Optimizing the use of Paxlovid in clinical practice

On December 22, 2021, the United States Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for nirmatrelvir/ritonavir (Paxlovid) for the treatment of mild to moderate coronavirus disease 2019 (COVID-19). The drug is authorized for use in patients 12 years of age and older weighing at least 40 kg who have tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and who are at high risk for progression to severe COVID-19. Nirmatrelvir, an orally bioavailable protease inhibitor that prevents SARS-CoV-2 replication by cleaving the two viral polyproteins, is packaged with ritonavir, a cytochrome P450 (CYP)3A4 inhibitor and pharmacokinetic boosting agent that increases nirmatrelvir concentrations. Although Paxlovid has demonstrated clinical efficacy in unvaccinated patients with COVID-19, its role in the treatment of other populations is less clear. This manuscript reviews what is known about Paxlovid and explores how this drug may be used in the future to treat patients with SARS-CoV-2 infection.