Analysis of the US FDA adverse event reporting system to identify adverse cardiac events associated with hydroxychloroquine in older adults.
adverse event
data signal
elderly
hydroxychloroquine
pharmacoepidemiology
reporting odds ratio
Journal
Pharmacoepidemiology and drug safety
ISSN: 1099-1557
Titre abrégé: Pharmacoepidemiol Drug Saf
Pays: England
ID NLM: 9208369
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
25
05
2020
revised:
01
10
2020
accepted:
14
10
2020
pubmed:
21
10
2020
medline:
25
11
2021
entrez:
20
10
2020
Statut:
ppublish
Résumé
The purpose of this study is to analyze the US FDA Adverse Event Reporting System (FAERS) to identify adverse cardiac events of hydroxychloroquine in older adults. A case/non-case method was used to determine adverse events associated with hydroxychloroquine as the primary suspect drug between January 1, 2004, and December 31, 2019, for older adults (≥65 years). Adverse events are preferred terms (PTs) defined in MedDRA. We used frequentist approaches, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) to measure disproportionality. We used Bayesian approaches to derive information component (IC) value and Empirical Bayesian Geometric Mean (EBGM) score. Signals were defined as the number of reports > 3 and the lower limit of 95% confidence intervals (CI) of ROR ≥ 2, PRR ≥ 2, IC > 0, EBGM > 1. We identified 334 adverse cardiac events comprising 71 different MedDRA PTs from 2004 to 2019 for hydroxychloroquine in older adults. Strong disproportionality signals were noted for "Restrictive cardiomyopathy" (ROR = 272.43 (138.09-537.47); EBGM = 149.78 (77.34-264.67), "Right ventricular hypertrophy" (219.49 (85.32-564.70); 102.74 (39.67-222.81), "Cardiac septal hypertrophy" (226.77 (78.65-653.80); 93.82 (32.19-219.81), "Myocardial fibrosis" (57.29 (21.06-155.85); 42.99 (14.74-100.75), and "Cardiotoxicity" (43.90 (26.66-72.27); 40.28 (24.02-63.72). The risk of cardiomyopathy and myocardial disorders is high following exposure to hydroxychloroquine in older adults. Due to the current lack of safety data from randomized controlled trials as well as large observational studies to confirm the risk of adverse cardiac events associated with hydroxychloroquine, findings from analyses of post-marketing data may serve as interim guidance.
Substances chimiques
Hydroxychloroquine
4QWG6N8QKH
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1689-1695Informations de copyright
© 2020 John Wiley & Sons Ltd.
Références
Jin Y, Yang H, Ji W, et al. Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses. 2020;12(4):372.
Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-733.
Sturrock BR, Chevassut TJ. Chloroquine and COVID-19 - a potential game changer? Clin Med. 2020;20:278-281.
Tu YF, Chien CS, Yarmishyn AA, et al. A review of SARS-CoV-2 and the ongoing clinical trials. Int J Mol Sci. 2020;21(7):2657.
Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020;55(4):105932.
Dal-Ré R, Porcher R, Gluud C. COVID-19 clinical trials: ethical and scientific consequences of the RECOVERY trial results. Basic Clin Pharmacol Toxicol. 2020 [Epub ahead of print]. https://doi.org/10.1111/bcpt.13489
Juurlink DN. Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection. CMAJ. 2020;192:E450-E453.
Abd-Elsalam S, Esmail ES, Khalaf M, et al. Hydroxychloroquine in the treatment of COVID-19: a multicenter randomized controlled study. Am J Trop Med Hyg. 2020;103:1635-1639.
Boulware DR, Pullen MF, Bangdiwala AS, et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19. N Engl J Med. 2020;383(6):517-525.
Abella BS, Jolkovsky EL, Biney BT, et al. Efficacy and safety of hydroxychloroquine vs placebo for pre-exposure SARS-CoV-2 prophylaxis among health care workers: a randomized clinical trial. JAMA Intern Med. 2020:e206319.
