Is Paxlovid (nirmatrelvir/ritonavir) still used in the treatment of COVID-19?

Paxlovid Use in COVID-19 Treatment

Paxlovid (nirmatrelvir/ritonavir) remains a strongly recommended treatment for COVID-19 in high-risk patients, with recent 2024-2025 guidelines continuing to support its use to reduce hospitalization risk by 39% and mortality risk by 61%. 1, 2

Current Indications and Patient Selection

Paxlovid is indicated for:

• Treatment of mild-to-moderate COVID-19 in adults at high risk for progression to severe disease 3
• Must be initiated within 5 days of symptom onset 1, 2, 3

Patient Prioritization:

• High priority (strong recommendation):

  • Advanced age (especially ≥65 years)
  • Uncontrolled chronic medical conditions
  • Immunocompromised status
  • Unvaccinated status
  • Pregnancy 2

• Moderate priority (conditional recommendation):

  • Patients with moderate risk factors 2

• Not recommended for low-risk patients as benefits are considered trivial 2

Efficacy Data

Recent large-scale evidence demonstrates significant benefits:

• 39% reduction in hospitalization risk (absolute risk reduction of 0.9 percentage points) 4
• 61% reduction in mortality risk (absolute risk reduction of 0.2 percentage points) 4
• Effective in both vaccinated and unvaccinated patients 4, 5
• Particularly beneficial in patients aged 65+ years 4
• May reduce long COVID incidence by 25% 2

Dosing and Administration

Standard dosing:

• 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), twice daily for 5 days 2, 3

Renal dosage adjustments:

• Moderate impairment (eGFR 30-60 mL/min): 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days 2, 3
• Severe impairment (eGFR <30 mL/min): 300 mg nirmatrelvir with 100 mg ritonavir once on Day 1, followed by 150 mg nirmatrelvir with 100 mg ritonavir once daily on Days 2-5 2, 3

Not recommended in:

• Patients with severe hepatic impairment (Child-Pugh Class C) 2, 3

Critical Considerations and Common Pitfalls

Drug Interactions

• Ritonavir is a strong CYP3A inhibitor that significantly affects metabolism of many medications 3, 6
• ALWAYS review all patient medications before prescribing 2, 3
• Use the Liverpool COVID-19 Drug Interaction Tool to check potential interactions 2
• Determine if concomitant medications require dose adjustment, temporary interruption, or additional monitoring 2, 3

Contraindications

• History of clinically significant hypersensitivity reactions to nirmatrelvir or ritonavir 3
• Co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations could cause serious reactions 3
• Co-administration with potent CYP3A inducers 3

Safety Considerations

• Hypersensitivity reactions including anaphylaxis and serious skin reactions have been reported 3
• Hepatotoxicity: Monitor for hepatic transaminase elevations, clinical hepatitis, and jaundice 3
• COVID-19 rebound has been reported but is rare and generally mild 7

Alternative Options When Paxlovid Is Contraindicated

• Remdesivir: Consider when Paxlovid is contraindicated due to drug interactions (requires 3-day IV administration) 2
• Molnupiravir: Less effective than Paxlovid but can be considered when other options are unavailable 1, 2, 8

Equity Considerations

• Disparities in Paxlovid treatment rates have been observed, with lower rates among Black and Hispanic/Latino patients and within socially vulnerable communities 4
• No significant differences in efficacy have been observed based on age or ethnicity in clinical studies 8

Paxlovid remains a cornerstone of COVID-19 treatment for high-risk patients, with strong evidence supporting its continued use to reduce hospitalization and mortality.