What are the considerations for using Paxlovid (nirmatrelvir/ritonavir) in treating COVID-19?

Paxlovid (Nirmatrelvir/Ritonavir) Considerations for COVID-19 Treatment

Paxlovid should be prescribed for patients with mild-to-moderate COVID-19 who are at high risk for progression to severe disease, as it demonstrates an 86% reduction in hospitalization risk and 100% reduction in mortality compared to placebo. 1

Patient Selection

Recommended for:

• Adults with mild-to-moderate COVID-19 at moderate-to-high risk of hospitalization 1, 2
• Patients with the following risk factors:
  • Advanced age (especially ≥65 years)
  • Uncontrolled chronic medical conditions
  • Immunocompromised status
  • Unvaccinated status
  • Pregnancy 1

Not recommended for:

• Patients with mild-to-moderate COVID-19 at low risk of hospitalization 1
• Patients with severe hepatic impairment (Child-Pugh Class C) 2
• Pre-exposure or post-exposure prophylaxis 2

Treatment Timing and Regimen

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

Renal Dose Adjustments:

• Moderate impairment (eGFR 30-60 mL/min): 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days 1, 2
• 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 1, 2
  • For hemodialysis patients, administer after dialysis 2

Drug Interactions - Critical Consideration

Paxlovid contains ritonavir, a strong CYP3A inhibitor, which can cause significant drug interactions. This is so important that it carries a boxed warning in the FDA label 2.

Before prescribing:

1. Review all patient medications to assess potential drug-drug interactions
2. Determine if concomitant medications require dose adjustment, interruption, or additional monitoring 2

Contraindicated with:

• Drugs highly dependent on CYP3A for clearance where elevated concentrations could lead to serious/life-threatening reactions 2
• Potent CYP3A inducers that could reduce nirmatrelvir/ritonavir concentrations 2

Common interacting drug classes:

• Corticosteroids
• Narcotic analgesics
• Anticoagulants
• Statins
• Sedatives/hypnotics 3

Efficacy and Safety

Efficacy:

• 39% reduction in hospitalization risk in real-world data 4
• 61% reduction in risk of death 4
• Effective even in vaccinated patients 5, 4
• Greatest absolute risk reduction in patients aged ≥65 years 4

Safety:

• Most common adverse effects: dysgeusia (taste disturbance) and diarrhea 1, 2
• Potential for hypersensitivity reactions including anaphylaxis 2
• Hepatotoxicity risk (transaminase elevations, clinical hepatitis, jaundice) 2
• COVID-19 rebound (recurrence of symptoms or positive test after initial improvement) has been reported but rarely leads to hospitalization 6

Special Populations

Pregnancy:

• Paxlovid represents a treatment option for pregnant people with COVID-19 1

HIV:

• Risk of HIV-1 developing resistance to protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection 2

Alternative Treatments

When Paxlovid is contraindicated or unavailable:

• Remdesivir (requires IV administration over 3 days) 1
• Molnupiravir (less effective than Paxlovid and contraindicated in pregnancy) 1

Important Caveats

• Antibiotics are not indicated following Paxlovid treatment unless there is clear evidence of a secondary bacterial infection 1
• Disparities in Paxlovid treatment have been observed, with lower rates among Black and Hispanic/Latino patients and within socially vulnerable communities 4
• The benefit of Paxlovid treatment must be weighed against the risk of potential drug-drug interactions for each individual patient 2