Paxlovid (Nirmatrelvir/Ritonavir) Dosing in Patients with Reduced eGFR
For patients with reduced eGFR, Paxlovid dosing must be adjusted based on the severity of renal impairment, with specific dose reductions required for moderate and severe renal dysfunction.
Dosing Recommendations Based on Renal Function
Normal to Mild Renal Impairment (eGFR ≥60 mL/min/1.73 m²)
- Standard dose: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) taken together twice daily for 5 days 1
- No dosage adjustment needed
Moderate Renal Impairment (eGFR ≥30 to <60 mL/min/1.73 m²)
- Reduced dose: 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) twice daily for 5 days 1
- This dose reduction is necessary as nirmatrelvir exposure increases by approximately 87% in patients with moderate renal impairment 2
Severe Renal Impairment (eGFR <30 mL/min/1.73 m²) 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 sessions 1
Pharmacokinetic Considerations
The dose adjustments are based on pharmacokinetic data showing:
- Nirmatrelvir is primarily eliminated by the kidneys when co-administered with ritonavir 2
- Systemic exposure increases with worsening renal function:
- Mild impairment: 24% increase
- Moderate impairment: 87% increase
- Severe impairment: 204% increase 2
Clinical Considerations
- Prescriptions should specify the numeric dose of each active ingredient within Paxlovid 1
- Administer at approximately the same time each day
- Can be taken with or without food
- Tablets should be swallowed whole, not chewed, broken, or crushed 1
- Treatment should be initiated as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset 1
Monitoring Recommendations
- Assess for drug-drug interactions before initiating therapy, as ritonavir is a potent CYP3A4 inhibitor 3
- Particular attention should be paid to patients on anticoagulants:
- Monitor renal function during treatment, especially in patients with fluctuating renal function
Recent Evidence for Severe CKD
Recent research suggests that modified dosing of nirmatrelvir-ritonavir in patients with eGFR <30 mL/min/1.73 m² (including those on dialysis) shows a favorable safety profile with effective viral suppression 5. However, the FDA-approved dosing recommendations should still be followed until these findings are incorporated into official guidelines.
Key Takeaways
- Renal function assessment is essential before prescribing Paxlovid
- Specific dose adjustments are required for moderate and severe renal impairment
- Drug-drug interactions must be carefully evaluated, particularly with medications commonly used in patients with kidney disease
- Completion of the full 5-day treatment course is important for optimal efficacy
Remember that the dose adjustments are designed to maintain therapeutic nirmatrelvir concentrations while minimizing the risk of adverse effects in patients with reduced renal clearance.