Clinicians have known for years that use of the antiepileptic drug valproate sodium (Depacon) and its derivatives increases the risk of major birth defects in fetuses exposed in utero. As these drugs are increasingly being prescribed for other conditions, the Food and Drug Administration (FDA) has issued a reminder (http://bit.ly/8JRHOr) to all prescribers of the risks to fetuses of neural tube defects, such as spina bifida and anencephaly; craniofacial defects, such as cleft lip and cleft palate; and cardiovascular malformations.
Originally used as antiepileptics, these drugs have more recently been approved for use in the treatment of bipolar disorder and migraine headache; the labels on the drugs have always included information on teratogenic risks, but the FDA fears that not all practitioners will be cognizant of those risks. The reminder covers valproate sodium and its related products, such as valproic acid (Depakene and Stavzor) and divalproex sodium (Depakote, Depakote CP, and Depakote ER).
Additional information on the risks of valproate products during pregnancy has emerged from data gathered in the Antiepileptic Drug Pregnancy Registry, which was created by Massachusetts General Hospital in Boston. Women taking any antiepileptic drug (for any indication) during pregnancy can voluntarily enroll in the registry, allowing data about their pregnancy and their baby's health to be recorded and analyzed.
Pregnancy registries are an important source of information on how drugs actually affect pregnant women, a group about whom little is known because they're usually excluded from clinical drug trials. According to the FDA, registry data on 149 women with epilepsy who used valproate alone revealed a rate of major malformations of almost 12%, nearly four times that of women taking other antiepileptic drugs.
The FDA will revise the labels of these drugs to more clearly indicate the increased risk of major birth defects. A medication guide, which explains the possible risks from a drug and accompanies each prescription, will be developed. Nurses should tell female patients of childbearing age who are receiving valproate sodium or any of its related products about the risk of fetal defects. They should also tell patients to thoroughly read the medication guide that comes with each dispensed prescription because the information can change. It's important that women taking valproate sodium and related medications be taught to use an effective contraceptive because many of the adverse effects occur in the early weeks of a pregnancy, before the pregnancy is confirmed. Patients taking these drugs who wish to become pregnant should be weaned off of them before they attempt to do so, if at all possible. Because suddenly stopping an antiepileptic drug can precipitate seizures or a flare-up of bipolar disease, women shouldn't just stop drug therapy but should work with their health care provider to make the transition to an alternative therapy; failure to treat epilepsy or bipolar disorder can also result in poor fetal outcomes or create pregnancy complications.
Women who wish to become pregnant should take a folic acid supplement before becoming pregnant, as well as during pregnancy, which decreases the risk of neural tube defects in the baby. Some women won't be able to switch from valproate sodium to another medication. Women who become pregnant while taking valproate sodium or any other antiepileptic drug should be encouraged to enroll in the Antiepileptic Drug Pregnancy Registry. They can do so by calling the toll-free number, (888) 233-2334, or by going to www.aedpregnancyregistry.org.