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Divalproex Sodium Dosage

Applies to the following strength(s): 250 mg125 mg500 mg

The information at Drugs.com is not a substitute for medical advice. ALWAYS consult your doctor or pharmacist.

Usual Adult Dose for:

Usual Pediatric Dose for:

Additional dosage information:

Usual Adult Dose for Epilepsy

For delayed-release, extended-release tablets, coated pellets (sprinkle capsules):
-COMPLEX PARTIAL SEIZURES:
Initial Therapy: 10 to 15 mg/kg/day orally
Titration: Increase by 5 to 10 mg/kg/week to achieve optimal clinical response
Maintenance: Usually below 60 mg/kg/day
Maximum dose: No recommendation regarding safety at doses above 60 mg/kg/day can be made
-SIMPLE AND COMPLEX ABSENCE SEIZURES:
Initial Therapy: 15 mg/kg/day orally
Titration: Increase at one week intervals by 5 to 10 mg/kg/day until seizures are controlled or side effects preclude further increases
Maximum Recommended Dose: 60 mg/kg/day

Comments:
-Extended-release tablets are intended for once a day oral administration.
-When using delayed-release tablets, total daily doses in excess of 250 mg should be given in divided doses.

Uses: As monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizures and also for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures

Usual Adult Dose for Mania

Delayed-release tablets:
Initial dose: 750 mg orally per day in divided doses
Titration: The dose should be rapidly titrated to achieve the lowest therapeutic dose which produces the desired clinical effect or the desired range of plasma concentrations.
Maximum dose: 60 mg/kg/day

Extended-release tablets:
Initial dose: 25 mg/kg orally once a day
Titration: Increase as rapidly as possible to achieve the lowest therapeutic dose which produces the desired clinical effect or the desired range of plasma concentrations.
Maximum dose: 60 mg/kg/day

Use: For the treatment of the manic episodes associated with bipolar disorder

Usual Adult Dose for Migraine Prophylaxis

Delayed-release tablets:
Initial dose: 250 mg orally 2 times a day
Maintenance dose: Some patients may benefit from doses up to 1000 mg per day.

Extended-release tablets:
Initial dose: 500 mg orally once a day for 1 week
Maintenance dose: May increase to 1000 mg orally once a day

Use: For prophylaxis of migraine headaches

Usual Pediatric Dose for Epilepsy

10 years of age and older:
For delayed-release, extended-release tablets, coated pellets (sprinkle capsules):
-COMPLEX PARTIAL SEIZURES:
Initial Therapy: 10 to 15 mg/kg/day orally
Titration: Increase by 5 to 10 mg/kg/week to achieve optimal clinical response
Maintenance: Usually below 60 mg/kg/day
Maximum dose: No recommendation regarding safety at doses above 60 mg/kg/day can be made
-SIMPLE AND COMPLEX ABSENCE SEIZURES:
Initial Therapy: 15 mg/kg/day orally
Titration: Increase at one week intervals by 5 to 10 mg/kg/day until seizures are controlled or side effects preclude further increases
Maximum Recommended Dose: 60 mg/kg/day

Comments:
-Extended-release tablets are intended for once a day oral administration.
-When using delayed-release tablets, total daily doses in excess of 250 mg should be given in divided doses.

Uses: As monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizures and also for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Severe hepatic dysfunction: Contraindicated

Dose Adjustments

-This drug should be started at a low dose and titrated to a clinically effective dose in patients who are stabilized on rufinamide therapy.
-In geriatric patients, the initial dose should be reduced. Dosing should also be increased more slowly. The ultimate therapeutic dose should be achieved on the basis of clinical response.
-The lowest effective dose should be adapted individually when continuing treatment of manic episodes in bipolar disorder.
-In patients already treated with anticonvulsants, therapy should be tapered with the target dose being achieved after about 2 weeks. This could be faster if plasma level monitoring is available.
-When used in combination with anticonvulsants that induce liver enzyme activity (e.g., phenytoin, phenobarbital, and carbamazepine), the dose could be increased by 5 to 10 mg/kg/day. A reduced dose of divalproex sodium could be used to maintain control if the known enzyme inducers have been removed.
-The barbiturate dose should be reduced during concomitant administration with divalproex sodium, especially if sedation is observed. A reduced dose of divalproex sodium could be required if used with other psychotropic drugs.
-The optimum dose of this drug is determined by control of symptoms. Where poor control or side effects are experienced, measurement of plasma levels should be available and may be helpful.

Precautions

US BOXED WARNINGS:
-Hepatic failure resulting in fatalities has occurred in patients taking this drug. Children younger than 2 years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease. This drug should be used with extreme caution and only as monotherapy. Fatal hepatotoxicity decreases considerably in older patients. This usually occurs during the first 6 months of treatment and may be preceded by nonspecific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting. In patients with epilepsy, a loss of seizure control may occur. Liver function tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first 6 months.
-This drug can cause teratogenic effects such as neural tube defects (e.g., spina bifida). Use in women of childbearing potential requires that benefit be weighed against the risk to the fetus. Use is contraindicated in pregnant patients for migraine headache.
-There is an increased risk of valproate-induced acute liver failure and deaths in patients with hereditary neurometabolic syndromes caused by DNA mutations of the mitochondrial DNA Polymerase y (POLG) gene (e.g., Alpers Huttenlocher Syndrome).
-Cases of life-threatening pancreatitis have been reported in patients receiving valproate; some cases were hemorrhagic with a rapid progression from initial symptoms to death. Cases have been reported initially and after prolonged use. Abdominal pain, nausea, vomiting and/or anorexia can be symptoms of pancreatitis. If pancreatitis is diagnosed, treatment should be discontinued.

Safety and efficacy have not been established in patients younger than 10 years for epilepsy or younger than 18 years for any other indication.

Consult WARNINGS section for additional precautions.

Dialysis

Hemodialysis reduces serum valproate concentrations by approximately 20%; however, no specific dose adjustment guidelines have been suggested

Other Comments

Administration advice:
-The daily dose of this drug should be determined according to age and body weight. The wide variation in individual sensitivity to this drug should be taken into account.
-This drug should not be used concomitantly with salicylates since they use the same metabolic pathway.
-The tablets are intended for oral administration only. They should be swallowed whole with water and not crushed or chewed.
-The delayed-release capsules may be swallowed whole or the contents may be sprinkled on soft food. The drug/food mixture should be swallowed immediately (avoid chewing).

Monitoring:
-Doses greater than 45 mg/kg/day need careful monitoring

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