May 9, 2013
FDA is notifying consumers and healthcare professionals about new labeling changes for valproate products (ie, valproic acid, valproate sodium, or divalproex sodium). FDA is updating labeling to change the pregnancy category from “D” to “X” in patients receiving valproate for migraine prophylaxis. This labeling change means valproate products are now contraindicated in pregnant patients for prevention of migraine headaches. Valproate products will continue to carry the pregnancy category D for use in seizure disorders and bipolar disorders. The category D means data showing risk to the fetus are available, but the benefit to the mother may outweigh the risk. A pregnancy category X means data showing risk to the fetus are available and the risks outweigh any potential benefit.
In earlier epidemiological studies, children born to mothers taking valproate products while pregnant performed worse on cognitive tests compared to children whose mothers were taking other anticonvulsant medications. The current information comes from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) trial. The study found children exposed to valproate in utero had lower IQ scores than children exposed to other antiepileptic drugs (ie, carbamazepine, lamotrigine, and phenytoin). It is unknown if the risk changes during various stages of pregnancy since patients in this study were taking valproate throughout the pregnancy.
Instruct patients who are pregnant and are taking valproate products to continue their medication and to contact their healthcare provider as soon as possible. Immediate discontinuation of valproate can cause serious life-threatening medical problems to the mother and her baby. Counsel women of childbearing age who are taking valproate on the following information:
- Use effective birth control while on valproate
- Children exposed to valproate in utero are at an increased risk of impaired cognitive development
- Neural tube defects and other malformations have been associated with valproate use during pregnancy
- Folic acid supplementation prior to pregnancy and during early pregnancy has been shown to reduce the risk of neural tube defects
FDA is continuing to evaluate reports and other information on valproate use in pregnant patients. Report adverse events to FDA MedWatch Safety Information and Adverse Event Reporting Program.
Additional information is available at the following links:
- MedWatch alert:
- Drug Safety Communication:
Previous information on valproate and pregnancy:
- MedWatch alert (June 30, 2011):
- Drug Safety Communication (June 30, 2011):
May 8, 2013; University of Utah, Drug Information Service. Copyright 2013, Drug Information Service, University of Utah, Salt Lake City, UT.