基于FAERS数据库的真实世界研究评估新型四环素的药物不良反应

Real-world study evaluating novel tetracycline adverse drug reactions based on the FAERS database

目的挖掘新型四环素类药物不良反应信号,为临床安全合理使用提供参考。方法提取美国食品药品监督管理局不良事件报告系统数据库中3种新型四环素所有不良事件(ADE)数据,获取奥马环素、替加环素和依拉环素列为“首要怀疑”报告,用报告比值比法(ROR)进行数据分析。结果本研究共识别5896份与新型四环素相关的ADE报告,其中替加环素ADE阳性信号99个,奥马环素为37个,依拉环素为8个。3种新型四环素ADE信号存在较大差异。凝血酶时间延长、淀粉酶异常等与替加环素相关性最强;而未执行规定药物剂量和牙齿变色等与奥马环素相关性较强;血纤维蛋白原降低和静脉炎等与依拉环素相关性最高。替加环素主要累及肝胆系统(ROR=7.15)和血液及淋巴系统(ROR=4.95);奥马环素则涉及胃肠系统(ROR=3.32);而依拉环素与各类检查(ROR=2.79)和循环系统(ROR=2.72)相关性强。本研究还发现多个四环素新ADE,如入睡障碍、胡言乱语、高铁血红蛋白血症、血纤维蛋白原降低等。结论新型四环素ADE信号和累积器官系统特点各不相同。临床在使用新型四环素类药物时,应结合药物ADE特点进行个体化用药和ADE监测。

Objective To provide references for the individualized medicine of tetracyclines through mining the adverse drug events(ADE)signal.Methods All the ADE data were obtained from the Food and Drug Administration adverse event reporting system.The reports of primary suspect for tigecycline,omadacyeline or eravacycline were extracted and analyzed by using the reporting odds ratio(ROR)method.Results We identified 5896 reports of ADE related to tetracyclines,and 99,37 and 8 ADE signals of tigecycline,omadacyeline and eravacycline,respectively.The safety profile of tetracyclines varies.The highest signal intensities of tigecycline were observed in thrombin time prolonged and amylase abnormal.Drug dose titration not performed and tooth discolouration were the highest signal intensities of omadacyeline,while blood fibrinogen decreased and pancreatic enzymes increased were found the highest signal intensities of eravacycline.Meanwhile,the main ADE signals in tigecycline were found in hepatobiliary(ROR=7.15)and blood and lymphatic systems(ROR=4.95),while gastrointestinal system in omadacyeline(ROR=3.32),and investigations(ROR=2.79)and vascular systems(ROR=2.72)in eravacycline,respectively.Furthermore,we also found ADE signals not reported in previous studies,such as sleep disorders and methemoglobinemia.Conclusion The safety profiles of tigecycline,omadacyeline and eravacycline varies.Individualized drug selection and monitoring of ADE according to the characteristics of tetracyclines are needed during treatment.