Safety and Tolerability of Paxlovid (Nirmatrelvir/Ritonavir) in High-risk Patients

to the editor—We read with great interest the analysis by Saliba and colleagues on the real-world experience with nirmatrelvir/ritonavir (Paxlovid) in reducing severe coronavirus disease 2019 (COVID-19) and mortality in high-risk patients [1]. This is the largest retrospective cohort study to date that demonstrated Paxlovid treatment and vaccination status were associated with significant decrease in the rate of severe COVID-19 or mortality with adjusted hazard ratio (HR) 0.54 (95% confidence interval, 0.39–0.75) and 0.2 (95% confidence interval, 0.17–0.22), respectively. Timely real-world data are important to evaluate the effectiveness of Paxlovid in populations outside of the clinical trial, but the authors were unable to assess medication tolerability and safety. As of 14 May 2022, Assistant Secretary for Preparedness and Response estimated 668 954 Paxlovid courses were given in the United States [2]. In the randomized clinical trial, EPIC-HR (Evaluation of Protease Inhibition for Covid-19 in High-Risk Patient), Paxlovid appeared to be well tolerated but real-world data are lacking [3]. At the University of Washington Medicine, we developed a standardized process to prioritize high-risk patients meeting National Institutes of Health Tier 1 and 2 criteria and assessed patient tolerability and safety through telephonic postprescription outreach when supplies were initially limited. Patients who were prescribed Paxlovid were interviewed over the phone using a standardized questionnaire to assess adverse effects and adherence within 1 week of starting therapy.