CYP2C19慢代谢患者应用伏立康唑致皮疹及黄视一例分析

One CYP2C19 Poor Metabolizers Patient with Rash and Xanthopsia Induced by Voriconazole:a Case Report

目的探讨CYP2C19基因多态性与伏立康唑药物不良反应的相关性,为临床安全用药提供参考。方法回顾性分析我院1例CYP2C19慢代谢型肺曲霉菌病患者应用伏立康唑后致皮疹、黄视的临床资料。结果患者因慢性阻塞性肺疾病急性发作期入院,痰培养提示烟熏曲霉菌生长,诊断为肺曲霉菌病,给予伏立康唑200 mg(首剂400 mg)每日2次静脉滴注,治疗后感染症状明显缓解,但用药后3 d双下肢多处出现皮疹,视物模糊、黄视,排除皮肤、眼部器质性病变后,临床药师高度怀疑伏立康唑相关性药疹。停用伏立康唑并行CYP2C19基因检测。停药次日患者黄视消失,皮疹减轻。CYP2C19基因检测示CYP2C19*2*3纯合子突变(慢代谢型)。调整伏立康唑剂量为100 mg每12 h 1次,治疗3周,病情好转出院。结论 CYP2C19基因多态性是伏立康唑不良反应发生的重要原因之一。CYP2C19基因检测可用于伏立康唑不良反应的监护及个体化治疗方案的制定,为临床合理用药提供客观依据。

Objective To investigate the correlation between CYP2C19 genetic polymorphism and adverse drug reaction induced by Voriconazole in order to provide references for rational drug use. Methods Clinical data of CYP2C19 poor metabolizers and pulmonary aspergillosis one patient with rash and xanthopsia induced by Voriconazole was retrospectively ana- lyzed. Results The patient was admitted for acute episode of chronic obstructive pulmonary disease. Pulmonary aspergillosis was found by sputum culture, and pulmonary aspergillosis was diagnosed, so the patient was treated with Voriconazole （200 mg, ivgtt, 2 times/d, and double dose for first time）. Infection symptom was relieved apparently, but a series of symptoms such as skin rash in both lower extremities, cloudy vision and xanthopsia were found after 3 days of medication. Clinical pharmacists highly suspected that the patient had drug eruptions induced by Voriconazole after excluding organic disease of skin and eyes, and therefore Voriconazole was stopped, and genotype of CYP2C19 was tested for the patient. Xanthopsia was disappeared, and skin rash was relieved on the next day after stopping medication. Gene test showed that CYP2C19 ＊ 2 ＊ 3 homozygote mutation （poor metabolizer）, so Voriconazole dose was adjusted to 100 mg （ivgtt, 2 times/d） subsequently. Patient was discharged after condition improvement by 3 weeks of therapeutics. Conclusion CYP2C19 gene polymorphism is one of important reasons of adverse reactions occurrence induced by Voriconazole, and therefore it can be used to detect Voriconazole adverse reactions, make individualized treatment plan and provide an objective basis for rational drug use in clinic.