Summary of adverse drug events for hydroxychloroquine, azithromycin, and chloroquine during the COVID-19 pandemic

Abstract

Objective: Given the increased use of hydroxychloroquine (HCQ), chloroquine (CQ), and azithromycin (AZM) during the early months of the coronavirus disease 2019 (COVID-19) pandemic, there is a need to evaluate the associated safety concerns. The objective of this study was to summarize the adverse drug events (ADEs) associated with HCQ, CQ, and AZM use during the national COVID-19 emergency and compare the results with known adverse reactions listed in the drugs' package inserts. Methods: A cross-sectional study design was used. The publicly available Food and Drug Administration Adverse Event Reporting System quarterly data extract files from January 1, 2020 to June 30, 2020 were downloaded. A disproportionality analysis was conducted using the proportional reporting ratio to identify possible ADE signals. A Poisson regression was used to assess if the number of ADE reports for the 3 drugs increased over time.Results: There was a statistically significant increasing trend in the reported ADEs for both HCQ (P < 0.001) and AZM (P < 0.001). Before the declaration of the national emergency, there were 592 reported drug-ADE pairs for the 3 drugs compared with 2492 drug-ADE pairs reported after March 13, 2020. These 2492 drug-ADE pairs represented 848 ADEs across the 3 drugs, of which 114 (13.4%) were identified as potential signals including 55 (48.2%) that were not listed in the prescribing information. Conclusions: Our results showed that the reported ADEs for HCQ and AZM have increased during the COVID-19 pandemic. Differences were observed in both the type of and frequency of the highest reported ADEs for the 3 selected drugs before and after the national emergency declaration. Although causation cannot be determined from ADE reports, further investigation of some reports may be warranted. Our results highlight the need for pharmacovigilance and education of health care professionals on the safety of these drugs when being used for COVID-19 prophylaxis or treatment.

Characterisation of Drug-Induced Liver Injury in Patients with COVID-19 Detected by a Proactive Pharmacovigilance Program from Laboratory Signals

“…A review of the FDA adverse drug reports for the period January to July 2020 for azithromycin, chloroquine and hydroxychloroquine showed a rise in reports from 592 before to 2492 after their emergency use authorization for COVID-19 infection, mostly for hydroxychloroquine (596 cases) and azithromycin (184 cases), the second most frequent event being hepatitis [ 35 ]. In Brazil, between March and August 2020, a total of 631 adverse event reports in 402 patients with COVID-19 were received, of which 56 cases (9%) were hepatic, including 28 attributed to hydroxychloroquine and 4 to azithromycin [ 36 ].…”

Immediate and long-term effects of COVID-19 on antibiotic dispensing: increasing use of Watch antibiotics

“…Azithromycin did not result in a superior clinical improvement of COVID-19 patients [28]. Despite the reported beneficial effect of co-treatment of hydroxychloroquine with azithromycin [29], many clinical trials using this combination therapy did not give encouraging results in COVID-19 therapy, primarily because of its treatment inefficiency and substantial cardiovascular adverse effects [8,30,31]. According to a review of studies between June 2020 and March 2021 on the global use of antibiotics in COVID-19 patients, the seven most frequently prescribed antibiotics were all Watch antibiotics [32].…”

Manzamine-A Alters In Vitro Calvarial Osteoblast Function

“…Note many drugs authorized for emergency usage, currently in clinical trials, or used in off-label contexts may not have adequate risk/benefit assessment for those patients who are being treated. This is especially poignant today as the current COVID crisis has altered our focus on emerging disease and has driven an increase in emergency authorizations and off-label use of many drugs as tools to contain emerging viruses but can also adversely affect vulnerable populations [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”