FAQs

In order to mitigate the risks of using this unapproved product under the EUA and to optimize the potential benefit of LAGEVRIO, use of LAGEVRIO under this EUA has certain requirements. For more information, please review "Mandatory Requirements for Administration of LAGEVRIO Under Emergency Use Authorization" in the Fact Sheet for Healthcare Providers.

AUTHORIZED USE
  • LAGEVRIO™ (molnupiravir) is authorized for use under an Emergency Use Authorization (EUA) for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults:
    • with positive results of direct SARS-CoV-2 viral testing, and
    • who are at high risk for progression to severe COVID-19, including hospitalization or death, and
    • for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate
  • LAGEVRIO is not approved for any use, including the treatment of COVID-19, but is authorized for emergency use by the FDA under an Emergency Use Authorization (EUA).
  • The emergency use of LAGEVRIO 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 Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1) unless the declaration is terminated or authorization revoked sooner.
Limitations of Authorized Use
  • LAGEVRIO is not authorized:
    • for use in patients who are less than 18 years of age
    • for initiation of treatment in patients hospitalized due to COVID-19. Benefit of treatment with LAGEVRIO has not been observed in subjects when treatment was initiated after hospitalization due to COVID-19
    • for use for longer than 5 consecutive days
    • for pre-exposure or post-exposure prophylaxis for prevention of COVID-19
  • LAGEVRIO may only be prescribed for an individual patient 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 LAGEVRIO belongs (i.e., anti-infectives).

The dosage in adult patients is 800 mg (four 200 mg capsules) taken orally every 12 hours for 5 days, with or without food. Take LAGEVRIO as soon as possible after a diagnosis of COVID-19 has been made, and within 5 days of symptom onset.

Completion of the full 5-day treatment course and continued isolation in accordance with public health recommendations are important to maximize viral clearance and minimize transmission of SARS-CoV-2.

LAGEVRIO is not authorized for use for longer than 5 consecutive days because the safety and efficacy have not been established.1

If the patient misses a dose of LAGEVRIO within 10 hours of the time it is usually taken, the patient should take it as soon as possible and resume the normal dosing schedule. If the patient misses a dose by more than 10 hours, the patient should not take the missed dose and instead take the next dose at the regularly scheduled time. The patient should not double the dose to make up for a missed dose.

Should a patient require hospitalization after starting treatment with LAGEVRIO, the patient may complete the full 5 day treatment course per the healthcare provider’s discretion.

Contraindications

  • No contraindications have been identified based on the limited available data on the emergency use of LAGEVRIO authorized under this EUA.

Warnings and Precautions

  • There are limited clinical data available for LAGEVRIO. Serious and unexpected adverse events may occur that have not been previously reported with LAGEVRIO use.
  • LAGEVRIO is not recommended for use during pregnancy. Based on findings from animal reproduction studies, LAGEVRIO may cause fetal harm when administered to pregnant individuals. There are no available human data on the use of LAGEVRIO in pregnant individuals to evaluate the risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.
  • LAGEVRIO is authorized to be prescribed to a pregnant individual only after the healthcare provider has determined that the benefits would outweigh the risks for that individual patient. If the decision is made to use LAGEVRIO during pregnancy, the prescribing healthcare provider must document that the known and potential benefits and the potential risks of using LAGEVRIO during pregnancy were communicated to the pregnant individual.
  • There is a pregnancy surveillance program that monitors pregnancy outcomes in individuals exposed to LAGEVRIO during pregnancy. The prescribing healthcare provider must document that a pregnant individual was made aware of Merck’s pregnancy surveillance program at 1-877-888-4231 or pregnancyreporting.msd.com. If the pregnant individual agrees to participate in the pregnancy surveillance program and allows the prescribing healthcare provider to disclose patient specific information to Merck, the prescribing healthcare provider must provide the patient’s name and contact information to Merck. Pregnant individuals exposed to LAGEVRIO can also report the exposure by contacting Merck at 1-877-888-4231 or pregnancyreporting.msd.com
  • Advise individuals of childbearing potential of the potential risk to a fetus and to use an effective method of contraception correctly and consistently during treatment with LAGEVRIO and for 4 days after the final dose.
  • Prior to initiating treatment with LAGEVRIO, assess whether an individual of childbearing potential is pregnant or not, if clinically indicated.
  • Hypersensitivity reactions, including anaphylaxis, have been reported with LAGEVRIO. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue LAGEVRIO and initiate appropriate medications and/or supportive care.
  • LAGEVRIO is not authorized for use in patients less than 18 years of age because it may affect bone and cartilage growth. The safety and efficacy of LAGEVRIO have not been established in pediatric patients.

