Lanreotide

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Subcutaneous:

Somatuline Depot: 60 mg/0.2 mL (0.2 mL [DSC]); 90 mg/0.3 mL (0.3 mL [DSC])

Solution, Subcutaneous [preservative free]:

Somatuline Depot: 120 mg/0.5 mL (0.5 mL); 60 mg/0.2 mL (0.2 mL); 90 mg/0.3 mL (0.3 mL)

Pharmacology

Mechanism of Action

Lanreotide is a synthetic octapeptide analogue of natural somatostatin which is a peptide inhibitor of multiple endocrine, neuroendocrine, and exocrine mechanisms. Lanreotide displays a greater affinity for somatostatin type 2 (SSTR2) and type 5 (SSTR5) receptors found in pituitary gland, pancreas, and growth hormone (GH) secreting neoplasms of pituitary gland and a lesser affinity for somatostatin receptors 1, 3, and 4. Lanreotide reduces GH secretion and also reduces the levels of insulin-like growth factor 1.

Pharmacokinetics/Pharmacodynamics

Distribution

15.14 L (Trocóniz 2009)

Excretion

Urine (<5% as unchanged drug); feces (<0.5% as unchanged drug)

Time to Peak

7 to 12 hours (Trocóniz 2009)

Half-Life Elimination

23 to 30 days

Use in Specific Populations

Special Populations: Renal Function Impairment

In patients with ESRD, there is approximately a 2-fold decrease in total serum clearance, with a consequent 2-fold increase in half-life and AUC.

Special Populations: Hepatic Function Impairment

A 30% reduction in clearance was observed in patients with moderate to severe hepatic impairment.

Special Populations: Elderly

Compared with healthy younger subjects, elderly subjects showed an 85% increase in half-life and a 65% increase in mean residence time.

Use: Labeled Indications

Acromegaly: 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 (the treatment goal is to reduce growth hormone and insulin growth factor-1 levels to normal).

The Endocrine Society suggests use of a somatostatin analog in select patients preoperatively to reduce surgical risk from severe comorbidities and as initial adjuvant therapy in patients with persistent, significant disease (ie, moderate to severe signs/symptoms of growth hormone excess and without local mass effects) following surgery. Alternative agents are suggested for patients with mild disease postoperatively (Endocrine Society [Katznelson 2014]).

Carcinoid syndrome: Treatment of carcinoid syndrome in adults (to reduce the frequency of short acting somatostatin analog rescue therapy).

Gastroenteropancreatic neuroendocrine tumors: Treatment (to improve progression-free survival) of unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults.

Contraindications

Hypersensitivity to lanreotide or any component of the formulation

Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to somatostatin or related peptides; complicated, untreated bile duct lithiasis

Dosage and Administration

Dosing: Adult

Acromegaly: SubQ: Initial dose: 90 mg once every 4 weeks for 3 months; after initial 3 months, continue monitoring and adjust dose as necessary based on clinical response of patient, growth hormone (GH) levels, and/or insulin-like growth factor 1 (IGF-1) levels as follows:

GH ≤1 ng/mL, IGF-1 normal, symptoms stable: Decrease dose to 60 mg once every 4 weeks; once stabilized on 60 mg once every 4 weeks, may consider regimen of 120 mg once every 6 or 8 weeks (extended-interval dosing)

GH >1 to 2.5 ng/mL, IGF-1 normal, symptoms stable: Continue 90 mg once every 4 weeks; once stabilized on 90 mg once every 4 weeks, may consider regimen of 120 mg once every 6 or 8 weeks (extended-interval dosing)

GH >2.5 ng/mL, IGF-1 elevated and/or uncontrolled symptoms: Increase dose to 120 mg once every 4 weeks. In some cases, individualized doses of 180 mg once every 4 weeks or 120 mg once every 3 weeks have been used successfully in partial responders (Giustina 2017).

Note: If clinical and/or biochemical response is inadequate at maximum dosage, consider combination therapy with pegvisomant or a dopamine agonist (eg, cabergoline) (Endocrine Society [Katznelson 2014]).

Carcinoid syndrome: SubQ: 120 mg once every 4 weeks (if already receiving lanreotide for treatment of gastroenteropancreatic neuroendocrine tumors [GEP-NETs], do not administer an additional dose for carcinoid syndrome)

GEP-NETs: SubQ: 120 mg once every 4 weeks until disease progression or unacceptable toxicity

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Allow to reach room temperature by removing sealed pouch from refrigerator 30 minutes prior to administration; keep in sealed pouch until just prior to administration. Product left in its sealed pouch at room temperature (<40°C [104°F]) for <24 hours may be returned to the refrigerator for storage and use at a later time. Lanreotide depot has a semi-solid phase with a gel-like viscous white to pale yellow appearance.

