通过制定循证药物遗传学指南来优化药物治疗,荷兰药物遗传学工作组(DPWG)旨在推进药物遗传学(PGx)的实施。本指南概述了CYP2C9和HLA-B与苯妥英的基因-药物相互作用,HLA-A和HLA-B与卡马西平和HLA-B与奥卡西平和拉莫三嗪。进行了系统评价,并制定了药物治疗建议。对于CYP2C9中间和不良代谢者,DPWG建议降低苯妥英的日剂量,并在7-10天后根据疗效和血清浓度进行调整.对于HLA-B*15:02携带者,与苯妥英相关的严重皮肤不良事件的风险,卡马西平,奥卡西平,拉莫三嗪的含量急剧增加.卡马西平,这种风险在HLA-B*15:11和HLA-A*31:01携带者中也增加.对于HLA-B*15:02,HLA-B*15:11和HLA-A*31:01阳性患者,DPWG建议选择替代抗癫痫药物.如果不可能,建议患者在使用卡马西平时报告任何皮疹,拉莫三嗪,立即服用奥卡西平或苯妥英。卡马西平不应用于HLA-B*15:02阳性患者。DPWG认为在苯妥英钠开始之前进行CYP2C9基因分型对预防毒性“至关重要”。对于具有上述HLA等位基因普遍存在的祖先的患者,DPWG在卡马西平开始之前考虑HLA-B*15:02基因分型,苯妥英,奥卡西平,和拉莫三嗪“有益”,以及在开始卡马西平之前对HLA-B*15:11和HLA-A*31:01进行基因分型。
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.