Drug interactions: a review of the unseen danger of experimental COVID-19 therapies

Hodge, Daryl ORCID: 0000-0003-2288-7020, Marra, Fiona ORCID: 0000-0003-1326-1149, Marzolini, Catia, Boyle, Alison, Gibbons, Sara, Siccardi, Marco ORCID: 0000-0002-3539-7867, Burger, David, Back, David and Khoo, Saye
(2020) Drug interactions: a review of the unseen danger of experimental COVID-19 therapies. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 75 (12). pp. 3417-3424.

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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.

Item Type: Article
Uncontrolled Keywords: Humans, Pneumonia, Viral, Coronavirus Infections, Antiviral Agents, Therapies, Investigational, Drug Interactions, Pandemics, Betacoronavirus, COVID-19, SARS-CoV-2
Depositing User: Symplectic Admin
Date Deposited: 13 Aug 2020 07:53
Last Modified: 01 Jul 2023 10:22
DOI: 10.1093/jac/dkaa340
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3097318