Drugs List

Therapeutic Indications

Uses

Acromegaly: other treatments unsuitable/ineffective
Cushing's syndrome - treatment

Treatment of patients with acromegaly for whom surgery is not an option or has not been curative and who are inadequately controlled on treatment with another somatostatin analogue.

Treatment of patients with Cushing's disease for whom surgery is not an option or for whom surgery has failed.

Administration

Pasireotide is to be administered by deep intramuscular injection into the gluteal muscle.

Contraindications

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

Precautions and Warnings

Family history of long QT syndrome
Bradycardia
Cardiac disorder
Diabetes mellitus
Electrolyte imbalance
End stage renal disease
History of torsade de pointes
Moderate hepatic impairment
New York Heart Association class III failure
New York Heart Association class IV failure
Non paced second/third degree AV block
Recent myocardial infarction
Severe renal impairment
Unstable angina
Ventricular fibrillation
Ventricular tachycardia

Correct electrolyte disorders before treatment
Patients with diabetes may experience fluctuations in blood glucose
Advise ability to drive/operate machinery may be affected by side effects
Not all available strengths are licensed for all indications
Vary injection site during prolonged therapy
Monitor blood glucose and HbA1c before treatment
Monitor gallbladder ultrasonically before treatment then every 6-12 months
Monitor hepatic function before treatment and regularly during treatment
Perform ECG before treatment
Advise diabetics to increase self-monitoring of glucose at start of therapy
Monitor adrenocortical function
Monitor blood glucose 4 weeks after treatment complete
Monitor blood glucose weekly for 4 to 6 weeks after any dose increase
Monitor blood glucose weekly for the first 3 months and then as indicated
Monitor closely patient with a history of congestive cardiac failure
Monitor ECG after 3 weeks of treatment and then as clinically indicated
Monitor HbA1c 3 months after end of treatment
Monitor hepatic function after first 2-3 weeks, then monthly for 3 months
Monitor patients with cardiac disorders
Monitor pituitary function as clinically indicated
Monitor serum electrolytes
Advise patient to report signs of hypocortisolism
If hypocortisolism occurs, reduce dose and/or institute steroid therapy
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Discontinue if AST or ALT level > 3x ULN and bilirubin > 2x ULN
Discontinue if AST or ALT level exceeds 5x ULN and persists
Discontinue if jaundice or other evidence of hepatic impairment occurs
Do not restart following significant hepatic dysfunction
Reduce dose or discontinue if persistent uncontrolled hyperglycaemia occurs
Female: Ensure adequate contraception during treatment

Pregnancy and Lactation

Pregnancy

Pasireotide is contraindicated in pregnancy.

Animal studies have shown reproductive toxicity, although the risk to humans is not known.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Pasireotide is contraindicated in breastfeeding.

Animal studies have shown that pasireotide is secreted in the milk of rats when administered subcutaneously. It is not known whether pasireotide is secreted in human breast milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal distension
Abdominal pain
Acute adrenal insufficiency
Alanine aminotransferase increased
Alopecia
Anaemia
Anorexia
Aspartate aminotransferase increased
Bradycardia
Cholecystitis
Cholelithiasis
Cholestasis
Creatine phosphokinase increased
Decreased appetite
Decreased glucose tolerance
Decreased serum sodium
Diabetes mellitus
Diarrhoea
Dizziness
Elevated amylase levels
Elevated serum lipase
Fatigue
Gamma glutamyl transferase (GGT) increased
Headache
Hyperglycaemia
Hyperkalaemia
Hypoglycaemia
Hypotension
Increase in serum glucose
Increased glycated haemoglobin (HbA1c) levels
Injection site reactions
Nausea
Prolongation of QT interval
Prothrombin time increased
Pruritus
Sinus bradycardia
Vomiting
Weakness

Presentation

Powder for suspension for intramuscular injection containing pasireotide.

