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

Criteria for Prescribing Paxlovid (Nirmatrelvir/Ritonavir)

Paxlovid should be prescribed to adults with mild-to-moderate COVID-19 who are at high risk for progression to severe disease, including hospitalization or death, and treatment should be initiated within 5 days of symptom onset. 1

Patient Eligibility Criteria

Required Conditions

• Confirmed COVID-19 diagnosis (positive test)
• Mild-to-moderate symptoms
• Within 5 days of symptom onset
• High risk for progression to severe disease

High-Risk Factors Include:

• Age ≥65 years
• Underlying medical conditions such as:
  • Cardiovascular disease
  • Chronic lung disease
  • Diabetes
  • Obesity
  • Immunocompromised state
  • Cancer
  • Chronic kidney disease

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
• Administer orally with or without food at approximately the same time each day 1

Renal Adjustment

• 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 with 100 mg ritonavir once
  • Days 2-5: 150 mg nirmatrelvir with 100 mg ritonavir once daily 1

Contraindications

1. History of clinically significant hypersensitivity to nirmatrelvir or ritonavir
2. Co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations could lead to serious reactions
3. Co-administration with potent CYP3A inducers that may reduce nirmatrelvir/ritonavir effectiveness 1

Drug Interaction Considerations

Before prescribing Paxlovid:

1. Review all medications taken by the patient to assess potential drug-drug interactions
2. Determine if concomitant medications require dose adjustment, interruption, or additional monitoring
3. Consider temporary discontinuation of interacting medications during the 5-day Paxlovid course when appropriate 1, 2

Clinical Evidence Supporting Use

• Paxlovid reduces the risk of hospitalization by approximately 39% and death by 61% in real-world studies 3
• The absolute risk reduction for hospitalization is 0.9 percentage points overall, with greater benefit observed in patients aged 65+ years 3
• Hospitalization or ED encounters after Paxlovid treatment are rare (<1% of patients) 4
• Effectiveness has been demonstrated across age groups and vaccination status, including those who received ≥3 mRNA COVID-19 vaccines 5

Important Considerations

• Paxlovid is not approved for pre-exposure or post-exposure prophylaxis
• Not recommended in patients with severe hepatic impairment (Child-Pugh Class C)
• Treatment should be initiated as soon as possible after diagnosis
• Patients should be counseled about possible "COVID rebound" symptoms after completing treatment
• Evaluate for potential drug interactions before prescribing, as ritonavir is a strong CYP3A inhibitor

Monitoring Recommendations

• Monitor for hypersensitivity reactions including anaphylaxis and serious skin reactions
• Be aware of potential hepatotoxicity (hepatic transaminase elevations, clinical hepatitis)
• Assess for drug interactions throughout treatment period

The evidence strongly supports the use of Paxlovid in eligible high-risk patients with COVID-19, with significant reductions in hospitalization and mortality when administered early in the disease course.