Adverse Reactions

  • The most common adverse reactions occurring in ≥1% of subjects in the LAGEVRIO treatment group in the Phase 3 double-blind MOVe-OUT study were diarrhea (2% versus placebo at 2%), nausea (1% versus placebo at 1%), and dizziness (1% versus placebo at 1%) all of which were Grade 1 (mild) or Grade 2 (moderate).
  • Serious adverse events occurred in 7% of subjects receiving LAGEVRIO and 10% receiving placebo; most serious adverse events were COVID-19 related. Adverse events leading to death occurred in 2 (<1%) of the subjects receiving LAGEVRIO and 12 (2%) of subjects receiving placebo.

Drug Interactions

  • No drug interactions have been identified based on the limited available data on the emergency use of LAGEVRIO. No clinical drug-drug interaction trials of LAGEVRIO with concomitant medications, including other treatments for mild to moderate COVID-19, have been conducted.

Pregnancy/Breastfeeding

  • There are no data on the presence of LAGEVRIO or its metabolites in human milk. It is unknown whether LAGEVRIO has an effect on the breastfed infant or effects on milk production. Based on the potential for adverse reactions in the infant from LAGEVRIO, breastfeeding is not recommended during treatment with LAGEVRIO and for 4 days after the final dose. A lactating individual may consider interrupting breastfeeding and may consider pumping and discarding breast milk during treatment and for 4 days after the last dose of LAGEVRIO.

Males of Reproductive Potential

  • Nonclinical studies to fully assess the potential for LAGEVRIO to affect offspring of treated males have not been completed. Advise sexually active individuals with partners of childbearing potential to use a reliable method of contraception correctly and consistently during treatment and for at least 3 months after the last dose of LAGEVRIO. The risk beyond three months after the last dose of LAGEVRIO is unknown.

Required Reporting for Serious Adverse Events and Medication Errors

  • The prescribing healthcare provider and/or the provider’s designee is/are responsible for mandatory reporting of all serious adverse events and medication errors potentially related to LAGEVRIO within 7 calendar days from the healthcare provider’s awareness of the event.
  • Submit adverse event and medication error reports, using FDA Form 3500, to FDA MedWatch using one of the following methods:
  • In addition, please provide a copy of all FDA MedWatch forms to:
  • Merck Sharp & Dohme LLC, Rahway, NJ USA by:
  • Fax: 215-616-5677
  • E-mail: dpoc.usa@merck.com

Before prescribing LAGEVRIO, please read the accompanying Fact Sheet for Healthcare Providers, including Mandatory Requirements for Administration of LAGEVRIO Under Emergency Use Authorization. The FDA Letter of Authorization and the Fact Sheet for Patients and Caregivers are also available.

As a prescribing healthcare practitioner, you must communicate to the patient and/or caregiver information consistent with the “FACT SHEET FOR PATIENTS AND CAREGIVERS” and document that information was provided. A copy of this Fact Sheet should be provided to the patient and/or caregiver prior to receiving LAGEVRIO.

Hypersensitivity Reactions

Inform patients that hypersensitivity reactions have been reported, even following a single dose of LAGEVRIO, and to discontinue the drug and to inform their healthcare provider at the first sign of a skin rash, hives or other skin reactions, a rapid heartbeat, difficulty in swallowing or breathing, any swelling suggesting angioedema (for example, swelling of the lips, tongue, face, tightness of the throat, hoarseness), or other symptoms of an allergic reaction.

