Classes
DEA Class; Rx
Common Brand Names; Depakote, Depakote ER, Depakote Sprinkles
- Anticonvulsants, Other
Description
Oral and parenteral anti-epileptic drug
Used for monotherapy and adjunctive therapy of complex partial seizures and simple and complex absence seizures, adjunctive therapy in patients with multiple seizure types, bipolar disorder, and migraine prophylaxis
Associated with life-threatening hepatic failure and pancreatitis and increased risk of suicidal ideation and behavior
Indications
Indicated for treatment of manic episodes associated with bipolar disorder
Epilepsy
- Complex partial seizures: Indicated as monotherapy and adjunctive therapy for complex partial seizures that occur either in isolation or in association with other types of seizures
- Simple and complex absence seizures: Also indicated 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
Indicated for prophylaxis of migraine headaches; there is no evidence of use for acute treatment
Contraindications
Hypersensitivity
Liver disease, significant hepatic impairment
Urea cycle disorders
Mitochondrial disorders caused by mutations in mitochondrial DNA polymerase-gamma (POLG; eg, Alpers-Huttenlocher Syndrome) and children <2 years of age who are suspected of having a POLG-related disorder
Migraine headache prevention in women who are pregnant or plan to become pregnant
Adverse Effects
- Nausea (48%)
- Headache (31%)
- Asthenia (27%)
- Vomiting (27%)
- Somnolence (27%)
- Tremor (25%)
- Dizziness (25%)
- Abdominal pain (23%)
- Diplopia (16%)
- Diarrhea (13%)
- Anorexia (12%)
- Amblyopia/blurred vision (12%)
- Flu syndrome (12%)
- Infection (12%)
- Dyspepsia (8%)
- Ataxia (8%)
- Nystagmus (8%)
- Fever (6%)
- Emotional lability (6%)
- Thinking abnormal (6%)
- Alopecia (6%)
- Weight loss (6%)
- Constipation (5%)
- Amnesia (5%)
- Bronchitis (5%)
- Rhinitis (5%)
- Cerebral pseudoatrophy (acute or subacute cognitive decline and behavioral changes (apathy or irritability)
Warnings
Probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations exceed 110 mcg/mL in females and 135 mcg/mL in males
Hepatotoxic (age <2 years, higher risk of fatal hepatotoxicity); see Black Box Warnings
POLG mutations; see Contraindications and Black Box Warnings
Discontinue if hyperammonemia/encephalopathy occurs; check ammonia level if emesis occurs or if the patient displays lethargy or abnormal behavior; evaluate patient for urea cycle disorder (see Contraindications) or hepatotoxicity (see Black Box Warnings);
Pancreatitis, including fatalities reported (see Black Box Warnings)
Hypothermia has been reported during valproate therapy with or without associated hyperammonemia; this adverse reaction can also occur in patients using concomitant topiramate
In utero exposure increases risk for poor cognitive outcomes and anatomical malformations, compared with 3 other common AEDs (carbamazepine, lamotrigine, phenytoin); see Black Box Warnings
Potential for thrombocytopenia, porphyria, and multiorgan hypersensitivity reaction (also known as drug reaction with eosinophilia and systemic symptoms or DRESS)
May produce false-positive urine ketone test and alter TFTs
Reversible cerebral and cerebellar atrophy reported; monitor motor and cognitive function routinely and assess for signs and symptoms of brain atrophy
May cause CNS depression and impair physical or mental abilities
Somnolence in the elderly can occur; divalproex dosage should be increased slowly and with regular monitoring for fluid and nutritional intake
Not for administration to post-traumatic seizure prophylaxis in patients with acute head trauma (increased mortality reported when used)
Pregnancy and Lactation
A pregnancy exposure registry monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), during pregnancy
Drug is excreted in human milk; data in the published literature describe presence of valproate in human milk; there are no data to assess effects of drug on milk production or excretion
Maximum Dosage
60 mg/kg/day PO or IV for the treatment of seizures; 1,000 mg/day PO for migraine prophylaxis; 60 mg/kg/day PO for bipolar mania.
60 mg/kg/day PO or IV for the treatment of seizures; 1,000 mg/day PO for migraine prophylaxis; 60 mg/kg/day PO for bipolar mania.
60 mg/kg/day PO or IV for seizures; 40 mg/kg (Max: 3,000 mg/dose) IV once for status epilepticus; 1,000 mg/day for migraine prophylaxis; 1,500 mg/day for conduct disorders.
10 to 12 years: 60 mg/kg/day PO or IV for seizures; 40 mg/kg (Max: 3,000 mg/dose) IV once for status epilepticus; 1,000 mg/day for migraine prophylaxis; 1,500 mg/day PO for conduct disorders.
2 to 9 years: Safety and efficacy have not been established. Specific maximum dosage information not available; individualize dosage based on clinical parameters and monitoring of serum valproate concentrations. FDA-approved labeling suggests 60 mg/kg/day for all dosage forms; little data regarding safety at doses above this exists. For status epilepticus, 40 mg/kg (Max: 3,000 mg/dose) IV once. Do not use extended-release products.
1 year: Safety and efficacy have not been established; use is not generally recommended due to an increased risk of fatal hepatotoxicity. Specific maximum dosage information not available; individualize dosage based on clinical parameters and monitoring of serum valproate concentrations. FDA-approved labeling suggests 60 mg/kg/day for all dosage forms; little data regarding safety at doses above this exists. For status epilepticus, 40 mg/kg IV once. Do not use extended-release products.
Safety and efficacy have not been established; use is not generally recommended due to an increased risk of fatal hepatotoxicity. Specific maximum dosage information not available; individualize dosage based on clinical parameters and monitoring of serum valproate concentrations. FDA-approved labeling suggests 60 mg/kg/day for all dosage forms; little data regarding safety at doses above this exists. For status epilepticus, 40 mg/kg IV once. Do not use extended-release products.
Safety and efficacy have not been established; use is not generally recommended due to an increased risk of fatal hepatotoxicity. Specific maximum dosage information not available; individualize dosage based on clinical parameters and monitoring of serum valproate concentrations. FDA-approved labeling suggests 60 mg/kg/day for all dosage forms; little data regarding safety at doses above this exists. For status epilepticus, 40 mg/kg IV once. Do not use extended-release products.
How supplied
Divalproex Sodium
Dosages expressed as valproic acid equivalents
tablet, delayed-release (Depakote)
- 125mg
- 250mg
- 500mg
tablet, extended-release (Depakote ER)
- 250mg
- 500mg
capsule (Depakote Sprinkles)
- 125mg
