Recommended Treatment Regimen for COVID-19 Using Paxlovid
The standard treatment regimen for COVID-19 using Paxlovid (nirmatrelvir/ritonavir) 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 within 5 days of symptom onset in high-risk patients with mild to moderate COVID-19. 1, 2
Patient Selection and Timing
- Paxlovid is indicated for adults with mild-to-moderate COVID-19 who are at high risk for progression to severe disease 3, 1
- High-risk patients include those with:
- Advanced age (especially ≥65 years)
- Uncontrolled chronic medical conditions
- Immunocompromised status
- Unvaccinated status
- Pregnancy 1
- Treatment must be initiated within 5 days of symptom onset to maximize efficacy 1, 2
- Paxlovid has demonstrated an 86% reduction in hospitalization risk and significant reduction in mortality compared to placebo in high-risk outpatients 1, 4
Dosing Regimen
Standard Dosing
- 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet)
- All 3 tablets taken together twice daily
- 5-day treatment course
- Can be taken with or without food 2
- Administer at approximately the same time each day 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) including 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 |
Note: For patients on hemodialysis, the dose should be administered after hemodialysis 1, 2
Contraindications and Drug Interactions
Contraindications
- 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, 5
- Co-administration with potent CYP3A inducers 2
- Not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 2
Drug Interactions
- Ritonavir is a strong CYP3A inhibitor that can significantly increase serum levels of many medications 1, 5
- Prior to prescribing, review all patient medications to assess potential drug-drug interactions 2, 5
- High-risk medication classes include:
Monitoring and Adverse Effects
- Most common adverse effects:
- Dysgeusia (taste disturbance) (5%)
- Diarrhea (3%) 2
- Less common adverse effects:
- Headache
- Hypertension
- Abdominal pain
- Nausea
- Vomiting
- Malaise 2
- Monitor for hypersensitivity reactions including anaphylaxis, toxic epidermal necrolysis, and Stevens-Johnson syndrome 2
- Monitor for hepatotoxicity in patients with pre-existing liver disease 2
Alternative Treatment Options
If Paxlovid is contraindicated due to drug interactions or unavailable:
Molnupiravir: Consider as an alternative treatment, though less effective than Paxlovid 3, 1
- Must be initiated within 5 days of symptom onset
- Contraindicated in pregnancy
Remdesivir: Consider for patients with contraindications to Paxlovid 1, 6
- Requires intravenous administration over 3 days
- Has moderate evidence for reducing hospital admission
Important Clinical Considerations
- Paxlovid is not approved for pre-exposure or post-exposure prophylaxis 2
- Antibiotics are not indicated following Paxlovid treatment unless there is clear evidence of a secondary bacterial infection 1
- For patients with persistent COVID-19 symptoms after completing Paxlovid, avoid blind use of antibacterial drugs unless bacterial infection is suspected 1
- Consider the benefit of Paxlovid in reducing hospitalization and death against the risk of potential drug-drug interactions 2
By following this treatment regimen, healthcare providers can effectively administer Paxlovid to high-risk COVID-19 patients while minimizing adverse effects and drug interactions.