Pharmacokinetics of nirmatrelvir and ritonavir in COVID-19 patients with end stage renal disease on intermittent haemodialysis (preprint)

ABSTRACT

Background: Nirmatrelvir/ritonavir is an effective therapy against SARS-CoV-2. Patients with end-stage renal disease (ESRD) are at high risk for severe COVID-19 and show impaired vaccine responses underlining the importance of antiviral therapy. However, use of nirmatrelvir/ritonavir is not recommended in these patients due to lack of clinical and pharmacokinetic data. Objective: To investigate pharmacokinetics and hepatic tolerance of nirmatrelvir/ritonavir in patients with ESRD and haemodialysis (HD). Patients and methods: Four patients diagnosed with SARS-CoV-2 infection received nirmatrelvir/ritonavir 150/100mg twice daily as recommended for renal impairment; HD ran in two- to three-day intervals. Plasma and serum samples were drawn before and after each HD during the 5-day treatment and for ensuing 3-5 days. Results: Median peak levels of nirmatrelvir obtained two hours after medication pre-HD in three patients were 7745ng/mL on day 3 and 6653ng/mL on day 5; median post-HD levels (C6h) declined to 5765ng/mL (74%) and 5521ng/mL (83%), on days 3 and 5 of treatment, respectively. Three days after end of treatment, median levels were 365ng/mL pre-HD and 30ng/mL post-HD. Measurements of the fourth patient, six hours after drug intake pre-HD showed nirmatrelvir-levels of 3704ng/mL on treatment day 3 which fell to 2308ng/mL post-HD, at one hour before intake of the next dose (Cmin). Conclusion: Use of nirmatrelvir/ritonavir in patients with ESRD results in high nirmatrelvir blood concentrations, which are still within the range known from patients without renal failure. No accumulation of nirmatrelvir took place and levels declined to zero within few days after end of treatment.