Valpros Pedia Warnings

Hepatotoxicity: Hepatic failure resulting in fatalities has occurred in patients receiving valproate and its derivatives, usually during the first 6 months of treatment. Children less than two years old are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease. Above this age group, experience in epilepsy has indicated that the incidence of fatal hepatotoxicity decreased considerably in progressively older patient (see Precautions).
There is an increased risk of valproate-induced acute liver failure and resultant deaths in patients with hereditary neurometabolic syndromes caused by DNA mutations of the mitochondrial DNA polymerase-γ (POLG) gene (e.g., Alpers Huttenlocher Syndrome). Sodium valproate is contraindicated in patients known to have mitochondrial disorders caused by POLG mutations and children < 2 years old who are clinically suspected of having a mitochondrial disorder (see Contraindications).
Fetal Risk: Valproate can produce teratogenic effects such as neural tube defects (e.g., spina bifida). In addition, valproate can cause decreased IQ scores following in utero exposure. Accordingly, the use of sodium valproate syrup in women of childbearing potential requires that the benefits of its use be weighed against the risk of injury to the fetus (see Statement on Usage in High Risks Groups under Precautions).
Pancreatitis: Cases of life-threatening pancreatitis have been reported in both adults and children receiving sodium valproate. Some of the cases have been described as hemorrhagic with a rapid progression from initial symptoms to death. Cases have been reported shortly after initial use as well as after several years of use.
Young children are at particular risk for pancreatitis. However, the risk is decreased with increasing age. Potential risk factors include severe seizures, neurological impairment or anticonvulsant polytherapy. Hepatic failure with pancreatitis increases the risk of fatal outcome. Patients and guardians should be warned that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis that require prompt medical evaluation. if pancreatitis is diagnosed, sodium valproate should ordinarily be discontinued. Alternative treatment for the underlying medical condition should be initiated as clinically indicated.