Elsevier. PharmaPendium Fact Sheet 2019 [cited April 25, 2020]. https://supportcontent.elsevier.com/Support%20Hub/Pharmapendium/Documents/7420_PharmaPendium_Corporate_Efficacy_Module_Fact_Sheet_Feb_2016.pdf
Rees KE, Chyou TY, Nishtala PS. A disproportionality analysis of the adverse drug events associated with Lurasidone in Paediatric patients using the US FDA adverse event reporting system (FAERS). Drug Saf. 2020;43:607-609.
Clark M, Steger-Hartmann T. A big data approach to the concordance of the toxicity of pharmaceuticals in animals and humans. Regul Toxicol Pharmacol. 2018;96:94-105.
Bate A, Evans SJ. Quantitative signal detection using spontaneous ADR reporting. Pharmacoepidemiol Drug Saf. 2009;18(6):427-436.
R Core Team. R: A language and environment for statistical computing Vienna, Austria: R Foundation for Statistical Computing; 2019 [R Studio v1.2.1335].
Centre for Disease Control and Prevention. Risk for Severe Illness Increases with Age. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/older-adults.html [cited September 29, 2020].
Chatre C, Roubille F, Vernhet H, Jorgensen C, Pers YM. Cardiac complications attributed to chloroquine and hydroxychloroquine: a systematic review of the literature. Drug Saf. 2018;41(10):919-931.
O'Laughlin JP, Mehta PH, Wong BC. Life threatening severe QTc prolongation in patient with systemic lupus erythematosus due to hydroxychloroquine. Case Rep Cardiol. 2016;2016:4626279.
Chen CY, Wang FL, Lin CC. Chronic hydroxychloroquine use associated with QT prolongation and refractory ventricular arrhythmia. Clin Toxicol (Phila). 2006;44(2):173-175.
Sapp JL, Alqarawi W, MacIntyre CJ, et al. Guidance on minimizing risk of drug-induced ventricular arrhythmia during treatment of COVID-19: a statement from the Canadian Heart Rhythm Society. Can J Cardiol. 2020;36:948-951.
Bessière F, Roccia H, Delinière A, et al. Assessment of QT intervals in a case series of patients with coronavirus disease 2019 (COVID-19) infection treated with hydroxychloroquine alone or in combination with azithromycin in an intensive care unit. JAMA Cardiol. 2020;5(9):1067-1069.
Mercuro NJ, Yen CF, Shim DJ, et al. Risk of QT interval prolongation associated with use of hydroxychloroquine with or without concomitant azithromycin among hospitalized patients testing positive for coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(9):1036-1041.
Sumpter MD, Tatro LS, Stoecker WV, Rader RK. Evidence for risk of cardiomyopathy with hydroxychloroquine. Lupus. 2012;21(14):1594-1596.
Soong TR, Barouch LA, Champion HC, Wigley FM, Halushka MK. New clinical and ultrastructural findings in hydroxychloroquine-induced cardiomyopathy-a report of 2 cases. Hum Pathol. 2007;38(12):1858-1863.
Yogasundaram H, Putko BN, Tien J, et al. Hydroxychloroquine-induced cardiomyopathy: case report, pathophysiology, diagnosis, and treatment. Can J Cardiol. 2014;30(12):1706-1715.
Katayama M, Panse PM, Kendall CB, et al. Left ventricular septal hypertrophy in elderly patients with aortic stenosis. J Ultrasound Med. 2018;37(1):217-224.
Park KM, Im SI, Kim EK, et al. Atrial fibrillation in hypertrophic cardiomyopathy: is the extent of septal hypertrophy important? PLoS One. 2016;11(6):e0156410.
Varnava AM, Elliott PM, Sharma S, McKenna WJ, Davies MJ. Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease. Heart. 2000;84(5):476-482.
Rahman MM, Alatawi Y, Cheng N, et al. Methodological considerations for comparison of brand versus generic versus authorized generic adverse event reports in the US Food and Drug Administration adverse event reporting system (FAERS). Clin Drug Investig. 2017;37(12):1143-1152.