| 16 | 0 | 49 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 基于日本药物不良事件报告数据库（JADER）对萘莫司他的药物不良事件（ADEs）数据进行分析和挖掘，总结其ADEs的规律和特征，为安全用药提供参考。方法 基于JADER获取2004年1月至2025年12月的萘莫司他ADEs报告，以报告比值比（ROR）、比例报告比值（PRR）、贝叶斯置信传播神经网络（BCPNN）及经验贝叶斯几何平均数（EBGM）等算法作为阳性信号判断标准，同时分析阳性信号的临床优先级、ADEs发生时间规律和死亡结局的风险因素。结果 在首选术语（PT）水平上，共得到萘莫司他阳性信号25个，包括过敏性休克、休克、高钾血症、血压降低和速发性严重过敏反应等ADEs，其中新的阳性信号9个，包括寒战、获得性因子V缺乏症、淀粉酶升高、烧灼感和腹壁血肿等ADEs。在系统器官分类（SOC）水平上，以免疫系统疾病和血管与淋巴管类疾病为主；以过敏性休克为临床高优先级信号；所有ADEs的中位发生时间为1 d，且不同SOC的ADEs发生时间存在差异（P<0.000 1）。年龄与合并用药数量是萘莫司他死亡ADEs的相关危险因素（OR分别为1.06和1.10 , P<0.01）。结论 萘莫司他上报的ADEs案例中以老年患者、男性为主，症状集中于过敏反应和出血倾向。ADEs发生迅速，ADEs死亡结局风险与患者年龄及合并用药数量相关。
Abstract：AIM To analyze and characterize adverse drug events(ADEs) of nafamostat using the JADER database, and to provide evidence for its safe clinical use. METHODS Based on the JADER database, ADE reports for nafamostat were retrieved from January 2004 to December 2025. Reporting odds ratio(ROR), proportional reporting ratio(PRR), Bayesian confidence propagation neural network(BCPNN), and empirical Bayesian geometric mean(EBGM) were employed as the criteria for determining positive signals. Concurrently, the clinical priority of positive signals, time to onset(TTO) of ADEs, and the risk factors death outcomes were analyzed. RESULTS At the preferred term(PT) level, 25 positive signals were identified for nafamostat, primarily including anaphylactic shock, shock, hyperkalemia, decreased blood pressure, and immediate hypersensitivity reactions. Among these, 9 were novel positive signals, including chills, acquired factor V deficiency, increased amylase, burning sensation, and abdominal wall hematoma. At the system organ class(SOC) level, ADEs were mainly distributed in immune system disorders and vascular disorders. Anaphylactic shock was identified as a high-priority clinical signal. The median TTO for all ADEs was 1 day, with significant differences observed across different SOCs(P < 0.000 1). Age and concomitant medication count were identified as risk factors for fatal ADEs outcomes(OR were 1.06 and 1.10 respectively, P < 0.01). CONCLUSION ADEs reported for nafamostat predominantly occurred in elderly male patients, with clinical manifestations centered on allergic reactions and hemorrhagic tendencies. These ADEs developed rapidly across different types. The risk of fatal outcomes correlated with patients' age and the number of concomitant medications.
[1]丁小强,毛永辉.甲磺酸萘莫司他的血液净化抗凝应用专家共识[J].上海医药,2024,47(3):129.
[2]刘志艳,向倩,崔一民.甲磺酸萘莫司他临床应用的研究现状[J].中国临床药理学杂志,2020,36(15):2368.
[3]MINAKATA D,FUJIWARA S I,IKEDA T,et al.Comparison of gabexate mesilate and nafamostat mesilate for disseminated intravascular coagulation associated with hematological malignancies[J].Int J Hematol,2019,109(2):141.
[4]DOI K,NISHIDA O,SHIGEMATSU T,et al.The Japanese clinical practice guideline for acute kidney injury 2016[J].Clin Exp Nephrol,2018,22(5):985.
[5]LIN Y,SHAO Y M,LIU Y C,et al.Efficacy and safety of nafamostat mesilate anticoagulation in blood purification treatment of critically ill patients:a systematic review and meta-analysis[J].Ren Fail,2022,44(1):1263.
[6]LEE Y K,LEE H W,CHOI K H,et al.Ability of nafamostat mesilate to prolong filter patency during continuous renal replacement therapy in patients at high risk of bleeding:a randomized controlled study[J].PLoS One,20 14,9(10):e108737.
[7]CHOI J Y,KANG Y J,JANG H M,et al.Nafamostat mesilate as an anticoagulant during continuous renal replacement therapy in patients with high bleeding risk:a randomized clinical trial[J].Medicine,2015,94(52):e2392.
