Valproate sodium (Intravenous)

Hepatotoxicity (some cases fatal), usually occurring during the first 6 months of treatment, has been reported in patients receiving valproate and its derivatives. Loss of seizure control may also occur in patients with epilepsy. Children younger than 2 years, especially receiving multiple anticonvulsants, those with congenital metabolic disorders, severe seizure disorders with mental retardation, with organic brain disease, and patients with hereditary mitochondrial disease are at a considerably increased risk of developing fatal hepatotoxicity. For patients under 2 years, valproate sodium should be used with extreme caution as a sole agent. Use is contraindicated in patients with known mitochondrial disorders caused by mitochondrial DNA polymerase gamma (POLG) gene mutations and in children younger than 2 years in which mitochondrial disorder is clinically suspected. Failure of other anticonvulsants is the only indication for valproate sodium in patients older than 2 years with hereditary mitochondrial disease. Perform POLG mutation screening as clinically indicated. Monitor patients closely and perform liver function tests prior to therapy and at frequent intervals thereafter, especially during the first 6 months. Valproate can impair cognitive development with prenatal exposure and produce major congenital malformations, particularly neural tube defects (eg, spina bifida). In addition, valproate can caused decreased IQ scores and neurodevelopmental disorders following in utero exposure. Valproate is contraindicated for prophylaxis of migraine headaches in pregnant women and women of childbearing potential who are not using effective contraception. Valproate should not be administered to a woman of childbearing potential unless other medications have failed or are otherwise unacceptable. Effective contraception should be used in such situations. Life-threatening pancreatitis has been reported in both children and adults receiving valproate. Cases have occurred shortly after initiation as well as several years after use. If pancreatitis is diagnosed, valproate should ordinarily be discontinued .