Rapid review of suspected adverse drug events due to remdesivir in the WHO database; findings and implications

Abstract

Objectives: Remdesivir has shown promise in the management of patients with COVID-19 although recent studies have shown concerns with its effectiveness in practice. Despite this there is a need to document potential adverse drug events (ADEs) to guide future decisions as limited ADE data available before COVID-19 pandemic. Methods: Interrogation of WHO VigiBase® from 2015 to 2020 coupled with published studies of ADEs in COVID-19 patients. The main outcome measures are the extent of ADEs broken down by factors including age, seriousness, region and organ. Results: A total 1086 ADEs were reported from the 439 individual case reports up to 19 July 2020 in the VigiBase®, reduced to 1004 once duplicates were excluded. Almost all ADEs concerned COVID-19 patients (92.5%), with an appreciable number from the Americas (67.7%). The majority of ADEs were from males > 45 years and were serious (82.5%). An increase in hepatic enzymes (32.1%), renal injury (14.4%), rise in creatinine levels (11.2%) respiratory failure (6.4%) were the most frequently reported ADEs. Conclusions: Deterioration of liver and kidney function are frequently observed ADEs with remdesivir; consequently, patients should be monitored for these ADEs. The findings are in line with ADEs included in regulatory authority documents.

Systematic Review on the Therapeutic Options for COVID-19: Clinical Evidence of Drug Efficacy and Implications

“…45 , 138–141 Patient’s liver and kidney function must be monitored during treatment to help minimize any adverse drug reactions. 142 However, more recent evidence has resulted in WHO guidelines no longer recommending the use of remdesivir in hospitalized patients with COVID-19. This is based on the reports that remdesivir could not reduce mortality, the need for mechanical ventilation, or the duration of hospital stay.…”

Nucleoside Analogs and Nucleoside Precursors as Drugs in the Fight against SARS-CoV-2 and Other Coronaviruses

“…Apart from the more common low-grade side effects occurring during or soon after the time of drug infusion (such as low blood pressure, nausea, vomiting, and sweating [ 153 ]), marked sinus bradycardia, occurring acutely on the initiation of drug therapy and resolving almost immediately on its cessation, was reported [ 154 ]. An accurate study on the adverse drug events (ADEs) associated with remdesivir administration to COVID-19 patients analyzed 439 cases that reported 1004 adverse effects [ 155 ]. These ADEs, classified as severe in more than 80% of cases, were mainly from male patients older than 45 and corresponded mostly to: rise in hepatic enzyme levels, kidney injury, increased creatinine levels, and respiratory failure [ 155 ].…”

“…An accurate study on the adverse drug events (ADEs) associated with remdesivir administration to COVID-19 patients analyzed 439 cases that reported 1004 adverse effects [ 155 ]. These ADEs, classified as severe in more than 80% of cases, were mainly from male patients older than 45 and corresponded mostly to: rise in hepatic enzyme levels, kidney injury, increased creatinine levels, and respiratory failure [ 155 ]. Overall, deterioration of hepatic, renal, and, less frequently, cardiac function were observed as ADEs associated with remdesivir administration, highlighting the need to monitor remdesivir-receiving patients for these ADEs carefully.…”

Understanding the Co-Epidemic of Obesity and COVID-19: Current Evidence, Comparison with Previous Epidemics, Mechanisms, and Preventive and Therapeutic Perspectives

“…If available, remdesivir is suggested for hospitalized patients with severe COVID-19. Remdesivir, which was recently approved by the FDA for hospitalized adults and pediatric patients above 12 years of age and weighing at least 40 kg for the treatment of COVID-19, is not recommended when serum alanine aminotransferase (ALT) are 5 times the upper limit of normal and should be discontinued if ALT rises above this level during treatment [202][203][204][205]. The pharmacokinetics of remdesivir in the setting of renal insufficiency is unclear.…”