- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Solution for subcutaneous injection containing pasireotide.
Cushing's syndrome - treatment
The recommended initial dose of pasireotide is 600micrograms by subcutaneous injection twice a day.
Two months after the start of pasireotide therapy, patients should be evaluated for clinical benefit. Patients who experience a significant reduction in urinary free cortisol levels should continue to receive pasireotide as long as benefit is derived.
A dose increase to 900micrograms may be considered based on the response to the treatment, as long as the 600micrograms dose is well tolerated by the patient.
Patients who have not responded to pasireotide after two months of treatment should be considered for discontinuation.
Management of suspected adverse reactions at any time during the treatment may require temporary dose reduction of pasireotide. Dose reduction by decrements of 300micrograms twice a day is suggested.
Patients with Hepatic Impairment
Moderate hepatic impairment (Child Pugh B)
The recommended initial dose of 300micrograms twice a day. The maximum recommended dose for these patients is 600micrograms twice a day.
Additional Dosage Information
If switching from intramuscular injection to subcutaneous injection, maintain at least a 28 day interval from last intramuscular injection to first subcutaneous injection. Dose adjustments may be required, monitor patient for response and tolerability.
If dose is missed, next injection should be administered at the scheduled time. The dose should not be doubled to make up for missed dose.
Pasireotide is to be administered subcutaneously by self injection.
Patients should receive instructions from the physician or a healthcare professional on how to inject pasireotide subcutaneously.
Preferred injection sites for subcutaneous injections are the top of the thighs and the abdomen (excluding the navel or waistline).
Children under 18 years
Long QT syndrome
Severe hepatic impairment
Torsade de pointes
Precautions and Warnings
Family history of long QT syndrome
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
QTc interval greater than or equal to 500 msec
Recent myocardial infarction
Severe renal impairment
Patients with diabetes may experience fluctuations in blood glucose
Advise ability to drive/operate machinery may be affected by side effects
Vary injection site during prolonged therapy
Correct hypokalaemia before or during treatment
Correct hypomagnesaemia prior to administration
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
Consider monitoring ECG in patients at risk of QT prolongation
Monitor adrenocortical function
Monitor blood glucose 4 weeks after treatment complete
Monitor blood glucose for 2 to 4 weeks after any dose increase
Monitor blood glucose weekly for 8 to 12 weeks then as indicated
Monitor closely patient with a history of congestive cardiac failure
Monitor ECG after 1 week and then as clinically indicated
Monitor HbA1c 3 months after end of treatment
Monitor hepatic function after 1, 2, 4, 8 and 12 weeks of treatment
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
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
Discontinue if no response after 2 months
Do not restart following significant hepatic dysfunction
Reduce dose or discontinue if persistent uncontrolled hyperglycaemia occurs
Female: Ensure adequate contraception during treatment
Treatment with pasireotide leads to rapid suppression of ACTH (adrenocorticotropic hormone) secretion in Cushing's disease patients. Rapid, complete or near-complete suppression of ACTH may lead to a decrease in circulating levels of cortisol and potentially to transient hypocortisolism/hypoadrenalism.
Pregnancy and Lactation
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 ).
Pasireotide is contraindicated in breastfeeding.
It is not known whether pasireotide is secreted in the human milk, but animal studies show that it is found in the milk of rats.
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
Acute adrenal insufficiency
Alanine aminotransferase increased
Aspartate aminotransferase increased
Decreased glucose tolerance
Elevated amylase levels
Elevated serum lipase
Gamma glutamyl transferase (GGT) increased
Increase in serum glucose
Increased glycated haemoglobin (HbA1c) levels
Injection site reactions
Prolongation of QT interval
Prothrombin time increased
Upper abdominal pain
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 ).
Last Full Review Date: April 2018.
Summary of Product Characteristics: Signifor solution for injection 0.3mg, 0.6mg, 0.9mg. Novartis Pharmaceuticals. Revised September 2017.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 06 April 2018.
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.