Drug interactions: a review of the unseen danger of experimental COVID-19 therapies.
Identifieur interne : 000F91 ( Main/Corpus ); précédent : 000F90; suivant : 000F92Drug interactions: a review of the unseen danger of experimental COVID-19 therapies.
Auteurs : Catherine Hodge ; Fiona Marra ; Catia Marzolini ; Alison Boyle ; Sara Gibbons ; Marco Siccardi ; David Burger ; David Back ; Saye KhooSource :
- The Journal of antimicrobial chemotherapy [ 1460-2091 ] ; 2020.
English descriptors
- KwdEn :
- Antiviral Agents (adverse effects), Antiviral Agents (pharmacokinetics), Antiviral Agents (therapeutic use), Betacoronavirus (MeSH), COVID-19 (MeSH), Coronavirus Infections (drug therapy), Drug Interactions (MeSH), Humans (MeSH), Pandemics (MeSH), Pneumonia, Viral (drug therapy), SARS-CoV-2 (MeSH), Therapies, Investigational (adverse effects).
- MESH :
- chemical , adverse effects : Antiviral Agents.
- chemical , pharmacokinetics : Antiviral Agents.
- chemical , therapeutic use : Antiviral Agents.
- adverse effects : Therapies, Investigational.
- drug therapy : Coronavirus Infections, Pneumonia, Viral.
- Betacoronavirus, COVID-19, Drug Interactions, Humans, Pandemics, SARS-CoV-2.
Abstract
As global health services respond to the coronavirus pandemic, many prescribers are turning to experimental drugs. This review aims to assess the risk of drug-drug interactions in the severely ill COVID-19 patient. Experimental therapies were identified by searching ClinicalTrials.gov for 'COVID-19', '2019-nCoV', '2019 novel coronavirus' and 'SARS-CoV-2'. The last search was performed on 30 June 2020. Herbal medicines, blood-derived products and in vitro studies were excluded. We identified comorbidities by searching PubMed for the MeSH terms 'COVID-19', 'Comorbidity' and 'Epidemiological Factors'. Potential drug-drug interactions were evaluated according to known pharmacokinetics, overlapping toxicities and QT risk. Drug-drug interactions were graded GREEN and YELLOW: no clinically significant interaction; AMBER: caution; RED: serious risk. A total of 2378 records were retrieved from ClinicalTrials.gov, which yielded 249 drugs that met inclusion criteria. Thirteen primary compounds were screened against 512 comedications. A full database of these interactions is available at www.covid19-druginteractions.org. Experimental therapies for COVID-19 present a risk of drug-drug interactions, with lopinavir/ritonavir (10% RED, 41% AMBER; mainly a perpetrator of pharmacokinetic interactions but also risk of QT prolongation particularly when given with concomitant drugs that can prolong QT), chloroquine and hydroxychloroquine (both 7% RED and 27% AMBER, victims of some interactions due to metabolic profile but also perpetrators of QT prolongation) posing the greatest risk. With management, these risks can be mitigated. We have published a drug-drug interaction resource to facilitate medication review for the critically ill patient.
DOI: 10.1093/jac/dkaa340
PubMed: 32750131
PubMed Central: PMC7454591
Links to Exploration step
pubmed:32750131Le document en format XML
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Catia" uniqKey="Marzolini C" first="Catia" last="Marzolini">Catia Marzolini</name><affiliation><nlm:affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel, Basel, Switzerland.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>University of Basel, Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Boyle, Alison" sort="Boyle, Alison" uniqKey="Boyle A" first="Alison" last="Boyle">Alison Boyle</name><affiliation><nlm:affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Pharmacy, NHS Greater Glasgow and Clyde, 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Pharmacy, NHS Greater Glasgow and Clyde, Glasgow, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Marzolini, Catia" sort="Marzolini, Catia" uniqKey="Marzolini C" first="Catia" last="Marzolini">Catia Marzolini</name><affiliation><nlm:affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel, Basel, Switzerland.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>University of Basel, Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Boyle, Alison" sort="Boyle, Alison" uniqKey="Boyle A" first="Alison" last="Boyle">Alison Boyle</name><affiliation><nlm:affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Pharmacy, NHS Greater Glasgow and Clyde, Glasgow, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Gibbons, Sara" sort="Gibbons, Sara" uniqKey="Gibbons S" first="Sara" last="Gibbons">Sara Gibbons</name><affiliation><nlm:affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Siccardi, Marco" sort="Siccardi, Marco" uniqKey="Siccardi M" first="Marco" last="Siccardi">Marco Siccardi</name><affiliation><nlm:affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Burger, David" sort="Burger, David" uniqKey="Burger D" first="David" last="Burger">David Burger</name><affiliation><nlm:affiliation>Radboud University Medical Centre, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Back, David" sort="Back, David" uniqKey="Back D" first="David" last="Back">David Back</name><affiliation><nlm:affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Khoo, Saye" sort="Khoo, Saye" uniqKey="Khoo S" first="Saye" last="Khoo">Saye Khoo</name><affiliation><nlm:affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Royal Liverpool University Hospital, Liverpool, UK.