When should a patient take Paxlovid (nirmatrelvir/ritonavir) for COVID-19?

When to Take Paxlovid for COVID-19

Paxlovid should be administered to symptomatic patients with confirmed mild to moderate COVID-19 who are within 5 days of symptom onset and at high risk for progressing to severe disease. 1

Patient Selection Criteria

• Paxlovid is indicated for adults with mild-to-moderate COVID-19 who are at high risk for progression to severe disease, including hospitalization or death 2
• Treatment should be initiated as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset for optimal effectiveness 2
• High-risk factors that warrant Paxlovid treatment include:
  • Advanced age (especially ≥65 years) 3, 4
  • Underlying medical conditions that increase risk for severe COVID-19 3
  • Unvaccinated or incompletely vaccinated status 4

Dosing and Administration

• 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 are required for patients with 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 for patients with severe hepatic impairment (Child-Pugh Class C) 2

Effectiveness and Benefits

• Recent studies show Paxlovid reduces the risk of hospitalization by 39% and death by 61% when administered within 5 days of symptom onset 4
• Effectiveness has been demonstrated even in the era of Omicron subvariants 4
• The absolute risk reduction is particularly significant in patients aged 65 years and older 4
• Hospitalization and emergency department visits after Paxlovid treatment are rare (<1% of patients) 3

Important Drug Interaction Considerations

• Ritonavir, a component of Paxlovid, is a strong CYP3A inhibitor that causes many drug-drug interactions 5, 6
• Before prescribing Paxlovid:
  • Review all medications taken by the patient to assess potential drug-drug interactions 2
  • Use resources like the Liverpool COVID-19 Drug Interaction Tool to check for specific interactions 5, 6
  • Determine if concomitant medications require dose adjustment, interruption, or additional monitoring 2
• Contraindicated medications include certain:
  • Antiarrhythmics (amiodarone, flecainide, propafenone) 6
  • Anticoagulants (rivaroxaban) 6
  • Statins (lovastatin, simvastatin) 6
  • Other drugs highly dependent on CYP3A for clearance where elevated concentrations could lead to serious reactions 2

Monitoring and Follow-up

• Monitor patients for common adverse effects, including:
  • Dysgeusia (altered taste) 5, 2
  • Diarrhea 5, 2
  • Potential hepatotoxicity 5, 6
• For patients who must continue interacting medications during Paxlovid treatment, close monitoring for adverse effects is essential 6

Special Considerations

• Some evidence suggests Paxlovid may still be effective when initiated beyond 5 days (up to 10 days) after symptom onset, particularly when patients still have a high viral load 7
• However, the FDA-approved indication and strongest evidence support initiation within the first 5 days 2
• Treatment disparities exist, with lower rates of Paxlovid use among Black and Hispanic/Latino patients and those in socially vulnerable communities 4