Recommendations for the Management of Drug-Drug Interactions Between the COVID-19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications



Marzolini, Catia, Kuritzkes, Daniel R, Marra, Fiona, Boyle, Alison, Gibbons, Sara, Flexner, Charles, Pozniak, Anton, Boffito, Marta, Waters, Laura, Burger, David
et al (show 2 more authors) (2022) Recommendations for the Management of Drug-Drug Interactions Between the COVID-19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications. CLINICAL PHARMACOLOGY & THERAPEUTICS, 112 (6). pp. 1191-1200.

Access the full-text of this item by clicking on the Open Access link.
[thumbnail of Recommendations for the Management of Drug-Drug Interactions Between the COVID-19 Antiviral NirmatrelvirRitonavir (Paxlovid).pdf] PDF
Recommendations for the Management of Drug-Drug Interactions Between the COVID-19 Antiviral NirmatrelvirRitonavir (Paxlovid).pdf - Published version

Download (443kB) | Preview

Abstract

The coronavirus disease 2019 (COVID-19) antiviral nirmatrelvir/ritonavir (Paxlovid) has been granted authorization or approval in several countries for the treatment of patients with mild to moderate COVID-19 at high risk of progression to severe disease and with no requirement for supplemental oxygen. Nirmatrelvir/ritonavir will be primarily administered outside the hospital setting as a 5-day course oral treatment. The ritonavir component boosts plasma concentrations of nirmatrelvir through the potent and rapid inhibition of the key drug-metabolizing enzyme cytochrome P450 (CYP) 3A4. Thus nirmatrelvir/ritonavir, even given as a short treatment course, has a high potential to cause harm from drug-drug interactions (DDIs) with other drugs metabolized through this pathway. Options for mitigating risk from DDIs with nirmatrelvir/ritonavir are limited due to the clinical illness, the short window for intervention, and the related difficulty of implementing clinical monitoring or dosage adjustment of the comedication. Pragmatic options are largely confined to preemptive or symptom-driven pausing of the comedication or managing any additional risk through counseling. This review summarizes the effects of ritonavir on drug disposition (i.e., metabolizing enzymes and transporters) and discusses factors determining the likelihood of having a clinically significant DDI. Furthermore, it provides a comprehensive list of comedications likely to be used in COVID-19 patients which are categorized according to their potential DDI risk with nirmatrelvir/ritonavir. It also discusses recommendations for the management of DDIs which balance the risk of harm from DDIs with a short course of ritonavir, against unnecessary denial of nirmatrelvir/ritonavir treatment.

Item Type: Article
Uncontrolled Keywords: Humans, Ritonavir, Antiviral Agents, Drug Interactions, COVID-19 Drug Treatment
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 28 Oct 2022 15:03
Last Modified: 02 Feb 2023 21:35
DOI: 10.1002/cpt.2646
Open Access URL: https://doi.org/10.1002/cpt.2646
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3165853