Risk of Adverse Drug Events Following the Virtual Addition of COVID-19 Repurposed Drugs to Drug Regimens of Frail Older Adults with Polypharmacy
Risk of Adverse Drug Events Following the Virtual Addition of COVID-19 Repurposed Drugs to Drug Regimens of Frail Older Adults with Polypharmacy
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DOI：
10.3390/jcm9082591
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发表时间：
2020-08-01
影响因子：
3.9
通讯作者：
Michaud, Veronique
中科院分区：
文献类型：
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作者：
Al Rihani, Sweilem B.;Smith, Matt K.;Michaud, Veronique
在患有多种药物的老年人中，必须确定与使用2019年新型冠状病毒病（COVID-19）再用途药物相关的风险获益比。我们的目标是开发和验证一种策略，以评估与使用羟氯喹（HCQ）和氯喹（CQ）单独或与阿奇霉素（AZ）联合使用以及洛匹那韦/利托那韦（LPV/r）联合使用的COVID-19再用途药物相关的药物不良事件（ADE）风险。这些药物实际上是一次一种地添加到12 383名老年人全面护理方案参与者的药物治疗方案中。MedWise风险评分（MRSTM）是根据198，323例药物索赔确定的。结果表明，添加每种重新用途的药物导致MRS（TM）值的频率分布发生显著变化（p< 0.05）;增加是由于药物诱导的长QT综合征（LQTS）或CYP 450药物相互作用负担风险评分增加。使用HCQ + AZ和CQ + AZ观察到的LQTS风险增加与将特非那定或特非那定+ AZ（用作药物诱导LQTS的阳性对照）添加到药物方案中时估计的风险增加幅度相同。所执行的基于模拟的策略提供了一种评估药物ADE风险的方法，用于有潜在医学合并症和多种药物使用的人群，这些人群有COVID-19感染的风险，而不会暴露于这些药物。
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 MRS(TM)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.