What is the recommended dosing for Paxlovid (nirmatrelvir and ritonavir) in adults with COVID-19?

Paxlovid (Nirmatrelvir/Ritonavir) Dosing Recommendations

The standard dosing for 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. 1

Standard Dosing Protocol

• Timing: Initiate treatment as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset 2, 1
• Administration: Take orally with or without food, at approximately the same time each day 1
• Duration: Complete the full 5-day course 1

Dose Adjustments for Special Populations

Renal Impairment 1, 3

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. 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
   • For hemodialysis patients: Administer dose after hemodialysis

Hepatic Impairment

• Mild to moderate hepatic impairment: No dosage adjustment needed 1
• Severe hepatic impairment (Child-Pugh Class C): Not recommended 1

Important Clinical Considerations

Drug Interactions

Ritonavir is a strong CYP3A inhibitor that can cause significant drug-drug interactions 2, 1:

• Before prescribing:

  1. Review all medications taken by the patient
  2. Determine if concomitant medications require dose adjustment, interruption, or additional monitoring
  3. Consider using the Liverpool COVID-19 Drug Interaction Tool 2

• Contraindications: Avoid co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations could lead to serious reactions 1

Efficacy and Benefits

• Reduces risk of hospitalization by 39% and death by 61% in real-world studies 4
• Particularly beneficial for older adults (65+ years) and those at high risk for disease progression 4
• Treatment should be initiated within 5 days of symptom onset for maximum effectiveness 1, 5

Adverse Effects

• Most common: Dysgeusia (altered taste, 5.6%) and diarrhea (3.1%) 5
• Generally well-tolerated with similar overall adverse event rates to placebo 5
• Monitor for hypersensitivity reactions and hepatotoxicity 1

Practical Implementation

1. Confirm eligibility: Mild-to-moderate COVID-19 in adults at high risk for progression to severe disease
2. Screen for drug interactions: Review all medications before prescribing
3. Assess renal function: Determine appropriate dosage based on eGFR
4. Initiate promptly: Start within 5 days of symptom onset
5. Ensure adherence: Emphasize importance of completing the full 5-day course

Paxlovid has demonstrated significant efficacy in reducing hospitalization and death in high-risk patients with COVID-19 when initiated early in the disease course, making it an important treatment option despite the need for careful management of potential drug interactions.