The Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) to 2 oral antiviral therapies for COVID-19. Concise drug information for molnupiravir and Paxlovid is provided below. Prior to initiating treatment, careful consideration should be given to the known and potential risks and benefits associated with use of an unapproved treatment.
|Generic Name and Formulation||Molnupiravir 200mg; capsules.||Nirmatrelvir 150mg; ritonavir 100mg; tablets.|
|Pharmacological Class||Nucleoside analogue that inhibits SARS-CoV-2 replication by viral mutagenesis.||SARS-CoV-2 main protease inhibitor + HIV-1 protease inhibitor and CYP3A inhibitor.|
|Indication||For the treatment of mild to moderate COVID-19 in adults with positive results of direct SARS-CoV-2 viral testing who are at high risk for progressing to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options authorized by FDA are not accessible or clinically appropriate. Prior to initiating treatment carefully consider the known and potential risks and benefits.||For the treatment of mild to moderate COVID-19 in adults and pediatric patients 12 years of age and older weighing at least 40kg 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.|
|Limitations of Use||Molnupiravir is not authorized for patients less than 18 years of age; for those requiring hospitalization due to COVID-19; for use longer than 5 consecutive days; or for preexposure or postexposure prophylaxis for prevention of COVID-19.||Paxlovid is not authorized for initiation of treatment in patients requiring hospitalization due to severe or critical COVID-19; for preexposure or postexposure prophylaxis for prevention of COVID-19; or for use longer than 5 consecutive days.|
|Dosage||Take as soon as possible after a diagnosis of COVID-19 has been made and within 5 days of symptom onset.
Swallow whole. 800mg (four 200mg capsules) taken orally every 12 hours for 5 days. May be taken with or without food.
Safety and efficacy not established in pediatric patients.
|Initiate as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset.
Prescriptions should specify the numeric dose of each active ingredient within Paxlovid.
Swallow whole. 300mg nirmatrelvir (two 150mg tablets) with 100mg ritonavir (one 100mg tablet), with all 3 tablets taken together twice daily for 5 days. May be taken with or without food.
Moderate renal impairment (eGFR ≥30 to <60 mL/min): 150mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet), with both tablets taken together twice daily for 5 days.
Severe renal impairment (eGFR <30 mL/min): not recommended.
Severe hepatic impairment (Child-Pugh Class C): not recommended.
Not authorized for use in pediatric patients younger than 12 years old or weighing less than 40kg.
|Contraindications||None have been identified based on limited available data.||Coadministration with drugs highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions.
Coadministration with potent CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance.
|Warnings and Precautions||Embryo-fetal toxicity; not recommended for use during pregnancy. Individuals of childbearing potential should use effective contraception for the duration of treatment and for 4 days after the last dose. Nursing mothers: not recommended during treatment and for 4 days after the last dose. May affect bone and cartilage growth.||Ritonavir has been associated with hepatic transaminase elevations, clinical hepatitis, and jaundice. May lead to a risk of HIV-1 developing resistance to HIV protease inhibitors in patients with uncontrolled or undiagnosed HIV-1 infection.|
|Drugs Interactions||None have been identified based on limited available data.||See Contraindication. Drugs that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce Paxlovid therapeutic effect. Paxlovid can alter the plasma concentrations of other drugs. Consider the potential for drug interactions prior to and during Paxlovid therapy and review concomitant medications during treatment.|
|Adverse Reactions||Most common: Diarrhea, nausea, and dizziness.||Most common: Dysgeusia, diarrhea, hypertension, and myalgia.|
|How Supplied||Capsules (200mg)—40 count bottles.||Blister Card—30 tablets divided in 5 daily-dose blister cards. Each blister card contains 4 nirmatrelvir tablets (150mg each) and 2 ritonavir tablets (100mg each). Morning and evening doses indicated on card.|
Clinical Trial Summary – Molnupiravir
The EUA was supported by data from the phase 3 MOVe-OUT trial (ClinicalTrials.gov Identifier: NCT04575597), which compared the efficacy and safety of molnupiravir to placebo in nonhospitalized adults with symptom onset within 5 days of randomization. Results showed that 6.8% (n=48/709) of patients treated with molnupiravir were either hospitalized or died through day 29 following randomization compared with 9.7% (n=68/699) of patients treated with placebo (absolute risk reduction, 3.0%; 95% CI, 0.1-5.9; nominal P =.0218), corresponding to a relative risk reduction of 30% (relative risk, 0.70; 95% CI, 0.49-0.99). There was 1 death reported in the molnupiravir arm and 9 deaths in the placebo arm.
Clinical Trial Summary – Paxlovid
The randomized, double-blind, 2-arm, EPIC-HR study (ClinicalTrials.gov Identifier: NCT04960202) included 2246 patients with laboratory-confirmed SARS-CoV-2 infection and mild to moderate symptoms. Final results demonstrated that Paxlovid significantly reduced the risk of COVID-19-related hospitalization or death from any cause by 88% (within 5 days of symptom onset) compared with placebo (P <.0001). Through day 28, 0.8% (8/1039) of patients in the Paxlovid arm were either hospitalized or died vs 6.3% (66/1046) of those in the placebo arm.
- Molnupiravir fact sheet for health care providers. Accessed January 11, 2022. https://www.fda.gov/media/155054/download.
- Paxlovid fact sheet for health care providers. Accessed January 11, 2022. https://www.fda.gov/media/155050/download.