Risk of Adverse Drug Events Following the Virtual Addition of COVID-19 Repurposed Drugs to Drug Regimens of Frail Older Adults with Polypharmacy

• Published in: Journal of clinical medicine Vol. 9; no. 8; p. 2591
• Main Authors: Al Rihani, Sweilem B, Smith, Matt K, Bikmetov, Ravil, Deodhar, Malavika, Dow, Pamela, Turgeon, Jacques, Michaud, Veronique
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.08.2020; MDPI
• Subjects: Clinical medicine; Coronaviruses; COVID-19; Drug dosages; Polypharmacy; Prescription drugs; United States > US; COVID-19; older adults; adverse drug events; simulation; polypharmacy
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm9082591

Determination of the risk-benefit ratio associated with the use of novel coronavirus disease 2019 (COVID-19) repurposed drugs in older adults with polypharmacy is mandatory. Our objective was to develop and validate a strategy to assess risk for adverse drug events (ADE) associated with COVID-19 repurposed drugs using hydroxychloroquine (HCQ) and chloroquine (CQ), alone or in combination with azithromycin (AZ), and the combination lopinavir/ritonavir (LPV/r). These medications were virtually added, one at a time, to drug regimens of 12,383 participants of the Program of All-Inclusive Care for the Elderly. The MedWise Risk Score (MRS ) was determined from 198,323 drug claims. Results demonstrated that the addition of each repurposed drug caused a rightward shift in the frequency distribution of MRS values ( < 0.05); the increase was due to an increase in the drug-induced Long QT Syndrome (LQTS) or CYP450 drug interaction burden risk scores. Increases in LQTS risk observed with HCQ + AZ and CQ + AZ were of the same magnitude as those estimated when terfenadine or terfenadine + AZ, used as positive controls for drug-induced LQTS, were added to drug regimens. The simulation-based strategy performed offers a way to assess risk of ADE for drugs to be used in people with underlying medical comorbidities and polypharmacy at risk of COVID-19 infection without exposing them to these drugs.