Li Wenwen, Liu Cuncheng, Zhang Zhongyi, Cai Zhikai, Lv Tailong, Zhang Ruiyuan, Zuo Yaoyao, Chen Shouqiang
Second School of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
Department of Neonatology, Weifang Traditional Chinese Hospital, Weifang, China.
Front Pharmacol. 2024 Sep 2;15:1443555. doi: 10.3389/fphar.2024.1443555. eCollection 2024.
This project aims to identify the top 30 drugs most commonly associated with constipation and their signal values within the FDA Adverse Event Reporting System database.
We extracted adverse drug events (ADEs) related to constipation from the FAERS database spanning from January 1, 2004, to September 30, 2023. We compiled the 30 most frequently reported drugs based on the frequency of constipation events. We employed signal detection methodologies to ascertain whether these drugs elicited significant signals, including reporting odds ratio, proportional reporting ratio, multi-item gamma Poisson shrinker, and information component given by the Bayesian confidence propagation neural network. Furthermore, we conducted a time-to-onset (TTO) analysis for drugs generating significant signals using the medians, quartiles, and the Weibull shape parameter test.
We extracted a total of 50, 659, 288 ADEs, among which 169,897 (0.34%) were related to constipation. We selected and ranked the top 30 drugs. The drug with the highest ranking was lenalidomide (7,730 cases, 4.55%), with the most prevalent drug class being antineoplastic and immunomodulating agents. Signal detection was performed for the 30 drugs, with constipation risk signals identified for 26 of them. Among the 26 drugs, 22 exhibited constipation signals consistent with those listed on the FDA-approved drug labels. However, four drugs (orlistat, nintedanib, palbociclib, and dimethyl fumarate) presented an unexpected risk of constipation. Ranked by signal values, sevelamer carbonate emerged as the drug with the strongest risk signal [reporting odds ratio (95% CI): 115.51 (110.14, 121.15); PRR (χ): 83.78 (191,709.73); EBGM (EB05): 82.63 (79.4); IC (IC025): 6.37 (4.70)]. A TTO analysis was conducted for the 26 drugs that generated risk signals, revealing that all drugs exhibited an early failure type. The median TTO for orlistat was 3 days, the shortest of all the drugs, while the median TTO for clozapine was 1,065 days, the longest of all the drugs.
Our study provides a list of drugs potentially associated with drug-induced constipation (DIC). This could potentially inform clinicians about some alternative medications to consider when managing secondary causes of constipation or caring for patients prone to DIC, thereby reducing the incidence and mortality associated with DIC.
本项目旨在确定美国食品药品监督管理局（FDA）不良事件报告系统数据库中与便秘最常相关的30种药物及其信号值。
我们从2004年1月1日至2023年9月30日的FDA不良事件报告系统（FAERS）数据库中提取了与便秘相关的药物不良事件（ADE）。我们根据便秘事件的发生频率编制了报告最频繁的30种药物。我们采用信号检测方法来确定这些药物是否引发了显著信号，包括报告比值比、比例报告比、多项伽马泊松收缩器以及贝叶斯置信传播神经网络给出的信息成分。此外，我们使用中位数、四分位数和威布尔形状参数检验对产生显著信号的药物进行了起效时间（TTO）分析。
我们总共提取了50659288例药物不良事件，其中169897例（0.34%）与便秘相关。我们挑选并列出了排名前30的药物。排名最高的药物是来那度胺（7730例，4.55%），最常见的药物类别是抗肿瘤和免疫调节药物。对这30种药物进行了信号检测，其中26种药物发现了便秘风险信号。在这26种药物中，22种药物的便秘信号与FDA批准的药物标签上列出的信号一致。然而，有四种药物（奥利司他、尼达尼布、哌柏西利和富马酸二甲酯）出现了意外的便秘风险。按信号值排名，碳酸司维拉姆是风险信号最强的药物[报告比值比（95%可信区间）：115.51（110.14，121.15）；比例报告比（χ）：83.78（191709.73）；经验贝叶斯伽马模型（EB05）：82.63（79.4）；信息成分（IC025）：6.37（4.70）]。对产生风险信号的26种药物进行了起效时间分析，结果显示所有药物均表现为早期失效类型。奥利司他的中位起效时间为3天，是所有药物中最短的，而氯氮平的中位起效时间为1065天，是所有药物中最长的。
我们的研究提供了一份可能与药物性便秘（DIC）相关的药物清单。这可能会为临床医生在处理便秘的继发原因或护理易患药物性便秘的患者时考虑一些替代药物提供参考，从而降低与药物性便秘相关的发病率和死亡率。
