Indications for Starting Paxlovid (Nirmatrelvir/Ritonavir)
Paxlovid is indicated for the treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death, and should be initiated as soon as possible after diagnosis and within 5 days of symptom onset. 1, 2
Patient Selection Criteria
Patients who would benefit most from Paxlovid include those with:
- Advanced age (especially ≥65 years)
- Uncontrolled chronic medical conditions
- Immunocompromised status (including those with hematological malignancies)
- Unvaccinated status
- Pregnancy
- Other high-risk factors for severe COVID-19 1
Timing of Treatment
- Treatment must be initiated within 5 days of symptom onset
- Earlier initiation is associated with better outcomes
- Treatment beyond 5 days may result in reduced efficacy 1
Dosing Recommendations
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
- Administer orally with or without food at approximately the same time each day 1, 2
Renal Dose Adjustments
| Renal Function | Dosing Recommendation |
|---|---|
| Normal renal function | 300 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days |
| Moderate impairment (eGFR ≥30 to <60 mL/min) | 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days |
| Severe impairment (eGFR <30 mL/min) | Day 1: 300 mg nirmatrelvir with 100 mg ritonavir once; Days 2-5: 150 mg nirmatrelvir with 100 mg ritonavir once daily |
Note: For patients on hemodialysis, administer after dialysis 1, 2
Contraindications
Paxlovid is contraindicated in patients with:
- History of clinically significant hypersensitivity reactions to nirmatrelvir or ritonavir
- Co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations may lead to serious/life-threatening reactions
- Co-administration with potent CYP3A inducers that may reduce nirmatrelvir/ritonavir concentrations 1, 2
Drug Interactions
- Ritonavir is a strong CYP3A inhibitor that can significantly increase serum levels of many medications
- Prior to prescribing, review all patient medications to assess potential drug-drug interactions
- Consider alternative COVID-19 treatments when significant drug interactions cannot be managed 1, 2
Efficacy
Paxlovid has demonstrated:
- 86% reduction in hospitalization risk
- 100% reduction in mortality compared to placebo in high-risk outpatients
- Real-world data shows 39-46% reduction in hospitalization risk and 61% reduction in mortality 1, 3, 4
Alternative Therapies When Paxlovid is Contraindicated
When Paxlovid cannot be used due to contraindications or drug interactions:
- Remdesivir - Requires intravenous administration over 3 days
- Molnupiravir - Less effective than Paxlovid and contraindicated in pregnancy 1
Special Populations
Immunocompromised Patients
- Patients with hematological malignancies or post-hematopoietic cell transplantation may particularly benefit from antiviral treatment due to prolonged viral phase 5
Pregnant Patients
- Paxlovid represents an option for pregnant people with COVID-19 to reduce disease progression risk
- Breastfeeding is not contraindicated during Paxlovid treatment 1
Common Adverse Effects
Monitoring and Follow-up
- Monitor for potential drug interactions throughout treatment course
- Assess for hypersensitivity reactions
- Monitor hepatic function in patients with pre-existing liver disease
- Be aware of potential COVID-19 rebound symptoms, though hospitalization after Paxlovid treatment is rare (<1% of patients) 1, 6