Drug interactions: a review of the unseen danger of experimental COVID-19 therapies. (4th August 2020)

• Record Type: Journal Article
• Authors: Hodge, Catherine; Marra, Fiona; Marzolini, Catia; Boyle, Alison; Gibbons, Sara; Siccardi, Marco; Burger, David; Back, David; Khoo, Saye
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 75:Number 12(2020)
• Page Start: 3417
• Page End: 3424
• Publication Date: 2020-08-04
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkaa340
• Languages: English
• ISSNs: 0305-7453

Abstract

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.