Everolimus Personalized Therapy: Second Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.

Florian Lemaitre, Phil Walson, Roland Lawson, Pawel K Kunicki, Kamisha Johnson-Davis, Taihei Ito, Kirsten Bornemann-Kolatzki, Sander Vinks, Smita Pattanaik, Tomoyuki Mizuno, Maja-Theresa Dieterlen, Teun van Gelder, Stein Bergan, Pierre Marquet, Raman Venkataramanan, Markus J Barten, Ron van Schaik, Laure Elens, Jean-Baptiste Woillard, Eberhard Wieland, Maria Shipkova, Michael Oellerich, Mercè Brunet, Dirk Jan A R Moes, Nuria Lloberas, Loralie J Langman, Olga Millan, Satohiro Masuda, Christoph Seger, Tomasz Pawinski, Ofelia Noceti, Brenda de Winter

Journal: Therapeutic drug monitoring 2025;47(1):4-31

PMID: 39331837

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Abstract

The Immunosuppressive Drugs Scientific Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology established the second consensus report to guide therapeutic drug monitoring (TDM) of everolimus (EVR) and its optimal use in clinical practice 7 years after the first version was published in 2016. This version provides information focused on new developments that have arisen in the last 7 years. For the general aspects of the pharmacology and TDM of EVR that have retained their relevance, readers can refer to the 2016 document. This edition includes new evidence from the literature, focusing on the topics updated during the last 7 years, including indirect pharmacological effects of EVR on the mammalian target of rapamycin complex 2 with the major mechanism of direct inhibition of the mammalian target of rapamycin complex 1. In addition, various concepts and technical options to monitor EVR concentrations, improve analytical performance, and increase the number of options available for immunochemical analytical methods have been included. Only limited new pharmacogenetic information regarding EVR has emerged; however, pharmacometrics and model-informed precision dosing have been constructed using physiological parameters as covariates, including pharmacogenetic information. In clinical settings, EVR is combined with a decreased dose of calcineurin inhibitors, such as tacrolimus and cyclosporine, instead of mycophenolic acid. The literature and recommendations for specific organ transplantations, such as that of the kidneys, liver, heart, and lungs, as well as for oncology and pediatrics have been updated. EVR TDM for pancreatic and islet transplantation has been added to this edition. The pharmacodynamic monitoring of EVR in organ transplantation has also been updated. These updates and additions, along with the previous version of this consensus document, will be helpful to clinicians and researchers treating patients receiving EVR.

Address: Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Japan.; Université de Rennes, CHU Rennes, Inserm, EHESP, IRSET-UMR S 1085, Rennes, France.; INSERM, Centre d'Investigation Clinique 1414, Rennes, France.; FHU SUPPORT, Rennes, France.; Department of Cardiac and Vascular Surgery, University Heart and Vascular Center Hamburg, Hamburg, Germany.; Department of Pharmacology, Oslo University Hospital and Department of Pharmacy, University of Oslo, Norway.; Bioscientia Healthcare, Ingelheim, Germany.; Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, the Netherlands.; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.; NDA Partners, A Propharma Group Company, Washington District of Columbia.; Chronix Biomedical GmbH, Göttingen, Germany.; Pharmacology and Toxicology Laboratory, Biochemistry and Molecular Genetics Department, Biomedical Diagnostic Center, Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, CIBERehd, Spain.; Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.; Laboratory Management Research Laboratory, Cardiac Surgery Clinic, Heart Center Leipzig GmbH, University Hospital, Leipzig, Germany.; Integrated Pharmacometrics, Pharmacogenetic and Pharmacokinetics Research Group (PMGK) Louvain Drug for Research Institute (LDRI), Catholic University of Louvain, (UCLouvain), Brussels, Belgium.; Department of Organ Transplant Surgery; Fujita Health University School of Medicine, Toyoake Aichi, Japan.; University of Utah Health Sciences Center and ARUP Laboratories, Salt Lake City, Utah.; Department of Drug Chemistry, Pharmaceutical and Biomedical Analysis, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland.; University of Limoges, Inserm U1248, Pharmacology & Transplantation, Limoges, France.; Nephrology Department, Hospital Universitari de Bellvitge-Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain.; University of Limoges, Inserm U1248, Pharmacology & Transplantation, Limoges, France.; Department of Pharmacology, Toxicology and Pharmacovigilance, CHU de Limoges, France.; Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.; National Center for Liver Transplantation and Liver Diseases, Army Forces Hospital, Montevideo, Uruguay.; Department of Clinical Pharmacology, University Medical Center Göttingen, Georg-August-University Göttingen, Göttingen, Germany.; Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.; Labordiagnostic St. Gallen West AG, St. Gallen, Switzerland.; Department of Clinical Chemistry, Erasmus MC University Medical Center, Rotterdam, the Netherlands.; Department of Pharmaceutical Sciences, School of Pharmacy and Department of Pathology, Starzl Transplantation Institute, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.; University Medical School, Göttingen, Germany.; Department of Pharmacology, Toxicology and Pharmacovigilance, CHU de Limoges, Limoges, France; and.; Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.

DOI: 10.1097/FTD.0000000000001250

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MeSH Terms: Humans, Drug Monitoring, Everolimus, Immunosuppressive Agents, Precision Medicine, Consensus, Pharmacogenetics, Organ Transplantation