Valproic Acid - Adverse Effects

Adverse Effects

The extent of the adverse effects is related to the dosage. The less valproic acid used, the less adverse effects, and the more valproic used, the more adverse effects experienced.

The foremost and most severe concern for anyone taking valproic acid is its potential for sudden and severe, possibly fatal, fulminating impairments in liver and impairments of hematopoietic and/or pancreatic function, especially in those just starting the medication. This particular warning is the first one listed on any drug adverse effect listing when one receives the drug at the pharmacy.

In rare reports, individuals having used valproic acid for a long time (chronic users) have suffered renal impairment, usually as a result of having been injured or ill or on a drug regimen already and, so, having been overwhelmed.

Valproate is also cautioned against in many patients because it can cause weight gain.

Pre-existing severe hepatic (liver) and/or renal (kidney) damage and certain cases of metastatic cancer, severe hepatitis or pancreatitis, end-stage AIDS HIV infection, marked bone marrow depression, urea cycle disorders, and coagulation hematological disorders that have caused impairment are absolute contraindications. Some patients with symptomatic but manageable AIDS, cancer, and hepatic or renal disease are kept on the medication (usually at a reduced dose with more frequent blood tests) to avoid having to manipulate the drug regimen for as long as possible.

Common side effects are dyspepsia and/or weight gain. Less common are fatigue, peripheral edema, acne, dizziness, drowsiness, hair loss, headaches, nausea, sedation, and tremors. Valproic acid also causes hyperammonemia, an increase of ammonia levels in the blood, which can lead to vomiting and sluggishness, and ultimately to mental changes and brain damage. Valproate levels within the normal range are capable of causing hyperammonemia and ensuing encephalopathy. Taking lactulose may alleviate the hyperammonemia. There have been reports of the development of brain encephalopathy without hyperammonemia or elevated valproate levels.

In rare circumstances, valproic acid can cause blood dyscrasia, impaired liver function, jaundice, thrombocytopenia, and prolonged coagulation (clotting) times due to a lack of blood cells. In about 5% of pregnant users, valproic acid will cross the placenta and cause congenital anomalies that resemble fetal alcohol syndrome, with a possibility of cognitive impairment. Due to these side effects, most doctors will try to continue the medication, but will ask for blood tests, initially as often as once a week and then once every two months (those taking it for a long period may go six months before being retested; if a pregnant woman and her doctor decide to keep using the drug and to keep the pregnancy, then frequent blood testing, and possibly a higher frequency of diagnostic ultrasounds to identify fetal problems, is a must). Temporary liver enzyme increase has been reported in 20% of cases during the first few months of taking the drug. Inflammation of the liver (hepatitis), the first symptom of which is jaundice, is found in rare cases.

Valproic acid may also cause acute hematological toxicities, especially in children, including rare reports of myelodysplasia and acute leukemia-like syndrome.

Cognitive dysfunction, Parkinsonian symptoms, and even (reversible) pseudoatrophic brain changes have been reported in long-term treatment with valproic acid.

According to the information provided with a prescription of this drug, some individuals have become depressed or had a suicidal ideation while on the drug; those taking it should be monitored for this side effect.