Sarayani Amir, Cicali Brian, Henriksen Carl H, Brown Joshua D
Center for Drug Evaluation and Safety, Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville, FL, USA.
Center for Systems Pharmacology and Pharmacometrics, Department of Pharmaceutics, University of Florida College of Pharmacy, Orlando, FL, USA.
Res Social Adm Pharm. 2021 Feb;17(2):483-486. doi: 10.1016/j.sapharm.2020.04.016. Epub 2020 Apr 19.
Combinations of hydroxychloroquine (HCQ) and azithromycin have been promoted as treatments for COVID-19 based on small, uncontrolled clinical trials that have not assessed potential risks. Risks of treatment include QT segment prolongation, Torsades de Pointes (TdP), and death. This comparative pharmacovigilance analysis evaluated the risk of these events.
Data from the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) (>13 million total reports) were used. Queries extracted reports based on exposures of HCQ/chloroquine (CQ) alone, azithromycin alone, HCQ/CQ + azithromycin, amoxicillin alone, HCQ/CQ + amoxicillin alone. Amoxicillin served as a control. Events of interest included death and TdP/QT prolongation as well as accidents/injuries and depression as control events. Proportional Reporting Ratios (PRR) and 95% confidence intervals (CI) were calculated where a lower limit of the of 95% CI (Lower95CI) value of ≥2.0 is interpreted as a potential safety signal.
Lower95CIs for HCQ/CQ alone showed no potential safety signals for TdP/QT prolongation, death, or any of the control events included. The PRRs and 95% CIs for TdP/QT prolongation was 1.43 (1.29-2.59) with HCQ/CQ use alone and 4.10 (3.80-4.42) for azithromycin alone. For the combined HCQ/CQ + azithromycin group, the PRR and 95% CI was 3.77 (1.80-7.87). For the control of amoxicillin, there were no safety signals when used alone or in combination with HCQ/CQ.
HCQ/CQ use was not associated with a safety signal in this analysis of FAERS data. However, azithromycin used alone was associated with TdP/QT prolongation events and should be used with caution.
基于未评估潜在风险的小型非对照临床试验，羟氯喹（HCQ）和阿奇霉素的联合用药已被推广用于治疗新型冠状病毒肺炎（COVID-19）。治疗风险包括QT段延长、尖端扭转型室速（TdP）和死亡。这项比较性药物警戒分析评估了这些事件的风险。
使用了美国食品药品监督管理局不良事件报告系统（FAERS）的数据（总计超过1300万份报告）。查询提取了基于单独使用HCQ/氯喹（CQ）、单独使用阿奇霉素、HCQ/CQ +阿奇霉素、单独使用阿莫西林、单独使用HCQ/CQ +阿莫西林的暴露情况的报告。阿莫西林作为对照。感兴趣的事件包括死亡和TdP/QT延长以及作为对照事件的事故/伤害和抑郁。计算比例报告率（PRR）和95%置信区间（CI），其中95%CI下限（Lower95CI）值≥2.0被解释为潜在的安全信号。
单独使用HCQ/CQ的Lower95CIs未显示TdP/QT延长、死亡或任何纳入的对照事件的潜在安全信号。单独使用HCQ/CQ时TdP/QT延长的PRR和95%CI为1.43（1.29 - 2.59），单独使用阿奇霉素时为4.10（3.80 - 4.42）。对于联合使用的HCQ/CQ +阿奇霉素组，PRR和95%CI为3.77（1.80 - 7.87）。对于阿莫西林对照，单独使用或与HCQ/CQ联合使用时均无安全信号。
在对FAERS数据的这项分析中，使用HCQ/CQ未显示安全信号。然而，单独使用阿奇霉素与TdP/QT延长事件相关，应谨慎使用。
