What are the alternatives to Paxlovid (nirmatrelvir/ritonavir) for the treatment of COVID-19?

Alternatives to Paxlovid for COVID-19 Treatment

Remdesivir is the best alternative to Paxlovid (nirmatrelvir/ritonavir) for the treatment of COVID-19 when Paxlovid is contraindicated or unavailable, followed by molnupiravir as a third-line option. 1

First-Line Treatment: Paxlovid

Paxlovid remains the preferred first-line treatment for COVID-19 in high-risk patients due to its superior efficacy:

• 86% reduction in hospitalization risk and 100% reduction in mortality compared to placebo 1
• 39% reduction in hospitalization risk and 61% reduction in death in real-world data 2
• Must be initiated within 5 days of symptom onset 1

Alternative Treatments When Paxlovid is Contraindicated

Second-Line: Remdesivir

• Dosing: Intravenous administration over 3 days 1, 3
  • Adults and pediatric patients ≥40kg: 200mg IV on day 1, followed by 100mg IV daily 3
  • Pediatric patients <40kg: Weight-based dosing 3
• Efficacy: Moderate certainty evidence for reducing hospital admission 1
• Timing: Must be initiated within 7 days of symptom onset 1
• Advantages: Option when Paxlovid is contraindicated due to drug interactions 1
• Considerations: Requires intravenous administration, making it less convenient than oral options 1

Third-Line: Molnupiravir

• Dosing: Oral administration for 5 days 1, 4
• Efficacy: Less effective than Paxlovid and remdesivir but still shows benefit in reducing mortality 1, 5
• Timing: Must be initiated within 5 days of symptom onset 1
• Advantages: No significant drug interactions, unlike Paxlovid 5
• Contraindications: Pregnancy (due to mutagenesis concerns) and children 1
• Safety concerns: Potential for viral mutagenesis and theoretical risk of host DNA mutation 5

Patient Selection for Alternatives

When to Consider Alternatives to Paxlovid:

1. Drug-drug interactions: Paxlovid (particularly ritonavir) is a strong CYP3A inhibitor that can significantly increase serum levels of many medications 1
2. Severe renal impairment: While no dosage adjustment is recommended, clinical judgment may favor alternatives in some cases 3
3. Hypersensitivity to nirmatrelvir or ritonavir 1
4. Availability issues: When Paxlovid is not accessible 1

High-Risk Patients Who Benefit Most from Antiviral Therapy:

• Advanced age (especially ≥65 years) 1, 2
• Uncontrolled chronic medical conditions 1
• Immunocompromised status 1
• Unvaccinated status 1
• Pregnancy (except for molnupiravir) 1

Ineffective Treatments to Avoid

The following treatments are not recommended for COVID-19:

• Ivermectin 1
• Sotrovimab 1
• Prophylactic antibiotics (unless clear evidence of bacterial infection) 1

Special Considerations

Moderate to Severe COVID-19

For patients requiring oxygen support:

• Dexamethasone: 6 mg once daily for up to 10 days 1
  • For moderate COVID-19 (requiring O₂ support, saturation >90%)
  • For severe COVID-19 (saturation <90-94%, respiratory rate >30/min)

Pregnancy

• Paxlovid is the preferred option 1
• Remdesivir is an acceptable alternative 1
• Molnupiravir is contraindicated 1, 5

Treatment Algorithm

1. Assess patient risk: Determine if patient is high-risk for progression to severe disease
2. Check timing: Ensure treatment can be initiated within appropriate timeframe (5 days for Paxlovid/molnupiravir, 7 days for remdesivir)
3. Evaluate for Paxlovid contraindications:
   • Review all medications for potential drug interactions
   • Check for hypersensitivity to components
4. Select treatment:
   • First choice: Paxlovid (if no contraindications)
   • Second choice: Remdesivir (if Paxlovid contraindicated)
   • Third choice: Molnupiravir (if both Paxlovid and remdesivir contraindicated, and patient is not pregnant or a child)
5. Monitor for adverse effects:
   • Paxlovid: Dysgeusia (taste disturbance) and diarrhea 1
   • Remdesivir: Potential kidney injury 3
   • Molnupiravir: Monitor for potential mutagenic effects 5