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

Sydney B. Ross, MSc; Marnie Goodwin Wilson, MD, MSc; Louise Papillon-Ferland, BPharm, MSc; Sarah Elsayed, BSc; Peter E. Wu, MD, MSc; Kiran Battu, BPharm; Sandra Porter, BPharm; Babak Rashidi, MD, MS; Robyn Tamblyn, PhD; Louise Pilote, MD, PhD; James Downar, MD, MPH; Andre Bonnici, BPharm; Allen Huang, MD; Todd C. Lee, MD, MPH; Emily G. McDonald, MD, MSc


J Am Geriatr Soc. 2020;68(8):1636-1646. 

In This Article

Abstract and Introduction


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. J Am Geriatr Soc 68:1636–1646, 2020.


The first cluster of cases of 2019 coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported to the World Health Organization (WHO) on December 31, 2019.[1,2] On March 11, 2020, the WHO declared COVID-19 a pandemic,[3] and at the time of writing, greater than 4.3 million laboratory-confirmed cases have been documented globally, with more than 290,000 related deaths.[4] In response, more than 600 interventional trials have been registered to investigate whether existing medications are safe and effective for the treatment of COVID-19.[5]

One class of medications that has demonstrated therapeutic properties in vitro are the antimalarial agents chloroquine and hydroxychloroquine.[6] Following results from the early emerging literature, including several small clinical trials,[7–10] an uncontrolled case series,[11] and an open-label nonrandomized study from France,[12] the U.S. Food and Drug Administration (FDA) granted an Emergency Use Authorization for hydroxychloroquine for hospitalized patients with COVID-19 who are unable to participate in clinical trials.[13–15] These studies were heavily referenced in the media despite inconclusive data, and trials for use as prophylaxis and treatment are ongoing.[12,16] More recently, an observational study on hydroxychloroquine was published showing no improvement in clinical outcomes in patients hospitalized with COVID-19.[17] At the present time, the FDA and the Infectious Diseases Society of America recommend against its use outside of clinical trials.[18] The results of randomized controlled trials are forthcoming, and the medication may still be prescribed outside of a trial, for lack of any alternative treatment.

One population in critical need of effective treatments for COVID-19 are older adults with comorbidities such as diabetes, hypertension, and cardiac conditions. Studies suggest older adults are more susceptible to infection with COVID-19 and at a higher risk of severe complications when compared with the general population.[19,20] Outbreaks in long-term care facilities resulting in death have emphasized the vulnerability of this population.[21] With increasing age, higher rates of medical conditions are observed, leading to a higher prevalence of polypharmacy (taking multiple medications)[22,23] As many as 56.7% of community-dwelling North Americans older than 65 years of age are taking five or more regular medications.[24,25] Polypharmacy is harmful, given the association with falls, fractures, and other adverse drug events.[26] However, we are now encountering another problem from taking multiple medications: a substantial risk of drug-drug interactions with potential therapies for COVID-19.[27] Many of these interacting medications are potentially inappropriate medications (PIMs) that themselves carry an increased risk for adverse drug events and could be deprescribed (stopped, tapered, or switched to a safer alternative).[28–31]

We hypothesized that due to polypharmacy and clinically significant drug-drug interactions, many older adults with their current drug regimens will be ineligible for COVID-19 therapeutic trials and/or treatment with medications that are currently under investigation, including, but not limited to, the antimalarial hydroxychloroquine. This despite older adults being at an increased risk of complications as a result of COVID-19 and representing a population most likely to benefit from different therapeutic options. We postulated that many of these drug-drug interactions are due to PIMs that could be deprescribed proactively. In light of a recent FDA warning regarding risk of QTc prolongation, we examined hydroxychloroquine[14] (as a test case) to estimate the prevalence of prescribed medications with drug-drug interactions in a cohort of hospitalized older adults with polypharmacy. We aimed to better characterize the burden of PIMs that could be deprescribed with the impetus of the COVID-19 pandemic.