Somatostatin Analogs

Restricted Product(s):

• lanreotide (Somatuline® Depot) subcutaneous injection for administration by a healthcare professional
• octreotide (Sandostatin®) intravenous infusion or subcutaneous injection for administration by a healthcare professional
• octreotide (Sandostatin® LAR Depot) gluteal intramuscular injection for administration by a healthcare professional
• pasireotide (Signifor® LAR) intramuscular injection for administration by a healthcare professional

FDA Approved Use:

• Lanreotide (Somatuline® Depot)
  • For long-term treatment of acromegalic patients who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy
  • For treatment of adults with unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival
  • For treatment of adults with carcinoid syndrome; when used, it reduces the frequency of short-acting somatostatin analog rescue therapy
• Octreotide (Sandostatin®)
  • For treatment of acromegaly in patients who have had an inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses
  • For symptomatic treatment of patients with metastatic carcinoid tumors, to suppress or inhibit severe diarrhea and flushing episodes associated with the disease
  • For treatment of profuse watery diarrhea associated with Vasoactive Intestinal Peptide (VIP)-secreting tumors
  • Limitations of use: Improvement in clinical signs and symptoms, or reduction in tumor size or rate of growth, were not shown in clinical trials performed with this product; these trials were not optimally designed to detect such effects.
• Octreotide (Sandostatin® LAR Depot)
  • For long-term maintenance treatment of acromegaly in patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option
  • For long-term treatment of severe diarrhea/flushing episodes associated with metastatic carcinoid tumors in patients who have responded to and tolerated octreotide subcutaneous injection
  • For long-term treatment of profuse watery diarrhea associated with Vasoactive Intestinal Peptide (VIP)-secreting tumors in patients who have responded to and tolerated octreotide subcutaneous injection
  • Limitations of use: In patients with carcinoid syndrome and VIP-secreting tumors, effect on tumor size, rate of growth and development of metastases, has not been determined
• Pasireotide (Signifor® LAR)
  • For treatment of acromegaly in patients who have had an inadequate response to surgery and/or for whom surgery is not an option
  • For treatment of Cushing’s disease in patients for whom pituitary surgery is not an option or has not been curative

Criteria for Medical Necessity:

The restricted product(s) may be considered medically necessary when the following criteria are met:

Initial Criteria for Approval:

1. The requested medication is pasireotide (Signifor LAR); AND
   1. The patient has a diagnosis of acromegaly; AND
      1. The patient has persistent or recurrent disease despite pituitary gland surgery or is not a candidate for pituitary gland surgery;
         AND
      2. The provider has submitted documentation demonstrating the following [medical record documentation required]:
         1. Insulin-like growth factor-1 (IGF-1) levels greater than upper limit of normal for reference range; AND
         2. Oral glucose tolerance test (OGTT) with measurement of growth hormone (GH) levels > 1 ng/mL; AND
      3. ONE of the following:
         1. The patient has experienced a therapeutic failure or inadequate response to a somatostatin analog (i.e., octreotide or lanreotide) AND a dopamine agonist (i.e., cabergoline); OR
         2. The patient has a documented intolerance, FDA labeled contraindication, or hypersensitivity to ALL somatostatin analogs and ALL dopamine agonists; OR
   2. The patient has a diagnosis of Cushing’s disease; AND
      1. The patient has persistent or recurrent disease despite pituitary gland surgery or is not a candidate for pituitary gland surgery;
         AND
      2. ONE of the following:
         1. The patient has experienced a therapeutic failure or inadequate response to TWO of the following oral agents:
            1. Oral ketoconazole
            2. Oral cabergoline
            3. Oral Metopirone (metyrapone)
            4. Oral Lysodren (mitotane); OR
         2. The patient has a documented intolerance, hypersensitivity, or FDA labeled contraindication to ALL conventional agents; AND
      3. The provider has submitted documentation demonstrating one of the following [medical record documentation required]:
         1. Mean of at least two 24-hour urine free cortisol (UFC) levels greater than upper limit of normal for reference range; OR
         2. Late night salivary cortisol (two measurements) greater than upper limit of normal for reference range; OR
         3. 1 mg overnight dexamethasone suppression test (DST) > 1.8 mcg/dL; AND
   3. The patient does not have severe decompensated liver disease (Child-Pugh C); AND
   4. The patient is being managed by or in consultation with a specialist in the area of the patient’s diagnosis (e.g., endocrinologist); OR
2. The requested medication is octreotide (Sandostatin OR Sandostatin LAR Depot); AND
   1. The patient has a diagnosis of acromegaly; AND
      1. The use of the requested agent is for adjunctive therapy with pituitary irradiation to alleviate acromegaly symptoms; OR
      2. The patient has had an inadequate response to surgical resection or pituitary irradiation defined by ONE of the following documented parameters [medical record documentation required]:
         1. Growth hormone level > 5 ng/mL; OR
         2. IGF-1 level > 1.9 U/mL for males or > 2.2 U/mL for females; OR
      3. The patient is not a candidate for surgical resection or pituitary irradiation; OR
   2. The patient has a diagnosis of carcinoid tumor, locally advanced/metastatic gastroenteropancreatic neuroendocrine tumor or poorly differentiated (high-grade)/large or small cell neuroendocrine tumor, pancreas islet cell neuroendocrine tumor, or vasoactive intestinal polypeptidoma; AND
      1. ONE of the following:
         1. The patient will be using the medication for symptom control for carcinoid syndrome or hormone hypersecretion; OR
         2. The patient has had an inadequate response to or is not a candidate for surgical resection or radiation therapy; OR
3. The requested medication is lanreotide (Somatuline Depot); AND
   1. The patient has a diagnosis of acromegaly; AND
      1. The use of the requested agent is for adjunctive therapy with pituitary irradiation to alleviate acromegaly symptoms; OR
      2. The patient has had an inadequate response to surgical resection or pituitary irradiation defined by ONE of the following documented parameters [medical record documentation required]:
         1. Growth hormone level > 5 ng/mL; OR
         2. IGF-1 level > 1.9 U/mL for males or > 2.2 U/mL for females; OR
      3. The patient is not a candidate for surgical resection or pituitary irradiation; OR
   2. The patient has a diagnosis of carcinoid tumor, locally advanced/metastatic gastroenteropancreatic neuroendocrine tumor or poorly differentiated (high-grade)/large or small cell neuroendocrine tumor, pancreas islet cell neuroendocrine tumor, or vasoactive intestinal polypeptidoma; AND
      1. ONE of the following:
         1. The patient will be using the medication for symptom control for carcinoid syndrome or hormone hypersecretion; OR
         2. 2. The patient has had an inadequate response to or is not a candidate for surgical resection or radiation therapy; AND
4. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
5. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*

