Among women of child-bearing potential, a study shows less prenatal exposure to phentermine-topiramate — a product that requires a Risk Evaluation and Mitigation Strategy (REMS) — than with topiramate alone or other antiobesity medications (AOMs). Topiramate is a known teratogen whose use is associated with oral clefts, premature delivery, low birthweight, and delivery of live-born infants that are small for gestational age. When used alone, it does not require a REMS.
Researchers examined a nationwide health insurance claims database retrospectively to identify females aged 12 to 55 years with no infertility diagnosis or sterilization procedure. They created cohorts of those taking phentermine-topiramate and compared them with cohorts of those using topiramate alone or other AOMs (liraglutide, lorcaserin, or bupropion–naltrexone).
“A total of 156,280 treatment episodes were observed,” the authors report. “Adjusted prevalence of pregnancy at treatment initiation was 0.9 versus 1.6 per 1000 episodes (prevalence ratio, 0.54 [95% CI, 0.31 to 0.95]) for phentermine–topiramate versus topiramate. The incidence rate of conception during treatment was 9.1 versus 15.0 per 1000 person-years (rate ratio, 0.61 [CI, 0.40 to 0.91]) for phentermine–topiramate versus topiramate. Both outcomes were similarly lower for phentermine–topiramate compared with AOM. Prenatal exposure was marginally lower in topiramate users compared with AOM users. Approximately 20% of patients in all cohorts had at least 50% of treatment days covered by contraceptives. Few patients had pregnancy tests before treatment (≤5%), but this was more common among phentermine–topiramate users.”
“Our study showed that prenatal exposure was generally low among older women across study cohorts but substantially higher in women younger than 40 years,” the authors conclude. “However, patients using phentermine–topiramate under a REMS program had less prenatal exposure than topiramate and AOM users. Still, potential exposures were detected, suggesting the need for further clinical vigilance and risk mitigation. Pregnancy testing before and during treatment seemed to be significantly higher among phentermine–topiramate users, albeit at low absolute levels, likely contributing to lower prenatal exposures. However, contraceptive use patterns seemed unchanged, requiring further research to understand patients’ experiences with these recommendations and potential modification of the REMS to facilitate behavior change.”