吉非替尼致CYP2D6基因中间代谢型肺腺癌患者肝损伤药学监护实践

Pharmaceutical Care of Liver Injury Induced by Gefitinib in a Lung-Adenocarcinoma Patient with Intermediate Metabolic CYP2D6 Gene

目的探讨临床药师参与肿瘤患者药物性肝损伤(DILI)防治的药学监护作用。方法总结临床药师参与的1例CYP2D6基因中间代谢型肺腺癌患者使用吉非替尼诱发急性DILI的药学监护实践。临床药师结合患者的病史、治疗史及肝毒性表现(3级),判定急性DILI可能性最大,且与吉非替尼的关联性为“很可能”,建议暂时停服吉非替尼片,并给予多烯磷脂酰胆碱注射液静脉滴注及复方甘草酸苷胶囊保肝治疗,同时行药物代谢酶基因多态性检测。结果医师采纳临床药师建议,调整治疗方案。药物代谢酶基因多态性检测结果示CYP2D610/10纯合突变型,提示患者CYP2D6基因为中间代谢型(酶活性部分降低),其余代谢酶基因无突变。且后续治疗用药由吉非替尼片换为盐酸埃克替尼片,患者转氨酶基本正常。出院后随访,患者胸部CT检查示病灶较入院时基本无变化,肝功能正常。结论临床药师发挥专业所长,充分运用循证证据,在不良反应鉴别分析、相关药物治疗方案拟订方面给予医师建议,可最大限度地保障患者用药的合理性、有效性、安全性,在临床药物治疗中发挥了积极作用。

Objective To investigate the role of clinical pharmacists'practice in pharmaceutical care of tumor patients in the prevention and treatment of drug-induced liver injury(DILI).Methods The clinical pharmacists'practice in pharmaceutical care of a lung-adenocarcinoma patient with intermediate metabolic CYP2D6 gene occurring acute DILI induced by gefitinib was summarized.Based on the patient's medical history,treatment history and hepatotoxicity(grade 3),clinical pharmacists determined that the patient's adverse drug reaction was most likely acute DILI,and was"very likely"associated with gefitinib.They suggested that Gefitinib Tablets should be temporarily stopped,and Polyene Phosphatidylcholine Injection should be given intravenously and Compound Glycyrrhizin Capsules should be taken orally for hepatoprotective treatment,and gene polymorphism testing of drug metabolism enzyme should be performed at the same time.Results Physicians adopted the suggestions of clinical pharmacists and adjusted the treatment plan.The result of gene polymorphism testing of drug metabolism enzyme was CYP2D610/10 homozygous mutant,which indicated that the CYP2D6 gene of the patient was intermediate metabolic(the enzyme activity partially decreasing),and the other metabolic enzyme genes were not mutant.In the follow-up treatment,the drug was changed from Gefitinib Tablets to Icotinib Hydrochloride Tablets,and the patient's aminotransferase level was basically normal.During the follow up after discharge,the patient's chest lesion of CT examination was similar to that on admission,and the liver function was normal.Conclusion Clinical pharmacists give full play to their professional expertise,make full use of evidence-based evidence,and provide physician suggestions in the identification,analysis of adverse reactions and formulation of relevant drug treatment plans,which can ensure the rationality,effectiveness and safety of drug use for patients to the greatest extent,and play a positive role in clinical drug treatment.