The high risk of neural tube defects and other major malformations in babies exposed to valproate sodium and the related products, valproic acid and divalproex sodium, during the first trimester is the focus of a Food and Drug Administration notice to health care professionals.
The FDA statement also emphasizes the need for health practitioners to counsel women of childbearing potential about these teratogenic risks, and to “consider alternative therapies, especially if using valproate to treat migraines or other conditions not usually considered life-threatening.”
The statement was posted on the FDA's MedWatch site in December.
The risk of a neural tube defect in a baby born to a mother who took valproate or one of the two related products during the first 12 weeks of pregnancy is 1 in 20, compared with the background rate of 1 in 1,500 in the United States, according to the FDA.
The notice cites data from the North American Antiepileptic Drug (NAAED) Pregnancy Registry, which indicate that the major malformation rate in babies born to women who have epilepsy and take valproate alone is nearly fourfold greater than among the babies born to women with epilepsy who take a different antiepileptic: 10.7%, compared with 2.9%.
The 16 major malformations among the babies in the registry who were exposed to valproate during the first trimester of pregnancy included neural tube defects, craniofacial defects, cardiovascular malformations, and malformations involving other body systems.
Included in the FDA statement were comments on the importance of taking folic acid supplements before and during the first trimester of pregnancy in order to reduce the risk of neural tube defects, and a recommendation that women who are treated with one of these drugs and who are not planning a pregnancy use an effective method of contraception.
Valproic acid, which is marketed as Depakene and as Stavzor, was approved in 1978 for the treatment of epilepsy. Valproate, marketed as Depacon, was approved more recently for the treatment of bipolar disorder and migraine headaches.
“As valproate's indications for use expand, it is critical that health care professionals caring for women of childbearing potential and taking valproate for any indication be informed that valproate causes an increased risk of major birth defects,” the FDA statement said.
“Awareness of the therapeutic benefits and risks of valproate and alternative therapies, as well as the risks of untreated disease is critical for informed prescribing and counseling of all women taking valproate.”
Divalproex sodium is marketed as Depakote, Depakote CP, and Depakote ER, and is approved for migraine prophylaxis, manic episodes associated with bipolar disorder, as well as epilepsy.
The FDA notice also includes an information section specific to patients.
The agency is working with the manufacturers of these products to make labeling changes that reflect the information regarding teratogenic risk.
The notice can be found at: www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192788.htmwww.aedpregnancyregistry.orgwww.fda.gov/medwatch/