What is the recommended dosing regimen for Paxlovid (nirmatrelvir/ritonavir) in the treatment of COVID-19?

Paxlovid Dosing for COVID-19

The standard dosing regimen for Paxlovid (nirmatrelvir/ritonavir) is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) taken together twice daily for 5 days, with treatment initiated as soon as possible after diagnosis and within 5 days of symptom onset. 1, 2

Standard Dosing Guidelines

• Normal renal function or mild impairment: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) twice daily for 5 days 1, 2
• Administer orally with or without food 2
• Take at approximately the same time each day 2
• All three tablets should be taken together 2

Dose Adjustments for Special Populations

Renal Impairment

• Moderate renal impairment (eGFR ≥30 to <60 mL/min):

  • 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) twice daily for 5 days 1, 2

• Severe renal impairment (eGFR <30 mL/min) including those requiring 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 2
  • For hemodialysis patients, administer dose after hemodialysis 2

Hepatic Impairment

• Mild to moderate hepatic impairment (Child-Pugh Class A or B): No dose adjustment needed 1
• Severe hepatic impairment (Child-Pugh Class C): Paxlovid is not recommended 1, 2

Important Clinical Considerations

Timing of Treatment

• Initiate treatment as soon as possible after diagnosis of COVID-19 2
• Must begin within 5 days of symptom onset for optimal efficacy 1, 2
• Early initiation is associated with better outcomes, with a 39% reduction in hospitalization risk and 61% reduction in mortality risk 3

Drug Interactions

• WARNING: Significant drug interactions are possible due to ritonavir's strong CYP3A inhibition 2
• Before prescribing:
  1. Review all medications the patient is taking
  2. Determine if concomitant medications require dose adjustment, interruption, or additional monitoring
  3. Use the Liverpool COVID-19 drug interaction tool to check for potential interactions 1

Contraindications

• History of clinically significant hypersensitivity to nirmatrelvir or ritonavir 2
• Co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations may cause serious reactions 2
• Co-administration with potent CYP3A inducers 2

Common Adverse Effects

• Most common: dysgeusia (altered taste) and diarrhea 1, 2
• Most adverse events are mild in severity 1

Efficacy

Paxlovid has demonstrated significant efficacy in reducing COVID-19 progression to severe disease, with studies showing:

• 89% reduction in risk of hospitalization or death when initiated within 3 days of symptom onset 1
• Greater absolute risk reduction in older adults (≥65 years) compared to younger patients 3
• Effective in both vaccinated and unvaccinated patients 3

Monitoring

• Assess kidney and hepatic function at baseline and during treatment 1
• Monitor for hypersensitivity reactions, including infusion-related and anaphylactic reactions 1
• Discontinue if ALT levels increase to ≥5 times the upper limit of normal or if any ALT elevation is accompanied by signs of liver inflammation 1

Paxlovid represents an important treatment option for COVID-19 when properly dosed according to patient characteristics, particularly renal function, and with careful attention to potential drug interactions.