Octreotide

Octreotide mimics endogenous somatostatin but with substantially greater potency and duration. It produces broad inhibitory effects on the secretion of growth hormone and a wide range of gastrointestinal and pancreatic peptide hormones.

Mechanism of Action

• SSTR2 and SSTR5 agonism: octreotide binds G-protein-coupled somatostatin receptors — primarily SSTR2 and to a lesser extent SSTR5 — coupling through Gαi/o to inhibit adenylyl cyclase and through phospholipase C, modulating downstream calcium and potassium currents.
• Endocrine effects: profound inhibition of growth hormone (GH) release in the brain; suppression of TSH, glucagon, insulin, gastrin, motilin, secretin, VIP, and pancreatic polypeptide.
• Anti-tumour activity: in SSTR2-positive neuroendocrine tumours, sustained receptor activation triggers cell-cycle arrest, apoptosis, and inhibition of pro-angiogenic signalling, producing anti-proliferative effects beyond symptom control.
• Vascular and splanchnic effects: reduces splanchnic blood flow, useful in variceal bleeding adjuncts; smooth muscle effects on the GI tract.

Pharmacokinetics

• Absorption:
  • Subcutaneous: complete absorption; peak plasma concentration at approximately 30 minutes.
  • Oral (Mycapssa): paired with a permeation-enhancer formulation that enables intestinal absorption; peak concentration at 1.67–2.5 hours; peak ~33% lower than subcutaneous. Food reduces oral absorption by ~90% — take on an empty stomach.
• Protein binding: approximately 65%, primarily to lipoproteins and albumin.
• Volume of distribution: ~13.6 L (healthy volunteers); 18.1–30.4 L after IV.
• Metabolism: extensively metabolised in the liver.
• Half-life: subcutaneous terminal half-life ~1.7 hours; oral 2.3–2.7 hours; LAR depot releases drug over weeks supporting once-monthly dosing.
• Excretion: ~32% in urine (oral) and 30–40% in faeces; ~11% as unchanged drug in urine.
• Clearance: total body clearance 7–10 L/h.

• Acromegaly: in patients with inadequate response to surgery and/or radiotherapy, or for whom these are inappropriate. Sandostatin IR and Sandostatin LAR are first-line medical therapies; Mycapssa is approved for long-term maintenance in patients who have responded to and tolerated injectable octreotide or lanreotide.
• Symptomatic control of flushing and diarrhoea in carcinoid syndrome associated with metastatic carcinoid tumours.
• Symptomatic control of secretory diarrhoea in vasoactive intestinal peptide-secreting tumours (VIPomas).
• Adjunctive management of selected GEP-NETs (often as long-acting depot, with anti-proliferative intent).
• Off-label uses: variceal haemorrhage, refractory diarrhoea (chemotherapy-, AIDS-, dumping-syndrome-related), pancreatic fistula, chylothorax.

• Hypersensitivity to octreotide or any excipient.

Very common (≥1/10): injection site reactions (pain, induration, erythema); abdominal pain, diarrhoea, nausea, flatulence; cholelithiasis (asymptomatic gallstones develop in up to 25% of patients on long-term therapy).

Common (≥1/100 to <1/10): hyperglycaemia, hypoglycaemia (in insulinoma and during dose changes), headache, dizziness, bradycardia, steatorrhoea, vomiting, biliary sludge, cholecystitis, transient elevation of liver enzymes, hair loss, fatigue, vitamin B12 deficiency on prolonged use.

Uncommon (≥1/1,000 to <1/100): hypothyroidism, thyroid dysfunction, dyspnoea, pancreatitis, hepatitis, jaundice, hypersensitivity reactions, rash, thrombocytopenia.

Rare (<1/1,000): anaphylaxis, QT prolongation, arrhythmia, severe hepatotoxicity.

