Flores Jerome, Flank Jacqueline, Polito Samantha, Dhillon Patwant, Pang Ian, Ho Lina, Yee Karen Wl
University Health Network, Toronto, Canada.
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.
J Oncol Pharm Pract. 2025 Oct;31(7):1094-1103. doi: 10.1177/10781552241284528. Epub 2024 Sep 19.
IntroductionMalignant hematology (MH) patients are susceptible to invasive fungal infections due to prolonged neutropenia and immunosuppressive therapies, which may require voriconazole therapy. Although voriconazole therapeutic drug monitoring (TDM) is common, evidence describing this practice is limited. The primary objective of this study was to describe the current practice of voriconazole TDM in MH patients at the Princess Margaret Cancer Centre (PM).MethodsA retrospective chart review was conducted for MH inpatients initiated on voriconazole at PM between November 1st, 2019 and November 13th, 2020. Data regarding voriconazole doses, levels, dose changes, and adverse effects were collected. The primary endpoint was the proportion of patients with initial voriconazole levels within therapeutic range (1-5 mg/L).ResultsFifty-six patients were included in the study. The most common reason for starting voriconazole was possible invasive fungal infection (44 patients, 78.6%). Fifty-one patients (91.1%) received a loading dose of voriconazole, averaging 386.5 ± 78.5 mg. The average maintenance dose was 242.1 ± 45.7 mg. An average of 2.6 ± 2.9 levels were drawn per patient with an average level of 3.2 ± 2.4 mg/L. Forty-one patients (73.2%) had an initial voriconazole level within therapeutic range and 90 out of 145 total levels (62.1%) were within therapeutic range. There were 52 dose modifications made; 31 (60.8%) doses adjusted, 12 (23.5%) doses held, and 9 (17.6%) doses discontinued. For the 31 dose adjustments, 26 (83.9%) had a level redrawn and 17 (65.4%) of those levels were within therapeutic range. Twenty-three (41.1%) patients developed adverse effects, 8 (34.8%) of which were associated with supratherapeutic levels. Of these 23 patients, 19 (33.9%) experienced transaminitis, 3 (5.4%) experienced both transaminitis and neurotoxicity, and 1 (1.8%) experienced photopsia.ConclusionOverall, 41 (73.2%) patients achieved an initial voriconazole level within therapeutic range. Of these 41 patients, 30 (73.2%) remained within therapeutic range for the duration of their inpatient voriconazole therapy. These findings suggest that the current practice of voriconazole TDM at our institution is yielding largely positive results, but still has room for improvement.
引言
恶性血液学（MH）患者由于长期中性粒细胞减少和免疫抑制治疗，易发生侵袭性真菌感染，可能需要伏立康唑治疗。尽管伏立康唑治疗药物监测（TDM）很常见，但描述这种做法的证据有限。本研究的主要目的是描述玛格丽特公主癌症中心（PM）对MH患者进行伏立康唑TDM的当前做法。
方法
对2019年11月1日至2020年11月13日期间在PM开始使用伏立康唑的MH住院患者进行回顾性病历审查。收集有关伏立康唑剂量、血药浓度、剂量变化和不良反应的数据。主要终点是初始伏立康唑血药浓度在治疗范围内（1 - 5mg/L）的患者比例。
结果
56名患者纳入研究。开始使用伏立康唑最常见的原因是可能存在侵袭性真菌感染（44例患者，78.6%）。51名患者（91.1%）接受了伏立康唑负荷剂量，平均为386.5±78.5mg。平均维持剂量为242.1±45.7mg。每位患者平均检测2.6±2.9次血药浓度，平均血药浓度为3.2±2.4mg/L。41名患者（73.2%）初始伏立康唑血药浓度在治疗范围内，145次总血药浓度中有90次（62.1%）在治疗范围内。共进行了52次剂量调整；31次（60.8%）剂量调整，12次（23.5%）剂量暂停，9次（17.6%）剂量停用。对于31次剂量调整，26次（83.9%）重新检测了血药浓度，其中17次（65.4%）血药浓度在治疗范围内。23名患者（41.1%）出现不良反应，其中8名（34.8%）与血药浓度高于治疗范围有关。在这23名患者中，19名（33.9%）出现转氨酶升高，3名（5.4%）同时出现转氨酶升高和神经毒性，1名（1.8%）出现视幻觉。
结论
总体而言，41名患者（73.2%）初始伏立康唑血药浓度在治疗范围内。在这41名患者中，30名（73.2%）在住院伏立康唑治疗期间血药浓度一直保持在治疗范围内。这些结果表明，我们机构目前的伏立康唑TDM做法在很大程度上取得了积极成果，但仍有改进空间。
