What is the recommended dose of Paxlovid (nirmatrelvir/ritonavir) for patients with normal or impaired renal function?

Recommended Dosage of Paxlovid for Patients with Normal or Impaired Renal Function

For patients with normal renal function or mild renal impairment (eGFR ≥60 mL/min), the recommended dose of Paxlovid is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) taken together orally twice daily for 5 days. 1

Dosage Adjustments Based on Renal Function

Normal Renal Function or Mild Impairment

• eGFR ≥60 mL/min: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) twice daily for 5 days 1

Moderate Renal Impairment

• eGFR 30-59 mL/min: 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) twice daily for 5 days 1, 2

Severe Renal Impairment

• eGFR <30 mL/min (including patients on 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 1
  • For patients on hemodialysis, the dose should be administered after hemodialysis 1

Important Administration Guidelines

1. Timing: Treatment should be initiated as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset 2, 1

2. Administration: Paxlovid can be taken with or without food 1

3. Tablet integrity: Tablets should be swallowed whole and not chewed, broken, or crushed 1

4. Missed doses:

   • If within 8 hours of scheduled time: Take as soon as possible
   • If more than 8 hours: Skip the missed dose and take the next dose at regular time
   • Never double the dose to make up for a missed dose 1

Special Considerations

Hepatic Impairment

• No dose adjustment needed for mild to moderate hepatic impairment (Child-Pugh A or B)
• Not recommended for patients with severe hepatic impairment (Child-Pugh C) 1, 2

Drug Interactions

• Ritonavir is a strong CYP3A inhibitor and can significantly affect the metabolism of many medications 2, 1
• Prior to prescribing Paxlovid:
  1. Review all medications to assess potential drug-drug interactions
  2. Determine if concomitant medications require dose adjustment, interruption, or additional monitoring
• The Liverpool COVID-19 drug interaction tool is recommended as a resource for checking drug interactions 2, 3

Contraindications

• History of clinically significant hypersensitivity to nirmatrelvir or ritonavir
• Co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations may cause serious reactions
• Co-administration with potent CYP3A inducers 1

Clinical Efficacy and Safety

• Paxlovid has demonstrated significant efficacy in reducing the risk of hospitalization and death in high-risk patients with COVID-19 2, 3
• Common adverse effects include dysgeusia (altered taste) and diarrhea 2, 3, 1

Important Caveats

• Pharmacokinetic studies show that nirmatrelvir exposure increases with declining renal function, with severe renal impairment resulting in up to 3-fold higher exposure 4
• Elderly patients (>65 years) may have higher plasma concentrations, particularly when taking renally excreted medications 5
• Completion of the full 5-day treatment course is important to maximize viral clearance and minimize transmission 1

By following these dosing recommendations based on renal function, healthcare providers can optimize the efficacy of Paxlovid while minimizing potential adverse effects in patients with COVID-19.