Bhumbra Nasreen A, Sahloff Eric G, Oehrtman Sandra J, Horner James M
Department of Pediatrics, College of Medicine, University of Toledo, Toledo, OH, USA.
Ann Pharmacother. 2007 Jul;41(7):1306-9. doi: 10.1345/aph.1K075. Epub 2007 May 29.
To describe a case of Cushing syndrome in a child during concurrent use of inhaled fluticasone propionate, nasal mometasone, and a highly active antiretroviral regimen including lopinavir/ritonavir.
A 9-year-old boy with HIV infection and asthma developed moon facies, increased facial hair, and increased weight after fluticasone propionate inhalation (1 puff; 220 microg) therapy was begun. His antiretroviral regimen contained the protease inhibitor combination lopinavir/ritonavir at a dose of 216/54 mg twice daily, and he had been stable for the previous 5 years. He had also been receiving intranasal mometasone for 11 months for the management of allergic rhinitis. Serum cortisol and adrenocorticotropic hormone levels were consistent with adrenal suppression. These physical findings and symptoms and laboratory values normalized after discontinuation of the fluticasone propionate. The Naranjo probability scale indicated that a probable interaction occurred between lopinavir/ritonavir and fluticasone propionate, leading to subsequent adrenal suppression.
Protease inhibitors are associated with numerous drug interactions due to inhibition of the CYP3A4 isoenzyme. Pharmaceutical agents used to treat comorbidities in HIV-infected individuals often can interact with protease inhibitors, leading to toxic drug concentrations or untoward effects. Inhaled corticosteroids such as fluticasone propionate are often necessary to treat asthma in young children and are metabolized by CYP3A4. Interactions between protease inhibitors and inhaled fluticasone propionate have been reported in the adult population, but reports are limited in the pediatric literature.
This case raises awareness of the interaction between fluticasone propionate and lopinavir/ritonavir and adverse effects in children receiving both medications.
描述一名儿童在同时使用吸入性丙酸氟替卡松、鼻用莫米松和包括洛匹那韦/利托那韦在内的高效抗逆转录病毒治疗方案期间发生库欣综合征的病例。
一名9岁感染HIV且患有哮喘的男孩在开始丙酸氟替卡松吸入治疗（1吸；220微克）后出现满月脸、面部毛发增多和体重增加。他的抗逆转录病毒治疗方案包含蛋白酶抑制剂组合洛匹那韦/利托那韦，剂量为每日两次，每次216/54毫克，且在之前5年病情一直稳定。他还因过敏性鼻炎接受鼻用莫米松治疗11个月。血清皮质醇和促肾上腺皮质激素水平与肾上腺抑制相符。停用丙酸氟替卡松后，这些体格检查结果、症状和实验室值恢复正常。纳兰霍概率量表表明，洛匹那韦/利托那韦与丙酸氟替卡松之间可能发生了相互作用，导致随后的肾上腺抑制。
蛋白酶抑制剂由于抑制CYP3A4同工酶而与众多药物相互作用有关。用于治疗HIV感染者合并症的药物常常会与蛋白酶抑制剂相互作用，导致药物毒性浓度或不良影响。吸入性皮质类固醇如丙酸氟替卡松通常是治疗幼儿哮喘所必需的，且由CYP3A4代谢。蛋白酶抑制剂与吸入性丙酸氟替卡松之间的相互作用在成人中已有报道，但儿科文献中的报道有限。
本病例提高了对丙酸氟替卡松与洛匹那韦/利托那韦之间相互作用以及同时接受这两种药物治疗的儿童不良反应的认识。
