Lagevrio (molnupiravir)

Lagevrio (molnupiravir)

Hello, I’m Dr. Colin Shepard. I serve as the CDC Liaison to the HHS Assistant Secretary for Preparedness and Response, also called ASPR. I want to talk about one of the therapeutics that can help people with COVID-19—Lagevrio, also known as molnupiravir.

What is Lagevrio?

Lagevrio is an oral antiviral used to help fight the coronavirus infection by stopping the coronavirus from replicating in the body. This lowers the viral load, reducing the chances of the illness progressing to more serious symptoms and hospitalization.

Who is eligible for Lagevrio?

Lagevrio is for adults who are at high risk for developing serious symptoms of COVID-19 that may lead to hospitalization or death. For more information about who is at high risk, please see the resources provided in the description. Lagevrio is for people who have a positive COVID-19 rapid or PCR test with mild to moderate symptoms and who are not in the hospital. It should be administered as early as possible but needs to be given within 5 days of symptom onset.

How is Lagevrio administered?

Lagevrio requires a prescription. It is available through a pharmacy or health care clinic, including Test to Treat locations where these antivirals are being distributed for use at home. Patients will take pills twice a day for 5 days.

What are the limitations of use for Lagevrio?

Lagevrio is not for everyone. The medication is not for anyone under the age of 18 or pregnant women. It is not appropriate to start Lagevrio if you are already hospitalized for COVID-19. There are no known drug interactions with Lagevrio.

Lagevrio is one of several COVID-19 therapeutic options. Watch the other Outpatient COVID-19 Therapeutics Videos in this series for more information. Visit us online at https://aspr.hhs.gov/COVID-19 and please see the resources linked in the description to learn more. You can connect with ASPR on social media platforms to stay up to date on our latest posts and information that we share. Please email any questions to COVID19therapeutics@hhs.gov.

Thank you for your time.

Lagevrio is not authorized for:

• Use in patients less than 18 years of age.
• Initiation of treatment in patients requiring hospitalization due to COVID-19. Benefit of treatment with Lagevrio has not been observed in when treatment was initiated after hospitalization due to COVID-19.
• Use for longer than 5 consecutive days.
• Pre-exposure or post-exposure prophylaxis for prevention of COVID-19.

As of November 1, 2023, Lagevrio became available for purchase through the commercial market. Specific federal entities can continue to use the HHS Health Partners Ordering Portal to order from the U.S. government (USG) inventory until the supply is depleted.

USG-distributed inventory must be used at no cost to patients until the product is depleted or expires, whichever comes first. Learn more about the Lagevrio Ordering and Distribution Timeline.

Rebound, which is defined as experiencing recurrence of symptoms and/or SARS CoV-2 antigen positivity after initial resolution, has been observed not only among patients treated with Lagevrio but also occurs in patients receiving no treatment or in patients treated with other COVID-19 therapeutics.

Recent studies suggest patients experiencing rebound have an extremely low probability of developing severe COVID-19, including a study published in CDC's Morbidity and Mortality Weekly Report in December 2023, which found no consistent association between treatment with COVID-19 antivirals and rebound. Further studies on this phenomenon are ongoing.

Additional guidance on the management of patients experiencing rebound is available.

• NIH Therapeutic Management of Nonhospitalized Adults With COVID-19
• FDA Fact Sheet for Healthcare Providers for Lagevrio
• Side-by-Side Outpatient Therapeutics Overview
• Therapeutics Clinical Implementation Guide
• COVID-19 Therapeutics Decision Aid
• Email any questions to COVID19therapeutics@hhs.gov.

Lagevrio is for adults 18 years and older who are at high risk for developing serious COVID-19 disease including hospitalization and/or death. Lagevrio should be considered for non-hospitalized patients who meet all of the following criteria:

• Have current diagnosis of mild to moderate COVID-19 and are within 5 days of symptom onset.
• Have one or more risk factors for severe COVID-19.
• Alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate.

Please see the FDA Fact Sheet for Healthcare Providers for additional information on Lagevrio eligibility criteria and risks associated with use.

Per the current CDC’s Interim Clinical Considerations for COVID-19 Treatment in Outpatients guidelines, risk factors include:

• Age 50 years or older, with risk increasing substantially at age ≥ 65 years
• Being unvaccinated or not being up to date on COVID-19 vaccinations
• Specific medical conditions and behaviors

For additional information, please see the National Institutes of Health’s COVID-19 Treatment Guidelines: Clinical Spectrum of SARS-CoV-2 Infection.

Health care providers should proactively counsel high-risk patients about the availability of effective therapeutics and discuss a COVID-19 Action Plan with their patients.

Antiviral treatment of outpatients at risk for severe COVID-19 may reduce the risk of hospitalization and death.

