Drugs List

Therapeutic Indications

Uses

Cushing's syndrome

Treatment of endogenous Cushing's syndrome in adults.

Contraindications

Children under 18 years
Breastfeeding
Long QT syndrome
Pregnancy
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Patients over 65 years
Cardiac disorder
Electrolyte imbalance
History of torsade de pointes
Moderate hepatic impairment
Moderate renal impairment

Consider reducing initial dose in hepatic impairment
Correct electrolyte disorders before treatment
Advise patient that dizziness/fatigue may initially affect ability to drive
Renal impairment: Consider alternative parameter to urinary free cortisol
Treatment to be initiated and supervised by a specialist
Exclude pregnancy prior to initiation of treatment
Perform ECG before and during treatment
Monitor cortisol levels every 1 to 2 weeks until stable adequate response
Monitor serum electrolytes
Advise patient to report signs of hypocortisolism
Consider discontinuation if patient develops corticotroph tumour
If hypocortisolism occurs, reduce dose and/or institute steroid therapy
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Suspend/review treatment if QTcF interval greater than 480 msec
Female: Contraception required during and for 1 week after treatment
Breastfeeding: Do not breastfeed during & for 1 week after treatment

Additional monitoring is recommended during conditions which increase cortisol demand such as psychological or physical stress, or concomitant medications that affect osilodrostat exposure.

It is recommended to use an additional barrier method of contraception if hormonal contraceptives other than oral combination of ethinylestradiol and levonorgestrel are used.

Patients with symptoms of hypocortisolism should be monitored for hypotension, hyponatraemia, hyperkalaemia and/or hypoglycaemia.

Pregnancy and Lactation

Pregnancy

Osilodrostat is contraindicated during pregnancy.

The manufacturer does not recommend using osilodrostat during pregnancy. Animal studies have shown reproductive toxicity.

Lactation

Osilodrostat is contraindicated during breastfeeding.

The manufacturer states that breastfeeding should be discontinued during treatment with osilodrostat and for at least one week after treatment. It is unknown whether osilodrostat or its metabolites are excreted in human milk and a risk to the newborn/infant cannot be excluded.

Side Effects

Abdominal pain
Acne
Adrenal insufficiency
Decreased appetite
Diarrhoea
Dizziness
Elevated blood testosterone
Fatigue
Headache
Hirsutism
Hypokalaemia
Hypotension
Increase of liver transaminases
Increased blood corticotrophin
Nausea
Oedema
Prolongation of QT interval
Rash
Syncope
Tachycardia
Vomiting

Presentation

Oral formulation of osilodrostat.

Drugs List

Therapeutic Indications

Uses

Cushing's syndrome

Treatment of endogenous Cushing's syndrome in adults.

Dosage

Dosage is determined by individual response and tolerability with the aim of achieving normal cortisol levels.

Adults

Patients with Hepatic Impairment

Contraindications

Children under 18 years
Breastfeeding
Long QT syndrome
Pregnancy
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Patients over 65 years
Cardiac disorder
Electrolyte imbalance
History of torsade de pointes
Moderate hepatic impairment
Moderate renal impairment

Consider reducing initial dose in hepatic impairment
Correct electrolyte disorders before treatment
Advise patient that dizziness/fatigue may initially affect ability to drive
Renal impairment: Consider alternative parameter to urinary free cortisol
Treatment to be initiated and supervised by a specialist
Exclude pregnancy prior to initiation of treatment
Perform ECG before and during treatment
Monitor cortisol levels every 1 to 2 weeks until stable adequate response
Monitor serum electrolytes
Advise patient to report signs of hypocortisolism
Consider discontinuation if patient develops corticotroph tumour
If hypocortisolism occurs, reduce dose and/or institute steroid therapy
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Suspend/review treatment if QTcF interval greater than 480 msec
Female: Contraception required during and for 1 week after treatment
Breastfeeding: Do not breastfeed during & for 1 week after treatment

Additional monitoring is recommended during conditions which increase cortisol demand such as psychological or physical stress, or concomitant medications that affect osilodrostat exposure.

It is recommended to use an additional barrier method of contraception if hormonal contraceptives other than oral combination of ethinylestradiol and levonorgestrel are used.

Patients with symptoms of hypocortisolism should be monitored for hypotension, hyponatraemia, hyperkalaemia and/or hypoglycaemia.

Pregnancy and Lactation

Pregnancy

Osilodrostat is contraindicated during pregnancy.

The manufacturer does not recommend using osilodrostat during pregnancy. Animal studies have shown reproductive toxicity.

Lactation

Osilodrostat is contraindicated during breastfeeding.

The manufacturer states that breastfeeding should be discontinued during treatment with osilodrostat and for at least one week after treatment. It is unknown whether osilodrostat or its metabolites are excreted in human milk and a risk to the newborn/infant cannot be excluded.

Side Effects

Abdominal pain
Acne
Adrenal insufficiency
Decreased appetite
Diarrhoea
Dizziness
Elevated blood testosterone
Fatigue
Headache
Hirsutism
Hypokalaemia
Hypotension
Increase of liver transaminases
Increased blood corticotrophin
Nausea
Oedema
Prolongation of QT interval
Rash
Syncope
Tachycardia
Vomiting

Effects on Laboratory Tests

It is recommended to use laboratory methods that do not exhibit significant cross-reactivity with cortisol precursors such as 11-deoxycortisol.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: May 2021

Reference Sources

Summary of product characteristics: Isturisa 1mg, 5mg, 10mg film coated tablets. Recordati Rare Diseases UK ltd. Revised May 2020.