What is the recommended use and dosage of Octreotide (Somatostatin analogue) LAR (Long-Acting Release)?

Octreotide LAR: Recommended Use and Dosage

Octreotide LAR is recommended at standard doses of 20-30 mg intramuscularly every 4 weeks for chronic management of symptoms in patients with carcinoid syndrome, with dose and frequency adjustments based on symptom control. 1

Indications for Use

• Octreotide LAR is primarily indicated for:
  • Control of symptoms in patients with carcinoid syndrome 1
  • Control of tumor growth in patients with clinically significant tumor burden or progressive neuroendocrine tumors 1
  • Management of symptoms in patients with functional neuroendocrine tumors including gastrinomas and VIPomas 1

Dosing Recommendations

Standard Dosing

• Initial dosage: 20-30 mg intramuscularly every 4 weeks 1
• Therapeutic levels are not achieved until 10-14 days after LAR injection 1
• For carcinoid tumors, the suggested initial daily dosage during the first 2 weeks ranges from 100-600 mcg/day in 2-4 divided doses using short-acting octreotide before transitioning to LAR 2

Dose Adjustments

• Dose and frequency may be increased for symptom control as needed 1
• Short-acting octreotide (usually 150-250 mcg subcutaneously 3 times daily) can be added for:
  • Rapid relief of symptoms at initiation of therapy 1
  • Management of breakthrough symptoms 1

Monitoring and Efficacy

• In carcinoid syndrome, clinical symptoms such as flushing and diarrhea should be monitored to assess response 1
• For tumor control, imaging studies every 3-12 months are recommended to assess disease stability 1
• Blood levels of octreotide correlate with dosage; 60 mg/month achieves plasma levels of approximately 10,925 pg/mL compared to 5,241 pg/mL with 30 mg/month 3

Clinical Evidence Supporting Use

• The PROMID study demonstrated that octreotide LAR significantly extended time to tumor progression compared to placebo (14.3 vs 6.0 months, p=0.000072) in patients with metastatic midgut NETs 1
• After 6 months of treatment, stable disease was observed in 66.7% of patients in the octreotide LAR group compared to 37.2% in the placebo group 1
• Long-term survival data from PROMID showed median overall survival was not reached in the octreotide arm compared to 84 months in the placebo arm, though this difference was not statistically significant (HR 0.85,95% CI 0.46-1.56, p=0.59) 1

Administration Considerations

• Octreotide LAR must be administered intramuscularly, not subcutaneously 2, 4
• Improper subcutaneous administration (instead of intramuscular) occurs in approximately 44% of patients and is more likely in patients with:
  • Skin-to-muscle distance >38 mm (the length of the octreotide LAR needle) 4
  • Obesity 4
• Patient weight is inversely related to plasma octreotide levels; heavier patients may require higher doses to achieve similar plasma concentrations 3

Adverse Effects

• Gastrointestinal symptoms occur in about 30% of patients but are usually transient and mild to moderate 5
• Gallbladder abnormalities (sediment, sludge, microlithiasis, gallstones) can develop, with approximately 1% becoming symptomatic 5, 6
• Glucose metabolism can be affected in some patients; about 15% develop hyperglycemia, usually mild 5, 6
• A cardiology consultation and echocardiogram should be considered in patients with carcinoid syndrome who have signs/symptoms of heart disease or are planning major surgery 1

Special Considerations

• For patients with carcinoid heart disease, which occurs in up to 59% of patients with carcinoid syndrome, careful monitoring is essential 1
• Patients with 5-HIAA levels ≥300 mcmol (57 mg) over 24 hours and ≥3 flushing episodes per day are at higher risk of carcinoid heart disease 1
• In asymptomatic patients with metastatic NETs and low tumor burden, there is no clear consensus on timing of octreotide LAR initiation; it may be reasonable to defer until evidence of tumor progression 1