Manchester Adult Cystic Fibrosis Centre, University Hospital of South Manchester, Southmoor Road, Manchester, M23 9LT, UK.
J Cyst Fibros. 2013 Jul;12(4):399-402. doi: 10.1016/j.jcf.2012.10.007. Epub 2012 Dec 28.
Although there have been case reports of hypothalamic-pituitary-adrenal (HPA) axis suppression in patients with cystic fibrosis (CF) caused by the combination of oral itraconazole and inhaled fluticasone, to date no study has assessed the incidence of this potentially serious side effect.
Synacthen tests were conducted on all patients with CF receiving itraconazole and inhaled fluticasone and an equal number of patients with CF receiving inhaled fluticasone but not itraconazole. Itraconazole levels were measured in patients receiving the therapy.
Twelve patients receiving itraconazole and fluticasone underwent synacthen tests. All 12 had abnormal synacthen test results and 10/12 (83%) had HPA axis suppression. Two patients had severe HPA axis suppression with a peak cortisol <75 nmol/L and further 3 patients had moderately severe suppression with a peak cortisol <250 nmol/L. In contrast, only 2/12 on fluticasone alone had HPA axis suppression (both mild). The median (range) basal cortisol levels were significantly lower in those patients receiving itraconazole and inhaled fluticasone compared to those on fluticasone alone (219(22-508)nmol/L v 348(41-738)nnmol/L, p=0.02), similar results were seen for peak cortisol levels (404(59-706)nmol/L v 672(432-1178)nmol/L, p<0.001) and cortisol rise (179(37-240)nmol/L v 368(210-539)nmol/L, p<0.001). The median (range) itraconazole level was 5.5(1.7-14.7)mg/L. Neither itraconazole levels nor fluticasone dose correlated with the degree of adrenal suppression.
In this study, all patients receiving itraconazole and inhaled fluticasone had abnormal synacthen test results. The incidence of HPA axis suppression with this treatment combination appears to be higher than that previously reported with itraconazole and inhaled budesonide.
尽管有病例报告称,口服伊曲康唑和吸入氟替卡松联合治疗囊性纤维化(CF)患者可导致下丘脑-垂体-肾上腺(HPA)轴抑制,但迄今为止,尚无研究评估这种潜在严重副作用的发生率。
对所有接受伊曲康唑和吸入氟替卡松治疗的 CF 患者以及接受吸入氟替卡松但未接受伊曲康唑治疗的 CF 患者进行 Synacthen 测试。测量接受治疗的患者的伊曲康唑水平。
12 名接受伊曲康唑和氟替卡松治疗的患者接受了 Synacthen 测试。所有 12 名患者的 Synacthen 测试结果均异常,其中 10/12(83%)患者存在 HPA 轴抑制。2 名患者的 HPA 轴抑制严重,皮质醇峰值<75nmol/L,另有 3 名患者的 HPA 轴抑制中度严重,皮质醇峰值<250nmol/L。相比之下,仅 2/12 名单独接受氟替卡松治疗的患者出现 HPA 轴抑制(均为轻度)。与单独接受氟替卡松治疗的患者相比,接受伊曲康唑和吸入氟替卡松治疗的患者的基础皮质醇中位数(范围)水平明显更低(219(22-508)nmol/L 比 348(41-738)nmol/L,p=0.02),峰值皮质醇水平(404(59-706)nmol/L 比 672(432-1178)nmol/L,p<0.001)和皮质醇升高(179(37-240)nmol/L 比 368(210-539)nmol/L,p<0.001)也更低。伊曲康唑中位数(范围)水平为 5.5(1.7-14.7)mg/L。伊曲康唑水平和氟替卡松剂量均与肾上腺抑制程度无关。
在这项研究中,所有接受伊曲康唑和吸入氟替卡松治疗的患者的 Synacthen 测试结果均异常。与伊曲康唑和吸入布地奈德联合治疗相比,这种治疗组合的 HPA 轴抑制发生率似乎更高。