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FDA Drug Safety Podcast for Healthcare Professionals: Risk of oral clefts in children born to mothers taking Topamax (topiramate)

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Welcome, my name is Jennifer Shepherd, a pharmacist in the Division of Drug Information. On March 4, 2011, the Food and Drug Administration issued a Drug Safety Communication informing the public of new data that show that there is an increased risk for the development of cleft lip and/or cleft palate (also known as oral clefts) in infants born to women treated with Topamax, or topiramate, during pregnancy.

The benefits and the risks of topiramate should be carefully weighed when prescribing this drug to women of childbearing age, particularly for conditions 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 for these patients. If the decision is made to use topiramate in women of childbearing age, effective birth control should be used. Oral clefts occur in the first trimester of pregnancy before many women know they are pregnant. Inform women of childbearing age of the increased risk for having a baby with an oral cleft if they become pregnant while using topiramate.

Topiramate was previously classified as a Pregnancy Category C drug, which means that data from animal studies suggested potential fetal risks, but no adequate data from human clinical trials or studies were available at the time of approval. However, because of new human data that show an increased risk for oral clefts, topiramate is being placed in Pregnancy Category D. Pregnancy Category D means there is positive evidence of human fetal risk based on human data but the potential benefits from use of the drug in pregnant women may be acceptable in certain situations despite its risks.

Data from the North American Antiepileptic Drug, or NAAED, Pregnancy Registry indicate an increased risk of oral clefts in infants exposed to topiramate monotherapy during the first trimester of pregnancy. The prevalence of oral clefts was 1.4% compared to a prevalence of 0.38% - 0.55% in infants exposed to other antiepileptic drugs, also known as AEDs, and a prevalence of 0.07 % in infants of mothers without epilepsy or treatment with other AEDs. The relative risk of oral clefts in topiramate-exposed pregnancies in the NAAED Pregnancy Registry was 21.3 as compared to the risk in a background population of untreated women. 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 to the risk in their background population (0.2%).

Cleft lip and cleft palate range from a small notch in the lip to a groove that runs into the roof of the mouth and nose, possibly leading to problems with eating, talking and ear infections. Surgery is often used to close the lip and palate. With treatment, most children with cleft lip or palate do well.

At this time, FDA recommends that Healthcare Professionals be aware that:

  1. You should inform women of childbearing age of the increased risk for oral clefts when topiramate is used in the first trimester of pregnancy.
  2. 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.
  3. 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.
  4. You should inform patients of the North American Antiepileptic Drug Pregnancy Registry and encourage patients who become pregnant to enroll by calling 1-888-233-2334.
  5. You should report adverse events involving topiramate to the FDA MedWatch program at www.fda.gov/medwatch.

Thank you for listening. The FDA is committed to keeping healthcare professionals informed of the latest safety information. To learn more about this Drug Safety Communication, go to www.fda.gov/drugs. If you have drug questions, you can reach us at: druginfo@fda.hhs.gov.

 

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