Older adults with polypharmacy at risk of drug-drug interactions with nirmatrelvir-ritonavir

Drug-drug interactions with nirmatrelvir-ritonavir, used to treat COVID-19, are common in older adults with polypharmacy, but planned deprescribing of other problematic medications could increase the number of patients who benefit from the drug. This is a strategy proposed by researchers who conducted a study investigating patients who receive at least one prescribed medication that would interact with nirmatrelvir-ritonavir. Findings were published in JAMA Network Open. Using data from the Canadian Medsafer trial, researchers enrolled hospitalized adults aged 65 years and up who were taking five or more medications. The researchers then theoretically exposed the trial cohort to treatment with nirmatrelvir-ritonavir. They then identified which medications the patients were using that would have important drug-drug interactions (DDIs), especially via CYP3A4 inhibition. The researchers also identified potentially inappropriate medications (PIMs) which the study stated were candidate drugs for deprescribing. The DDIs were identified from three main sources: product monographs, a drug interaction checker website, and exclusion criteria from the EPIC-HR trial. The interactions were linked with potential harms, which were classified as other, moderate, or severe. The study included 5,698 patients who had a mean age of 78 years and about half were women. The median number of daily medications in the cohort was 10 (ranging from 8 to 14) and use of PIMs was a median of two. Of the entire cohort, 3,869 (67.9%) were taking at least one interacting medication prescription. The most common DDIs were with antithrombotic medications 2,131 (37.4%) or statins 1,901 (33.4%). Of the patients who had interacting medication prescriptions, 823 (21.3%) had at least one PIM, of whom 627 (76.2%) had a high-risk DDI with nirmatrelvir-ritonavir. Because of potential DDIs, many older adults with polypharmacy would not be able to safely receive nirmatrelvir-ritonavir. Also, many DDIs could not be mitigated by simply holding or dose-reducing a medication. After analyzing the data, “We crafted mitigation strategies to diminish DDIs. Strategies included (1) anticipatory deprescribing for drugs that cannot simply be held or dose-reduced at the time of nirmatrelvir-ritonavir exposure, and/or (2) deprescribing at the approximate time of nirmatrelvir-ritonavir receipt,” the study said. “Common deprescribing opportunities included dual anticoagulant therapy without a recent coronary event or intervention, 200 of 489 (41.0%), alfuzosin or tamsulosin for benign prostatic hypertrophy in a person with orthostatic hypotension or recurrent falls, 174 of 779 (22.3%), and antipsychotics for sleep or agitation 62 of 274 (22.6%)."

Older adults with polypharmacy at risk of drug-drug interactions with nirmatrelvir-ritonavir

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