Proposal for a Simple Algorithmic Approach to Manage Drug-Drug Interactions of Oral Anticoagulants with Nirmatrelvir/Ritonavir in COVID-19 Outpatients Comment

In December 2021, the U.S. Food and Drug Administration (FDA) issued emergency use authorizations (EUAs) for two oral antiviral at-home treatments for coronavirus disease 2019 (COVID-19), nirmatrelvir/ritonavir (Paxlovid [Pfizer]), and molnupiravir (Merck).[1] While their mechanisms of action somewhat differ, these agents are considered “game-changers” by some observers, since they do not require administration by intravenous infusion as monoclonal antibodies do. Initial efficacy studies suggest that nirmatrelvir/ritonavir may be more effective than molnupiravir,[1] but it also has more drug interactions of potential concern, especially related to anticoagulant therapy.[1] Molnupiravir does not have any reported interaction with anticoagulant agents.[2] Additionally, remdesivir (Veklury [Gilead]) and bebtelovimab (Lilly) are parenteral agents recently granted an EUA for use in the outpatient setting as treatment of mild-to-moderate COVID-19 in adults with positive results of direct SARS-CoV-2 viral testing, who are at high risk for progression to severe COVID-19, including hospitalization or death.[3] Neither of these agents have any known interaction with anticoagulants.[2]