Valproic Acid Dosage
This dosage information may not include all the information needed to use Valproic Acid safely and effectively. See additional information for Valproic Acid.
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Usual Adult Dose for:
Usual Pediatric Dose for:
Additional dosage information:
Usual Adult Dose for Seizure Prophylaxis
Valproate sodium injection:
Initial dose: 10 to 15 mg/kg/day intravenously divided over 4 doses administered every 6 hours.
Maintenance dose: 30 to 60 mg/kg/day intravenously divided over 4 doses administered every 6 hours.
Intravenous doses may be broken into 2 to 3 divided doses/day. However, if this frequency is chosen, trough levels should be carefully monitored.
Use of valproate sodium injection for periods of more than 14 days has not been studied. Patients should be switched to oral valproate products as soon as it is clinically feasible.
Capsules or syrup:
Initial dose: 10 to 15 mg/kg/day orally in 1 to 3 divided doses
Maintenance dose: 30 to 60 mg/kg/day orally in 2 to 3 divided doses
Total daily doses in excess of 250 mg should be given in divided doses.
Usual Adult Dose for Mania
Initial dose: 750 mg valproic acid delayed release capsules orally daily in divided doses. Delayed release capsules must be swallowed whole.
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 placebo-controlled clinical trials of acute mania, patients were dosed to a clinical response with a trough plasma concentration between 50 and 125 mcg per mL. Maximum concentrations were generally achieved within 14 days.
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 valproic acid delayed release capsules 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 systematically obtained data to support the benefits of valproic acid delayed release capsules in such longer-term treatment.
Usual Adult Dose for Migraine Prophylaxis
Initial dose: 250 mg valproic acid delayed release capsules orally twice daily. Valproic acid delayed release capsules must be swallowed whole.
Some patients may benefit from doses up to 1000 mg/day. In clinical trials, there was no evidence that higher doses led to greater efficacy.
Usual Pediatric Dose for Seizure Prophylaxis
Limited data are available for neonatal dosing; further studies are needed.
Refractory seizures: Oral: Loading dose: 20 to 25 mg/kg, followed by a maintenance dose of 5 to 10 mg/kg every 12 hours; a report of 6 neonates (30-41 weeks gestation) showed oral valproic acid effectively controlled seizure activity in 5 of 6 patients; therapy was discontinued in 50% of the patients due to hyperammonemia; frequent monitoring is recommended.
Refractory status epilepticus: IV: Loading dose: 20 to 40 mg/kg followed by a continuous infusion of 5 mg/kg/hour was used in 5 neonates; once patients were seizure free for 12 hours and no longer had seizure activity on EEG, the infusion rate was decreased every 2 hours by 1 mg/kg/hour.
Note: Use of Depakote-ER (R) in pediatric patients less than 10 years of age is not recommended; do not confuse Depakote-ER (R) with Depakote (R). Erroneous substitution of Depakote (R) (delayed release tablets) for Depakote-ER (R) has resulted in toxicities; only Depakote-ER (R) is intended for once daily administration.
Seizures disorders: Children and Adults:
Oral: Initial: 10 to 15 mg/kg/day in 1 to 3 divided doses; increase by 5 to 10 mg/kg/day at weekly intervals until therapeutic levels are achieved; maintenance: 30 to 60 mg/kg/day in 2 to 3 divided doses; Depakote (R) and Depakote (R) Sprinkle can be given twice daily.
Note: Children receiving more than 1 anticonvulsant (i.e., polytherapy) may require doses up to 100 mg/kg/day in 3 to 4 divided doses. Due to differences in bioavailability, children greater than or equal to 10 years of age and adult epilepsy patients receiving Depakote (R) may be switched to Depakote-ER (R) by using a once daily Depakote-ER (R) dose that is 8 to 20% higher than the total daily dose of Depakote (R) (see Depakote-ER (R) package insert for details).
IV: Total daily IV dose is equivalent to the total daily oral dose, however, IV dose should be divided with a frequency of every 6 hours; if IV form is administered 2 to 3 times/day, close monitoring of trough levels is recommended; switch patients to oral product as soon as possible (IV use has not been studied for greater than 14 days).
Rectal: Dilute syrup 1:1 with water for use as a retention enema; loading dose: 17 to 20 mg/kg one time; maintenance: 10 to 15 mg/kg/dose every 8 hours.
Refractory status epilepticus:
Infants and Children:
IV: Loading dose: Initial: Optimal dosage is not established; pediatric studies have used initial loading doses of 20 to 40 mg/kg.
Note: In one retrospective study, an initial loading dose of 25 mg/kg administered 3 mg/kg/minute was effective in stopping seizure activity within 20 minutes after the end of the infusion in all 18 patients treated for status epilepticus. A separate retrospective trial found a higher efficacy rate in pediatric patients (n=41) who received an initial loading dose of 30 to 40 mg/kg (compared to 20 to 30 mg/kg or greater than 40 mg/kg). In an open label, randomized comparative trial, an initial loading dose of 30 mg/kg was administered (n=20; age range: 7 months to 10 years of age; mean age: 3 years); a repeat bolus of 10 mg/kg could be administered if seizures were not controlled within 10 minutes; mean required dose: 37.5 plus or minus 4.4 mg/kg; median required dose: 40 mg/kg. Further studies are needed.
IV: Maintenance dose: IV infusion: Optimal dosage is not established; pediatric studies used continuous infusions of 5 mg/kg/hour after the loading dose; once patients were seizure free for 6 hours, the infusion rate was decreased by 1 mg/kg/hour every 2 hours. Further studies are needed.
Renal Dose Adjustments
Data not available
Liver Dose Adjustments
Valproic acid should not be used in patients with hepatic disease or significant dysfunction.
The dose can be increased by 5 to 10 mg/kg/day until seizures are controlled or side effects preclude further increases.
Hemodialysis reduces valproate concentrations by about 20%.
No recommendations regarding the safety of doses above 60 mg/kg/day can be made.
Valproic acid may be administered with food to decrease adverse gastrointestinal side effects.