When to use Paxlovid (nirmatrelvir/ritonavir) for treating COVID-19?

When to Use Paxlovid (Nirmatrelvir/Ritonavir) for COVID-19

Paxlovid should be used for patients with mild to moderate COVID-19 who are at high risk for disease progression, with treatment initiated within 5 days of symptom onset. 1

Patient Selection Algorithm

Recommended for:

• High-risk patients (strong recommendation) 1, 2:
  • Advanced age (especially ≥65 years)
  • Uncontrolled chronic medical conditions
  • Immunocompromised status
  • Unvaccinated status

Consider for:

• Moderate-risk patients (conditional recommendation) 1
• Pregnant or breastfeeding individuals with non-severe COVID-19 1, 2

Not recommended for:

• Low-risk patients (conditional recommendation against) 1
• Patients with severe hepatic impairment (Child-Pugh Class C) 3

Timing and Administration

• Must be initiated within 5 days of symptom onset 1, 3
• Standard dosage: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) twice daily for 5 days 3
• Administer orally with or without food at approximately the same time each day 3

Dose Adjustments for Special Populations

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

Clinical Effectiveness

• High-risk patients: 39% reduction in hospitalization risk and 61% reduction in mortality 4
• Older adults (≥65 years): Greater absolute risk reduction compared to younger patients 4
• Vaccinated patients: Similar absolute risk reduction for hospitalization compared to unvaccinated patients 4
• Post-treatment COVID-19 related hospitalizations or ED visits are rare (<1% of treated patients) 5

Drug Interactions - Critical Consideration

• Ritonavir is a strong CYP3A inhibitor that can cause significant drug-drug interactions 3, 6
• Before prescribing:
  1. Review all medications to assess potential drug-drug interactions
  2. Determine if concomitant medications require dose adjustment, interruption, or additional monitoring
  3. Use the Liverpool COVID-19 Drug Interaction Tool to check potential interactions 2

Contraindications

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

Alternative Options When Paxlovid is Contraindicated

• Remdesivir: Requires intravenous administration over 3 days 1, 2
• Molnupiravir: Less effective than Paxlovid but can be considered when other options are unavailable 1, 2

Special Considerations

• COVID-19 rebound: Recurrence of symptoms or positive test results 2-8 days after recovery may occur, but severe illness after Paxlovid treatment is rare 5, 7
• Equity concerns: Lower treatment rates have been observed among Black and Hispanic/Latino patients and within socially vulnerable communities 4

Key Pitfalls to Avoid

1. Delaying treatment beyond the 5-day window after symptom onset
2. Missing critical drug interactions that could lead to serious adverse events
3. Inappropriate use in low-risk patients where benefits are trivial relative to potential risks
4. Overlooking dose adjustments needed for patients with renal impairment

Paxlovid remains effective in the era of SARS-CoV-2 Omicron subvariants, with consistent benefits observed across vaccination status, though the greatest absolute benefit is seen in older adults and those at highest risk for disease progression 4.