When is Paxlovid (nirmatrelvir and ritonavir) recommended for a patient with COVID-19?

When to Prescribe Paxlovid for COVID-19

Paxlovid (nirmatrelvir/ritonavir) is strongly recommended for adults with confirmed mild-to-moderate COVID-19 who are at high risk for progression to severe disease, initiated within 5 days of symptom onset. 1, 2, 3

Patient Selection Criteria

High-Risk Patients Who Should Receive Paxlovid

You should prescribe Paxlovid to patients meeting ALL of the following:

• Confirmed COVID-19 diagnosis (positive test) with mild-to-moderate symptoms 3
• Within 5 days of symptom onset - this timing is critical for effectiveness 4, 3
• At least one high-risk factor for progression to severe disease 2, 4

Defining High-Risk Factors

High-risk patients include those with: 2

• Immunocompromised status (including transplant recipients, active immunosuppressive therapy) 2
• Hematological malignancies or history of hematopoietic cell transplantation 2
• Unvaccinated status 4
• Advanced age (≥65 years) 5
• Multiple comorbidities (diabetes, cardiovascular disease, chronic kidney disease, chronic lung disease) 2

Patients Who Should NOT Receive Paxlovid

Do not prescribe Paxlovid for: 4

• Low-risk patients without risk factors for severe disease - the World Health Organization explicitly recommends against treatment in this population 1, 4
• Patients beyond 5 days of symptom onset - efficacy drops significantly after this window 4, 3
• Patients requiring supplemental oxygen or hospitalization - Paxlovid is indicated only for mild-to-moderate disease 3
• Patients with severe hepatic impairment (Child-Pugh Class C) 3

Critical Pre-Prescribing Requirements

Mandatory Drug Interaction Review

Before prescribing Paxlovid, you MUST conduct a comprehensive medication review because ritonavir is a potent CYP3A4 inhibitor that can cause life-threatening drug interactions. 3, 6

The FDA includes a boxed warning specifically about significant drug interactions - this is not optional screening. 3

Contraindicated medications include: 3

• Drugs highly dependent on CYP3A for clearance where elevated concentrations cause serious/life-threatening reactions
• Potent CYP3A inducers that may reduce Paxlovid effectiveness

Management options for problematic interactions: 6

• Temporarily pause the interacting medication during the 5-day treatment course
• Switch to an alternative COVID-19 therapy (remdesivir or molnupiravir) 7

Renal Function Assessment

Dose adjustment is required based on kidney function: 3

• Normal renal function (eGFR ≥60): Standard dose - 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir twice daily for 5 days 3

• Moderate impairment (eGFR 30-59): Reduced dose - 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir twice daily for 5 days 3

• Severe impairment (eGFR <30) including hemodialysis:

  • Day 1: 300 mg nirmatrelvir with 100 mg ritonavir once daily
  • Days 2-5: 150 mg nirmatrelvir with 100 mg ritonavir once daily
  • Administer after hemodialysis on dialysis days 3

Administration Details

Dosing instructions: 3

• Take all three tablets together (two nirmatrelvir + one ritonavir) twice daily
• Can be taken with or without food
• Administer at approximately the same time each day
• Complete the full 5-day course

Evidence of Effectiveness

Real-world effectiveness data demonstrates: 5

• 39% relative risk reduction in hospitalization (0.9 percentage point absolute risk reduction)
• 61% relative risk reduction in death (0.2 percentage point absolute risk reduction)
• Benefits observed in both vaccinated and unvaccinated patients
• Greatest absolute benefit in patients aged ≥65 years

The evidence shows Paxlovid remains effective against Omicron subvariants through August 2023. 5

Alternative Therapies When Paxlovid Is Not Suitable

If Paxlovid cannot be used due to drug interactions or contraindications: 1, 7

• Remdesivir (3-day IV course) - preferred alternative, particularly for patients with problematic drug interactions or pregnancy 1, 7
• Molnupiravir - less effective than Paxlovid but oral option when others unavailable 1, 7

The WHO guidelines indicate nirmatrelvir/ritonavir is superior to molnupiravir based on indirect comparisons showing greater reduction in hospitalization. 1

Common Pitfalls to Avoid

• Do not prescribe to all COVID-positive patients - only those at high risk benefit, and low-risk patients face unnecessary drug interaction risks 4
• Do not delay beyond 5 days - effectiveness diminishes significantly after this window 4, 3
• Do not skip the medication review - the boxed warning exists because serious adverse events can occur from drug interactions 3
• Do not forget renal dose adjustments - standard dosing in severe renal impairment can lead to toxicity 3
• Do not use for pre- or post-exposure prophylaxis - this is not an approved indication 3

Special Populations

Pregnant and breastfeeding patients: The American College of Physicians and WHO indicate these patients may consider Paxlovid use, though this requires shared decision-making about potential risks versus benefits. 1

HIV-positive patients: Be aware that Paxlovid may lead to HIV-1 protease inhibitor resistance in individuals with uncontrolled or undiagnosed HIV-1 infection. 3