摘要
目的对奈玛特韦片/利托那韦片治疗重症新型冠状病毒感染(COVID-19)的安全性文献进行系统回顾,以期为奈玛特韦片/利托那韦片的安全用药提供参考。方法计算机检索中国期刊全文数据库、万方数据库知识服务平台、维普资讯、Pubmed、Embase、The Cochrane Library和WHO COVID-19 Research Data⁃base,检索时间为数据库建库至2023年1月16日。统计关于奈玛特韦片/利托那韦片相关ADR的病例报告和病例系列并进行归纳分析,同时围绕ADR机制、处理措施等问题及所提示的特殊人群、相互作用等临床关注点进行综述和讨论。结果共检索844篇文献,最终纳入12篇病例报告,涉及12例患者,年龄最小5岁,中位年龄43岁。报告最多的ADR为药物相互作用引起肾损伤(8例),相互作用药物均为他克莫司,其余ADR分别为皮疹(1例)、疾病反弹(1例)、肾功能异常(1例)和中性粒细胞减少(1例)。经Naranjo量表进行因果关系判定,除疾病反弹和中性粒细胞减少判定为“可能”外,其他ADR均为“很可能”或“肯定”。除病例报告外,其他类型研究对疾病反弹、儿童、肾损伤、肝损伤、免疫抑制和妊娠期妇女等特殊群体用药提供了部分证据。除可疑的疾病反弹风险,奈玛特韦片/利托那韦片在真实世界的常见ADR与临床试验基本一致。结论不应因担心疾病反弹风险而拒绝奈玛特韦片/利托那韦片应用于COVID-19高危人群。奈玛特韦片/利托那韦片与他克莫司的相互作用报道较多,但通过监测他克莫司血药浓度,风险可控。针对12岁以下儿童和严重肝损伤患者使用奈玛特韦片/利托那韦片证据不充分。部分研究对药品说明书中禁止的重度肾损伤患者的剂量做出推荐,但仍需进一步研究。妊娠期和哺乳期妇女使用奈玛特韦片/利托那韦片的短期结局似乎较安全。
Objective To make a systematic review of the safety of nirmatrelvir/ritonavir tablets in the treatment of severe corona virus disease(COVID-19)and provide reference for the safe clinical use.Methods Cases of adverse drug reactions(ADR)related to nirmatrelvir/ritonavir were collected from CNKI,Wanfang Data,VIP,PubMed,Embase,the Cochrane Library and WHO COVID-19 Research Database.Clinical critically concerns such as special population or drug-drug interaction,and the mechanism and treatment of ADR were discussed.The retrieval time was limited from the establishment of the database to January 16,2023.Results A total of 844 literatures were retrieved,and 12 case reports were included with a total of 12 patients.The median age was 43 years old and the youngest patient was 5 years old.The most reported ADRs were drug-drug interaction induced kidney injury(n=8),all of which were interacted with tacrolimus,and the other ADRs were rash(n=1),disease recurrence(n=1),abnormal renal function(n=1)and neutropenia(n=1).According to the causality analysis by Naranjo scale,disease recurrence and neutropenia were"possible",while the other ADRs were"probable"or"definite".In addition to case reports,other types of publications provide limited evidence for nirmatrelvir/ritonavir in special population such as disease recurrence,children,renal impairment,liver impairment,immunosuppression and pregnant women.The common ADRs of nirmatrelvir/ritonavir in the real world are largely consistent with clinical trials,except for the suspected risk of disease recurrence.Conclusion Application of nirmatrelvir/ritonavir in high-risk population for COVID-19 shouldn't be denied because of the concerns about the risk of disease recurrence.Interactions between nirmatrelvir/ritonavir and tacrolimus have been widely reported,but the risk can be controlled by monitoring tacrolimus concentrations.There is insufficient evidence for the use of nirmatrelvir/ritonavir in children under 12 years old and in patients with severe liver injury.Some studies recommen
作者
安鹏姣
刘鑫
张波
AN Peng-jiao;LIU Xin;ZHANG Bo(Department of Pharmacy,State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China)
出处
《临床药物治疗杂志》
2023年第9期36-43,共8页
Clinical Medication Journal
基金
中央高水平医院临床科研业务费资助项目(2022-PUMCH-B-059)
中国医学科学院医学与健康科技创新工程2021年“揭榜挂帅”项目,中国罕见病的精准诊疗研究(2021-I2M-1-003)。
