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QT Prolongation and Torsade De Pointes Related to Antimalarial Drugs and Azithromycin: A Pharmacovigilance Study in the Context of the COVID-19 Crisis
29 Pages Posted: 2 Jun 2020More...
Background: Hydroxychloroquine, an antimalarial drug, combined with azithromycin have recently been considered a miracle cure in the treatment of COVID-19. However, these drugs have the potential to cause electrocardiogram QT prolongation (QTp) and torsade de pointes (TdP). Here, we quantified the association between seven antimalarial drugs and/or azithromycin and two adverse events, QTp and TdP.
Methods: We conducted a case/non‐case analysis of the FDA Adverse Event Reporting System (FAERS) to identify antimalarial drugs and azithromycin-induced QTp (n: 13,713) and TdP (n: 3,748) and related to other drugs (n: 7,687,270) through 12/2019. We measured the associations between antimalarial drugs and/or azithromycin and QTp and TdP using adjusted Reporting-Odds-Ratio (aROR).
Findings: Disproportionality in the reporting of QTp was lower for hydroxychloroquine [aROR: 1·99 (1·72 - 2·30)] than atovaquone [aROR: 2·12 (1·27 - 3·54)], mefloquine [aROR of 2·69 (1·41 - 5·30)], quinine [aROR of 4·17 (2·95 - 5·90)], chloroquine [aROR: 6·44 (4·25 - 9·78)], and primaquine [aROR:19·35 (8·84 - 42·32)]. Atovaquone combined with azithromycin increased the reporting odds of QTp by 25 times [aROR: 24·61 (12·90 - 46·92)]. Disproportionality for TdP was lower for hydroxychloroquine [aROR: 3·00 (2·42 - 3·71)] than quinine [aROR: 5·37 (3·27 - 8·80)] and chloroquine [aROR: 16·63 (10·80 - 25·59)].
Interpretation: Using hydroxychloroquine alone increases the odds for QTp and TdP two and three times the odds than for all other drugs in the FAERS, respectively.
Funding Statement: The study was not funded.
Declaration of Interests: The authors declare no competing interests.
Keywords: Antimalarial drugs; Hydroxychloroquine; Azithromycin; Electrocardiogram QT prolonged; Torsade de Pointes; COVID-19
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