What is the efficacy of Paxlovid (nirmatrelvir/ritonavir) in treating COVID-19?

Paxlovid Efficacy in COVID-19 Treatment

Paxlovid (nirmatrelvir/ritonavir) significantly reduces hospitalization risk by 39% and mortality by 61% in high-risk COVID-19 patients when initiated within 5 days of symptom onset. 1

Patient Selection and Efficacy

High-Risk Patients

• Strong recommendation for use in high-risk patients including those with:

  • Advanced age (especially ≥65 years)
  • Uncontrolled chronic medical conditions
  • Immunocompromised status
  • Unvaccinated status 2, 3

• The efficacy in high-risk patients is substantial:

  • 39% reduction in hospitalization risk 1
  • 61% reduction in mortality 1
  • Greatest absolute benefit observed in patients ≥65 years 1

Moderate-Risk Patients

• Conditional recommendation for use in patients with non-severe COVID-19 at moderate risk of hospitalization 2
• Provides important reduction in hospitalization risk, though smaller than in high-risk patients 2

Low-Risk Patients

• Not recommended for patients at low risk of hospitalization 2
• Benefits are considered trivial in this population (high certainty evidence) 2

Treatment Protocol

• Treatment must be initiated within 5 days of symptom onset 3, 4
• Standard dosage: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) twice daily for 5 days 4
• Dose adjustments required for renal impairment:
  • Moderate impairment (eGFR ≥30 to <60 mL/min): 150 mg nirmatrelvir with 100 mg ritonavir twice daily 3, 4
  • Severe impairment (eGFR <30 mL/min): 300 mg nirmatrelvir with 100 mg ritonavir once on day 1, then 150 mg nirmatrelvir with 100 mg ritonavir once daily for days 2-5 4

Real-World Effectiveness

• Multiple real-world studies confirm Paxlovid's effectiveness:

  • A large U.S. electronic health record study found 39% reduction in hospitalization risk and 61% reduction in mortality risk 1
  • A study from Israel demonstrated a 46% reduction in severe COVID-19 or mortality (adjusted HR 0.54,95% CI 0.39-0.75) 5
  • A Chinese study showed significant reduction in 28-day mortality, particularly in severe COVID-19 patients 6

• However, some studies show variable results:

  • A Malaysian study did not find statistically significant differences in 28-day hospitalization or all-cause death 7

Special Considerations

Drug Interactions

• Major concern: Ritonavir is a strong CYP3A inhibitor that can cause significant drug-drug interactions 3, 4
• Before prescribing:
  1. Review all patient medications
  2. Determine if dose adjustments, interruptions, or additional monitoring is needed
  3. Consider using the Liverpool COVID-19 Drug Interaction Tool 3

Pregnancy and Breastfeeding

• Paxlovid can be considered for pregnant or breastfeeding individuals with non-severe COVID-19 2, 3
• No reports of serious adverse reactions in pregnant or breastfeeding individuals have been documented in WHO Vigibase 3

Immunocompromised Patients

• May have increased benefit due to prolonged viral phase 2
• Particularly effective in immunosuppressed patients (significant interaction effect) 5

Alternative Treatments When Paxlovid Is Contraindicated

• Remdesivir: Requires intravenous administration over 3 days; consider when Paxlovid is contraindicated due to drug interactions 2, 3
• Molnupiravir: Less effective than Paxlovid but can be considered when other options are unavailable 2, 3

Safety Profile

• Most common adverse reactions (≥1% incidence):
  • Dysgeusia (altered taste)
  • Diarrhea 4
• Rare but serious adverse events:
  • Hypersensitivity reactions
  • Hepatotoxicity 4
• COVID-19 rebound (recurrence of symptoms or positive test after initial recovery) has been reported but is rare 8

Clinical Pitfalls to Avoid

1. Delayed initiation: Efficacy decreases when started beyond 5 days of symptom onset
2. Missing drug interactions: Always screen for potential interactions before prescribing
3. Inappropriate use in low-risk patients: Benefits are trivial in this population
4. Failure to adjust dosing in renal impairment: Can lead to toxicity
5. Combining with other antiviral therapies: No evidence supports combination therapy 2