What is the recommended treatment with Paxlovid (nirmatrelvir/ritonavir) for patients with COVID-19?

Paxlovid Treatment Recommendations for COVID-19

Paxlovid (nirmatrelvir/ritonavir) is strongly recommended for the treatment of mild-to-moderate COVID-19 in adults at high risk for progression to severe disease and must be initiated within 5 days of symptom onset.

Patient Selection

• High-risk patients who should be considered for Paxlovid treatment include:

  • Advanced age (especially ≥65 years)
  • Uncontrolled chronic medical conditions
  • Immunocompromised status
  • Unvaccinated status
  • Pregnancy 1

• Paxlovid has demonstrated significant clinical benefits:

  • Reduces hospitalization risk by 39%
  • Reduces death risk by 61%
  • Particularly beneficial for patients aged 65+ years
  • Effective in both vaccinated and unvaccinated patients 1, 2

Dosing Regimen

Standard Dosing

• 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet)
• Take all three tablets together twice daily for 5 days
• Administer orally with or without food at approximately the same time each day 1, 3

Renal Dose Adjustments

• 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):

  • 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 1, 3

Hepatic Considerations

• Not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 3

Critical Drug Interaction Management

• IMPORTANT: Ritonavir is a strong CYP3A inhibitor that can significantly increase serum levels of many medications 1, 3

• Before prescribing Paxlovid:

  1. Review all patient medications to assess potential drug-drug interactions
  2. Determine if concomitant medications require dose adjustment, temporary interruption, or additional monitoring
  3. Use the Liverpool COVID-19 Drug Interaction Tool to check potential interactions 1, 3

• Contraindications:

  • History of clinically significant hypersensitivity reactions 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 3

Alternative Treatment Options

• When Paxlovid is contraindicated:
  • Remdesivir may be considered (requires intravenous administration over 3 days)
  • Molnupiravir is less effective but can be considered when other options are unavailable (must also be started within 5 days of symptom onset) 1

Monitoring and Follow-up

• Monitor for potential COVID-19 rebound symptoms, which have been documented 2-8 days after recovery or negative test results 4
• Hospitalization or ED encounters after Paxlovid treatment are rare (<1% of patients) 4
• For patients with persistent COVID-19 symptoms after completing Paxlovid, antibiotics are not indicated unless there is clear evidence of a secondary bacterial infection 1

Special Populations

• Paxlovid is an option for pregnant people with COVID-19 to reduce disease progression risk
• Breastfeeding is not contraindicated during Paxlovid treatment 1
• May reduce the incidence of long COVID by 25% when used for acute COVID-19 treatment 1

Paxlovid represents a highly effective early treatment option for COVID-19 patients at risk of severe disease progression, with demonstrated benefits in reducing hospitalization and mortality across various patient populations. Proper patient selection, timely initiation, and careful management of drug interactions are essential for optimal outcomes.