Molnupiravir, sold under the brand name Lagevrio, is an oral antiviral medication developed by Merck for the treatment of COVID-19. It is designed to prevent mild or moderate illness from progressing to a more severe case. This drug is not approved by the U.S. Food and Drug Administration (FDA) but has been granted an Emergency Use Authorization (EUA) to make it available during the pandemic.
How Molnupiravir Works Against COVID-19
Molnupiravir functions by interfering with the replication process of the SARS-CoV-2 virus. The medication is a prodrug, which means the body converts it into its active form, a molecule called β-D-N4-hydroxycytidine (NHC). This active compound mimics the natural building blocks of RNA, the virus’s genetic material. The viral machinery, specifically an enzyme called RNA-dependent RNA polymerase (RdRp), is responsible for copying the viral genome.
During this copying process, the RdRp enzyme mistakenly incorporates NHC into the new viral RNA strands. The incorporation of NHC introduces widespread errors into the virus’s genetic code. This phenomenon is known as “viral error catastrophe” or “lethal mutagenesis.”
As the virus continues to replicate, these errors accumulate, leading to defective viral particles unable to infect new cells. This process reduces the overall viral load in the body, helping to control the illness.
Eligibility for Treatment
Molnupiravir is authorized for adults with mild-to-moderate COVID-19 who are at high risk for their illness progressing to severe disease. It is specifically intended for individuals for whom other FDA-approved or authorized COVID-19 treatments are not accessible or clinically appropriate. The authorization is not for preventing COVID-19 before or after exposure.
Treatment must be initiated as soon as possible after a COVID-19 diagnosis and within five days of the first symptoms appearing. The standard dosage is 800 mg, which consists of four 200 mg capsules, taken orally every 12 hours for five consecutive days. Patients should complete the entire five-day course of treatment. The medication is not authorized for use in patients who are already hospitalized due to COVID-19 or for anyone under 18 years of age.
Clinical Efficacy Data
The primary evidence for molnupiravir’s effectiveness comes from the Phase 3 MOVe-OUT clinical trial. This study focused on non-hospitalized, unvaccinated adults with risk factors for severe disease. The trial was a randomized, double-blind, placebo-controlled study, where neither participants nor researchers knew who received the active drug.
In the final analysis of all 1,433 participants, treatment with molnupiravir showed a reduction in the risk of hospitalization or death. Among patients who received the drug, 6.8% were hospitalized or died through day 29, compared to 9.7% of patients in the placebo group. This represents an absolute risk reduction of 3.0%.
Regarding mortality rates, one death was reported in the molnupiravir group through day 29, while nine deaths were reported in the placebo group. Subsequent analyses from real-world data have suggested that the medication retains effectiveness against various variants, including in populations with some level of vaccination or previous infection, though absolute risk reduction was more modest in these cases.
Potential Side Effects and Safety Profile
The most commonly reported side effects in clinical trials for molnupiravir were mild to moderate and included diarrhea, nausea, and dizziness. Allergic reactions are also possible, with symptoms such as hives, rash, or swelling of the face and throat requiring immediate medical attention.
A significant safety concern is the use of molnupiravir during pregnancy. Based on findings from animal studies, the medication may cause fetal harm and is not recommended for use in pregnant individuals. It is used during pregnancy only when other treatment options are unavailable and after discussing the risks and benefits. Women who can become pregnant are advised to use reliable contraception during treatment and for four days after the last dose.
Men who are sexually active with partners who could become pregnant are advised to use a reliable method of contraception during treatment and for at least three months after their final dose. The drug is not authorized for patients younger than 18 years old because it may affect bone and cartilage growth.