硫酸羟氯喹致视觉损害不良反应信号检测与分析

doi:10.19803/j.1672-8629.2022.06.16

摘要/Abstract

摘要： 目的利用数据挖掘技术,评价《上海市2019冠状病毒病综合救治专家共识》推荐的治疗新型冠状病毒肺炎（COVID-19）的药品硫酸羟氯喹上市后安全性信号,为临床安全应用该药提供依据。方法对2004年1月1日至2020年12月31日安徽省药品不良反应监测系统收集的怀疑药品通用名称为硫酸羟氯喹的药品不良反应（ADR）,采用报告比值比法（ROR）进行信号检测,重点对视觉损害相关ADR病例进行提取分析与数据挖掘。结果提取的292份病例报告中,ADR主要涉及皮肤及其附件、中枢及外周神经系统、胃肠系统、视觉损害、听觉和前庭功能障碍等。信号检测中,有30例病例涉及视觉损害系统,占ADR病例数的10.3%。信号值排名前10位中,涉及畏光、视物模糊、视觉异常、眼异常等视觉损害系统。原患疾病为系统性红斑狼疮者发生视觉损害的比例最高。视觉损害病例发生ADR时间间隔范围较广。结论基于真实世界的ADR信号检测,有助于硫酸羟氯喹上市后安全性评价,可为抗COVID-19疫情的临床合理使用提供参考,为临床上的老药新用提供信息。

关键词: 硫酸羟氯喹, 新型冠状病毒肺炎, 视觉损害, 信号检测, 药品不良反应

Abstract: Objective To evaluate the post marketing safety signals of hydroxychloroquine sulfate recommended by the expert consensus on comprehensive treatment of coronavirus diseases in Shanghai in 2019 in order to provide evidence for safe clinical use of this drug. Methods ADR related to the suspected drug commonly known as "hydroxychloroquine sulfate" that were collected by Anhui ADR monitoring system between Jan 1, 2004 and Dec 31, 2020 were selected. The report odds ratio (ROR) method was used for signal detection, focusing on the extraction, analysis, evaluation and data mining of cases of such adverse reactions as visual impairment. Results Among the 292 case reports, ADR mostly involved the skin and its appendages, central and peripheral nervous systems and the gastrointestinal system, and were manifested as visual impairment, hearing and vestibular dysfunction. According to signal detection, 30 cases involved visual impairment, accounting for 10.3% of the total cases of ADR. The top ten signal values were related to photophobia, blurred vision, visual abnormalities, adverse reactions of eyes and other visual impairment. The incidence of visual impairment was the highest among patients whose primary disease was systemic lupus erythematosus. The time interval of ADR was wide among patients with visual impairment. Conclusion Signal detection of ADR based on the real world can help assess the safety of hydroxychloroquine sulfate, which is expected to provide reference for the rational use of drugs for COVID-19 and for clinical utilization of conventional drugs.

Key words: hydroxychloroquine sulfate, COVID-19, visual impairment, signal detection, adverse drug reaction

中图分类号:

R994.11

王铁柱. 硫酸羟氯喹致视觉损害不良反应信号检测与分析[J]. 中国药物警戒, 2022, 19(6): 657-660.

WANG Tiezhu. Signal detection and analysis of adverse reaction of hydroxychloroquine sulfate induced visual impairment[J]. Chinese Journal of Pharmacovigilance, 2022, 19(6): 657-660.

