Dauner DG, Dauner KN. J Am Pharm Assoc (2003). 2021 May-Jun;61(3):293-298.
The United States declared a national emergency concerning the coronavirus disease 2019 (COVID-19) outbreak on March 13, 2020, and on March 28, 2020, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the use of oral formulations of hydroxychloroquine (HCQ) and chloroquine (CQ) in patients weighing ≥ 50 kg who were hospitalized for the treatment of COVID-19. On April 24, 2020, the FDA issued a Drug Safety Communication cautioning against the use of HCQ and CQ for the treatment of COVID-19 outside of the hospital setting or as part of a clinical trial because of the risk for heart rhythm problems. In this same communication, the FDA also stated they were aware of reports of serious heart rhythm problems in COVID-19 patients and increased outpatient prescriptions for the drugs. Subsequently, on June 15, 2020, the FDA revoked the EUA citing a randomized, double-blind trial that found no statistically significant difference between the drugs and placebo treatments for post-exposure prophylaxis. Research from two additional groups supported the FDA’s initial concerns about increased outpatient prescriptions. One study indicated an 80-fold increase in new prescriptions for HCQ and CQ in March 2020 compared with March 2019 from primary and specialty care physicians who would not normally prescribe these drugs. These results were further corroborated by a second study of prescription fill data during the pandemic. Both studies pointed to the use of these drugs outside the original population specified in the EUA. However, neither study addressed if there was a corresponding increase in adverse drug event (ADE) reports.
Investigating the risks associated with these drugs is good pharmacovigilance and of interest to the FDA. This cross-sectional study summarized the ADEs associated with HCQ, CQ, and azithromycin use during the COVID-19 national emergency and compared the results with known adverse reactions listed in the drugs’ package inserts. We used publicly available data from the Food and Drug Administration Adverse Event Reporting System, and the 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, and a Poisson regression was used to assess if the number of ADE reports for the 3 drugs increased over time. There was a statistically significant increasing trend in the reported ADEs for both hydroxychloroquine (p < 0.001) and azithromycin (p < 0.001). Differences were observed in both the type 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 the ADE reports, further investigation of some reports may be warranted. Overall, our results added further evidence supporting the FDA’s decision to revoke the EUA in June 2020 and highlighted the need for health care providers to be aware of the possible ADEs when treating COVID-19. Future research should monitor the prescribing of these drugs beyond this time period and look for additional safety concerns.
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About the Author:
Daniel G. Dauner, PharmD, MSPH, BCPS brings over 20 years of experience to the SafetyCall team. His diverse background includes contributions in the areas of pharmacy, epidemiology, data analytics, and academics. He has authored multiple peer-reviewed manuscripts and a book chapter and given presentations at both the local and national levels. His professional interests are using diverse data sets and data analytics to help solve pharmacy, pharmacovigilance, and healthcare problems.