Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.
Royal Dutch Pharmacists Association (KNMP), The Hague, The Netherlands.
Eur J Hum Genet. 2022 Oct;30(10):1105-1113. doi: 10.1038/s41431-021-00920-y. Epub 2021 Jul 15.
The current Dutch Pharmacogenetics Working Group (DPWG) guideline, describes the gene-drug interaction between CYP2D6 and the opioids codeine, tramadol and oxycodone. CYP2D6 genotype is translated into normal metaboliser (NM), intermediate metaboliser (IM), poor metaboliser (PM) or ultra-rapid metaboliser (UM). Codeine is contraindicated in UM adults if doses >20 mg every 6 h (q6h), in children ≥12 years if doses >10 mg q6h, or with additional risk factors. In PMs, an alternative analgesic should be given which is not or to a lesser extent metabolised by CYP2D6 (not tramadol). In IMs with insufficient analgesia, a higher dose or alternative analgesic should be given. For tramadol, the recommendations for IMs and PMs are the same as the recommendation for codeine and IMs. UMs should receive an alternative drug not or to a lesser extent metabolised by CYP2D6 or the dose should be decreased to 40% of the commonly prescribed dose. Due to the absence of effect on clinical outcomes of oxycodone in PMs, IMs and UMs no action is required. DPWG classifies CYP2D6 genotyping for codeine "beneficial" and recommends testing prior to, or shortly after initiation of treatment in case of higher doses or additional risk factors. CYP2D6 genotyping is classified as "potentially beneficial" for tramadol and can be considered on an individual patient basis.
当前荷兰药物遗传学工作组(DPWG)指南描述了 CYP2D6 与阿片类药物可待因、曲马多和羟考酮之间的基因-药物相互作用。CYP2D6 基因型分为正常代谢者(NM)、中间代谢者(IM)、弱代谢者(PM)或超快代谢者(UM)。如果 UM 成人剂量超过 20mg/6 小时(q6h),儿童≥12 岁剂量超过 10mg/q6h,或有其他危险因素,应禁忌使用可待因。PM 患者应给予非 CYP2D6 代谢或较少代谢的替代镇痛药物(非曲马多)。IM 患者镇痛不足时,应给予更高剂量或替代镇痛药物。对于曲马多,IM 和 PM 的建议与可待因和 IM 的建议相同。UM 应使用非 CYP2D6 代谢或较少代谢的替代药物,或将剂量减少至常用剂量的 40%。由于 PM、IM 和 UM 患者使用羟考酮对临床结局无影响,因此无需采取任何措施。DPWG 将 CYP2D6 基因分型用于可待因归类为“有益”,建议在较高剂量或有其他危险因素时,在开始治疗前或治疗后不久进行检测。CYP2D6 基因分型对曲马多为“潜在有益”,可根据个体患者情况考虑。