What is the recommended treatment regimen for COVID-19 using Paxlovid (nirmatrelvir/ritonavir)?

Recommended Treatment Regimen for COVID-19 Using Paxlovid (Nirmatrelvir/Ritonavir)

The recommended treatment regimen for COVID-19 using Paxlovid is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all three tablets taken together twice daily for 5 days, initiated within 5 days of symptom onset in high-risk patients. 1, 2

Patient Selection

• Paxlovid is indicated for the treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe disease, including hospitalization or death 1
• Treatment should be initiated as soon as possible after diagnosis and within 5 days of symptom onset 2, 1
• High-risk patients show the greatest absolute benefit with significant reduction in hospitalization risk 2, 3
• Not recommended for patients at low risk of hospitalization as benefits are considered trivial relative to potential risks 2

Standard Dosing Protocol

• Standard dose: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) twice daily for 5 days 1
• Administer orally with or without food 1
• Take at approximately the same time each day 1

Dose Adjustments for Special Populations

Renal Impairment 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
• Severe renal impairment (eGFR <30 mL/min) including 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
  • For hemodialysis patients, administer dose after hemodialysis

Hepatic Impairment

• Not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 1

Drug Interactions Management

Paxlovid includes ritonavir, a strong CYP3A inhibitor, which can cause significant drug-drug interactions 1, 4:

1. Prior to prescribing:

   • Review all medications taken by the patient to assess potential drug-drug interactions
   • Determine if concomitant medications require dose adjustment, interruption, or additional monitoring

2. High-risk interactions:

   • Avoid co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations may cause serious/life-threatening reactions 1
   • Avoid co-administration with potent CYP3A inducers that could reduce nirmatrelvir/ritonavir concentrations 1
   • Use the Liverpool COVID-19 Drug Interaction Tool to check potential interactions 2, 4

3. Management options for drug interactions during the 5-day treatment course 4:

   • Temporarily pause the interacting medication if clinically appropriate
   • Adjust dosage of interacting medication
   • Provide counseling about potential interaction risks
   • Consider alternative COVID-19 treatment if interactions cannot be managed safely

Efficacy and Outcomes

• Paxlovid reduces risk of hospitalization by approximately 39% (absolute risk reduction of 0.9 percentage points) 3
• Reduces risk of death by approximately 61% (absolute risk reduction of 0.2 percentage points) 3
• Greatest benefit observed in patients aged 65+ years 3
• Effective in both vaccinated and unvaccinated patients 3, 5
• Associated with shorter viral shedding time and faster symptom resolution compared to standard treatment 6

Monitoring and Safety

• Most common adverse reactions (≥1% incidence) are dysgeusia and diarrhea 1
• Monitor for potential hypersensitivity reactions including anaphylaxis and serious skin reactions 1
• Watch for hepatotoxicity (hepatic transaminase elevations, clinical hepatitis, and jaundice) 1
• Be aware of the potential for COVID-19 rebound (recurrence of symptoms or positive test) 2-8 days after recovery, though severe illness after Paxlovid treatment is rare (<1%) 7

Key Practice Points

• Paxlovid is preferred over remdesivir for non-severe COVID-19 in high-risk patients due to its oral administration, comparable efficacy, and favorable risk-benefit profile 2
• Consider remdesivir when Paxlovid is contraindicated due to drug interactions 2
• The American College of Physicians strongly recommends Paxlovid for high-risk patients and conditionally recommends it for moderate-risk patients 2
• Treatment must begin within 5 days of symptom onset for maximum benefit 2, 1