Valproic Acid Derivatives (valproate sodium [Depacon], valproic acid [Depakene, Stavzor], divalproex sodium [Depakote, Depakote CP, Depakote ER]) and Birth Defect Risk
December 3, 2009
The FDA informed healthcare professionals of serious congenital anomalies in infants exposed to valproate sodium [Depacon], valproic acid [Depakene, Stavzor], divalproex sodium [Depakote, Depakote CP, Depakote ER]) during pregnancy. These abnormalities include neural tube defects, craniofacial defects, and cardiovascular malformations. Risk of these birth defects is highest when exposure occurs during the first trimester, often before the patient knows they are pregnant.
Data from the North American Antiepileptic Drug (NAAED) Pregnancy Registry found neural tube defects in 1 in 20 babies exposed to valproic acid during the first 12 weeks of pregnancy, compared to a background rate of 1 in 1500 babies in the general population. In women being treated for epilepsy, major malformations occurred in 10.7% (95% CI 6.3 – 16.9) of babies whose mothers received valproic acid during pregnancy and in 2.9% (95% CI 2 – 4.1) of babies whose mothers received any other antiepileptic drug during pregnancy.
The Medication Guide for valproic acid products will be updated with this information. The pregnancy risk category of valproic acid derivatives is pregnancy category “D” (positive evidence of fetal harm.). However, the risk of maternal and fetal complications increases in pregnant patients with inadequately treated epilepsy or bipolar disorder. Healthcare professionals must consider the risk of complications as well as the risk of birth defects.
Consider alternative therapies in women of childbearing potential whenever possible, especially for the treatment of migraine and other non-life-threatening conditions. Use valproic acid products in these patients only when absolutely essential. If valproic acid derivatives are used in women of childbearing potential, counsel patients on risk of fetal harm from exposure during pregnancy and encourage patients to use effective contraception if they are not actively planning to become pregnant. If valproic acid derivatives are used during pregnancy, encourage patients to enroll in the NAAED Pregnancy Registry at 888-233-2334, or at www.aedpregnancyregistry.org. Encourage patients to take prescription folic acid supplements throughout pregnancy to further reduce the risk of neural tube defects.
Additional information is available at the following links:
- MedWatch Alert:
- Information for Healthcare Professionals:
- Valproate Information:
December 3, 2009; University of Utah, Drug Information Service. Copyright 2009, Drug Information Service, University of Utah, Salt Lake City, UT.