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=Volume 14 - 2023

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=Background: 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. 
Objectives: 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. 
Method: This was a prospective, two step, nonrandomized, open-label study. Participants were treated with nirmatrelvir 150mg or 300mg once a day (another 75mg or 150mg supplied after hemodialysis) and ritonavir 100mg 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. 
Results: Adverse events were happened in 3 and 7 participants in the step 1 and step 2 group, respectively(P=0.025). Among them, 2 and 6 participants were identified as drug-related adverse events(P=0.054). No SAE or liver function damage happened. The Cmin of nirmatrelvir in step 1 and step 2 group were 5294.65±2370.59 ng/mL and 7675.67±2745.22 ng/mL (P=0.125). Compared to hemodialysis patients without nirmatrelvir/ritonavir, there were no statistical differences in overall viral elimination time (P=0.232).
Conclusions: 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.