What is the recommended treatment regimen for Lagevrio (molnupiravir) in adults with mild to moderate COVID-19?

Lagevrio (Molnupiravir) Treatment Regimen for COVID-19

For adults with mild to moderate COVID-19, Lagevrio (molnupiravir) should be administered as 800 mg (four 200 mg capsules) taken orally every 12 hours for 5 days, and must be initiated within 5 days of symptom onset. 1, 2

Patient Selection

Molnupiravir is recommended differently based on patient risk stratification:

1. High-risk patients: Conditional recommendation FOR use 1

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

2. Moderate-risk patients: Conditional recommendation AGAINST use 1

3. Low-risk patients: Strong recommendation AGAINST use 1

Efficacy and Considerations

Molnupiravir has demonstrated:

• Reduction in hospitalization risk (7.3% vs 14.1% in placebo group) 2
• Probable reduction in mortality (RR 0.43, moderate certainty evidence) 3
• Faster normalization of inflammatory markers (CRP) and oxygen saturation 4
• Decreased need for respiratory interventions (RRR 34.3%) 4

Important Clinical Considerations

Prioritization of Treatments

• Nirmatrelvir/ritonavir (Paxlovid) and remdesivir are superior choices to molnupiravir due to:
  • Greater reductions in hospitalization
  • Fewer safety concerns 1, 5
  • Use molnupiravir only when these preferred options are contraindicated or unavailable

Safety Concerns

• Potential mutagenic effects based on mechanism of action
• Contraindicated in pregnancy due to mutagenesis concerns 5
• Not recommended for children 5
• Long-term safety data is limited 1

Timing of Treatment

• Must be initiated within 5 days of symptom onset for maximum efficacy 5, 2
• Earlier treatment associated with better outcomes

Monitoring

• No specific laboratory monitoring required during treatment
• No dose adjustments needed for renal or hepatic impairment

Common Adverse Effects

• Generally well-tolerated with similar adverse event rates to placebo (30.4% vs 33.0%) 2
• Most common side effects include:
  • Diarrhea
  • Nausea
  • Dizziness

Clinical Pitfalls to Avoid

1. Inappropriate patient selection: Using molnupiravir in low-risk patients where risks outweigh benefits 1

2. Delayed initiation: Starting treatment beyond 5 days of symptom onset significantly reduces efficacy 5, 2

3. Use in pregnancy: Molnupiravir should not be used during pregnancy due to potential fetal harm 5

4. Overreliance on molnupiravir: Consider it a third-line option after nirmatrelvir/ritonavir and remdesivir when possible 1, 5

5. Inappropriate antibiotic use: Antibiotics should not be prescribed following COVID-19 treatment unless there is clear evidence of bacterial infection 5

The evidence consistently shows that while molnupiravir provides benefit for high-risk patients with mild to moderate COVID-19, it should be considered after other more effective antivirals when possible, and treatment must begin within 5 days of symptom onset.