Severe sinus bradycardia associated with Remdesivir in a child with severe SARS-CoV-2 infection

Sánchez-Códez, María Isabel; Rodríguez-González, Moisés; Gutiérrez-Rosa, Irene

doi:10.1007/s00431-021-03940-4

Cited by 31 publications

(41 citation statements)

References 4 publications

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“…2 Recent case reports suggest that remdesivir may also cause brady cardia. 5,7,8 Our patient had both an elevated ALT and sinus brady cardia. Although there were no adverse clinical sequelae of the latter, if remdesivir does cause bradycardia, it will be particularly relevant for patients who are admitted to hospital with COVID-19 and have other risk factors for bradycardia (e.g., older age, concomitant β-blocker use).…”

Section: Bradycardia Associated With Remdesivir Therapy For Covid-19 In a 59-year-old Manmentioning

confidence: 69%

“…7 Sanchez-Codez and colleagues described a case of severe sinus bradycardia (heart rate 40 beats/min) in an otherwise healthy 13-year-old boy after he received his third dose of remdesivir. 5 The bradycardia resolved within 24 hours of discontinuing remdesivir. Transient sinus bradycardia associated with QT prolongation (QTc 439 ms to 555 ms) was also reported in a 26-year-old woman with a past medical history of obesity, who was receiving remdesivir for treatment of COVID-19.…”

Section: Bradycardia Associated With Remdesivir Therapy For Covid-19 In a 59-year-old Manmentioning

confidence: 99%

“…9 Recent case reports have described 4 cases of sinus bradycardia in patients with COVID-19 who received remdesivir (Table 1). 5,7,8 Gubitosa and colleagues described a case of a 54-year-old woman with a baseline left bundle branch block of unknown cause, who developed marked sinus bradycardia to 38 beats/min within 24 hours after her first dose of remdesivir for COVID-19, along with mild widening of the QRS and lengthening of her QT interval (QTc 496 ms from 440 ms). Her bradycardia worsened to a nadir of 34 beats/min after her third dose and she required atropine temporarily for angina and hypotension.…”

Section: Bradycardia Associated With Remdesivir Therapy For Covid-19 In a 59-year-old Manmentioning

confidence: 99%

“…11 Although remdesivir has a markedly high binding affinity for viral polymerases, any cross-reactivity with human mitochondrial RNA polymerase could lead to mitochondrial dysfunction, which is an established mechanism for drug-induced cardiotoxicity. 5,8 Drug-induced cardiac myocyte cytotoxicity has been shown in in-vitro studies of cardiomyocytes derived from human stem cells treated with remdesivir. 12 Choi and colleagues showed that the cytotoxic effects of remdesivir on cardiomyocytes increased over time, such that a longer duration of treatment (48 v. 24 h) was associated with reduced cell viability.…”

Section: Bradycardia Associated With Remdesivir Therapy For Covid-19 In a 59-year-old Manmentioning

confidence: 99%

“…12 Additionally, as an adenosine analogue, remdesivir could affect atrioventricular nodal conduction, which could explain the QRS prolongation seen in previous cases. 5,7,8 Further studies to evaluate these mechanisms and their effect specifically on sinoatrial node activity are needed.…”

Section: Bradycardia Associated With Remdesivir Therapy For Covid-19 In a 59-year-old Manmentioning

confidence: 99%

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Bradycardia associated with remdesivir therapy for COVID-19 in a 59-year-old man

