Summary of Adverse Drug Events for Hydroxychloroquine, Azithromycin, and Chloroquine During the COVID-19 Pandemic

Dauner, Daniel G.; Dauner, Kim Nichols

Objective Given the increased use of hydroxychloroquine (HCQ), chloroquine (CQ), and azithromycin (AZM) during the early months of the SARS-CoV-2 (COVID-19) pandemic, there is a need to evaluate associated safety concerns. The objective of the study was to summarize the adverse drug events (ADEs) associated with HCQ, CQ, and AZM use during the COVID-19 national emergency declaration and compare the results to 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 through June 30, 2020 were downloaded. A disproportionality analysis was conducted using the proportional reporting ratio (PRR) to identify possible ADE signals. Poisson regression was used to assess if the number of ADE reports for the three drugs increased over time. Results There was a significant increasing trend in reported ADEs for both HCQ (p < 0.001) and AZM (p < 0.001). Before the national emergency declaration, there were 592 reported ADEs for the three drugs compared to 2,492 ADEs reported since March 13, 2020. Fifty-nine (51.8%) ADEs were listed in the prescribing information, and the remaining 55 (48.2%) were not listed representing possible signals. Conclusions Our results show 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 top reported ADEs for the three selected drugs before and after the national emergency declaration. Even though causation cannot be determined from ADE reports, further investigation of some reports may be warranted. Our results highlight the need for pharmacovigilance and education for health care professionals on the safety of these drugs when being used for COVID-19 prophylaxis or treatment.