What are the current recommendations for prescribing Paxlovid (nirmatrelvir/ritonavir) for COVID-19?

Current Recommendations for Paxlovid Prescription

Paxlovid (nirmatrelvir/ritonavir) is strongly recommended for patients with non-severe COVID-19 who are at high risk for progression to severe disease, and should be initiated within 5 days of symptom onset. 1

Patient Selection and Risk Stratification

High-Risk Patients (Strong Recommendation)

• Paxlovid is strongly recommended for patients with confirmed mild to moderate COVID-19 who are at high risk for hospitalization 1
• High-risk patients show the greatest absolute benefit with a significant reduction in hospitalization risk 1, 2
• Treatment should be initiated as soon as possible after diagnosis and within 5 days of symptom onset 3

Moderate-Risk Patients (Conditional Recommendation)

• For patients with non-severe COVID-19 at moderate risk of hospitalization, Paxlovid is conditionally recommended 1
• The benefit is present but smaller than in high-risk patients 1

Low-Risk Patients (Not Recommended)

• Paxlovid is not recommended for patients at low risk of hospitalization 1
• Benefits in this population are considered trivial relative to potential risks 1

Dosing Recommendations

Standard Dosing

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

Renal Dose Adjustments

• Moderate renal impairment (eGFR 30-59 mL/min): 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days 1, 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
  • For hemodialysis patients, administer after dialysis 3

Hepatic Considerations

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

Drug Interactions

Critical Consideration

• Ritonavir is a strong CYP3A inhibitor that can cause significant drug-drug interactions 1, 2, 3
• Before prescribing:
  1. Review all medications taken by the patient
  2. Determine if concomitant medications require dose adjustment, interruption, or additional monitoring 3
• The Liverpool COVID-19 Drug Interaction Tool is recommended as a resource for checking potential interactions 1

Evidence for Effectiveness

• Real-world data shows Paxlovid reduces hospitalization risk by approximately 39-49% across various populations 4, 5
• Mortality reduction of approximately 61% has been observed in real-world studies 5
• Benefits observed across age groups, with greatest absolute risk reduction in patients aged 65+ years 5
• Effective in both vaccinated and unvaccinated patients 5

Special Populations

Immunocompromised Patients

• Paxlovid is appropriate for immunocompromised patients 2
• The prolonged viral phase in these patients may increase the benefit of antiviral treatments 2

Pregnant Patients

• Paxlovid represents an option for pregnant people with COVID-19 to reduce risk of disease progression 1
• No reports of serious adverse reactions in pregnant or breastfeeding individuals have been documented in WHO Vigibase 1

Common Pitfalls to Avoid

1. Delayed initiation: Treatment must begin within 5 days of symptom onset for maximum benefit 1, 3

2. Missing drug interactions: Failure to check for potential drug interactions can lead to serious adverse events 1, 3

3. Incorrect dosing in renal impairment: Dose adjustments are required for patients with renal impairment 1, 3

4. Treatment inequity: Lower rates of Paxlovid treatment have been observed among Black and Hispanic/Latino patients and within socially vulnerable communities 5

5. Inappropriate use in low-risk patients: Resources should be prioritized for high-risk patients when availability is limited 1

Algorithmic Approach to Paxlovid Prescription

1. Confirm COVID-19 diagnosis and assess symptom onset timing (must be within 5 days)

2. Assess patient risk status:

   • High risk → Strongly recommend Paxlovid
   • Moderate risk → Consider Paxlovid
   • Low risk → Not recommended

3. Check renal function and adjust dosing accordingly

4. Screen for drug interactions using Liverpool COVID-19 Drug Interaction Tool

5. Assess hepatic function (avoid in severe impairment)

6. Prescribe appropriate dose based on above factors

7. Educate patient on administration timing and potential side effects (diarrhea and dysgeusia are common)