Lanreotide – Uses, Dosage, Side Effects, Interaction

Mechanism of Action

Lanreotide is a somatostatin analog (SSA) and has mainly inhibitory effects which are mediated via somatostatin receptors (SSTRs) 2 and 5 and include inhibition of growth hormone release in the brain. Tumor SSTR activation induces downstream cell cycle arrest and/or apoptosis, and also results in blunted production of substances that support tumor growth as well as tumor angiogenesis. This leads to the antiproliferative effects of Lanreotide.

Lanreotide exhibits antisecretory effects through cAMP suppression and activation of ion currents such as K+ and Ca2+ which leads to hyperpolarization of the membrane and inhibition of Ca2+-mediated depolarization. Furthermore, through direct and indirect mechanisms, Lanreotide has potent antiproliferative effects.

Indications

  • Lanreotide is indicated for the long-term treatment of patients with acromegaly who have had an inadequate response to, or cannot be treated with, surgery and/or radiotherapy. It is also indicated in the treatment of adult patients with unresectable, well- or moderately-differentiated, locally advanced, or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival. Lanreotide is additionally indicated for the treatment of adults with carcinoid syndrome – when used, it reduces the frequency of short-acting somatostatin analog rescue therapy.
  • Lanreotide is a somatostatin analog used for the treatment of unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors and acromegaly.
  • Treatment of acromegaly, Treatment of gastrointestinal fistulae, Treatment of metastases to the peritoneum, Treatment of pituitary gigantism, Treatment of pituitary neoplasms
  • Lanreotide is a synthetic polypeptide analog of somatostatin that resembles the native hormone in its ability to suppress levels and activity of growth hormone, insulin, glucagon, and many other gastrointestinal peptides. Because its half-life is longer than somatostatin, lanreotide can be used clinically to treat neuroendocrine tumors that secrete excessive amounts of growth hormone (acromegaly) or other active hormones or neuropeptides.
  • Lanreotide is used in the treatment of acromegaly, due to both pituitary and non-pituitary growth hormone-secreting tumors, and the management of symptoms caused by neuroendocrine tumors, particularly carcinoid tumors, and VIPomas. In the United States and Canada, lanreotide is only indicated for the treatment of acromegaly. In the United Kingdom, it is also indicated in the treatment of thyrotrophic adenoma,[rx] a rare tumor of the pituitary gland which secretes TSH. Lanreotide also shows activity against non-endocrine tumors, and, along with other somatostatin analogs, is being studied as a possible general antitumor agent.
  • Acromegaly
  • Carcinoid Syndrome
  • Unresectable, locally advanced enteropancreatic neuroendocrine tumors
  • Unresectable, locally advanced well- or moderately-differentiated Gastroenteropancreatic Neuroendocrine Tumors
  • Unresectable, metastatic enteropancreatic neuroendocrine tumors
  • Unresectable, metastatic well- or moderately-differentiated Gastroenteropancreatic Neuroendocrine Tumors

Use in Cancer

Lanreotide acetate is approved to treat:

Lanreotide acetate is also being studied in the treatment of other conditions or types of cancer.

Contraindications

  • Bradycardia, cardiac disease. Use lanreotide with caution in patients with underlying cardiac disease or preexisting bradycardia.
  • Diabetes mellitus.
  • Gallbladder disease.
  • Hepatic disease.
  • Hypothyroidism, thyroid disease.
  • Pregnancy.
  • Infertility, reproductive risk.
  • Breast-feeding.
  • a condition with low thyroid hormone levels
  • low blood sugar
  • high blood pressure
  • slow heartbeat
  • liver problems
  • gallstones
  • disease of the gallbladder
  • high blood sugar
  • a patient who is producing milk and breastfeeding
  • chronic kidney disease stage 3A (moderate)
  • chronic kidney disease stage 3B (moderate)
  • chronic kidney disease stage 4 (severe)
  • chronic kidney disease stage 5 (failure)
  • kidney disease with likely reduction in kidney function

Dosage

Strengths: 60 mg/0.2 mL; 90 mg/0.3 mL; 120 mg/0.5 mL

Acromegaly

  • Initial dose: 90 mg, by deep subcutaneous injection, every 4 weeks for 3 months
  • The goal of treatment is to reduce growth hormone (GH) and insulin-like growth factor (IGF-1) levels to normal.
  • Adjust dose after initial 3 months.
  • No dose adjustment is required for elderly patients.
  • Long-term treatment of acromegalic patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option.

