PMID- 36787141 OWN - NLM STAT- MEDLINE DCOM- 20230216 LR - 20230221 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 6 IP - 2 DP - 2023 Feb 1 TI - Identification of Bradycardia Following Remdesivir Administration Through the US Food and Drug Administration American College of Medical Toxicology COVID-19 Toxic Pharmacovigilance Project. PG - e2255815 LID - 10.1001/jamanetworkopen.2022.55815 [doi] LID - e2255815 AB - IMPORTANCE: The 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. OBJECTIVE: To evaluate the magnitude and duration of bradycardic events following remdesivir administration. DESIGN, SETTING, AND PARTICIPANTS: A 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. EXPOSURES: Remdesivir administration. MAIN OUTCOMES AND MEASURES: Linear 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 <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. RESULTS: A 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 < .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 RELEVANCE: In this cohort study, bradycardia occurred during remdesivir infusion and persisted. Given the widespread use of remdesivir, practitioners should be aware of this safety signal. FAU - Devgun, Jason M AU - Devgun JM AD - Department of Emergency Medicine, Washington University School of Medicine, St Louis, Missouri. FAU - Zhang, Rongmei AU - Zhang R AD - Center for Drug Evaluation and Research Food and Drug Administration, Silver Spring, Maryland. FAU - Brent, Jeffrey AU - Brent J AD - Department of Medicine, University of Colorado School of Medicine, Aurora. FAU - Wax, Paul AU - Wax P AD - American College of Medical Toxicology, Phoenix, Arizona. AD - Department of Emergency Medicine, The University of Texas Southwestern Medical Center, Dallas. FAU - Burkhart, Keith AU - Burkhart K AD - Center for Drug Evaluation and Research Food and Drug Administration, Silver Spring, Maryland. FAU - Meyn, Alison AU - Meyn A AD - American College of Medical Toxicology, Phoenix, Arizona. FAU - Campleman, Sharan AU - Campleman S AD - American College of Medical Toxicology, Phoenix, Arizona. FAU - Abston, Stephanie AU - Abston S AD - American College of Medical Toxicology, Phoenix, Arizona. FAU - Aldy, Kim AU - Aldy K AD - American College of Medical Toxicology, Phoenix, Arizona. AD - Department of Emergency Medicine, The University of Texas Southwestern Medical Center, Dallas. CN - Toxicology Investigators Consortium FACT Study Group LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, U.S. Gov't, P.H.S. DEP - 20230201 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 3QKI37EEHE (remdesivir) SB - IM MH - Humans MH - Male MH - Female MH - United States/epidemiology MH - *COVID-19 MH - Cohort Studies MH - Pharmacovigilance MH - Bradycardia/chemically induced/epidemiology MH - United States Food and Drug Administration MH - COVID-19 Drug Treatment PMC - PMC9929701 COIS- Conflict of Interest Disclosures: None reported. FIR - Amirshahi, Maryann IR - Amirshahi M FIR - Boyle, Katherine IR - Boyle K FIR - Buchanan, Jennie IR - Buchanan J FIR - Carey, Jennifer IR - Carey J FIR - Heard, Kennon IR - Heard K FIR - Hendrickson, Robert IR - Hendrickson R FIR - Kazzi, Ziad IR - Kazzi Z FIR - Lavonas, Eric IR - Lavonas E FIR - Levine, Michael IR - Levine M FIR - Olives, Travis IR - Olives T FIR - Pizon, Anthony IR - Pizon A FIR - Schimmel, Jonathan IR - Schimmel J FIR - Sharma, Kapil IR - Sharma K FIR - Spyres, Meghan IR - Spyres M FIR - Wiegand, Timothy IR - Wiegand T EDAT- 2023/02/15 06:00 MHDA- 2023/02/17 06:00 PMCR- 2023/02/14 CRDT- 2023/02/14 11:33 PHST- 2023/02/14 11:33 [entrez] PHST- 2023/02/15 06:00 [pubmed] PHST- 2023/02/17 06:00 [medline] PHST- 2023/02/14 00:00 [pmc-release] AID - 2801411 [pii] AID - zoi221590 [pii] AID - 10.1001/jamanetworkopen.2022.55815 [doi] PST - epublish SO - JAMA Netw Open. 2023 Feb 1;6(2):e2255815. doi: 10.1001/jamanetworkopen.2022.55815.