Classes
DEA Class; Rx
Common Brand Names; Depakene (DSC), Stavzor (DSC)
- Anticonvulsants, Other
Description
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 as monotherapy and adjunctive therapy for complex partial seizures that occur either in isolation or in association with other types of 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
Indicated for treatment of manic episodes associated with bipolar disorder
Contraindications
Hypersensitivity
Liver disease, significant hepatic impairment
Urea cycle disorder
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 (31%)
- Headache (<31%)
- Increased bleeding time (26-30%)
- Thrombocytopenia (26-30%)
- Tremor (25%)
- Alopecia (<24%)
- Asthenia (16-20%)
- Infection (16-20%)
- Somnolence (16-20%)
- Amblyopia (11-15%)
- Diarrhea (11-15%)
- Diplopia (11-15%)
- Dizziness (11-15%)
- Dyspepsia (11-15%)
- Nystagmus (11-15%)
- Tinnitus (11-15%)
- Vomiting (11-15%)
- Ataxia (<8%)
- Increased appetite (<6%)
- Rash (<6%)
- Abdominal pain (<5%)
- Tremor (<5%)
- Back pain (<5%)
- Mood changes (<5%)
- Anxiety (<5%)
- Confusion (<5%)
- Abnormal gait (<5%)
- Paresthesia (<5%)
- Hallucinations (<5%)
- Catatonia (<5%)
- Dysarthria (<5%)
- Tardive dyskinesia (<5%)
- Vertigo (<5%)
- Irregular menses (<5%)
- Weight gain (4%)
- Anorexia
- Acute pancreatitis (may be life-threatening)
- Hepatic toxicity
- Hyperammonemia
- Weight loss
- Fractures
- Osteoporosis
- Osteopenia
- Decreased bone mineral density
- 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; because of reports of cytopenias, inhibition of secondary phase of platelet aggregation, and abnormal coagulation parameters (eg, low fibrinogen, coagulation factor deficiencies, acquired von Willebrand’s disease)
Measurements of complete blood counts and coagulation tests are recommended before initiating therapy and at periodic intervals; recommended that patients receiving drug be monitored for blood counts and coagulation parameters prior to planned surgery and during pregnancy; evidence of hemorrhage, bruising, or a disorder of hemostasis/coagulation is an indication for reduction of dosage or withdrawal of therapy
Medication residue in the stool reported; some patients have had anatomic (including ileostomy or colostomy) or functional gastrointestinal disorders with shortened GI transit times; in some reports, medication residues have occurred in the context of diarrhea; recommended that plasma valproate levels be checked in patients who experience medication residue in the stool, and patients’ clinical condition monitored; If clinically indicated, may consider alternative treatment
Bleeding and other hematopoietic disorders may occur; monitor platelet counts and coagulation tests
Hepatotoxic (age <2 years, higher risk of fatal hepatotoxicity); evaluate high risk populations and monitor serum liver tests; risk factors include organic brain disease, mental retardation with severe seizure disorders, congenital metabolic disorders, and patients on multiple anticonvulsants; discontinue immediately with signs/symptoms of significant or suspected impairment
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
Valproic acid
capsule
- 250mg
syrup
- 250mg/5mL
injectable solution (as valproate sodium)
- 100mg/mL
