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Review
. 2020 Oct;177(19):4353-4374.
doi: 10.1111/bph.15204. Epub 2020 Aug 13.

Safety perspectives on presently considered drugs for the treatment of COVID-19

Sophie L Penman  1 , Robyn T Kiy  1 , Rebecca L Jensen  1 , Christopher Beoku-Betts  2 , Ana Alfirevic  1 , David Back  1 , Saye H Khoo  1 , Andrew Owen  1 , Munir Pirmohamed  1 , B Kevin Park  1 , Xiaoli Meng  1 , Christopher E Goldring  1 , Amy E Chadwick  1
Affiliations
Review

Safety perspectives on presently considered drugs for the treatment of COVID-19

Sophie L Penman et al. Br J Pharmacol. 2020 Oct.

Abstract

Intense efforts are underway to evaluate potential therapeutic agents for the treatment of COVID-19. In order to respond quickly to the crisis, the repurposing of existing drugs is the primary pharmacological strategy. Despite the urgent clinical need for these therapies, it is imperative to consider potential safety issues. This is important due to the harm-benefit ratios that may be encountered when treating COVID-19, which can depend on the stage of the disease, when therapy is administered and underlying clinical factors in individual patients. Treatments are currently being trialled for a range of scenarios from prophylaxis (where benefit must greatly exceed risk) to severe life-threatening disease (where a degree of potential risk may be tolerated if it is exceeded by the potential benefit). In this perspective, we have reviewed some of the most widely researched repurposed agents in order to identify potential safety considerations using existing information in the context of COVID-19.

Keywords: COVID-19; drug repurposing; drug safety; toxicology.

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Conflict of interest statement

A.A., B.K.P., C.B.‐B., C.E.G., R.L.J., R.T.K., S.H.K., S.L.P., and X.M. declare that they have no conflicts of interest. A.O. declares no direct conflict of interest but is Director and CSO for Tandem Nano Ltd and a co‐inventor of patents relating to drug delivery of infectious disease medicines. A.E.C. reports no direct conflict of interest but receives research funding for the support of S.L.P. and R.L.J. from Servier Pharmaceuticals and AstraZeneca; these are unrelated to the published work. A.E.C. receives additional unrelated research funding from Janssen Pharmaceuticals. A.O. has received consultancy and/or research funding from ViiV Healthcare, Merck, AstraZeneca, Gilead, and Janssen unrelated to the current paper. D.B. received educational grants and/or consultancy from AbbVie, Novartis, Merck, Gilead, and ViiV Healthcare outside the submitted work. M.P. receives research funding from various organisations including the MRC, NIHR, EU Commission, and Health Education England. He has also received partnership funding for the following: MRC Clinical Pharmacology Training Scheme (co‐funded by MRC and Roche, UCB, Eli Lilly, and Novartis) and a PhD studentship jointly funded by EPSRC and Astra Zeneca. He has also unrestricted educational grant support for the UK Pharmacogenetics and Stratified Medicine Network from Bristol‐Myers Squibb and UCB. None of the funding received is related to the current paper.

Figures

FIGURE 1
FIGURE 1
Overview of the mechanisms of action of the repurposed drugs undergoing clinical trials for the treatment of COVID‐19 that are reviewed here. Compounds in red represent those that are viral entry inhibitors, compounds in green represent disruptors of cellular viral processing, compounds in blue are modulators of the hyperinflammatory phase of infection, and compounds in yellow stimulate host immunomodulatory and antiviral activity. ISRE, IFN‐stimulated response element; P, phosphate; RdRp, RNA‐dependent RNA polymerase; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2
See this image and copyright information in PMC

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