Topamax Cleft Lip, Palate Risk From First-Trimester Use Reviewed

Researchers and doctors are still debating the extent of the risk women face of giving birth to a child with a cleft palate or cleft lip from Topamax when the antiseizure drug is used during the first trimester of pregnancy.

A roundtable discussion was published online this week by the American Journal of Obstetrics and Gynecology, reviewing the impact and findings of a study published in the same journal in July, which found a five-fold increase in the risk of cleft palate and cleft lip birth defects from Topamax when the antiseizure drug was used early in pregnancy.

Researchers discussed the findings of the study, concluding that it definitely appears there is an association between Topamax and cleft palate and cleft lip birth defects, but pointed out that there needs to be more research.

One participant said that a dose-response study should be conducted to determine whether higher doses of Topamax increased the risk of cleft palate and cleft lip infants. Another said that while not fully conclusive, women should be aware there may be a risk associated with continuing to use the medication after they become pregnant.

“Personally, if I see someone exposed to [Topamax], I am going to have the lips and palate well-visualized on ultrasound,” said Dr. Alison Cahill, an assistant professor of Obstetrics and Gynecology at Washington University in St. Louis. “But I’m not at the point where I would tell a patient who is on [Topamax] to stop the medication before conception.”

Topamax (known generically as topiramate) was approved by the FDA in 2004 for treatment of epilepsy and later was also approved for treatment of migraines.  It became available as a generic in 2006.

In March 2011, the FDA required new warnings about the risk of birth defects with Topamax and generic topiramate when the medication is used during the first trimester of pregnancy, a time when many women do not even know that they are pregnant.

At that time, the FDA urged doctors to avoid giving Topamax to pregnant women or women who are of child-bearing age and at a high risk of pregnancy, as the agency determined that alternative epilepsy and migraine medications were available that may not carry the same risk.

Johnson & Johnson’s McNeil Pharmaceutical subsidiary, which manufacturers the epilepsy drug, currently faces a number of Topamax lawsuits filed on behalf of children who were born with cleft palate, cleft lip and other malformations or defects. The complaints allege that the drug makers failed to adequately research the side effects of Topamax use by pregnant women and warn about the risk of problems for unborn children.