基于FAERS数据库对利巴韦林、洛匹那韦/利托那韦、磷酸氯喹不良事件检测与评价

Detection and evaluation of adverse event signals of ribavirin, lopinavir/ritonavir and chloroquine phosphate based on FAERS database

目的挖掘和评价利巴韦林、洛匹那韦/利托那韦(LPV/r)、磷酸氯喹上市后安全信号,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(FDA)不良事件报告系统(FAERS)2004年1月1日至2019年12月31日收录的不良事件报告进行信号挖掘,重点分析3种目标药物上报频数前30位药品不良事件(ADE)信号及特定医学事件(designated medical event, DME)信号。结果 3种目标药物上报频数前30位ADE较为相似,利巴韦林以血液系统毒性信号较显著,LPV/r以肝毒性、免疫重建炎症综合征信号较显著,磷酸氯喹以心脏毒性、眼毒性信号较显著;三者DME共性信号为肝衰竭、溶血症、溶血性贫血、骨髓功能衰竭、Steven-Johnson综合征等。结论基于真实世界自发上报数据库的ADE信号检测有助于利巴韦林、LPV/r、磷酸氯喹的安全性评价,降低临床用药风险。

Objective To mine and evaluate the safety signals of ribavirin, lopinavir/ritonavir, chloroquine phosphate and to provide reference for clinical rational drug use. Methods The reporting odd ratio(ROR) data mining algorithm was used to investigate ADE risk signals from FAERS submitted to the FDA between January 1, 2004 and December 31,2019. The top 30 reporting ADE and designated medical event(DME) signals were the focus of analysis. Results The top 30 ADEs of the three target drugs were similar. What was more significant was the signals from the hematological toxicity of ribavirin, the hepatotoxicity, cardiac toxicity and immune reconstitution inflammatory syndrome of lopinavir/ritonavir and from the cardiotoxicity and ocular toxicity of chloroquine phosphate. The common DME signals of the three drugs were involved in liver failure, hemolysis, hemolytic anemia, bone marrow failure and Steven-Johnson syndrome.Conclusion The detection of ADE signals based on the real-world spontaneous reporting database can contribute to safety evaluation of ribavirin, lopinavir/ritonavir, chloroquine phosphate while reducing the risk of clinical medication.