Lanreotide (Somatuiline) is a long-acting somatostatin receptor analog that is used to treat patients with acromegaly, carcinoid syndrome, and neuroendocrine tumors.

Lanreotide (Somatuiline) Indications:

• Acromegaly:

  • It is indicated for the treatment of patients with acromegaly who have an inadequate response to surgery or radiotherapy or for who surgery or radiotherapy is not an option.
  • The aim of treatment in these patients is to reduce the levels of growth hormone and insulin-like growth factor-1.
  • To reduce perioperative surgical risks and as initial adjuvant therapy in patients with moderate to severe signs and symptoms of growth hormone excess following surgery without mass effects, the Endocrine Society suggests the use of somatostatin analogs.
  • Alternative agents may be used postoperatively in patients with mild disease.

• Carcinoid syndrome:

  • It is indicated for the treatment of carcinoid syndrome in adults with the aim to reduce the frequency of somatostatin analog rescue therapy.

• Gastroenteropancreatic neuroendocrine tumors:

  • It is indicated in patients with locally advanced or metastatic well- or moderately-differentiated GEP-NETs (gastroenteropancreatic neuroendocrine tumors) which are not surgically resectable.
  • The aim of therapy in these patients is to improve progression-free survival.

Lanreotide (Somatuiline) Dose in Adults:

Lanreotide dose in the treatment of Acromegaly:

• 90 mg subQ initially once every 4 weeks for 3 months.
• After the initial three months, adjust the dose if necessary based on the clinical and biochemical response (Growth hormone and IGF-1 levels) as follows:

• GH ≤1 ng/mL, IGF-1 normal, symptoms stable:

  • Reduce the dose to 60 mg once every four weeks.
  • If the patient is stabilized on the reduced dose administered 4 weekly, the extended-release formulation regimen of 120 mg may be used every 6 - 8 weeks.

• GH >1 to 2.5 ng/mL, IGF-1 normal, symptoms stable:

  • Continue the same dose i.e. 90 mg 4 weekly.
  • If the patient is stabilized on 90 mg once every 4 weeks, the extended-interval regimen may be considered (120 mg subQ administered once every 6 - 8 weeks.

• GH >2.5 ng/mL, IGF-1 elevated and/or uncontrolled symptoms:

  • Increase the dose from 90 mg to 120 mg subQ once every four weeks.
  • Patients who respond only partially may be advised 180 mg once every four weeks or 120 mg once every three weeks.

Note:

If despite the maximum dose, the clinical and biochemical response is inadequate, combination therapy with pegvisomant or a dopamine agonist like cabergoline may be used.

Lanreotide Dose in the treatment of Carcinoid syndrome:

• 120 mg subQ once every four weeks
• Additional doses should not be administered if the patient is already receiving lanreotide for GEP-NETs (Gastroenteropancreatic-neuroendocrine tumors)

GEP-NETs ((Gastroenteropancreatic-neuroendocrine tumors):

• 120 mg SubQ once every 4 weeks until toxicity occurs or the disease progresses.

Use in children:

Children aged 16 years or more: Refer to adult dosing.

Pregnancy Risk Category: C

• Limited data are available on the pregnancy effects of lanreotide.
• For the treatment of acromegaly, or worsening symptoms like headaches, alternative agents may be used during pregnancy.
• Because of the possible misinterpretation of maternal serum levels of IGF-1 and growth hormone, they are not recommended for routine use.
• Effective contraception is advised for women who are pregnant.
• Normalization of growth hormones with therapy can restore fertility, leading to an unplanned pregnancy.
• The Endocrine Society recommends that long-acting somatostatin analogues be stopped at least two months before a planned pregnancy
• Short-term somatostatin analogs can be used in these cases.

Lanreotide use during breastfeeding:

• It is unknown if the drug will be excreted into breastmilk.
• It is not advised to breastfeed during therapy or for at least six months after the last dose due to the possible adverse effects on infants (bradycardia, altered glucose metabolism).

Lanreotide (Somatuiline) dose in Renal impairment:

• Acromegaly:

  • CrCl ≥60 mL/minute:

    • Adjustment in the dose is not necessary.

  • CrCl <60 mL/minute:

    • 60 mg subQ initially once every 4 weeks for three months.
    • The dose is then adjusted based on the clinical and biochemical response (growth hormone and insulin-like growth factor-1 levels).
    • The use of extended-release formulations of 120 mg once every 6 - 8 weeks should be done with caution.

• Carcinoid syndrome or gastroenteropancreatic neuroendocrine tumors (GEP-NETs):

  • CrCl ≥30 mL/minute:

    • The manufacturer has not recommended any adjustments in the dose, however, the total clearance of the drug is least likely to be affected.

  • CrCl <30 mL/minute:

    • The manufacturer has not recommended any adjustments in the dose as it has not been studied in these patients.

Lanreotide (Somatuiline) dose in Liver disease:

• Acromegaly:

  • Mild impairment (Child-Pugh class A):

    • Adjustment in the dose is not necessary.

  • Moderate to severe impairment (Child-Pugh classes B and C):

    • 60 mg subQ initially once every 4 weeks for three months.
    • The dose is then adjusted based on the clinical and biochemical response (growth hormone levels and IGF-1 levels.
    • The use of extended-interval formulations every 6 - 8 weeks should be done with caution.

• Carcinoid syndrome or gastroenteropancreatic neuroendocrine tumors (GEP-NETs):

  • It has not been studied in patients with GEP-NETs.
  • The manufacturer has not recommended any adjustments in the dose in these patients.

