What are the recommendations for using PAXLOVID (nirmatrelvir and ritonavir) in patients with impaired renal function?

PAXLOVID Dosing Recommendations in Renal Impairment

For patients with impaired renal function, PAXLOVID (nirmatrelvir and ritonavir) requires specific dose adjustments based on the severity of renal impairment, with different dosing regimens for moderate and severe renal dysfunction. 1

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: All 3 tablets taken together twice daily for 5 days
• No dosage adjustment required 1

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: Both tablets taken together twice daily for 5 days 1
• This dose reduction is supported by pharmacokinetic data showing that moderate renal impairment increases nirmatrelvir exposure by approximately 87% 2

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 1
• For hemodialysis patients: Administer dose after hemodialysis on dialysis days 1
• Pharmacokinetic studies show that severe renal impairment increases nirmatrelvir exposure by approximately 204% 2

Important Clinical Considerations

Drug Interactions

• PAXLOVID contains ritonavir, a strong CYP3A inhibitor that can significantly increase concentrations of drugs metabolized by CYP3A 1
• Prior to prescribing:
  • Review all medications to assess potential drug-drug interactions
  • Determine if concomitant medications require dose adjustment, interruption, or additional monitoring 1
• Particularly concerning interactions include:
  • Immunosuppressants (e.g., tacrolimus, cyclosporine) - may require significant dose reductions or temporary discontinuation 3
  • Certain cardiovascular medications (amiodarone, antiarrhythmics) 4
  • Some statins (lovastatin, simvastatin) 4

Monitoring Recommendations

• Regular monitoring of renal function during treatment, especially in patients with baseline renal impairment 4
• Monitor for hepatotoxicity as hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir 4
• In a study of PAXLOVID prescribing, 24.3% of patients had both renal impairment and drug-drug interactions, highlighting the need for careful assessment 5

Administration Guidelines

• PAXLOVID should be administered at approximately the same time each day for 5 days 1
• Tablets should be swallowed whole and not chewed, broken, or crushed 1
• Can be taken with or without food 1

Special Populations

Patients on Dialysis

• PAXLOVID can be used in patients on hemodialysis with appropriate dose adjustments 1
• Administer dose after hemodialysis on dialysis days 1

HIV Co-infection

• PAXLOVID use may lead to a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection 1
• In patients already on antiretroviral therapy, careful consideration of drug interactions is essential 6

Common Pitfalls to Avoid

1. Failure to properly adjust dosage based on renal function, which can lead to toxicity
2. Missing critical drug-drug interactions, particularly with immunosuppressants, which may require significant dose adjustments
3. Not administering doses after hemodialysis on dialysis days
4. Overlooking the need for different dosing on Day 1 vs. Days 2-5 in severe renal impairment

By following these specific dosing recommendations and monitoring guidelines, PAXLOVID can be safely administered to patients with renal impairment while maintaining efficacy and minimizing adverse effects.