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

Ravil Bikmetov,Matt K Smith,Veronique Michaud,Malavika Deodhar,Sweilem B Al Rihani,Jacques Turgeon,Pamela Dow

doi:10.3390/jcm9082591

Ravil Bikmetov, Matt K Smith + Show 5 more

Open Access

https://doi.org/10.3390/jcm9082591

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Abstract

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 (MRSTM) 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 MRSTM values (p < 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.

Highlights

In December 2019, an unidentified pneumonia was reported in Wuhan, China [1]
The most common diseases/symptoms observed in our Programs of All-inclusive Care for the Elderly (PACE) population were hypertension, dyslipidemia, pain, vitamin D deficiency, constipation, type 2 diabetes, gastro-esophageal reflux disorder (GERD), and chronic obstructive pulmonary disease (COPD)
Our study used a simulation strategy based on a medication risk score assessment used clinically to improve drug safety and reduce risks of adverse drug events (ADE) in people with underlying medical comorbidities and polypharmacy

Summary

Introduction

The World Health Organization (WHO) declared an epidemiological alert on 31 December 2019 [1,2]. As of 5 August 2020, COVID-19 has been diagnosed in more than 18,601,795 patients and associated with over 702,045 deaths all over the world [3]. Hydroxychloroquine (HCQ), chloroquine (CQ), and remdesivir have received US Food and Drug Administration (FDA) emergency use authorization (EUA) based on preliminary results from numerous ongoing clinical trials [4,5]. Several other medications are being tested in numerous clinical trials [6]. Remdesivir and dexamethasone show promise as COVID-19 treatment in severely ill hospitalized patients [7,8], while the search continues for a treatment that decreases symptoms or rate of severe complications in the community

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