What is the recommended dosing for Paxlovid (nirmatrelvir/ritonavir) in the treatment of COVID-19?

Recommended Dosing for Paxlovid (Nirmatrelvir/Ritonavir) in COVID-19 Treatment

The standard dose of Paxlovid is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) taken together twice daily for 5 days, with dose adjustments required for patients with renal impairment. 1, 2

Standard Dosing Regimen

• Normal renal function or mild impairment: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) twice daily for 5 days 1, 2
• Treatment should be initiated as soon as possible after diagnosis and within 5 days of symptom onset 1
• Administer orally with or without food at approximately the same time each day 2

Dose Adjustments for Special Populations

Renal Impairment

• Moderate renal impairment (eGFR ≥30 to <60 mL/min):

  • 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) twice daily for 5 days 1, 2, 3

• Severe renal impairment (eGFR <30 mL/min) including those requiring hemodialysis:

  • Day 1: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) once
  • Days 2-5: 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) once daily 2
  • For hemodialysis patients, the dose should be administered after hemodialysis 2

Hepatic Impairment

• Mild to moderate hepatic impairment: No dose adjustment needed 1, 2
• Severe hepatic impairment (Child-Pugh Class C): Not recommended 1, 2

Important Drug Interaction Considerations

• Ritonavir is a strong CYP3A inhibitor that can significantly affect the metabolism of many medications 1, 2
• Prior to prescribing:
  1. Review all medications to assess potential drug-drug interactions
  2. Determine if concomitant medications require dose adjustment, interruption, or additional monitoring 2
• The Liverpool COVID-19 drug interaction tool is recommended for checking drug interactions 1

Contraindications

• History of clinically significant hypersensitivity to nirmatrelvir or ritonavir 2
• Co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations may cause serious reactions 2
• Co-administration with potent CYP3A inducers that may reduce nirmatrelvir or ritonavir plasma concentrations 2

Clinical Efficacy and Safety

• Paxlovid demonstrated 89% reduction in risk of hospitalization or death when initiated within 3 days of symptom onset 1, 4
• Most common adverse events are dysgeusia (altered taste) and diarrhea 1, 2, 4
• Treatment-related adverse events are generally mild in severity 3

Pharmacokinetic Considerations

• Nirmatrelvir is primarily eliminated renally when co-administered with ritonavir 5, 3
• Systemic nirmatrelvir exposure increases with increasing renal impairment, necessitating dose adjustments 3
• Ritonavir acts as a pharmacokinetic enhancer by inhibiting nirmatrelvir's CYP3A4-mediated metabolism 5

The dosing recommendations are based on pharmacokinetic studies that ensure adequate nirmatrelvir concentrations are maintained above the antiviral effective concentration while minimizing potential toxicity in patients with renal impairment 6, 3.