Valproate Raises Risk of Neural Tube Defects, Other Birth Defects, FDA SaysDec 3, 2009 | Parker Waichman LLP
Valproate has been associated with a higher risk of neural tube defects and other major birth defects, such as craniofacial defects and cardiovascular malformations, when taken by pregnant women. In a reminder to health care providers, the U.S. Food & Drug Administration (FDA) said women of childbearing potential should only use valproate if it is essential to manage their medical condition.
Women not actively planning a pregnancy should use effective contraception if they are taking valproate, as birth defect risks are particularly high during the first trimester, before many women know they are pregnant.
Valproate was approved in 1978 for the treatment of epilepsy. More recently, the FDA approved valproate for the treatment of bipolar disorder and migraine headaches. Valproate sodium is marketed as Depacon. Dilvalproex sodium is marketed as Depakote, Depakote CP, Depakote ER. Valproic acid is marketed as Depakene and as Stavzor.
According to the agency, in the U.S., about 1 in 1500 babies is born with a neural tube defect. The risk of neural tube defects is much higher in babies born to mothers treated with valproate during the first 12 weeks of pregnancy, with the risk increasing to 1 in 20 babies, the agency said.
According to data from the North American Antiepileptic Drug (NAAED) Pregnancy Registry, the rate of major malformations in babies born to women with epilepsy taking valproate as monotherapy is almost 4 times higher than the rate of major malformations in babies born to women with epilepsy taking a different antiepileptic drug. The NAAED Registry reported a major malformation rate of 10.7% children born to women exposed to an average of 1,000 mg/day of valproic acid monotherapy during pregnancy. Sixteen major malformations occurred in the offspring of 149 women who used valproate during pregnancy, and these malformations included neural tube defects, craniofacial defects, cardiovascular malformations and malformations involving other body systems.
In contrast, the major malformation rate among the internal comparison group of 1,048 women with epilepsy who received any other antiepileptic drug monotherapy during pregnancy was 2.9%, the FDA said.
The FDA said it will be working with the manufacturers of valproate products to address labeling changes. In the meantime, the agency is encouraging women who become pregnant while taking valproate or other antiepileptic drug to enroll in the NAAED Pregnancy Registry by calling the toll-free number 1-888-233-2334. Information on the registry can also be found at the website www.aedpregnancyregistry.org. The NAAED registry gathers information about the effects of antiepileptic drugs during pregnancy.