Risk of Fetal Toxicity

Advise patients that LAGEVRIO is not recommended for use in pregnancy because it may cause fetal harm. Advise individuals of childbearing potential to inform their healthcare provider of a known or suspected pregnancy.

Advise individuals of childbearing potential to use effective contraception correctly and consistently while taking LAGEVRIO and for 4 days after the last dose.

While the risk is regarded as low, nonclinical studies to fully assess the potential for LAGEVRIO to affect offspring of treated males have not been completed. Advise sexually active individuals with partners of childbearing potential to use a reliable method of contraception consistently and correctly while taking LAGEVRIO and for at least 3 months after the last dose of LAGEVRIO. The risk beyond 3 months after the last dose of LAGEVRIO is unknown. Studies to understand the risk beyond three months are ongoing.

Risk of Bone and Cartilage Toxicity

LAGEVRIO is not authorized for use in patients less than 18 year of age as it may affect bone growth and cartilage formation.

Pregnancy Surveillance Program

There is a pregnancy surveillance program that monitors pregnancy outcomes in individuals exposed to LAGEVRIO during pregnancy. Encourage participation and advise patients about how they may enroll in the pregnancy surveillance program. Advise patients who have taken LAGEVRIO during pregnancy to report their pregnancy to Merck Sharp & Dohme LLC, Rahway, NJ USA at 1-877-888-4231 or pregnancyreporting.msd.com.

Lactation

Breastfeeding is not recommended while taking LAGEVRIO and for 4 days after the last dose of LAGEVRIO. Advise lactating individuals to consider interrupting breastfeeding and to consider pumping and discarding breast milk during treatment and for 4 days after the last dose of LAGEVRIO.

Administration Instructions

Inform patients to take LAGEVRIO with or without food. Advise patients to swallow LAGEVRIO capsules whole, and to not open, break, or crush the capsules. Instruct patients that if they miss a dose of LAGEVRIO and it is within 10 hours of the time it is usually taken, the patient should take it as soon as possible and resume the normal dosing schedule. If the patient misses a dose by more than 10 hours, the patient should not take the missed dose and instead take the next dose at the regularly scheduled time. Advise the patient to not double the dose to make up for a missed dose.

Alert the patient of the importance of completing the full 5-day treatment course and to continuing isolation in accordance with public health recommendations to maximize viral clearance and minimize transmission of SARS-CoV-2.

An EUA is a FDA authorization for the emergency use of an unapproved product or unapproved use of an approved product (i.e., drug, biological product, or device) in the United States under certain circumstances including, but not limited to, when the Secretary of HHS declares that there is a public health emergency that affects the national security or the health and security of United States citizens living abroad, and that involves biological agent(s) or a disease or condition that may be attributable to such agent(s). Criteria for issuing an EUA include:

  • The biological agent(s) can cause a serious or life-threatening disease or condition;
  • Based on the totality of the available scientific evidence (including data from adequate and well-controlled clinical trials, if available), it is reasonable to believe that
    • the product may be effective in diagnosing, treating, or preventing the serious or life-threatening disease or condition; and
    • the known and potential benefits of the product - when used to diagnose, prevent, or treat such disease or condition - outweigh the known and potential risks of the product, taking into consideration the material threat posed by the biological agent(s);
  • There is no adequate, approved, and available alternative to the product for diagnosing, preventing, or treating the serious or life-threatening disease or condition.

For information on clinical trials that are testing the use of LAGEVRIO for COVID-19, please visit www.clinicaltrials.gov.

No amino acid substitutions in SARS-CoV-2 associated with resistance to NHC have been identified in Phase 2 clinical trials evaluating LAGEVRIO for the treatment of COVID-19.

Studies to evaluate selection of resistance to NHC with SARS-CoV-2 in cell culture have not been completed.

