Molnupiravir and Nirmatrelvir-Ritonavir: Oral COVID Antiviral Drugs

At a crucial time with rapid spread of Omicron SARS-CoV-2 virus variant globally, the United States Food and Drug Administration has issued an emergency use authorization for two oral antivirals molnupiravir (>18 years) and nirmatrelvir-ritonavir (Paxlovid) (≥12 years; >40kg ) for the outpatient treatment of mild to moderate COVID-19 patients who are at risk for progression. Molnupiravir is a nucleoside analogue, whereas nirmatrelvir is a SARS-CoV-2 main protease inhibitor, and ritonavir is an HIV-1 protease inhibitor. Drug interactions are a major concern for nirmatrelvir-ritonavir. Nirmatrelvir-ritonavir demonstrated a greater risk reduction in hospitalization and death than molnupiravir compared to placebo. Both drugs need to be started within five days of symptoms onset and given for five days duration. This article will review the two oral COVID-19 antiviral drugs including the mechanisms of action, antiviral activity, pharmacokinetics, drug interactions, clinical experience including trials, adverse events, recommended indications, and formulary considerations.