Topiramate Linked to Infants' Risk for Oral Birth Defects

FDA Adds New Warnings to Drug for Epilepsy, Migraines

March 08, 2011 04:45 pm News Staff

Family physicians need to be aware of an increased risk for oral clefts in infants born to women who use the anticonvulsant medication topiramate during pregnancy, say FDA officials. According to new safety data, topiramate, which is marketed as Topamax, increases the risk for cleft lip and cleft palate in these infants, and the agency is urging physicians to educate women of childbearing age about those risks.

Jennifer Shepherd, a pharmacist in the FDA's Division of Drug Information, said during a March 4 podcast( that cleft lip and cleft palate occur during the first trimester of pregnancy -- before many women know they are pregnant.

"The benefits and the risks of topiramate should be carefully weighed when prescribing this drug to women of childbearing age, particularly for conditions not usually associated with permanent injury or death," Shepherd said. "Alternative medications that have a lower risk of oral clefts and other adverse birth outcomes should be considered for these patients.

"If the decision is made to use topiramate in women of childbearing age, effective birth control should be used."

In a March 4 safety announcement(, the FDA said physicians also should be aware of the potential for a decrease in hormonal exposure and a possible decrease in contraceptive efficacy in patients who use estrogen-containing birth control while taking topiramate.

Topiramate is approved to treat patients with epilepsy and to prevent migraine headaches. From 2007 through 2010, more than 32 million topiramate prescriptions were dispensed in the United States, and more than 4 million patients filled topiramate prescriptions at the nation's retail pharmacies, according to figures provided by the health care analytics firm SDI Health LLC.

Data from the North American Antiepileptic Drug, or NAAED, Pregnancy Registry show that the prevalence of oral clefts in infants exposed to topiramate monotherapy during the first trimester of pregnancy was 1.4 percent, compared with a prevalence of 0.38 percent to 0.55 percent in infants exposed to other antiepileptic drugs during the same period. Infants of mothers without epilepsy or treatment with other antiepileptic drugs had a prevalence of 0.07 percent.

The agency said in its safety announcement that the patient medication guide and prescribing information for topiramate will be updated to reflect the new safety data.

The FDA also said that topiramate is being reclassified as a pregnancy category D drug, meaning there is positive evidence of fetal risk based on human data, but the potential benefits from use of the drug in pregnant women may be acceptable in certain situations despite its risks. The drug had been classified as a pregnancy category C drug because at the time of its approval, data from animal studies suggested potential fetal risks but data from human clinical trials or studies were inadequate or unavailable.

In addition to the recommendations Shepherd made, the FDA offered the following recommendations for health care professionals:

  • inform patients of the NAAED Pregnancy Registry and encourage patients who become pregnant while taking topiramate to enroll by calling (888) 233-2334; and
  • report adverse events involving topiramate to the FDA's MedWatch program(

The agency said women should not stop talking topiramate -- even if they are pregnant -- without first consulting their physician because not treating epilepsy during pregnancy can be harmful to both women and their infants.