Version May 2024
COVID-19, mild to moderate; treatment (alternative agent):
Note: For patients at high risk of progression to severe COVID-19, including hospitalization or death (Ref).
Oral: 800 mg every 12 hours for 5 days; initiate as soon as possible after COVID-19 diagnosis, and within 5 days of symptom onset. After initiating treatment with molnupiravir, if hospitalization is required, completion of 5-day course is at the health care provider's discretion (Ref).
Missed dose:If a dose is missed within 10 hours of usual administration time, administer the missed dose as soon as possible, and resume normal dosing schedule. If a dose is missed by more than 10 hours, do not administer the missed dose, and resume dosing at the next scheduled administration time. Do not double the dose to make up for a missed dose (Ref).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary (Ref).
eGFR <30 mL/minute/1.73 m2: No dosage adjustment necessary (Ref). Note: Molnupiravir has not been formally evaluated in this population, but kidney impairment is unlikely to substantially impact pharmacokinetics as only 3% is eliminated in the urine (Ref). Several case series report the safety and tolerability of molnupiravir in patients with eGFR <30 mL/minute/1.73 m2; nausea may be more common in patients with chronic kidney disease (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzability (unknown; has not been studied):
No dosage adjustment necessary (Ref); when scheduled doses fall on a hemodialysis day, administration after hemodialysis may be preferred (Ref). Note: Molnupiravir has not been formally evaluated in this population, but kidney impairment is unlikely to substantially impact pharmacokinetics (Ref). Several case series support the safety and tolerability of molnupiravir in patients receiving hemodialysis (Ref).
Peritoneal dialysis: No dosage adjustment necessary (Ref). Note: Molnupiravir has not been formally evaluated in this population, but kidney impairment is unlikely to substantially impact pharmacokinetics (Ref).
CRRT: No dosage adjustment likely to be necessary (Ref). Note: Since there are no data describing the pharmacokinetics of molnupiravir in critical illness or in patients receiving CRRT the use of an alternative agent may be considered (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment likely to be necessary; when scheduled dose falls on a PIRRT day, administer after PIRRT may be preferred when feasible (Ref). Note: Since there are no data describing the pharmacokinetics of molnupiravir in critical illness or in patients receiving PIRRT the use of an alternative agent may be considered (Ref).
No dosage adjustment necessary (Ref).
Refer to adult dosing.
(For additional information see "Molnupiravir (United States: Authorized for use): Pediatric drug information")
Note: Do not use in patients <18 years of age due to the potential for bone and cartilage toxicity (Ref).
COVID-19, mild to moderate; treatment (outpatients with high risk of progression to severe illness) (alternative agent):
Adolescents ≥18 years: Oral: 800 mg every 12 hours for 5 days; initiate as soon as possible after COVID-19 diagnosis, and within 5 days of symptom onset. After initiating treatment with molnupiravir, if hospitalization is required, completion of 5-day course is at the health care provider's discretion (Ref).
Adolescents ≥18 years: No dosage adjustment necessary (Ref).
Adolescents ≥18 years: No dosage adjustment necessary (Ref).
Immediate hypersensitivity reactions, including anaphylaxis and angioedema, have been reported. Delayed hypersensitivity reactions, including skin rash, acne vulgaris, allergic dermatitis, and exfoliation of the skin, have also been reported (Ref).
Mechanism: Non–dose-related; immunologic. Immediate hypersensitivity reactions (eg, anaphylaxis) can be non–IgE-mediated or IgE-mediated. Delayed hypersensitivity reactions, including rash, are commonly T-cell-mediated (Ref).
Onset: Immediate hypersensitivity reactions: Rapid; occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref). Delayed hypersensitivity reactions: Nonspecific rash: Intermediate; occur 6 to 10 days after initiation (Ref).
Adverse reactions and incidences are derived from the FDA-issued emergency use authorization (EUA). Adverse reactions reported in adults. Refer to EUA for information regarding reporting adverse reactions (FDA 2023).