</nlm:affiliation></affiliation></author></analytic><series><title level="j">The Journal of antimicrobial chemotherapy</title><idno type="eISSN">1460-2091</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral Agents (adverse effects)</term><term>Antiviral Agents (pharmacokinetics)</term><term>Antiviral Agents (therapeutic use)</term><term>Betacoronavirus (MeSH)</term><term>COVID-19 (MeSH)</term><term>Coronavirus Infections (drug therapy)</term><term>Drug Interactions (MeSH)</term><term>Humans (MeSH)</term><term>Pandemics (MeSH)</term><term>Pneumonia, Viral (drug therapy)</term><term>SARS-CoV-2 (MeSH)</term><term>Therapies, Investigational (adverse effects)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiviral Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Antiviral Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiviral Agents</term></keywords><keywords scheme="MESH" qualifier="adverse effects" xml:lang="en"><term>Therapies, Investigational</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Betacoronavirus</term><term>COVID-19</term><term>Drug Interactions</term><term>Humans</term><term>Pandemics</term><term>SARS-CoV-2</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">As global health services respond to the coronavirus pandemic, many prescribers are turning to experimental drugs. This review aims to assess the risk of drug-drug interactions in the severely ill COVID-19 patient. Experimental therapies were identified by searching ClinicalTrials.gov for 'COVID-19', '2019-nCoV', '2019 novel coronavirus' and 'SARS-CoV-2'. The last search was performed on 30 June 2020. Herbal medicines, blood-derived products and in vitro studies were excluded. We identified comorbidities by searching PubMed for the MeSH terms 'COVID-19', 'Comorbidity' and 'Epidemiological Factors'. Potential drug-drug interactions were evaluated according to known pharmacokinetics, overlapping toxicities and QT risk. Drug-drug interactions were graded GREEN and YELLOW: no clinically significant interaction; AMBER: caution; RED: serious risk. A total of 2378 records were retrieved from ClinicalTrials.gov, which yielded 249 drugs that met inclusion criteria. Thirteen primary compounds were screened against 512 comedications. A full database of these interactions is available at www.covid19-druginteractions.org. Experimental therapies for COVID-19 present a risk of drug-drug interactions, with lopinavir/ritonavir (10% RED, 41% AMBER; mainly a perpetrator of pharmacokinetic interactions but also risk of QT prolongation particularly when given with concomitant drugs that can prolong QT), chloroquine and hydroxychloroquine (both 7% RED and 27% AMBER, victims of some interactions due to metabolic profile but also perpetrators of QT prolongation) posing the greatest risk. With management, these risks can be mitigated. We have published a drug-drug interaction resource to facilitate medication review for the critically ill patient.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32750131</PMID><DateCompleted><Year>2020</Year><Month>11</Month><Day>27</Day></DateCompleted><DateRevised><Year>2021</Year><Month>01</Month><Day>10</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1460-2091</ISSN><JournalIssue CitedMedium="Internet"><Volume>75</Volume><Issue>12</Issue><PubDate><Year>2020</Year><Month>12</Month><Day>01</Day></PubDate></JournalIssue><Title>The Journal of antimicrobial chemotherapy</Title><ISOAbbreviation>J Antimicrob Chemother</ISOAbbreviation></Journal><ArticleTitle>Drug interactions: a review of the unseen danger of experimental COVID-19 therapies.</ArticleTitle><Pagination><MedlinePgn>3417-3424</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1093/jac/dkaa340</ELocationID><Abstract><AbstractText>As global health services respond to the coronavirus pandemic, many prescribers are turning to experimental drugs. This review aims to assess the risk of drug-drug interactions in the severely ill COVID-19 patient. Experimental therapies were identified by searching ClinicalTrials.gov for 'COVID-19', '2019-nCoV', '2019 novel coronavirus' and 'SARS-CoV-2'. The last search was performed on 30 June 2020. Herbal medicines, blood-derived products and in vitro studies were excluded. We identified comorbidities by searching PubMed for the MeSH terms 'COVID-19', 'Comorbidity' and 'Epidemiological Factors'. Potential drug-drug interactions were evaluated according to known pharmacokinetics, overlapping toxicities and QT risk. Drug-drug interactions were graded GREEN and YELLOW: no clinically significant interaction; AMBER: caution; RED: serious risk. A total of 2378 records were retrieved from ClinicalTrials.gov, which yielded 249 drugs that met inclusion criteria. Thirteen primary compounds were screened against 512 comedications. A full database of these interactions is available at www.covid19-druginteractions.org. Experimental therapies for COVID-19 present a risk of drug-drug interactions, with lopinavir/ritonavir (10% RED, 41% AMBER; mainly a perpetrator of pharmacokinetic interactions but also risk of QT prolongation particularly when given with concomitant drugs that can prolong QT), chloroquine and hydroxychloroquine (both 7% RED and 27% AMBER, victims of some interactions due to metabolic profile but also perpetrators of QT prolongation) posing the greatest risk. With management, these risks can be mitigated. We have published a drug-drug interaction resource to facilitate medication review for the critically ill patient.</AbstractText><CopyrightInformation>© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hodge</LastName><ForeName>Catherine</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marra</LastName><ForeName>Fiona</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pharmacy, NHS Greater Glasgow and Clyde, Glasgow, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marzolini</LastName><ForeName>Catia</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel, Basel, Switzerland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University of Basel, Basel, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boyle</LastName><ForeName>Alison</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pharmacy, NHS Greater Glasgow and Clyde, Glasgow, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gibbons</LastName><ForeName>Sara</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Siccardi</LastName><ForeName>Marco</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Burger</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Radboud University Medical Centre, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Back</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Khoo</LastName><ForeName>Saye</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Royal Liverpool University Hospital, Liverpool, UK.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>J Antimicrob Chemother</MedlineTA><NlmUniqueID>7513617</NlmUniqueID><ISSNLinking>0305-7453</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000073640" MajorTopicYN="Y">Betacoronavirus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName><QualifierName UI="Q000188" 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