Women who take valproate sodium or related products during pregnancy may be putting their child's cognitive ability at risk, according to the FDA.
The agency said in a June 30 safety announcement(www.fda.gov) that several epidemiological studies have indicated that children exposed to valproate or related products during pregnancy have lower cognitive test scores than children who were exposed to other antiepileptic drugs -- including lamotrigine, carbamazepine and phenytoin -- and those who were not exposed to any antiepileptic drugs.
Valproate products, which are approved for the treatment of seizures, manic-depressive disorder and migraine headaches, are considered Pregnancy Category D drugs, which means there is evidence of human fetal risk, but potential benefits of the medication may warrant use of the drug in pregnant women. The FDA previously warned(www.fda.gov) physicians and patients about the increased risk of neural tube defects and other birth defects in infants exposed to valproate sodium.
The FDA said the labels and medications guides for valproate products will be updated with information regarding the increased risk of cognitive impairment. Valproate product labels also are being updated to include a stronger warning about the increased risk of neural tube defects and other major birth defects, such as craniofacial defects and cardiovascular malformations, in infants born to mothers exposed to valproate during pregnancy.
The changes affect the following brand-name products, as well as the generic versions:
- valproate sodium, which is marketed as Depacon;
- divalproex sodium, which is marketed as Depakote, Depakote CP, and Depakote ER; and
- valproic acid, which is marketed as Depakene and Stavzor.
The FDA said patients, including pregnant women, should not stop taking valproate products without talking to their physicians.
The agency released the following information for physicians:
- Inform women of childbearing age of the increased risk for adverse effects on cognitive development with prenatal valproate exposure.
- Counsel women of childbearing potential who take valproate about the increased risk of major malformations, including neural tube defects, when valproate is used during pregnancy.
- Weigh the benefits and risks of valproate when prescribing this drug to women of childbearing age, particularly when treating a condition not usually associated with permanent injury or death. Alternative medications that have a lower risk of adverse outcomes should be considered. Physicians should discuss the relative risks and benefits of alternative therapies with their patients.
- Untreated or inadequately treated epilepsy or bipolar disorder during pregnancy increases the risk of complications in both the woman and her infant.
- If the decision is made to prescribe valproate to women of childbearing age, physicians should recommend use of effective contraception for women who are not planning a pregnancy.
- Inform patients of the North American Antiepileptic Drug (NAAED) Pregnancy Registry, and encourage those who become pregnant to enroll by calling (888) 233-2334.
- Report adverse events to the FDA's MedWatch program(www.accessdata.fda.gov).
In a related document(www.fda.gov), the FDA said women who took valproate during a previous pregnancy should talk to their child's health care professional about whether assessment or monitoring of the child is needed.
The agency also said that women who are breastfeeding while taking valproate should talk to their physicians about the best way to feed their infant while using the drug. Valproate passes into breast milk, but its effects on children via this route are unknown, said the FDA.