Introduction
Sandostatin (octreotide acetate) is a synthetic cyclic octapeptide that mimics the natural hormone somatostatin. It is a potent inhibitor of growth hormone, glucagon, and insulin secretion. First approved by the FDA in 1988, Sandostatin has become a cornerstone therapy for various endocrine and gastrointestinal disorders, particularly those involving hormone-secreting tumors.
Mechanism of Action
Sandostatin acts as a somatostatin analog that binds with high affinity to somatostatin receptors (primarily subtypes 2 and 5). This binding inhibits the secretion of numerous hormones and peptides including:
- Growth hormone (GH)
- Glucagon
- Insulin
- Gastrin
- Vasoactive intestinal peptide (VIP)
- Serotonin
- Pancreatic polypeptide
- Motilin
- Secretin
Additionally, Sandostatin reduces splanchnic blood flow, inhibits intestinal motility, and decreases secretion of water and electrolytes from the gastrointestinal tract.
Indications
FDA-approved indications include:
- Acromegaly: Long-term maintenance therapy in patients who have had inadequate response to or cannot be treated with surgery and/or radiotherapy
- Severe diarrhea and flushing episodes associated with metastatic carcinoid tumors
- Watery diarrhea associated with VIP-secreting tumors (VIPomas)
Off-label uses include:
- Treatment of gastrointestinal and pancreatic fistulas
- Variceal bleeding prevention and treatment
- TSH-secreting pituitary adenomas
- Chemotherapy-induced diarrhea
- Dumping syndrome
- Small bowel obstruction
Dosage and Administration
Acromegaly:- Initial: 50 mcg SC tid, titrated based on GH and IGF-1 levels
- Maintenance: 100-500 mcg SC tid (most patients respond at 300 mcg/day)
- Long-acting formulation (Sandostatin LAR): 20 mg IM every 4 weeks
- Initial: 100-600 mcg/day SC in 2-4 divided doses
- Maintenance: 450 mcg/day SC
- LAR formulation: 20 mg IM every 4 weeks
- Initial: 200-300 mcg/day SC in 2-4 divided doses
- Maintenance: 200-300 mcg/day SC
- LAR formulation: 20 mg IM every 4 weeks
- Renal impairment: No dosage adjustment required
- Hepatic impairment: Use with caution; monitor closely
- Elderly: Initiate at lower end of dosing range
- Pediatrics: Safety and efficacy not established
Pharmacokinetics
Absorption: Rapidly absorbed after SC administration with bioavailability of 100% Distribution: Volume of distribution: 13.6 L; 65% bound to plasma proteins Metabolism: Primarily hepatic via peptidase enzymes Elimination: Half-life: 1.7-1.9 hours; excreted primarily in urine (32% unchanged) LAR formulation: Provides sustained release over 4 weeks with peak effect at 2-4 weeksContraindications
- Hypersensitivity to octreotide or any component of the formulation
- Patients with hypersensitivity to related peptides
Warnings and Precautions
Cardiac: May cause bradycardia, conduction abnormalities, and arrhythmias Endocrine: May alter glucose regulation; monitor blood glucose levels Gallbladder: High incidence of gallbladder abnormalities including sludge, stones, and biliary duct dilatation Gastrointestinal: May cause steatorrhea and malabsorption Renal: May decrease renal perfusion; use caution in patients with renal impairment Pregnancy: Category B; use only if clearly needed Lactation: Excreted in breast milk; use cautionDrug Interactions
Cyclosporine: Reduced cyclosporine levels Bromocriptine: Increased bromocriptine bioavailability Beta-blockers: Additive effect on heart rate Oral hypoglycemics/Insulin: Altered requirements; monitor glucose closely CYP3A4 substrates: Potential interaction with drugs metabolized by CYP3A4 QT-prolonging drugs: Potential additive effect on cardiac repolarizationAdverse Effects
Common (≥10%):- Injection site reactions (pain, swelling, redness)
- Nausea, abdominal pain, diarrhea, flatulence
- Gallbladder sludge/stones
- Hyperglycemia/hypoglycemia
- Headache, dizziness
- Cardiac arrhythmias
- Pancreatitis
- Hepatitis
- Thyroid dysfunction
- Intestinal obstruction
Monitoring Parameters
- Growth hormone and IGF-1 levels (acromegaly)
- 5-HIAA levels (carcinoid)
- Blood glucose levels
- Thyroid function tests
- Gallbladder ultrasound (baseline and periodic)
- Electrolytes and liver function tests
- ECG (in patients with cardiac history)
- Vitamin B12 levels (long-term therapy)
Patient Education
- Proper injection technique and site rotation
- Importance of regular monitoring appointments
- Recognition of hypo/hyperglycemia symptoms
- Report any abdominal pain, yellowing of skin, or dark urine
- Inform all healthcare providers about Sandostatin use
- Storage requirements (refrigerate, protect from light)
- Potential for gallbladder complications
- Do not stop medication abruptly without medical supervision
References
1. FDA Prescribing Information: Sandostatin (octreotide acetate) Injection 2. Melmed S, et al. A consensus statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018 3. Oberg K, et al. Consensus guidelines for the management of patients with digestive neuroendocrine tumors. Neuroendocrinology. 2008 4. Lamberts SW, et al. Octreotide. N Engl J Med. 1996 5. Anthony L, et al. Long-acting octreotide in the treatment of carcinoid syndrome. Cancer. 2018 6. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Acromegaly. Endocr Pract. 2011