Materia Medica
Paxlovid: The First Authorized Oral Antiviral for COVID-19 Treatment in Non-Hospitalized Patients Elizabeth Posney, Pharm.D., PGY-1 Pharmacy Resident - Ambulatory Care, Allegheny Health Network, Allegheny General Hospital, Pittsburgh, PA Pfizer’s anti-COVID medication, Paxlovid (nirmatrelvir/ritonavir), is the newest tool in the healthcare provider’s toolkit to treat COVID-19 in nonhospitalized patients. It was authorized for emergency use by the FDA in December of 2021, and the COVID-19 treatment guidelines have recently been updated to include Paxlovid as the most preferred agent to use for COVID-19 treatment in the outpatient setting.1 Given the expanded access of this medication and still-rising numbers of COVID-19 cases, it is important for practitioners to stay updated on Paxlovid safety and efficacy data.
Figure 1. COVID-19 Treatment Guidelines: therapeutic management of non-hospitalized adults with COVID-191
How it works Pfizer took a novel approach to fighting the virus—instead of targeting the spike protein of SARS-CoV-2 like other COVID-19 treatments, this medication targets an intra-cellular protease that drives viral replication. Paxlovid is sold as two separate antiviral medications, nirmatrelvir and ritonavir, that are packaged together in a dose card blister pack. Patients take three oral tablets twice daily for 5 days: two tablets of nirmatrelvir 150 mg with one tablet of ritonavir 100 mg. Nirmatrelvir works by blocking the actions of SARS-CoV-2-3 26
chymotrypsin-like cysteine protease Mpro (3CL protease), which is an enzyme used for viral replication at the proteolysis stage, before viral RNA replication takes place (Figure 2). This enzyme was targeted because there is a low likelihood of off-target activity, and there are no recognized human analogues.2 Additionally, there is thought to be less mutation in this site compared to spike protein sites on the virus, which means there is a higher likelihood that efficacy can be maintained across variants.
The purpose of the ritonavir component is not to provide additional antiviral activity; instead, it is used to block the elimination of nirmatrelvir so that anti-viral activity is maintained. Ritonavir is a strong CYP3A4 inhibitor and allows for nirmatrelvir concentrations to be maintained at 5-6 times the concentration needed to block viral replication of SARS-CoV-2.2 In terms of pharmacokinetics, the medication is cleared hepatically by CYP3A4 (major) and CYP2D6 (minor) and has an elimination half-life of about 6 hours.3 www.acms.org
