Abstract
Some effective drugs have been approved or issued an Emergency Use Authorization for the treatment of COVID-19 in hospitalized patients, but post-market surveillance is warranted to monitor adverse events. We reviewed clinical trials and case reports in patients with moderate-to-severe COVID-19 infection who received remdesivir, baricitinib, tocilizumab, or sarilumab. The drug-specific pharmacokinetics, toxicity, and drug interactions are summarized in this study. Remdesivir and baricitinib are small-molecule drugs that are mainly metabolized by the kidneys, while tocilizumab and sarilumab are monoclonal antibody drugs with metabolic pathways that are currently not fully understood. The most common adverse events of these drugs are alterations in liver function, but serious adverse events have rarely been attributed to them. Only a few studies have reported that remdesivir might be cardiotoxic and that baricitinib might cause thromboembolism. Biological agents such as baricitinib, tocilizumab, and sarilumab could inhibit the pathway of inflammatory processes, leading to immune dysregulation, so the risk of secondary infection should be assessed before prescribing. Further recognition of the pathogenic mechanism and risk factors of adverse events is essential for optimizing treatment strategies.
Highlights
As of 20 September 2021, there have been 228.4 million confirmed cases of coronavirus disease 2019 (COVID-19), which is caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), and these cases include 4.7 million deaths [1]
Venous thromboembolism, and pulmonary embolism occurred in 6%, 4%, and 1% of patients treated with baricitinib plus remdesivir, respectively, which did not achieve statistically significant differences compared to those treated with remdesivir alone [17]
Data on the absorption, distribution, metabolism, and excretion of sarilumab are still lacking in COVID-19 patients, sarilumab has a molecular weight of approximately 150 kDa [19,91], which is similar to tocilizumab, which implies that it might not be readily excreted from the kidneys
Summary
As of 20 September 2021, there have been 228.4 million confirmed cases of coronavirus disease 2019 (COVID-19), which is caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), and these cases include 4.7 million deaths [1]. For moderate-to-severe infections, in addition to corticosteroids and emergency use of convalescent plasma [8,9], the US FDA approved or issued an EUA for remdesivir, remdesivir plus baricitinib, and tocilizumab. The US FDA approved corticosteroids in July 2020 [8] and issued an EUA for emergency use of convalescent plasma in August 2020 [9] for hospitalized COVID-19 patients, but the available drugs for moderate-to-severe infections were still limited. The US FDA approved remdesivir in intravenous injection form in October 2020 [10] based on the ACTT-1 clinical trial [20], and issued an EUA for baricitinib oral tablets in combination with remdesivir in November.
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