Risk Assessment of Drug-Induced Long QT Syndrome for Some COVID-19 Repurposed Drugs.
Identifieur interne : 000188 ( Main/Exploration ); précédent : 000187; suivant : 000189Risk Assessment of Drug-Induced Long QT Syndrome for Some COVID-19 Repurposed Drugs.
Auteurs : Veronique Michaud [États-Unis, Canada] ; Pamela Dow [États-Unis] ; Sweilem B. Al Rihani [États-Unis] ; Malavika Deodhar [États-Unis] ; Meghan Arwood [États-Unis] ; Brian Cicali [États-Unis] ; Jacques Turgeon [États-Unis, Canada]Source :
- Clinical and translational science [ 1752-8062 ] ; 2021.
Descripteurs français
- KwdFr :
- MESH :
- effets indésirables : Antiviraux, Azithromycine, Hydroxychloroquine.
- induit chimiquement : Syndrome du QT long.
- Appréciation des risques, Humains, Repositionnement des médicaments.
English descriptors
- KwdEn :
- MESH :
- chemical , adverse effects : Antiviral Agents, Azithromycin, Hydroxychloroquine.
- chemically induced : Long QT Syndrome.
- drug therapy : COVID-19.
- Drug Repositioning, Humans, Risk Assessment, SARS-CoV-2.
Abstract
The risk-benefit ratio associated with the use of repurposed drugs to treat severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2)-related infectious coronavirus disease 2019 (COVID-19) is complicated because benefits are awaited, not proven. A thorough literature search was conducted to source information on the pharmacological properties of 5 drugs and 1 combination (azithromycin, chloroquine, favipiravir, hydroxychloroquine, remdesivir, and lopinavir/ritonavir) repurposed to treat COVID-19. A risk assessment of drug-induced long QT syndrome (LQTS) associated with COVID-19 repurposed drugs was performed and compared with 23 well-known torsadogenic and 10 low torsadogenic risk compounds. Computer calculations were performed using pharmacokinetic and pharmacodynamic data, including affinity to block the rapid component of the delayed rectifier cardiac potassium current (IKr ) encoded by the human ether-a-go-go gene (hERG), propensity to prolong cardiac repolarization (QT interval) and cause torsade de pointes (TdP). Seven different LQTS indices were calculated and compared. The US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was queried with specific key words relating to arrhythmogenic events. Estimators of LQTS risk levels indicated a very high or moderate risk for all COVID-19 repurposed drugs with the exception for azithromycin, although cases of TdP have been reported with this drug. There was excellent agreement among the various indices used to assess risk of drug-induced LQTS for the 6 repurposed medications and 23 torsadogenic compounds. Based on our results, monitoring of the QT interval shall be performed when some COVID-19 repurposed drugs are used, as such monitoring is possible for hospitalized patients or with the use of biodevices for outpatients.
DOI: 10.1111/cts.12882
PubMed: 32888379
PubMed Central: PMC7877829
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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<front><div type="abstract" xml:lang="en">The risk-benefit ratio associated with the use of repurposed drugs to treat severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2)-related infectious coronavirus disease 2019 (COVID-19) is complicated because benefits are awaited, not proven. A thorough literature search was conducted to source information on the pharmacological properties of 5 drugs and 1 combination (azithromycin, chloroquine, favipiravir, hydroxychloroquine, remdesivir, and lopinavir/ritonavir) repurposed to treat COVID-19. A risk assessment of drug-induced long QT syndrome (LQTS) associated with COVID-19 repurposed drugs was performed and compared with 23 well-known torsadogenic and 10 low torsadogenic risk compounds. Computer calculations were performed using pharmacokinetic and pharmacodynamic data, including affinity to block the rapid component of the delayed rectifier cardiac potassium current (I<sub>Kr</sub>
) encoded by the human ether-a-go-go gene (hERG), propensity to prolong cardiac repolarization (QT interval) and cause torsade de pointes (TdP). Seven different LQTS indices were calculated and compared. The US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was queried with specific key words relating to arrhythmogenic events. Estimators of LQTS risk levels indicated a very high or moderate risk for all COVID-19 repurposed drugs with the exception for azithromycin, although cases of TdP have been reported with this drug. There was excellent agreement among the various indices used to assess risk of drug-induced LQTS for the 6 repurposed medications and 23 torsadogenic compounds. Based on our results, monitoring of the QT interval shall be performed when some COVID-19 repurposed drugs are used, as such monitoring is possible for hospitalized patients or with the use of biodevices for outpatients.</div>
</front>
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<Abstract><AbstractText>The risk-benefit ratio associated with the use of repurposed drugs to treat severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2)-related infectious coronavirus disease 2019 (COVID-19) is complicated because benefits are awaited, not proven. A thorough literature search was conducted to source information on the pharmacological properties of 5 drugs and 1 combination (azithromycin, chloroquine, favipiravir, hydroxychloroquine, remdesivir, and lopinavir/ritonavir) repurposed to treat COVID-19. A risk assessment of drug-induced long QT syndrome (LQTS) associated with COVID-19 repurposed drugs was performed and compared with 23 well-known torsadogenic and 10 low torsadogenic risk compounds. Computer calculations were performed using pharmacokinetic and pharmacodynamic data, including affinity to block the rapid component of the delayed rectifier cardiac potassium current (I<sub>Kr</sub>
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