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


The MedSafer pilot study[32] was a large controlled before and after deprescribing trial that took place between September 2016 and May 2017 on four Canadian academic internal medicine clinical teaching units. The trial was designed to assess whether a computer-assisted medication review tool augmented the deprescribing of PIMs at discharge in a population of hospitalized older adults with polypharmacy. The software's algorithm identified PIMs and provided deprescribing recommendations for each individual patient by applying rules derived from widely available consensus documents for safer prescribing in older adults.[30,31,33]

Details of the trial are described elsewhere.[32] Briefly, patients were identified on admission via the emergency department to one of the designated units after discussion with the treating team to see if they met the broad inclusion criteria of 65 years and older and taking five or more medications. Patient data concerning medical conditions, validated medications, and some lab results were collected and entered into the MedSafer deprescribing electronic decision support software that identified PIMs through drug-disease combinations, drug-drug interactions, or those that should be avoided or used with caution in older adults. The MedSafer system generated a report of the PIM that included a level of harm (high risk, intermediate risk, or low risk but little added value), the rationale for deprescribing, and, when appropriate, a tapering protocol.

For the present study, we reanalyzed the MedSafer data as a representative sample of vulnerable older adults with polypharmacy. We first searched the literature for medications with known drug-drug interactions with hydroxychloroquine by examining the product monograph,[34] referring to drug-drug interaction websites,[35,36] and reviewing the exclusion criteria for a currently enrolling FDA and Health Canada approved hydroxychloroquine trial for COVID-19 (NCT04308668).[5,37,38] Medications with known interactions with hydroxychloroquine were grouped according to the American Hospital Formulary Service classification[39] (Table 1) and divided into two categories: chronic medications and medications typically prescribed for a short course such as antibiotics. We analyzed all patients in the MedSafer study who consented to participate in the deprescribing trial and who had a complete medication reconciliation performed on admission.

We theoretically "exposed" this patient cohort to treatment with hydroxychloroquine (minimum 5 days at a minimum dose of 600 mg daily as in NCT04308668) and identified possible drug interactions, as well as potential harmful outcomes such as increased toxicity of hydroxychloroquine, risk of QTc prolongation or malignant cardiac arrhythmia, or risk of other adverse drug events requiring closer monitoring during therapy such as severe hypoglycemia (Table 2). From all interacting medications we ran the MedSafer algorithms to determine the proportion of medications that were PIMs and that could be deprescribed. We also identified the triggering condition associated with each PIM (eg, atrial fibrillation, heart failure, dementia, delirium, or renal failure).

Finally, we developed recommendations for how to manage potential drug interaction including the option of not receiving hydroxychloroquine. Recommendations were based on the literature and expert consensus generated by the authors (experts in infectious diseases [T.C.L.], general internal medicine [T.C.L., E.G.M., J.D., B.R., and P.E.W.], clinical pharmacy [R.W., K.B., S.P., and L.P.F.], geriatrics [A.H. and L.P.F.], and clinical pharmacology/toxicology [P.E.W.]). Ideally PIMs would be deprescribed proactively, before infection with COVID-19, but logistically this may not always be feasible, and thus we have made recommendations for these patients. Examples of recommendations included medications that can be safely and abruptly held during treatment, those that require monitoring if there is to be ongoing use, and medications that likely cannot be stopped due to risk of an adverse drug withdrawal event.