Raad Issam I, Graybill John R, Bustamante Ana Beatriz, Cornely Oliver A, Gaona-Flores Veronica, Afif Claude, Graham Donald R, Greenberg Richard N, Hadley Susan, Langston Amelia, Negroni Ricardo, Perfect John R, Pitisuttithum Punnee, Restrepo Angela, Schiller Gary, Pedicone Lisa, Ullmann Andrew J
The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Clin Infect Dis. 2006 Jun 15;42(12):1726-34. doi: 10.1086/504328. Epub 2006 May 8.
Invasive fungal infections are found most frequently in immunosuppressed and critically ill hospitalized patients. Antifungal therapy is often required for long periods. Safety data from the clinical development program of the triazole antifungal agent, posaconazole, were analyzed.
A total of 428 patients with refractory invasive fungal infections (n = 362) or febrile neutropenia (n = 66) received posaconazole in 2 phase II/III open-label clinical trials. Also, 109 of these patients received posaconazole therapy for > or = 6 months. Incidences of treatment-emergent, treatment-related, and serious adverse events and abnormal laboratory parameters were recorded during these studies.
Treatment-emergent, treatment-related adverse events were reported in 38% of the overall patient population. The most common treatment-related adverse events were nausea (8%) and vomiting (6%). Treatment-related serious adverse events occurred in 8% of patients. Low rates of treatment-related corrected QT interval and/or QT interval prolongation (1%) and elevation of hepatic enzymes (2%) were reported as adverse events. Treatment-emergent, treatment-related adverse events occurred at similar rates in patients who received posaconazole therapy for < 6 months and > or = 6 months.
Prolonged posaconazole treatment was associated with a generally favorable safety profile in seriously ill patients with refractory invasive fungal infections. Long-term therapy did not increase the risk of any individual adverse event, and no unique adverse event was observed with longer exposure to posaconazole.
侵袭性真菌感染在免疫抑制和危重症住院患者中最为常见。通常需要长期进行抗真菌治疗。对三唑类抗真菌药物泊沙康唑临床研发项目的安全性数据进行了分析。
在两项II/III期开放标签临床试验中，共有428例难治性侵袭性真菌感染患者（n = 362）或发热性中性粒细胞减少患者（n = 66）接受了泊沙康唑治疗。此外，其中109例患者接受泊沙康唑治疗≥6个月。在这些研究中记录了治疗中出现的、与治疗相关的严重不良事件以及异常实验室参数的发生率。
在全部患者人群中，38%报告了治疗中出现的、与治疗相关的不良事件。最常见的与治疗相关的不良事件为恶心（8%）和呕吐（6%）。8%的患者发生了与治疗相关的严重不良事件。报告的与治疗相关的校正QT间期和/或QT间期延长（1%）以及肝酶升高（2%）的发生率较低。接受泊沙康唑治疗<6个月和≥6个月的患者中，治疗中出现的、与治疗相关的不良事件发生率相似。
对于患有难治性侵袭性真菌感染的重症患者，长期泊沙康唑治疗的总体安全性良好。长期治疗并未增加任何个体不良事件的风险，且未观察到因长期使用泊沙康唑而出现的独特不良事件。
