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Prescribing Information
SIGNIFOR LAR (pasireotide) for injectable suspension
For US Healthcare Professionals Only

SIGNIFOR LAR (pasireotide) for injectable suspension Signifor

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In medically naïve patients... SIGNIFOR LAR DEMONSTRATED SUPERIOR EFFICACY OVER OCTREOTIDE LAR

SIGNIFOR LAR was directly compared with Octreotide LAR24

A prospective, multicenter, double-blind, randomized, parallel-group, phase 3 study in adults with active acromegaly defined by elevated GH and IGF-1 levels* in medically naïve patients.24

Illustration of study design
Illustration of study design

Study Design: A multicenter, randomized, double-blind study was conducted to assess the safety and efficacy of SIGNIFOR LAR in drug-naïve patients with active acromegaly. A total of 358 patients naïve to drugs used to treat acromegaly were randomized in a 1:1 ratio to SIGNIFOR LAR or octreotide LAR. Randomization was stratified based on previous pituitary surgical status (eg, at least 1 prior pituitary surgery versus no prior pituitary surgery).

*As confirmed by a 2-hour five-point mean GH level >5 μg/L or lack of suppression of GH nadir to <1 μg/L after an OGTT and elevated IGF-1 for age and sex-matched controls.
†De novo patients with a pituitary adenoma visible on MRI but who refused pituitary surgery or for whom surgery was contraindicated were also eligible.
‡Stratified into two groups: 1) after pituitary surgery or 2) de novo. A dose increase to pasireotide LAR 60 mg or octreotide LAR 30 mg was permitted, but not mandatory, at month 3 or 7 based on biochemical response (mean GH ≥2.5 g/L and/or IGF-1 above the ULN).

SIGNIFOR LAR demonstrated superior efficacy over octreotide LAR

Significantly more medically naïve patients achieved biochemical control§ with SIGNIFOR LAR (P<0.01)3,24

  • 31.3% of patients receiving SIGNIFOR LAR (n=176) achieved biochemical control compared with 19.2% of those on octreotide LAR (n=182) overall
Chart of percent of patients achieving biochemical control
Chart of percent of patients achieving biochemical control
  • The primary endpoint was biochemical control defined as a GH level less than 2.5 ug/L and an IGF-1 level that was normal for the patient’s sex and age
  • Significantly more patients treated with SIGNIFOR LAR achieved biochemical control than those treated with octreotide LAR
  • While the study was not powered to detect treatment differences between subgroups, there was an increased response in patients who had previously undergone surgery

§Biochemical control defined as achieving GH <2.5 μg/L and normal IGF-1 for age and sex at month 12.24

Adverse events documented in medically naïve patients

Adverse reactions chart Adverse reactions chart

llDiabetes mellitus includes the terms diabetes mellitus and type 2 diabetes mellitus.
¶Sinus bradycardia includes the following PTs: bradycardia and sinus bradycardia.
SEE SECTION 6.1 IN FULL PRESCRIBING INFORMATION FOR COMPLETE ADVERSE REACTION TABLE.

Learn how to manage hyperglycemia

INDICATIONS AND USAGE

SIGNIFOR LAR® (pasireotide) is a somatostatin analog indicated for the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option.

IMPORTANT SAFETY INFORMATION

Hyperglycemia, Diabetes, and Ketoacidosis: SIGNIFOR LAR can cause increases in blood glucose levels which are sometimes severe. Monitor glucose levels as clinically appropriate during therapy. There have been postmarketing cases of ketoacidosis with SIGNIFOR LAR in patients with or without history of diabetes. Patients with poor baseline glycemic control are at higher risk of developing severe hyperglycemia. Patients who develop significant hyperglycemia on SIGNIFOR LAR may require initiation of anti-diabetic treatment or adjustment in their current anti-diabetic treatment. The optimal treatment for the management of SIGNIFOR LAR-induced hyperglycemia is not known. If hyperglycemia cannot be controlled despite medical management, reduce the dose or discontinue SIGNIFOR LAR. Patients who present with signs and symptoms consistent with severe metabolic acidosis should be assessed for ketoacidosis regardless of diabetes history. If ketoacidosis is suspected, discontinue SIGNIFOR LAR and promptly evaluate and treat the patient.

