What are the indications for Paxlovid (nirmatrelvir/ritonavir)?

Indications for Paxlovid (Nirmatrelvir/Ritonavir)

Paxlovid is indicated for the treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death. 1

Patient Selection Criteria

Paxlovid should be prescribed to patients who meet the following criteria:

• Adults with confirmed mild-to-moderate COVID-19
• Treatment must be initiated within 5 days of symptom onset 2
• Patients at high risk for disease progression, which includes:
  • Advanced age (especially ≥65 years)
  • Uncontrolled chronic medical conditions
  • Immunocompromised status
  • Unvaccinated status
  • Pregnancy 2

The benefit of Paxlovid is most pronounced in high-risk populations, with studies showing:

• 39% reduction in hospitalization risk and 61% reduction in mortality 3
• Greatest absolute risk reduction observed in adults aged 65+ years 3
• Significant benefit in severely immunocompromised individuals 4

Dosing Regimen

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 1

Renal dose adjustments:

• Moderate renal impairment (eGFR ≥30 to <60 mL/min): 150 mg nirmatrelvir with 100 mg ritonavir 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 and Precautions

Paxlovid is contraindicated in:

• Patients with history of hypersensitivity to nirmatrelvir or ritonavir
• Co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations may cause serious reactions
• Co-administration with potent CYP3A inducers which may reduce nirmatrelvir/ritonavir concentrations 1

Important precautions:

• Prior to prescribing, review all patient medications to assess potential drug-drug interactions with ritonavir (a strong CYP3A inhibitor) 1
• Not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 1
• Monitor for hypersensitivity reactions including anaphylaxis and serious skin reactions 1

Clinical Efficacy

Paxlovid has demonstrated significant clinical benefits:

• 86% reduction in hospitalization risk and 100% reduction in mortality compared to placebo in high-risk outpatients with mild-to-moderate COVID-19 2
• Real-world data shows effectiveness across various age groups (18-49 years: aHR = 0.59; 50-64 years: aHR = 0.40; ≥65 years: aHR = 0.53) 5
• Effective in both vaccinated and unvaccinated patients 5, 3

Common Adverse Effects

The most common adverse effects include:

• Dysgeusia (taste disturbance)
• Diarrhea 2
• Potential for acute encephalopathy due to drug-drug interactions, particularly with benzodiazepines and narcotics 6

Limitations of Use

Paxlovid is not approved for:

• Pre-exposure prophylaxis
• Post-exposure prophylaxis for prevention of COVID-19 1
• Patients at low risk of hospitalization (benefits considered trivial compared to potential risks) 2

Clinical Pearls and Pitfalls

• Critical timing: Treatment must be initiated within 5 days of symptom onset for maximum efficacy 2
• Drug interaction screening is essential: Ritonavir is a strong CYP3A inhibitor that can significantly increase serum levels of many medications 2, 1
• Disparities in treatment access: Lower rates of Paxlovid treatment have been observed among Black and Hispanic/Latino patients and within socially vulnerable communities 3
• Antibiotics not indicated: For patients who completed Paxlovid but still have persistent COVID-19 symptoms, antibiotics are not indicated unless there is clear evidence of a secondary bacterial infection 2