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

Paxlovid (Nirmatrelvir/Ritonavir) Dosing Regimen for COVID-19

The standard recommended dosage of Paxlovid for COVID-19 is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) taken together twice daily for 5 days, with treatment initiated as soon as possible after diagnosis and within 5 days of symptom onset. 1, 2, 3

Standard Dosing Protocol

• Timing: Initiate treatment as soon as possible after diagnosis and within 5 days of symptom onset 3
• Standard dose: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) twice daily for 5 days 1, 3
• Administration: Take all three tablets together at the same time, twice daily 3
• Food considerations: Can be administered with or without food 3
• Timing consistency: Administer at approximately the same time each day 3

Dose Adjustments for Special Populations

Renal Impairment 2, 3, 4

• 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 patients:

  • 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 2, 3

• Mild to moderate hepatic impairment (Child-Pugh Class A or B): No dose adjustment needed
• Severe hepatic impairment (Child-Pugh Class C): Not recommended

Important Clinical Considerations

Drug Interactions

• Ritonavir is a strong CYP3A inhibitor that can significantly affect the metabolism of many medications 2, 3
• Prior to prescribing Paxlovid:
  1. Review all medications to assess potential drug-drug interactions
  2. Determine if concomitant medications require dose adjustment, interruption, or additional monitoring
• The Liverpool COVID-19 drug interaction tool is recommended as a resource for checking drug interactions 2

Contraindications 3

• History of clinically significant 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 that may reduce nirmatrelvir/ritonavir concentrations

Common Adverse Effects 1, 2

• Dysgeusia (altered taste)
• Diarrhea

Efficacy and Safety Profile

Paxlovid has demonstrated significant efficacy in reducing the risk of COVID-19 progression to severe disease 2, 5. Low-certainty evidence suggests nirmatrelvir/ritonavir reduces the risk of all-cause mortality and hospital admission or death in high-risk, unvaccinated COVID-19 outpatients 5.

Pitfalls and Caveats

1. Drug interactions: The most significant pitfall is potential drug interactions due to ritonavir's strong CYP3A inhibition. Always conduct a thorough medication review before prescribing.

2. Timing: Efficacy depends on early initiation - must be started within 5 days of symptom onset.

3. Renal function assessment: Accurate assessment of renal function is critical for appropriate dosing.

4. Pregnancy and breastfeeding: Limited data available, though guidelines acknowledge Paxlovid represents an option for pregnant people with COVID-19 1, 2.

5. COVID-19 rebound: Some patients may experience symptom recurrence after completing treatment 6.

The dosing recommendations are supported by population pharmacokinetic analyses and quantitative systems pharmacology modeling to ensure adequate viral suppression while maintaining safety 4, 7.