Divalproex Sodium (4 brand names, 3 dosage forms, 1 route)
Available dosage forms: TABLET, EXTENDED RELEASE, CAPSULE, DELAYED REL PELLETS, TABLET, DELAYED RELEASE.
Routes of administration: ORAL.
Brand Names
- DEPAKOTE
- DEPAKOTE CP
- DEPAKOTE ER
- DIVALPROEX SODIUM
Related Health Topics
Boxed 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 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 is 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 is contraindicated in patients known to have mitochondrial disorders caused by POLG mutations and children under two years of age who are clinically suspected of having a mitochondrial disorder [see Contraindications (4)]. In patients over two years of age who are clinically suspected of having a hereditary mitochondrial disease, divalproex sodium should only be used after other anticonvulsants have failed. This older group of p
Dosage and Administration
Divalproex sodium delayed-release tablets are intended for oral administration. Divalproex sodium delayed-release tablets should be swallowed whole and should not be crushed or chewed. Patients should be informed to take divalproex sodium delayed-release tablets every day as prescribed. If a dose is missed it should be taken as soon as possible, unless it is almost time for the next dose. If a dose is skipped, the patient should not double the next dose.
Contraindications
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 (5.1)]. with known hypersensitivity to divalproex sodium, sodium valproate, or valproic acid. Reactions have included multiorgan hypersensitivity, serious dermatologic reactions, and angioedema [see Warnings and Precautions (5.12, 5.13, 5.14)]. with known urea cycle disorders [see Warnings and Precautions (5.6)]. being treated for prophylaxis of migraine headaches who are pregnant or 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)].
Adverse Reactions
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 and Neurodevelopmental Disorders 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 Warnings and Precautions (5.13)] Angioedema [see Warnings and Precautions (5.14)] Somnolence in the Elderly [see Warnings and Precautions (5.16)] Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Overdosage
Overdosage with valproate may result in somnolence, heart block, deep coma, and hypernatremia. Fatalities have been reported; however patients have recovered from valproate levels as high as 2,120 mcg/mL. In overdose situations, the fraction of drug not bound to protein is high and hemodialysis or tandem hemodialysis plus hemoperfusion may result in significant removal of drug. The benefit of gastric lavage or emesis will vary with the time since ingestion. General supportive measures should be applied with particular attention to the maintenance of adequate urinary output. Naloxone has been reported to reverse the CNS depressant effects of valproate overdosage. Because naloxone could theoretically also reverse the antiepileptic effects of valproate, it should be used with caution in patients with epilepsy.