Cushing’s syndrome due to interaction between ritonavir or cobicistat and corticosteroids: a case–control study in the French Pharmacovigilance Database

Objectives To explore the frequent interaction between antiretroviral-boosting agents and corticosteroids causing Cushing’s syndrome (CS) in the French Pharmacovigilance Database (FPVD). Methods 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. Results 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). Conclusions 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.