FDA: Cleft Palate Risk With Seizure Drug in Pregnancy

By John Gever, Senior Editor, MedPage Today
Published: March 04, 2011

Clinicians should be extra cautious about prescribing the epilepsy drug topiramate (Topamax) to women of childbearing age because of a risk of cleft palates and lips in their offspring should they become pregnant, the FDA warned Friday.

"The benefits and the risks of topiramate should be carefully weighed when prescribing this drug for women of childbearing age, particularly when topiramate is considered for a condition not usually associated with permanent injury or death. Appropriate alternative treatment should be considered," the FDA urged.

Topiramate also is approved to prevent migraine headaches, but not to relieve the pain of migraines.

The drug's labeling will be changed to strengthen an existing warning about use during pregnancy. Topiramate had previously been designated as Class C for risk during pregnancy, reflecting a lack of human data.

Based on a new review of clinical information, topiramate will now be labeled as Class D, the FDA said.

That designation indicates 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 new human data came from the North American Antiepileptic Drug (NAAED) Pregnancy Registry, the FDA said.

The review found a 1.4% prevalence of oral clefts with topiramate compared with a prevalence of 0.38% to 0.55% in infants exposed to other antiepileptic drugs (AEDs), and a prevalence of 0.07 % in infants of mothers without epilepsy or treatment with other AEDs.

The prevalence difference in oral clefts translated to a relative risk of 21.3 for topiramate versus the background population of untreated women (95% CI 7.9 to 57.1).

In addition, according to the FDA, the UK Epilepsy and Pregnancy Register reported a similarly increased prevalence of oral clefts (3.2%) among infants exposed to topiramate monotherapy, a 16-fold increase in risk compared with the risk in their background population (0.2%).

http://www.medpagetoday.com/Neurology/Seizures/25188