FDA: Drug Prescribed for Epilepsy and Migraines Causes Oral Birth Defects

March 4, 2011

A drug prescribed for the treatment of epilepsy and prevention of migraines can cause cleft palate and cleft lip birth defects.

The U.S. Food and Drug Administration (FDA) announced that the agency is requiring Topamax (topiramate) and generic equivalents to carry warnings of potential birth defects if taken by a woman who is pregnant or becomes pregnant.

Topamax and generic topiramate drugs are in a class of drugs called anticonvulsants. Doctors prescribe this medication to treat seizures in people with epilepsy and Lennox-Gastaut syndrome. They also prescribed it for the prevention of migraine headaches.

The FDA made the change after reviewing from data from the North American Antiepileptic Drug (AED) Pregnancy Registry showing an increased risk of oral birth defects including cleft lip and cleft palate in babies exposed to the Topamax in the womb. These oral clefts occur when parts of the lip or palate do not completely fuse together early in the first trimester of pregnancy.

The agency said it would change the drug to a Pregnancy Category D, meaning there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks.

“Health care professionals should carefully consider the benefits and risks of topiramate when prescribing it to women of childbearing age,” said Russell Katz, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “Alternative medications that have a lower risk of birth defects should be considered.”

The FDA has this advice for patients:

• If you take topiramate during pregnancy, there is a higher risk that your baby will develop a cleft lip and/or cleft palate. Oral clefts happen early in pregnancy, before many women even know they are pregnant. For this reason, women of childbearing age should talk to their healthcare professionals about other treatment options.
• Women of childbearing age who do decide to take topiramate and are not planning a pregnancy should use effective birth control (contraception) while taking topiramate. Women should talk to their healthcare professionals about the best kind of birth control to use while taking topiramate.
• Before you start topiramate, you should tell your healthcare professional if you are pregnant or are planning to become pregnant. Healthcare professionals may discuss other treatment options with you.
• You should tell your healthcare professional right away if you become pregnant while taking topiramate. You and your healthcare provider should decide if you will continue to take topiramate while you are pregnant.
• Topiramate should not be stopped without talking to a healthcare professional, even in pregnant women. Stopping topiramate suddenly can cause serious problems. Not treating epilepsy during pregnancy can be harmful to women and their developing babies.
• If you become pregnant while taking topiramate, you should talk to your healthcare professional about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect additional information about the safety of antiepileptic drugs during pregnancy. Information about the North American Drug Pregnancy Registry can be found at http://www.massgeneral.org/aed/.
• Topiramate passes into breast milk, but its effects on developing babies remain unknown. You should talk to your healthcare professional about the best way to feed your baby if you take topiramate.
• You should report any side effects you experience to the FDA MedWatch program using the information in the "Contact Us" box at the bottom of the page.
• You should read the Medication Guide when picking up a prescription for topiramate. It will help you understand the potential risks and benefits of this medication.

The FDA says healthcare professionals should do the following:

• You should inform women of childbearing age of the increased risk for oral clefts when topiramate is used in the first trimester of pregnancy.
• You should weigh the benefits and risks of topiramate when prescribing this drug to women of childbearing age, particularly when treating a condition not usually associated with permanent injury or death. Alternative medications that have a lower risk of oral clefts and other adverse birth outcomes should be considered. Healthcare professionals should discuss the relative risks and benefits of appropriate alternative therapies.
• If the decision is made to prescribe topiramate to women of childbearing age, healthcare professionals should recommend use of effective contraception for women who are not planning a pregnancy, keeping in mind the potential for a decrease in hormonal exposure and a possible decrease in contraceptive efficacy when using estrogen-containing birth control with topiramate.
• You should inform patients of the North American Antiepileptic Drug (NAEED) Pregnancy Registry and encourage patients who become pregnant to enroll by calling 1-888-233-2334.
• You should report adverse events involving topiramate to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of the page.