FDA: Risk of oral birth defects in children born to mothers taking Topamax

On March 4, 2011, the FDA reported that new data suggests that the drug Topamax (topiramate) and its generic versions increase the risk for the birth defects cleft lip and cleft palate in babies born to women who use the medication during pregnancy.

The FDA strongly advised physicians that before prescribing Topamax, approved to treat certain types of seizures in people who have epilepsy, health care professionals should warn patients of childbearing age about the potential hazard to the fetus if a woman becomes pregnant while using the drug.   Topamax also is approved to prevent migraine headaches, but not to relieve the pain of migraines. 

The FDA states that “Health care professionals should carefully consider the benefits and risks of Topamax when prescribing it to women of childbearing age,” said Russell Katz, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “Alternative medications that have a lower risk of birth defects should be considered.”

Cleft lip and cleft palate, collectively called oral clefts, are birth defects that occur when parts of the lip or palate do not completely fuse together early in the first trimester of pregnancy, a time when many women do not know they are pregnant. The defects range from a small notch in the lip to a groove that runs into the roof of the mouth and nose, possibly leading to problems with eating, talking, and to ear infections. Surgery often is performed to close the lip and palate and most children do well after treatment.

Data from the North American Antiepileptic Drug (AED) Pregnancy Registry indicate an increased risk of oral clefts in infants exposed to Topamax during the first trimester of pregnancy. Infants exposed to Topamax as a single therapy experienced a 1.4 percent prevalence of oral clefts, compared with a prevalence of 0.38 percent – 0.55 percent in infants exposed to other antiepileptic drugs.

Infants of mothers who did not have epilepsy and were not being treated with other antiepileptic drugs had a prevalence of 0.07 percent. Similar data from the United Kingdom Epilepsy and Pregnancy Register supported the North American AED Pregnancy Registry data.

Based on the data, Topamax is now required to have a stronger warning in its prescribing information (labeling). The pregnancy category will be changed to Pregnancy Category D. This means that there is positive evidence of human fetal risk based on human data, but the potential benefits of the drug in pregnant women may outweigh the risks in certain situations. The FDA previously designated Topamax as Pregnancy Category C because of the lack of human data.

The patient medication guide and prescribing information for Topamax and generic topiramate will be updated with the new information.