What are the criteria for prescribing Paxlovid (nirmatrelvir/ritonavir) for COVID-19 positive patients?

Criteria for Prescribing Paxlovid for COVID-19 Positive Patients

Paxlovid (nirmatrelvir/ritonavir) is indicated for adults with confirmed mild-to-moderate COVID-19 who are at high risk for progression to severe disease, including hospitalization or death, and should be initiated as soon as possible after diagnosis and within 5 days of symptom onset.

High-Risk Patient Populations

• Paxlovid is specifically indicated for adults with confirmed mild-to-moderate COVID-19 who are at high risk for progressing to severe disease 1, 2
• Treatment should be initiated as soon as possible after diagnosis and within 5 days of symptom onset for maximum effectiveness 2
• High-risk factors include:
  • Advanced age, particularly those 65 years and older 3, 4
  • Underlying medical conditions that increase risk for severe COVID-19 1, 4
  • Hematological malignancies or history of hematopoietic cell transplantation 1
  • Immunosuppression or immunocompromised status 1

Contraindications and Precautions

• Paxlovid is contraindicated in patients with:

  • History of clinically significant hypersensitivity reactions to nirmatrelvir or ritonavir 2
  • Co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations could lead to serious reactions 2
  • Co-administration with potent CYP3A inducers that may reduce nirmatrelvir or ritonavir plasma concentrations 2

• Before prescribing Paxlovid:

  • Review all medications taken by the patient to assess potential drug-drug interactions 2
  • Determine if concomitant medications require dose adjustment, interruption, or additional monitoring 2

Dosage Recommendations

• Standard dosage: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all 3 tablets taken together twice daily for 5 days 2

• Dose adjustments for renal impairment:

  • Moderate renal impairment (eGFR ≥30 to <60 mL/min): 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days 2
  • Severe renal impairment (eGFR <30 mL/min): 300 mg nirmatrelvir with 100 mg ritonavir once on day 1, followed by 150 mg nirmatrelvir with 100 mg ritonavir once daily for days 2-5 2

• Paxlovid is not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 2

Clinical Evidence for Effectiveness

• Real-world data demonstrates that Paxlovid reduces the risk of hospitalization by 39% and death by 61% among eligible patients 3
• The absolute risk reduction for hospitalization is approximately 0.9 percentage points overall, with greater benefit observed in patients aged 65 years and older 3, 4
• Effectiveness has been demonstrated across vaccination status groups, including those who have received ≥3 mRNA COVID-19 vaccines 4
• Hospitalization or emergency department encounters for COVID-19 during the 5-15 days after Paxlovid treatment are rare (<1% of patients) 5

Special Considerations

• Drug interactions must be carefully evaluated before prescribing due to ritonavir being a strong CYP3A inhibitor 2
• Paxlovid may also reduce the incidence of post-COVID-19 condition (long COVID) 1
• Disparities in Paxlovid treatment have been observed, with lower rates among Black and Hispanic or Latino patients and within socially vulnerable communities 3
• Plasma concentrations of nirmatrelvir and ritonavir may be higher than reference values in patients with advanced age and those taking renally excreted medications 6

Alternative Therapies

• For patients who cannot take Paxlovid due to contraindications or drug interactions, alternative therapies include:
  • Remdesivir for patients with mild-to-moderate COVID-19 at high risk for progression 1
  • Molnupiravir, though it has less efficacy than Paxlovid 1, 7

Common Pitfalls to Avoid

• Delaying treatment beyond 5 days of symptom onset significantly reduces effectiveness 2
• Failing to thoroughly review potential drug-drug interactions before prescribing 2
• Inappropriate dosing in patients with renal impairment 2
• Not considering Paxlovid for vaccinated patients, as the medication remains effective regardless of vaccination status 3, 4