TY - JOUR
T1 - Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of CYP2C9, HLA-A and HLA-B with anti-epileptic drugs
AU - Manson, Lisanne E.N.
AU - Nijenhuis, Marga
AU - Soree, Bianca
AU - de Boer-Veger, Nienke J.
AU - Buunk, Anne Marie
AU - Houwink, Elisa J.F.
AU - Risselada, Arne
AU - Rongen, Gerard A.P.J.M.
AU - van Schaik, Ron H.N.
AU - Swen, Jesse J.
AU - Touw, Daan J.
AU - van Westrhenen, Roos
AU - Deneer, Vera H.M.
AU - Guchelaar, Henk Jan
N1 - Funding Information:
This project has 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:
© The Author(s), under exclusive licence to European Society of Human Genetics 2024.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - 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 CYP2C9 and HLA-B with phenytoin, HLA-A and HLA-B with carbamazepine and HLA-B with oxcarbazepine and lamotrigine. A systematic review was performed and pharmacotherapeutic recommendations were developed. For CYP2C9 intermediate 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*15:02 carriers, 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*15:11 and HLA-A*31:01 carriers. For HLA-B*15:02, HLA-B*15:11 and HLA-A*31:01 positive 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*15:02 positive patient. DPWG considers CYP2C9 genotyping 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*15:02 genotyping before the start of carbamazepine, phenytoin, oxcarbazepine, and lamotrigine “beneficial”, as well as genotyping for HLA-B*15:11 and HLA-A*31:01 before initiating carbamazepine.
AB - 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 CYP2C9 and HLA-B with phenytoin, HLA-A and HLA-B with carbamazepine and HLA-B with oxcarbazepine and lamotrigine. A systematic review was performed and pharmacotherapeutic recommendations were developed. For CYP2C9 intermediate 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*15:02 carriers, 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*15:11 and HLA-A*31:01 carriers. For HLA-B*15:02, HLA-B*15:11 and HLA-A*31:01 positive 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*15:02 positive patient. DPWG considers CYP2C9 genotyping 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*15:02 genotyping before the start of carbamazepine, phenytoin, oxcarbazepine, and lamotrigine “beneficial”, as well as genotyping for HLA-B*15:11 and HLA-A*31:01 before initiating carbamazepine.
U2 - 10.1038/s41431-024-01572-4
DO - 10.1038/s41431-024-01572-4
M3 - Article
SN - 1018-4813
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
ER -