrations, and therapeutic effect. However, a therapeutic valproate serum concentration for most patients with absence seizures is considered to range from 50 to 100 mcg/mL. Some patients may be controlled with lower or higher serum concentrations (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
As the divalproex sodium dosage is titrated upward, blood concentrations of phenobarbital and/or phenytoin may be affected (see Pharmacology under Actions).
Antiepilepsy 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.
Migraine Prophylaxis: The recommended starting dose is 500 mg once daily for one week, thereafter increasing to 1,000 mg once daily. Although doses other than 1,000 mg once daily of divalproex sodium extended-release have not been evaluated in patients with migraine, the effective dose range of divalproex sodium enteric-coated tablets in these patients is 500 to 1,000 mg/day. As with other valproate products, doses of divalproex sodium extended-release should be individualized and dose adjustment may be necessary. Divalproex sodium extended-release tablets are not bioequivalent to divalproex sodium enteric-coated tablets (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). If a patient requires smaller dose adjustments than that available with divalproex sodium extended-release, divalproex sodium enteric-coated tablets should be used instead.
Divalproex sodium should only be initiated and supervised by a specialist experienced in the management of migraine. Treatment should only be initiated if other treatments are ineffective or not tolerated and the benefit and risk should be carefully reconsidered at regular treatment reviews.
Conversion to Divalproex Sodium Extended-Release: In adult patients and pediatric patients 10 years of age or older with epilepsy previously receiving divalproex sodium, the divalproex sodium ER should be administered once-daily using 8 to 20% higher than the total daily dose of divalproex sodium (see Table 4). For patients whose divalproex sodium total daily dose cannot be directly converted to divalproex sodium ER, consideration may be given at the clinician's discretions to increase the patient's divalproex sodium total daily dose to the next higher dosage before converting to the appropriate total daily dose of divalproex sodium ER. There is insufficient data to allow a conversion factor recommendation for patients with divalproex sodium doses above 3,125 mg/day. (See Table 4.)
Click on icon to see table/diagram/imagePlasma valproate Cmin concentrations for divalproex sodium ER are equivalent to divalproex sodium but may vary across patients after conversion. 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).
General Dosage Advice: Geriatric: Due to a 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. Starting doses in the elderly lower than 250 mg can only be achieved by the use of other divalproex sodium formulations. 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 both tolerability and clinical response (see Use in the Elderly under Precautions and Pharmacology: Pharmacokinetics: Special Populations: Geriatric under Actions).
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. Irritation: Patients who experience G.I. irritation may benefit from administration of the drug with food or by therapy with a lower dose of divalproex sodium enteric-coated tablets.
Compliance: Patients should be informed to take divalproex sodium extended-release every day as prescribed. If a dose is missed, it should be taken as soon as possible, unless it is almost time for the next dose. If a dose is skipped, the patient should not double the next dose.
Divalproex sodium (Depakote ER) extended-release tablets are for oral administration.
Divalproex sodium (Depakote ER) extended-release tablets are intended for once-a-day oral administration.
Divalproex sodium (Depakote ER) extended-release tablets should be swallowed whole and should not be crushed or chewed. A divalproex sodium extended-release tablet is an extended-release product intended for once-a-day administration.
Continue with Google