The FDA has alerted healthcare 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 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 and treatment of manic episodes associated with bipolar disorder.
Medicines that contain valproate already have a boxed warning for fetal risk, including birth defects. The recently published Neurodevelopmental Effects of Antiepileptic Drugs study found further evidence of the IQ risk, leading to the 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 children outweigh any treatment benefits for this use,” Russell Katz, MD, director of the Division of Neurology Products in the FDAs Center for Drug Evaluation and Research, said in a news release.
For treatment of bipolar disorder and seizures, valproate may have some value in pregnant women, according to the FDA, but it should be taken only 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 healthcare professional immediately. Women should not stop taking their medication without talking to their healthcare professional because stopping treatment suddenly can cause serious and life-threatening medical problems for the woman or the developing fetus, the FDA noted. Women of childbearing age who take valproate products should use effective birth control.
It is not known whether 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 FDAs 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 with 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 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 modify the drug labels to reflect this new information and to change the pregnancy category for prevention of migraine headaches to category X (the drugs risks outweigh the drugs benefits for this use) from category D (the drugs benefits outweigh the drugs risks for this use).
Valproate products will remain category D for the other two approved indications, epilepsy and manic episodes associated with bipolar disorder.
For more information: www.fda.gov/Drugs/DrugSafety/ucm350684.htm.