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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 2020

See all articles by Vakaramoko Diaby

Vakaramoko Diaby

University of Florida, College of Pharmacy, Department of Pharmaceutical Outcomes and Policy

Reem D. Almutairi

Princess Nourah Bint Abdulrahman University - Department of Pharmacy Practice

Ziyan Chen

University of Florida, College of Pharmacy, Department of Pharmaceutical Outcomes and Policy

Richard K. Moussa

Ecole Nationale Supérieure de Statistique et d'Economie Appliquée (ENSEA)

Abdrahmane Berthe

Government of Northwest Territories

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Abstract

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

Suggested Citation

Diaby, Vakaramoko and Almutairi, Reem D. and Chen, Ziyan and Moussa, Richard K. and Berthe, Abdrahmane, QT Prolongation and Torsade De Pointes Related to Antimalarial Drugs and Azithromycin: A Pharmacovigilance Study in the Context of the COVID-19 Crisis (4/23/2020). Available at SSRN: https://ssrn.com/abstract=3586697 or http://dx.doi.org/10.2139/ssrn.3586697

Vakaramoko Diaby (Contact Author)

University of Florida, College of Pharmacy, Department of Pharmaceutical Outcomes and Policy ( email )

United States

Reem D. Almutairi

Princess Nourah Bint Abdulrahman University - Department of Pharmacy Practice ( email )

Riyadh
Saudi Arabia

Ziyan Chen

University of Florida, College of Pharmacy, Department of Pharmaceutical Outcomes and Policy ( email )

United States

Richard K. Moussa

Ecole Nationale Supérieure de Statistique et d'Economie Appliquée (ENSEA)

Abidjan
Ivory Coast (Cote D'ivoire)

Abdrahmane Berthe

Government of Northwest Territories

Canada