What is the recommended treatment regimen for Paxlovid (nirmatrelvir/ritonavir) in adults with mild to moderate COVID-19?

Paxlovid Treatment Regimen for Adults with Mild to Moderate COVID-19

The standard treatment regimen for Paxlovid (nirmatrelvir/ritonavir) in adults with mild to moderate COVID-19 is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), taken together twice daily for 5 days. 1, 2

Patient Selection and Timing

• Treatment must be initiated as soon as possible after diagnosis and within 5 days of symptom onset 1
• Paxlovid is indicated for adults with mild-to-moderate COVID-19 who are at high risk for progression to severe disease 2
• High-risk patients who benefit most include:
  • Adults aged ≥65 years
  • Patients with uncontrolled chronic medical conditions
  • Immunocompromised individuals
  • Unvaccinated individuals
  • Pregnant patients 1

Dosing Considerations

Standard Dosing

• 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet)
• All 3 tablets taken together twice daily for 5 days
• Administer orally with or without food at approximately the same time each day 2

Renal Dose Adjustments

1. 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 2

2. 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 2
   • For hemodialysis patients, administer dose after hemodialysis 2

Hepatic Considerations

• Not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 2

Drug Interactions

Paxlovid includes ritonavir, a strong CYP3A inhibitor, which can lead to significant drug-drug interactions. Prior to prescribing:

1. Review all patient medications to assess potential interactions 2, 3
2. Determine if concomitant medications require dose adjustment, interruption, or additional monitoring 2

Contraindications

• History of 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 that may reduce nirmatrelvir/ritonavir concentrations 2

Clinical Efficacy

• Paxlovid has demonstrated an 86% reduction in hospitalization risk and 100% reduction in mortality compared to placebo in high-risk outpatients 1
• Real-world evidence shows significantly lower hospitalization rates among Paxlovid-treated patients (adjusted hazard ratio = 0.49) 4
• Benefits observed across all age groups:
  • 18-49 years: aHR = 0.59
  • 50-64 years: aHR = 0.40
  • ≥65 years: aHR = 0.53 4
• Effective in both vaccinated and unvaccinated individuals 4

Adverse Effects and Monitoring

• Most common adverse effects:
  • Dysgeusia (altered taste)
  • Diarrhea 1
• Monitor for hepatotoxicity (hepatic transaminase elevations, clinical hepatitis, and jaundice) 2
• Watch for hypersensitivity reactions, including anaphylaxis and serious skin reactions 2

Alternative Treatments

When Paxlovid is contraindicated or unavailable, consider:

1. Remdesivir: Intravenous administration over 3 days 1
2. Molnupiravir: Oral alternative when other options aren't suitable 1

Special Considerations

• Pregnancy: Paxlovid may be considered for pregnant patients with COVID-19 to reduce disease progression risk 1
• Post-treatment care: Antibiotics should not be prescribed prophylactically following Paxlovid treatment unless there is clear evidence of bacterial infection 1
• COVID-19 rebound: Hospitalization or ED visits during the 5-15 days after Paxlovid treatment are rare (<1% of patients) 5

Common Pitfalls to Avoid

1. Missing drug interactions: Always screen for potential drug interactions before prescribing
2. Delayed initiation: Starting treatment beyond 5 days of symptom onset significantly reduces effectiveness
3. Incorrect dosing: Failing to adjust dosing for renal impairment
4. Inappropriate patient selection: Prescribing to patients without risk factors for severe disease
5. Unnecessary antibiotics: Avoid prescribing antibiotics for persistent symptoms unless bacterial infection is confirmed

By following this treatment regimen and considering these important factors, Paxlovid can effectively reduce the risk of hospitalization and death in high-risk patients with mild to moderate COVID-19.