Department of Biostatistics and Clinical Research, University Hospital of Caen Normandy, Caen, France.
Centre Régional de Pharmacovigilance, University Hospital of Caen Normandy, Caen, France.
J Antimicrob Chemother. 2019 Nov 1;74(11):3291-3294. doi: 10.1093/jac/dkz324.
To explore the frequent interaction between antiretroviral-boosting agents and corticosteroids causing Cushing's syndrome (CS) in the French Pharmacovigilance Database (FPVD).
We conducted a retrospective case-control study describing CS recorded in the FPVD between 1996 and 2018. Case was defined as CS occurring in people living with HIV (PLWH) and control was defined as CS in uninfected individuals. Drug-drug interaction (DDI) was defined as an interaction between corticosteroids and CYP3A4 inhibitors. Data concerning the DDI, corticosteroids involved, route of administration and seriousness of the CS were described.
Among the 139 instances of CS identified, 34/35 cases (97%) had DDIs (31 with ritonavir and 3 with cobicistat) and 7/104 controls (7%) had DDIs (6 with itraconazole and 1 with verapamil). The main corticosteroid involved was inhaled fluticasone (28/35, 80%) among the cases and oral prednisone (38/104, 37%) among the controls. More CS cases (30/35, 86%) than CS controls (62/104, 60%) were serious (OR = 4.0, 95% CI = 1.4-14.4; P = 0.007).
Antiretroviral-boosting agents were responsible for one out of four iatrogenic CS cases in a French national database. Prescribers should be aware of the risk of potentially serious DDIs between antiretroviral-boosting agents and corticosteroids, including single-tablet regimens containing cobicistat.
在法国药物警戒数据库（FPVD）中探索抗逆转录病毒增效剂与皮质类固醇频繁相互作用导致库欣综合征（CS）的情况。
我们进行了一项回顾性病例对照研究，描述了 1996 年至 2018 年期间 FPVD 中记录的 CS。病例定义为 HIV 感染者（PLWH）中发生的 CS，对照定义为未感染者中的 CS。药物-药物相互作用（DDI）定义为皮质类固醇和 CYP3A4 抑制剂之间的相互作用。描述了 DDI、涉及的皮质类固醇、给药途径和 CS 的严重程度的数据。
在确定的 139 例 CS 中，34/35 例（97%）存在 DDI（31 例与利托那韦，3 例与考比司他），7/104 例对照（7%）存在 DDI（6 例与伊曲康唑，1 例与维拉帕米）。病例中主要涉及的皮质类固醇是吸入用氟替卡松（28/35，80%），对照中主要涉及的皮质类固醇是口服泼尼松（38/104，37%）。与 CS 对照（62/104，60%）相比，更多的 CS 病例（30/35，86%）为严重（OR ⁇ 4.0，95%CI ⁇ 1.4-14.4；P ⁇ 0.007）。
在法国国家数据库中，抗逆转录病毒增效剂导致四分之一的医源性 CS 病例。处方者应意识到抗逆转录病毒增效剂与皮质类固醇之间存在潜在严重 DDI 的风险，包括含有考比司他的单片复方制剂。
