Clinically Relevant Interactions Between Ritonavir-Boosted Nirmatrelvir and Concomitant Antiseizure Medications: Implications for the Management of COVID-19 in Patients with Epilepsy.


Journal

Clinical pharmacokinetics
ISSN: 1179-1926
Titre abrégé: Clin Pharmacokinet
Pays: Switzerland
ID NLM: 7606849

Informations de publication

Date de publication:
09 2022
Historique:
accepted: 26 06 2022
pubmed: 28 7 2022
medline: 9 9 2022
entrez: 27 7 2022
Statut: ppublish

Résumé

Ritonavir-boosted nirmatrelvir (RBN) has been authorized recently in several countries as an orally active anti-SARS-CoV-2 treatment for patients at high risk of progressing to severe COVID-19 disease. Nirmatrelvir is the active component against the SARS-CoV-2 virus, whereas ritonavir, a potent CYP3A inhibitor, is intended to boost the activity of nirmatrelvir by increasing its concentration in plasma to ensure persistence of antiviral concentrations during the 12-hour dosing interval. RBN is involved in many clinically important drug-drug interactions both as perpetrator and as victim, which can complicate its use in patients treated with antiseizure medications (ASMs). Interactions between RBN and ASMs are bidirectional. As perpetrator, RBN may increase the plasma concentration of a number of ASMs that are CYP3A4 substrates, possibly leading to toxicity. As victims, both nirmatrelvir and ritonavir are subject to metabolic induction by concomitant treatment with potent enzyme-inducing ASMs (carbamazepine, phenytoin, phenobarbital and primidone). According to US and European prescribing information, treatment with these ASMs is a contraindication to the use of RBN. Although remdesivir is a valuable alternative to RBN, it may not be readily accessible in some settings due to cost and/or need for intravenous administration. If remdesivir is not an appropriate option, either bebtelovimab or molnupiravir may be considered. However, evidence about the clinical efficacy of bebtelovimab is still limited, and molnupiravir, the only orally active alternative, is deemed to have appreciably lower efficacy than RBN and remdesivir.

Identifiants

pubmed: 35895276
doi: 10.1007/s40262-022-01152-z
pii: 10.1007/s40262-022-01152-z
pmc: PMC9325946
doi:

Substances chimiques

Antibodies, Neutralizing 0
Antiviral Agents 0
bebtelovimab 8YL4SYR6CU
Ritonavir O3J8G9O825

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

1219-1236

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

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Auteurs

Maor Wanounou (M)

Clinical Pharmacology Unit, Division of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Faculty of Medicine, School of Pharmacy, Institute of Drug Research, Hebrew University, Jerusalem, Israel.

Yoseph Caraco (Y)

Clinical Pharmacology Unit, Division of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

René H Levy (RH)

Department of Pharmaceutics and Neurological Surgery, University of Washington, Seattle, WA, USA.

Meir Bialer (M)

Faculty of Medicine, School of Pharmacy, Institute of Drug Research, Hebrew University, Jerusalem, Israel. meirb@ekmd.huji.ac.il.
David R. Bloom Center for Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel. meirb@ekmd.huji.ac.il.

Emilio Perucca (E)

Department of Medicine (Austin Health), The University of Melbourne, Melbourne, VIC, Australia.
Department of Neuroscience, Monash University, Melbourne, VIC, Australia.

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Classifications MeSH