Post-authorization:
Dermatologic: Acne vulgaris (Pupo Correia 2022), allergic dermatitis (Pupo Correia 2022), erythema of skin, exfoliation of skin (Pupo Correia 2022), pruritus (Pupo Correia 2022), skin rash (Pupo Correia 2022), urticaria (Kimata 2023)
Gastrointestinal: Diarrhea (Kimata 2023), vomiting (Kimata 2023)
Hypersensitivity: Anaphylaxis, angioedema
Nervous system: Dizziness (Kimata 2023), headache (Kimata 2023)
There are no contraindications listed in the FDA emergency use authorization (EUA) fact sheet for health care providers.
Concerns related to adverse effects:
• Bone and cartilage effects: Bone and cartilage toxicity was observed in animals after repeat dosing; molnupiravir is not authorized for use in patients <18 years of age because it may affect bone and cartilage growth (FDA 2023).
Other warnings/precautions:
• Viral rebound: Viral rebound and recurrence of COVID-19 symptoms have been reported in some patients after completing treatment. The frequency, mechanism, and clinical implications of these events are unclear. Viral rebound and recurrence of COVID-19 symptoms can occur in the absence of treatment. Concern for viral rebound and/or recurrence of symptoms should not be a reason to avoid antiviral therapy (NIH 2023).
Molnupiravir approved for emergency use authorization by the FDA December 2021.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Lagevrio: 200 mg
No
Capsules (Lagevrio Oral)
200 mg (per each): $0.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Molnupiravir is not commercially available; it is available as part of ongoing clinical trials and under an emergency use authorization (EUA) from the FDA. Molnupiravir is available from the distributor, AmerisourceBergen.
As part of the EUA, information consistent with fact sheets pertaining to emergency use of molnupiravir are required to be available for health care providers and patients/caregivers, and certain mandatory requirements for molnupiravir administration under the EUA must be met as outlined in the FDA EUA letter; the fact sheets may be accessed at https://www.molnupiravir.com. Additionally, health care providers must track and report all medication errors and serious adverse events potentially associated with molnupiravir use by either submitting a MedWatch form (https://www.fda.gov/medwatch/report.htm), FDA Form 3500 (health professional; available at: https://www.fda.gov/safety/medwatch-forms-fda-safety-reporting/instructions-completing-form-fda-3500) by mail (MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787) or fax (1-800-FDA-0178), or by calling 1-800-FDA-1088 to request a reporting form; a copy of all MedWatch forms should also be provided to Merck & Co., Inc. (phone: 1-800-672-6372; fax: 1-215-616-5677; e-mail: [email protected]).
Oral: Administer with or without food. Swallow capsules whole; do not open, break, or crush (Ref).
Nasogastric or orogastric feeding tube (NG or OG tube): For patients unable to swallow capsules whole, capsule contents may be dispersed in water to be administered via nasogastric (NG) or orogastric (OG) tube. Open capsules and transfer contents to a container with a lid; add 40 mL of water to the container and shake thoroughly (3 minutes). Flush NG/OG tube with 5 mL of water prior to administration; draw up entire contents in container using a catheter-tip syringe and administer immediately through the NG/OG tube (≥12F). If contents remain in container, add 10 mL of water to the container, mix, and draw up into the same syringe administering via the NG/OG tube; repeat as needed until container and syringe are empty. Flush NG/OG tube twice with 5 mL of water (10 mL total) after administering the mixture. Note: Capsule contents may not dissolve completely and visible undissolved particulates are acceptable; do not store mixture for future use (Ref).
Oral: Administer with or without food. Swallow capsules whole; do not open, break, or crush (Ref).
Nasogastric (NG) or orogastric (OG) tube (12 French or larger): Empty 4 capsules (800 mg) into a clean container with a lid. Add 40 mL water, close the lid, and shake for 3 minutes; capsule contents may not completely dissolve; undissolved particles are acceptable to administer. Flush NG or OG tube with 5 mL water, then administer prepared mixture immediately using a catheter tip syringe. If any capsule contents remain in container, add 10 mL of water, mix, and administer through the NG or OG tube with the same syringe; repeat as needed until no capsule contents remain in syringe or container. After administering the full dose, flush the NG or OG tube with 5 mL of water twice (10 mL total).
Missed dose: If a dose is missed within 10 hours of usual administration time, administer the missed dose as soon as possible, and resume normal dosing schedule. If a dose is missed by >10 hours, do not administer the missed dose, and resume dosing at the next scheduled administration time. Do not double the dose to make up for a missed dose (Ref).
