Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2D6, CYP3A4and CYP1A2and antipsychotics

Autor: Beunk, Lianne, Nijenhuis, Marga, Soree, Bianca, de Boer-Veger, Nienke J., Buunk, Anne-Marie, Guchelaar, Henk Jan, Houwink, Elisa J. F., Risselada, Arne, Rongen, Gerard A. P. J. M., van Schaik, Ron H. N., Swen, Jesse J., Touw, Daan, van Westrhenen, Roos, Deneer, Vera H. M., van der Weide, Jan
Zdroj: European Journal of Human Genetics: EJHG; March 2024, Vol. 32 Issue: 3 p278-285, 8p
Abstrakt: The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate pharmacogenetics implementation in clinical practice by developing evidence-based guidelines to optimize pharmacotherapy. A guideline describing the gene-drug interaction between the genes CYP2D6, CYP3A4and CYP1A2and antipsychotics is presented here. The DPWG identified gene-drug interactions that require therapy adjustments when respective genotype is known for CYP2D6with aripiprazole, brexpiprazole, haloperidol, pimozide, risperidone and zuclopenthixol, and for CYP3A4with quetiapine. Evidence-based dose recommendations were obtained based on a systematic review of published literature. Reduction of the normal dose is recommended for aripiprazole, brexpiprazole, haloperidol, pimozide, risperidone and zuclopenthixol for CYP2D6-predicted PMs, and for pimozide and zuclopenthixol also for CYP2D6IMs. For CYP2D6UMs, a dose increase or an alternative drug is recommended for haloperidol and an alternative drug or titration of the dose for risperidone. In addition, in case of no or limited clinical effect, a dose increase is recommended for zuclopenthixol for CYP2D6UMs. Even though evidence is limited, the DPWG recommends choosing an alternative drug to treat symptoms of depression or a dose reduction for other indications for quetiapine and CYP3A4PMs. No therapy adjustments are recommended for the other CYP2D6and CYP3A4predicted phenotypes. In addition, no action is required for the gene-drug combinations CYP2D6and clozapine, flupentixol, olanzapine or quetiapine and also not for CYP1A2and clozapine or olanzapine. For identified gene-drug interactions requiring therapy adjustments, genotyping of CYP2D6or CYP3A4prior to treatment should not be considered for all patients, but on an individual patient basis only.
Databáze: Supplemental Index
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