Neuroendocrine Carcinoma

  • 120 mg, by deep subcutaneous injection, every 4 weeks
  • No dose adjustment is required for elderly patients.
  • Treatment of patients with unresectable, well or moderately-differentiated, locally advanced, or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival.

Carcinoid Syndrome

  • 120 mg by deep subcutaneous injection every 4 weeks
  • If patients are already being treated for GEP-NETs, do not administer an additional dose for the treatment of carcinoid syndrome.
  • For the treatment of carcinoid syndrome; when used, it reduces the frequency of short-acting somatostatin analog rescue therapy.

Renal Dose Adjustments

Acromegaly:

  • Moderate to severe renal impairment: Initial dose: 60 mg, by deep subcutaneous injection, every 4 weeks for 3 months, followed by dose adjustments as described for non-really impaired patients.
  • Use caution when considering an extended dosing interval (120 mg every 6 or 8 weeks) in moderate or severe renal impairment.

Gastroenteropancreatic Neuroendocrine Tumors:

  • No adjustment is recommended for mild to moderate renal impairment
  • Data not available for severe renal impairment

Liver Dose Adjustments

Acromegaly:

  • Moderate to severe hepatic impairment: Initial dose: 60 mg, by deep subcutaneous injection, every 4 weeks for 3 months, followed by dose adjustments as described for non-hepatically impaired patients.

Gastroenteropancreatic Neuroendocrine Tumors:

  • Data not available for any level of hepatic impairment

Dose Adjustments

Acromegaly:
After the initial 3 month dosing, adjust dose based on growth hormone (GH) and insulin-like growth factor (IGF-1) levels:

  • GH over 1 and up to 2.5 ng/mL, IGF-1 normal, and symptoms controlled: 90 mg, by deep subcutaneous (SC) injection, every 4 weeks
  • GH over 2.5 ng/mL, IGF-1 elevated, and/or symptoms uncontrolled: 120 mg, by deep SC injection, every 4 weeks
  • GH less than 1 ng/mL, IGF-1 normal, symptoms controlled: 60 mg, by deep SC injection, every 4 weeks
  • Adjust dose according to patient response, as judged by a reduction in GH and/or IGF-1 levels, and/or changes in acromegaly symptoms.
  • Patients controlled on 60 mg or 90 mg may be considered for an extended dosing interval of 120 mg every 6 or 8 weeks; obtain GH and IGF-1 levels 6 weeks after this change to evaluate persistence of patient response.
  • Continued monitoring of patient response with dose adjustments for biochemical and clinical symptom control, as necessary, is recommended.
  • No dose adjustment is required for elderly patients.
  • No difference in safety and effectiveness was seen in elderly patients, however greater sensitivity cannot be ruled out.
  • In general, dose selection for elderly patient should be cautious, starting at the low end of the dosing range.
  • No dose adjustment is required for elderly patients.

Administration advice:

  • Healthcare providers should administer this drug.
  • Administer in the superior external quadrant of the buttock; alternate between right and left sides with each injection.
  • Remove from refrigerator 30 minutes before administration, but keep pouch sealed until ready to administer.

Side Effects

The Most Common

  • diarrhea
  • loose stools
  • constipation
  • gas
  • vomiting
  • weight loss
  • headache
  • redness, pain, itching, or a lump at the injection site
  • depression
  • pain in the upper right part of the stomach, center of the stomach, back, or shoulder
  • muscle pain or discomfort
  • yellowing of the skin and eyes
  • fever with chills
  • nausea
  • swelling of the face, throat, tongue, lips, or eyes
  • tightness in the throat
  • difficulty breathing and swallowing
  • wheezing
  • hoarseness
  • rash
  • itching
  • hives
  • shortness of breath
  • slowed or irregular heartbeat

