Paxlovid (Nirmatrelvir/Ritonavir) Dosing Regimen
The standard dose of Paxlovid is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), taken together twice daily for 5 days, with dose adjustments required for patients with renal impairment. 1, 2
Standard Dosing
- Normal renal function: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), twice daily for 5 days
- Administer orally with or without food
- Take at approximately the same time each day
- Must be initiated within 5 days of symptom onset
Dose Adjustments for Renal Impairment
| Renal Function | Days of Treatment | Dose and Frequency |
|---|---|---|
| Moderate impairment (eGFR ≥30 to <60 mL/min) | Days 1-5 | 150 mg nirmatrelvir (one tablet) with 100 mg ritonavir (one tablet) twice daily |
| Severe impairment (eGFR <30 mL/min) including hemodialysis | Day 1 | 300 mg nirmatrelvir (two tablets) with 100 mg ritonavir (one tablet) once |
| Days 2-5 | 150 mg nirmatrelvir (one tablet) with 100 mg ritonavir (one tablet) once daily |
Note: For patients on hemodialysis, administer Paxlovid after hemodialysis sessions 2
Important Clinical Considerations
Drug Interactions
- Ritonavir is a strong CYP3A inhibitor that can significantly increase serum levels of many medications
- Critical safety step: Review all patient medications prior to prescribing to assess potential drug-drug interactions
- Some medications are absolutely contraindicated with Paxlovid due to risk of serious/life-threatening reactions 1, 2
Pharmacokinetics
- Nirmatrelvir exhibits absorption-limited nonlinear pharmacokinetics
- When co-administered with ritonavir, renal elimination becomes the primary route of nirmatrelvir elimination 3
- Nirmatrelvir clearance increases proportionally to body surface area-normalized creatinine clearance up to 70 ml/min/1.73 m² 4
Contraindications
- History of clinically significant hypersensitivity reactions to nirmatrelvir or ritonavir
- Co-administration with drugs highly dependent on CYP3A for clearance
- Co-administration with potent CYP3A inducers 2
Common Adverse Effects
Special Populations
- Hepatic impairment: Not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 2
- Pregnancy: Paxlovid represents a treatment option for pregnant people with COVID-19 1
- Breastfeeding: Not contraindicated during Paxlovid treatment 1
Clinical Pearls
- Dosing recommendations are based on pharmacokinetic modeling to maintain nirmatrelvir concentrations above the antiviral EC90 value throughout the dosing interval 3
- Dose adjustments in renal impairment are critical as systemic nirmatrelvir exposure increases significantly with decreasing renal function 5
- The 5-day treatment duration is standard regardless of renal function; only the dose is adjusted 2
- COVID-19 rebound has been reported after Paxlovid treatment completion, but this does not require retreatment with Paxlovid 6
The dosing regimen is designed to maintain adequate antiviral concentrations while minimizing adverse effects, with careful consideration of renal function being essential for appropriate dosing.