Common Side Effects of Lanreotide (Somatuiline):

• Cardiovascular:

  • Bradycardia
  • Hypertension

• Central Nervous System:

  • Headache

• Dermatologic:

  • Injection Site Pruritus
  • Rash At Injection Site

• Endocrine & Metabolic:

  • Diabetes Mellitus
  • Hyperglycemia
  • Hypoglycemia
  • Weight Loss

• Gastrointestinal:

  • Diarrhea
  • Abdominal Pain
  • Cholelithiasis
  • Vomiting
  • Flatulence
  • Nausea

• Hematologic & Oncologic:

  • Anemia

• Hepatic:

  • Gallbladder Sludge

• Immunologic:

  • Antibody Development

• Local:

  • Inflammation At Injection Site
  • Injection Site Reaction
  • Pain At Injection Site
  • Residual Mass At Injection Site
  • Induration At Injection Site
  • Injection Site Nodule
  • Bleeding At Injection Site
  • Discomfort At Injection Site
  • Hematoma At Injection Site
  • Injection Site Extravasation
  • Injection Site Granuloma
  • Swelling At Injection Site

• Neuromuscular & Skeletal:

  • Musculoskeletal Pain

Less Common Side Effects of Lanreotide (Somatuiline):

• Cardiovascular:

  • Sinus bradycardia

• Central nervous system:

  • Dizziness
  • Depression

• Gastrointestinal:

  • Loose stools
  • Constipation

• Neuromuscular & skeletal:

  • Arthralgia
  • Muscle spasm

• Respiratory:

  • Dyspnea

Contraindication to Lanreotide (Somatuiline):

• You may have severe allergic reactions to any ingredient of the drug.
• Allergies to somatostatin and related peptides
• Biliary tract and complicated gall bladder stones

Warnings and precautions

• Cholelithiasis

  • Gall bladder disease may manifest as gall stones, gall stones, cholecystitis or cholangitis. It can also cause gall bladder dysfunction.
  • It is necessary to monitor the situation periodically.
  • Gall bladder disease patients should stop taking medication and be treated appropriately.

• Gastrointestinal effects:

  • It is possible to experience abdominal pain and diarrhea, which can affect intestinal absorption of concomitant medication.

• Effect on blood glucose:

  • Hyperglycemia or hypoglycemia can occur due to insulin secretion and glucagon secretion.
  • At treatment initiation and during dose adjustments, it is important to monitor blood glucose.
  • After treatment initiation, dose adjustment and dosage adjustments, diabetic patients may require dose adjustments to their anti-diabetic medication.

• Hypersensitivity

  • The treatment may cause severe hypersensitivity reactions, such as anaphylaxis or angioedema.Allergy reactions should be closely monitored.

• Thyroid disorders:

  • Therapy has been successful in reducing thyroid function abnormalities, but it is uncommon for clinically significant hypothyroidism.
  • If clinically indicated, thyroid function tests should always be performed.

• Cardiac disorders:

  • Patients with preexisting heart conditions and patients on heart rate reducing medications for treatment-associated bradycardia or hypertension should not use it.
  • Bradycardia, a decrease in heart rate, may also occur in patients with no pre-existing heart disease.
  • Patients with heart disease should have their heart rate monitored. If symptomatic bradycardia develops, the appropriate treatment should be started.

• Hepatic impairment

  • The drug should not be used in patients suffering from acromegalic hepatic impairment.
  • Patients with elevated systemic exposure should receive lower doses of treatment.
  • Patients with neuroendocrine tumors and hepatic impairment have not had lanreotide studied.

• Renal impairment

  • Patients with severe or moderate renal impairment should be treated with caution and in lower doses at first.

Monitor:

• Monitor the serum growth hormone and insulin-like growth factor 1 levels at baseline and at three months after treatment initiation in patients with acromegaly.
• When switching to the extended-interval dosing, growth hormone levels should be measured after 6 weeks of therapy.
• Monitor blood glucose periodically. Diabetic patients should have their glycemic control assessed frequently and the dose should be adjusted periodically and especially following dose adjustment.
• Monitor thyroid function as clinically indicated
• Heart rate
• Monitor for gallbladder disease. Routine ultrasound is not necessary, however, if the patient develops right hypochondria symptoms should be assessed with hepatobiliary functions and an ultrasound scan.

How to administer Lanreotide (Somatuiline)?

• It is intended for subQ use only.
• Avoid other methods of administration (such as intravenous, intradermal, and intramuscular administration).
• The sealed pouch is removed from the refrigerator at least 30 minutes prior to administration and allowed to reach room temperature.
• While it is kept at room temperature, the seal should not be removed until just prior to administration.
• It is administered into the superior outer quadrant of the buttock as a deep subQ injection. The site of the injection should be rotated between alternate buttocks.

Mechanism of action of Lanreotide (Somatuiline):

• Lanreotide, a synthetic analog to the natural somatostatin, reduces the production of insulin-like growth factors and growth hormone.
• It reduces the production of multiple endocrine and neuroendocrine peptides, hormones, and exocrine metabolically activated peptides.
• It has a stronger affinity for somatostatin types 2 (SSTR2), and 5 (SSTR5) receptors.
• These receptors are primarily located in the pituitary (especially the growth hormone secreting tumors of pituitary) and the pancreas. It is less attracted to somatostatin receptors 1, 3 and 4.

It is bioavailable at a rate of69% to 78%, and the half-life elimination Between 23 and 30 days Time to get there peak plasma concentration It takes between 7 and 12 hours. Excretion: Urine (5% unchanged drug); feces 0.5% unchanged drug

International Brands of Lanreotide:

• Somatuline Depot
• Ipstyl
• Somatuiline
• Somatulin
• Somatulina
• Somatuline
• Somatuline Autogel
• Somatuline Depot
• Somatuline LA
• Somatuline LP
• Somatuline

Lanreotide Brand Names in Pakistan:

No Brands Available in Pakistan.