COVID‐SAFER: Deprescribing Guidance for Hydroxychloroquine Drug Interactions in Older Adults

Abstract

BACKGROUND/OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes high morbidity and mortality in older adults with chronic illnesses. Several trials are currently underway evaluating the antimalarial drug hydroxychloroquine as a potential treatment for acute infection. However, polypharmacy predisposes patients to increased risk of drug-drug interactions with hydroxychloroquine and may render many in this population ineligible to participate in trials. We aimed to quantify the degree of polypharmacy and burden of potentially inappropriate medications (PIMs) that older hospitalized adults are taking that would interact with hydroxychloroquine. METHODS:We reanalyzed data from the cohort of patients 65 years and older enrolled in the MedSafer pilot study. We first identified patients taking medications with potentially harmful drug-drug interactions with hydroxychloroquine that might exclude them from participation in a typical 2019 coronavirus disease (COVID-19) therapeutic trial. Next, we identified medications that were flagged by MedSafer as potentially inappropriate and crafted guidance around medication management if contemplating the use of hydroxychloroquine. RESULTS: The cohort contained a total of 1,001 unique patients with complete data on their home medications at admission. Of these 1,001 patients, 590 (58.9%) were receiving one or more home medications that could potentially interact with hydroxychloroquine, and of these, 255 (43.2%) were flagged as potentially inappropriate by the MedSafer tool. Common classes of PIMs observed were antipsychotics, cardiac medications, and antidiabetic agents. CONCLUSION: The COVID-19 pandemic highlights the importance of medication optimization and deprescribing PIMs in older adults. By acting now to reduce polypharmacy and use of PIMs, we can better prepare this vulnerable population for inclusion in trials and, if substantiated, pharmacologic treatment or prevention of COVID-19.

Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19

“…It is possible that hydroxychloroquine is more effective in populations at higher risk for complications, such as older persons in long-term care facilities (23). Performing randomized trials in long-term care facilities could test whether hydroxychloroquine can reduce hospitalizations; however, the risk for medication adverse effects and drug-drug interactions will also be higher (24).…”

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

“…The COVID-Safer study exploited a similar strategy by using retrospective data from hospitalized older adults with polypharmacy included in the primary MedSafer study, and they theoretically exposed this patient population cohort to a treatment of HCQ (5 days at a minimum dose of 600 mg daily) [50]. They identified possible drug-drug interactions as well as potential harmful outcomes such as increased toxicity of HCQ, risk of QTc prolongation or malignant cardiac arrhythmia, or risk of other adverse drug events requiring closer monitoring during therapy.…”

Meta-analysis on outcome-worsening comorbidities of COVID-19 and related potential drug-drug interactions

“…It was shown that in northern Italy COVID-19 patients experienced significant elevated plasma concentrations of direct oral anti-coagulants while on medications used in the course of COVID-19 [ 10 ]. Unfortunately, with the exception of hydroxychloroquine and QTc-time prolongation due to co-administration of other drugs, the issue of potential harmful DDI in COVID-19 comorbid patients seems to be of minor attention with a limited number of published studies currently available [ [11] , [12] , [13] , [14] , [15] ]. Also, of a public health concern is the use of self-medication being potentially harmful or without evidence of clinical benefit taking place particularly in low- and middle-income countries with restricted access to quality healthcare and where drug dispensing is less controlled in the communities [ 16 , 17 ].…”