What are the indications for Octreotide (somatostatin analog)?

Octreotide Indications

Octreotide is FDA-approved for three primary indications: acromegaly (to reduce GH and IGF-1 levels), symptomatic treatment of metastatic carcinoid tumors (for severe diarrhea and flushing), and VIPomas (for profuse watery diarrhea). 1

FDA-Approved Indications

Acromegaly

• Indicated to reduce blood levels of growth hormone (GH) and insulin growth factor-1 (IGF-1) in patients who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine at maximally tolerated doses. 1
• Initial dosage is 50 mcg three times daily subcutaneously during the initial 2 weeks, with maintenance doses ranging from 100 mcg to 500 mcg three times daily. 1

Carcinoid Tumors

• Indicated for symptomatic treatment of patients with metastatic carcinoid tumors to suppress or inhibit severe diarrhea and flushing episodes. 1
• Recommended dosage range is 100 mcg to 600 mcg daily in two to four divided doses during the initial 2 weeks of therapy. 1
• Provides substantial relief of flushing and diarrhea in the majority of patients with midgut and lung carcinoid syndromes, though hormone levels are not normalized. 2

Vasoactive Intestinal Peptide Tumors (VIPomas)

• Indicated for treatment of profuse watery diarrhea associated with VIP-secreting tumors. 1
• Recommended dosage range is 200 mcg to 300 mcg daily in two to four divided doses during the initial 2 weeks. 1
• Patients with this rare life-threatening syndrome frequently respond dramatically to small doses with cessation of diarrhea. 2

Guideline-Supported Indications for Neuroendocrine Tumors

Symptomatic Control in Functional NETs

• Somatostatin analogues are the only proven hormonal management for NETs and should be started as soon as clinical and biochemical signs indicate hypersecretory NETs, even before precise localization is confirmed. 2
• Somatostatin receptors are present in 70-95% of NETs, making octreotide effective for most gastroenteropancreatic neuroendocrine tumors. 2
• Long-acting formulations (octreotide LAR 20-30 mg intramuscularly every 4 weeks or lanreotide 60-120 mg every 4 weeks) should be considered standard of care for symptomatic treatment. 2

Tumor Growth Control

• In patients with clinically significant tumor burden or progressive disease, initiation of octreotide or lanreotide is recommended to potentially control tumor growth. 2
• Biochemical response rates (inhibition of hormone production) occur in 30-70% of patients with symptomatic control in the majority; tumor growth may stabilize and rarely shrinkage occurs. 2

Prevention of Carcinoid Crisis

• In instances of stress (anesthesia, surgical operations, hepatic artery embolization), patients with carcinoid syndrome or even with the tumor but without syndrome should receive increased coverage with short-acting octreotide by intravenous administration (50 mcg/h). 2
• This extra coverage should be administered 12 hours before, during, and 48 hours after the procedure to prevent cardiovascular carcinoid crisis. 2

Specific Functional NET Syndromes

Glucagonomas:

• Improvement has been reported in patients with the syndrome, though circulating glucagon levels cannot be normalized due to massive amounts of circulating glucagon. 2
• The characteristic rash of necrolytic migratory erythema can be life-threatening and may respond to treatment. 2

Gastrinomas:

• Proton pump inhibitors are the treatment of choice for gastric acid hypersecretion-associated symptoms. 2
• Somatostatin analogues are not first-choice agents and should only be used in refractory cases. 2

Insulinomas:

• Only 50% of insulinomas have type II somatostatin receptors, limiting effectiveness. 2
• Diazoxide is preferred for controlling hypoglycemic symptoms in patients with insulinoma. 2

Off-Label/Emerging Indications

Variceal Bleeding

• Octreotide causes splanchnic vasoconstriction at pharmacological doses and is safe for continuous use for 5 days or longer. 2
• Typically administered as an initial IV bolus of 50 mcg followed by continuous infusion of 50 mcg/hour. 2

Chylothorax of Lymphatic Origin

• Initial dose is 50 mcg followed by continuous infusion at 50 mcg/hour. 3
• Dose can be escalated up to 500 mcg three times daily if necessary. 3
• IV continuous infusion should be maintained for 2-5 days or until resolution of drainage. 3

Important Clinical Caveats

Limitations

• Improvement in clinical signs and symptoms, or reduction in tumor size or rate of growth, were not shown in clinical trials; these trials were not optimally designed to detect such effects. 1
• Somatostatin receptors are identified in only 50-60% of insulinomas and are less evident in poorly differentiated NETs and somatostatinomas. 2

Monitoring Requirements

• Monitor circulating and urinary hormone levels during treatment periods. 2
• Cardiac monitoring should be considered in patients receiving octreotide intravenously due to increased risk for higher degree atrioventricular blocks. 1
• Monitor for cholelithiasis and gallbladder complications periodically. 1
• Glucose monitoring is recommended as hypoglycemia or hyperglycemia may occur. 1
• Monitor thyroid function periodically as hypothyroidism may occur. 1

Common Side Effects

• Fat malabsorption, gallstones and gallbladder dysfunction, vitamin A and D malabsorption, headaches, diarrhea, dizziness, and hypo- and hyperglycemia. 2, 3
• Most adverse effects are mild and include injection site pain, abdominal cramps, nausea, bloating, and flatulence, which usually abate with time. 2