Is LAGEVRIO (molnupiravir) available and recommended for prescribing to adults with mild to moderate COVID-19?

LAGEVRIO (Molnupiravir) Availability and Prescribing Recommendations

LAGEVRIO (molnupiravir) is available and should be prescribed only as a third-line option for high-risk COVID-19 patients when both Paxlovid and remdesivir are contraindicated or unavailable, due to its inferior efficacy and significant safety concerns. 1, 2

Current Availability

• LAGEVRIO received its first approval in the UK on November 4,2021, and has emergency use authorization in multiple countries including the USA, Japan, and EU nations 3
• The medication is commercially available as an oral formulation of 800 mg taken every 12 hours for 5 days 4

Treatment Algorithm: When to Consider LAGEVRIO

First-Line: Nirmatrelvir/Ritonavir (Paxlovid)

• Paxlovid is the preferred first-line treatment for high-risk patients with mild-to-moderate COVID-19 within 5 days of symptom onset 1, 5
• Demonstrates superior efficacy with 39% relative risk reduction in hospitalization and 61% reduction in death 5

Second-Line: Remdesivir

• Remdesivir is the primary alternative when Paxlovid is contraindicated due to drug interactions, pregnancy, or use in children 1, 2
• Reduced progression to severe COVID-19/hospitalization from 5.3% to 0.7% in high-risk patients 2

Third-Line: LAGEVRIO (Molnupiravir)

• Use only when both Paxlovid and remdesivir are unavailable or contraindicated 1, 2
• The WHO conditionally recommends molnupiravir only for high-risk patients, with significant concerns about toxicity 4, 1

Patient Selection Criteria for LAGEVRIO

High-Risk Patients ONLY (Conditional Recommendation)

• Age ≥65 years, immunosuppression, unvaccinated status, or multiple comorbidities 1
• Must initiate within 5 days of symptom onset 4, 1
• The WHO recommends against molnupiravir for moderate-risk patients and strongly recommends against use in low-risk patients 4, 1

Critical Safety Concerns and Absolute Contraindications

Reproductive Toxicity

• Absolutely contraindicated in pregnancy due to embryo-fetal toxicity observed in animal studies 1
• Contraindicated during breastfeeding 2
• Men of reproductive age must use reliable contraception during treatment and for at least 3 months after the last dose due to genotoxicity concerns 1, 2

Genotoxicity and Carcinogenesis

• Preclinical data shows potential for malignancy, mutagenesis, and impact on bone growth plates in children 4, 1
• Not recommended for children due to evidence of decreased bone formation in animal studies 1
• Long-term safety data in humans remains unavailable 4

Comparative Efficacy Data

Modest Clinical Benefits

• Reduced hospitalization/death from 9.7% to 6.8% in clinical trials 2, 6
• Probably reduces mortality (RR 0.43; 95% CI 0.20-0.94) and hospital admission (RR 0.67; 95% CI 0.45-0.99) with moderate certainty evidence 7
• May reduce time to viral clearance by 1.81 days and time to symptom resolution by 2.39 days 7

Inferior to Alternatives

• Paxlovid demonstrates greater reduction in hospitalization compared to molnupiravir based on indirect comparisons 4, 2
• Remdesivir may result in larger reductions in hospitalization than molnupiravir 4, 2
• The WHO emphasizes that nirmatrelvir/ritonavir and remdesivir represent superior choices due to greater efficacy and better safety profiles 4

Dosing and Administration

• Standard dose: 800 mg orally every 12 hours for 5 days 4, 3
• Must be initiated within 5 days of symptom onset for optimal effectiveness 4, 1
• Can be taken with or without food 8

Common Pitfalls to Avoid

1. Do not prescribe to low or moderate-risk patients - the toxicity concerns outweigh any marginal benefits 4, 1
2. Do not use as first-line therapy - always consider Paxlovid or remdesivir first 1, 2
3. Do not prescribe without thorough reproductive counseling - ensure contraception compliance in men and absolute avoidance in women of childbearing potential 1, 2
4. Do not delay treatment beyond 5 days - efficacy significantly diminishes after this window 4, 1
5. Do not use in children - safety concerns regarding bone development 1

Clinical Decision Summary

LAGEVRIO should be reserved as a last-resort option when superior alternatives are unavailable, and only for carefully selected high-risk patients who can comply with strict reproductive safety measures and understand the uncertain long-term safety profile. 4, 1, 2