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 the 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 July 19, 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%), and 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.

KEYWORDS:

• Remdesivir
• adverse drug events
• COVID-19
• Vigibase®
• hepatic enzyme changes
• renal injury

Article highlights

• Remdesivir is one of the proposed medicines for the treatment of the COVID – 19; however, there is paucity of data regarding its safety.

• We analyzed all the ADEs suspected to be caused by remdesivir reported in the WHO database durimg the last five years.

• Rise in hepatic enzymes, as well as renal injury, rises in blood creatinine, respiratory failure, tachy or bradyarrhythmia, hypotension, and rashes were the most frequent ADEs reported in the WHO database. Similar reporting was observed in data reported from clinical trials.

• Majority of these ADEs were of a serious nature and many of the serious ADEs were fatal but in the absence of causality assessment these cannot be attributed to remdesivir with certainty.

• Overall, reported ADEs are in line with the adverse drug reactions reported from the clinical trials.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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Funding

This paper was not funded.