What is the recommended dosing of Paxlovid (nirmatrelvir/ritonavir) for a patient with Chronic Kidney Disease (CKD) and impaired renal function, specifically a Glomerular Filtration Rate (GFR) of 40?

Paxlovid Dosing in CKD with GFR 40

For patients with CKD and GFR 40 mL/min/1.73m², the recommended dosage of Paxlovid is 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days. 1

Rationale for Dose Adjustment

The FDA-approved labeling for Paxlovid provides clear guidance for patients with moderate renal impairment (eGFR ≥30 to <60 mL/min), which includes patients with GFR 40:

• Nirmatrelvir is primarily eliminated by the kidneys when co-administered with ritonavir
• Patients with moderate renal impairment have approximately 87% higher systemic exposure to nirmatrelvir compared to those with normal renal function 2
• Dose reduction prevents potential toxicity while maintaining therapeutic efficacy

Specific Dosing Instructions

1. Use the specific Paxlovid dose pack for moderate renal impairment (150 mg nirmatrelvir/100 mg ritonavir)
2. Administer at approximately the same time each day for 5 days
3. Can be taken with or without food
4. Tablets should be swallowed whole and not chewed, broken, or crushed

Monitoring Recommendations

• Start treatment as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset
• Complete the full 5-day treatment course even if symptoms improve
• If a dose is missed within 8 hours of the scheduled time, take it as soon as possible
• If a dose is missed by more than 8 hours, skip the missed dose and take the next dose at the regular time
• Do not double the dose to make up for a missed dose

Safety Considerations

• Pharmacokinetic studies show that the reduced dose (150 mg nirmatrelvir/100 mg ritonavir) in moderate renal impairment provides appropriate drug exposure 2
• The most recent evidence indicates that Paxlovid has an acceptable safety profile in patients with CKD when appropriately dosed 3
• No significant worsening of renal function has been observed in CKD patients receiving appropriately dosed Paxlovid 4

Important Drug Interactions

Since ritonavir is a potent CYP3A4 inhibitor, be aware of potential drug interactions with:

• Certain antiarrhythmics
• Anticoagulants
• Statins
• Immunosuppressants
• Other medications metabolized by CYP3A4

Clinical Pearls

• For patients with GFR <30 mL/min, a different dosing regimen would be required (300 mg nirmatrelvir/100 mg ritonavir on day 1, followed by 150 mg nirmatrelvir/100 mg ritonavir once daily for days 2-5) 1
• For patients on hemodialysis with GFR <30 mL/min, administer the dose after hemodialysis 1
• No dosage adjustment is needed for mild hepatic impairment, but Paxlovid is not recommended for severe hepatic impairment 1

Following these dosing recommendations will help ensure optimal efficacy while minimizing the risk of adverse effects in patients with CKD and GFR 40 mL/min/1.73m².