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High concentrations of nirmatrelvir/ritonavir in critically ill patients receiving continuous renal replacement
Rong Dong1, Yizhen Huang2, Xiao Ling3
1Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University, School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; Department of Clinical Pharmacy, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
Objectives:
Nirmatrelvir/ritonavir is a highly efficacious agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although dose adjustment is recommended in patients with renal impairment according to the package insert for Paxlovid (Pfizer), there is no dose recommendation for patients with severe renal impairment who require continuous renal replacement therapy (CRRT).
Methods:
To characterise the features of nirmatrelvir/ritonavir in critically ill Chinese patients undergoing CRRT, therapeutic drug monitoring of nirmatrelvir/ritonavir was performed by high-performance liquid chromatography tandem mass spectrometry assay in eight patients.
Results:
Nirmatrelvir trough concentrations ranged from 3325.34 ng/mL to 15 625.46 ng/mL. Concentrations were up to 7-fold higher compared with patients with normal renal function and 2-fold higher compared with patients with end-stage renal disease undergoing haemodialysis.
Conclusions:
These results suggest that a dose reduction should be implemented in the treatment of patients with CRRT.
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