Trend changes of national zolpidem users and exposure cases after FDA drug safety communications

Abstract

Purpose: To evaluate the impact of FDA's 2013 zolpidem Drug Safety Communications (DSCs), which recommended lowering the initial dose to mitigate drowsiness, on national estimates of zolpidem users and zolpidem exposure cases. Methods:We analyzed trend changes of national zolpidem users from the IQVIA Total Patient Tracker (TPT) and zolpidem exposure cases reported to the National Poison Data System (NPDS), 2009-2018. To control for time varying confounding, the adjusted trends were analyzed using simple and controlled interrupted time series (ITS). We also adjusted for seasonal changes. Three sedating antidepressants were used together as a control. Results:The national estimates of high-dose zolpidem users in TPT decreased significantly in the month immediately post-DSC; the absolute level decrease was À12.51 (95% CI: À14.12, À10.89) per 10 000 U.S. population relative to sedating antidepressants. The trend continuously decreased post-DSC, resulting in a 59% overall decrease by the end of the study period. There was a larger decrease in high-dose zolpidem use in females than in males. There was a level decrease of zolpidem exposure cases in the NPDS immediately post-DSC, À0.37 absolute decline (95% CI, À0.53, À0.20) per 10 000 national zolpidem users; or À1.33 absolute decline (95% CI, À1.54, À1.13) per 1000 total NPDS exposure cases relative to sedating antidepressants. Similar patterns were observed for cases reporting drowsiness. The results from the single ITS and controlled ITS were similar.Conclusions: Zolpidem users and exposure cases decreased significantly post-DSC, suggesting practitioners and patients became aware of and responded to the zolpidem DSCs. K E Y W O R D S controlled interrupted time series, drug safety communication, regulatory impact Key Points• A controlled interrupted time series analysis was performed to evaluate the impact of the FDA's zolpidem DSCs in 2013, which recommended lowering the initial dose to mitigate drowsiness.