中国药物警戒 ›› 2024, Vol. 21 ›› Issue (12): 1425-1431.
DOI: 10.19803/j.1672-8629.20240036

• 安全与合理用药 • 上一篇    下一篇

基于美国FAERS数据库的左甲状腺素钠片不良事件信号挖掘与分析

陈崇泽1, 周甜雨2, 孙思曼2, 郭姝姝3, 靳洪涛4,5,*   

  1. 1福建省福州市长乐区人民医院药剂科,福建 福州 350200;
    2陕西中医药大学药学院,咸阳712046;
    3沈阳药科大学生命科学与生物制药学院,辽宁 沈阳 110016;
    4中国医学科学院北京协和医学院药物研究所新药安全评价研究中心,北京 100050;
    5北京协和建昊医药技术开发有限责任公司,北京100176
  • 收稿日期:2024-01-11 出版日期:2024-12-15 发布日期:2024-12-16
  • 通讯作者: *靳洪涛,男,博士,研究员·博导,药物毒害因素识别与有效防控。E-mail: jinhongtao@imm.ac.cn
  • 作者简介:陈崇泽,男,硕士,副主任药师,药品不良反应监测与临床药学。
  • 基金资助:
    中国毒理学会临床毒理专项（CST2021CT101）

Risk Signal Mining of Adverse Events Related to Levothyroxine Sodium Tablets Based on FAERS

CHEN Chongze1, ZHOU Tianyu2, SUN Siman2, GUO Shushu3, JIN Hongtao4,5,*   

  1. 1Department of Pharmacy, Fuzhou Changle District People's Hospital, Fuzhou Fujian 350200, China;
    2College of Pharmacy, Shaanxi University of Traditional Chinese Medicine, Xianyang 712046,China;
    3School of Life Sciences and Biopharmaceutical Science, Shenyang Pharmaceutical University, Liaoning Shenyang 110016, China;
    4New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;
    5Beijing Union-Genius Pharmaceutical Technology Development Co., Ltd., Beijing 100176, China
  • Received:2024-01-11 Online:2024-12-15 Published:2024-12-16

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摘要： 目的 分析和挖掘左甲状腺素钠片的药品不良事件（ADE）,为临床安全合理用药提供参考。方法 检索美国食品药品监督管理局(Food and Drug Administration, FDA)不良事件报告系统(Adverse Event Reporting System, FAERS）数据库,收集自2015年第一季度至2023年第二季度以左甲状腺素钠片为首要怀疑药物有关的ADE数据。采用报告比值比法（Reporting Odds Ration, ROR）、比例报告比值法（Proportional Reporting Ratio, PRR）、贝叶斯置信区间神经传播网络法（Bayesian Confidence Interval Neural Propagation Network Method, BCPNN）和多重伽马-泊松收缩估计法(Multi-item Gamma Poisson Shrinker, MGPS)筛选ADE的有效信号。结果 共收集到以左甲状腺素钠片为首要怀疑药物的ADE报告271 356例,主要报告人群为女性（198 219份,73.05%）;报告年龄分布以18~85岁患者居多（62.46%）;挖掘出左甲状腺素钠片ADE信号5 991个,排除非ADE信号后得到3 371个信号,累及系统-器官20个。报告例次数排名前5位的首选术语（PT）是疲劳（22 511例次）、恶心（17 591例次）、腹泻（16 400例次）、头痛（15 043例次）和呼吸困难（12 866例次）。报告信号强度排名前5位的PT是新生儿坏疽（ROR=267.57, IC025=4.66）、支气管结石症（ROR=187.30, IC025=267.57）、谐音联想（ROR=107.03, IC025=267.57）、反式三碘甲腺原氨酸升高（ROR=89.19, IC025=4.42）、游离甲状腺素指数下降（ROR=80.27, IC025=4.38）; 对产生ADE信号进行二次筛选,新生儿风险信号强度排名前3位的PT分别为新生儿坏疽、新生儿肠扩张、新生儿甲状腺毒症;结石风险信号强度排前3位PT分别为支气管结石症、脑结石、鹿角状结石;共发现说明书未记载的ADE信号146个,主要表现在各类检查、胃肠系统疾病、感染及侵染类疾病、各类神经系统疾病、良性和恶性及性质不明的肿瘤等。结论 左甲状腺素钠片在甲状腺功能减退患者中有潜在新生儿、结石、感染及继发性肿瘤ADE风险,建议服用左甲状腺素钠片的患者进行临床多学科随访。

关键词: 左甲状腺素钠片, 美国食品药品监督管理局不良事件报告系统, 报告比值比法, 比例报告比值法, 贝叶斯置信区间神经传播网络法, 多重伽马-泊松收缩估计法, 自发报告, 不相称性分析, 数据挖掘

Abstract: Objective To analyze the adverse drug events (ADE) caused by levothyroxine sodium tablets to provide a reference for rational and safe clinical use. Methods The U. S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) was searched to retrieve the ADE data on the primarily suspected drug collected from the first quarter of 2015 to the second quarter of 2023. The reporting odds ratio (ROR)、proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCNPP) and multi-item gamma poisson shrinker (MGPS) methods were used to screen for effective signals of ADEs of drugs. Results A total of 271 356 ADEs related to levothyroxine tablets as the primary suspect were reported. Most of the people involved were women (198 219, 73.05%) and the patients ranged from 18 to 85 in age (62.46%). A total of 5 991 adverse events of levothyroxine sodium tablets were mined, 3 371 signals were obtained after excluding non-drug adverse event signals, and 20 organ systems were found to be involved. Fatigue (22 511 items), nausea (17 591 items), diarrhea (16 400 items), headache (15 043 items) and dyspnea (12 866 items)were the top five ADEs reported.Analysis showed that neonatal gangrene (ROR=267.57, IC025=4.66), bronchiolithiasis (ROR=187.30, IC025=267.57), homophonic association (ROR=107.03, IC025=267.57), increased trans-triiodothyronine (ROR=89.19, IC025=4.42), and decreased free thyroxine indexes (ROR=80.27, IC025=4.38）were the top five ADEs in terms of intensities of signals. Based on secondary screening, the top three PTs related to the neonatal risk signal intensity were neonatal gangrene, neonatal intestinal dilation, and neonatal thyrotoxicosis. The top three PTs regarding the stone risk signal intensity were bronchial stones, cerebral stones, and staghorn stones. A total of 146 signals that were not recorded in the instructions were found, which were mostly manifested in various examinations, gastrointestinal system diseases, infections and invasive diseases, nervous system diseases, benign and malignant tumors of unknown nature. Conclusion Levothyroxine sodium tablets can potentially cause such ADRs as calculuses, infections and secondary tumors in patients with hypothyroidism. Clinical multidisciplinary follow-up is recommended for patients taking levothyroxine sodium tablets.

Key words: Levothyroxine Sodium Tablets, FAERS, Reporting Odds Ratio (ROR), Proportional Reporting ratio (PRR), Bayesian Confidence Interval Neural Propagation Network Method (BCPNN), Multi-item Gamma Poisson Shrinker, (MGPS), Spontaneous Reporting, Uncommensurate Analysis, Data Mining

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