The US Food and Drug Administration (FDA) is advising healthcare professionals and women that the anti-seizure medication valproate sodium and related products, valproic acid and divalproex sodium, are contraindicated and should not be taken by pregnant women for the prevention of migraine headaches.
Based on information from a recent study, there is evidence that these medications can cause decreased IQ scores in children whose mothers took them while pregnant.
Stronger warnings about use during pregnancy will be added to the drug labels, and valproate’s pregnancy category for migraine use will be changed from "D" (the potential benefit of the drug in pregnant women may be acceptable despite its potential risks) to "X" (the risk of use in pregnant women clearly outweighs any possible benefit of the drug).
With regard to valproate use in pregnant women with epilepsy or bipolar disorder, valproate products should only be prescribed if other medications are not effective in treating the condition or are otherwise unacceptable.
Valproate products will remain in pregnancy category D for treating epilepsy and manic episodes associated with bipolar disorder.
With regard to women of childbearing age who are not pregnant, valproate should not be taken for any condition unless the drug is essential to the management of the woman's medical condition. All non-pregnant women of childbearing age taking valproate products should use effective birth control.
This alert is based on the final results of the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study showing that children exposed to valproate products while their mothers were pregnant had decreased IQs at age 6 compared to children exposed to other anti-epileptic drugs.
The difference in average IQ between the children who had been exposed to valproate and the children who had been exposed to other anti-epileptic drugs varied between 8 and 11 points depending on the drug to which valproate was compared.
FDA previously communicated initial findings about this risk in a June 2011 Drug Safety Communication.
At that time, FDA also worked with valproate manufacturers to revise the drug labels after interim results from the NEAD study showed lower cognitive test scores at age 3 in children exposed to valproate compared to children exposed to other anti-epileptic drugs.
Women who are pregnant and taking a valproate medication should not stop their medication but should talk to their healthcare professionals immediately.
Stopping valproate treatment suddenly can cause serious and life-threatening medical problems to the woman or her baby.
It is not known whether there is a specific time period during pregnancy when valproate exposure can result in negative cognitive effects. Similarly, there is no known time during pregnancy in which exposure may be considered to have less risk for decreased IQ in children.
Because the women in the NEAD study were exposed to anti-epileptic drugs throughout pregnancy, whether the risk for decreased IQ was related to a particular time period during pregnancy could not be assessed.
FDA is working with manufacturers to change the drug labels for valproate products with this updated risk information. FDA continues to evaluate information about the potential risks of valproate use during pregnancy and will update the public as more information becomes available.
Pregnancy Category X means that studies in animals or humans have shown positive evidence of fetal risk, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefits.
Category D means there is positive evidence of risk to a baby based on data from studies or other experience in humans, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks.