Laboratório de Células, Tecidos e Genes, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brasil.
Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil.
Cad Saude Publica. 2022 Jul 25;38(7):e00001022. doi: 10.1590/0102-311XEN001022. eCollection 2022.
Off-label use of azithromycin, hydroxychloroquine, and ivermectin (the "COVID kit") has been suggested for COVID-19 treatment in Brazil without clinical or scientific evidence of efficacy. These drugs have known adverse drug reactions (ADR). This study aimed to analyze if the sales of drugs in the "COVID kit" are correlated to the reported number of ADR after the COVID-19 pandemic began. Data was obtained from the Brazilian Health Regulatory Agency (Anvisa) website on reported sales and ADRs for azithromycin, hydroxychloroquine, and ivermectin for all Brazilian states. The period from March 2019 to February 2020 (before the pandemic) was compared to that from March 2020 to February 2021 (during the pandemic). Trend adjustment was performed for time series data and cross-correlation analysis to investigate correlation between sales and ADR within the same month (lag 0) and in the following months (lag 1 and lag 2). Spearman's correlation coefficient was used to assess the magnitude of the correlations. After the pandemic onset, sales of all investigated drugs increased significantly (69.75% for azithromycin, 10,856,481.39% for hydroxychloroquine, and 12,291,129.32% for ivermectin). ADR levels of all medications but azithromycin were zero before the pandemic, but increased after its onset. Cross-correlation analysis was significant in lag 1 for all drugs nationwide. Spearman's correlation was moderate for azithromycin and hydroxychloroquine but absent for ivermectin. Data must be interpreted cautiously since no active search for ADR was performed. Our results show that the increased and indiscriminate use of "COVID kit" during the pandemic correlates to an increased occurrence of ADRs.
阿齐霉素、羟氯喹和伊维菌素(“COVID 套装”)的标签外使用已被建议用于巴西的 COVID-19 治疗,但没有临床或科学证据证明其疗效。这些药物有已知的药物不良反应(ADR)。本研究旨在分析 COVID-19 大流行开始后,“COVID 套装”中药物的销售是否与报告的 ADR 数量相关。从巴西卫生监管机构(Anvisa)网站上获取了阿齐霉素、羟氯喹和伊维菌素在巴西所有州的报告销售和 ADR 数据。将 2019 年 3 月至 2020 年 2 月(大流行前)与 2020 年 3 月至 2021 年 2 月(大流行期间)进行了比较。对时间序列数据进行了趋势调整,并进行了交叉相关分析,以调查同月(滞后 0)和下一个月(滞后 1 和滞后 2)内销售和 ADR 之间的相关性。使用 Spearman 相关系数评估相关性的大小。大流行开始后,所有调查药物的销售均显著增加(阿齐霉素增加 69.75%,羟氯喹增加 10,856,481.39%,伊维菌素增加 12,291,129.32%)。大流行前,所有药物的 ADR 水平均为零,但大流行开始后增加。全国范围内,所有药物在滞后 1 时的交叉相关分析均有统计学意义。Spearman 相关在阿齐霉素和羟氯喹中为中度相关,但在伊维菌素中不存在。由于没有主动搜索 ADR,因此必须谨慎解释数据。我们的结果表明,大流行期间“COVID 套装”的使用增加且无差别,与 ADR 发生率的增加相关。