Octreotide

• Approved Indications:
• Management of acromegaly to reduce growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels in patients inadequately controlled by surgery or radiotherapy.
• Treatment of severe diarrhea and flushing associated with carcinoid tumors.
• Control of symptoms caused by vasoactive intestinal peptide tumors (VIPomas).
• Management of bleeding esophageal varices by reducing portal venous pressure.
• Off-label and Clinically Accepted Uses:
• Management of secretory diarrhea from chemotherapy or AIDS.
• Prevention of complications after pancreatic surgery.
• Adjunct treatment in certain hormone-secreting tumors such as gastrinomas.
• Control of chylous effusions and fistulas.

• Acromegaly:
• Initial dose: 50 mcg subcutaneously three times daily.
• Dose may be adjusted in increments of 50 mcg every 1-2 weeks based on clinical response, up to 500 mcg/day.
• Long-acting depot formulation: 20 mg intramuscularly every 4 weeks; adjust based on response (range 10–30 mg every 4 weeks).
• Carcinoid Tumors and VIPomas:
• Initial dose: 50 mcg subcutaneously three times daily.
• Dose titrated based on symptom control, typically 100–600 mcg/day.
• Long-acting depot available with similar dosing intervals as above.
• Bleeding Esophageal Varices:
• Initial IV bolus: 50 mcg over 1 minute.
• Continuous IV infusion: 25–50 mcg/hour for 2–5 days.
• Special Populations:
• Renal Impairment: Use with caution; dose adjustment may be needed.
• Hepatic Impairment: Monitor closely; adjust dose as necessary.
• Elderly: No specific dose adjustments recommended.
• Pediatrics: Safety and efficacy not established.
• Administration Routes:
• Subcutaneous injection for short-acting formulations.
• Intramuscular injection for long-acting depot.
• Intravenous infusion for acute bleeding control.

Octreotide acetate is a synthetic octapeptide analog of somatostatin that mimics natural somatostatin effects but with a longer half-life. It binds to somatostatin receptors (primarily subtype 2 and 5) on target cells, inhibiting the secretion of several hormones including growth hormone, insulin, glucagon, serotonin, and vasoactive intestinal peptide. This receptor binding leads to decreased hormone hypersecretion, reduced gastrointestinal motility and splanchnic blood flow, and suppression of hormone-mediated symptoms in neuroendocrine tumors.

• Absorption:
• Rapid absorption following subcutaneous injection.
• Peak plasma concentration achieved within 30 minutes to 2 hours after subcutaneous dosing.
• Distribution:
• Volume of distribution approximately 0.27 L/kg.
• Approximately 65% bound to plasma proteins.
• Metabolism:
• Metabolized mainly by the liver and kidneys.
• No active metabolites identified.
• Elimination:
• Excreted primarily in urine (about 40%) and feces.
• Plasma half-life approximately 1.5 to 2 hours after subcutaneous administration.
• Long-acting formulations have an apparent half-life of about 1 week due to slow release from depot.

• Pregnancy:
• FDA Pregnancy Category B.
• Animal studies show no teratogenic effects, but no adequate controlled studies in humans.
• Use during pregnancy only if clearly needed.
• Lactation:
• Unknown whether excreted in human milk.
• Caution advised; breastfeeding is generally not recommended during treatment.
• Data Limitations: Limited human data; use with caution.

• Primary therapeutic class: Somatostatin analog
• Subclass: Long-acting synthetic peptide hormone analog

• Known hypersensitivity to octreotide or any component of the formulation.
• Bradycardia or other severe cardiac conduction abnormalities (use with caution).
• Use in neonates and infants not well established.
• Hypoglycemia risk in patients with insulinomas; use cautiously.

• Gallbladder Disorders: Risk of gallstones and biliary sludge due to reduced gallbladder motility; periodic ultrasound recommended.
• Glucose Metabolism: May cause hyperglycemia or hypoglycemia; monitor blood glucose regularly.
• Cardiac Effects: Bradycardia, arrhythmias; ECG monitoring advised in high-risk patients.
• Gastrointestinal Effects: Abdominal pain, nausea, diarrhea, or steatorrhea may occur.
• Injection Site Reactions: Common with subcutaneous administration.
• Thyroid Function: Possible reduction in thyroid-stimulating hormone (TSH); monitor thyroid function.

• Common:
• Gastrointestinal: Diarrhea, abdominal pain, nausea, flatulence.
• Injection site reactions: Pain, swelling, erythema.
• Gallbladder-related: Gallstones, biliary sludge.
• Metabolic: Hyperglycemia, hypoglycemia.
• Serious:
• Bradycardia and arrhythmias.
• Severe hypersensitivity reactions.
• Rare:
• Pancreatitis.
• Steatorrhea.
• Thyroid dysfunction.

• Insulin and Antidiabetic Agents: May potentiate or antagonize effects; monitor blood glucose carefully.
• Beta-blockers and Calcium Channel Blockers: Additive cardiac effects; monitor heart rate and rhythm.
• Cyclosporine: May decrease cyclosporine absorption; monitor levels.
• Drugs Affecting Gastrointestinal Motility: May have additive effects on slowing GI transit.
• Drug-Food: No significant interactions noted.
• Alcohol: No direct interaction but may exacerbate GI or metabolic side effects.

• Updated guidelines emphasize the role of octreotide long-acting release (LAR) formulations in improving quality of life for acromegaly and neuroendocrine tumor patients.
• Recent trials have supported octreotide use in reducing perioperative complications in pancreatic surgery.
• FDA has approved expanded indications for long-acting formulations.
• Recommendations now include routine gallbladder monitoring during chronic therapy.

• Store short-acting formulations refrigerated at 2°C to 8°C (36°F to 46°F).
• Protect from light.
• Long-acting depot formulations should also be refrigerated.
• Do not freeze.
• Allow refrigerated depot formulation to reach room temperature before injection.
• Use reconstituted solutions immediately.
• Keep out of reach of children.