参考文献

[1] CUI C, MO XT, TU SQ, et al.Progress in clinical pharmacology of hydroxychloroquine sulfate[J]. Chinese Journal of Clinical Pharma-cology and Therapeutics(中国临床药理学与治疗学), 2020, 25(2): 221-226.
[2] Expert group on clinical treatment of coronavirus diseases in Shanghai in 2019. Expert consensus on comprehensive treatment of coronavirus diseases in Shanghai in 2019 in 2019. Expert consensus on comprehensive treatment of coronavirus diseases in Shanghai in 2019[J]. Chinese Journal of Infectious Diseases(中华传染病杂志), 2020, 38(3): 134-138.
[3] ZHANG SL, MIAO CY.Pharmacological characteristics of chloroquine and hydroxychloroquine and application of New Coronavirus pneumonia (COVID-19) treatment[J]. China Journal of Pharmacology and Toxicology(中国药理学与毒理学杂志), 2020, 34(4): 261-270.
[4] CHRISTOPHE B, WASSIM D, NATASCHA C, et al.Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities[J]. J Med Chem, 2006, 49(9): 2845-2849.
[5] WANG T, LIU JC, PANG Y.Pharmacological mechanism and safety risk analysis of hydroxychloroquine[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2020,17(7): 385-388.
[6] JORGE A, UNG C, YOUNG LH, et al.Hydroxychloroquine retinopathy-implications of research advances for rheumatology care[J]. Nat Rev Rheumatol, 2018, 14(12): 693-703.
[7] National Center for ADR monitoring, Center for drug reevaluation of State Food and drug administration. WHO terminology of adverse drug reactions(WHO药品不良反应术语集)[M]. Beijing: China Medical Science Press, 2002: 1-172.
[8] LI SS, DING YX, YIN AQ.Signal mining of 392 spontaneous reports of cefoperazone / sulbactam adverse reactions[J]. Journal of Pharmacoepidemiology(药物流行病学杂志), 2018, 27(12): 815-818.
[9] KOU GX, WANG Y, GUO J, et al.Signal mining and analysis of adverse reaction events of digestive dysfunction induced by sofosbuvir[J]. Journal of Clinical Hepatobiliary Diseases(临床肝胆病杂志), 2018, 34(1): 68-72.
[10] SRINIVASA A, TOSOUNIDOU S, GORDON C.Increased incidence of gastrointestinal side effects in patients taking hydroxychloroquine:a brand-related issue?[J]. J Rheumatol, 2017, 44(3): 398.
[11] COSTEDOAT-CHALUMEAU N, HULOT JS, AMOURA Z, et al.Heart conduction disorders related to antimalarials toxicity:an analysis of electrocardiograms in 85 patients treated with hydroxy-chloroquine for connective tissue diseases[J]. Rheumatology, 2007, 46(5): 808-810.
[12] YUSUF I, FOOT B, GALLOWAY J, et al.The Royal College of Ophthalmologists recommendations on screening for hydroxych-loroquine and chloroquine users in the United Kingdom:executive summary[J]. Eye, 2018, 32(7): 1168-1173.
[13] WANG L, ZHANG N, GONG L, et al.Detection and evaluation of adverse reaction signals of chloroquine and hydroxychloroquine based on FDA adverse event database and designated medical events[J]. Chinese Journal of Hospital Pharmacy(中国医院药学杂志), 2020,40(18): 1921-1928.
[14] PONTICELLI C, MORONI G.Hydroxychloroquine in systemic lupus erythematosus (SLE)[J]. Expert Opinion on Drug Saf, 2017, 16(1/6): 411-419.
[15] GAO Q.Chloroquine pharmacological characteristics and recomm-endations for the treatment of New Coronavirus pneumonia[J]. China Journal of Schistosomiasis Control, 2020, 32(2): 119-122, 139.
[16] NOAH F.Embracing the unknown: disentangling the complexities of the soil microbiome[J]. Nat Rev Microbiol, 2017, 15(10): 579-590.
[17] SUN WJ, XU BX, LIU YQ.51 case analysis of antiviral drugs in new coronavirus pneumonia patients[J]. China Hospital Drug Evaluation and Analysis(中国医院用药评价与分析), 2021, 21(3): 362-365.
[18] State Health Commission of the People's Republic of China. Novel coronavirus pneumonia for adjusting the dosage and dosage of chloroquine[EB/OL]. (2020-02-28)[2020-02-28]. http://www.nhc.gov.cn/yzygj/s7653p/202002/0293d017621941f6b2a4890035243730.shtml.