Gordon Rachael, Yen Bo, Dewey Katherine, Jariwala Ripal, Kukreja Jasleen, Hays Steven, Singer Jonathan P, Florez Rebecca
Department of Clinical Pharmacy, University of California, San Francisco, California, USA.
Department of Surgery, University of California, San Francisco, California, USA.
Transpl Infect Dis. 2025 Jan-Feb;27(1):e14402. doi: 10.1111/tid.14402. Epub 2024 Nov 4.
Invasive fungal infections can cause serious complications after lung transplant; therefore, prophylaxis with posaconazole is common. The posaconazole delayed-release (DR) tablet is preferred. Although the package insert states DR tablets cannot be crushed, recent data suggest it is reasonable. We hypothesized that crushed posaconazole DR tablets could reach therapeutic levels in lung transplant recipients.
A retrospective study of lung transplant recipients between January 2018 and July 2023, who received crushed posaconazole DR for at least 5 days was completed. Posaconazole troughs were evaluated, and differences were compared between subjects who were therapeutic to those who were subtherapeutic. A cost analysis was also performed.
Thirty subjects received crushed posaconazole DR and 50% were therapeutic. The median trough was 1 mg/L for those who were therapeutic and 0.4 mg/L for those who were not (p < 0.001). The median cumulative dose was 2000 mg, and there were no significant differences in the incidence of diarrhea or tube feeds. More subjects in the therapeutic group were loaded (33% vs. 13%), although this was not statistically significant (p = 0.39). No subjects had breakthrough aspergillus one month after starting crushed therapy.
Crushed posaconazole DR tablets are a viable and cost savings option, but loading doses and higher maintenance doses may be required to reach therapeutic levels. Those who received loading doses (intravenously or crushed) followed by a daily crushed dose of 400 mg were more likely to be therapeutic. Limitations of our study include that it is single-center, small in sample size, and retrospective.
侵袭性真菌感染可在肺移植后引起严重并发症；因此，使用泊沙康唑进行预防很常见。泊沙康唑缓释（DR）片是首选。尽管药品说明书指出DR片不能碾碎，但最近的数据表明这样做是合理的。我们假设碾碎的泊沙康唑DR片在肺移植受者中可达到治疗水平。
完成了一项对2018年1月至2023年7月期间接受碾碎的泊沙康唑DR治疗至少5天的肺移植受者的回顾性研究。评估了泊沙康唑谷浓度，并比较了治疗组与亚治疗组受试者之间的差异。还进行了成本分析。
30名受试者接受了碾碎的泊沙康唑DR治疗，其中50%达到治疗水平。达到治疗水平的受试者的谷浓度中位数为1mg/L，未达到治疗水平的受试者为0.4mg/L（p<0.001）。累积剂量中位数为2000mg，腹泻或鼻饲发生率无显著差异。治疗组中接受负荷剂量的受试者更多（33%对13%），尽管这无统计学意义（p=0.39）。开始碾碎治疗一个月后，没有受试者发生突破性曲霉感染。
碾碎的泊沙康唑DR片是一种可行且节省成本的选择，但可能需要负荷剂量和更高的维持剂量才能达到治疗水平。接受负荷剂量（静脉注射或碾碎）然后每日碾碎剂量400mg的受试者更有可能达到治疗水平。我们研究的局限性包括它是单中心的、样本量小且为回顾性研究。
