治疗药物监测下奈玛特韦片/利托那韦片组合包装与伏立康唑的联合应用

Therapeutic Drug Monitoring of Nematavir Tablet/Ritonavir Tablet in Combination with Voriconazole

目的:研究奈玛特韦片/利托那韦片组合包装(以下简称“奈马特韦/利托那韦”)与伏立康唑联合应用时,是否会影响伏立康唑的暴露量。方法:回顾性纳入国家呼吸医学中心2022年12月至2023年1月北京新型冠状病毒感染暴发期间同时使用伏立康唑和奈马特韦/利托那韦的患者,对药物剂量、联合用药情况、伏立康唑血药浓度测定和不良反应进行记录和分析。结果:共纳入14例患者的17个伏立康唑血药浓度监测结果。仅有1例患者伏立康唑血药浓度偏低,2例患者超过治疗上限的50%,多数患者的伏立康唑血药浓度均在治疗范围内;具有基线伏立康唑浓度数据的7例患者中,除1例患者因浓度过高减量外,其余患者联合用药时浓度均与基线浓度类似或略高。与同期其他伏立康唑血药浓度数据比较,联合治疗中伏立康唑血药浓度偏高的比例略有增加。未发现可归因于两药的不良反应。结论:与药品说明书标示不同,在我国人群中,伏立康唑与奈马特韦/利托那韦的联合应用是可行的,并建议监测血药浓度,以保证用药安全性和有效性。

OBJECTIVE:To investigate whether Nematavir tablet/Ritonavir tablet(co-packaged)(hereinafter referred to as“nematavir/ritonavir”)in combination with voriconazole would affect voriconazole exposure.METHODS:Patients who were concurrently treated with voriconazole and nirmatrelvir/ritonavir during the COVID-19 outbreak in Beijing from Dec.2022 to Jan.2023 at the National Center for Respiratory Medicine were retrospectively enrolled.Dosage,drug combination,voriconazole concentration and adverse drug reactions were recorded and analyzed.RESULTS:A total of 17 voriconazole concentrations of 14 patients were included.Only 1 patient had low blood drug concentration,2 patients exceeded 50%of the upper limit of treatment,most patients were within the therapeutic range.Among the 7 patients with baseline voriconazole concentration data,all but 1 patient’voriconazole concentration was similar to or slightly higher than the baseline concentration.Compared with other data of voriconazole concentration,the proportion of higher voriconazole concentration was slightly increased in the combined one.No adverse drug reactions attributable to the two drugs were found.CONCLUSIONS:Different from the instructions,the combined use of voriconazole and nirmatrelvir/ritonavir is feasible in Chinese population.Therapeutic drug monitoring is recommended to ensure safety and effectiveness.