Osilodrostat Disease Interactions

Dosage adjustment of osilodrostat is required for patients with moderate to severe liver dysfunction. The recommended starting dose for patients with moderate liver dysfunction is 1 mg orally twice a day, and for patients with severe liver dysfunction is 1 mg orally once a day in the evening. No dose adjustment is required in patients with mild liver dysfunction. More frequent monitoring of adrenal function may be needed during dose titration in all patients with liver dysfunction.

No dosage adjustment of osilodrostat is required for patients with impaired renal function. However, in patients with moderate to severe renal dysfunction, urinary free cortisol (UFC) levels should be interpreted with caution due to reduced UFC excretion.

The use of osilodrostat is associated with a dose-dependent QT interval prolongation, which may cause cardiac arrhythmias. It is recommended to perform an ECG to obtain a baseline QTc interval measurement before starting therapy and to monitor for an effect on the QTc interval thereafter. Temporary discontinuation of osilodrostat should be considered in the case of an increase in QTc interval greater than 480 milliseconds. Hypokalemia and hypomagnesemia should be corrected before initiating treatment and monitored regularly during treatment. Electrolyte abnormalities should be corrected if indicated. Care should be exercised when using this agent in patients with risk factors for QT prolongation and more frequent ECG monitoring should be considered.

Osilodrostat lowers cortisol levels and can lead to hypocortisolism and sometimes life-threatening adrenal insufficiency. Patients should be evaluated for precipitating causes of hypocortisolism. Serum/plasma cortisol, 24-hour urine free cortisol, and patient's signs/symptoms should be monitored periodically during treatment. Osilodrostat should be decreased or temporarily discontinued if urine free cortisol levels fall below the target range, there is a rapid decrease in cortisol levels, and/or patients report hypocortisolism symptoms. Therapy should be stopped and exogenous glucocorticoid replacement therapy should be administered if serum/plasma cortisol levels are below the target range and patients have symptoms of adrenal insufficiency. Osilodrostat should be restarted at a lower dose when urine free cortisol and serum/plasma cortisol levels are within the target range, and/or patient symptoms have resolved.