The U.S. Food and Drug Administration (FDA) has issued a warning to pregnant women against using valproate sodium products, prescribed for migraine prevention, over risks to their unborn babies.
Valproate products include Depacon (valproate sodium); Depakote, Depakote CP, and Depakote ER (divalproex sodium); and Depakene and Stavzor (valproic acid); and Stavzor), and their generics.
The agency is alerting health care providers and patients that medications including and related to valproate sodium can cause decreased IQ scores in children whose mothers took the medication during pregnancy. These drugs are now contraindicated for—and should never be used by—pregnant women for the prevention of migraine headaches.
“Valproate medications should never be used in pregnant women for the prevention of migraine headaches because we have even more data now that show the risks to the children outweigh any treatment benefits for this use,” said Russell Katz, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research.
Valproate products are approved for the prevention of migraine headaches, the treatment of epilepsy (seizures), and treatment of manic episodes associated with bipolar disorder (manic-depressive disorder). For its other approved uses, valproate may have some value in pregnant women, but should only be taken if other drugs have not controlled the symptoms or are otherwise unacceptable. Also, women who can become pregnant should not use valproate unless essential to managing their medical condition.
Valproate-containing drugs have contained a boxed warning for fetal risk, including birth defects; however, the recently published Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study discovered further evidence of the IQ risk, which prompted this newest, stronger warning.
Women who are pregnant, or who become pregnant while taking a medication containing valproate are strongly advised to speak with their health care professional immediately, the FDA urges. The FDA also points out that these women should not stop taking their medication without talking to their health care professional as stopping treatment suddenly can cause serious and life-threatening medical problems for the woman or the developing fetus. Women of childbearing age taking valproate products should use effective birth control.
It is not known if there is a certain time period during pregnancy when valproate exposure can lead to decreased IQ. The women in the NEAD study were exposed to antiepileptic drugs throughout their pregnancies. The FDA’s strengthened recommendations are based on the final results of the study, which found that children exposed to valproate products in utero had decreased IQ at age six when compared to children exposed to other antiepileptic drugs. The difference in average IQ between the two groups of children varied between 8 and 11 points depending on the drug.
In a June 2011 alert, the FDA released interim results from the NEAD study revealing reduced cognitive test scores in the valproate-exposed children at age three, which prompted a label update. The FDA and drug manufacturers are collaborating on newer drug label changes to reflect this new information and to change the pregnancy category for prevention of migraine headaches to category X (the drug’s risks outweigh the drug’s benefits for this use) from category D (the drug’s benefits outweigh the drug’s risks for this use). Valproate products will remain category D for the other two approved indications. In the current drug safety communication, the FDA provided a summary of the new data and recommendations for health care professionals and patients.
We recently wrote about an increased risk of autism in the babies born of women who took valproate during pregnancy, according to study published in the Journal of the American Medical Association. Valproate has also been linked to increased risks for congenital malformations and delayed cognitive development.
A prior Danish study revealed additional evidence that fetal exposure to Depakote, specifically its active ingredient, valproate, increases a baby’s risk of developing autism spectrum disorders (ASD) three-fold. Depakote has also been associated with birth defects when taken by pregnant women.
Just prior, 26 women filed lawsuits claiming that the makers of Depakote illegally marketed the drug for off-label purposes and failed to warn of the side effects of the drug. Each of the women claimed they were prescribed and took Depakote just before getting pregnant or during the first trimester of their pregnancy and that the drug caused them to give birth to children with a wide array of severe, some life-threatening, birth defects.