INDICATIONS AND USAGE

SIGNIFOR LAR® (pasireotide) is a somatostatin analog indicated for the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option.

IMPORTANT SAFETY INFORMATION

Hyperglycemia, Diabetes, and Ketoacidosis: SIGNIFOR LAR can cause increases in blood glucose levels which are sometimes severe. Monitor glucose levels as clinically appropriate during therapy. There have been postmarketing cases of ketoacidosis with SIGNIFOR LAR in patients with or without history of diabetes. Patients with poor baseline glycemic control are at higher risk of developing severe hyperglycemia. Patients who develop significant hyperglycemia on SIGNIFOR LAR may require initiation of anti-diabetic treatment or adjustment in their current anti-diabetic treatment. The optimal treatment for the management of SIGNIFOR LAR-induced hyperglycemia is not known. If hyperglycemia cannot be controlled despite medical management, reduce the dose or discontinue SIGNIFOR LAR. Patients who present with signs and symptoms consistent with severe metabolic acidosis should be assessed for ketoacidosis regardless of diabetes history. If ketoacidosis is suspected, discontinue SIGNIFOR LAR and promptly evaluate and treat the patient.

Bradycardia and QT Prolongation: Bradycardia has been reported with the use of SIGNIFOR LAR. Patients with cardiac disease and/or risk factors for bradycardia, such as history of clinically significant bradycardia, high grade heart block, or concomitant use of drugs associated with bradycardia, should be monitored. Adjustments in the dose of drugs known to slow the heart rate (e.g., beta-blockers, calcium channel blockers) and correction of electrolyte disturbances may be necessary when initiating or during the course of SIGNIFOR LAR treatment. In cardiac electrophysiology studies with pasireotide via subcutaneous route, QT prolongation occurred at therapeutic and supra-therapeutic doses. Use with caution in patients at significant risk; evaluate ECG and electrolytes prior to dosing and periodically while on treatment. Hypokalemia or hypomagnesemia must be corrected prior to initiating SIGNIFOR LAR and should be monitored periodically during therapy.

Liver Test Elevations: Increases in liver enzymes have been observed with SIGNIFOR LAR. Evaluate liver enzyme tests prior to and during treatment.

Cholelithiasis and Complications of Cholelithiasis: There have been reports of cholelithiasis resulting in complications including cholecystitis or cholangitis and requiring cholecystectomy in patients taking SIGNIFOR LAR. Monitor periodically. Discontinue SIGNIFOR LAR if complications of cholelithiasis are suspected and treat appropriately.

Pituitary Hormone Deficiency(ies): Suppression of anterior pituitary hormones may occur on SIGNIFOR LAR. Monitor for occurrence periodically and treat if clinically indicated.

Steatorrhea and Malabsorption of Dietary Fats: New onset steatorrhea, stool discoloration, loose stools, abdominal bloating, and weight loss may occur. If new occurrence or worsening of these symptoms are reported, evaluate for potential pancreatic exocrine insufficiency.

The most common adverse reactions occurring in ≥ 20% of patients with acromegaly were diarrhea, hyperglycemia, cholelithiasis, and diabetes mellitus.

To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases Inc. at 1-888-575-8344, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions

Females and Males of Reproductive Potential: Advise premenopausal females of the potential for an unintended pregnancy.

SIGNIFOR LAR® (pasireotide) for injectable suspension, for intramuscular use, is available as 10 mg, 20 mg, 30 mg, 40 mg, and 60 mg powder in a vial to be reconstituted with the provided 2 mL diluent.

Please see the accompanying full Prescribing Information and Patient Information.

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