Pasireotide Diaspartate

Registered South African indications:

• Cushing's disease

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
• Gallbladder disorders
• Hypocortisolism

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

Cushing’s disease
- For patients whom pituitary surgery is not an option or has not been curative

• SC: Initial: 0.9mg, 12hrly (Pre-diabetes or diabetes: Initial: 0.6mg, 12hrly)

The dose should be based on response and tolerability. For patients who are started on 0.6mg, 12hrly, a dosage increase to 0.9mg, 12hrly may be considered after two months based on the response to treatment

Individualised dose reduction may be considered for patients with a stable response at the discretion of the treating physician  

Patients who do not experience clinical benefit from pasireotide after two months of treatment should be considered for discontinuation (see additional prescribing points)

Management of suspected adverse reactions may require temporary dose reduction of pasireotide. Dose reduction by decrements of 0.3mg 12hrly is suggested

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

Fertility

• Studies in rats have shown effects on female reproductive parameters. The clinical relevance of these effects in humans is unknown
• The therapeutic benefits of a reduction or normalisation of serum cortisol levels in female patients with Cushing's disease could potentially restore fertility
• Female patients of childbearing potential should be advised to use adequate contraception during treatment with pasireotide diaspartate

Renal impairment

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

Hepatic impairment

• Mild (Child-Pugh class A): No dose adjustment recommended
• Moderate (Child-Pugh class B): Caution; dose adjustment recommended
  Initial: 0.3mg, 12hrly; Max: 0.6mg, 12hrly
• 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

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

Administration directions

• Pasireotide diaspartate is to be administered subcutaneously by self-injection. Patients should receive instructions from the medical practitioner on how to inject pasireotide subcutaneously
• Use of the same injection site for two consecutive injections is not recommended
• Sites showing signs of inflammation or irritation should be avoided
• Prefered injection sites for subcutaneous injections are the top of the thighs and the abdomen (excluding the navel and waistline)
• Pasireotide is to be used without any dilution and must not be mixed with other medicines

Treatment duration

• Patients should be evaluated for treatment response (clinically meaningful reduction in Urinary Free Cortisol [UFC] levels and/or improvement in signs or symptoms of the disease) and should continue receiving therapy with pasireotide as long as benefit is derived
• Maximum UFC reduction is typically seen by two months of treatment

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 binds and activates four of the five human somatostatin receptor subtypes (hsst), especially hsst5, in corticotrophs of adrenocorticotropic hormone (ACTH) producing pituitary adenomas, resulting in inhibition of ACTH secretion.

Injection (per ml) 0.3mg

• Signifor (Norvatis) Originator

Injection (per ml) 0.6mg

• Signifor (Norvatis) Originator

Injection (per ml) 0.9mg

• Signifor (Norvatis) Originator