Division of Epidemiology II (DEPI-II), Office of Pharmacovigilance and Epidemiology(OPE), Office of Surveillance and Epidemiology (OSE), Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA), Silver Spring, MD, USA.
Associate Director, Epidemiology, IQVIA Government Solutions, Virginia, USA.
Pharmacoepidemiol Drug Saf. 2023 Jul;32(7):735-751. doi: 10.1002/pds.5603. Epub 2023 Feb 27.
To evaluate the impact of increased federal restrictions on hydrocodone combination product (HCP) utilization, misuse, abuse, and overdose death.
We assessed utilization, misuse, abuse, and overdose death trends involving hydrocodone versus select opioid analgesics (OAs) and heroin using descriptive and interrupted time-series (ITS) analyses during the nine quarters before and after the October 2014 rescheduling of HCPs from a less restrictive (CIII) to more restrictive (CII) category.
Hydrocodone dispensing declined >30% over the study period, and declines accelerated after rescheduling. ITS analyses showed that immediately postrescheduling, quarterly hydrocodone dispensing decreased by 177M dosage units while codeine, oxycodone, and morphine dispensing increased by 49M, 62M, and 4M dosage units, respectively. Postrescheduling, hydrocodone-involved misuse/abuse poison center (PC) case rates had a statistically significant immediate drop but a deceleration of preperiod declines. There were small level increases in codeine-involved PC misuse/abuse and overdose death rates immediately after HCP's rescheduling, but these were smaller than level decreases in rates for hydrocodone. Heroin-involved PC case rates and overdose death rates increased across the study period, with exponential increases in PC case rates beginning 2015.
HCP rescheduling was associated with accelerated declines in hydrocodone dispensing, only partially offset by smaller increases in codeine, oxycodone, and morphine dispensing. The net impact on hydrocodone and other OA-involved misuse/abuse and fatal overdose was unclear. We did not detect an immediate impact on heroin abuse or overdose death rates; however, the dynamic nature of the crisis and data limitations present challenges to causal inference.
评估联邦对氢可酮复方制剂(HCP)使用、误用、滥用和过量死亡限制增加的影响。
我们使用描述性和中断时间序列(ITS)分析,评估了涉及氢可酮与选定的阿片类镇痛药(OA)和海洛因的利用、误用、滥用和过量死亡趋势,在 HCP 从限制较少的(CIII)类别重新分类为限制更多的(CII)类别前后的九个季度进行。
研究期间,氢可酮的配药量下降了>30%,重新分类后下降速度加快。ITS 分析显示,重新分类后立即,每季度氢可酮的配药量减少了 1.77 亿剂量单位,而可待因、羟考酮和吗啡的配药量分别增加了 4900 万、6200 万和 400 万剂量单位。重新分类后,氢可酮相关误用/滥用中毒控制中心(PC)病例率立即出现统计学显著下降,但前期下降速度放缓。可待因相关 PC 误用/滥用和过量死亡病例率略有上升,但小于氢可酮病例率的下降幅度。海洛因相关 PC 病例率和过量死亡病例率在整个研究期间呈上升趋势,PC 病例率的指数增长始于 2015 年。
HCP 的重新分类与氢可酮配药量的加速下降有关,仅部分被可待因、羟考酮和吗啡配药量的较小增加所抵消。对氢可酮和其他 OA 相关误用/滥用和致命过量的净影响尚不清楚。我们没有发现对海洛因滥用或过量死亡病例率的即时影响;然而,危机的动态性质和数据限制对因果推断提出了挑战。