Which patients should receive Paxlovid (nirmatrelvir/ritonavir)?

Paxlovid (Nirmatrelvir/Ritonavir) Treatment Recommendations

Paxlovid should be prescribed to high-risk patients with COVID-19 within 5 days of symptom onset, including those aged ≥65 years, those with uncontrolled chronic medical conditions, immunocompromised individuals, unvaccinated persons, and pregnant people. 1

Patient Selection Criteria

High-Risk Patients (Strong Recommendation for Treatment)

High-risk patients who will benefit most from Paxlovid include:

• Adults aged ≥65 years 1, 2
• Patients with at least one of the following risk factors 2:
  • Diabetes
  • Overweight (BMI >25)
  • Chronic lung disease (including asthma)
  • Chronic kidney disease
  • Current smoker
  • Immunosuppressive disease or immunosuppressive treatment
  • Cardiovascular disease
  • Hypertension
  • Sickle cell disease
  • Neurodevelopmental disorders
  • Active cancer
  • Medically-related technological dependence

Paxlovid demonstrated an 86% reduction in hospitalization risk and prevented mortality in high-risk outpatients with mild-to-moderate COVID-19 1, 2.

Moderate-Risk Patients (Conditional Recommendation for Treatment)

For patients with non-severe COVID-19 at moderate risk of hospitalization, Paxlovid is suggested as a treatment option 3. Real-world data shows Paxlovid reduces hospitalization rates across all age groups, including those 18-49 years (aHR = 0.59) and 50-64 years (aHR = 0.40) 4.

Low-Risk Patients (Recommendation Against Treatment)

For patients with non-severe COVID-19 at low risk of hospitalization, Paxlovid is not recommended 3. The benefits in this population are considered trivial compared to potential risks.

Timing and Administration

• Treatment must be initiated within 5 days of symptom onset 1, 2
• Standard dosing: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) taken together twice daily for 5 days 1, 2
• Administer orally with or without food at approximately the same time each day 2

Renal Dose Adjustments

Renal function must be assessed before prescribing. Dose adjustments are required for patients with renal impairment 1, 2:

• Moderate impairment (eGFR 30-60 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

Contraindications and Drug Interactions

Paxlovid is contraindicated in patients with:

• History of hypersensitivity to nirmatrelvir or ritonavir 1
• Significant drug-drug interactions 1, 5
• Co-administration with drugs highly dependent on CYP3A for clearance or potent CYP3A inducers 1, 5

Prior to prescribing, all patient medications must be reviewed for potential drug-drug interactions, as ritonavir is a strong CYP3A inhibitor that can significantly increase serum levels of many medications 1, 5.

Special Populations

Pregnant and Breastfeeding Women

• Paxlovid represents a treatment option for pregnant people with COVID-19 1
• Breastfeeding is not contraindicated during Paxlovid treatment 1

Elderly Patients

• Elderly patients (≥65 years) show significant benefit from Paxlovid treatment 6, 7
• Real-world data shows reduced hospitalization (aHR = 0.53) in patients ≥65 years 4
• In elderly patients (median age 82), Paxlovid reduced hospital stay from 15 to 13 days and viral shedding time from 20 to 16.5 days 7

Efficacy and Safety

• Clinical trials showed 86% relative risk reduction in hospitalization and death compared to placebo 2
• Real-world effectiveness studies demonstrate 39% reduction in hospitalization risk and 61% reduction in death risk 6
• Less than 1% of patients treated with Paxlovid require hospitalization or emergency department visits for COVID-19 during the 5-15 days after treatment 8
• Most common adverse effects are dysgeusia (taste disturbance) and diarrhea 1

Alternative Treatments When Paxlovid is Contraindicated

When Paxlovid is contraindicated due to drug interactions or unavailable:

1. Remdesivir: May be considered as an alternative, requiring intravenous administration over 3 days 1
2. Molnupiravir: May be considered when Paxlovid and remdesivir are not options, but is less effective and contraindicated in pregnancy 1

Important Considerations

• Paxlovid is effective against all SARS-CoV-2 variants, including Omicron subvariants 6
• Vaccinated patients still benefit from Paxlovid treatment (aHR = 0.50 for those with ≥3 mRNA COVID-19 vaccines) 4
• "COVID rebound" (recurrence of symptoms or positive test after initial improvement) may occur in a small percentage of patients but is rarely associated with severe outcomes 8
• Antibiotics should not be prescribed following Paxlovid treatment unless there is clear evidence of a secondary bacterial infection 1

By following these recommendations, clinicians can appropriately select patients who will benefit most from Paxlovid while minimizing potential risks from drug interactions.