基于不良反应文献分析探讨洛匹那韦/利托那韦在新型冠状病毒肺炎中的安全使用

Safe Use of Lopinavir/Ritonavir for COVID-19 Based on Literature Analysis of Adverse Reactions

目的探究洛匹那韦/利托那韦致不良反应的临床特点,为其在新型冠状病毒肺炎中安全使用提供参考。方法检索中国知网、万方、维普、Pubmed和Embase数据库,收集截至2020年2月15日发表的洛匹那韦/利托那韦致不良反应的文献,对患者的基本信息、药物使用情况、累及系统-器官、临床表现、药物相互作用、治疗及转归等进行回顾性分析。结果共纳入99篇文献,120例患者,其中男性81例,女性39例,平均年龄(39.6±14.8)岁;艾滋病110例,艾滋病毒暴露后预防10例。不良反应中位出现时间为1.0(0.3~5.0)个月,用药10天内出现的有40例。所有时间段内不良反应累及系统-器官主要以内分泌代谢系统、皮肤及其附件、心血管系统、消化系统损害等为主;用药10天内累及系统-器官主要以心血管系统、血液系统、皮肤及其附件、消化系统、泌尿系统损害为主,其中急性肾损伤、白细胞减少、完全性房室传导阻滞、血小板减少、心律失常、皮疹、瘙痒等较为多见。120例不良反应中48例是由于药物相互作用所致,主要涉及氟替卡松、曲安奈德、长春碱、他克莫司、华法林、左甲状腺素、多西他赛、麦角胺等。经过治疗后,111例患者不良反应症状好转,4例患者症状恶化,5例患者死亡。结论应重视用药初期洛匹那韦/利托那韦所致的不良反应,避免药物相互作用,确保用药安全。

Objective To explore the clinical characteristics of adverse reactions induced by lopinavir/ritonavir so as to provide reference for its safe use in COVID-19 patients.Methods Literature related to adverse reactions induced by lopinavir/ritonavir published as of February 15,2020 was retrieved from CNKI,VIP Chinese full-text database,Wanfang database,Pubmed and Embase,and analyzed statistically in terms of the basic information of patients,use of medicines,systems or organs involved,clinical symptoms,drug-drug interactions,treatment and outcomes.Results A total of 99 papers involving 120 cases were enrolled with an average age of(39.6±14.8)years,including 81 males and 39 females.110 of these cases were AIDS patients and 10 were cases of post-exposure prophylaxis.The median onset time of adverse reactions was 1.0(0.3 to 5.0)month,with 40 cases within 10 days of administration.Adverse reactions related to systems or organs at any time point occurred mainly in the form of damage to the endocrine and metabolic system,skin and its accessories,cardiovascular system and the digestive system.However,within 10 days of administration,adverse reactions were mostly manifested as damage to the cardiovascular system,blood system,skin and its accessories,digestive system,and urinary system.Acute renal injury,leucopenia,complete atrioventricular block,thrombocytopenia,arrhythmia,rash and pruritus were common.Of the 120 cases of adverse reactions,48 were due to drug-drug interactions involving fluticasone,triamcinolone,vinblastine,tacrolimus,warfarin,levothyroxine,docetaxel,and ergotamine.After treatment,symptoms improved in 111 patients,but worsened in 4 patients and 5 patients died.Conclusion We should be alert to the adverse reactions induced by lopinavir/ritonavir in the early stage of medication in order to prevent drug-drug interactions and to ensure the safety of medication.