Lagevrio (Molnupiravir): An Oral Antiviral for COVID-19
Lagevrio (molnupiravir) is an oral antiviral medication authorized for treatment of mild-to-moderate COVID-19 in high-risk adults who are within 5 days of symptom onset, but should not be used in pregnant women, children, or low-risk patients due to safety concerns about potential genotoxicity.
Mechanism of Action
- Molnupiravir is an oral prodrug that is rapidly converted to N-hydroxycytidine (NHC) in the body 1
- NHC is phosphorylated inside cells to NHC-triphosphate, which acts as a competitive substrate for the viral RNA-dependent RNA polymerase 1
- Unlike Paxlovid which inhibits viral replication, molnupiravir induces viral replication errors that lead to viral inactivation 2
- This mechanism creates a high barrier to viral resistance development 1
Clinical Indications
- Authorized for treatment of adults with confirmed mild-to-moderate COVID-19 who are at high risk for progression to severe disease 3
- Must be initiated within 5 days of symptom onset for optimal effectiveness 3
- Recommended dosage is 800 mg (four 200 mg capsules) taken orally every 12 hours for 5 days 3
Efficacy
- In the phase 3 MOVe-OUT trial of unvaccinated high-risk adults, molnupiravir reduced the risk of hospitalization or death compared to placebo 4
- The final analysis showed a 3.0 percentage point reduction in hospitalization or death (6.8% vs 9.7%) 4
- Treatment resulted in improved clinical outcomes for most participant-reported COVID-19 symptoms compared to placebo 5
- Patients treated with molnupiravir had shorter median time to first resolution (18 vs 20 days) and first alleviation (13 vs 15 days) of symptoms 5
Important Safety Concerns
- Molnupiravir should not be used in pregnant women due to embryo-fetal toxicity observed in animal studies 6
- Not recommended for children due to evidence of impact on growth plates and decreased bone formation in animal studies 6
- Men who might father a child should use reliable contraception during treatment and for at least three months after the last dose 3
- Concerns exist about potential genotoxicity (ability to mutate DNA), particularly in younger patients 3, 2
Comparative Effectiveness
- Nirmatrelvir/ritonavir (Paxlovid) is generally considered more efficacious than molnupiravir for reducing hospitalization in high-risk patients 3, 2
- The main advantage of molnupiravir over Paxlovid is that it does not have significant drug interactions 2
- For moderate-risk patients, the WHO suggests against using molnupiravir as concerns about toxicity outweigh benefits 3
- For low-risk patients, the WHO strongly recommends against molnupiravir use 3
Regulatory Status
- Received Emergency Use Authorization in the United States 7
- Approved or authorized in more than 25 countries worldwide 1
- First oral antiviral for COVID-19 to receive full regulatory approval in the UK (November 2021) 7