Government-mandated drug safety program effective in reducing prenatal exposure to weight-loss drug phentermine-topiramate

A study of nationwide automated health care records found that prenatal exposure to phentermine and topiramate extended-release capsules (phentermine-topiramate) was generally low under the Food and Drug Administration Risk Evaluation and Mitigation Strategy, or REMS, compared to using topiramate or other antiobesity medications. The findings were published March 21 in the Annals of Internal Medicine journal. The study’s lead authors were Almut Winterstein, Ph.D., R.Ph., a distinguished professor of pharmaceutical outcomes and policy in the UF College of Pharmacy and director for the Center for Drug Evaluation and Safety, and Amir Sarayani, Pharm.D., Ph.D., M.P.H., a 2022 graduate of the UF College of Pharmacy.

Dr. Amir Sarayani
Dr. Amir Sarayani

In 2012, the FDA approved the use of the combination product phentermine-topiramate for long-term obesity management. Single-ingredient topiramate product, approved for treatment of epilepsy in 1996, is now used for a variety of indications, including weight loss. Its association with risks for birth defects is well established. Because of specific focus on weight loss for the new combination product, representing many persons of child-bearing age, phentermine-topiramate was approved with the requirement of a REMS aimed at preventing prenatal exposure. REMS is an FDA-mandated drug safety program implemented by the manufacturer to ensure that prescribers, pharmacists and patients are informed about certain drug safety risks.

Researchers from the University of Florida College of Pharmacy studied insurance claim data for 156,280 treatment episodes among women aged 12 to 55 to evaluate the rate of prenatal exposure, contraceptive use and pregnancy testing among patients initiating phentermine–topiramate compared to those who started topiramate (with birth defect risk) or other antiobesity medications (without birth defect risk).

Winterstein, Almut 400x600
Dr. Almut Winterstein

The authors found that the use of phentermine-topiramate was associated with half the risk for exposure during pregnancy compared to either of the control groups. They also found that only 1 in 5 patients used contraceptives before and during treatment overall, and only 1 in 20 patients had pregnancy tests before medication initiation. The authors note that younger patients used more contraceptives and pregnancy tests than their older counterparts, but the absolute risk for prenatal exposures was also higher. The authors note that the effectiveness of the REMS in reducing prenatal exposure is promising, but also emphasize the need for further clinical vigilance and risk mitigation, including topiramate products which do not have a REMS and exhibited higher prenatal exposure rates.

This summary was provided courtesy of the Annals of Internal Medicine journal. The research study was conducted as part of Dr. Sarayani’s Ph.D. dissertation project.