Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Haiyuncang Lane, Dongcheng District, Beijing, 100700, China.
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Dongcheng District, Beijing, China.
J Ethnopharmacol. 2022 Jun 28;292:115076. doi: 10.1016/j.jep.2022.115076. Epub 2022 Feb 25.
In China, Xiyanping (XYP) has been widely used in combination with Ribavirin (RB) for the treatment of infectious diseases. It has been found that this combination may change the severity of XYP-associated adverse events (AEs).
To provide a comprehensive review about the clinal features of AEs of XYP-RB combination from randomized controlled trials, cohort studies, case-control studies, case reports, case series, and data from the National Adverse Drug Reaction Monitoring Information System (NADRMIS).
Seven electronic databases were searched in March 2021. Articles on AEs associated with XYP published from January 2004 to December 2020 in the NADRMIS were included. Data on the incidence of AEs, distribution of AEs, occurrence time of AEs, type and possible signal of AEs, primary diseases, allergic history, family history of allergies, dosage, and combination interval were extracted.
We included 228 cases of AEs with XYP-RB combination (63 cases from randomized controlled trials, 1 from a cohort study, and 164 from the NADRMIS). The most common primary disease was hand-foot-and-mouth disease. The main age distribution was 0-6 years (118 cases, 72%) and 8 cases (6.8%) experienced serious AEs. The combination group showed a significant reduction than the RB group in the incidence of AEs in those with hand-foot-and-mouth disease (risk ratio = 0.54, 95% confidence interval = 0.38-0.78, P = 0.0008) and children with viral pneumonia (risk ratio = 0.36, 95% confidence interval = 0.14-0.95, P = 0.04). Allergic history and infusion interval were not described in the randomized controlled trials. AEs were reported in 57.9% of cases in the first combination (XYP-RB were combined for the first time) (NADRMIS), 56.4% of which were skin and appendage reactions, and the risk signal of skin and appendage reactions was a maximum (Information Component = 6.21).
The major AE associated with XYP-RB combination was skin and appendage reactions. Most of the combination AEs were pseudo-allergic reactions. These findings suggest that we should increase awareness about the safety of XYP-RB combination treatment and standardize medication protocol, especially for children. Unless absolutely necessary, children should avoid combination therapy. More rigorous high-quality studies are needed to obtain more evidence.
在中国，喜炎平（XYP）已广泛与利巴韦林（RB）联合用于治疗传染病。现已发现，这种联合用药可能会改变 XYP 相关不良事件（AE）的严重程度。
对从随机对照试验、队列研究、病例对照研究、病例报告、病例系列和国家药品不良反应监测信息系统（NADRMIS）中获得的 XYP-RB 联合用药相关 AE 的临床特征进行全面综述。
2021 年 3 月检索了 7 个电子数据库。纳入了 2004 年 1 月至 2020 年 12 月期间 NADRMIS 中发表的与 XYP 相关的 AE 相关文章。提取 AE 发生率、AE 分布、AE 发生时间、AE 类型和可能信号、主要疾病、过敏史、过敏家族史、剂量和联合间隔的数据。
共纳入了 228 例 XYP-RB 联合用药的 AE 病例（63 例来自随机对照试验、1 例来自队列研究、164 例来自 NADRMIS）。最常见的主要疾病是手足口病。主要年龄分布为 0-6 岁（118 例，72%），8 例（6.8%）发生严重 AE。与利巴韦林组相比，联合组在手足口病（风险比=0.54，95%置信区间=0.38-0.78，P=0.0008）和病毒性肺炎患儿（风险比=0.36，95%置信区间=0.14-0.95，P=0.04）中 AE 的发生率明显降低。过敏史和输注间隔在随机对照试验中未被描述。NADRMIS 中首次联合（XYP-RB 首次联合）时报告了 57.9%（132/228）的病例出现 AE，其中 56.4%为皮肤和附件反应，皮肤和附件反应的风险信号最大（信息成分=6.21）。
XYP-RB 联合用药相关的主要 AE 是皮肤和附件反应。大多数联合用药 AE 是假性过敏反应。这些发现表明，我们应该提高对 XYP-RB 联合治疗安全性的认识，并规范用药方案，尤其是对儿童。除非绝对必要，儿童应避免联合治疗。需要进行更多严格的高质量研究以获得更多证据。