See "Use: Off Label."
COVID-19, treatment, mild to moderate (alternative agent)
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Evaluate and verify pregnancy status prior to use in patients who may become pregnant.
Pregnancy testing is recommended for patients who do not have regular menstrual cycles, who are unsure of the first day of their last cycle, or who do not use contraception correctly and consistently. Pregnancy status does not need confirmed in patients using an intrauterine system or contraceptive implant, patients who have undergone permanent sterilization, or when pregnancy is otherwise not possible.
Patients who may become pregnant should use reliable contraception correctly and consistently during therapy and for 4 days after the last dose of molnupiravir. Sexually active males with partners who may become pregnant should also use effective contraception during therapy and for at least 3 months after the last molnupiravir dose.
Based on data from animal reproduction studies, in utero exposure to molnupiravir may cause fetal harm. Molnupiravir is currently available under FDA emergency use authorization (EUA) for the treatment of COVID-19; pregnant patients were not eligible for inclusion in a phase 3 study (Jayk Bernal 2021).
The risk of severe illness from COVID-19 infection is increased in symptomatic pregnant patients compared to nonpregnant patients. Pregnant and recently pregnant patients with moderate or severe infection are at increased risk of complications such as hypertensive disorders of pregnancy, postpartum hemorrhage, or other infections compared to pregnant patients without COVID-19. Symptomatic pregnant patients may require ICU admission, mechanical ventilation, or ventilatory support (ECMO) compared to symptomatic nonpregnant patients. Other adverse pregnancy outcomes include preterm birth and stillbirth. The risk of coagulopathy, cesarean delivery, and maternal death may be increased; neonates have an increased risk for NICU admission. Maternal age and comorbidities such as diabetes, hypertension, lung disease, and obesity may also increase the risk of severe illness in pregnant and recently pregnant patients (ACOG 2022; NIH 2022).
In general, the treatment of COVID-19 infection during pregnancy is the same as in nonpregnant patients. However, because data for most therapeutic agents in pregnant patients are limited, treatment options should be evaluated as part of a shared decision-making process (NIH 2022). Use of molnupiravir in pregnancy is not recommended unless no other options are available, and therapy is clearly indicated. In pregnant patients at high risk of progressing to severe disease, use may be considered after the period of embryogenesis (eg, >10 weeks' gestation) when preferred treatments are not available (NIH 2022). If the decision is made to use molnupiravir in a pregnant patient, the prescriber must document that the known and potential risks, as outlined in the Fact Sheet for Patients and Caregivers, have been communicated to the patient. Information related to the treatment of COVID-19 during pregnancy continues to emerge; refer to current guidelines for the treatment of pregnant patients.
Data collection to monitor pregnancy and infant outcomes following exposure to molnupiravir is ongoing. Health care providers must document that the pregnant patient was made aware of the molnupiravir pregnancy surveillance program. Health care providers must enroll patients who agree to participate (https://covid-pr.pregistry.com or 1-800-616-3791, or by contacting the manufacturer at 1-877-888-4231). Patients may also enroll themselves.
It is not known if molnupiravir is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 4 days after the last molnupiravir dose; patients may express and discard breast milk during this time.
Information related to COVID-19 and breastfeeding is available from the World Health Organization (https://www.who.int/news/item/28-04-2020-new-faqs-address-healthcare-workers-questions-on-breastfeeding-and-covid-19).
Pregnancy test prior to initiation, as clinically indicated (FDA 2023).
Molnupiravir is metabolized to the cytidine nucleoside analog, NHC, which is further phosphorylated to the active ribonucleoside triphosphate (NHC-TP). NHC-TP is incorporated into SARS-CoV-2 RNA by viral RNA polymerase, resulting in errors in viral genome and subsequently inhibition of replication (FDA 2023).
Distribution: NHC: 142 L (FDA 2023).
Protein binding: NHC: Does not appear to be protein bound (FDA 2023).
Metabolism: Molnupiravir is metabolized to NHC; NHC undergoes phosphorylation to pharmacologically active ribonucleoside triphosphate.
Half-life elimination: NHC: 3.3 hours (FDA 2023).
Time to peak: NHC: 1.5 hours (FDA 2023).
Excretion: NHC: Urine (3%) (FDA 2023).
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