Overview
11 DESCRIPTION LAGEVRIO capsules contain molnupiravir, a nucleoside analogue that inhibits SARS-CoV-2 replication by viral mutagenesis and is the 5´-isobutyrate ester of the ribonucleoside analog N4-hydroxycytidine (NHC). The chemical name for molnupiravir is {(2R,3S,4R,5R)-3,4-Dihydroxy-5-[(4Z)-4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl]oxolan-2-yl}methyl 2-methylpropanoate.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Molnupiravir is a prodrug with antiviral activity against SARS-CoV-2. It is metabolized to the cytidine nucleoside analogue, NHC which distributes into cells where NHC is phosphorylated to form the pharmacologically active ribonucleoside triphosphate (NHC-TP). NHC-TP incorporation (as NHC-monophosphate [NHC-MP]) into SARS-CoV-2 RNA by the viral RNA polymerase (nsp12) results in an accumulation of errors in the viral genome leading to inhibition of replication. The mechanism of action (known as viral error catastrophe or viral lethal mutagenesis) is supported by biochemical and cell culture data, studies of SARS-CoV-2 infection in animal models, and analyses of SARS-CoV-2 genome sequences in human subjects treated with LAGEVRIO. 12.
Common Doses
- 800 mg
- 200 mg
- 40 mL
- 5 mL
Dosage
2 DOSAGE AND ADMINISTRATION 2.1 Dosage for Emergency Use of LAGEVRIO in Adult Patients The dosage in adult patients is 800 mg (four 200 mg capsules) taken orally every 12 hours for 5 days, with or without food [see Clinical Pharmacology (12.3) ] . Take LAGEVRIO as soon as possible after a diagnosis of COVID-19 has been made, and within 5 days of symptom onset [see Emergency Use Authorization (1) and Clinical Studies (14) ] .
Black Box Warning
MANDATORY REQUIREMENTS FOR ADMINISTRATION OF LAGEVRIO UNDER EMERGENCY USE AUTHORIZATION In order to mitigate the risks of using this unapproved product under the EUA and to optimize the potential benefit of LAGEVRIO, the following steps are required. Use of LAGEVRIO under this EUA is limited to the following (all requirements must be met): Treatment of adults with 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 FDA are not accessible or clinically...
Contraindications
- 4 CONTRAINDICATIONS No contraindications have been identified based on the limited available data on the emergency use of LAGEVRIO authorized under this EUA.
Side Effects
- 6 ADVERSE REACTIONS 6.1 Adverse Reactions from Clinical Studies The following adverse reactions have been observed in the clinical study of LAGEVRIO that supported the EUA. The adverse reaction rates observed in these clinical trials cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Additional adverse events associated with LAGEVRIO may become apparent with more widespread use. Overall, more than 900 subjects have been exposed to LAGEVRIO 800 mg twice daily in clinical trials.
Interactions
- 7 DRUG INTERACTIONS No drug interactions have been identified based on the limited available data on the emergency use of LAGEVRIO authorized under this EUA. No clinical drug-drug interaction trials of LAGEVRIO with concomitant medications, including other treatments for mild-to-moderate COVID-19, have been conducted [see Clinical Pharmacology (12.3) ].