William H.K. SchillingNicholas J. WhiteFaculty of Tropical Medicine, Mahidol UniversityNuffield Department of Medicine2022-08-042022-08-042021-01-01Expert Opinion on Pharmacotherapy. Vol.22, No.10 (2021), 1257-126617447666146565662-s2.0-85102786897https://repository.li.mahidol.ac.th/handle/20.500.14594/78793Introduction: The 4-aminoquinolines, chloroquine, and hydroxychloroquine have been used for over 70 years for malaria and rheumatological conditions, respectively. Their broad-spectrum antiviral activity, excellent safety profile, tolerability, low cost, and ready availability made them prime repurposing therapeutic candidates at the beginning of the COVID-19 pandemic. Areas covered: Here, the authors discuss the history of hydroxychloroquine and chloroquine, the in vitro data which led to their widespread repurposing and adoption in COVID-19 and their complex pharmacokinetics. The evidence for the use of these drugs is assessed through in vivo animal experiments and the wealth of conflicting data and interpretations published during COVID-19, including the more informative results from randomized controlled trials (RCTs). The safety aspects of these drugs, in particular cardiotoxicity, are then reviewed. Expert opinion: The evidence from clinical trials in COVID-19 supports the well-established safety record of the 4-aminoquinolines at currently recommended dosage. In hospitalized patients with severe COVID-19 RCTs show clearly that the 4-aminoquinolines are not beneficial. The only treatments with proven benefit at this stage of infection are immunomodulators (dexamethasone, IL-6 receptor antagonists). No antiviral drugs have proven life-saving in late-stage COVID-19.Mahidol UniversityMedicinePharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1080/14656566.2021.1898589