May 15, 2013
FDA: Valproate Sodium, Related Products Not for Use by Pregnant Women

Washington, D.C.—The antiseizure medications valproate sodium and related products, such as valproic acid and divalproex sodium, are contraindicated for use in pregnant women for prevention of migraine headaches and should be used in epilepsy or bipolar disorder only if other treatments have failed to provide adequate symptom control or are otherwise unacceptable, according to the FDA.

Drug labels will be changed to include stronger warnings about use during pregnancy, and valproate’s pregnancy category for migraine use will be changed from “D” (the potential benefit of the drug in pregnant women may be acceptable despite its potential risks) to "X" (the risk of use in pregnant women clearly outweighs any possible benefit of the drug).

This FDA said its alert is based on the final results of the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study “showing that children exposed to valproate products while their mothers were pregnant had decreased IQs at age 6 compared to children exposed to other antiepileptic drugs…The difference in average IQ between the children who had been exposed to valproate and the children who had been exposed to other antiepileptic drugs varied between 8 and 11 points depending on the drug to which valproate was compared.”

Authors of the study, which was published online in January by the The Lancet Neurology, note that “Fetal valproate exposure has dose-dependent associations with reduced cognitive abilities across a range of domains at 6 years of age. Reduced right-handedness and verbal (vs. non-verbal) abilities might be attributable to changes in cerebral lateralization induced by exposure to antiepileptic drugs. The positive association of periconceptional folate with IQ is consistent with other recent studies.”

The FDA cautioned that women who are pregnant and taking a valproate medication should not stop their medication, which could cause serious or life-threatening issues for the mother or unborn child, but should contact their health care professionals immediately.

The drugs also should be used cautiously in women of childbearing age who are not known to be pregnant, according to the agency, which noted that “valproate should not be taken for any condition unless the drug is essential to the management of the woman's medical condition. All non-pregnant women of childbearing age taking valproate products should use effective birth control.”

Valproate products include: valproate sodium (Depacon), divalproex sodium (Depakote, Depakote CP, and Depakote ER), valproic acid (Depakene and Stavzor), and their generics. The drugs are approved for the treatment of certain types of epilepsy, the treatment of manic episodes associated with bipolar disorder, and the prevention of migraine headaches. The drugs also frequently are used off-label for other, usually psychiatric, conditions.

Last month, a Danish study was published in the Journal of the American Medical Association, finding that maternal use of valproate during pregnancy was associated with a significantly increased risk of autism spectrum disorder and childhood autism in the offspring, even after adjusting for maternal epilepsy.

U.S. Pharmacist Social Connect