In clinical trials done prior to authorization, Lagevrio was associated with an adjusted relative risk reduction of 30% in all-cause hospitalization or death through Day 29.¹

Observational data, including from Israel² and Hong Kong³ is consistent with benefit in high-risk patients:

• 46% risk reduction in hospitalizations and death compared to the untreated for patients 75 and older²
• 49% risk reduction in death compared to non-users³

References

1. Angélica Jayk Bernal, et al. N Engl J Med 2022; 386:509-520 https://www.nejm.org/doi/full/10.1056/NEJMoa2116044
2. Ronza Najjar-Debbiny, et al. Clinical Infectious Diseases, 2022; ciac781, https://doi.org/10.1093/cid/ciac781
3. Carlos K.H. Wong, et al. Lancet Infectious Disease,2022; doi: https://doi.org/10.1016/S1473-3099(22)00507-2

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

No dosage adjustment is recommended based on renal or hepatic impairment or in geriatric patients.

Yes, health care providers and patients must be aware of the following warnings and precautions:

• Lagevrio is not recommended for use during pregnancy because of risk it may cause fetal harm. Prior to initiating treatment with Lagevrio, health care providers should assess whether an individual of childbearing potential is pregnant, if clinically indicated.
• Individuals with reproductive potential are advised to use a reliable method of contraception correctly and consistently, as applicable, for the duration of treatment and for appropriate time after the last dose per section 8.3 in the Fact Sheet for Healthcare Providers.
• Breastfeeding is not recommended during treatment with Lagevrio and for 4 days after final dose.
• Hypersensitivity reactions, including anaphylaxis, have been reported with Lagevrio. Please refer to the Lagevrio fact sheet for health care providers for additional information on warnings and precautions.

• Paxlovid (oral antiviral) is a preferred oral antiviral for the treatment of mild to moderate COVID-19 illness.
• Veklury (remdesivir) is a preferred treatment for mild to moderate COVID-19. Veklury is given intravenously, once a day for 3 consecutive days.

Yes; a prescription from a qualified health care provider is required.

An individual’s health care provider is the best first option for assessment and for prescribing patients who have symptoms consistent with mild to moderate COVID-19.

For individuals who do not have timely access to their own health care provider, patients can get tested, assessed for COVID-19 therapeutic eligibility, and have their prescription filled at Test to Treat sites nationwide. Telehealth options are also widely available. A Test to Treat call center is also available at 1-800-232-0233 (TTY 1-888-720-7489) to get help in English, Spanish, and more than 150 other languages. The Disability Information and Access Line (DIAL) is also available to specifically help people with disabilities access services. To get help, call 1-888-677-1199, Monday through Friday from 9 AM to 8 PM ET or email DIAL@usaginganddisability.org.

Find COVID-19 medications, including Lagevrio.

No. Although FDA continues to recommend that authorized prescribers use direct SARS-CoV-2 viral testing to help diagnose COVID-19, FDA removed the requirement for positive test results effective February 1, 2023. FDA recognizes that, in rare instances, individuals with a recent known exposure (e.g., a household contact with a positive direct SARS-CoV-2 viral test) who develop signs and symptoms consistent with COVID-19 may be diagnosed by an authorized prescriber as having COVID-19 even if they have a negative direct SARS-CoV-2 viral test result. In such instances, the authorized prescriber may determine that treatment with Lagevrio for COVID-19 is appropriate if the patient reports mild to moderate symptoms of COVID-19 and is at high risk for progression to severe COVID-19, including hospitalization or death, and the terms and conditions of the authorization are met, as detailed in the Fact Sheet for Healthcare Providers.

Licensed physicians and advanced practice providers are not required to perform additional laboratory testing when prescribing Lagevrio. Providers should use clinical judgement to determine if labs are necessary.

We anticipate an ample supply of Lagevrio continuing to be available on the commercial market.

Lagevrio should be considered as a therapeutic alternative for any COVID-19 patient who meets the eligibility criteria and for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate.

Oral antivirals are pills that stop the virus that causes COVID-19 from making copies of itself in your body. One oral antiviral is called Paxlovid (also known as nirmatrelvir co-packaged with ritonavir), and the other is called Lagevrio (also known as molnupiravir).

Find COVID-19 medications, including Lagevrio. A call center is also available at 1-800-232-0233 (TTY 1-888-720-7489) to get help in English, Spanish, and more than 150 other languages.

DIAL is also available to specifically help people with disabilities access services. To get help, call 1-888-677-1199, Monday through Friday from 9 AM to 8 PM ET or email DIAL@usaginganddisability.org.

• Patients are encouraged to discuss a COVID-19 Action Plan with their health care providers.
• Patients should have available electronic or printed health records from the past year, including the most recent blood work relating to kidney and liver problems. In addition, they will need a list of all medications they are taking, including over-the-counter medications.
• Learn more about COVID-19 Treatment Information for Patients.
• Fact Sheet for Patients and Caregivers