VALPROIC ACID

Warning

Hepatotoxicity, fetal risk, and pancreatitis

Contraindications

• Hepatic disease or significant hepatic dysfunction
• Known mitochondrial disorders caused by mutations in mitochondrial DNA polymerase γ (POLG)
• Known hypersensitivity to the drug
• Urea cycle disorders
• Pregnant women and women of childbearing potential who are not using effective contraception for prophylaxis of migraine headaches

Adverse Reactions

• Hepatic failure
• Birth defects
• Decreased IQ following in utero exposure
• Pancreatitis
• Hyperammonemic encephalopathy
• Suicidal behavior and ideation
• Bleeding and other hematopoietic disorders
• Hypothermia
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan hypersensitivity reactions
• Somnolence in the elderly

General Guidance

Dose adjustments should be made based on clinical response and plasma concentrations, with consideration for patients with hepatic or renal impairment, as well as those taking other medications that may interact with valproic acid.

Pregnancy

• Valproic acid is contraindicated for prophylaxis of migraine headaches in pregnant women and in women of childbearing potential who are not using effective contraception
• Valproate should not be used to treat women with epilepsy or bipolar disorder who are pregnant or who plan to become pregnant unless other medications have failed to provide adequate symptom control or are otherwise unacceptable

Nursing Mothers

• Valproic acid is excreted in human milk, and nursing mothers should be cautious when taking the drug

Pediatric Use

• Pediatric patients under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity
• The safety and tolerability of valproic acid in pediatric patients were shown to be comparable to those in adults in clinical trials

Geriatric Use

• No patients above the age of 65 years were enrolled in double-blind prospective clinical trials of mania associated with bipolar illness
• A higher percentage of patients above 65 years of age reported accidental injury, infection, pain, somnolence, and tremor in a case review study