What are the guidelines for ordering Paxlovid (nirmatrelvir/ritonavir) for COVID-19 treatment?

Guidelines for Ordering Paxlovid (Nirmatrelvir/Ritonavir) for COVID-19 Treatment

Paxlovid should be initiated as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset in patients with mild to moderate COVID-19 who are at high risk for progression to severe disease. 1

Patient Selection

High-Risk Patients (Strong Recommendation)

• Adults with mild-to-moderate COVID-19 at high risk for progression to severe disease, including:
  • Advanced age (especially ≥65 years)
  • Uncontrolled chronic medical conditions
  • Immunocompromised status
  • Unvaccinated status
  • Pregnancy 1

Risk Stratification

• High-risk patients: Strong recommendation for treatment
• Moderate-risk patients: Conditional recommendation for treatment
• Low-risk patients: Not recommended for treatment 1

Timing and Administration

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

Dosage Adjustments

Renal Impairment

• Moderate renal impairment (eGFR ≥30 to <60 mL/min):
  • 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days 1, 2
• Severe renal 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 2
  • For patients on hemodialysis, administer after hemodialysis 2

Hepatic Impairment

• Not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 1, 2

Drug Interaction Screening (Critical Step)

WARNING: Significant Drug Interactions

• Prior to prescribing Paxlovid, you must:
  1. Review all medications the patient is taking to assess potential drug-drug interactions
  2. Determine if concomitant medications require dose adjustment, temporary interruption, or additional monitoring 2, 3

Management of Drug Interactions

• Use the Liverpool COVID-19 Drug Interaction Tool to check potential interactions 1
• Options for managing interactions include:
  • Dose adjustment of concomitant medication
  • Temporary interruption of concomitant medication
  • Additional monitoring
  • Selection of alternative COVID-19 treatment if interactions cannot be managed 3

Efficacy and Benefits

• Reduces hospitalization risk by 39% and death risk by 61% 1, 4
• Absolute risk reduction of 0.9 percentage points for hospitalization and 0.2 percentage points for death 4
• Benefits observed across all age groups, but particularly significant in patients aged 65+ years 1, 4
• Effective in both vaccinated and unvaccinated patients 1, 4

Alternative Treatments

When Paxlovid is contraindicated due to drug interactions or other reasons:

• Remdesivir: Consider for patients ≥12 years with weight ≥40 kg, administered intravenously over 3 days 1
• Molnupiravir: Less effective than Paxlovid but can be considered when other options are unavailable 1

Common Pitfalls to Avoid

1. Failure to screen for drug interactions: This is the most critical potential error when prescribing Paxlovid
2. Delayed initiation: Efficacy decreases when started beyond 5 days of symptom onset
3. Improper dosing in renal impairment: Dose must be adjusted based on renal function
4. Inappropriate use of antibiotics: Avoid unless bacterial infection is suspected
5. Off-label use: Should be discouraged outside of approved indications 1

Monitoring After Prescription

• Monitor for potential COVID-19 rebound (recurrence of symptoms or positive test after initial improvement)
• While rebound may occur, severe outcomes after Paxlovid treatment are rare (<1% of patients require hospitalization or ED visits in the 5-15 days after treatment) 5