What is the mechanism of action and use of octreotide (somatostatin analogue) in treating various medical conditions?

What Octreotide Does

Octreotide is a synthetic somatostatin analogue that mimics the natural hormone somatostatin by potently inhibiting growth hormone, glucagon, insulin, and multiple gastrointestinal peptides (including serotonin, gastrin, VIP, secretin, motilin, and pancreatic polypeptide), making it essential for controlling symptoms in neuroendocrine tumors and reducing tumor growth in metastatic disease. 1

Core Mechanism of Action

Octreotide functions as an even more potent inhibitor than natural somatostatin itself, targeting:

• Anterior pituitary hormones: Suppresses growth hormone (GH) and thyroid-stimulating hormone (TSH) 1
• Gastrointestinal peptides: Inhibits release of serotonin, gastrin, VIP, secretin, motilin, and pancreatic polypeptide 1
• Metabolic hormones: More potent than somatostatin at inhibiting GH, glucagon, and insulin 1
• Vascular effects: Decreases splanchnic blood flow and causes splanchnic vasoconstriction at pharmacological doses 2, 1

The drug overcomes somatostatin's major limitations—short duration of action (1-3 minutes for somatostatin vs 1.7-1.9 hours for octreotide), need for IV administration, and postinfusion rebound hypersecretion 1, 3

FDA-Approved Indications

Acromegaly

• Reduces blood levels of GH and IGF-1 (somatomedin C) in patients who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine at maximally tolerated doses 1

Carcinoid Tumors (Metastatic)

• Symptomatic treatment to suppress or inhibit severe diarrhea and flushing episodes associated with carcinoid syndrome 1
• The American Gastroenterological Association confirms octreotide provides substantial relief in the majority of patients with midgut and lung carcinoid syndromes 2
• Standard dosing: 20-30 mg intramuscularly every 4 weeks (octreotide LAR), with dose and frequency increased as needed for symptom control 4, 2
• Short-acting octreotide (150-250 mcg subcutaneously 3 times daily) can be added for rapid relief or breakthrough symptoms 4, 2

VIPomas (Vasoactive Intestinal Peptide Tumors)

• Treatment of profuse watery diarrhea associated with VIP-secreting tumors 1

Tumor Growth Control

Beyond symptom control, octreotide has antiproliferative effects that slow tumor progression in neuroendocrine tumors. 4

• The National Comprehensive Cancer Network recommends initiating octreotide or lanreotide to potentially control tumor growth in patients with clinically significant tumor burden or progressive disease 2
• The PROMID study demonstrated median time to tumor progression of 14.3 months with octreotide LAR versus 6.0 months with placebo (P=0.000072) in metastatic midgut NETs 4
• After 6 months of treatment, stable disease was observed in 66.7% of patients receiving octreotide LAR versus 37.2% receiving placebo 4
• Biochemical response rates occur in 30-70% of patients 2

Critical Clinical Applications

Prevention of Carcinoid Crisis

• Patients with carcinoid syndrome or at risk of carcinoid crisis require increased coverage with short-acting octreotide by IV administration, typically 50 mcg/h, starting 12 hours before procedures, continuing during, and for 48 hours after procedures that may trigger a crisis 2

Specific Functional NET Syndromes

• Glucagonomas: Improvement reported with characteristic necrolytic migratory erythema responding to treatment, though circulating glucagon levels cannot be normalized due to massive amounts of circulating glucagon 2

Off-Label Uses with Evidence

• Variceal bleeding: Administered as initial IV bolus of 50 mcg followed by continuous infusion of 50 mcg/hour, safe for continuous use for 5 days or longer 2
• Chylothorax of lymphatic origin: Initial dosages of 50 mcg followed by continuous infusion at 50 mcg/hour, with dose escalation up to 500 mcg three times daily if necessary 2
• Chemotherapy-induced diarrhea: Initial dosing 100-150 mcg subcutaneously or IV three times daily, with escalation up to 500 mcg three times daily or 25-50 mcg/hour by continuous IV infusion 2
• Dumping syndrome: 50-100 mcg subcutaneously before meals, typically every 12 hours 2

Pharmacokinetics and Practical Considerations

• Absorption: Rapid and complete after subcutaneous injection, with peak concentrations reached in 0.4 hours 1
• Half-life: 1.7-1.9 hours (compared to 1-3 minutes for natural somatostatin) 1
• Duration of action: Variable but extends up to 12 hours depending on tumor type 1
• Excretion: About 32% excreted unchanged in urine 1
• LAR formulation delay: Therapeutic levels not achieved for 10-14 days after LAR injection 4, 2

Common Pitfalls and Side Effects

Most adverse effects are mild and gastrointestinal in nature:

• Injection site pain, abdominal cramps, nausea, bloating, flatulence, diarrhea, and steatorrhea (fat malabsorption) 2, 3
• Gallstones and gallbladder dysfunction: Markedly increased incidence due to inhibition of gallbladder contractility and decreased bile secretion 2, 1
• Vitamin A and D malabsorption 2
• Hypo- and hyperglycemia 2
• Headaches and dizziness 2

Serious adverse effects (rare, typically with overdose):

• Arrhythmia, complete atrioventricular block, hypotension, cardiac arrest 1
• Cardiac monitoring recommended in patients receiving octreotide intravenously due to increased risk for higher degree AV blocks 2

Special Populations Requiring Dose Adjustment

• Elderly patients: Significant increase in half-life (46%) and decrease in clearance (26%), necessitating cautious dose selection starting at the low end of dosing range 1
• Severe renal failure requiring dialysis: Half-life may be increased, requiring adjustment of maintenance dosage 1
• Liver cirrhosis: Half-life may be increased, necessitating adjustment of maintenance dosage 1

Monitoring Requirements

• Circulating and urinary hormone levels during treatment periods 2
• Cardiac monitoring in patients receiving IV octreotide 2
• Assessment for gallbladder disease given increased risk of cholelithiasis 1