Nirmatrelvir/Ritonavir for hemodialysis patients with COVID-19

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

doi:10.3389/fphar.2023.1161897

Nirmatrelvir/Ritonavir for hemodialysis patients with COVID-19

Front Pharmacol. 2023 May 12:14:1161897. doi: 10.3389/fphar.2023.1161897. eCollection 2023.

Authors

Jiayue Lu¹, Hong Cai¹, Yujun Hao², Zhang Lin², Shang Liu¹, Yaping Zhan¹, Li Ding¹, Meilan Huang³, Zhenyuan Li¹, Lan Xu⁴, Xiujuan Yan³, Li Yang³, He Zhang¹, Wei Zhang³, Li Zhao³, Junli Zhao⁵, Ting Wang⁴, Leyi Gu¹

Affiliations

¹ Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Renji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
² State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Department of Gastroenterology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
⁴ Department of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
⁵ Department of Nephrology, Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, China.

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 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. 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 5,294.65 ± 2,370.59 ng/mL and 7,675.67 ± 2,745.22 ng/mL (p = 0.125). The Cmin of the control group was 2,274.10 ± 1,347.25 ng/mL (p = 0.001 compared to step 2 and p = 0.059 compared to step 1). Compared to hemodialysis patients without nirmatrelvir/ritonavir, there were no statistical differences in overall viral elimination time (p = 0.232). Conclusion: 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.

Keywords: COVID-19; hemodialysis; nirmatrelvir; pharmacokinetics; ritonavir.

Grants and funding

This work was supported by National Nature Science Foundation Grant of China (81970610) and Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant (20172015) to LG.