Molnupiravir

by Editorial Board last updated 2021-11-22 10:42:16.847040-05:00
Lagevrio
  • Molnupiravir is a new antiviral agent for treatment of COVID-19.
  • The drug is a 5'-isobutyrate prodrug that is hydrolyzed to the ribonucleoside analog N-hydroxycytidine (NHC) prior to reaching the systemic circulation. Intracellular triphosphorylation of NHC produces NHC-TP, which competes with natural CTP for incorporation into nascent viral RNA by RNA polymerase. This results in viral error catastrophe.
  • On November 4, 2021, the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK authorized the use of molnupiravir for use in people who have:
    • Been symptomatic for no more than 3-5 days
    • Have mild to moderate COVID-19 and
    • Have at least one risk factor for developing severe illness. Such risk factors include obesity, older age (>60 years), diabetes mellitus, and  heart disease.
  • 800 mg (four 200 mg capsules) po q12h for five days, with or without food.
  • Capsules should not be open, crushed, or chewed.
  • Safety and efficacy in patients under 18 years of age not established.
  • No dosage adjustment in renal impairment required.
  • No dosage adjustment in hepatic impairment required.
  • Diarrhea (3%)
  • Nausea (2%)
  • Dizziness (1%)
  • Headache (1%)
  • Rash, urticaria
Class  Ribonucleoside analog
PK/PD Index  No data
Pharmaceutical
Preparation
 200 mg capsules
Usual Adult Dose  800 mg q12h x5 days
Pregnancy
Category
 Not recommended during pregnancy
Food Effect1  Take with or without food
Oral
Absorption2 (%)
 No data
Tmax (hr)  1.5
Peak Serum Level3
(μg/mL)
 2.97
Protein Binding
(%)
Negligible
Average Serum
Half-life4 (hr)
3.3 (NHC)
Biliary Penetration5 (%)  No data
CSF/Blood
Penetration6 (%)
 No data
Therapeutic Levels in CSF7  No data
Volume of Distribution8
(Vd)
 No data
AUC9
(μg*hr/mL)
 8.26 (AUC12)
CYP450, Transporter
Interactions
None known
  • Notes:
    • 1 Adult preparations unless otherwise noted.
    • 2 Absorption under optimal conditions.
    • 3 Total drug; adjust for protein binding to determine free drug concentration.
      • SD = after single dose
      • SS = steady state after multiple doses
    • 4 Assumes CrCl > 80 mL/min
    • 5 Peak concentration in bile/peak concentration in serum x 100
    • 6 CSF levels with inflammation
    • 7 Judgment based on drug dose & organism susceptibility. CSF concentration ideally ≥10x above MIC.
    • 8 Volume of Distribution (Vd):
      • V/F = Vd/oral bioavailability
      • Vss = Vd at steady state
      • Vss/F = Vd at steady state/oral bioavailability
    • 9 Area under the plasma concentration versus time curve
  • No data