Use of the anticonvulsant drug topiramate during pregnancy is associated with an increased risk of birth defects, such as cleft lip or cleft palate, according to a new warning from the US Food and Drug Administration.
The warning is based on data from the North American Antiepileptic Drug Pregnancy Registry that suggest the prevalence of oral clefts in infants exposed to topiramate during the first trimester of pregnancy was 1.4%, compared with a prevalence of 0.38% to 0.55% among infants exposed to other antiepileptic drugs during that sensitive period, and a prevalence of 0.07% among unexposed infants born to mothers without epilepsy. Data from the UK Epilepsy and Pregnancy Register also showed an increased prevalence of oral clefts (3.2%) among topiramate-exposed infants.
The findings have important implications because off-label use of topiramate has increased in recent years. Although the drug is approved only for the treatment of epilepsy and the prevention of migraines, it has been used off-label to treat alcohol dependence, eating disorders, and an array of psychiatric disorders, as well as to promote weight loss. In fact, the drug’s manufacturers agreed to pay more than $81 million in criminal and civil fines in April 2010 for illegally promoting the drug for psychiatric use, according to the US Department of Justice.
Physicians should carefully weigh the risks and benefits of using topiramate in women of childbearing age, especially when the drug is used to treat conditions that are not associated with permanent injury or death, urged the FDA.
“Alternative medications that have a lower risk of birth defects should be considered,” said Russell Katz, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, in a statement.
Topiramate was the second widely used drug to be linked to serious birth defects this week. Researchers from the US Centers for Disease Control and Prevention (CDC) published data that suggest that taking opioid medications during pregnancy or shortly before becoming pregnant is associated with an increased risk of several serious birth defects. Key findings from the study are available on the CDC’s Website .