Nirmatrelvir: peptidomimetic inhibitor of the SARS-CoV-2 main protease (Mpro; also known as 3C-like protease or nsp5 protease); inhibition of Mpro prevents processing of polyprotein precursors, resulting in inhibition of viral replication. Ritonavir: pharmacokinetic enhancer with no activity against SARS-CoV-2 Mpro; Ritonavir inhibits CYP3A-mediated metabolism of nirmatrelvir, resulting in increased nirmatrelvir plasma concentrations
藥動學
Distribution: 1.Vz/F: (Nirmatrelvir, when given with ritonavir) 104.7 L; (Ritonavir) 112.4 L 2. Protein binding: (Nirmatrelvir, when given with ritonavir): 69%; (Ritonavir) 98-99% Metabolism: 1. Nirmatrelvir, when given with ritonavir: Minimal 2. Ritonavir: Hepatic via CYP3A4 (major) and CYP2D6 (minor) Excretion: 1. Nirmatrelvir, when given with ritonavir: Urine (35.3%); feces (49.6%) 2. Ritonavir: Urine (11.3%); feces (86.4%) Half-life elimination: 1. Nirmatrelvir, when given with ritonavir: 6.05 ± 1.79 hours 2. Ritonavir: 6.15 hours Time to peak: 1. Nirmatrelvir, when given with ritonavir: 3 hours (range: 1.02 to 6 hours) 2. Ritonavir: 3.98 hours
禁忌症
1. Not authorized for initiation of treatment in patients requiring hospitalization due to severe or critical COVID-19 2. Not authorized for pre-exposure or post-exposure prophylaxis for prevention of COVID-19 3. Not authorized for use longer than 5 consecutive days
懷孕分類
There are no available human data on the use of nirmatrelvir during pregnancy
哺乳分類
There are no available data on the presence of nirmatrelvir in human or animal milk, the effects onthe breastfed infant, or the effects on milk production.
副作用
Dysgeusia, diarrhea, hypertension, myalgia
劑量和給藥方法
1. Dosage: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), all three tablets taken together twice daily for 5 days, with or without food 2. Administration: Initiate PAXLOVID treatment as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset
小兒調整劑量
Use in children ≥12 years of age and weighing at least 40 kg
腎功能調整劑量
1. Moderate renal impairment (eGFR 30-60 mL/min): 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet), with both tablets taken together twice daily for 5 days 2. Severe renal impairment (eGFR <30 mL/min): Use is not recommended
肝功能調整劑量
1. Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary 2. Severe impairment (Child-Pugh class C): Use is not recommended (has not been studied)