Drugs List

Therapeutic Indications

Uses

Acromegaly: other treatments unsuitable/ineffective
Cushing's syndrome - treatment

Treatment of patients with acromegaly for whom surgery is not an option or has not been curative and who are inadequately controlled on treatment with another somatostatin analogue.

Treatment of patients with Cushing's disease for whom surgery is not an option or for whom surgery has failed.

Dosage

Adults

Patients with Hepatic Impairment

Additional Dosage Information

Administration

Pasireotide is to be administered by deep intramuscular injection into the gluteal muscle.

Contraindications

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

Precautions and Warnings

Family history of long QT syndrome
Bradycardia
Cardiac disorder
Diabetes mellitus
Electrolyte imbalance
End stage renal disease
History of torsade de pointes
Moderate hepatic impairment
New York Heart Association class III failure
New York Heart Association class IV failure
Non paced second/third degree AV block
Recent myocardial infarction
Severe renal impairment
Unstable angina
Ventricular fibrillation
Ventricular tachycardia

Correct electrolyte disorders before treatment
Patients with diabetes may experience fluctuations in blood glucose
Advise ability to drive/operate machinery may be affected by side effects
Not all available strengths are licensed for all indications
Vary injection site during prolonged therapy
Monitor blood glucose and HbA1c before treatment
Monitor gallbladder ultrasonically before treatment then every 6-12 months
Monitor hepatic function before treatment and regularly during treatment
Perform ECG before treatment
Advise diabetics to increase self-monitoring of glucose at start of therapy
Monitor adrenocortical function
Monitor blood glucose 4 weeks after treatment complete
Monitor blood glucose weekly for 4 to 6 weeks after any dose increase
Monitor blood glucose weekly for the first 3 months and then as indicated
Monitor closely patient with a history of congestive cardiac failure
Monitor ECG after 3 weeks of treatment and then as clinically indicated
Monitor HbA1c 3 months after end of treatment
Monitor hepatic function after first 2-3 weeks, then monthly for 3 months
Monitor patients with cardiac disorders
Monitor pituitary function as clinically indicated
Monitor serum electrolytes
Advise patient to report signs of hypocortisolism
If hypocortisolism occurs, reduce dose and/or institute steroid therapy
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Discontinue if AST or ALT level > 3x ULN and bilirubin > 2x ULN
Discontinue if AST or ALT level exceeds 5x ULN and persists
Discontinue if jaundice or other evidence of hepatic impairment occurs
Do not restart following significant hepatic dysfunction
Reduce dose or discontinue if persistent uncontrolled hyperglycaemia occurs
Female: Ensure adequate contraception during treatment

Pregnancy and Lactation

Pregnancy

Pasireotide is contraindicated in pregnancy.

Animal studies have shown reproductive toxicity, although the risk to humans is not known.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Pasireotide is contraindicated in breastfeeding.

Animal studies have shown that pasireotide is secreted in the milk of rats when administered subcutaneously. It is not known whether pasireotide is secreted in human breast milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal distension
Abdominal pain
Acute adrenal insufficiency
Alanine aminotransferase increased
Alopecia
Anaemia
Anorexia
Aspartate aminotransferase increased
Bradycardia
Cholecystitis
Cholelithiasis
Cholestasis
Creatine phosphokinase increased
Decreased appetite
Decreased glucose tolerance
Decreased serum sodium
Diabetes mellitus
Diarrhoea
Dizziness
Elevated amylase levels
Elevated serum lipase
Fatigue
Gamma glutamyl transferase (GGT) increased
Headache
Hyperglycaemia
Hyperkalaemia
Hypoglycaemia
Hypotension
Increase in serum glucose
Increased glycated haemoglobin (HbA1c) levels
Injection site reactions
Nausea
Prolongation of QT interval
Prothrombin time increased
Pruritus
Sinus bradycardia
Vomiting
Weakness

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: July 2018.

Reference Sources

Summary of Product Characteristics: Signifor powder and solvent for injection. Novartis Pharmaceuticals UK Ltd. Revised April 2018.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 25 July 2018