Increased Risk of Embryo-Fetal Toxicity

• Qsymia is contraindicated in pregnant patients because the use of Qsymia can cause fetal harm and weight loss offers no clear benefit to a pregnant patient
• Available data indicate an increased risk of major congenital malformations, including but not limited to cleft lip and/or cleft palate (oral clefts), and of being small for gestational age (SGA)

Studies evaluating the risk of major congenital malformations and/or oral clefts with exposure to topiramate during the first trimester of pregnancy include the following:

• The North American Anti-Epileptic Drug (NAAED) Pregnancy Registry (2010) analysis
• A retrospective observational study using 4 U.S. electronic healthcare databases (FORTRESS)
• A case-control study using data from the Slone Epidemiology Center Birth Defects Study (BDS, 1997-2009) and the Centers for Disease Control's (CDC's) National Birth Defects Prevention Study (NBDPS, 1996-2007)
• The UK Epilepsy and Pregnancy Register

The NAAED Pregnancy Registry suggested an estimated increase in risk for oral clefts of 9.60 (95% CI 3.60 – 25.70). The UK Epilepsy and Pregnancy Register reported a prevalence of oral clefts among infants exposed to topiramate monotherapy (3.2%) that was 16 times higher than the background rate in the UK (0.2%). An increase in oral clefts was observed with all dose strengths of topiramate.

These data show that exposure to topiramate in pregnancy is associated with a 2- to 5-fold increase in risk of oral clefts. The FORTRESS study found an excess risk of 1.5 (95% CI = -1.1 to 4.1) oral cleft cases per 1,000 infants exposed to topiramate during the first trimester. Other data sources confirm the increased risk of oral clefts with topiramate exposure during pregnancy (i.e., animal studies and Adverse Event Reporting System data for topiramate).

Small for Gestational Age

• Data from the NAAED Pregnancy Registry and population-based birth registry cohort indicate that exposure to topiramate in utero is associated with an increased risk of SGA newborns (birth weight <<10th percentile).
• In the NAAED Pregnancy Registry, 19.7% of topiramate-exposed newborns were SGA compared to 7.9% of newborns exposed to a reference AED and 5.4% of newborns of mothers without epilepsy and without AED exposure.
• In the medical Birth Registry of Norway, a population-based pregnancy registry, 25% of newborns in the topiramate monotherapy exposure group were SGA compared to 9% in the comparison group unexposed to AEDs; the long-term consequences of the SGA findings are not known.