The U.S. Food and Drug Administration 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. Therefore, these drugs are being contraindicated for (should never be used by) pregnant women for the prevention of migraine headaches. Valproate products include valproate sodium (Depacon), divalproex sodium (Depakote, Depakote CP, and Depakote ER), valproic acid (Depakene and Stavzor), and their generics.
Valproate products have several FDA-approved uses including: prevention of migraine headaches; treatment of epilepsy (seizures); and treatment of manic episodes associated with bipolar disorder (manic-depressive disorder).
Medicines that contain valproate already have a boxed warning for fetal risk, including birth defects. The recently published Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study found further evidence of the IQ risk, leading to today’s strengthened warnings.
“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.
For its other approved uses — bipolar disorder and seizures — valproate may have some value in pregnant women, but it should only be taken if other medications have not controlled the symptoms or are otherwise unacceptable. Women who can become pregnant should not use valproate unless it is essential to managing their medical condition.
Women who are pregnant, or who become pregnant while taking one of these medications, should talk to their health care professional immediately. Women should not stop taking their medication without talking to their health care professional because 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 result in 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 NEAD study, which showed that children exposed to valproate products in utero had decreased IQ at age 6 when compared to children who were exposed to other antiepileptic drugs. The difference in average IQ between the children who had been exposed to valproate and the children who had been exposed to other antiepileptic drugs varied between 8 and 11 points depending on the antiepileptic drug.
In a June 2011 alert, the FDA released interim results from the NEAD study that showed reduced cognitive test scores in these valproate-exposed children at age 3, and at that time the drug labels were updated.
The FDA is working with the manufacturers to make changes to the drug labels 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, epilepsy and manic episodes associated with bipolar disorder.
In a drug safety communication issued today, the FDA provided a summary of the new data and recommendations for health care professionals and patients.
For additional information:
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
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