Assessment of the Risk Evaluation and Mitigation Strategy (REMS) for Phentermine-Topiramate to Prevent Exposure During Pregnancy.

BACKGROUND

The U.S. Food and Drug Administration approved phentermine-topiramate for obesity in 2012 and required a Risk Evaluation and Mitigation Strategy (REMS) to prevent prenatal exposure. No such requirement was introduced for topiramate.

OBJECTIVE

To evaluate the rate of prenatal exposure, contraceptive use, and pregnancy testing among patients with phentermine-topiramate compared with topiramate or other antiobesity medications (AOMs).

DESIGN

Retrospective cohort study.

SETTING

Nationwide health insurance claims database.

PARTICIPANTS

Females aged 12 to 55 years with no infertility diagnosis or sterilization procedure. Patients with other indications for topiramate were excluded to identify a cohort that was likely treated for obesity.

MEASUREMENTS

Patients initiated use of phentermine-topiramate, topiramate, or an AOM (liraglutide, lorcaserin, or bupropion-naltrexone). Pregnancy at treatment initiation, conception during treatment, contraceptive use, and pregnancy testing outcomes were ascertained. Measurable confounders were adjusted for, and extensive sensitivity analyses were done.

RESULTS

A total of 156 280 treatment episodes were observed. 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.

LIMITATIONS

Outcome misclassification; unmeasured confounding due to lack of prescriber data to account for possible clustering and spillover effects.

CONCLUSION

Prenatal exposure seemed to be significantly lower among phentermine-topiramate users under the REMS. Pregnancy testing and contraceptive use appeared to be inadequate for all groups, which deserves attention to prevent the remaining potential exposures.

PRIMARY FUNDING SOURCE

None.