Duration of Approval: 180 days (6 months)

Continuation Criteria for Approval:

1. The requested medication is pasireotide (Signifor LAR); AND
   1. The patient has been approved through Blue Cross NC initial criteria for approval (above) or would have met initial criteria for approval upon the start of therapy; AND
   2. The patient is continuing therapy for one of the indications in the initial coverage criteria; AND
   3. The patient has a diagnosis of acromegaly; AND
      1. There is documentation that the patient has shown improvement with the requested medication as indicated by decreasing GH and IGF-1 levels [medical record documentation required]; OR
   4. The patient has a diagnosis of Cushing’s disease; AND
      1. There is documentation that the patient has shown improvement with the requested medication as indicated by improvement in 24-hour urine free cortisol (UFC), late night salivary cortisol, or 1 mg overnight dexamethasone suppression test (DST) [medical record documentation required]; AND
   5. The patient is being managed by or in consultation with a specialist in the area of the patient’s diagnosis (e.g., endocrinologist); OR
2. The requested medication is octreotide (Sandostatin OR Sandostatin LAR Depot); AND
   1. The patient has been approved through Blue Cross NC initial criteria for approval (above) or would have met initial criteria for approval upon the start of therapy; AND
   2. The patient is continuing therapy for one of the indications in the initial coverage criteria; AND
   3. If the request is for Sandostatin, the patient has been on Sandostatin therapy within the last 180 days (6 months) (NOTE: For patients with a greater than 6-month gap in therapy, use initial coverage criteria); OR
   4. If the request is for Sandostatin LAR Depot, the patient has been on Sandostatin LAR Depot therapy within the last 180 days (6 months) (NOTE: For patients with a greater than 6-month gap in therapy, use initial coverage criteria; AND
   5. The patient has objective markers for improvement, exemplified by ONE of the following [medical record documentation required]:
      1. Growth hormone (GH) level < 5 ng/mL; OR
      2. IGF-1 level < 1.9 U/mL for a male or < 2.2 U/mL for a female; OR
      3. Clinical improvement in conditions related to the approved diagnosis:
         1. Reduction in tumor size; OR
         2. Decreased headaches; OR
         3. Improved cardiovascular symptoms; OR
         4. Improved respiratory symptoms; OR
         5. Decreased severity and frequency of diarrhea and/or flushing symptoms; OR
3. The requested medication is lanreotide (Somatuline Depot); AND
   1. The patient has been approved through Blue Cross NC initial criteria for approval (above) or would have met initial criteria for approval upon the start of therapy; AND
   2. The patient is continuing therapy for one of the indications in the initial coverage criteria; AND
   3. The patient has been on Somatuline Depot therapy within the last 180 days (6 months) (NOTE: For patients with a greater than 6-month gap in therapy, use initial coverage criteria); AND
   4. The patient has objective markers for improvement, exemplified by ONE of the following [medical record documentation required]:
      1. Growth hormone (GH) level < 5 ng/mL; OR
      2. IGF-1 level < 1.9 U/mL for a male or < 2.2 U/mL for a female; OR
      3. Clinical improvement in conditions related to the approved diagnosis:
         1. Reduction in tumor size; OR
         2. Decreased headaches; OR
         3. Improved cardiovascular symptoms; OR
         4. Improved respiratory symptoms; OR
         5. Decreased severity and frequency of diarrhea and/or flushing symptoms; AND
4. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
5. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*

Duration of Approval: 365 days (1 year)