Paxlovid (Nirmatrelvir/Ritonavir) Dosage for COVID-19 Treatment
The standard recommended dosage of Paxlovid is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all three tablets taken together twice daily for 5 days. 1, 2
Standard Dosing Regimen
- Initiate treatment as soon as possible after diagnosis and within 5 days of symptom onset
- Administer orally with or without food
- Take at approximately the same time each day
- Complete the full 5-day treatment course
Dosage Adjustments for Special Populations
Renal Impairment 2, 3
Moderate renal impairment (eGFR ≥30 to <60 mL/min):
- 150 mg nirmatrelvir (one tablet) with 100 mg ritonavir (one tablet) twice daily for 5 days
Severe renal impairment (eGFR <30 mL/min) including those requiring 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
- For hemodialysis patients, administer dose after hemodialysis
Hepatic Impairment 1, 2
- No dose adjustment needed for mild to moderate hepatic impairment
- Not recommended for patients with severe hepatic impairment (Child-Pugh Class C)
Important Clinical Considerations
Drug Interactions
- Ritonavir is a strong CYP3A inhibitor that can significantly affect the metabolism of many medications 1, 2
- Prior to prescribing:
- Review all medications to assess potential drug-drug interactions
- Determine if concomitant medications require dose adjustment, interruption, or additional monitoring
- Use the Liverpool COVID-19 drug interaction tool for checking interactions 1
Contraindications 2
- History of clinically significant hypersensitivity to nirmatrelvir or ritonavir
- Co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations may cause serious reactions
- Co-administration with potent CYP3A inducers that may reduce nirmatrelvir/ritonavir effectiveness
Adverse Effects
- Most common adverse reactions (≥1% incidence) are dysgeusia (altered taste) and diarrhea 1, 2, 4
- Monitor for potential hepatotoxicity (hepatic transaminase elevations, clinical hepatitis, and jaundice) 2
Efficacy
Paxlovid has demonstrated significant efficacy in reducing the risk of COVID-19 progression to severe disease, with an 89% reduction in risk of hospitalization or death when initiated within 3 days of symptom onset 1, 4.
Practical Dosing Tips
- The pharmacokinetic profile of nirmatrelvir supports the twice-daily dosing regimen to maintain concentrations above the antiviral effective concentration 5, 6
- Renal dose adjustments are critical as nirmatrelvir is primarily eliminated by the kidneys when co-administered with ritonavir 3
- Ritonavir serves as a pharmacokinetic enhancer by inhibiting nirmatrelvir's CYP3A4-mediated metabolism 6
The dosing recommendations are based on pharmacokinetic studies showing that systemic nirmatrelvir exposure increases with increasing renal impairment, necessitating dose adjustments to maintain appropriate drug levels while minimizing toxicity 3.