Dutch pharmacogenetics working group (DPWG) guideline for the gene-drug interaction of CYP2D6 and COMT with atomoxetine and methylphenidate

Autor: Marga Nijenhuis, Bianca Soree, Wafa O. M. Jama, Nienke J. de Boer-Veger, Anne Marie Buunk, Henk-Jan Guchelaar, Elisa J. F. Houwink, Gerard A. Rongen, Ron H. N. van Schaik, Jesse J. Swen, Daan Touw, Jan van der Weide, Roos van Westrhenen, Vera H. M. Deneer, Arne Risselada
Přispěvatelé: Pharmaceutical Analysis, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Groningen Research Institute for Asthma and COPD (GRIAC), Medicinal Chemistry and Bioanalysis (MCB), Clinical Chemistry, Psychiatry 1, RS: MHeNs - R2 - Mental Health
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: European Journal of Human Genetics. SPRINGERNATURE
European Journal of Human Genetics
European Journal of Human Genetics. Nature Publishing Group
ISSN: 1018-4813
Popis: Pharmacogenetics (PGx) studies the effect of heritable genetic variation on drug response. Clinical adoption of PGx has remained limited, despite progress in the field. To promote implementation, the Dutch Pharmacogenetics Working Group (DPWG) develops evidence-based guidelines on how to optimize pharmacotherapy based on PGx test results. This guideline describes optimization of atomoxetine therapy based on genetic variation in the CYP2D6 gene. The CYP2D6 enzyme is involved in conversion of atomoxetine into the metabolite 4-hydroxyatomoxetine. With decreasing CYP2D6 enzyme activity, the exposure to atomoxetine and the risk of atomoxetine induced side effects increases. So, for patients with genetically absent CYP2D6 enzyme activity (CYP2D6 poor metabolisers), the DPWG recommends to start with the normal initial dose, bearing in mind that increasing this dose probably will not be required. In case of side effects and/or a late response, the DPWG recommends to reduce the dose and check for sustained effectiveness for both poor metabolisers and patients with genetically reduced CYP2D6 enzyme activity (CYP2D6 intermediate metabolisers). Extra vigilance for ineffectiveness is required in patients with genetically increased CYP2D6 enzyme activity (CYP2D6 ultra-rapid metabolisers). No interaction was found between the CYP2D6 and COMT genes and methylphenidate. In addition, no interaction was found between CYP2D6 and clonidine, confirming the suitability of clonidine as a possible alternative for atomoxetine in variant CYP2D6 metabolisers. The DPWG classifies CYP2D6 genotyping as being "potentially beneficial " for atomoxetine. CYP2D6 testing prior to treatment can be considered on an individual patient basis.
Databáze: OpenAIRE
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