Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of CYP2C9, HLA-Aand HLA-Bwith anti-epileptic drugs

Autor: Manson, Lisanne E. N., Nijenhuis, Marga, Soree, Bianca, de Boer-Veger, Nienke J., Buunk, Anne-Marie, Houwink, Elisa J. F., Risselada, Arne, Rongen, Gerard A. P. J. M., van Schaik, Ron H. N., Swen, Jesse J., Touw, Daan J., van Westrhenen, Roos, Deneer, Vera H. M., Guchelaar, Henk-Jan
Zdroj: European Journal of Human Genetics: EJHG; August 2024, Vol. 32 Issue: 8 p903-911, 9p
Abstrakt: By developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy, the Dutch Pharmacogenetics Working Group (DPWG) aims to advance the implementation of pharmacogenetics (PGx). This guideline outlines the gene-drug interaction of CYP2C9and HLA-Bwith phenytoin, HLA-Aand HLA-Bwith carbamazepine and HLA-Bwith oxcarbazepine and lamotrigine. A systematic review was performed and pharmacotherapeutic recommendations were developed. For CYP2C9intermediate and poor metabolisers, the DPWG recommends lowering the daily dose of phenytoin and adjust based on effect and serum concentration after 7–10 days. For HLA-B*15:02carriers, the risk of severe cutaneous adverse events associated with phenytoin, carbamazepine, oxcarbazepine, and lamotrigine is strongly increased. For carbamazepine, this risk is also increased in HLA-B*15:11and HLA-A*31:01carriers. For HLA-B*15:02, HLA-B*15:11and HLA-A*31:01positive patients, the DPWG recommends choosing an alternative anti-epileptic drug. If not possible, it is recommended to advise the patient to report any rash while using carbamazepine, lamotrigine, oxcarbazepine or phenytoin immediately. Carbamazepine should not be used in an HLA-B*15:02positive patient. DPWG considers CYP2C9genotyping before the start of phenytoin “essential” for toxicity prevention. For patients with an ancestry in which the abovementioned HLA-alleles are prevalent, the DPWG considers HLA-B*15:02genotyping before the start of carbamazepine, phenytoin, oxcarbazepine, and lamotrigine “beneficial”, as well as genotyping for HLA-B*15:11and HLA-A*31:01before initiating carbamazepine.
Databáze: Supplemental Index
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