To evaluate the safety of the novel oral cortisol synthesis inhibitor osilodrostat in the treatment of Cushing syndrome (CS) through data mining of real-world databases.

Data on adverse drug events (ADEs) of osilodrostat from January 1, 2016 to March 31, 2025 were retrieved from the US Food and Drug Administration's Adverse Event Reporting System (FAERS). The reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to assess the occurrence of ADEs in the treatment of CS with osilodrostat.

A total of 1453 reports of osilodrostat-related ADEs were obtained from FAERS, with off-label use being the most common, followed by fatigue and nausea. Among the reports withknown patient gender, the proportion of females (14.38%) was higher than that of males (6.34%). The known reported ages included patients from 12 to over 85 years old, with the majority being adults aged 18 to 65. Signal strength assessment of osilodrostat ADEs revealed that the ROR for cortisol reduction was 898.35 and for adrenal insufficiency was 164.87, both reflecting the risk of hypothalamic-pituitary-adrenal axis regulation abnormalities.

Personalized monitoring during osilodrostat treatment for CS is crucial for the effective management of ADEs. Pre-treatment medication assessment and ADE-related indicator monitoring during treatment for CS patients receiving osilodrostat are of great importance. Once ADEs or disease progression occur, timely and active intervention measures should be taken to ensure the rational and safe use of the drug.