[8]SHU Y M,HE X C, WU P,et al.Gastrointestinal adverse events associated with semaglutide:a pharmacovigilance study based on FDA adverse event reporting system[J].Front Public Health,2022,10:996179.
[9]WANG J Y,ZHANG Z,LIU X Z,et al.Exploring novel adverse events of nefecon[J].Kidney Int Rep,2024,9(9):2705.
[10]SHU Y M,CHEN J, DING Y L,et al.Adverse events with risankizumab in the real world:postmarketing pharmacovigilance assessment of the FDA adverse event reporting system[J].Front Immunol,2023,14:1169735.
[11]CECCO S,PULIGHEDDU S,FUSAROLI M,et al.Emerging toxicities of antibody-drug conjugates for breast cancer:clinical prioritization of adverse events from the FDA adverse event reporting system[J].Target Oncol,2024,19(3):435.
[12]CHESNAYE N C,CARRERO J J,HECKING M,et al.Differences in the epidemiology,management and outcomes of kidney disease in men and women[J].Nat Rev Nephrol,2024,20(1):7.
[13]BOEHM T,ALIX M,PETROCZI K, et al.Nafamostat is a potent human diamine oxidase inhibitor possibly augmenting hypersensitivity reactions during nafamostat administration[J].J Pharmacol Exp Ther,2022,382(2):113.
[14]MORPETH S C, VENKATESH B,TOTTERDELL J A,et al.A randomized trial of nafamostat for covid-19[J].NEJM Evid,2023,2(11):EVIDoa2300132.
[15]MATSUMOTO T,OKUWAKI K,IMAIZUMI H,et al.Nafamostat mesylate is not effective in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis[J].Dig Dis Sci,2021,66(12):4475.
[16]EHTISHAM M,SHAFIQ M A,SHAFIQUE M,et al.Owren's disease:a rare deficiency[J].Cureus,2021,13(8):e17047.
[17]HALAB Y R, POPMA C J,COHEN A,et al.D-Dimer elevation and adverse outcomes[J].J Thromb Thrombolysis,2015,39(1):55.
[18]BARBARA M,TSEN A,ROSENKRANZ L.Acute pancreatitis in chronic dialysis patients[J].Pancreas,2018,47(8):946.
[19]VIDALES-BRAZ B M,DA SILVA N M O, LOBATO R,et al.Detection of hepatitis C virus in patients with terminal renal disease undergoing dialysis in southern Brazil:prevalence,risk factors,genotypes,and viral load dynamics in hemodialysis patients[J].Virol J,2015,12:8.
[20]SHEPSHELOVICH D,YELIN D,BACH L O,et al.Chills during hemodialysis:prediction and prevalence of bacterial infections-a retrospective cohort study[J].Am J Med,2017,130(4):477
[21]DUFOUR I,BRIOL S,VAN REGEMORTER E,et al.A case of acute intravascular hemolysis during dialysis:a quiz[J].Am J Kidney Dis,2023,81(3):A12.
[22]FUJITA H,SAKUMA R,FUJIMOTO S,et al.Nafamostat mesilate,a noncalcium compound,as an anticoagulant,induces calciumdependent haemolysis when infused with packed erythrocytes[J].Transfus Med,2012,22(3):186.
[23]LIU Q,CUI Z W,DENG C,et al.A real-world pharmacovigilance analysis of adverse events associated with irbesartan using the FAERS and JADER databases[J].Front Pharmacol,2024,15:1485190.
[24]Joint Task Force on Practice Parameters;American Academy of Allergy,Asthma and Immunology;American College of Allergy,Asthma and Immunology;Joint Council of Allergy,Asthma and Immunology.Drug allergy:an updated practice parameter[J].Ann Allergy Asthma Immunol,2010,105(4):259.
[25]BÖHM R, PROKSCH E,SCHWARZ T,et al.Drug hypersensitivity.Dtsch Arztebl Int, 2018,15(29-30):501.
[26]FLETCHER B R,DAMERY S,AIYEGBUSI O L,et al.Symptom burden and health-related quality of life in chronic kidney disease:a global systematic review and meta-analysis[J].PLoS Med,2022,19(4):e1003954.
[27]COSGRAVE N,FRYDENLUND J,BEIRNE F,et al.Hospital admissions due to adverse drug reactions and adverse drug events in older adults:a systematic review[J].Age Ageing,2025,54(8):afaf231.
基本信息:
DOI：10.19577/j.1007-4406.2026.04.009
中图分类号:R969
引用信息:
[1]王晓婉,方欢,谢菁.基于JADER数据库的萘莫司他不良事件分析[J].中国临床药学杂志,2026,35(04):341-347.DOI:10.19577/j.1007-4406.2026.04.009.
2026-04-25
2026-04-25