Day

Abdel‐Qadir

Fralick

2021

CMAJ

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Section: Bradycardia Associated With Remdesivir Therapy For Covid-19 In a 59-year-old Manmentioning

confidence: 69%

Section: Bradycardia Associated With Remdesivir Therapy For Covid-19 In a 59-year-old Manmentioning

confidence: 99%

Section: Bradycardia Associated With Remdesivir Therapy For Covid-19 In a 59-year-old Manmentioning

confidence: 99%

Section: Bradycardia Associated With Remdesivir Therapy For Covid-19 In a 59-year-old Manmentioning

confidence: 99%

Section: Bradycardia Associated With Remdesivir Therapy For Covid-19 In a 59-year-old Manmentioning

confidence: 99%

See 3 more Smart Citations

Bradycardia associated with remdesivir therapy for COVID-19 in a 59-year-old man

Day

Abdel‐Qadir

Fralick

2021

CMAJ

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Identification of Bradycardia Following Remdesivir Administration Through the US Food and Drug Administration American College of Medical Toxicology COVID-19 Toxic Pharmacovigilance Project

et al. 2023

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ImportanceThe rapid spread and mortality associated with COVID-19 emphasized a need for surveillance system development to identify adverse events (AEs) to emerging therapeutics. Bradycardia is a remdesivir infusion–associated AE listed in the US Food and Drug Administration–approved prescribing information.ObjectiveTo evaluate the magnitude and duration of bradycardic events following remdesivir administration.Design, Setting, and ParticipantsA multicenter cohort study of patients with recorded heart rate less than 60 beats per minute within 24 hours after administration of a remdesivir dose was conducted between November 23, 2020, and October 31, 2021. Participants included patients hospitalized with COVID-19 at 15 medical centers across the US. Patients excluded had AEs unrelated to bradycardia, AEs in addition to bradycardia, or first onset of bradycardia after 5 remdesivir doses.ExposuresRemdesivir administration.Main Outcomes and MeasuresLinear mixed-effect models for the minimum HR before starting remdesivir and within 24 hours of each dose included doses as fixed effects. Baseline covariates were age (≥65 years vs &lt;65 years), sex (male vs female), cardiovascular disease history (yes vs no), and concomitant use of bradycardia-associated medications. The interactions between variables and doses were considered fixed-effects covariates to adjust models.ResultsA total of 188 patients were included in the primary analysis and 181 in the secondary analysis. The cohort included 108 men (57.4%); 75 individuals (39.9%) were non-Hispanic White and mean (SD) age was 61.3 (15.4) years. Minimum HR after doses 1 to 5 was lower than before remdesivir. Mean minimum HR was lowest after dose 4, decreasing by −15.2 beats per minute (95% CI, −17.4 to −13.1; P &lt; .001) compared with before remdesivir administration. Mean (SD) minimum HR was 55.6 (10.2) beats per minute across all 5 doses. Of 181 patients included in time-to-event analysis, 91 had their first episode of bradycardia within 23.4 hours (95% CI, 20.1-31.5 hours) and 91 had their lowest HR within 60.7 hours (95% CI, 54.0-68.3 hours). Median time to first bradycardia after starting remdesivir was shorter for patients aged 65 years or older vs those younger than 65 years (18.7 hours; 95% CI, 16.8-23.7 hours vs 31.5 hours; 95% CI, 22.7-39.3 hours; P = .04). Median time to lowest HR was shorter for men vs women (54.2 hours; 95% CI, 47.3-62.0 hours vs 71.0 hours; 95% CI, 59.5-79.6 hours; P = .02).Conclusions and RelevanceIn this cohort study, bradycardia occurred during remdesivir infusion and persisted. Given the widespread use of remdesivir, practitioners should be aware of this safety signal.

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Remdesivir therapy associated with Bradycardia in SARS‐CoV2

Kumar¹,

Arcuri²,

Chaudhuri³

et al. 2021

Clinical Cardiology

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Severe sinus bradycardia associated with Remdesivir in a child with severe SARS-CoV-2 infection

Cited by 31 publications

References 4 publications

Bradycardia associated with remdesivir therapy for COVID-19 in a 59-year-old man

Bradycardia associated with remdesivir therapy for COVID-19 in a 59-year-old man

Identification of Bradycardia Following Remdesivir Administration Through the US Food and Drug Administration American College of Medical Toxicology COVID-19 Toxic Pharmacovigilance Project

Remdesivir therapy associated with Bradycardia in SARS‐CoV2

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