Octreotide - Drug Monograph

Introduction

Octreotide is a synthetic octapeptide analog of the naturally occurring hormone somatostatin. First approved by the FDA in 1988, it mimics the pharmacological effects of somatostatin but with a significantly longer duration of action. Octreotide is available in immediate-release (subcutaneous and intravenous) and long-acting release (intramuscular) formulations, making it a versatile agent for managing various endocrine and gastrointestinal disorders.

Mechanism of Action

Octreotide exerts its effects by binding to somatostatin receptors (primarily subtypes 2 and 5) with higher affinity than natural somatostatin. This binding inhibits the secretion of multiple hormones, including:

• Growth hormone (GH)
• Gastrin
• Vasoactive intestinal peptide (VIP)
• Insulin
• Glucagon
• Secretin
• Motilin
• Pancreatic polypeptide

It also reduces splanchnic blood flow, inhibits intestinal secretion and motility, and decreases gallbladder contractility. The drug's effects on tumor cells expressing somatostatin receptors include inhibition of cell proliferation and induction of apoptosis.

Indications

• Acromegaly: To reduce GH and IGF-1 levels in patients who have had inadequate response to or cannot be treated with surgery and/or radiotherapy
• Severe diarrhea and flushing episodes associated with carcinoid tumors
• Vasoactive intestinal peptide-secreting tumors (VIPomas)
• Gastroenteropancreatic neuroendocrine tumors (GEP-NETs)
• Esophageal variceal bleeding (adjunct therapy)

• Treatment of chemotherapy-induced diarrhea
• Dumping syndrome
• Pancreatic fistula closure
• AIDS-related diarrhea
• Small bowel fistula output reduction
• Hypoglycemia disorders (nesidioblastosis, insulinomas)
• Thyroid-stimulating hormone-secreting pituitary adenomas

Dosage and Administration

• Acromegaly: Initial dose 50-100 mcg SC TID; titrate based on GH and IGF-1 levels (range: 100-500 mcg TID)
• Carcinoid tumors: 100-600 mcg/day SC in 2-4 divided doses
• VIPomas: 200-300 mcg/day SC in 2-4 divided doses

• Acromegaly: 20 mg IM every 4 weeks initially; may increase to 30 mg every 4 weeks if needed
• NETs: 20 mg IM every 4 weeks initially; may increase to 30 mg every 4 weeks if needed

• Renal impairment: No dosage adjustment needed
• Hepatic impairment: Use with caution; monitor closely
• Elderly: No specific dosage adjustment required
• Pediatrics: Safety and effectiveness not established

• Immediate-release: Rotate subcutaneous injection sites
• LAR formulation: Administer by deep IM gluteal injection
• For IV administration (variceal bleeding): 50 mcg bolus followed by 50 mcg/hour continuous infusion

Pharmacokinetics

• SC bioavailability: Approximately 100%
• Tmax: 0.4 hours for SC injection
• LAR formulation: Initial release within first hour, then sustained release over 4 weeks

• Volume of distribution: 13.6 L
• Protein binding: 40-65% (primarily lipoproteins and albumin)
• Crosses placenta; minimal distribution to breast milk

• Primarily hepatic via peptidase enzymes
• Extensive first-pass metabolism

• Half-life: 1.7-1.9 hours (SC); 30 days (LAR)
• Excretion: 32% in urine as unchanged drug
• Clearance: 10 L/hr

Contraindications

• Hypersensitivity to octreotide or any component of the formulation
• Patients with hypersensitivity to somatostatin analogs

Warnings and Precautions

• May cause bradycardia, conduction abnormalities, and arrhythmias
• Monitor patients with cardiac disease

• May cause hypoglycemia or hyperglycemia
• Monitor blood glucose levels
• Thyroid function abnormalities may occur

• May reduce gallbladder contractility and cause biliary sludge or stones
• Monitor with gallbladder ultrasonography periodically
• Can cause diarrhea, nausea, and abdominal discomfort

• May affect absorption of orally administered drugs
• Use with caution in patients with renal or hepatic impairment
• Monitor vitamin B12 levels during long-term therapy

Drug Interactions

• Cyclosporine: Reduced cyclosporine levels
• Bromocriptine: Increased bromocriptine availability
• Beta-blockers: Additive bradycardic effects
• Oral hypoglycemics/Insulin: Altered glucose control
• CYP3A4 substrates: Possible altered metabolism
• Digoxin: Reduced digoxin absorption
• Oral medications: May alter absorption of other drugs

Adverse Effects

• Injection site reactions (pain, swelling)
• Gastrointestinal effects (nausea, diarrhea, abdominal pain)
• Headache
• Hyperglycemia/hypoglycemia
• Cholelithiasis
• Constipation
• Flatulence

• Cardiac conduction abnormalities
• Pancreatitis
• Hepatitis
• Thyroid dysfunction
• Vitamin B12 deficiency
• Anaphylaxis (rare)
• Pulmonary hypertension (rare)

Monitoring Parameters

• Acromegaly: GH and IGF-1 levels every 3-6 months
• Blood glucose: Regularly, especially in diabetic patients
• Thyroid function: Periodically
• Gallbladder: Ultrasonography every 6-12 months
• Vitamin B12: Annually with long-term therapy
• Cardiac function: In patients with pre-existing conditions
• Electrolytes: Particularly in patients with diarrhea
• Liver function tests: Periodically

Patient Education

• Instruct on proper injection technique and site rotation
• Explain potential gastrointestinal side effects
• Advise to report any signs of gallstones (abdominal pain, nausea, vomiting)
• Educate about symptoms of hypoglycemia and hyperglycemia
• Inform about possible drug interactions
• Discuss importance of regular monitoring appointments
• Advise to inform all healthcare providers about octreotide use
• For LAR formulation: Explain the dosing schedule and importance of not missing doses

References

1. Melmed S, et al. A consensus statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018;14(9):552-561. 2. Anthony L, et al. Gastroenteropancreatic neuroendocrine tumors. Cancer Netw. 2019;33(7):875-886. 3. Octreotide acetate prescribing information. US FDA. 2021. 4. Oberg K, et al. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol. 2004;15(6):966-973. 5. Bruns C, et al. SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor receptor binding and a unique antisecretory profile. Endocrinology. 2002;143(11):4123-4130. 6. National Comprehensive Cancer Network (NCCN) Guidelines: Neuroendocrine and Adrenal Tumors. Version 2.2023. 7. American Association of Clinical Endocrinologists (AACE) Acromegaly Guidelines. Endocr Pract. 2021;27(12):1233-1245.