At what level of impaired renal function (creatinine clearance) should the dose of PAXLOVID (nirmatrelvir/ritonavir) be adjusted?

PAXLOVID Dose Adjustment Based on Creatinine Clearance

PAXLOVID dose should be reduced when creatinine clearance is below 60 mL/min, with specific adjustments required for moderate renal impairment (eGFR ≥30 to <60 mL/min) and severe renal impairment (eGFR <30 mL/min). 1

Specific Dosing Recommendations 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 dose adjustment needed

Moderate Renal Impairment (eGFR ≥30 to <60 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
• This represents a 50% reduction in nirmatrelvir dose

Severe Renal Impairment (eGFR <30 mL/min) including 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
• For hemodialysis patients, administer dose after hemodialysis

Pharmacokinetic Rationale for Dose Adjustment

The dose adjustment recommendations are based on pharmacokinetic studies showing increased nirmatrelvir exposure with declining renal function 2:

• Mild renal impairment: 24% increase in nirmatrelvir exposure
• Moderate renal impairment: 87% increase in nirmatrelvir exposure
• Severe renal impairment: 204% increase in nirmatrelvir exposure

This occurs because nirmatrelvir is primarily eliminated by the kidneys when given with ritonavir, with renal clearance decreasing by:

• 47% in moderate renal impairment
• 80% in severe renal impairment

Clinical Implications and Monitoring

Failure to adjust PAXLOVID dosing in renal impairment can lead to:

• Excessive drug accumulation
• Increased risk of adverse effects
• Potential toxicity

A retrospective analysis found that in 2.1% of cases, PAXLOVID was prescribed despite being contraindicated due to severe renal impairment, highlighting the importance of proper screening 3.

Practical Application

1. Always check renal function before prescribing PAXLOVID

   • Calculate eGFR or creatinine clearance
   • Select appropriate dosing based on renal function category

2. Timing considerations for hemodialysis patients

   • Administer PAXLOVID after hemodialysis sessions to prevent removal of the medication

3. Monitor for adverse effects

   • Particularly in patients with fluctuating renal function
   • Be alert for drug-drug interactions, which were noted in 57.1% of PAXLOVID prescriptions in one study 3

By following these specific dosing recommendations based on creatinine clearance, clinicians can optimize the efficacy of PAXLOVID while minimizing the risk of adverse effects in patients with renal impairment.