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

SIGNIFOR LAR (pasireotide) for injectable suspension Signifor

Rx Form Download Rx FORM Contact form CONTACT

Managing Hyperglycemia HYPERGLYCEMIA MAY OCCUR AND CAN BE MANAGED

Hyperglycemia can occur in patients treated with SIGNIFOR LAR24,*

  • Hyperglycemia is reversible upon SIGNIFOR LAR discontinuation25
  • Metformin alone or in combination with other anti-diabetic medication may help control elevations in glucose levels that may occur with SIGNIFOR-LAR treatment25,†
  • Most patients who had hyperglycemia were able to achieve the American Diabetes Association Goal of 7% with medical management25
  • Key elements in addressing hyperglycemia include close monitoring, patient education, and prompt action25
  • There have been postmarketing cases of ketoacidosis with SIGNIFOR LAR in patients with history of diabetes and in patients without history of diabetes. Assess patients who present with signs and symptoms consistent with ketoacidosis during SIGNIFOR LAR treatment3

Importantly, in patients with poorly controlled diabetes mellitus, optimize anti-diabetic treatment before starting SIGNIFOR LAR3

Testing blood sugar icon

*Up to a third of patients experienced hyperglycemia with SIGNIFOR LAR:
— 29% of medically naive patients treated with SIGNIFOR LAR experienced hyperglycemia1
— 33% and 30% of previously inadequately controlled patients experienced hyperglycemia when switched to 40 and 60 mg SIGNIFOR LAR, respectively1
†Glucose control generally defined as HbA1c <7% by the ADA guidelines.26

Current antidiabetic treatment therapies may help you manage hyperglycemia in patients treated with SIGNIFOR LAR.

The first prospective, multicenter, randomized, open-label phase 4 study to investigate the management of pasireotide-associated hyperglycemia27

Syringe icon

The objective of this study was to assess the efficacy of incretin-based or insulin therapy in patients with pasireotide-associated hyperglycemia who were eligible for randomization

  • Patients eligible for randomization had an average fasting blood sugar of ≥126 mg/dL on three consecutive days during pre-randomization period, despite optimized treatment with metformin/other permitted OADs
Person icon

Some patients receiving pasireotide did not develop treatment-associated hyperglycemia requiring antidiabetic medication

  • Of 249 patients enrolled in the study (190 with acromegaly and 59 with Cushing’s disease), 103 (41%) did not require antidiabetic medication
Pill icon

For some patients who developed hyperglycemia with pasireotide, antidiabetic treatment options such as metformin, incretin-based therapy, and/or insulin, were shown to be effective

  • 46 (18%) patients were managed with metformin or other oral antidiabetic drugs
  • Among patients requiring additional therapy (N=81/249), incretin-based therapy was more effective than insulin in lowering HbA1c

In this study, hyperglycemia observed during pasireotide treatment was manageable in most patients without the need for treatment discontinuation.27

Learn about dosing and administration

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.