• Insulin and oral antidiabetics: octreotide alters glucose homeostasis — dose adjustment of insulin and other antidiabetics is often required, in both directions depending on baseline.
• Ciclosporin: octreotide reduces ciclosporin absorption — monitor levels.
• Bromocriptine: octreotide increases bromocriptine bioavailability.
• CYP3A4 substrates with narrow therapeutic index (e.g. quinidine, terfenadine): octreotide may inhibit CYP3A4 — monitor.
• Beta-blockers, calcium-channel blockers, agents controlling fluid and electrolyte balance: additive bradycardia and rhythm disturbance — monitor and adjust as needed.
• Bromocriptine, cabergoline, dopamine agonists: occasional additive effects in acromegaly co-therapy; no significant interaction otherwise.

Acromegaly

• Sandostatin (IR) subcutaneous: initiate 50–100 mcg every 8 hours; titrate to maintenance dose based on GH and IGF-1 levels (typical maintenance 100–200 mcg three times daily; maximum 1.5 mg/day).
• Sandostatin LAR Depot intramuscular: switch from IR after at least 2 weeks of stable response. Typical dose 20 mg every 4 weeks; range 10–40 mg every 4 weeks based on GH/IGF-1 and tolerability.
• Mycapssa oral: 40 mg/day (20 mg twice daily) initially in patients already maintained on injectable somatostatin analog; titrate up to 80 mg/day (40 mg twice daily) as needed. Take on an empty stomach — at least 1 hour before or 2 hours after a meal — with water; do not chew or crush.

Carcinoid Syndrome and VIPomas

• Sandostatin (IR) subcutaneous: 100–600 mcg/day divided into 2–4 doses (carcinoid); up to 1,000 mcg/day for VIPoma. Titrate to symptom control.
• Sandostatin LAR Depot intramuscular: 20 mg every 4 weeks after switch from IR; range 10–30 mg every 4 weeks.

Variceal Bleeding (Off-Label, IV)

Bolus 50 mcg followed by continuous IV infusion 25–50 mcg/hour for up to 5 days; alongside endoscopic and supportive measures per local protocols.

Renal Impairment

In severe impairment requiring dialysis, half-life is approximately doubled — reduce maintenance LAR dose and titrate cautiously.

Hepatic Impairment

Reduce maintenance LAR dose in patients with hepatic cirrhosis; IR dosing is generally unaffected.

Missed Dose (LAR)

Administer as soon as the missed dose is identified and resume the 4-weekly schedule. Patients on IR should not double the next dose.

Gallbladder Disease

Long-term octreotide markedly increases the prevalence of asymptomatic and symptomatic gallstones. Baseline gallbladder ultrasound is recommended before starting long-term therapy and periodically thereafter (e.g. every 6–12 months).

Glucose Metabolism

Octreotide inhibits both insulin and glucagon secretion; net effect on glucose is variable. Monitor closely on initiation and dose changes, particularly in patients with diabetes or insulinoma.

Thyroid Function

TSH and free T4 may decrease on long-term therapy; monitor thyroid function annually.

Pregnancy and Lactation

• Pregnancy: limited human data — use only if clearly indicated. Octreotide is classified as Pregnancy Category B in the US; consider with specialist input.
• Breastfeeding: passage into breast milk is unknown; risk-benefit decision required.

Elderly

No specific dose adjustment for age alone; monitor renal and cardiac function.

Paediatric

Limited experience outside of selected congenital hyperinsulinism and other specialist indications; specialist supervision required.

Effect on Driving

No or negligible influence; patients should be cautious if dizziness or somnolence occurs.

• Sandostatin IR ampoules and vials: store at 2–8°C (refrigerator) in the original packaging, protected from light. May be stored at room temperature up to 25°C for the day of use; for short trips, ampoules can be kept at room temperature (below 25°C) for up to 14 days before use.
• Sandostatin LAR Depot: refrigerator (2–8°C). May be kept at room temperature (below 25°C) for up to 24 hours before injection but should not be exposed to higher temperatures. Reconstitute and administer immediately.
• Mycapssa: store in the original bottle at room temperature (15–30°C); protect from moisture and excursions above 30°C.

• Sandostatin IR: 5 years; Sandostatin LAR: 3 years; Mycapssa: 2 years. Brand-specific. Do not use after the expiry date printed on the packaging.

Prescription required (Rx).