Potential Drug-Drug Interactions With Nirmatrelvir/Ritonavir Among Long-Term Care Facility Residents

Objectives Nirmatrelvir/ritonavir (Paxlovid) is an oral antiviral for COVID-19. Although effective, its use is complicated by clinically important potential drug-drug interactions (DDIs). Long-term care facility (LTCF) residents are especially vulnerable to both COVID-19 and the adverse effects of potential DDIs because of advanced age, multimorbidity, and polypharmacy. The objective of this study was to quantify the prevalence and duration of potential DDIs among US LTCF residents administered nirmatrelvir/ritonavir. Design We conducted a cohort study of LTCF residents using electronic medication administration record data from the Long-Term Care Data Cooperative linked to Medicare claims (January 2022-January 2025). Methods Days of nirmatrelvir/ritonavir administration were identified, and concurrent exposure to 236 potentially interacting medications was assessed. A potential DDI was defined as same-day coadministration, reflecting concurrent exposure rather than clinical adverse effects. We estimated the prevalence of potential DDIs and the median duration of overlapping exposure. Results Among 48,260 LTCF residents treated with nirmatrelvir/ritonavir, the mean age was 78.8 years (SD, 10.9), 58% were female, and 76% were non-Hispanic White. Overall, 86% were exposed to at least 1 potential DDI. The most common potentially interacting medications were atorvastatin (28.1%; 95% confidence limits CLs, 27.7-28.50), amlodipine (21.6%; 95% CLs, 21.2-21.9), and apixaban (15.9%; 95% CLs, 15.6-16.3). Median days of overlapping exposure ranged from 5 to 6 days. Discussion Potential DDIs most frequently involve medications requiring temporary withholding or dose adjustment rather than contraindication. The high prevalence of potential DDIs likely reflects the complexity of medication management in LTCFs, where antiviral use must be weighed against comorbidities and polypharmacy. Conclusions and Implications Potential DDIs with nirmatrelvir/ritonavir were common among LTCF residents, though contraindicated ones were uncommon. These findings underscore the need for ongoing medication reviews and clinician and pharmacist oversight to ensure safe antiviral use in LTCFs.