A biological pharmacology network to secure the risk of drug–drug interaction with nirmatrelvir/ritonavir - 22/08/24

Doi : 10.1016/j.therap.2024.07.003

Florian Lemaitre ^a,^b,^c,⁎ , Lidvine Boland ^d,^e, Camille Tron ^a,^b,^c, Matthieu Grégoire ^f,^g, Véronique Lelong-Boulouard ^h,ⁱ, Peggy Gandia ^j,^k, Françoise Goirand ^l,^m, Nicolas Gambier ^n,^o, Christelle Boglione-Kerrien ^a,^b,^c, Bénédicte Franck ^a,^b,^c, Sébastien Lalanne ^a,^b,^c, Arnaud Devresse ^p,^q, Sebastien Briol ^p,^q,^r, Vincent Haufroid ^d,^e, Marie-Clémence Verdier ^a,^b,^c
on behalf of the
SFPT Therapeutic Drug Monitoring, Treatment Personalization group (STP-PT) of the French Society of Pharmacology, Therapeutics (SFPT)
^a Université de Rennes, CHU de Rennes, Inserm, EHESP, Institut de recherche en santé, environnement et travail (Irset), UMR S 1085, 35000 Rennes, France
^b Inserm, Clinical Investigation Center 1414, 35000 Rennes, France
^c FHU SUPORT, 35000 Rennes, France
^d Department of Clinical Chemistry, Cliniques universitaires Saint-Luc, 1000 Brussels, Belgium
^e Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, 1000 Brussels, Belgium
^f Nantes Université, CHU de Nantes, Cibles et médicaments des infections et de l’immunité, IICiMed, UR 1155, 44000 Nantes, France
^g Nantes Université, CHU de Nantes, service de pharmacologie clinique, 44000 Nantes, France
^h Normandie Université, UNICAEN, Inserm COMETE, U1075, 14000 Caen, France
ⁱ CHU de Caen, Pharmacology Department, 14000 Caen, France
^j Laboratoire de pharmacocinétique et toxicologie, Institut fédératif de biologie, CHU de Toulouse, 31000 Toulouse, France
^k INTHERES, Université de Toulouse, INRAE, ENVT, 31000 Toulouse, France
^l Laboratoire de pharmacologie et toxicologie, centre hospitalier universitaire Dijon-Bourgogne, 21000 Dijon, France
^m University of Burgundy, Faculty of Medicine and Pharmacy, 21000 Dijon, France
ⁿ CHRU de Nancy, service de pharmacologie clinique et toxicologie, 54000 Nancy, France
^o Université de Lorraine, CNRS, IMoPA, 54000 Nancy, France
^p Department of Nephrology, Cliniques universitaires Saint-Luc, 1000 Brussels, Belgium
^q Department of Surgery and Abdominal Transplant, Cliniques universitaires Saint-Luc, 1000 Brussels, Belgium
^r Department of Internal Medicine and Infectious Disease, Cliniques universitaires Saint-Luc, 1000 Brussels, Belgium

^⁎Corresponding author. Department of Biological Pharmacology, Hôpital Pontchaillou, CHU de Rennes, 2, rue Henri-Le-Guilloux, 35000 Rennes, France.Department of Biological Pharmacology, Hôpital Pontchaillou, CHU de Rennes2, rue Henri-Le-GuillouxRennes35000France

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Thursday 22 August 2024

Summary

Nirmatrelvir/ritonavir is a protease inhibitor antiviral drug indicated in the treatment of severe acute respiratory syndrome coronavirus-2 infections in high-risk patients for a severe disease. Unfortunately, ritonavir, used to boost nirmatrelvir pharmacokinetics, can also inhibit or induce the metabolism of other co-administered drugs substrates. This may lead to a subsequent risk of adverse drug reaction and lack of efficacy. In this study, we aimed at describing the expert advices provided by the biological pharmacology network of the SFPT (i.e., the therapeutic drug monitoring specialists working in the laboratories of the pharmacology departments in France/Belgium). From February to August 2022, we collected all specialized advices provided by the biological pharmacology network of the SFPT. Seven pharmacology departments actively participated in the study (Brussels Saint-Luc Hospital in Belgium, Caen, Dijon, Nantes, Nancy, Rennes and Toulouse in France). We collected the following data: patient's age, date of nirmatrelvir/ritonavir initiation, clinical department requiring the expert advice, patient's treatments, and advice provided. One hundred and six expert advice on 753 drugs were provided during the seven months of data collection. Two centers provided 83% of all the expert advice (around 8/month). Patients originated form a transplantation department in 65% of the cases. The most common request were for cardiac drugs (28%), immunosuppressive drugs (24%) and endocrine drugs (18%). The advice were distributed as follows: treatment continuation, treatment discontinuation during the antiviral course, dosage adjustment, and treatment switch in 59%, 28%, 11%, and 1.6% of the cases, respectively. Only 2 pieces of advice (0.3%) constituted treatment contra-indications. Drug monitoring was proposed in 10% of prescription lines. Expert advice provided by the biological pharmacology network of the SFPT allows securing the combination of nirmatrelvir/ritonavir with other concomitant drugs. Most of eligible patients to the antiviral drug can benefit from it despite the risk of drug–drug interaction.

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Keywords : COVID-19, Drug monitoring, Safety, Cytochrome P450, Antivirals