When can you treat COVID-19 (Coronavirus disease 2019) with Paxlovid (nirmatrelvir/ritonavir)?

When to Treat COVID-19 with Paxlovid

Paxlovid (nirmatrelvir/ritonavir) should be prescribed to symptomatic patients with confirmed mild to moderate COVID-19 who are within 5 days of symptom onset and at high risk for progressing to severe disease. 1, 2

Patient Selection Criteria

High-Risk Patients (Strong Recommendation)

• Advanced age (especially ≥65 years)
• Uncontrolled chronic medical conditions
• Immunocompromised status
• Unvaccinated status 2

Moderate-Risk Patients (Conditional Recommendation)

• May be considered for treatment due to reduction in hospitalization risk, though benefit is smaller than in high-risk patients 2

Low-Risk Patients (Not Recommended)

• Patients at low risk of hospitalization should not receive Paxlovid as benefits are considered trivial 2

Timing of Treatment

• Must be initiated within 5 days of symptom onset 1, 2, 3
• Earlier treatment is associated with better outcomes
• Treatment should begin as soon as possible after diagnosis 3

Standard Dosage Regimen

• 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet)
• Taken together twice daily for 5 days
• Can be administered with or without food 3

Dose Adjustments for Special Populations

Renal Impairment 3

• Moderate renal impairment (eGFR ≥30 to <60 mL/min):

  • 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days

• Severe renal 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
  • For hemodialysis patients, administer after dialysis

Hepatic Impairment

• Not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 3

Drug Interactions

• Ritonavir is a strong CYP3A inhibitor that can cause significant drug-drug interactions 2, 3
• Prior to prescribing:
  1. Review all medications taken by the patient
  2. Determine if concomitant medications require dose adjustment, interruption, or additional monitoring
• Use the Liverpool COVID-19 Drug Interaction Tool to check potential interactions 2

Clinical Evidence Supporting Use

Recent evidence shows Paxlovid reduces:

• All-cause mortality (61% reduction) 4
• Hospitalization risk (39% reduction) 4
• Emergency department visits 5

A large electronic health record study of 703,647 patients showed an absolute risk reduction of 0.9 percentage points for hospitalization and 0.2 percentage points for death 4. This benefit was observed across all age groups but was particularly significant in patients aged 65+ years.

Alternative Therapies When Paxlovid is Contraindicated

• Remdesivir (requires intravenous administration over 3 days)
• Molnupiravir (less effective than Paxlovid but can be considered when other options are unavailable) 2

Common Pitfalls and Caveats

1. Delayed treatment: Efficacy significantly decreases if started beyond 5 days of symptom onset
2. Drug interactions: Failure to check for significant drug-drug interactions
3. COVID-19 rebound: Symptom recurrence may occur after treatment completion but is rarely severe 6
4. Inappropriate use in low-risk patients: Limited benefit in patients without risk factors for severe disease
5. Incorrect dosing in renal impairment: Failure to adjust dose based on kidney function

Special Considerations

• Pregnant or breastfeeding individuals with non-severe COVID-19 can be considered for treatment 2
• Immunocompromised patients, including those with hematological malignancies, may particularly benefit from treatment 2
• Avoid combining with other antiviral therapies 2

Paxlovid has demonstrated significant benefits in reducing hospitalization and death in high-risk patients when administered early in the course of COVID-19 infection, making it an important treatment option for appropriate patients.