New Birth Defect Warning for Topamax

March 4, 2011 -- Taking the epilepsy drug topiramate (Topamax) during pregnancy raises the risk of oral cleft birth defects such as cleft lip and cleft palate, according to a new warning issued by the FDA.

New drug registry data show that the risk of oral birth defects is up to 16 times higher among women who took topiramate or its generic equivalents during pregnancy.

Topiramate is approved by the FDA for treating seizures associated with epilepsy and to prevent migraines. But it is also sometimes used on an off-label basis to treat other conditions, such as obesity, bipolar disorder, and alcoholism.

"Health care professionals should carefully consider the benefits and risks of topiramate when prescribing it to women of childbearing age," Russell Katz, MD, director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research, says in a statement. "Alternative medications that have a lower risk of birth defects should be considered."

Citing information from the North American Antiepileptic Drug (AED) Pregnancy Registry, the FDA says 1.4% of infants exposed to topiramate during pregnancy developed cleft lip or cleft palate, compared with 0.38-0.55% of infants exposed to other epilepsy drugs. The risk of these oral cleft birth defects was much lower among infants of mothers who did not take epilepsy drugs during pregnancy (0.07%).

Similar results have been reported in European drug registries.

Upgraded Pregnancy Warning

In response to this new information, the FDA says topiramate will have a stronger warning on its label. The warning in the pregnancy category has been changed from category C to a category D risk, which means there is positive evidence of fetal risk based on human data.

Cleft lip and cleft palate are birth defects that occur when parts of the lip or palate do not fuse together during the first trimester of pregnancy. The defects range from a small notch in the lip to a groove that runs into the roof of the mouth and nose that can lead to problems with eating and talking and to ear infections.

Researchers say with treatment, usually corrective surgery, most children with cleft lip or cleft palate do well.

FDA officials warn that pregnant women and women of childbearing age should discuss other treatment options with their health care professional before taking topiramate. Women taking topiramate should tell their health care professional immediately if they are pregnant or planning to become pregnant.

People taking topiramate should not stop taking it unless told to do so by their doctor.