Dutch pharmacogenetics working group (DPWG) guideline for the gene–drug interaction between UGT1A1 and irinotecan

Emma C. Hulshof, Maarten J. Deenen, Marga Nijenhuis*, Bianca Soree, Nienke J. de Boer-Veger, Anne Marie Buunk, Elisa J.F. Houwink, Arne Risselada, Gerard A.P.J.M. Rongen, Ron H.N. van Schaik, Daan J. Touw, Jan van der Weide, Roos van Westrhenen, Vera H.M. Deneer, Henk Jan Guchelaar, Jesse J. Swen

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the starting dose optimization of the anti-cancer drug irinotecan to decrease the risk of severe toxicity, such as (febrile) neutropenia or diarrhoea. Uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1 encoded by the UGT1A1 gene) enzyme deficiency increases risk of irinotecan-induced toxicity. Gene variants leading to UGT1A1 enzyme deficiency (e.g. UGT1A1*6, *28 and *37) can be used to optimize an individual’s starting dose thereby preventing carriers from toxicity. Homozygous or compound heterozygous carriers of these allele variants are defined as UGT1A1 poor metabolisers (PM). DPWG recommends a 70% starting dose in PM patients and no dose reduction in IM patients who start treatment with irinotecan. Based on the DPWG clinical implication score, UGT1A1 genotyping is considered “essential”, indicating that UGT1A1 testing must be performed prior to initiating irinotecan treatment.

Original languageEnglish
JournalEuropean Journal of Human Genetics
DOIs
Publication statusPublished - 28 Nov 2022

Bibliographical note

Funding Information:
The U-PGx consortium received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 668353. The DPWG received funding from the Royal Dutch Pharmacists Association.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to European Society of Human Genetics.

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