Lanreotide

Lanreotide produces sustained somatostatin-receptor activation from a deep subcutaneous depot, suppressing growth hormone and a range of gastroenteropancreatic hormones. Anti-secretory effects underpin symptom control; anti-proliferative effects underpin progression-free survival benefit in GEP-NETs.

Mechanism of Action

• SSTR2 and SSTR5 agonism: binding to G-protein-coupled somatostatin receptors couples through Gαi/o to inhibit adenylyl cyclase and through phospholipase C and ion channels, hyperpolarising target cells and suppressing hormone release.
• Endocrine effects: inhibition of GH and IGF-1, glucagon, insulin, and gastroenteropancreatic peptides.
• Antiproliferative effects in NETs: SSTR activation triggers cell-cycle arrest and apoptosis; reduces tumour angiogenesis and growth-supporting cytokines. Demonstrated to prolong progression-free survival in the CLARINET trial in metastatic, well-/moderately-differentiated GEP-NETs.

Pharmacokinetics

• Absorption: biphasic from the depot — an initial rapid release within the first few days, followed by slow, passive diffusion from the precipitated drug reservoir over ~28 days. Absorption is independent of body weight, sex, and dose.
• Volume of distribution: estimated ~15 L.
• Protein binding: data limited; clinically not significant for dosing.
• Half-life: terminal half-life approximately 22 days for the Autogel formulation — supports once-monthly dosing and extended intervals in some patients.
• Excretion: minimal renal excretion (<5%) and minimal unchanged faecal excretion (<0.5%), suggesting predominantly biliary elimination after metabolism.
• Clearance: estimated ~23.1 L/h.

• Acromegaly: long-term treatment of patients with inadequate response to, or who cannot be treated with, surgery and/or radiotherapy.
• Gastroenteropancreatic neuroendocrine tumours (GEP-NETs): treatment of adult patients with unresectable, well- or moderately-differentiated, locally advanced or metastatic GEP-NETs of midgut, pancreatic, or unknown origin to improve progression-free survival.
• Carcinoid syndrome: management of symptoms (flushing, diarrhoea) in adults — reduces requirement for short-acting somatostatin analog rescue therapy.

• Hypersensitivity to lanreotide, any somatostatin analog, or any excipient.

Very common (≥1/10): gastrointestinal disorders (diarrhoea, abdominal pain, nausea — typically mild-to-moderate, transient, and most pronounced after the first injections); cholelithiasis (gallstones develop in up to 30% of patients with long-term therapy).

Common (≥1/100 to <1/10): injection-site reactions (induration, nodule, pain, erythema, pruritus); flatulence, vomiting, abdominal distension, steatorrhoea; hyperglycaemia, hypoglycaemia, diabetes mellitus; biliary dilatation, biliary sludge; sinus bradycardia; asthenia, fatigue; alopecia, hypotrichosis; nasopharyngitis; hypothyroidism, decreased free thyroxine.

Uncommon (≥1/1,000 to <1/100): hot flushes, dizziness, headache, insomnia, lethargy; pancreatitis, transaminase elevations, increased bilirubin; rash, pruritus; reductions in left ventricular end-diastolic and end-systolic volumes.

Rare (<1/1,000): hypersensitivity reactions including anaphylaxis (very rare); arrhythmia.

• Insulin and oral antidiabetics: lanreotide affects glucose homeostasis — adjustments to antidiabetic therapy are commonly required.
• Ciclosporin: lanreotide may reduce intestinal absorption of ciclosporin — monitor levels and adjust dose.
• Bromocriptine: lanreotide may increase bromocriptine availability.
• CYP3A4 substrates with narrow therapeutic index (e.g. quinidine, terfenadine): lanreotide is a weak CYP3A4 inhibitor — monitor.
• Beta-blockers and other bradycardia-inducing drugs: additive bradycardia possible — monitor heart rate.

Lanreotide Autogel / Depot is administered by deep subcutaneous injection into the superior external quadrant of the buttock (or other appropriate site per labelling) every 4 weeks. Patients or carers can be trained to self-administer where appropriate.

Acromegaly

• Starting dose: 90 mg deep subcutaneously every 4 weeks; some regimens start at 60 mg in treatment-naïve patients.
• Titration based on GH/IGF-1: increase to 120 mg every 4 weeks or extend interval (90 mg every 6–8 weeks) for very well-controlled disease. The 60 mg strength is an option for de-escalation.

Gastroenteropancreatic Neuroendocrine Tumours

• Standard dose: 120 mg deep subcutaneously every 4 weeks.

Carcinoid Syndrome

• Standard dose: 120 mg deep subcutaneously every 4 weeks; titration to symptom control. Short-acting somatostatin rescue may be used between scheduled injections in breakthrough symptoms.

Renal Impairment

In severe renal impairment, systemic exposure to lanreotide is increased; consider starting at 60 mg every 4 weeks in acromegaly and titrate cautiously. No adjustment required for GEP-NET dosing.

Hepatic Impairment

Mild-to-moderate hepatic impairment does not require dose adjustment; data are limited in severe impairment.

Missed Dose

Administer the next dose as soon as possible and resume the 4-weekly schedule. Avoid administering two doses within a short interval.

Gallbladder Monitoring

Long-term somatostatin analog therapy causes asymptomatic gallstones in a substantial minority of patients. Baseline ultrasound is recommended before therapy and periodic monitoring (e.g. every 6–12 months) thereafter.

Glucose Metabolism

Lanreotide inhibits both insulin and glucagon. Monitor blood glucose closely on initiation and dose changes; pre-existing diabetes may require dose adjustment of antidiabetic agents.

Thyroid Function

Mild decreases in thyroid function are common; monitor TSH and free T4 annually.

Cardiac Monitoring

Sinus bradycardia may occur; caution and ECG monitoring are advisable in patients with pre-existing cardiac disease, particularly those on bradycardia-inducing co-medication.

Pregnancy and Lactation

• Pregnancy: limited data — use only if clearly indicated. Lanreotide is classified as Pregnancy Category C in the US.
• Breastfeeding: not recommended — passage into breast milk and effects on the infant are unknown.

Injection Technique and Site

Inject deeply into the subcutaneous tissue without aspiration; alternate sides at each administration. Bring the syringe to room temperature for 30 minutes before injection (still in its sealed pouch) for comfort and ease of injection.

Effect on Driving

No or negligible influence; advise caution if dizziness or asthenia occurs.

Store in the original packaging at 2–8°C (refrigerator), protected from light. Do not freeze. The pre-filled syringe may be kept in its original sealed pouch below 40°C for a single period of up to 72 hours before administration. Discard if exposed to temperature excursions beyond labelling.

3 years from the date of manufacture. Do not use after the expiry date printed on the packaging.

Prescription required (Rx).