IMPORTANT SAFETY INFORMATION

Warnings and Precautions: Hyperglycemia and Diabetes: SIGNIFOR LAR can cause increases in blood glucose levels which are sometimes severe. Patients with poor baseline glycemic control are at…+

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INDICATION: SIGNIFOR® LAR (pasireotide) for injectable suspension, for intramuscular use 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.

Expert Insights

Addressing Unmet Needs in Acromegaly

ADDRESSING UNMET NEEDS IN ACROMEGALY WITH SIGNIFOR LAR (pasireotide)

Thomas Blevins, MD - Endocrinologist, Texas Diabetes & Endocrinology, Austin Texas
Dr. Blevins discusses unmet needs in the treatment of acromegaly, the importance of biochemical control, and the mechanism of action of SIGNIFOR LAR (pasireotide).

SIGNIFOR LAR in Drug-Naive Patients

SIGNIFOR LAR (pasireotide) IN THE TREATMENT OF DRUG-NAIVE PATIENTS WITH ACROMEGALY

Lewis Blevins MD - Clinical Professor of Medicine and Neurological Surgery, Medical Director, California Center for Pituitary Disorders, University of California, San Francisco, California
Dr. Blevins discusses the clinical management of a hypothetical drug-naive acromegaly patient with SIGNIFOR LAR (pasireotide) and discusses results of the Phase III clinical study comparing SIGNIFOR LAR with first-generation somatostatin analog therapy in drug-naive patients.

SIGNIFOR LAR in Inadequately Controlled Patients

SIGNIFOR LAR (pasireotide) IN THE TREATMENT OF ACROMEGALY PATIENTS INADEQUATELY CONTROLLED ON OTHER SOMATOSTATIN ANALOGS

Lewis Blevins MD - Clinical Professor of Medicine and Neurological Surgery, Medical Director, California Center for Pituitary Disorders, University of California, San Francisco, California
Dr. Blevins discusses the clinical management of a hypothetical acromegaly patient who did not achieve biochemical control with a first-generation somatostatin analog and presents results of the Phase III clinical study comparing SIGNIFOR LAR (pasireotide) with continuation of previous therapy in uncontrolled patients.

SIGNIFOR LAR and Blood Glucose

SIGNIFOR LAR (pasireotide) FOR INJECTABLE SUSPENSION: BLOOD GLUCOSE

Tony Heaney MD – Associate Professor, David Geffen School of Medicine, University of California, Los Angeles (UCLA)
Dr. Heaney discusses the potential mechanism by which SIGNIFOR LAR (pasireotide) for injectable suspension may affect blood glucose levels in patients with acromegaly as well as the approaches for the management of elevated blood glucose associated with SIGNIFOR LAR treatment.

SIGNIFOR® LAR (pasireotide) for injectable suspension, for intramuscular use

INDICATION

SIGNIFOR LAR 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

Warnings and Precautions:

  • Hyperglycemia and Diabetes: SIGNIFOR LAR can cause increases in blood glucose levels which are sometimes severe. Patients with poor baseline glycemic control are at higher risk of developing severe hyperglycemia.

    A majority of patients, including those with normal glucose tolerance, pre-diabetes and diabetes, experienced increased glucose levels within the first 2 to 3 months of treatment with SIGNIFOR LAR.

    Fasting plasma glucose and hemoglobin A1c should be assessed prior to starting treatment with SIGNIFOR LAR. In patients with poorly controlled diabetes mellitus, anti-diabetic treatment should be optimized before SIGNIFOR LAR treatment is started. Blood glucose monitoring should be done weekly for the first 3 months after initiating SIGNIFOR LAR and the first 4 to 6 weeks after dose increases. Periodic monitoring should continue thereafter, as clinically appropriate.

    Patients who develop significant hyperglycemia on SIGNIFOR LAR may require initiation of anti-diabetic therapy(ies) or adjustment in the dose or type of anti-diabetic therapy(ies) per standard of care. The optimal treatment for the management of SIGNIFOR LAR-induced hyperglycemia is not known. If hyperglycemia cannot be controlled, despite medical management, the dose of SIGNIFOR LAR should be reduced or discontinued.

    After treatment discontinuation, fasting plasma glucose and hemoglobin A1c should be assessed if indicated. Patients on anti-diabetic therapy discontinuing SIGNIFOR LAR may require more frequent blood glucose monitoring and anti-diabetic dose adjustment to mitigate the risk of hypoglycemia.

  • Bradycardia and QT Prolongation

    Bradycardia

    Bradycardia has been reported with the use of SIGNIFOR LAR. Patients with cardiac disease and/or risk factor 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.

    QT Prolongation

    SIGNIFOR LAR is associated with QT prolongation and should be used with caution in patients who are at significant risk of developing prolongation of the QT interval. A baseline ECG is recommended prior to initiating therapy with SIGNIFOR LAR 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. ALT or AST elevation greater than 3 times the upper limit of normal (ULN) were observed in 3% of patients and ALT or AST elevation greater than 5 times the upper limit of normal (ULN) were observed in 1% of patients treated with SIGNIFOR LAR.

    Assessment of liver function is recommended prior to treatment with SIGNIFOR LAR, and after the first 2 to 3 weeks, then monthly for 3 months. Thereafter, liver function should be monitored as clinically indicated. Patients who develop increased transaminase levels should be monitored until values return to pre-treatment levels. Treatment with SIGNIFOR LAR should be discontinued if signs or symptoms suggestive of clinically significant liver impairment develop.

  • Cholelithiasis: Cholelithiasis was reported in up to 33% of patients treated with SIGNIFOR LAR in clinical trials. Patients should be monitored periodically.
  • Pituitary Hormone Deficiency(ies): Suppression of pituitary hormones other than GH/IGF-1, may occur on SIGNIFOR LAR. Monitoring pituitary function (e.g., thyroid, adrenal, gonadal) prior to initiation of therapy with SIGNIFOR LAR, as well as periodically during treatment, as clinically appropriate, is recommended. Patients should be monitored for and instructed on the signs and symptoms of adrenal insufficiency during therapy. If adrenal insufficiency is suspected it should be confirmed and treated per standard of care with exogenous glucocorticoids at replacement doses.

Adverse Reactions

Adverse reactions associated with SIGNIFOR LAR and occurring in ≥20% of patients were diarrhea, cholelithiasis, hyperglycemia and diabetes mellitus.

Drug Interactions

Caution is advised when co-administering drugs that prolong the QT interval with SIGNIFOR LAR

The following drugs may require monitoring and possible dose adjustment when used with SIGNIFOR LAR: cyclosporine and bromocriptine

Contraindications

None

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