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.