Keywords: Topamax Birth Defects Cleft Palate Male Genitalia Migraine
Topamax (topiramate ), a drug used to treat epilepsy and migraine headaches, has been linked to birth defects in a small study conducted by researchers at the Royal Group of Hospitals in Belfast, Northern Ireland. The study looked at 203 women who became pregnant while taking Topamax for the treatment of epilepsy and found that the risk of birth defects increased by as much as 14-fold.
Topamax, made by Ortho-McNeil Neurologics, a division of Johnson & Johnson, was originally approved to treat epilepsy in adults and children. In 2004, the approved uses of Topamax were expanded to include the prevention of migraine headaches. Generic versions of Topamax were approved by the Food & Drug Administration (FDA) in 2006. Topamax is also used off-label to treat bipolar disorder.
Although the study, published in the July 22 issue of the journal of “Neurology”, was small, it was the first to link Topamax to birth defects in humans, and confirmed earlier animal studies that showed evidence of fetal harm. The researchers who conducted the study said that the connection between Topamax and birth defects warrants further study.
Of the 178 live births that occurred among women in the study, three babies whose mothers took Topamax alone and 13 whose mothers took Topamax along with other anti-epilepsy drugs had major birth defects. Those other drugs included Frisium, Sabril, Epilim or Depakine, Zarontin, Keppra as well as generic drugs carbamazepine, phenobarbitral or phenytoin.
The rate at which the birth defects occurred were 11 to 14 times higher than one would expect among women not taking the drug, the researchers said in a news release from the American Academy of Neurology. The birth defects seen in the Topamax study included:
· Cleft Palate - a condition in which the two plates of the skull that form the hard palate (roof of the mouth) are not completely joined. The soft palate is in these cases cleft as well. In most cases, cleft lip is also present. Cleft palate occurs in about one in 700 live births worldwide.
· Defects of the male genitalia
· Hole above the buttocks
· Flattened head
· Toe webbing
· Clicky hips and immature hip joints
Four of the babies had cleft palates or cleft lips, which was 11 times higher than would be expected among women not taking epilepsy medication. Four male babies had genital birth defects, with two of these classified as major birth defects.
Drugs to treat epilepsy are known to increase the chance of miscarriage and birth defects. The researchers said that the birth defect rate associated with Topamax in their study was in line with those of other anti-seizure drugs, though a larger study is needed to draw definitive conclusions.
However, more birth defects occurred in women taking Topamax along with the drug valproate, or valproic acid, than in women taking other epilepsy drugs or other Topamax drug combinations. Valproate is sold as Depakote by Abbott Laboratories and as Depakine by Sanofi- Aventis.
Previous research has shown that valproate is associated with an increased risk of birth defects such as heart defects and spina bifida. Valproate carries a box warning on its label regarding this risks. The FDA recommends that valproate be avoided during pregnancy.
Maintaining effective epilepsy treatment during pregnancy is crucial because seizures may cause harm to the fetus. Researchers suggest that those epileptic women who depend on this drug to control their convulsive seizures should continue it. However, if they are taking it for migraine prevention, the drug should be discontinued before conception.
When it was approved, Topamax received a pregnancy category C classification from the FDA, which means the drug hasn’t been studied in pregnant women, though it appears to cause harm to the fetus in animal studies. The drug caused birth defects, miscarriages, and decreased fetal weight in rabbits, rats and mice, according to the U.S. prescribing information.
Three major databases currently track birth defects among babies born to women taking epilepsy drugs, but only one has so far provided information on Topamax. When the other databases report, the extent of Topamax’s association with birth defects should become clearer.
The lead researcher on the Topamax study said that a pregnant woman using this treatment for either epilepsy or migraines should be informed of the potential risks to her child. Others are advocating that Topamax use in women who plan on conceiving should be restricted to those in whom the drug is definitely needed for seizure control or other indications.
Women with who are currently taking Topamax who are considering becoming pregnant, or who are already pregnant, should speak with their doctors about this drug. For epileptic patients, doctors will have to weigh the birth defect risks of Topamax against the risks epileptic seizures pose to developing fetuses.