Products
Osilodrostate was approved in many countries, in the EU and in the US in 2020 in the form of film-coated tablets (Isturisa).
Structure and properties
Osilodrostat (C13H10FN3, Mr = 227.24 g/mol) is present in the drug as osilodrostat phosphate.
Effects
Osilodrostate (ATC H02CA02) inhibits the biosynthesis of cortisol. The effects are due to inhibition of 11β-hydroxylase (CYP11B1). This enzyme is responsible for the final step of cortisol synthesis in the adrenal gland. The half-life is about 4 hours. It is longer than that of the related metyrapone, which allows a reduction in the dosing interval.
Indications
For the treatment of Cushing’s syndrome and other causes of endogenous hypercortisolism (eg, adrenocortical adenoma, bilateral NNR hyperplasia, ectopic ACTH secretion).
Dosage
According to the SmPC. Tablets are taken in the morning and evening independently of meals.
Contraindications
- Hypersensitivity
For complete precautions, see the drug label.
Interactions
Drug-drug interactions are possible with agents that prolong the QT interval. Osilodrostate is metabolized by CYP450 isoenzymes and UDP-glucuronosyltransferases. These include CYP3A4, CYP2B6, and CYP2D6.
Adverse effects
The most common potential adverse effects include adrenal insufficiency, fatigue, edema, vomiting, nausea, and headache. Osilodrostate may prolong the QT interval.