Resistance selection studies have been conducted with other coronaviruses (MHV and MERS-CoV) and showed a low likelihood of resistance development to NHC.

Following 30 passages in cell culture, only a 2-fold decrease in susceptibility was observed and no NHC resistance-associated amino acid substitutions were identified. NHC retained activity in cell culture against virus with polymerase (nsp 12) substitutions (e.g., F480L, V557L and E802D) associated with decreased remdesivir sensitivity, indicating a lack of cross-resistance.

In clinical trials, encoded amino acid changes (substitutions, deletions or insertions) were more likely to be detected in viral sequences in subjects treated with LAGEVRIO compared to placebo. In a small number of subjects, amino acid changes in the spike protein occurred at positions targeted by monoclonal antibodies and vaccines. The clinical and public health significance of these changes are unknown.

The prescribing healthcare provider and/or the provider’s designee is/are responsible for mandatory reporting of all serious adverse events* and medication errors potentially related to LAGEVRIO within 7 calendar days from the healthcare provider’s awareness of the event, using FDA Form 3500 (for information on how to access this form, see below). The FDA requires that such reports, using FDA Form 3500, include the following:

  • Patient demographics and baseline characteristics (e.g., patient identifier, age or date of birth, gender, weight, ethnicity, and race).
  • A statement "LAGEVRIO use for COVID-19 under Emergency Use Authorization (EUA)” under the “Describe Event, Problem, or Product Use/Medication Error” heading.
  • Information about the serious adverse event or medication error (e.g., signs and symptoms, test/laboratory data, complications, timing of drug initiation in relation to the occurrence of the event, duration of the event, treatments required to mitigate the event, evidence of event improvement/disappearance after stopping or reducing the dosage, evidence of event reappearance after reintroduction, clinical outcomes).
  • Patient’s preexisting medical conditions and use of concomitant products.
  • Information about the product (e.g., dosage, route of administration, NDC #).

Submit adverse event and medication error reports, using Form 3500, to FDA MedWatch using one of the following methods:

In addition, please provide a copy of all FDA MedWatch forms to:

Merck Sharp & Dohme LLC, Rahway, NJ USA by:

Fax: 215-616-5677

E-mail: dpoc.usa@msd.com

The prescribing healthcare provider and/or the provider’s designee is/are responsible for mandatory responses to requests from FDA for information about adverse events and medication errors following receipt of LAGEVRIO.

*Serious adverse events are defined as:

  • Death;
  • A life-threatening adverse event;
  • Inpatient hospitalization or prolongation of existing hospitalization;
  • A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions;
  • A congenital anomaly/birth defect;
  • Other important medical event, which may require a medical or surgical intervention to prevent death, a life-threatening event, hospitalization, disability, or congenital anomaly.

Other therapeutics are currently authorized or approved for the same use as LAGEVRIO. For additional information on all products authorized for treatment or prevention of COVID-19, please see https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization.

The U. S. government is currently allocating the product. Dispensing sites should contact their state’s department of health or their eligible jurisdiction’s department of health for ordering instructions.

AmerisourceBergen will only ship what is allocated by the states. Ordering facilities that do not receive all the product they requested will have to contact their state's health department or eligible jurisdiction's health department regarding any additional quantities available.

Please contact your state’s or eligible jurisdiction’s department of health for ordering instructions.

No. Please set up an account with your state’s or eligible jurisdiction’s department of health, which will be placing orders for the time being.

Yes. Under the authorization, LAGEVRIO may only be prescribed for an individual patient 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 LAGEVRIO belongs (i.e., anti-infectives).

To find U.S. Government-procured COVID-19 therapeutics, visit the U.S. Department of Health and Human Services' (HHS) COVID-19 Therapeutics Locator.a

aThis link will take you to a database that is owned and operated by HHS. Merck is not responsible for the content or maintenance of this site.​​​​​​​

Yes. To fill a prescription for LAGEVRIO, patients require positive results from a direct SARS-CoV-2 viral test.