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

Molnupiravir Treatment Regimen for COVID-19

Molnupiravir should be administered as 800 mg orally every 12 hours for 5 days, initiated within 5 days of symptom onset, and reserved exclusively for high-risk adults with mild-to-moderate COVID-19 who cannot receive nirmatrelvir/ritonavir (Paxlovid). 1

Dosing Protocol

• Standard dose: 800 mg orally twice daily (every 12 hours) for 5 consecutive days 1
• Timing is critical: Must be started within 5 days of symptom onset for optimal effectiveness 1, 2
• No dose adjustment needed: Safe to use without modification in patients with hepatic or renal impairment, including severe renal disease 3

Patient Selection Criteria

High-Risk Patients (Treatment Recommended)

Consider molnupiravir ONLY for patients meeting ALL of the following: 1, 2

• Confirmed mild-to-moderate COVID-19
• Within 5 days of symptom onset
• High risk for progression to severe disease (age ≥60 years, immunosuppression, chronic medical conditions like hypertension, diabetes, obesity, cardiovascular disease)
• Nirmatrelvir/ritonavir is contraindicated or unavailable (due to drug interactions or other reasons)

Patients Who Should NOT Receive Molnupiravir

Absolute contraindications: 1, 2, 4

• Pregnant women: Causes embryo-fetal lethality and teratogenicity in animal studies 1, 2, 4
• Breastfeeding women: Risk of harm to infant 1, 4
• Children: Evidence of growth plate damage and decreased bone formation in animal studies 1, 2, 4
• Women of childbearing potential without contraception: Perform pregnancy test before treatment; require reliable contraception during treatment and for at least 4 days after last dose 1
• Men planning conception: Must use reliable contraception during treatment and for at least 3 months after last dose due to potential genotoxic effects on sperm 1, 2, 4

Relative contraindications (recommend against use): 1

• Moderate-risk patients: Toxicity concerns outweigh modest benefits 1
• Low-risk patients: No meaningful benefit 1
• Younger adults without high-risk features: Unknown long-term genotoxicity risk is higher in younger patients 1, 4

Treatment Hierarchy

Nirmatrelvir/ritonavir (Paxlovid) is superior to molnupiravir and should be first-line therapy when available. 1, 2 Paxlovid demonstrates greater reduction in hospitalization rates compared to molnupiravir 1, 2. However, approximately 61% of patients have comedications that are contraindicated or have major drug-drug interactions with ritonavir-containing regimens, making molnupiravir a necessary alternative 5.

Remdesivir also shows potentially greater efficacy than molnupiravir but requires intravenous administration, limiting outpatient feasibility 1.

Expected Clinical Outcomes

When used appropriately in high-risk patients, molnupiravir provides: 6, 7

• Faster symptom resolution (median 18 vs 20 days to resolution compared to placebo) 6
• Reduction in hospitalization risk (1.7% COVID-19-related hospitalization rate in real-world data) 5
• Faster normalization of inflammatory markers (CRP) and oxygen saturation by day 3 of therapy 7
• 34% reduction in need for respiratory interventions 7
• 32% reduction in acute care visits 7
• 3 days shorter hospital stay for those who do require hospitalization 7

Critical Safety Monitoring

Due to molnupiravir's mutagenic mechanism of action, implement the following safeguards: 1

• Active SARS-CoV-2 sequence monitoring in treated patients to detect emergence of resistant mutations 1
• Active pharmacovigilance programs for long-term safety signals 1
• Avoid use in younger patients without compelling high-risk features due to theoretical long-term carcinogenesis risk from preclinical data 1, 4

Common Pitfalls to Avoid

• Do not prescribe beyond 5 days of symptom onset: Efficacy drops significantly with delayed initiation 1, 2
• Do not use as first-line when Paxlovid is available: Molnupiravir is second-line due to inferior efficacy and safety concerns 1, 2
• Do not prescribe for moderate or low-risk patients: Risk-benefit ratio is unfavorable 1
• Do not forget contraception counseling: Both men and women require specific contraception guidance with defined timeframes 1, 2, 4