PMID- 34594487 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231107 IS - 2042-0986 (Print) IS - 2042-0994 (Electronic) IS - 2042-0986 (Linking) VI - 12 DP - 2021 TI - The safety, tolerability and mortality reduction efficacy of remdesivir; based on randomized clinical trials, observational and case studies reported safety outcomes: an updated systematic review and meta-analysis. PG - 20420986211042517 LID - 10.1177/20420986211042517 [doi] LID - 20420986211042517 AB - INTRODUCTION: Remdesivir, an experimental antiviral drug has shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both in vitro and in vivo. The present systematic review and meta-analysis were performed to quantify the safety and tolerability of remdesivir, based on safety outcome findings from randomized controlled trials, observational studies and case reports of remdesivir in coronavirus disease 2019 (COVID-19) patients. METHODS: We have performed a systematic search in the PubMed, Google Scholar and Cochrane Library using specific keywords such as 'COVID-19' OR 'SARS CoV-2' AND 'Remdesivir'. The study endpoints include total adverse events (AEs), serious adverse events (SAEs), grade 3 and grade 4 AEs, mortality and drug tolerability. Statistical analysis was carried out by using Revman 5.4 software. RESULTS: Total 15 studies were included for systematic review, but only 5 randomized clinical trials (RCTs) (n = 13,622) were included for meta-analysis. Visual inspection of the forest plots for remdesivir 10-day versus placebo and remdesivir 10-day versus 5-day groups revealed that there is a significant difference in SAEs [10-day remdesivir versus control (odds ratio [OR] = 0.55, 0.40-0.74) p = 0.0001; I (2) = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 0.56, 0.38-0.84) p = 0.005; I (2) = 13%]. In grade 4 AEs, there is a significant difference in 10-day remdesivir versus control (OR = 0.32, 0.19-0.54) p = 0.0001; I (2) = 0%, but not in comparison to 5-day remdesivir (OR = 0.95, 0.59-1.54) p = 0.85; I (2) = 0%. But there is no significant difference in grade 3 AEs [remdesivir 10 day versus control (OR = 0.81, 0.59-1.11) p = 0.19; I (2) = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.24, 0.86-1.80) p = 0.25; I (2) = 0%], in total AEs [remdesivir 10 day versus control (OR = 1.07, 0.66-1.75) p = 0.77; I (2) = 79%; remdesivir 10 day versus 5 day (OR = 1.08, 0.70-1.68) p = 0.73; I (2) = 54%)], in mortality [10-day remdesivir versus control (OR = 0.93, 0.80-1.08) p = 0.32; I (2) = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.39, 0.73-2.62) p = 0.32; I (2) = 0%)] and tolerability [remdesivir 10 day versus control (OR = 1.05, 0.51-2.18) p = 0.89; I (2) = 65%, 10-day remdesivir versus 5-day remdesivir (OR = 0.86, 0.18-4.01) p = 0.85; I (2) = 78%]. DISCUSSION & CONCLUSION: Ten-day remdesivir was a safe antiviral agent but not tolerable over control in the hospitalized COVID-19 patients with a need of administration cautiousness for grade 3 AEs. There was no added benefit of 10- or 5-day remdesivir in reducing mortality over placebo. To avoid SAEs, we suggest for prior monitoring of liver function tests (LFT), renal function tests (RFT), complete blood count (CBC) and serum electrolytes for those with preexisting hepatic and renal impairments and patients receiving concomitant hepatotoxic or nephrotoxic drugs. Furthermore, a number of RCTs of remdesivir in COVID-19 patients are suggested. PLAIN LANGUAGE SUMMARY: Ten-day remdesivir is a safe antiviral drug with common adverse events in comparison to placebo.The rate of serious adverse events and grade 3 adverse events were significantly lower in 10-day remdesivir in comparison to placebo/5-day remdesivir.There was no significant difference in the rate of tolerability and mortality reduction in 10-day remdesivir over placebo/5-day remdesivir.There were no new safety signals reported in vulnerable populations, paediatric, pregnant and lactating women. CI - (c) The Author(s), 2021. FAU - Santenna, Chenchula AU - Santenna C AUID- ORCID: 0000-0001-7466-1037 AD - Chenchula Santenna Department of Pharmacology, All India Institute of Medical Sciences, Bhopal, 3rd floor, Medical College Building, Saket Nagar, Bhopal 462020, Madhya Pradesh, India. FAU - Vidyasagar, Kota AU - Vidyasagar K AD - Department of Pharmacy Practice, University College of Pharmaceutical Sciences (UCPSc) Hanmakonda, India. FAU - Amarneni, Krishna Chaitanya AU - Amarneni KC AD - All India Institute of Medical Sciences, Bhopal, Bhopal, India. FAU - Ghanta, Sai Nikhila AU - Ghanta SN AD - All India Institute of Medical Sciences, Bhopal, Bhopal, India. FAU - Sadasivam, Balakrishnan AU - Sadasivam B AD - Department of Pharmacology, All India Institute of Medical Sciences, Bhopal, Bhopal, India. FAU - Pathan, Saman AU - Pathan S AD - Department of Pharmacology, All India Institute of Medical Sciences, Bhopal, Bhopal, India. FAU - Padmavathi, R AU - Padmavathi R AD - SVS Medical College and Hospital, Hyderabad, India. LA - eng PT - Journal Article DEP - 20210924 PL - England TA - Ther Adv Drug Saf JT - Therapeutic advances in drug safety JID - 101549074 PMC - PMC8477695 OTO - NOTNLM OT - COVID-19 OT - mortality OT - remdesivir OT - safety OT - tolerability COIS- Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article. EDAT- 2021/10/02 06:00 MHDA- 2021/10/02 06:01 PMCR- 2021/09/24 CRDT- 2021/10/01 07:28 PHST- 2020/10/28 00:00 [received] PHST- 2021/07/28 00:00 [accepted] PHST- 2021/10/01 07:28 [entrez] PHST- 2021/10/02 06:00 [pubmed] PHST- 2021/10/02 06:01 [medline] PHST- 2021/09/24 00:00 [pmc-release] AID - 10.1177_20420986211042517 [pii] AID - 10.1177/20420986211042517 [doi] PST - epublish SO - Ther Adv Drug Saf. 2021 Sep 24;12:20420986211042517. doi: 10.1177/20420986211042517. eCollection 2021.