What are the guidelines for prescribing Paxlovid (nirmatrelvir/ritonavir) to patients with impaired renal function (kidney disease)?

Paxlovid (Nirmatrelvir/Ritonavir) Dosing Guidelines for Patients with Kidney Disease

For patients with kidney disease, Paxlovid dosage must be reduced based on renal function, with 300/100 mg twice daily for normal/mild impairment, 150/100 mg twice daily for moderate impairment, and 150/100 mg once daily for severe impairment, administered after hemodialysis in dialysis patients. 1

Dosing Algorithm Based on Renal Function

Normal to Mild Renal Impairment (eGFR ≥60 mL/min)

• Standard dose: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet)
• Frequency: Twice daily for 5 days
• No dosage adjustment needed 1

Moderate Renal Impairment (eGFR 30-59 mL/min)

• Reduced dose: 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet)
• Frequency: Twice daily for 5 days
• Special packaging available specifically for these patients 1

Severe Renal Impairment (eGFR <30 mL/min) including Hemodialysis

• Reduced dose: 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet)
• Frequency: Twice daily for 5 days
• Special packaging available with different dosing for Day 1 vs Days 2-5 1
• For hemodialysis patients: Administer dose after hemodialysis sessions 1

Pharmacokinetic Rationale

The dose adjustment recommendations are based on pharmacokinetic studies showing:

• Nirmatrelvir is primarily eliminated by the kidneys when given with ritonavir 2
• Systemic exposure increases with declining renal function:
  • Mild impairment: 24% increase in exposure
  • Moderate impairment: 87% increase in exposure
  • Severe impairment: 204% increase in exposure 2

Clinical Efficacy in Kidney Disease

Recent evidence suggests that Paxlovid remains effective in patients with chronic kidney disease:

• Early initiation of Paxlovid (within 5 days of diagnosis) in CKD patients was associated with lower all-cause mortality compared to late initiation or no treatment 3
• Particularly beneficial for CKD patients with high comorbidity burden (Charlson Comorbidity Index >7) 3
• Even in patients on hemodialysis, no significant worsening of renal function was observed with appropriate dosing 4

Important Drug Interactions

Ritonavir is a potent CYP3A4 inhibitor and can significantly affect metabolism of many medications. Particular caution is needed with:

• Colchicine: Concomitant use with ritonavir/nirmatrelvir (Paxlovid) is contraindicated due to risk of increased colchicine exposure 5
• Other medications metabolized by CYP3A4 system require careful evaluation
• Consider using the Liverpool COVID-19 drug interaction tool to check for potential interactions 5

Clinical Pearls and Pitfalls

1. Complete the full course: The full 5-day treatment course should be completed to maximize viral clearance 1

2. Timing is critical: Initiate as soon as possible after diagnosis and within 5 days of symptom onset 1

3. Missed doses: If a dose is missed by less than 8 hours, take it as soon as possible; if missed by more than 8 hours, skip that dose and take the next dose at the regular time 1

4. Administration: Can be taken with or without food; tablets should be swallowed whole 1

5. Common adverse effects: Diarrhea and dysgeusia (altered taste) are more common with nirmatrelvir/ritonavir than placebo 5

6. Monitoring: Regular monitoring of renal function is advisable, especially in patients with fluctuating kidney function 5

By following these guidelines, clinicians can safely prescribe Paxlovid to patients with kidney disease while minimizing risks and maintaining efficacy in reducing COVID-19 complications.