Gregory M. Mazzie, BS

 The information provided in this month’s New Drug Review column is based on the FDA’s emergency use authorization (EUA). Per the EUA,

 “molnupiravir has not been approved but has been authorized for emergency use by FDA under an EUA for the treatment of mild to moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options authorized by FDA are not accessible or clinically appropriate; and the emergency use of molnupiravir is only authorized for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biological products during the COVID-19 pandemic under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization revoked sooner.”

On December 23, 2021, the FDA issued an EUA for molnupiravir (Lagevrio). Molnupiravir is an oral antiviral developed by Merck for the treatment of confirmed mild to moderate COVID-19 in adults 18 years or older who are at high risk of severe disease.

 Molnupiravir is currently available by prescription only and should be initiated as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset.

Results from a phase 3 randomized, placebo-controlled, double-blind trial support the EUA for molnupiravir.

 evaluated 1433 nonhospitalized adults with mild to moderate COVID-19 and 1 or more predefined risk factors for disease progression. Participants were symptomatic within 5 days of randomization with a laboratory confirmed SARS-CoV-2 infection, and were excluded if previously vaccinated against SARS-CoV-2.

Primary efficacy end point was the percentage of patients who were hospitalized or died through day 29 due to any cause. In an interim analysis of 762 participants, 7.3% who received molnupiravir were either hospitalized or died through day 29 vs 14.1% of the placebo group, a 51% reduction. Adjusted risk difference was –6.8% (95% CI, –11.3% to –2.4%). Analyses were adjusted by the stratification factor of time of COVID-19 symptom onset (< 3 days vs > 3 [4-5] days).

The most common adverse events (AEs) included grade 1 or grade 2 diarrhea, nausea, and dizziness.

 Serious AEs occurred in 7% of participants receiving molnupiravir and were mostly COVID-19 related.

 The prescribing provider or provider designee is responsible for mandatory reporting of all serious AEs and medication errors potentially related to molnupiravir within 7 calendar days of event awareness. Molnupiravir may cause fetal harm and therefore is not recommended for use in pregnancy.

Molnupiravir is supplied as 200-mg capsules. Current dosing recommendation is 800 mg (four 200-mg capsules) taken orally every
12 hours for 5 days with or without food. Molnupiravir should be taken as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset, as safety and efficacy for extended use past 5 consecutive days has not been established.

Completion of the full 5-day treatment course and continued isolation in accordance with CDC recommendations are important to maximize viral clearance and minimize transmission of COVID-19. If patients miss a dose within 10 hours of the scheduled time, the dose should be taken as soon as possible. If the missed dose is greater than 10 hours, the next dose should be taken at the scheduled time; do not double the dose. 

Dosing recommendations, safety, and efficacy have not yet been established in pediatric patients. 

There are currently no dosage adjustment recommendations based on renal or hepatic impairment or in geriatric patients.

 No significant drug interactions have been identified based on limited available data within the EUA.

Gregory M. Mazzie, BS, is a PharmD candidate at the University of Connecticut School of Pharmacy (Class of 2022).

Cassandra R. Doyno, PharmD, BCPS, BCCCP, is an assistant clinical professor at the University of Connecticut School of Pharmacy in Storrs.

O’Shaughnessy JA. RE: Emergency Use Authorization 108. FDA. December 23, 2021. Accessed February 7, 2022. https://www.fda.gov/media/155053/download

Coronavirus (COVID-19) update: FDA authorizes additional oral antiviral for treatment of COVID-19 in certain adults. FDA. December 23, 2021. Accessed February 7, 2022. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-oral-antiviral-treatment-covid-19-certain

Fact sheet for healthcare providers: Emergency use authorization for molnupiravir. Merck Sharp & Dohme Corp; 2021. Accessed February 7, 2022. 

https://www.merck.com/eua/molnupiravir-hcp-fact-sheet.pdf

Efficacy and safety of molnupiravir (MK-4482) in non-hospitalized adult participants with COVID-19 (MK-4482-002). ClinicalTrials.gov. Updated November 4, 2021. Accessed February 8, 2022. 

https://clinicaltrials.gov/ct2/show/NCT04575597

Articles

Molnupiravir is an oral antiviral for the treatment of mild to moderate COVID-19 in adults at high risk of severe disease.