Cardiovascular adverse events associated with hydroxychloroquine and chloroquine: A comprehensive pharmacovigilance analysis of pre‐COVID‐19 reports

Goldman, Adam; Bomze, David; Dankner, Rachel; Hod, Hanoch; Meirson, Tomer; Boursi, Ben; Maor, Elad

doi:10.1111/bcp.14546

Cited by 46 publications

(41 citation statements)

References 42 publications

(96 reference statements)

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“…Finally, the increased number of reports of QT prolongation underlines the importance of carefully considering potential drug-drug interactions and cardiac comorbidities during treatment with (hydroxy)chloroquine. 20 Our results also showed reports involving (hydroxy)chloroquine use during pregnancy in the first pandemic time interval with a peak in March 2020. Indeed, this could be related to the overall increased awareness of (hydroxy)chloroquine safety.…”

Section: Discussionsupporting

confidence: 83%

Global COVID‐19 pandemic and reporting behavior ‐ An analysis of the Food and Drug Administration adverse events reporting system

Dörks

Jobski

Hoffmann

et al. 2021

Pharmacoepidemiology and Drug

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Purpose To describe the characteristics of adverse event reporting in the United States (US) Food and Drug Administration Adverse Event Reporting System (FAERS) before and after the outbreak of the COVID‐19 pandemic. Methods We included all FAERS reports from the US and Canada from November 7, 2019 to July 15, 2020 and divided the study period into three equal time intervals (pre‐pandemic, first pandemic, second pandemic). We focused on methotrexate, a broadly used drug unrelated to COVID‐19, and (hydroxy)chloroquine, another broadly used drug implicated in COVID‐19 treatment. Using descriptive statistics, we compared reporting characteristics before and after the COVID‐19 outbreak. Results During the study period, 366 998 cases (60% female, median age: 59 years) were submitted to FAERS. The daily median number of reports (1796 in the pre‐pandemic, 1810 in the second pandemic time interval) and other characteristics remained stable. The daily median number of reports for methotrexate decreased from 28 in the pre‐pandemic to 15 in the second pandemic time interval, with no considerable differences in other characteristics. The daily median number of reports for (hydroxy)chloroquine increased slightly from 1 in the pre‐pandemic to 3 in the second pandemic time interval, while there were also changes in the demographics of cases and an increase in the proportion of cases reported by health professionals. Conclusions The overall reporting to FAERS did not change after the outbreak of the COVID‐19 pandemic. However, some stimulated reporting was observed for (hydroxy)chloroquine, highlighting the need for caution when conducting pharmacovigilance analyses with substances related to COVID‐19.

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Section: Discussionsupporting

confidence: 83%

Global COVID‐19 pandemic and reporting behavior ‐ An analysis of the Food and Drug Administration adverse events reporting system

Dörks

Jobski

Hoffmann

et al. 2021

Pharmacoepidemiology and Drug

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“…Fourth, as a recent study suggested a risk of cardiac arrhythmias with hydroxychloroquine, we performed a head-to-head comparison (remdesivir versus hydroxychloroquine). [ 7 ] In addition, to address the effect of age and sex, we used stratification analyses according age groups (≤44 years, 45-64 years and ≥ 65 years) and sex.…”

Section: Methodsmentioning

confidence: 99%

Serious bradycardia and remdesivir for coronavirus 2019 (COVID-19): a new safety concerns

Touafchia

Bagheri

Carrié

et al. 2021

Clinical Microbiology and Infection

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Objectives In recent clinical trials some cardiac arrhythmias were reported with use of remdesivir for COVID-19. To address this safety concern, we investigated whether use of remdesivir for COVID-19 is associated with an increased risk of bradycardia. Methods Using VigiBase®, the World Health Organization Global Individual Case Safety Reports database, we compared the cases of bradycardia reported in COVID-19 patients exposed to remdesivir with those reported in COVID-19 patients exposed to hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids. All reports of patients with COVID-19 registered up to the 23 th of September 2020 were included. We conducted disproportionality analyses allowing the estimation of reporting odds ratios (RORs) with 95% Confident Intervals (95% CI). Results We found 302 cardiac effects including 94 bradycardia (31%) among the 2,603 reports with remdesivir prescribed in COVID-19 patients. Most of reports were serious (75, 80%) and in 16 reports (17%) evolution was fatal. Compared with hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids, the use of remdesivir was associated with an increased risk of reporting bradycardia (ROR 1.65; 95% CI 1.23, 2.22). Consistent results were observed in other sensitivity analyses. Conclusions This post-marketing study in a real-world setting suggests that the use of remdesivir is significantly associated with an increased risk of reporting bradycardia and serious bradycardia when compared with the use of with hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids. This result is in line with pharmacodynamic properties of the remdesivir.

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“…Subsequent clinical review and research are needed to assess causality. In addition to the known ADEs for HCQ, such as higher rates of cardiovascular event reports, 15 we found evidence of ADEs related to herpes simplex hepatitis, vessel puncture site hemorrhage, and a prolonged electrocardiogram QRS complex. Likewise, several ADEs related to the use of AZM were found.…”

Section: Discussionmentioning

confidence: 54%

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

Dauner¹,

Dauner²

2021

Journal of the American Pharmacists Association

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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.

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Cardiovascular adverse events associated with hydroxychloroquine and chloroquine: A comprehensive pharmacovigilance analysis of pre‐COVID‐19 reports

Cited by 46 publications

References 42 publications

Global COVID‐19 pandemic and reporting behavior ‐ An analysis of the Food and Drug Administration adverse events reporting system

Global COVID‐19 pandemic and reporting behavior ‐ An analysis of the Food and Drug Administration adverse events reporting system

Serious bradycardia and remdesivir for coronavirus 2019 (COVID-19): a new safety concerns

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

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