Adult Dosing

Cushing’s disease

• Initial dose: 0.6 mg or 0.9 mg SC bid
• Dose range: 0.3-0.9 mg SC bid

• Dose titration is advised based on response and tolerability
• Two consecutive injections at the same site is not recommended

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Treatment of Cushing's disease in adult patients for whom pituitary surgery is not an option or has not been curative

• Hypersensitivity to any of the ingredients of the product

• N/A

Renal Dose Adjustment

• Renal impairment: No dose adjustments

Hepatic Dose Adjustment

• Mild hepatic impairment (Child-Pugh A): No dose adjustments
• Moderate hepatic impairment (Child-Pugh B): Initial: 0.3 mg bid. Max: 0.6 mg bid
• Severe hepatic impairment (Child-Pugh C): Avoid use

• Therapy may decrease circulating levels of cortisol leading to hypocortisolism. Monitor patients for signs and symptoms associated with hypocortisolism such as weakness, fatigue, anorexia, nausea, vomiting, hypotension, hyponatremia or hypoglycemia. If hypocortisolism occurs, decrease dose or discontinue pasireotide and exogenous glucocorticoid replacement therapy
• Increased blood glucose levels have been reported after initiation of therapy. Worsening of glycemic levels may occur in pre-diabetics, diabetics, and those with normal blood glucose levels. High risk of severe hyperglycemia and related complications may occur in patients with poor glycemic levels. If hyperglycemia persists, decrease or discontinue dose of pasireotide
• Bradycardia may occur with the use of pasireotide. Monitor patients with cardiac disease such as those with significant bradycardia, high-grade heart block, or concomitant use of drugs associated with bradycardia. Consider dose adjustments of beta-blockers, calcium channel blockers, or correction of electrolyte disturbances
• QT prolongation may occur at therapeutic and supra-therapeutic doses of pasireotide. Patients with congenital long QT prolongation, uncontrolled or significant cardiac disease such as myocardial infarction, congestive heart failure, unstable angina or clinically significant bradycardia, on anti-arrhythmic therapy with hypokalemia and/or hypomagnesemia are at risk of developing prolongation of QTc
• ALT or AST levels were found to be >3x upper limit of normal (ULN) and bilirubin was found to be >2x ULN. Discontinue the therapy if ALT levels increase. ALT, AST, alkaline phosphatase and bilirubin values resolves to near normal, pasireotide therapy may be resumed with caution and with close observation
• Cholelithiasis may be frequently reported during therapy
• Pasireotide may inhibit pituitary hormones other than ACTH. Increased risk for deficiency of pituitary hormones may be reported in patients who have undergone transsphenoidal surgery and pituitary irradiation

Pregnancy Category:C

Breastfeeding: It is unknown whether pasireotide is excreted in human milk, however it was found to be excreted in rat milk at levels 30% of the plasma level, hence risk to breastfeeding children cannot be excluded. Manufacturer advises caution.

• CV: Bradycardia, QT prolongation, hypertension, hypotension, sinus bradycardia
• CNS: Headache, dizziness, insomnia, vertigo
• NEURO: Asthenia, peripheral edema
• PSYCHIATRIC: Anxiety
• GI: Diarrhea, nausea, abdominal pain, decreased appetite, constipation, vomiting, abdominal distension
• HEMA: Anemia
• METABOLIC: Hypokalemia
• DERM: Alopecia, pruritus, dry skin
• RESP: Nasopharyngitis
• ENDO: Hypocortisolism, hyperglycemia, diabetes, cholelithiasis, pituitary hormone deficiency, hypercholesterolemia, hypoglycemia, type 2 diabetes mellitus, adrenal insufficiency
• MUSC: Myalgia, arthralgia, back pain, pain in extremity
• MISC: Fatigue, influenza
• LABTEST: Liver test elevations, increased glycosylated hemoglobin, increased blood amylase, prolonged prothrombin time
• HYPERSENSITIVITY: Injection site reactions

• Somatostatin analog; binds to somatostatin receptors (ssts) and inhibits ACTH secretion leading to decreased cortisol secretion
• Metabolized by liver
• Excreted in urine, bile, and feces
• Half-life: 12 hrs

US Trade Name(s)

• Signifor

US Availability

Signifor

• INJ: 0.3 mg/mL
• INJ: 0.6 mg/mL
• INJ: 0.9 mg/mL

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• Signifor

UK Availability

Signifor

• INJ: 0.3 mg/mL
• INJ: 0.6 mg/mL
• INJ: 0.9 mg/mL

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Endocrine/Metabolic

Metabolic Agents

somatostatin Analog