Clinical Data for LAGEVRIO™ (molnupiravir)

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:
- 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
- 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

SELECTED SAFETY INFORMATION

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. [ Read More ]

Contraindications

No contraindications have been identified based on the limited available data on the emergency use of LAGEVRIO authorized under his EUA.… [ Read More ]

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 registry 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 the pregnancy registry at https://covid-pr.pregistry.com or 1-800-616-3791. Pregnant individuals exposed to LAGEVRIO or their healthcare providers can also report the exposure by contacting Merck Sharp & Dohme LLC, Rahway, NJ USA at 1-877-888-4231.
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:
- Complete and submit the report online: www.fda.gov/medwatch/report.htm
- Complete and submit a postage-paid FDA Form 3500 (https://www.fda.gov/media/76299/download)and return by:
  - Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787, or
  - Fax to 1-800-FDA-0178, or
- Call 1-800-FDA-1088 to request a reporting form
In addition, please provide a copy of all FDA MedWatch forms to:
Merck Sharp & Dohme LLC, Rahway, NJ USA:
Fax: 215-616-5677
E-mail: dpoc.usa@merck.com

Before prescribing LAGEVRIO™ (molnupiravir), 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.

AUTHORIZED USE

LAGEVRIO™ (molnupiravir) is authorized for use under an Emergency Use Authorization (EUA) for the treatment of adults with a current diagnosis of mild-to-moderate coronavirus disease 2019 (COVID-19):
- 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).

SELECTED SAFETY INFORMATION

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 registry 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 the pregnancy registry at https://covid-pr.pregistry.com or 1-800-616-3791. Pregnant individuals exposed to LAGEVRIO or their healthcare providers can also report the exposure by contacting Merck Sharp & Dohme LLC, Rahway, NJ USA at 1-877-888-4231.
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:
- Complete and submit the report online: www.fda.gov/medwatch/report.htm
- Complete and submit a postage-paid FDA Form 3500 (https://www.fda.gov/media/76299/download) and return by:
  - Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787, or
  - Fax to 1-800-FDA-0178, or
- Call 1-800-FDA-1088 to request a reporting form
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™ (molnupiravir), 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.

BMI=body mass index; CI=confidence interval; EUA=emergency use authorization; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2.

Reference: 1. Fact sheet for healthcare providers: emergency use authorization for LAGEVRIO™ (molnupiravir) capsules. Merck & Co., Inc. 2023.

Clinical Data

Study Design ¹

Baseline Characteristics ¹

Efficacy Results ¹

Efficacy Results in Non-Hospitalized Adults with COVID-19^1,a

Adverse Reactions from Clinical Studies¹

Adverse Reactions Occurring in Greater Than or Equal to 1% of Subjects Receiving LAGEVRIO in MOVe-OUT ^1,b

Laboratory Abnormalities¹

Contraindications

Warnings and Precautions

Contraindications

Contraindications

Warnings and Precautions

Adverse Reactions

Drug Interactions

Pregnancy/Breastfeeding

Males of Reproductive Potential

Required Reporting for Serious Adverse Events and Medication Errors

AUTHORIZED USE

SELECTED SAFETY INFORMATION

Contraindications

Warnings and Precautions

Adverse Reactions

Drug Interactions

Pregnancy/Breastfeeding

Males of Reproductive Potential

Required Reporting for Serious Adverse Events and Medication Errors

Clinical Data

Study Design 1

Baseline Characteristics 1

Efficacy Results 1

Efficacy Results in Non-Hospitalized Adults with COVID-191,a

Adverse Reactions from Clinical Studies1

Adverse Reactions Occurring in Greater Than or Equal to 1% of Subjects Receiving LAGEVRIO in MOVe-OUT 1,b

Laboratory Abnormalities1

Contraindications

Warnings and Precautions

Contraindications

Contraindications

Warnings and Precautions

Adverse Reactions

Drug Interactions

Pregnancy/Breastfeeding

Males of Reproductive Potential

Required Reporting for Serious Adverse Events and Medication Errors

AUTHORIZED USE

SELECTED SAFETY INFORMATION

Contraindications

Warnings and Precautions

Adverse Reactions

Drug Interactions

Pregnancy/Breastfeeding

Males of Reproductive Potential

Required Reporting for Serious Adverse Events and Medication Errors

Study Design ¹

Baseline Characteristics ¹

Efficacy Results ¹

Efficacy Results in Non-Hospitalized Adults with COVID-19^1,a

Adverse Reactions from Clinical Studies¹

Adverse Reactions Occurring in Greater Than or Equal to 1% of Subjects Receiving LAGEVRIO in MOVe-OUT ^1,b

Laboratory Abnormalities¹