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[32] cohort contained 1,001 patients with complete data on their home medications. The median age of the cohort was 80 years; approximately 50% were women. More than one-half had hypertension, approximately 40% had diabetes, and close to 50% were moderately to severely frail as defined by the Clinical Frailty Scale.[40] All patients were hospitalized in a tertiary care hospital and admitted to one of four general medical wards in one of three Canadian academic centers in Montreal, Ottawa, and Toronto.

We analyzed 1,001 participants and found that 590 (58.9%) were prescribed one or more usual home medications that could potentially interact with hydroxychloroquine. The most commonly prescribed drug classes with known interactions were antidiabetic medications (330/1001 [33%]), the selective serotonin/norepinephrine reuptake inhibitors (SSRIs/SNRIs) (173/1001 [17.3%]), antipsychotics (typical and atypical) (136/1001 [13.6%]), and antiarrhythmics such as digoxin and amiodarone (64/1001 [6.4%]) (Table 3). The most common classes of antidiabetics were insulin, 138 of 1,001 (13.8%), and sulfonylureas, 90 of 1,001 (9.0%) (Table 3). The most serious interaction identified was a risk of QTc prolongation, torsade de pointes, and sudden death. A common but less severe interaction was a risk of hypoglycemia requiring increased monitoring. Lowering of the seizure threshold and pharmacokinetic interactions leading to increased hydroxychloroquine levels was uncommon.

We then determined how many PIMs (as identified by the MedSafer tool) with known interactions with hydroxychloroquine presented an opportunity to be deprescribed proactively. Of the 590 of 1,001 (58.9%) of participants who were prescribed a medication that could interact with hydroxychloroquine, 255 patients had the respective medication identified as a PIM, representing 43.2% of all patients with an interacting medication. Some common deprescribing opportunities that were identified included (1) too high a dose of digoxin for a patient's renal function, (2) antipsychotic use in patients with a known history of delirium or neurocognitive disorder (risk of stroke, falls, confusion), and (3) insulin and sulfonylureas in patients with a history of hypoglycemia and/or tight glycemic control (hemoglobin [Hb]A1c <7.5%) (Table 4).

We prepared recommendations for the management of interacting medications in patients with COVID-19 who may want to receive treatment with hydroxychloroquine if found to be effective. Examples include holding low doses of antipsychotics or antidepressants during therapy, QTc monitoring and electrolyte optimization with continued use of QTc prolonging agents, and glucose monitoring with concurrent diabetes medications. We also highlight medications such as amiodarone that cannot be stopped on short notice for inclusion in clinical trials, due to its prolonged half-life (Table 2).