Divalproex Sodium Er

⛔ FDA Black Box Warning

Hepatotoxicity - General Population: Hepatic failure resulting in fatalities has occurred in patients receiving valproate and its derivatives. These incidents usually have occurred during the ... WARNING: LIFE THREATENING ADVERSE REACTIONS Hepatotoxicity General Population: Hepatic failure resulting in fatalities has occurred in patients receiving valproate and its derivatives. These incidents usually have occurred during the first six months of treatment. Serious or fatal hepatotoxicity may be preceded by non-specific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting. In patients with epilepsy, a loss of seizure control may also occur. Patients should be monitored closely for appearance of these symptoms. Serum liver tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six months [see Warnings and Precautions (5.1)]. Children under the age of two years 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. When divalproex sodium extended-release tablets are used in this patient group, it should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks. The incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups. Patients with Mitochondrial Disease: 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). Divalproex sodium extended-release tablets are contraindicated in patients known to have mitochondrial disorders caused by POLG mutations and children under two years of age who are c

Contraindications

Divalproex sodium extended-release tablets should not be administered to patients with hepatic disease or significant hepatic dysfunction [see Warnings and Precautions (5.1)]. Divalproex sodium extended-release tablets are contraindicated in patients known to have mitochondrial disorders caused by mutations in mitochondrial DNA polymerase γ (POLG; e.g, Alpers-Huttenlocher Syndrome) and children under two years of age who are suspected of having a POLG-related disorder [see Warnings and Precautions (5.1)] . Divalproex sodium extended-release tablets are contraindicated in patients with known hypersensitivity to the drug [see Warnings and Precautions (5.12)]. Divalproex sodium extended-release tablets are contraindicated in patients with known urea cycle disorders [see Warnings and Precautions (5.6)]. For use in prophylaxis of migraine headaches: Divalproex sodium extended-release tablet is contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see Warnings and Precautions (5.2, 5.3, 5.4) and Use in Specific Populations (8.1)] .