奈玛特韦/利托那韦治疗新型冠状病毒感染的安全性分析

Safety analysis of nirmatrelvir/ritonavir in the treatment of coronavirus disease 2019

目的探讨应用奈玛特韦/利托那韦(Paxlovid)治疗新型冠状病毒感染(COVID-19)的安全性。方法通过医院电子病历系统收集2022年3月23日至5月31日在首都医科大学附属北京地坛医院住院并应用Paxlovid治疗的COVID-19成年患者病历资料,对Paxlovid的不良反应发生情况(发生时间、临床表现、严重程度等)及转归进行回顾性分析,并比较有不良反应组和无不良反应组患者的临床特征。Paxlovid用法为奈玛特韦300 mg+利托那韦100 mg口服、1次/12 h,连续5 d。结果纳入分析的患者为364例,男性200例(54.9%),女性164例(45.1%),中位年龄60(19,92)岁。Paxlovid不良反应发生率为13.2%(48/364),不良反应发生在开始服用Paxlovid后1~7 d。48例患者中,出现消化系统症状者37例(主要表现为腹泻17例、口苦14例等),神经系统症状7例(头晕5例,头痛2例),呼吸系统症状4例(咽痛3例,咽痒1例),肾损伤2例,血尿酸升高、肌痛和皮疹各1例,其中2例同时出现消化系统和神经系统症状,1例同时出现消化系统和呼吸系统症状,1例同时出现消化系统、神经系统和呼吸系统症状;33例(68.8%)不良反应严重程度为1级,15例(31.2%)为2级,无≥3级的严重不良反应发生。除1例因不能耐受2级消化系统症状(恶心+口苦)而停药外,其他患者均完成了5 d的治疗。有不良反应组和无不良反应组患者的性别、年龄、体重指数、吸烟状况、基础疾病和COVID-19临床分型的差异均无统计学意义(均P>0.05)。结论Paxlovid治疗COVID-19的安全性较好,主要不良反应为消化系统症状,以腹泻、口苦较为多见,症状多较轻微,患者耐受性较好。

Objective To explore the safety of nirmatrelvir/ritonavir(Paxlovid)in the treatment of coronavirus disease 2019(COVID-19).Methods Medical records of adult patients with COVID-19 who were hospitalized and treated with Paxlovid in Beijing Ditan Hospital,Capital Medical University between March 23 and May 31,2022 were collected through the hospital electronic medical record system.The occurrence(time of occurrence,clinical manifestations,severity,etc.)and outcomes of adverse reactions were analyzed retrospectively and the clinical characteristics of patients with or without adverse reactions were compared.Paxlovid was administered orally with nirmatrelvir 300 mg and ritonavir 100 mg every 12 hours for 5 consecutive days.Results Three hundred and sixty-four patients were entered in the analysis,including 200 males(54.9%)and 164 females(45.1%),with a median age of 60(19,92)years.The incidence of adverse reactions of Paxlovid was 13.2%(48/364),and the adverse reactions occurred 1 to 7 days after taking Paxlovid.Among the 48 patients,37 patients had digestive system symptoms(mainly manifested as diarrhea in 17 patients,bitter mouth in 14 patients,etc.),7 patients had nervous system symptoms(dizziness in 5 patients,headache in 2 patients),4 patients had respiratory system symptoms(pharyngalgia in 3 patients,pharyngeal itching in 1 patient),2 patients had kidney injury,1 patient had elevated blood uric acid,1 patient had myalgia,and 1 patient had rash.Of them,2 patients had digestive and neurological symptoms at the same time,1 patient had digestive and respiratory symptoms at the same time,and 1 patient had digestive,neurological,and respiratory symptoms at the same time.The severity of adverse reactions was grade 1 in 33 patients(68.8%)and grade 2 in 15 patients(31.2%),and no serious adverse reactions of grade 3 and above occurred.All patients completed 5 days of treatment except 1 patient who discontinued the drug because of intolerance to grade 2 digestive symptoms(nausea and bitter mouth).There were no significant differences in gender,age,body mass index,smoking status,underlying diseases,and COVID-19 clinical classification between the patients with and without adverse reactions(all P>0.05).Conclusions Paxlovid has a good safety in the treatment of COVID-19.The main adverse reaction is digestive system symptoms,mainly diarrhea and bitter mouth.Most of the symptoms are mild and the patient′s tolerance is good.