References: 1. Gatto F, Barbieri F, Arvigo M, et al. Biological and biochemical basis of the differential efficacy of first and second generation somatostatin receptor ligands in neuroendocrine neoplasms. Int J Mol Sci. 2019;20(16):3940. 2. Poullot A-G, Chevalier N. New options in the treatment of Cushing’s disease: a focus on pasireotide. Res Rep Endocr Disord. 2013;3:31-38. 3. SIGNIFOR LAR (pasireotide) for injectable suspension, for intramuscular use [prescribing information]. Lebanon, NJ: Recordati Rare Diseases Inc.; 2020. 4. Acromegaly. UCLA Health System. https://www.uclahealth.org/medical-services/surgery/endocrine-surgery/patient-resources/patient-education/endocrine-surgery-encyclopedia/acromegaly. Accessed August 23, 2022. 5. Broder MS, Chang E, Cherepanov D, Neary MP, Ludlam WH. Incidence and Prevalence of Acromegaly in the United States: A Claims-Based Analysis. AACE Endocrine Practice. https://www.endocrinepractice.org/article/S1530-891X(20)35591-9/pdf. Published November 1, 2016. Accessed August 23, 2022. 6. Christofides EA. Clinical importance of achieving biochemical control with medical therapy in adult patients with acromegaly. Patient Prefer Adherence. 2016;10:1217-1225. 7. Acromegaly. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/endocrine-diseases/acromegaly. Accessed August 23, 2022. 8. Carmichael JD, Bonert VS, Nu.o M, Ly D, Melmed S. Acromegaly clinical trial methodology impact on reported biochemical efficacy rates of somatostatin receptor ligand treatments: a meta-analysis. J Clin Endocrinol Metab. 2014;99(5):1825-1833. 9. Carroll PV, Jenkins PJ. Acromegaly. In: Feingold KR, Anawalt B, Boyce A, et al, eds. Endotext [Internet]. South Dartmouth, MA: MDText.com, Inc.; 2016 10. Giustina A, Barkhoudarian G, Beckers A, et al. Multidisciplinary management of acromegaly: A consensus. Rev Endocr Metab Disord. 2020;21(4):667-678. 11. Katznelson L, Laws ER Jr, Melmed S, et al. Endocrine Society Acromegaly: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951. 12. Lavrentaki A, Paluzzi A, Wass JA, Karavitaki N. Epidemiology of acromegaly: review of population studies. Pituitary. 2017;20(1):4-9. 13. SOMATULINE® DEPOT (lanreotide) injection, for subcutaneous use [prescribing information]. Cambridge, MA: Ipsen Biopharmaceuticals, Inc.; 2019 14. SANDOSTATIN LAR DEPOT (octreotide acetate) for injectable suspension, for gluteal intramuscular use [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2021. 15. Coopmans EC, Muhammad A, van der Lely AD, et al. How to position pasireotide LAR treatment in acromegaly. J Clin Endocrinol Metab. 2019;104(6):1978-1988. 16. Shanik MH, Cao PD, Ludlam WH. Historical response rates of somatostatin analogues in the treatment of acromegaly: a systematic review. Endocr Pract. 2016;22(3):350-356. 17. Casar-Borota O, Heck A, Schulz S, et al. Expression of SSTR2a, but not of SSTRs 1, 3, or 5 in somatotroph adenomas assessed by monoclonal antibodies was reduced by octreotide and correlated with the acute and long-term effects of octreotide. J Clin Endocrinol Metab. 2013;98(11):E1730-E1739. 18. Silverstein JM. Hyperglycemia induced by pasireotide in patients with Cushing’s disease or acromegaly. Pituitary. 2016;19:536-543. 19. Zambre Y, Ling Z, Chen MC, et al. Inhibition of human pancreatic islet insulin release by receptor-selective somatostatin analogs directed to somatostatin receptor subtype 5. Biochem Pharmacol. 1999;57(10):1159-1164. 20. Singh V, Brendel MD, Zacharias S, et al. Characterization of somatostatin receptor subtype-specific regulation of insulin and glucagon secretion: an in vitro study on isolated human pancreatic islets. J Clin Endocrinol Metab. 2007;92(2):673-680. 21. Breitschaft A, Hu K, Hermosillo Res.ndiz K, Darstein C, Golor G. Management of hyperglycemia associated with pasireotide (SOM230): healthy volunteer study. Diabetes Res Clin Pract. 2014;103(3):458-465. 22. Henry RR, Ciaraldi TP, Armstrong D, Burke P, Ligueros-Saylan M, Mudaliar S. Hyperglycemia associated with pasireotide: results from a mechanistic study in healthy volunteers. J Clin Endocrinol Metab. 2013;98(8):3446-3453. 23. Gadelha MR, Bronstein MD, Brue T, et al. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2014;2(11):875-884. 24. Colao A, Bronstein MD, Freda P, et al. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab. 2014;99(3):791-799. 25. Gadelha MR, Gu F, Bronstein MD, et al. Risk factors and management of pasireotide-associated hyperglycemia in acromegaly. Endocr Connect. 2020;9(12):1178-1190. 26. American Diabetes Association. Standards of Medical Care in Diabetes-2020 Abridged for Primary Care Providers. Clin Diabetes. 2020;38(1):10-38. doi:10.2337/cd20-as01. 27. Samson SL, Gu F, Feldt-Rasmussen U, Zhang S, Yu Y, et al. Managing pasireotide-associated hyperglycemia: a randomized, open-label, Phase IV study. Pituitary. 2021;24(6):887-903.