Divalproex Sodium D/r

1.1 Mania Divalproex sodium is a valproate and is indicated for the treatment of the manic episodes associated with bipolar disorder. A manic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood. Typical symptoms of mania include pressure of speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity, poor judgment, aggressiveness, and possible hostility. The efficacy of divalproex sodium delayed-release tablets was established in 3-week trials with patients meeting DSM-III-R criteria for bipolar disorder who were hospitalized for acute mania [see Clinical Studies (14.1)].

The following serious adverse reactions are described below and elsewhere in the labeling: • Hepatic Failure [see Warnings and Precautions (5.1)] • Birth Defects [see Warnings and Precautions (5.2)] • Decreased IQ Following in Utero Exposure [see Warnings and Precautions (5.3)] • Pancreatitis [see Warnings and Precautions (5.5)] • Hyperammonemic Encephalopathy [see Warnings and Precautions (5.6, 5.9, 5.10)] • Suicidal Behavior and Ideation [see Warnings and Precautions (5.7)] • Bleeding and Other Hematopoietic Disorders [see Warnings and Precautions (5.8)] • Hypothermia [see Warnings and Precautions (5.11)] • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Reactions [see Warnings and Precautions (5.12)] • Serious Dermatologic Reactions [see Warning...

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. 5.1 Hepatotoxicity General Information on Hepatotoxicity Hepatic failure resulting in fatalities has occurred in patients receiving valproate. 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 of valproate therapy. Divalproex sodium is contraindicated in patients: with hepatic disease or significant hepatic dysfunction [see Warnings and Precautions (5.1)]. 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....