Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Recordati Rare Diseases, Immeuble Le Wilson, 70 avenue du Général de Gaulle, 92800 Puteaux, France
Isturisa is indicated for the treatment of endogenous Cushing’s syndrome in adults.
Treatment should be initiated and supervised by physicians experienced in endocrinology or internal medicine and with access to the appropriate facilities for monitoring of biochemical responses since the dose must be adjusted to meet the patient’s therapeutic needs, based on the normalisation of cortisol levels.
The recommended starting dose is 2 mg osilodrostat twice daily. For patients of Asian ancestry, a reduced starting dose of 1 mg twice daily is recommended (see section 5.2).
The dose can be gradually titrated (initially by dose increments of 1 or 2 mg) based on individual response and tolerability, with the aim to achieve normal cortisol levels. It is recommended that cortisol levels (e.g. 24-hour urinary free cortisol, serum/plasma cortisol) be monitored every 1-2 weeks until adequate clinical response is maintained. Thereafter, less frequent monitoring may be considered as clinically indicated, unless there are reasons for additional monitoring (see sections 4.4 and 4.5). Increases in dose should not occur more frequently than once every 1-2 weeks and should be guided by the results of cortisol assessments and by the individual clinical response.
The dose of osilodrostat should be decreased or treatment temporarily interrupted if cortisol levels are below the lower limit of normal, or if there is a rapid decrease in cortisol levels to the lower part of the normal range, or if the patient has signs or symptoms suggestive of hypocortisolism (see section 4.4). Isturisa may be resumed after resolution of symptoms at a lower dose, provided that cortisol levels are above the lower limit of normal in the absence of glucocorticoid substitution. Management of other suspected adverse reactions at any time during treatment may also require a temporary dose reduction or temporary interruption of treatment.
The usual maintenance dose in clinical studies varied between 2 and 7 mg twice daily.
The maximum recommended dose of Isturisa is 30 mg twice daily.
If a dose is missed, the patient should take the prescribed dose at the next scheduled time; the next dose should not be doubled.
There is no evidence to suggest that dose adjustment is required in patients aged 65 years or above. However, data on the use of osilodrostat in this population are limited and Isturisa should therefore be used with caution in this age group.
No dose adjustment is required for patients with renal impairment (see section 5.2). Urinary free cortisol (UFC) levels should be interpreted with caution in patients with moderate to severe renal impairment, due to reduced UFC excretion. Alternative methods for cortisol monitoring should be considered in these patients.
No dose adjustment is required for patients with mild hepatic impairment (Child-Pugh A). 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, with initial up-titration to 1 mg twice daily (see section 5.2).
Data on use in patients with hepatic impairment is limited. More frequent monitoring of adrenal function may be required in patients with hepatic impairment during dose titration.
The safety and efficacy of Isturisa in patients less than 18 years of age have not yet been established.
No data are available.
Oral use.
Isturisa can be taken with or without food.
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 interrupted, cortisol levels checked, and if necessary corticosteroid supplementation initiated. Close surveillance may be necessary including monitoring of the QT interval, blood pressure, glucose, fluid and electrolyte balance until the patient’s condition is stable.
3 years.
Do not store above 25°C. Store in the original package in order to protect from moisture.
Alu/Alu blister of 10 tablets.
Packs containing 60 tablets (6 blisters of 10 tablets).
No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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