Repurposed antimicrobial and antiviral drugs for COVID-19 treatment: safety and side effects in real clinical practice (scientific review)

The COVID-19 pandemic has posed a challenge for new etiotropic agents, leading to an urgent repurposing of antimicrobial and antiviral drugs to treat a new infection based on the results of in silico, in vitro, in vivo experimental studies, and clinical trials. However, less attention has been paid...

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Main Author: Marina V. Leonova
Format: Article
Language:Russian
Published: ZAO "Consilium Medicum" 2022-09-01
Series:Consilium Medicum
Subjects:
Online Access:https://consilium.orscience.ru/2075-1753/article/viewFile/119535/94183
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author Marina V. Leonova
author_facet Marina V. Leonova
author_sort Marina V. Leonova
collection DOAJ
description The COVID-19 pandemic has posed a challenge for new etiotropic agents, leading to an urgent repurposing of antimicrobial and antiviral drugs to treat a new infection based on the results of in silico, in vitro, in vivo experimental studies, and clinical trials. However, less attention has been paid to the safety of repurposed drugs. Exposure to repurposed drugs with limited risk-benefit evidence in COVID-19 required adaptation of safety monitoring, which affected the completeness and quality of reports, and making causality assessments the most difficult task. A review of data accumulated over the period of the COVID-19 pandemic on the nature of adverse reactions associated with the use of repurposed drugs (hydroxychloroquine, chloroquine, remdesivir, favipiravir, lopinavir/ritonavir, ribavirin) used in real practice is presented. The results of RCTs and observational studies, systematic reviews and meta-analyses were used. Systematized data on the safety of the use of hydroxychloroquine and chloroquine in patients with COVID-19 in short-term treatment (14 days), including a series of meta-analyses, the risk of adverse effects was increased by 1.52 times; the main manifestations are prolongation of the QT interval and arrhythmias (up to 25%), gastrointestinal disorders (up to 50%), increased levels of bilirubin (3%) and transaminases (up to 10%), dermatological (up to 10%) and neuropsychiatric side effects (up to 21.7%). Most of the side effects of repurposed antiviral drugs of the nucleoside analog group are associated with their direct cytotoxic effect, which is manifested by toxic damage to the gastrointestinal tract, hepatotoxicity, nephrotoxicity, cardiotoxicity, and hematotoxicity. The greatest number of side effects from the gastrointestinal tract and liver were observed for lopinavir/ritonavir in comparison with other drugs. New side effects have been identified for remdesivir when used in the context of the COVID-19 pandemic cardiotoxicity (bradycardia and severe hypotension) and nephrotoxicity, which was regarded by regulatory authorities as a safety signal. To solve the problems of assessing the cause-and-effect relationship, further more thorough research and analysis will be required. The accumulated information in the context of the ongoing COVID-19 pandemic should be subject to ongoing dynamic analysis and published in medical journals to alert clinicians.
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spelling doaj.art-7e4c503f145441f5a94f999f0be0891f2022-12-22T10:05:32ZrusZAO "Consilium Medicum"Consilium Medicum2075-17532542-21702022-09-0124956757310.26442/20751753.2022.9.2017634619Repurposed antimicrobial and antiviral drugs for COVID-19 treatment: safety and side effects in real clinical practice (scientific review)Marina V. Leonova0https://orcid.org/0000-0001-8228-1114Association of Clinical PharmacologistsThe COVID-19 pandemic has posed a challenge for new etiotropic agents, leading to an urgent repurposing of antimicrobial and antiviral drugs to treat a new infection based on the results of in silico, in vitro, in vivo experimental studies, and clinical trials. However, less attention has been paid to the safety of repurposed drugs. Exposure to repurposed drugs with limited risk-benefit evidence in COVID-19 required adaptation of safety monitoring, which affected the completeness and quality of reports, and making causality assessments the most difficult task. A review of data accumulated over the period of the COVID-19 pandemic on the nature of adverse reactions associated with the use of repurposed drugs (hydroxychloroquine, chloroquine, remdesivir, favipiravir, lopinavir/ritonavir, ribavirin) used in real practice is presented. The results of RCTs and observational studies, systematic reviews and meta-analyses were used. Systematized data on the safety of the use of hydroxychloroquine and chloroquine in patients with COVID-19 in short-term treatment (14 days), including a series of meta-analyses, the risk of adverse effects was increased by 1.52 times; the main manifestations are prolongation of the QT interval and arrhythmias (up to 25%), gastrointestinal disorders (up to 50%), increased levels of bilirubin (3%) and transaminases (up to 10%), dermatological (up to 10%) and neuropsychiatric side effects (up to 21.7%). Most of the side effects of repurposed antiviral drugs of the nucleoside analog group are associated with their direct cytotoxic effect, which is manifested by toxic damage to the gastrointestinal tract, hepatotoxicity, nephrotoxicity, cardiotoxicity, and hematotoxicity. The greatest number of side effects from the gastrointestinal tract and liver were observed for lopinavir/ritonavir in comparison with other drugs. New side effects have been identified for remdesivir when used in the context of the COVID-19 pandemic cardiotoxicity (bradycardia and severe hypotension) and nephrotoxicity, which was regarded by regulatory authorities as a safety signal. To solve the problems of assessing the cause-and-effect relationship, further more thorough research and analysis will be required. The accumulated information in the context of the ongoing COVID-19 pandemic should be subject to ongoing dynamic analysis and published in medical journals to alert clinicians.https://consilium.orscience.ru/2075-1753/article/viewFile/119535/94183antiviral drugsrepurposed drugscovid-19safetyside effects
spellingShingle Marina V. Leonova
Repurposed antimicrobial and antiviral drugs for COVID-19 treatment: safety and side effects in real clinical practice (scientific review)
Consilium Medicum
antiviral drugs
repurposed drugs
covid-19
safety
side effects
title Repurposed antimicrobial and antiviral drugs for COVID-19 treatment: safety and side effects in real clinical practice (scientific review)
title_full Repurposed antimicrobial and antiviral drugs for COVID-19 treatment: safety and side effects in real clinical practice (scientific review)
title_fullStr Repurposed antimicrobial and antiviral drugs for COVID-19 treatment: safety and side effects in real clinical practice (scientific review)
title_full_unstemmed Repurposed antimicrobial and antiviral drugs for COVID-19 treatment: safety and side effects in real clinical practice (scientific review)
title_short Repurposed antimicrobial and antiviral drugs for COVID-19 treatment: safety and side effects in real clinical practice (scientific review)
title_sort repurposed antimicrobial and antiviral drugs for covid 19 treatment safety and side effects in real clinical practice scientific review
topic antiviral drugs
repurposed drugs
covid-19
safety
side effects
url https://consilium.orscience.ru/2075-1753/article/viewFile/119535/94183
work_keys_str_mv AT marinavleonova repurposedantimicrobialandantiviraldrugsforcovid19treatmentsafetyandsideeffectsinrealclinicalpracticescientificreview