What are the guidelines for ordering Paxlovid (nirmatrelvir and ritonavir) for a patient with COVID-19?

Guidelines for Ordering Paxlovid (Nirmatrelvir and Ritonavir) for COVID-19 Patients

Paxlovid should be prescribed for patients with mild-to-moderate COVID-19 who are at high risk for progression to severe disease, and must be initiated within 5 days of symptom onset. 1

Patient Selection Criteria

High-Risk Patients Who Should Be Considered for Paxlovid

• Adults with confirmed COVID-19 who are:
  • ≥65 years of age
  • Unvaccinated or partially vaccinated
  • Have underlying medical conditions (e.g., cardiovascular disease, diabetes, chronic lung disease)
  • Immunocompromised
  • Pregnant

Timing Requirements

• Treatment must be initiated within 5 days of symptom onset
• Earlier treatment is associated with better outcomes

Prescribing Process

Step 1: Confirm COVID-19 Diagnosis

• Verify positive COVID-19 test result (PCR or rapid antigen test)
• Assess symptom onset timing to ensure within 5-day window

Step 2: Assess Risk Factors

• Determine if patient meets high-risk criteria
• Review medical history for conditions that increase risk for severe COVID-19

Step 3: Medication Review

• Critical step: Review all medications to assess potential drug-drug interactions 2
• Use the Liverpool COVID-19 Drug Interaction Tool to check for interactions
• Identify medications that are contraindicated with Paxlovid

Step 4: Evaluate Renal Function

• Check eGFR and adjust dosing accordingly:
  • Normal renal function: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) twice daily for 5 days
  • 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): 300 mg nirmatrelvir with 100 mg ritonavir on Day 1, followed by 150 mg nirmatrelvir with 100 mg ritonavir once daily on Days 2-5 1, 2

Step 5: Assess for Contraindications

• History of hypersensitivity to nirmatrelvir or ritonavir
• Severe hepatic impairment (Child-Pugh Class C)
• Concomitant use of drugs highly dependent on CYP3A for clearance
• Concomitant use of potent CYP3A inducers 2

Dosing and Administration Instructions

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

Administration Guidelines

• Can be taken with or without food
• Should be taken at approximately the same time each day
• Complete the full 5-day treatment course

Managing Drug Interactions

High-Risk Interactions

• Ritonavir is a strong CYP3A inhibitor that can significantly increase serum levels of many medications
• For medications with serious interaction potential:
  • Temporarily hold medication during Paxlovid treatment if clinically appropriate
  • Adjust dose of concomitant medication
  • Consider alternative COVID-19 treatment if interaction cannot be managed

Common Problematic Drug Classes

• Antiarrhythmics
• Anticoagulants
• Immunosuppressants
• Statins
• Sedatives/hypnotics
• Certain antipsychotics

Clinical Benefits and Outcomes

• Paxlovid reduces hospitalization risk by 39% and death risk by 61% in high-risk patients 1
• Benefits are observed across all age groups but are particularly significant in patients aged 65+ years
• Effective in both vaccinated and unvaccinated patients 3
• May reduce the incidence of long COVID by 25% 1
• Hospitalization or ED encounters after Paxlovid treatment are rare (<1% of patients) 4

Alternative Treatment Options

If Paxlovid is contraindicated due to drug interactions or other factors:

• Remdesivir: Requires intravenous administration over 3 days
• Molnupiravir: Less effective than Paxlovid but can be considered when other options are unavailable 1

Common Pitfalls to Avoid

• Failing to screen for drug interactions, which can lead to serious adverse events
• Initiating treatment beyond the 5-day window from symptom onset
• Incorrect dosing adjustments for patients with renal impairment
• Not completing the full 5-day treatment course
• Overlooking potential contraindications

By following these guidelines, healthcare providers can appropriately prescribe Paxlovid to high-risk COVID-19 patients, potentially reducing their risk of hospitalization and death while managing potential drug interactions and other safety considerations.