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

Abstract

ImportanceOlder adults, at high-risk of developing complications from COVID-19, could benefit from nirmatrelvir-ritonavir, an oral antiviral treatment for outpatients at high risk of complications from COVID-19; however, due to its potent CYP3A4 inhibition, nirmatrelvir-ritonavir is associated with many drug-drug interactions (DDI).ObjectivesIdentify how common DDIs are between nirmatrelvir-ritonavir, common medications, and PIMs in older adults with polypharmacy. Craft anticipatory deprescribing guidance for PIMs that interact with nirmatrelvir-ritonavir to help prioritize deprescribing resources, and increase the proportion of older adults potentially benefitting from treatment.DesignIn this secondary analysis, we retrospectively analyzed all patients in the MedSafer cluster randomized deprescribing trial (N=5698 participants) to investigate the proportion of older adults (age >65) with polypharmacy (≥5 usual home medications) who would be ineligible for treatment with nirmatrelvir-ritonavir due to pre-existing DDIs.SettingThe setting of the primary study was in medical inpatient units at 11 Canadian acute care hospitals.ParticipantsHospitalized persons, age 65 years and older, on 5 or more daily home medications, with an expected survival of 3 months or longer were included in this secondary analysis.Main outcomes and measuresWe identified the prevalence of (PIMs), as defined by the MedSafer software. We then developed deprescribing guidance, so clinicians could proactively deprescribe in an effort to increase the proportion of older adults eligible for safe treatment with nirmatrelvir-ritonavir in the event of a SARS-CoV-2 infection.ResultsOf 5698 participants, a total of 3869 (68%) were taking a medication with a known nirmatrelvir-ritonavir DDI, and of these 823 (21%) had at least one PIM. Of 823 PIMs, 627 (76%) were medications with a known high risk DDI and 213 (26%) were considered moderate risk DDIs with nirmatrelvir-ritonavir. Many of the PIMs required “advanced deprescribing” and could not simply be stopped, held, or adjusted at the time of nirmatrelvir-ritonavir receipt.Conclusions and relevanceOlder adults are at high risk of developing severe complications from COVID-19. Deprescribing PIMs in advance of a COVID-19 infection could increase the proportion of older adults who can safely receive nirmatrelvir-ritonavir, in addition to the usual benefits observed with medication management.Impact StatementWe certify that this work is novel. This timely clinical investigation explores the unforeseen consequences of polypharmacy and the use of potentially inappropriate medication in older adults during the COVID-19 pandemic. This manuscript addresses the many drug-drug interactions between nirmatrelvir-ritonavir, an antiviral treatment for COVID-19, and potentially inappropriate medications in older adults with polypharmacy from the MedSafer cluster randomized trial. Our work highlights that the pandemic has created an even greater urgency to examine the medication lists of older adults and proactively deprescribe to improve the safety and tolerability of different COVID-19 treatments.Key PointsQuestion: How does polypharmacy affect the eligibility of older adults to receive Nirmatrelvir-ritonavir?Findings: 68% of older adults in the MedSafer cluster randomized trial had a DDI with nirmatrelvir-ritonavir, and 21% were taking at least 1 potentially inappropriate medication.Meaning: Due to its potent CYP3A4 inhibition, nirmatrelvir-ritonavir is associated with many drug-drug interactions (DDI).

Evaluating Nirmatrelvir-Ritonavir (Paxlovid®) in Outpatient COVID-19 Treatment: Safety, Tolerability, and Adherence Insights from Primary Healthcare Clinics

“…Within this study's cohort of patients receiving prescriptions, a substantial proportion of 75.3% (n=143) exhibited drug-drug interactions with Paxlovid ® that necessitated intervention. This percentage is higher than the results of another study, which indicated that 68.0% (n=3,869) of patients were prescribed medications with potential interactions with Paxlovid ® [29]. In this study, within the medications falling under the high-risk interaction category, simvastatin, a lipid lowering agent, was the most prevalent.…”

“…In this study, a notable 75.3% (n=143) of the patient cohort faced drug-drug interactions with Paxlovid® that required proactive management. This incidence surpasses that reported in another research, where 68.0% (n=3,869) of patients were identi ed as taking medications potentially interacting with Paxlovid® [29]. Notably, within the category of high-risk interactions, simvastatin was most frequently implicated.…”

Paxlovid: Mechanism of Action, Synthesis, and In Silico Study

“…Older people are at higher risk for severe complications from COVID-19. Explanation of PIMs before COVID-19 infection can increase the relation of older people that can safely be given nirmatrelvir-ritonavir, in addition to the ordinary advantages seen with drug administration [50][51][52].…”

Electronic Decision Support for Deprescribing in Patients on Hemodialysis: Clinical Research Protocol for a Prospective, Controlled, Quality Improvement Study

“…Guidelines for deprescribing contain long lists of rules that preclude memorization; some may contain conflicting recommendations for patients taking 10 to 15 medications; and not all guidelines explain how to deprescribe (eg, when and how to taper and what rebound symptoms to watch out for). 2,[21][22][23] We therefore integrated the dialysis-specific deprescribing recommendations into the MedSafer ruleset, coupled them with links to patient deprescribing empowerment brochures, and added instructions for tapering where required.…”