Santenna Chenchula, Vidyasagar Kota, Amarneni Krishna Chaitanya, Ghanta Sai Nikhila, Sadasivam Balakrishnan, Pathan Saman, Padmavathi R
Chenchula Santenna Department of Pharmacology, All India Institute of Medical Sciences, Bhopal, 3rd floor, Medical College Building, Saket Nagar, Bhopal 462020, Madhya Pradesh, India.
Department of Pharmacy Practice, University College of Pharmaceutical Sciences (UCPSc) Hanmakonda, India.
Ther Adv Drug Saf. 2021 Sep 24;12:20420986211042517. doi: 10.1177/20420986211042517. eCollection 2021.
Remdesivir, an experimental antiviral drug has shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both and . 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.
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.
Total 15 studies were included for systematic review, but only 5 randomized clinical trials (RCTs) ( = 13,622) were included for meta-analysis. Visual inspection of the forest plots for remdesivir 10-day placebo and remdesivir 10-day 5-day groups revealed that there is a significant difference in SAEs [10-day remdesivir control (odds ratio [OR] = 0.55, 0.40-0.74) = 0.0001; = 0%; 10-day remdesivir 5-day remdesivir (OR = 0.56, 0.38-0.84) = 0.005; = 13%]. In grade 4 AEs, there is a significant difference in 10-day remdesivir control (OR = 0.32, 0.19-0.54) = 0.0001; = 0%, but not in comparison to 5-day remdesivir (OR = 0.95, 0.59-1.54) = 0.85; = 0%. But there is no significant difference in grade 3 AEs [remdesivir 10 day control (OR = 0.81, 0.59-1.11) = 0.19; = 0%; 10-day remdesivir 5-day remdesivir (OR = 1.24, 0.86-1.80) = 0.25; = 0%], in total AEs [remdesivir 10 day control (OR = 1.07, 0.66-1.75) = 0.77; = 79%; remdesivir 10 day 5 day (OR = 1.08, 0.70-1.68) = 0.73; = 54%)], in mortality [10-day remdesivir control (OR = 0.93, 0.80-1.08) = 0.32; = 0%; 10-day remdesivir 5-day remdesivir (OR = 1.39, 0.73-2.62) = 0.32; = 0%)] and tolerability [remdesivir 10 day control (OR = 1.05, 0.51-2.18) = 0.89; = 65%, 10-day remdesivir 5-day remdesivir (OR = 0.86, 0.18-4.01) = 0.85; = 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.
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.
瑞德西韦是一种实验性抗病毒药物，已显示出对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）具有抑制作用。本系统评价和荟萃分析基于瑞德西韦在2019冠状病毒病（COVID-19）患者中的随机对照试验、观察性研究和病例报告的安全性结果，对瑞德西韦的安全性和耐受性进行量化。
我们在PubMed、谷歌学术和Cochrane图书馆中使用特定关键词，如“COVID-19”或“SARS-CoV-2”以及“瑞德西韦”进行了系统检索。研究终点包括总不良事件（AE）、严重不良事件（SAE）、3级和4级AE、死亡率和药物耐受性。使用Revman 5.4软件进行统计分析。
共纳入15项研究进行系统评价，但仅纳入5项随机临床试验（RCT）（n = 13622）进行荟萃分析。对瑞德西韦10天与安慰剂组以及瑞德西韦10天与5天组的森林图进行直观检查发现，SAE存在显著差异[瑞德西韦10天与对照组（优势比[OR]=0.55，0.40 - 0.74）P = 0.0001；I² = 0%；瑞德西韦10天与瑞德西韦5天组（OR = 0.56，0.38 - 0.84）P = 0.005；I² = 13%]。在4级AE中，瑞德西韦10天与对照组存在显著差异（OR = 0.32，0.19 - 0.54）P = 0.0001；I² = 0%，但与瑞德西韦5天组相比无显著差异（OR = 0.95, 0.59 - 1.54）P = 0.85；I² = 0%。但在3级AE中无显著差异[瑞德西韦10天与对照组（OR = 0.81，0.59 - 1.11）P = 0.19；I² = 0%；瑞德西韦10天与瑞德西韦5天组（OR = 1.24，0.86 - 1.80）P = 0.25；I² = 0%]，在总AE中[瑞德西韦10天与对照组（OR = 1.07，0.66 - 1.75）P = 0.77；I² = 79%；瑞德西韦10天与5天组（OR = 1.08，0.70 - 1.68）P = 0.73；I² = 54%]，在死亡率[瑞德西韦10天与对照组（OR = 0.93，0.80 - 1.08）P = 0.32；I² = 0%；瑞德西韦10天与瑞德西韦5天组（OR = 1.39，0.73 - 2.
