Usual Adult Dose for Cushing's Syndrome

Initial dose: 2 mg orally twice a day
Titration: Initially by 1 to 2 mg twice a day, no more frequently than every 2 weeks

• Further titration (after reaching 10 mg orally twice a day): By 5 mg twice a day every 2 weeks

• The dose should be titrated based on rate of cortisol changes, individual tolerability, and individual improvement in signs/symptoms of Cushing's disease.
• If a patient tolerates 10 mg twice a day and continues to have elevated 24-hour urine free cortisol (UFC) level above the upper limit of normal (ULN), the dosage can be titrated further by 5 mg twice a day every 2 weeks.
• Cortisol levels should be monitored from at least two 24-hour UFC collections every 1 to 2 weeks until adequate clinical response is maintained.
• The maintenance dosage is individualized and determined by titration based on cortisol levels and patient's signs/symptoms; the maintenance dosage varied between 2 and 7 mg twice a day in clinical trials.
• Once maintenance dosage achieved, cortisol levels should be monitored at least every 1 to 2 months or as indicated.

Renal Dose Adjustments

Renal dysfunction: No adjustment recommended

Comments:

• UFC levels should be interpreted with caution in patients with moderate to severe renal dysfunction, due to reduced UFC excretion.

Liver Dose Adjustments

Mild liver dysfunction (Child-Pugh A): No adjustment recommended
Moderate liver dysfunction (Child-Pugh B): The recommended starting dose is 1 mg orally twice a day.
Severe liver dysfunction (Child-Pugh C): The recommended starting dose is 1 mg orally once a day in the evening.

Comments:

• More frequent monitoring of adrenal function may be needed in patients with liver dysfunction during dose titration.

Dose Adjustments

Dosage Interruptions and Modifications:

• This drug should be decreased or temporarily discontinued if UFC levels fall below target range, there is a rapid decrease in cortisol levels, and/or patients report symptoms of hypercortisolism; if needed, glucocorticoid replacement therapy should be started.
• This drug should be stopped and exogenous glucocorticoid replacement therapy should be administered if serum/plasma cortisol levels are below target range and patients have symptoms of adrenal insufficiency.
• If treatment is interrupted, this drug should be restarted at a lower dose when cortisol levels are within target ranges and patient symptoms have resolved.

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Correct hypokalemia and hypomagnesemia before starting this drug.
• Obtain baseline ECG; repeat ECG within 1 week after starting therapy and as clinically indicated thereafter.
• Administer with or without food.

• Store at 20C to 25C (68F to 77F); excursions permitted to 15C to 30C (59F to 86F).
• Protect from moisture.

• Cardiovascular: ECG (before starting therapy); for effect on QTc interval (during therapy), for worsening hypertension
• Endocrine: Cortisol levels (every 1 to 2 weeks until adequate clinical response maintained, then every 1 to 2 months or as indicated); 24-hour UFC and serum/plasma cortisol (periodically during therapy)
• General: Patient's signs/symptoms (periodically during therapy); for edema
• Metabolic: For hypokalemia and hypomagnesemia (during therapy)

• Read the US FDA-approved patient labeling (Patient Information).
• Laboratory monitoring is important; adhere to return visit schedule.
• Report symptoms of hypercortisolism to health care provider.
• Contact health care provider at once if signs/symptoms of QT prolongation occur.
• Report the occurrence of low potassium levels, worsening hypertension, edema, hirsutism, hypertrichosis, and acne (in females) to health care provider.
• If a dose is missed, take the next dose at the regularly scheduled time.
• Do not breastfeed during therapy and for at least 1 week after the last dose.