These highlights do not include all the information needed to use VALPROIC ACID CAPSULES safely and effectively. See full prescribing information for VALPROIC ACID CAPSULES.
VALPROIC ACID capsules for oral use
Initial U.S. Approval: 1978
WARNING: LIFE THREATENING ADVERSE REACTIONS
SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING.
Hepatotoxicity, including fatalities, usually during the first 6 months of treatment. Children under the age of two years and patients with mitochondrial disorders are at higher risk. Monitor patients closely, and perform serum liver testing prior to therapy and at frequent intervals thereafter (5.1)
Fetal Risk, particularly neural tube defects, other major malformations, and decreased IQ (5.2, 5.3, 5.4)
Pancreatitis, including fatal hemorrhagic cases (5.5)
INDICATIONS AND USAGE
Valproic Acid Capsules are an anti-epileptic drug indicated for:
Monotherapy and adjunctive therapy of complex partial seizures; sole and adjunctive therapy of simple and complex absence seizures; adjunctive therapy in patients with multiple seizure types that include absence seizures (1)
DOSAGE AND ADMINISTRATION
Valproic acid capsules are intended for oral administration. (2.1)
Simple and Complex Absence Seizures: Start at 10 to 15 mg/kg/day, increasing at 1 week intervals by 5 to 10 mg/kg/week until seizure control or limiting side effects (2.1)
Safety of doses above 60 mg/kg/day is not established (2.1, 2.2)
DOSAGE FORMS AND STRENGTHS
Capsules: 250 mg valproic acid (3)
CONTRAINDICATIONS
Hepatic disease or significant hepatic dysfunction (4, 5.1)
Known mitochondrial disorders caused by mutations in mitochondrial DNA polymerase
(POLG) (4, 5.1)
Suspected POLG-related disorder in children under two years of age (4, 5.1)
Known hypersensitivity to the drug (4, 5.12)
Urea cycle disorders (4, 5.6)
WARNINGS AND PRECAUTIONS
Hepatotoxicity; evaluate high risk populations and monitor serum liver tests (5.1)
Birth defects and decreased IQ following in utero exposure; only use to treat pregnant women with epilepsy if other medications are unacceptable; should not be administered to a woman of childbearing potential unless essential (5.2, 5.3, 5.4)
Pancreatitis; valproic acid capsules should ordinarily be discontinued (5.5)
Suicidal behavior or ideation; Antiepileptic drugs, including valproic acid capsules, increase the risk of suicidal thoughts or behavior (5.7)
Bleeding and other hematopoietic disorders; monitor platelet counts and coagulation tests (5.8)
Hyperammonemia and hyperammonemic encephalopathy; measure ammonia level if unexplained lethargy and vomiting or changes in mental status and also with concomitant topiramate use; consider discontinuation of valproate therapy (5.6, 5.9, 5.10)
Hypothermia; Hypothermia has been reported during valproate therapy with or without associated hyperammonemia. This adverse reaction can also occur in patients using concomitant topiramate (5.11)
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan hypersensitivity reaction; discontinue valproic acid capsules (5.12)
Somnolence in the elderly can occur. Valproic acid capsules dosage should be increased slowly and with regular monitoring for fluid and nutritional intake (5.14)
ADVERSE REACTIONS
Most common adverse reactions (reported >5%) are abdominal pain, alopecia, amblyopia/blurred vision, amnesia, anorexia, asthenia, ataxia, bronchitis, constipation, depression, diarrhea, diplopia, dizziness, dyspepsia, dyspnea, ecchymosis, emotional lability, fever, flu syndrome, headache, increased appetite, infection, insomnia, nausea, nervousness, nystagmus, peripheral edema, pharyngitis, rhinitis, somnolence, thinking abnormal, thrombocytopenia, tinnitus, tremor, vomiting, weight gain, weight loss. (6.1)
The safety and tolerability of valproate in pediatric patients were shown to be comparable to those in adults (8.4).
To report SUSPECTED ADVERSE REACTIONS, contact Upsher-Smith Laboratories, LLC at 1-855-899-9180 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
DRUG INTERACTIONS
Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. Therefore increased monitoring of valproate and concomitant drug concentrations and dosage adjustment are indicated whenever enzyme-inducing or inhibiting drugs are introduced or withdrawn (7.1)
Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1)
Coadministration of valproate can affect the pharmacokinetics of other drugs (e.g. diazepam, ethosuximide, lamotrigine, phenytoin) by inhibiting their metabolism or protein binding displacement (7.2)
Patients stabilized on rufinamide should begin valproate therapy at a low dose, and titrate to clinically effective dose (7.2)
Dosage adjustment of amitriptyline/nortriptyline, propofol, warfarin, and zidovudine may be necessary if used concomitantly with valproic acid capsules (7.2)
Topiramate: Hyperammonemia and encephalopathy (5.10, 7.3)
USE IN SPECIFIC POPULATIONS
Pregnancy: Valproic acid capsules can cause congenital malformations including neural tube defects and decreased IQ (5.2, 5.3, 8.1)
Pediatric: Children under the age of two years are at considerably higher risk of fatal hepatotoxicity (5.1, 8.4)
Geriatric: Reduce starting dose; increase dosage more slowly; monitor fluid and nutritional intake, and somnolence (5.14, 8.5)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 4/2018