Mahlab-Guri Keren, Asher Ilan, Gradstein Serge, Zung Amnon, Radian-Sade Sara, Elbirt Daniel, Sthoeger Zev
Clinical Immunology, Allergy and AIDS, Kaplan Medical Center, Rehovot, Israel.
J Asthma. 2011 Oct;48(8):860-3. doi: 10.3109/02770903.2011.606580. Epub 2011 Aug 22.
Ritonavir, a protease inhibitor (PI), is commonly used in the treatment of HIV-1 infection. It is a potent inhibitor of the hepatic cytochrome P450 superfamily. Therefore, its usage with other PI medications leads to significant increases in the levels of the latter PI, which allows a reduction in pill burden. Intranasal and inhaled corticosteroids are widely used for the treatment of allergic rhinitis and asthma. Inhaled steroids do not usually lead to systemic adverse events, since their plasma concentrations are quite low due to extensive first-pass metabolism and clearance by CYP3A4. However, the coadministration of Ritonavir with inhaled (or intranasal) corticosteroids may result in an increase in the plasma corticosteroid levels due to the potent CYP3A4 inhibition by Ritonavir. This may cause Cushing's syndrome (laboratory and clinical) with adrenal suppression.
Plasma cortisol and urinary-free cortisol levels were determined using immunoassays. In the Synacthen test, plasma cortisol levels were measured at time 0 as well as at times 60, 120, and 150 minutes following an intramuscular injection of 0.25 mg Synacthen.
We present here three HIV-1 female patients aged 12, 55 and 65 years who developed iatrogenic Cushing's syndrome with adrenal suppression following the coadministration of Ritonavir and inhaled Fluticasone, both at the standard recommended doses.
The coadministration of Ritonavir and Fluticasone at the recommended doses caused, in our three patients, iatrogenic Cushing's syndrome with adrenal suppression. We suggest that this adverse event is underdiagnosed and high clinical suspicion is needed for early diagnosis and prenention of Addisonian crises. Thus, Fluticasone treatment should be avoided in patients who are treated with Ritonavir. Alternative therapeutic options for asthma control such as oral Montelukast or bronchodilators alone should be considered.
利托那韦是一种蛋白酶抑制剂（PI），常用于治疗HIV-1感染。它是肝细胞色素P450超家族的强效抑制剂。因此，它与其他PI药物联合使用会导致后一种PI的水平显著升高，从而减少服药负担。鼻内和吸入性皮质类固醇广泛用于治疗过敏性鼻炎和哮喘。吸入性类固醇通常不会导致全身不良反应，因为由于CYP3A4的广泛首过代谢和清除作用，其血浆浓度相当低。然而，利托那韦与吸入性（或鼻内）皮质类固醇联合使用可能会由于利托那韦对CYP3A4的强效抑制作用而导致血浆皮质类固醇水平升高。这可能会导致伴有肾上腺抑制的库欣综合征（实验室检查和临床症状）。
使用免疫测定法测定血浆皮质醇和尿游离皮质醇水平。在促肾上腺皮质激素试验中，在肌肉注射0.25mg促肾上腺皮质激素后0分钟以及60、120和150分钟时测量血浆皮质醇水平。
我们在此报告三名年龄分别为12岁、55岁和65岁的HIV-1女性患者，她们在按照标准推荐剂量联合使用利托那韦和吸入性氟替卡松后出现了医源性库欣综合征并伴有肾上腺抑制。
在我们的三名患者中，按照推荐剂量联合使用利托那韦和氟替卡松导致了医源性库欣综合征并伴有肾上腺抑制。我们认为这种不良事件未得到充分诊断，早期诊断和预防肾上腺危象需要高度的临床怀疑。因此，接受利托那韦治疗的患者应避免使用氟替卡松治疗。应考虑使用其他控制哮喘的治疗选择，如口服孟鲁司特或单独使用支气管扩张剂。
