Usual Adult Dose for COVID-19

For investigational use only

800 mg orally every 12 hours for 5 days

Comments:

• The US FDA issued an Emergency Use Authorization (EUA) to allow the emergency use of the unapproved drug molnupiravir for the treatment of patients 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 US FDA are not accessible/clinically appropriate; this drug is not approved by the US FDA for this or any use.
• This drug should be administered as soon as possible after COVID-19 has been diagnosed and within 5 days of symptom onset.
• Safety and efficacy of use beyond 5 days have not been established.
• If hospitalization is required after starting treatment with this drug, the patient may complete the full 5-day treatment course per health care provider's discretion.
• No dose adjustment is recommended in older adult patients.
• For additional information: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs

Use: For the treatment of patients with a current diagnosis of mild to moderate 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 US FDA are not accessible/clinically appropriate

Renal Dose Adjustments

Renal dysfunction: No adjustment recommended

Liver Dose Adjustments

Liver dysfunction: No adjustment recommended

Precautions

US BOXED WARNINGS:
Mandatory Requirements for Administration of Molnupiravir Under EUA:

• To mitigate the risk of using this unapproved drug under the EUA and to optimize the potential benefit of this drug, the following steps are required; use of this drug under this EUA is limited to the following (all requirements must be met):

(1) Treatment of adults with a current diagnosis of mild to moderate 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 US FDA are not accessible/clinically appropriate
(2) The prescribing health care provider should review the Fact Sheet for Patients and Caregivers with the patient or caregiver before the patient receives this drug; health care providers must provide an electronic or hard copy of the Fact Sheet for Patients and Caregivers to the patient/caregiver before the patient receives this drug and must document that the patient/caregiver was given an electronic/hard copy of the Fact Sheet for Patients and Caregivers.
(3) The prescribing health care provider must inform the patient/caregiver that:

• This drug is unapproved and is authorized for use under this EUA.
• Other therapeutics are currently approved or authorized for the same use as this drug; the Fact Sheet for Health Care Providers should be consulted regarding approved available alternatives.
• There are benefits and risks of taking this drug as summarized in the Fact Sheet for Patients and Caregivers.
• There is a pregnancy registry.
• Females of childbearing potential should use reliable contraception correctly and consistently, as applicable, for the duration of therapy and for 4 days after the last dose.
• Males of reproductive potential who are sexually active with females of childbearing potential should use reliable contraception correctly and consistently during therapy and for at least 3 months after the last dose.

(4) The prescribing health care provider must assess whether a female of childbearing potential is pregnant or not, if clinically indicated.
(5) Based on findings from animal reproduction studies, this drug may cause fetal harm when administered to pregnant patients; if this drug is used during pregnancy, the prescribing health care providers must counsel the patient about the known and potential benefits and the potential risk of using this drug during pregnancy, as summarized in the Fact Sheet for Patients and Caregivers.
(6) If the decision is made to use this drug during pregnancy, the prescriber must document that the known and potential benefits and the potential risk of using this drug during pregnancy, as summarized in the Fact Sheet for Patients and Caregivers, were discussed with the patient.
(7) The prescribing health care provider must document that a pregnant patient was advised of the pregnancy registry at covid-pr.pregistry.com or 1-800-616-3791.
(8) The prescribing health care provider and/or the provider's designee is/are responsible for mandatory reporting of all medication errors and serious adverse events potentially related to this drug within 7 calendar days from health care provider's awareness of the event.

• ClinicalTrials.gov should be consulted for information on clinical trials of this and other therapies for the treatment of COVID-19.

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Dialysis

Data not available

Other Comments

Administration advice:

• Before starting this drug, carefully consider the known and potential risks and benefits.
• Before starting this drug, assess the pregnancy status for patients of childbearing potential, if clinically indicated.
• Administer with or without food.
• Swallow capsules whole; do not open, break, or crush.
• Capsule contents can be mixed with water and administered via nasogastric (NG) or orogastric (OG) tube (12 French or larger).
• Open 4 capsules and transfer the contents into a clean container with a lid. Add 40 mL of water to the container.
• Put the lid on the container and shake for 3 minutes to mix the capsule contents and water thoroughly. The capsule contents may not dissolve completely; the prepared mixture may have visible undissolved particulates which are acceptable for administration.
• Flush NG/OG tube with 5 mL of water before administration.
• Use a catheter tip syringe to draw up the entire contents from the container and administer immediately through the NG/OG tube (12 French or larger); do not keep the mixture for future use.
• If any of the capsule contents remain in the container, add 10 mL of water to the container, mix, use the same syringe to draw up the entire contents from the container, and administer through the NG/OG tube; repeat as needed until no capsule contents remain in the container or syringe.
• Flush the NG/OG tube with 5 mL of water twice (10 mL total) after administration of the mixture.
• Completion of the full 5-day treatment course and continued isolation (according to public health recommendations) are important to maximize viral clearance and minimize transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Storage requirements:

• Store at 20C to 25C (68F to 77F); excursions permitted to 15C to 30C (59F to 86F).

General:

• Limitations of Authorized Use:
• This drug is not authorized for use in patients younger than 18 years.
• This drug is not authorized for initiation of therapy in patients hospitalized due COVID-19; benefit of treatment with this drug has not been seen in patients when it was started after hospitalization due to COVID-19.
• This drug is not authorized for use longer than 5 consecutive days.
• This drug is not authorized for preexposure or postexposure prophylaxis for prevention of COVID-19.
• This drug may only be prescribed for an individual patient by physicians, advanced practice registered nurses, and physician assistants licensed/authorized under state law to prescribe drugs in the therapeutic class to which this drug belongs (i.e., anti-infectives).
• The US CDC website (https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html) should be consulted for information on medical conditions and factors associated with increased risk for progression to severe COVID-19 (including hospitalization and death); the benefit-risk should be considered for each patient.

Patient advice:

• Read the Fact Sheet for Patients and Caregivers.
• Avoid missing doses and complete the entire course of therapy.
• If a dose is missed within 10 hours of the usual time taken, administer the missed dose as soon as possible and resume the normal dosing schedule; if a dose is missed by more than 10 hours, do not administer the missed dose and just resume the usual dosing schedule; do not double the dose to make up for a missed dose.
• Continue to self-isolate according to public health recommendations.
• Discontinue this drug and inform health care provider at the first sign of skin rash, hives/other skin reactions, rapid heartbeat, difficulty in swallowing/breathing, any swelling suggesting angioedema (e.g., swelling of the lips, tongue, face, tightness of the throat, hoarseness), or other symptoms of an allergic reaction.
• Patients of childbearing potential: Notify health care provider of known/suspected pregnancy; use effective contraception correctly and consistently while taking this drug and for 4 days after the last dose.
• Sexually active patients of reproductive potential with partners of childbearing potential: Use reliable contraception correctly and consistently while taking this drug and for at least 3 months after the last dose.
• If exposure to this drug occurred during pregnancy, participation in the pregnancy registry is encouraged; you may enroll at covid-pr.pregistry.com or 1-800-616-3791.
• Lactating patients: Consider interrupting breastfeeding and consider pumping and discarding breast milk during therapy and for 4 days after the last dose.