Pasireotide Pamoate

Registered South African indications:

• Acromegaly

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Severe hepatic impairment

Cautions

• Pregnancy
• Breastfeeding
• Severe renal impairment
• Moderate hepatic impairment
• Pre-diabetic conditions
• Diabetes mellitus
• History or risk factors for bradycardia
• History of acute myocardial infarction
• High-grade heart block
• Congestive heart failure (NYHA Class III or IV)
• Unstable angina
• Sustained ventricular tachycardia
• Ventricular fibrillation
• Congenital long QT syndrome
• Uncontrolled or significant cardiac disease
• Hypokalaemia
• Hypomagnesaemia
• Female patients of childbearing potential
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj

Acromegaly
- As second line therapy after pituitary surgery (or when surgery is not feasible), in patients inadequately responding to other somatostatin analogues (SSAs) or where other SSAs cannot be used

• IM: Initial: 40mg, every 4 weeks; Max: 60mg/4 weeks

The dose may be increased to a maximum of 60mg for patients whose GH and/or IGF-1 levels are not fully controlled after 3 months of treatment with 40mg pasireotide

Management of suspected adverse reactions may require dose reduction of pasireotide. The dose may be decreased either temporarily or permanently by 20mg decrements

Cushing’s disease
- For patients whom surgery is not an option or for whom surgery has failed

• IM: Initial: 10mg, every 4 weeks; Titrate at intervals of 2-4 months; Max: 40mg/4 weeks

The patient should be evaluated for clinical benefit after the first month of treatment and periodically thereafter. Dose titration is based on response and tolerability. If no clinical benefit is observed, the patient should be considered for discontinuation

Management of suspected adverse reactions or over-response to treatment (cortisol levels < lower limit of normal) may require dose reduction, interruption or discontinuation of pasireotide

See additional prescribing points

Not established for use in children below 18 years 

Pregnancy

• Caution
• There is a limited amount of data from the use of pasireotide in pregnant women. Studies in animals have shown reproductive toxicity. Pasireotide is not recommended for use during pregnancy and in women of childbearing potential who are not using contraception

Breastfeeding

• Caution; not recommended
• It is unknown whether pasireotide is excreted in human milk. Available data in rats have shown excretion of pasireotide in milk. Breastfeeding should be discontinued during treatment with pasireotide

Renal impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; no dose adjustment recommended

Hepatic impairment

Acromegaly

• Mild (Child-Pugh class A): No dose adjustment recommended
• Moderate (Child-Pugh class B): Caution; dose adjustment recommended
  Initial: 20mg, every 4 weeks; Max: 40mg/4 weeks
• Severe (Child-Pugh class C): Contraindicated

Cushing's disease

• Mild (Child-Pugh class A): No dose adjustment recommended
• Moderate (Child-Pugh class B): Caution; dose adjustment recommended
  Initial: 10mg, every 4 weeks; Max: 20mg/4 weeks
• Severe (Child-Pugh class C): Contraindicated

Elderly

• No dose adjustment recommended

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness
• Fatigue

Cardiovascular Disorders

• Sinus bradycardia
• QT prolongation
• Hypotension

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Abdominal pain

Hepatobiliary Disorders

• Cholelithiasis
• Cholecystitis
• Cholestasis
• Increased gamma-glutamyltransferase
• Increased alanine aminotransferase 
• Increased aspartate aminotransferase  

Endocrine and Metabolic Disorders

• Adrenal insufficiency
• Hyperglycaemia
• Diabetes mellitus
• Decreased appetite
• Impaired glucose tolerance
• Increased glycosylated haemoglobin
• Increased lipase 
• Increased blood glucose 
• Increased amylase 

Musculoskeletal Disorders

• Myalgia
• Arthralgia

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Pruritus

Immune, Blood and Lymphatic System Disorders

• Anaemia
• Prolonged prothrombin time
• Increased blood creatine phosphokinase

Others

• Injection site reaction

• Ciclosporin
• QT prolonging agents
  - Class Ia antiarrhythmics (e.g. quinidine, procainamide, disopyramide)
  - Class III antiarrhythmics (e.g. amiodarone, dronedarone, sotalol, dofetilide, ibutilide)
  - Certain antibacterials (intravenous erythromycin, pentamidine injection, clarithromycin, moxifloxacin)
  - Certain antipsychotics (e.g. chlorpromazine, thioridazine, fluphenazine, pimozide, haloperidol, tiapride, amisulpride, sertindole, methadone)
  - Certain antihistamines (e.g. terfenadine, astemizole, mizolastine)
  - Antimalarials (e.g. chloroquine, halofantrine, lumefantrine)
  - Certain antifungals (ketoconazole, except in shampoo)
• Bradycardic agents
  - Beta-blockers (e.g. metoprolol, carteolol, propranolol, sotalol)
  - Acetylcholinesterase inhibitors (e.g. rivastigmine, physostigmine)
  - Certain calcium channel blockers (e.g. verapamil, diltiazem, bepridil)
  - Certain antiarrhythmics
• Insulin
• Antidiabetic agents (e.g. metformin, liraglutide, vildagliptin, nateglinide)

• Hepatic function
• Electrolytes
• Urinary free cortisol
• Full blood count
• Blood glucose
• Haemoglobin A1c
• Thyroid function
• Pituitary function
• ECG
• Gall bladder ultrasonography
• Signs and symptoms of hypocortisolism

Specific cases may require

• Heart rate
• Prothrombin time

Administration directions

• Pasireotide pamoate should only be administered by deep intramuscular injection by a trained health care professional
• Pasireotide pamoate suspension must only be prepared immediately before administration
• The site of repeat intramuscular injections should be alternated between the left and right gluteal muscle
• Reconstitution instructions: The injection kit must reach room temperate. Remove the injection kit from the fridge and let the kit stand at room temperature for a minimum of 30 minutes before reconstitution, but do not exceed 24 hours. After adding the diluent solution, shake the vial moderately in a horizontal direction for a minimum of 30 seconds until a uniform suspension is formed

Missed dose

• If a dose of pasireotide is missed the missed injection should be administered as soon as possible. The next dose should then be planned for 4 weeks after the injection is administered in order to resume the normal schedule of one dose every 4 weeks

Switch from subcutaneous to the intramuscular formulation in Cushing's disease

• There are no clinical data available on switching from the subcutaneous to the intramuscular pasireotide formulation. If such a switch should be required, the recommended initial dose for the treatment of Cushing's disease is 10 mg of pasireotide by deep intramuscular injection every 4 weeks. The patient should be monitored for response and tolerability and further dose adjustments may be needed

Pasireotide is a novel cyclohexapeptide, injectable somatostatin analogue. Pasireotide exerts its pharmacological activity via binding to somatostatin receptors, like the natural peptide hormones somatostatin-14 and somatostatin-28 (also known as somatotropin release inhibiting factor [SRIF]) and other somatostatin analogues. Pasireotide has the potential to stimulate both hsst2 and hsst5 subtype receptors relevant for inhibition of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion.

Injection (per Vial) 20mg

• Signifor LA 20mg (Key Oncologics) Originator

Injection (per Vial) 40mg

• Signifor LA 40mg (Key Oncologics) Originator

Injection (per Vial) 60mg

• Signifor LA 60mg (Key Oncologics) Originator