侵袭性真菌病患者伏立康唑不良反应分析及临床处理经验

Analysis of Adverse Reactions and Clinical Treatment Experience of Voriconazole in Patients with Invasive Fungal Disease

关键词:  伏立康唑  不良反应  临床治疗

Key words:  voriconazole  adverse reaction  clinical treatment

摘要:

目的 通过分析台州市中心医院发生伏立康唑不良反应的病历信息以及临床处理成效，为安全有效使用伏立康唑提供参考。方法 回顾性分析台州市中心医院2015年12月-2020年12月280例侵袭性真菌病患者伏立康唑血药浓度监测结果，采用Naranjo's量化评分表判断伏立康唑相关药物不良反应，NCI-CTCAE标准评价不良反应严重程度，同时总结归纳发生不良反应后临床主要处理措施及转归。结果 共52例患者出现不良反应，未见危及生命不良反应，中位谷浓度3.80（1.80，5.93）μg·mL^-1。主要不良反应为肝毒性、中枢神经系统毒性和视觉障碍，谷浓度分别为（5.17±3.39），（4.45±3.74）和（4.21±3.01）μg·mL^-1。发生不良反应者谷浓度高于未发生者（P<0.05），同时两者之间的年龄、性别、基础疾病、感染部位差异无统计学意义；发生肝毒性者谷浓度高于未发生不良反应者（P<0.05）。不良反应的处理方式主要为根据患者NCI分级和谷浓度，分别选择终止伏立康唑治疗、对症治疗、减量50%等。最终，51例患者经处理后转归良好。结论 伏立康唑不良反应不受年龄、性别、基础疾病和感染部位影响，但谷浓度高者更易发生。为保证安全用药，可尝试将4 μg·mL^-1作为谷浓度上限；处理不良反应时需要考虑谷浓度和NCI分级选择合适的处理方式。

Abstract:

OBJECTIVE To provide reference for the safe and effective use of voriconazole by analyzing the medical record information and clinical treatment effect of voriconazole adverse reactions in Taizhou Central Hospital. METHODS The blood concentration monitoring results of voriconazole in 280 patients with invasive fungal disease in Taizhou Central Hospital from December 2015 to December 2020 were retrospectively analyzed. Naranjo's quantitative score scale was used to determine the correlation of adverse reactions and NCI-CTCAE standard was used to evaluate the severity of adverse reactions. Meanwhile, the main clinical intervention measures and outcomes were summarized. RESULTS 52 patients had suffered from adverse reactions, the median trough concentration was 3.80(1.80, 5.93)μg·mL^-1, and no life-threatening adverse reactions were observed. Hepatotoxicity, central nervous system toxicity and visual impairment were the most common adverse reactions, and the trough concentration was (5.17±3.39), (4.45±3.74), and (4.21±3.01)μg·mL^-1, respectively. The incidence of adverse reactions was not related to age, gender, underlying disease and infection sites, valley concentrations in those with adverse reactions were higher than in none. Meanwhile, the concentration of patients suffered from hepatotoxicity was higher than without adverse reactions(P<0.05). The main treatment methods of the adverse reactions were withdrawn voriconazole, symptomatic treatment and reduction 50% dosage, according to the NCI grade and trough concentration. Finally, 51 patients had good prognosis. CONCLUSION Patients with high trough concentration are more likely to have adverse reactions, and the incidence of voriconazole adverse reactions is not affected by age, gender, underlying disease and infection site. And to ensure the safety of medication, the upper limit of trough concentration could be set to 4 μg·mL^-1. The trough concentration and NCI grade should be taken into account when dealing with the adverse reactions.