What is the recommended dosage and administration of Octreotide (Somatostatin analog) injection?

Octreotide Injection: Dosage and Administration

For symptomatic neuroendocrine tumors, start with octreotide 50-100 mcg subcutaneously three times daily, titrating up to 100-500 mcg three times daily based on symptom control, with long-acting formulations (octreotide LAR 20-30 mg intramuscularly every 4 weeks) becoming the standard of care after initial stabilization. 1, 2

Initial Dosing by Indication

Carcinoid Tumors (Symptomatic Control)

• Start with 100-300 mcg/day subcutaneously in 2-4 divided doses during the first 2 weeks 2
• The median maintenance dose is approximately 450 mcg/day, though some patients respond to as little as 50 mcg while others require up to 1,500 mcg/day 2, 3
• Titrate in increments of 50-100 mcg every 8 hours until adequate symptom control is achieved 3
• Monitor urinary 5-HIAA, plasma serotonin, and plasma Substance P to guide therapy 2

VIPomas (Watery Diarrhea)

• Start with 200-300 mcg/day subcutaneously in 2-4 divided doses during the first 2 weeks 2
• Dosage range: 150-750 mcg/day, though doses above 450 mcg/day are rarely needed 2
• Even small doses can produce dramatic cessation of diarrhea 4, 5
• Monitor plasma VIP levels to assess therapeutic response 2

Acromegaly

• Start with 50 mcg subcutaneously three times daily 2
• Most common effective dose is 100 mcg three times daily, with some patients requiring up to 500 mcg three times daily 2
• Doses greater than 300 mcg/day seldom provide additional biochemical benefit 2
• Monitor GH and IGF-1 levels every 2 weeks after initiation or dose changes 2
• Target: GH levels <5 ng/mL or IGF-1 levels within normal range 2

Intravenous Administration

Continuous Infusion (Variceal Bleeding, Carcinoid Crisis)

• Initial IV bolus of 50 mcg followed by continuous infusion at 50 mcg/hour 4, 6
• Duration: 2-5 days for variceal hemorrhage or until symptom resolution 4
• Can be safely administered continuously for 3-5 days 4

Carcinoid Crisis Prevention (Perioperative)

• Start IV infusion at 50 mcg/hour beginning 12 hours before the procedure 4, 5, 6
• Continue during the procedure and for 24-48 hours postoperatively 4, 5
• This prevents life-threatening hemodynamic instability during surgical manipulation of carcinoid tumors 6

Emergency Situations

• In carcinoid crisis, octreotide may be given by rapid IV bolus 2
• Doses of 100-500 mcg IV bolus are typically used, though higher doses up to 54,000 mcg have been reported in severe cases 7

Transition to Long-Acting Formulations

Long-acting formulations should be considered the standard of care for chronic symptomatic treatment, as they significantly improve quality of life compared to short-acting octreotide. 1

Octreotide LAR Dosing

• Licensed dosage: 10,20, or 30 mg intramuscularly every 4 weeks 1
• Start with 20 mg every 4 weeks as the recommended initial dose 8
• Start patients on lower doses and up-titrate to achieve stabilization 1
• Patients should be stabilized on short-acting octreotide for 10-28 days before converting to LAR 5
• Continue supplemental subcutaneous octreotide for approximately 2 weeks after initiating LAR, as therapeutic levels are not reached for 10-14 days 1, 8

Breakthrough Symptom Management

• Use rescue doses of subcutaneous octreotide 2-3 times daily, up to a maximum of 1 mg/day 1
• If breakthrough symptoms occur mainly during the week before the next LAR injection, consider reducing administration intervals from 4 weeks to 3 weeks 1

Administration Technique

• Administer subcutaneously or intravenously; rotate injection sites systematically 2
• Use the smallest volume possible to reduce injection site pain 2
• For IV infusion, dilute in 50-200 mL and infuse over 15-30 minutes, or give as IV push over 3 minutes 2
• Do not mix octreotide in Total Parenteral Nutrition solutions due to formation of inactive glycosyl conjugates 2

Critical Pitfalls and Caveats

Insulinomas: Use with Extreme Caution

• Octreotide is NOT effective in controlling hypoglycemia in most insulinoma patients and may transiently worsen hypoglycemia 1, 5
• Only effective in SSTR 2-positive insulinomas 1, 5
• Diazoxide (200-600 mg orally daily) is the preferred treatment for insulinoma-related hypoglycemia 1

Gastrinomas: Not First-Line

• Proton pump inhibitors are the treatment of choice for gastric acid hypersecretion 1
• Somatostatin analogues should only be used in refractory cases 1

Cardiac Monitoring Requirements

• Patients receiving IV octreotide are at increased risk for complete atrioventricular block, especially at higher doses or continuous infusion 2
• Cardiac monitoring is recommended during IV administration 6, 2
• Bradycardia (<50 bpm) occurred in 25% of acromegalic patients, with conduction abnormalities in 10% 2

Imaging Considerations

• Withdraw short-acting octreotide 24-48 hours before somatostatin receptor scintigraphy or 68Ga-PET imaging 1, 5
• For patients on long-acting analogues, schedule imaging toward the end of the dosing interval, just before the next injection 1

Common Adverse Effects

• Gastrointestinal symptoms occur in ~30% of patients but are usually transient and mild to moderate 9
• Fat malabsorption, vitamin A and D malabsorption, headaches, dizziness 4, 5, 6
• Gallbladder abnormalities (sludge, stones) can occur, but only 1% become symptomatic 9
• Alterations in glucose metabolism: ~15% develop hyperglycemia, usually mild 9
• Injection site pain, abdominal cramps, nausea, bloating, flatulence 6

Non-Functioning NETs

• The routine use of somatostatin analogues in non-functioning NETs cannot be recommended until further evidence is available 1, 5
• However, octreotide LAR demonstrated prolonged progression-free survival (14.3 vs 6 months) in metastatic midgut NETs with low hepatic tumor burden 1

Monitoring Requirements

• Monitor circulating and urinary hormone levels during treatment 6
• Assess total and/or free T4 levels at baseline and periodically during chronic therapy 2
• For acromegaly: GH and IGF-1 every 2 weeks initially 2
• For carcinoid: urinary 5-HIAA, plasma serotonin, plasma Substance P 2
• For VIPomas: plasma VIP levels 2
• Cardiac monitoring during IV administration 6, 2