ISTURISA Film-coated tablet Ref.[10371] Active ingredients: Osilodrostat

2.1 Laboratory Testing Prior to ISTURISA Initiation

• Correct hypokalemia and hypomagnesemia prior to starting ISTURISA [see Warnings and Precautions (5.2, 5.3)].
• Obtain baseline electrocardiogram (ECG). Repeat ECG within one week after treatment initiation, and as clinically indicated thereafter [see Warnings and Precautions (5.2)].

2.2 Recommended Dosage, Titration, and Monitoring

• Initiate dosing at 2 mg orally twice daily, with or without food.
• Initially, titrate the dosage by 1 to 2 mg twice daily, no more frequently than every 2 weeks based on the rate of cortisol changes, individual tolerability and improvement in signs and symptoms of Cushing’s disease. If a patient tolerates ISTURISA dosage of 10 mg twice daily and continues to have elevated 24 hour urine free cortisol (UFC) levels above upper normal limit, the dosage can be titrated further by 5 mg twice daily every 2 weeks. Monitor cortisol levels from at least two 24-hour urine free cortisol collections every 1-2 weeks until adequate clinical response is maintained.
• The maintenance dosage of ISTURISA is individualized and determined by titration based on cortisol levels and patient’s signs and symptoms.
• The maintenance dosage varied between 2 mg and 7 mg twice daily in clinical trials. The maximum recommended maintenance dosage of ISTURISA is 30 mg twice daily.
• Once the maintenance dosage is achieved, monitor cortisol levels at least every 1-2 months or as indicated.

2.3 Dosage Interruptions and Modifications

• Decrease or temporarily discontinue ISTURISA if urine free cortisol levels fall below the target range, there is a rapid decrease in cortisol levels, and/or patients report symptoms of hypocortisolism. If necessary, glucocorticoid replacement therapy should be initiated.
• Stop ISTURISA and administer exogenous glucocorticoid replacement therapy if serum or plasma cortisol levels are below target range and patients have symptoms of adrenal insufficiency [see Warnings and Precautions (5.1)].
• If treatment is interrupted, re-initiate ISTURISA at a lower dose when cortisol levels are within target ranges and patient symptoms have been resolved.

2.4 Recommended Dosage and Monitoring in Patients with Renal Impairment

• No dose adjustment is required for patients with renal impairment. Use caution in interpreting urine free cortisol levels in patients with moderate to severe renal impairment, due to reduced urine free cortisol excretion [see Clinical Pharmacology (12.3)].

2.5 Recommended Dosage and Monitoring in Patients with Hepatic Impairment

• For patients with moderate hepatic impairment (Child-Pugh B), the recommended starting dose is 1 mg twice daily. For patients with severe hepatic impairment (Child-Pugh C), the recommended starting dose is 1 mg once daily in the evening.
• No dose adjustment is required for patients with mild hepatic impairment (Child-Pugh A).
• More frequent monitoring of adrenal function may be required during dose titration in all patients with hepatic impairment [see Clinical Pharmacology (12.3)].

2.6 Missed Dose

If a dose of ISTURISA is missed, the patient should take their next dose at the regularly scheduled time.

Overdosage may result in severe hypocortisolism. Signs and symptoms suggestive of hypocortisolism may include nausea, vomiting, fatigue, low blood pressure, abdominal pain, loss of appetite, dizziness, and syncope.

In case of suspected overdosage, ISTURISA should be temporarily discontinued, cortisol levels should be checked, and if necessary, corticosteroid supplementation should be initiated. Close surveillance may be necessary, including monitoring of the QT interval, blood pressure, glucose, fluid, and electrolyte until the patient’s condition is stable.

Store at room temperature between 68°F to 77°F (20°C to 25°C); excursions permitted 15°C to 30°C (59°F to 86°F); protect from moisture.