What is the use and dosage of Octreotide (somatostatin analog)?

Octreotide: Uses and Dosing

Octreotide is a somatostatin analog used primarily for acromegaly, carcinoid syndrome, VIPomas, variceal bleeding, and chemotherapy-induced diarrhea, with dosing ranging from 50 mcg three times daily subcutaneously for chronic conditions to 50 mcg/hour IV infusion for acute situations. 1

FDA-Approved Indications and Dosing

Acromegaly

• Initial dose: 50 mcg subcutaneously three times daily for the first 2 weeks 1
• Maintenance dose: 100-500 mcg three times daily, titrated based on growth hormone (GH) and IGF-1 levels 1
• After stabilization, transition to octreotide LAR 20-30 mg intramuscularly every 4 weeks 2
• Octreotide LAR requires 10-14 days to reach therapeutic levels, so continue short-acting formulation during this transition period 2

Carcinoid Tumors (Carcinoid Syndrome)

• Initial dose: 100-600 mcg daily in 2-4 divided doses subcutaneously for the first 2 weeks 1
• Mean daily dosage: 300 mcg for symptom control 3
• For chronic management, transition to octreotide LAR 20-30 mg intramuscularly every 4 weeks 2
• Add short-acting octreotide 150-250 mcg subcutaneously three times daily for breakthrough symptoms 2
• For tumor growth control in metastatic disease, octreotide LAR showed median time to progression of 14.3 months versus 6 months with placebo 2

VIPomas (Vasoactive Intestinal Peptide Tumors)

• Initial dose: 200-300 mcg daily in 2-4 divided doses subcutaneously for the first 2 weeks 1
• Even small doses can produce dramatic cessation of watery diarrhea 4

Critical Care and Emergency Indications

Acute Variceal Bleeding

• Give 50 mcg IV bolus followed by continuous infusion at 50 mcg/hour 4
• Continue for 2-5 days until hemodynamic stability is achieved 4
• Common pitfall: Premature discontinuation before achieving hemodynamic stability 4

Carcinoid Crisis Prevention (Perioperative)

• Start IV infusion at 50 mcg/hour beginning 12 hours before procedure 4
• Continue for 24-48 hours after the procedure 4
• Obtain cardiology consultation and echocardiogram before major surgery, especially if 5-HIAA levels ≥300 mcmol/24 hours or ≥3 flushing episodes daily (higher risk for carcinoid heart disease) 2, 3

Chemotherapy-Induced Diarrhea

• For severe or loperamide-refractory diarrhea: continuous IV infusion at 25-50 mcg/hour until diarrhea resolves 4
• Higher doses (500 mcg three times daily) are significantly more effective than lower doses (100 mcg three times daily) in patients who fail loperamide (90% vs 61% complete resolution; P < 0.05) 2
• Upward titration of dose until symptoms are controlled is supported by evidence 2

Radiation Therapy-Induced Diarrhea

• For grade 2-3 diarrhea: 100 mcg subcutaneously three times daily 2
• Octreotide is significantly more effective than oral diphenoxylate, with complete resolution within 3 days in 61% versus 14% of patients 2

Malignant Bowel Obstruction

• Use octreotide early in diagnosis when gut function is no longer possible 2
• If helpful and life expectancy ≥1 month, consider depot form once optimal dose is established 2
• Avoid metoclopramide in complete obstruction (may use in partial obstruction) 2

Administration Routes

Subcutaneous (Preferred for Chronic Therapy)

• 50-100 mcg two to three times daily, with titration up to 1500 mcg daily as needed 5
• Not sedative, not addictive, and can be self-administered 5

Intravenous (Acute Situations)

• 50 mcg/hour by continuous infusion for rapid effect in high-risk situations 5
• Consider cardiac monitoring when administering intravenously due to increased risk of atrioventricular blocks 1

Long-Acting Depot Formulations

• Octreotide LAR: 20-30 mg intramuscularly every 4 weeks 2, 5
• Lanreotide: Deep subcutaneous injection every 2-4 weeks 5
• Lanreotide showed significant reduction in rescue octreotide use (34% vs 49% with placebo; P=0.02) 2

Important Monitoring and Precautions

Cardiac Effects

• Bradycardia, arrhythmias, and conduction abnormalities may occur 1
• Use with caution in at-risk patients; dosage adjustment of cardiac medications may be necessary 1

Cholelithiasis

• Monitor periodically for gallbladder abnormalities 1
• Discontinue if complications of cholelithiasis are suspected 1
• Incidence: 10-14% develop biliary sludge, 6-18% develop cholelithiasis 6

Glucose Metabolism

• Both hypoglycemia and hyperglycemia may occur 1
• Glucose monitoring is recommended; anti-diabetic treatment may need adjustment 1
• About 15% become hyperglycemic, usually mild in severity 7

Thyroid Function

• Hypothyroidism may occur; monitor thyroid levels periodically 1

Other Adverse Effects

• Fat malabsorption, vitamin A and D malabsorption, headaches, dizziness 4
• Gastrointestinal symptoms (abdominal cramps, nausea, diarrhea) occur in about 30% but are usually transient and mild to moderate 7
• Pain at injection site is common 8

Drug Interactions

• Monitor and adjust doses of: cyclosporine, insulin, oral hypoglycemic agents, beta-blockers, and bromocriptine 1
• Discontinue octreotide at least 24 hours prior to each lutetium Lu 177 dotatate dose 1

Common Pitfalls to Avoid

• Inadequate dosing for severe secretory diarrhea in carcinoid syndrome or VIPomas 4
• Failing to bridge with short-acting formulation when initiating LAR (therapeutic levels take 10-14 days) 2
• Premature discontinuation in variceal bleeding before hemodynamic stability 4
• Using metoclopramide in complete bowel obstruction 2