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

Paxlovid (Nirmatrelvir/Ritonavir) Dosing for COVID-19

The standard dose of Paxlovid 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

Standard Dosing Protocol

• Standard dose: 300 mg nirmatrelvir (two 150 mg tablets) + 100 mg ritonavir (one 100 mg tablet)
• Frequency: Twice daily
• Duration: 5 days
• Timing: Administer at approximately the same time each day
• Food: Can be taken with or without food 1, 2

Renal Dose Adjustments

Moderate Renal Impairment (eGFR ≥30 to <60 mL/min)

• 150 mg nirmatrelvir (one 150 mg tablet) + 100 mg ritonavir (one 100 mg tablet)
• Twice daily for 5 days 1, 2

Severe Renal Impairment (eGFR <30 mL/min) including those requiring hemodialysis

• Day 1: 300 mg nirmatrelvir (two 150 mg tablets) + 100 mg ritonavir (one 100 mg tablet) once
• Days 2-5: 150 mg nirmatrelvir (one 150 mg tablet) + 100 mg ritonavir (one 100 mg tablet) once daily
• For hemodialysis patients, dose should be administered after hemodialysis 1, 2

Hepatic Considerations

• No dose adjustment needed for mild to moderate hepatic impairment
• Not recommended for patients with severe hepatic impairment (Child-Pugh Class C) 1, 2

Important Prescribing Considerations

Drug Interactions

• Ritonavir is a strong CYP3A inhibitor that can significantly affect the metabolism of many medications
• Prior to prescribing:
  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
• Use the Liverpool COVID-19 drug interaction tool to check for potential interactions 1, 2

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/life-threatening reactions
3. Co-administration with potent CYP3A inducers that may reduce nirmatrelvir/ritonavir plasma concentrations 2

Common Adverse Effects

• Dysgeusia (altered taste)
• Diarrhea 1, 2, 3

Clinical Efficacy

Paxlovid has demonstrated significant efficacy in reducing the risk of COVID-19 progression to severe disease, with a reported 89% reduction in risk of hospitalization or death when initiated within 3 days of symptom onset 1, 3

Pitfalls to Avoid

1. Delayed initiation: Treatment must begin within 5 days of symptom onset for optimal efficacy
2. Overlooking drug interactions: Ritonavir has numerous significant drug interactions that must be carefully evaluated
3. Incorrect renal dosing: Failure to adjust dosing for renal impairment can lead to toxicity
4. Prescribing in severe hepatic impairment: Avoid use in Child-Pugh Class C patients
5. HIV drug resistance risk: Consider HIV testing in high-risk individuals with unknown HIV status, as ritonavir may lead to HIV protease inhibitor resistance in undiagnosed cases 1, 2

Paxlovid represents a valuable treatment option for high-risk patients with COVID-19 when properly dosed according to individual patient characteristics, particularly renal function.