​​Summary

The U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) PDF on December 23, 2021 for the use of molnupiravir, an oral nucleoside analogue that inhibits SARS-CoV-2 replication by viral mutagenesis, to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults (18 years or older) who have tested positive for COVID-19, and who are at high risk for progression to severe COVID-19, including hospitalization or death.

Molnupiravir is only authorized for treatment in patients for whom other FDA or National Institutes of Health (NIH) recommended treatments for COVID-19 are inaccessible or are not clinically appropriate. Please see the NIH Treatment Guidelines page on the prioritization of outpatient treatments, which presents a list of outpatient treatments in order of preference.

Clinical Trial Data

In a randomized, double-blind, placebo-controlled clinical trial, molnupiravir reduced the risk of hospitalization or death from 9.7% in the placebo group (68/699) to 6.8% (48/709) in the molnupiravir group, for an absolute risk reduction of 3.0% (95% confidence interval [CI]: 0.1, 5.9; nominal p-value=0.0218) and a relative risk reduction of 30% (relative risk 0.70; 95% CI: 0.49, 0.99).

Molnupiravir and SARS-CoV-2 Variants

Molnupiravir is expected to be effective against all variants currently circulating in California, including Omicron.

Additional Use Considerations

Molnupiravir is authorized for treatment only. The Fact Sheet for Health Care Providers (PDF), which includes criteria for the full authorization of use, contraindications, and drug interactions should be reviewed prior to administration of the medication. 

The following should be considered:

• Molnupiravir may only be prescribed by physicians, advanced practice registered nurses, and physician assistants that are licensed or authorized under state law to prescribe drugs in the therapeutic class to which molnupiravir belongs (i.e., anti-infectives).
• Molnupiravir is not authorized for the pre-exposure or post-exposure prevention of COVID-19 or for initiation of treatment in those requiring hospitalization due to severe or critical COVID-19. Molnupiravir is not a substitute for COVID-19 vaccination.
• Molnupiravir is not authorized for use in patients younger than 18 years of age because it affects bone and cartilage formation and growth.
• Molnupiravir may cause fetal harm when administered to pregnant individuals and Molnupiravir is not recommended for use during pregnancy or breastfeeding. Females of childbearing potential are advised to use a reliable method of birth control during treatment with molnupiravir and for four days after the final dose. Breastfeeding is not recommended during treatment and for 4 days after the last dose of molnupiravir. Males of reproductive potential who are sexually active with females of childbearing potential are advised to use a reliable method of birth control during treatment and for at least three months after the final dose.
  
• Because of its lower effectiveness, molnupiravir should not be used for treatment when other FDA authorized or NIH recommended treatments for COVID-19 are available. These include anti-SARS-CoV-2 monoclonal antibodies (for example, sotrovimab), Paxlovid, and remdesivir.

Patient Prioritization During Times of Limited Supply

The National Institutes of Health (NIH) treatment guidelines on prioritization should be followed during times when supply is limited.

Acquiring Molnupiravir

Allocation of molnupiravir will be to pharmacies and providers able to dispense the medication. The number of courses allocated to each county is determined using the overall COVID-19 cases in that county combined with an equity measure based on the Healthy Places Index (HPI).

Prescribing healthcare providers can locate sites where COVID-19 therapeutics are available using the HHS Therapeutics Locator. The Therapeutics Locator is based on shipments and reported utilization and is not a guarantee of availability. Providers should communicate with facilities to ensure that supply exists.

Originally published on January 19, 2022