Molnupiravir and Nirmatrelvir-Ritonavir: Oral Coronavirus Disease 2019 Antiviral Drugs

At a crucial time with rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant globally, the United States Food and Drug Administration has issued an emergency use authorization for 2 oral antivirals, molnupiravir (in persons aged ≥18 years) and nirmatrelvir-ritonavir (Paxlovid) (in persons aged ≥12 years weighing ≥40 kg), for the outpatient treatment of patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at risk for progression. Molnupiravir is a nucleoside analogue, whereas nirmatrelvir is a SARS-CoV-2 main protease inhibitor, and ritonavir is a human immunodeficiency virus type 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 5 days of symptoms onset and given for 5 days' duration. This article reviews the 2 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.