Valproate Sodium (2 brand names, 1 dosage form, 1 route)
Available dosage forms: INJECTABLE.
Routes of administration: INJECTION.
Brand Names
- DEPACON
- VALPROATE SODIUM
Related Health Topics
Contraindications
Valproate Sodium Injection should not be administered to patients with hepatic disease or significant hepatic dysfunction [see Warnings and Precautions (5.1)]. Valproate Sodium Injection is 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)]. Valproate Sodium Injection is contraindicated in patients with known hypersensitivity to the drug [see Warnings and Precautions (5.11)]. Valproate Sodium Injection is contraindicated in patients with known urea cycle disorders [see Warnings and Precautions (5.6)]. For use in prophylaxis of migraine headaches: Valproate 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)].
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, 5.8, 5.9)] Bleeding and other hematopoietic disorders [see Warnings and Precautions (5.7)] Hypothermia [see Warnings and Precautions (5.10)] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ hypersensitivity reactions [see Warnings and Precautions (5.11)] Somnolence in the elderly [see Warnings and Precautions (5.13)] 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. The adverse reactions that can result from Valproate Sodium Injection use include all of those associated with oral forms of valproate. The following describes experience specifically with Valproate Sodium Injection. Valproate Sodium Injection has been generally well tolerated in clinical trials involving 111 healthy adult male volunteers and 352 patients with epilepsy, given at doses of 125 to 6,000 mg (total daily dose). A total of 2% of patients discontinued treatment with Valproate Sodium Injection due to adverse reactions. The most common adverse reactions leading to discontinuation were 2 cases each of nausea/vomiting and elevated amylase. Other adverse reactions leading to discontinuation were hallucinations, pneumonia, headache, injection site reaction, and abnormal gait. Dizziness and injection site pain were observed more frequently at a 100 mg/min infusion rate than at rates up to 33 mg/min. At a 200 mg/min rate, dizziness and taste perversio
Mechanism of Action
Valproate sodium exists as the valproate ion in the blood. The mechanisms by which valproate exerts its therapeutic effects have not been established. It has been suggested that its activity in epilepsy is related to increased brain concentrations of gamma-aminobutyric acid (GABA).
Overdosage
Overdosage with valproate may result in somnolence, heart block, deep coma and hypernatremia. Fatalities have been reported; however patients have recovered from valproate serum concentrations 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. 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.