When should Paxlovid (nirmatrelvir/ritonavir) be started in patients with COVID-19?

When to Start Paxlovid for COVID-19 Treatment

Paxlovid (nirmatrelvir/ritonavir) must be initiated as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset to effectively reduce the risk of hospitalization and death in high-risk patients. 1, 2

Patient Selection and Timing

• Paxlovid is indicated for treatment of mild-to-moderate COVID-19 in adults at high risk for progression to severe disease 1
• High-risk patients include:
  • Advanced age (especially ≥65 years)
  • Uncontrolled chronic medical conditions
  • Immunocompromised status
  • Unvaccinated status
  • Pregnancy 1

Critical Timing Considerations

• The 5-day treatment course must be initiated within 5 days of symptom onset 1, 2
• Earlier initiation is associated with better outcomes
• The FDA label specifically states treatment should begin "as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset" 2
• Completion of the full 5-day treatment course is important to maximize viral clearance 2

Effectiveness Based on Timing

• Real-world data shows Paxlovid reduces hospitalization risk by 39% and death risk by 61% in high-risk patients when started within the recommended timeframe 3
• Benefits are observed across all age groups but are particularly significant in patients aged 65+ years 1
• Paxlovid is effective in both vaccinated and unvaccinated patients 3

Administration Protocol

• 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
• Dose adjustments required for patients with renal impairment 1, 2
• Can be taken with or without food 2
• Tablets should be swallowed whole and not chewed, broken, or crushed 2

Important Precautions Before Prescribing

• Review all medications to assess potential drug-drug interactions with ritonavir (a strong CYP3A inhibitor) 1, 2
• Determine if concomitant medications require dose adjustment, interruption, or additional monitoring 2
• The Liverpool COVID-19 Drug Interaction Tool is recommended for checking potential interactions 1
• Paxlovid is contraindicated in patients with history of clinically significant hypersensitivity reactions to nirmatrelvir or ritonavir 1

Special Considerations

• For patients who require hospitalization due to severe COVID-19 after starting Paxlovid, the full 5-day treatment course should still be completed per healthcare provider's discretion 2
• If a patient misses a dose within 8 hours of the usual time, they should take it as soon as possible; if more than 8 hours have passed, they should skip that dose and take the next dose at the regular time 2
• Patients should not double the dose to make up for a missed dose 2

While one study suggests potential benefits of Paxlovid even when started after 5 days in patients with high viral loads 4, the strongest evidence and official guidelines firmly support initiating treatment within the 5-day window from symptom onset for optimal effectiveness.