原研与仿制伏立康唑注射剂相关急性肾损伤真实世界监测评价研究

Real world monitoring and evaluation of acute kidney injury associated with original and generic voriconazole injection

目的:探讨伏立康唑注射制剂原研药与仿制药在住院人群中相关急性肾损伤(AKI)的发生率及危险因素。方法:依托医疗机构药物不良事件主动监测与智能评估警示系统(ADE-ASAS),回顾性自动监测某中心自2010年1月-2021年6月间使用伏立康唑注射制剂原研药与仿制药的所有住院患者,对相关AKI的发生率及特征进行分析,探究危险因素。结果:原研药相关AKI的发生率为2.58%(70/2717),仿制药相关AKI的发生率为1.51%(35/2322),原研药组的严重AKI占比高于仿制组(28.57%vs 17.14%);两组中阳性病例的中位年龄均高于总体人群。相关风险因素分析显示,联合使用≥3种肾毒性药物及白蛋白<30 g·L^(-1)在原研药与仿制药组均有统计学意义,原研药相关AKI的风险因素还有血红蛋白≤90 g·L^(-1)。结论:伏立康唑原研药与仿制药相关AKI发生率及风险因素的差异可能与辅料相关,但用药目标差异的影响有待证实;对住院期间合并低白蛋白、联合使用多种肾毒性药物、贫血的老年患者,临床应用该药时应注意监测其肾功能。

Objective:To investigate the incidence and risk factors of acute kidney injury(AKI)associated with original and generic voriconazole injection in hospitalized population.Methods:All inpatients receiving original and generic voriconazole injection from January 2010 to June 2021 were automatically and retrospectively monitored based on the adverse drug events active surveillance and assessment system(ADE-ASAS),and the incidence and characteristics of AKI were analyzed to explore relative risk factors.Results:The incidence of AKI related to original and generic voriconazole was 2.58%(70/2717)and 1.51%(35/2322),respectively.The proportion of severe AKI in patients using original voriconazole was higher than that of generic voriconazole(28.57%vs 17.14%).In both groups,the median age of positive cases was higher than that of the general population.Results of analysis on risk factors showed that combined use of three or more nephrotoxic drugs and albumin<30 g·L^(-1) were statistically significant in both groups,and hemoglobin≤90 g·L^(-1) was only the risk factor of AKI associated with original voriconazole.Conclusion:Differences in the incidence and risk factors of AKI associated with original and generic voriconazole injection might be related to excipients while the effect of different drug targets remained to be confirmed.For elderly patients with hypoalbumin,combined use of multiple nephrotoxic drugs and anemia during hospitalization,more attentions should be paid to monitoring renal function during clinical application of voriconazole.