More common

  • Blurred vision
  • chest pain or discomfort
  • dizziness
  • gaseous abdominal or stomach pain
  • headache
  • lightheadedness, dizziness, or fainting
  • nervousness
  • pale skin
  • pounding in the ears
  • recurrent fever
  • slow, fast, or irregular heartbeat
  • stomach fullness
  • troubled breathing with exertion
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • yellow eyes or skin
  • Difficulty having a bowel movement
  • difficulty with moving
  • excess air or gas in the stomach or bowels
  • feeling of fullness
  • inflammation, itching, lumps, or pain at the injection site
  • muscle pain or stiffness
  • pain in the joints
  • passing gas
  • weight loss

Rare

  • Bloating
  • chills
  • clay-colored stools
  • confusion
  • constipation
  • cough
  • dark urine
  • diarrhea
  • difficulty swallowing
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • fat in the stool
  • fever
  • hives, itching, skin rash
  • indigestion
  • large, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals
  • loss of appetite
  • nausea
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • severe nausea or vomiting
  • stomach pain or cramps
  • sudden loss of weight
  • sweating
  • tightness in the chest
  • unusual drowsiness, dullness, or feeling of sluggishness
  • vomiting
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Drug Interactions

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Pregnancy and Lactation

AU TGA pregnancy category: C
US FDA pregnancy category: Not assigned

Pregnancy

Limited available data based on post-marketing case reports with lanreotide use in pregnant women are not sufficient to determine a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, decreased embryo/fetal survival was observed in pregnant rats and rabbits at subcutaneous doses 5- and 2-times the maximum recommended human dose (MRHD) of 120 mg, respectively (see Data). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to
20%, respectively.

Lactation

There is no information available on the presence of lanreotide in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Studies show that lanreotide administered subcutaneously passes into the milk of lactating rats; however,
due to specifies-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk. Because of the potential for serious adverse reactions in breastfed infants from Lanreotide Injection, including effects on glucose metabolism and
bradycardia, advise women not to breastfeed during treatment with Lanreotide Injection and for 6 months (6 half-lives) following the last dose.

Why is this medication prescribed?

Lanreotide injection is used to treat people with acromegaly (a condition in which the body produces too much growth hormone, causing enlargement of the hands, feet, and facial features; joint pain; and other symptoms) who have not successfully, or cannot be treated with surgery or radiation. Lanreotide injection is also used to treat people with neuroendocrine tumors in the gastrointestinal (GI) tract or the pancreas (GEP-NETs) that have spread or cannot be removed by surgery. Lanreotide injection is in a class of medications called somatostatin agonists. It works by decreasing the amounts of certain natural substances produced by the body.

How should this medicine be used?

Lanreotide comes as a long-acting solution (liquid) to be injected subcutaneously (under the skin) into the upper outer area of your buttock by a doctor or nurse. Lanreotide long-acting injection is usually injected once every 4 weeks. Ask your doctor or pharmacist to explain any part you do not understand.

Your doctor will probably adjust your dose or the length of time between doses depending on your lab results. Ask your pharmacist or doctor for a copy of the manufacturer’s information for the patient. This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

What special precautions should I follow?

Before receiving lanreotide injection,

  • tell your doctor and pharmacist if you are allergic to lanreotide injection, any other medications, or any of the ingredients in lanreotide injection. Ask your pharmacist for a list of the ingredients.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: beta-blockers such as atenolol (Tenormin, in Tenoretic), labetalol (Trandate), metoprolol (Lopressor, Toprol XL, in Dutoprol), nadolol (Corgard, in Corzide), and propranolol (Hemangeol, Inderal, InnoPran); bromocriptine (Cycloset, Parlodel); cyclosporine (Gengraf, Neoral, Sandimmune); insulin and oral medications for diabetes; quinidine (in Nuedexta), or terfenadine (no longer available in the U.S.). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you have or have ever had diabetes, or gallbladder, heart, kidney, thyroid, or liver disease.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while receiving a lanreotide injection, call your doctor.
  • you should know that lanreotide injection may make you drowsy or dizzy. Do not drive a car or operate machinery until you know how this medication affects you.
References