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

Autor: Marzolini C; Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel and University of Basel, Basel, Switzerland.; Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK., Kuritzkes DR; Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Marra F; Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.; Department of Pharmacy, National Health Service Greater Glasgow and Clyde, Glasgow, UK., Boyle A; Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.; Department of Pharmacy, National Health Service Greater Glasgow and Clyde, Glasgow, UK., Gibbons S; Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK., Flexner C; Divisions of Clinical Pharmacology and Infectious Diseases, School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA., Pozniak A; Chelsea and Westminster Hospital National Health Service Foundation Trust, London, UK.; London School of Hygiene and Tropical Medicine, London, UK., Boffito M; Chelsea and Westminster Hospital National Health Service Foundation Trust, London, UK., Waters L; Mortimer Market Centre, Central and North West London, National Health Service Foundation Trust, London, UK., Burger D; Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.; Global DDI Solutions, Utrecht, The Netherlands., Back DJ; Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK., Khoo S; Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Jazyk: angličtina
Zdroj: Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2022 Dec; Vol. 112 (6), pp. 1191-1200. Date of Electronic Publication: 2022 Jun 07.
DOI: 10.1002/cpt.2646
Abstrakt: 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.
(© 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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