Patient Selection Criteria for Paxlovid (Nirmatrelvir/Ritonavir) in COVID-19
Paxlovid is indicated for the treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe disease, and treatment must be initiated within 5 days of symptom onset to maximize efficacy. 1, 2
High-Risk Patient Populations
Patients who will benefit most from Paxlovid therapy include:
- Adults with the following risk factors:
- Advanced age (especially ≥65 years)
- Uncontrolled chronic medical conditions
- Immunocompromised status (particularly patients with hematological malignancies or post-hematopoietic cell transplantation)
- Unvaccinated status
- Pregnancy 1
Timing of Treatment
- Treatment must be initiated within 5 days of symptom onset 1, 2
- Initiating treatment beyond this window significantly reduces efficacy 1
Dosing Considerations
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 2
Renal Dose Adjustments
| Renal Function | Days of Treatment | Dose and Frequency |
|---|---|---|
| Moderate impairment (eGFR ≥30 to <60 mL/min) | Days 1-5 | 150 mg nirmatrelvir (one tablet) with 100 mg ritonavir (one tablet) twice daily |
| Severe impairment (eGFR <30 mL/min) | 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 patients on hemodialysis, administer dose after hemodialysis 2
Contraindications
Paxlovid is contraindicated in:
Patients with history of clinically significant hypersensitivity to nirmatrelvir or ritonavir 2
Co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations may cause serious reactions 2, 3
Co-administration with potent CYP3A inducers that may reduce nirmatrelvir/ritonavir concentrations 2
Patients with severe hepatic impairment (Child-Pugh Class C) 2
Drug-Drug Interaction Assessment
Prior to prescribing Paxlovid:
- 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, 3
Efficacy Considerations
Paxlovid has demonstrated:
- 86% reduction in hospitalization risk
- 100% reduction in mortality compared to placebo in high-risk outpatients 1
- Less than 1% of patients treated with Paxlovid required hospitalization or emergency department visits for COVID-19 during the 5-15 days after treatment 4
- Recent real-world data shows 39% reduction in hospitalization risk and 61% reduction in death risk 5
Common Pitfalls and Caveats
Timing is critical: Delaying treatment beyond 5 days of symptom onset significantly reduces efficacy 1
Drug interactions: Ritonavir is a potent CYP3A inhibitor that can significantly increase serum levels of many medications 3
Rebound symptoms: Some patients may experience recurrence of COVID-19 symptoms after completing treatment, but severe illness after Paxlovid treatment is rare 4
Renal adjustment: Failure to adjust dosing for renal impairment may lead to toxicity 2
Treatment disparity: Lower treatment rates have been observed among Black and Hispanic/Latino patients and within socially vulnerable communities 5
By following these selection criteria and considering the contraindications and drug interactions, clinicians can appropriately identify patients who will benefit most from Paxlovid while minimizing risks associated with treatment.