替格瑞洛上市后出血不良反应信号检测与分析

目的:检测替格瑞洛上市后出血不良反应信号,并分析其影响因素,为临床合理用药提供参考。方法:采用报告比值比法(ROR)对美国食品药品监督管理局不良事件报告系统(AERS)数据库进行替格瑞洛不良反应信号检测,应用标准MedDRA分析查询(SMQ)检索其中的出血信号,并利用SPSS 17.0分析年龄、性别、用药时长对出血信号的影响。结果:总的药物不良反应报告6806330份,以替格瑞洛为首要怀疑药物的不良反应报告5279份,经ROR法检测,共得到158个替格瑞洛不良反应信号,其中出血信号42个。统计学分析结果显示:维持剂量时,与其他ADR相比,出血ADR在年龄(P=0.003)、用药时长(P=0.026)分布中差异有统计学意义,在性别(P=0.417)分布中差异无统计学意义;负荷剂量时,与其他ADR相比,出血ADR在年龄(P=0.000)分布中差异有统计学意义,在性别(P=0.846)分布中差异无统计学意义。其中,年龄大于75岁负荷剂量时,维持剂量用药半年内,发生出血ADR风险更大。结论:检测到的替格瑞洛不良反应信号和影响因素,有必要进行进一步信号评价和验证,为临床安全用药提供依据。

Signal detection and evaluation of ticagrelor induced hemorrhage ADR in post marketing experience

OBJECTIVE To detect safety signals of ticagrelor in post-marketing experience, analyze signal effect factors, and provide references for clinical practice.METHODS Reporting odd ratio (ROR) algorithm was used to find out signals from AERS submitted to FDA. Hemorrhage signals were verified by standardized MedDRA queries (SMQ). Analysis of signal effect factors including gender, age and duration of therapy was performed by SPSS 17.0.RESULTS A total of 6806330 reports were found out for all drugs, 5279 reports among them were mainly induced by ticagrelor. A total of 158 signals related to ticagrelor were identified, and 42 of these signals were related to hemorrhage. At maintenance doses, significant differences were observed in age (P=0.003) and medication duration (P=0.026), but not in gender (P=0.417), compared with other ADRs. When administrated at loading doses, significant difference were observed in age (P=0.000) but not in gender (P=0.846), compared with other ADRs. Age older than 75 years old at loading dose and medication duration of 6 months at maintenance dose were risk factors.CONCLUSION Detection and evaluation of safety signals of ticagrelor show that further research is needed to provide references for safety in clinical medication.