AUTHOR=Lu Jiayue , Cai Hong , Hao Yujun , Lin Zhang , Liu Shang , Zhan Yaping , Ding Li , Huang Meilan , Li Zhenyuan , Xu Lan , Yan Xiujuan , Yang Li , Zhang He , Zhang Wei , Zhao Li , Zhao Junli , Wang Ting , Gu Leyi 

TITLE=Nirmatrelvir/Ritonavir for hemodialysis patients with COVID-19

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1161897

DOI=10.3389/fphar.2023.1161897

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Hemodialysis patients have a high risk of severe/critical COVID-19 and related high mortality, but nirmatrelvir/ritonavir is not recommended for hemodialysis patients with COVID-19 infection because of lack of evidence of safety.</p><p><bold>Objectives:</bold> Our study aims to evaluate the minimum plasma concentration (Cmin) of nirmatrelvir and its safety of different doses of nirmatrelvir/ritonavir in hemodialysis patients with mild COVID-19.</p><p><bold>Method:</bold> This was a prospective, two step, nonrandomized, open-label study. Participants were treated with nirmatrelvir 150 mg or 300 mg once a day (another 75 mg or 150 mg supplied after hemodialysis) and ritonavir 100 mg twice daily for 5 days, respectively. The primary outcome was the safety of nirmatrelvir/ritonavir, including the Cmin of nirmatrelvir and the number of adverse events (AE). The secondary outcome was the time of viral elimination in hemodialysis patients.</p><p><bold>Results:</bold> Adverse events were happened in 3 and 7 participants in the step 1 and step 2 group, respectively (<italic>p</italic> = 0.025). Among them, 2 and 6 participants were identified as drug-related adverse events (<italic>p</italic> = 0.054). No SAE or liver function damage happened. The Cmin of nirmatrelvir in step 1 and step 2 group were 5,294.65 ± 2,370.59 ng/mL and 7,675.67 ± 2,745.22 ng/mL (<italic>p</italic> = 0.125). The Cmin of the control group was 2,274.10 ± 1,347.25 ng/mL (<italic>p</italic> = 0.001 compared to step 2 and <italic>p</italic> = 0.059 compared to step 1). Compared to hemodialysis patients without nirmatrelvir/ritonavir, there were no statistical differences in overall viral elimination time (<italic>p</italic> = 0.232).</p><p><bold>Conclusion:</bold> In our study, two doses of nirmatrelvir/ritonavir appeared to be excessive for hemodialysis patients. Although all of the patients tolerated 5-day administration, nearly half of the patients experienced drug-related adverse events. In addition, the medication group did not show a significant advantage in the time of viral elimination.</p>