Administration

SubQ: Administer by deep subcutaneous injection (only) into superior outer quadrant of buttocks. Alternate injection sites between the right and left sides from one injection to the next. Remove sealed pouch from refrigerator 30 minutes prior to administration in order to reach room temperature. Keep pouch sealed until just prior to injection.

Storage

Store at 2°C to 8°C (36°F to 46°F). Protect from light; store in the original package.

Drug Interactions

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Monitor therapy

Bromocriptine: Somatostatin Analogs may increase the serum concentration of Bromocriptine. Somatostatin Analogs may also delay bromocriptine absorption and time to maximum plasma concentrations. Monitor therapy

Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Exceptions are discussed in separate monographs. Consider therapy modification

Codeine: Somatostatin Analogs may decrease the metabolism of Codeine. The formation of two major codeine metabolites (morphine and norcodeine) may be impaired by somatostatin analogs. Monitor therapy

CycloSPORINE (Systemic): Somatostatin Analogs may decrease the serum concentration of CycloSPORINE (Systemic). Consider therapy modification

Fexinidazole [INT]: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole [INT]. Avoid combination

Gallium Ga 68 Dotatate: Somatostatin Analogs may diminish the therapeutic effect of Gallium Ga 68 Dotatate. Specifically, a false negative PET scan may occur if Gallium GA 68 Dotatate is used during treatment with somatostatin analogs. Management: Imaging with gallium Ga 68 dotatate positron emission tomography (PET) should be performed just prior to dosing with long-acting somatostatin analogs. Short-acting somatostatin analogs can be used up to 24 hours before imaging with gallium Ga 68 dotatate. Consider therapy modification

Gallium Ga 68 Dotatoc: Somatostatin Analogs may diminish the therapeutic effect of Gallium Ga 68 Dotatoc. Management: Imaging with gallium Ga 68 dotatoc positron emission tomography (PET) should be performed just prior to dosing with long-acting somatostatin analogs. Short-acting somatostatin analogs can be used up to 24 hours before imaging with gallium Ga 68 dotatoc. Consider therapy modification

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Monitor therapy

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Monitor therapy

Lutetium Lu 177 Dotatate: Somatostatin Analogs may diminish the therapeutic effect of Lutetium Lu 177 Dotatate. Specifically, the therapeutic effect of Lutetium Lu 177 Dotatate may be diminished if the timing of Somatostatin Analog administration is not carried out as recommended. Management: Discontinue long-acting somatostatin analogs at least 4 weeks and short-acting octreotide at least 24 hours prior to each lutetium Lu 177 dotatate dose. Administer short- and long-acting octreotide during treatment as recommended. See full monograph. Consider therapy modification

Macimorelin: Somatostatin Analogs may diminish the diagnostic effect of Macimorelin. Avoid combination

Maitake: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pegvisomant: Somatostatin Analogs may enhance the adverse/toxic effect of Pegvisomant. Specifically, this combination may increase the risk for significant elevations of liver enzymes. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Consider therapy modification

Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. Consider therapy modification

Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

Adverse Reactions

>10%:

Cardiovascular: Bradycardia (3% to 18%), hypertension (5% to 14%)

Central nervous system: Headache (5% to 16%)

Dermatologic: Injection site pruritus (≤17%), rash at injection site (≤15%)

Endocrine & metabolic: Diabetes mellitus (≤14%), hyperglycemia (≤14%), hypoglycemia (≤14%), weight loss (5% to 11%)

Gastrointestinal: Diarrhea (26% to 65%), abdominal pain (7% to 34%), cholelithiasis (2% to 27%), vomiting (5% to 19%), flatulence (6% to 15%), nausea (9% to 11%)

Hematologic & oncologic: Anemia (3% to 14%)

Hepatic: Gallbladder sludge (≤20%)

Immunologic: Antibody development (≤11%)

Local: Inflammation at injection site (≤22%), injection site reaction (≤22%), pain at injection site (≤22%), residual mass at injection site (≤22%), induration at injection site (≤17%), injection site nodule (≤17%), bleeding at injection site (≤15%), discomfort at injection site (≤15%), hematoma at injection site (≤15%), injection site extravasation (≤15%), injection site granuloma (≤15%), swelling at injection site (≤15%)

Neuromuscular & skeletal: Musculoskeletal pain (19%)

1% to 10%:

Cardiovascular: Sinus bradycardia (3% to 7%)

Central nervous system: Dizziness (7% to 9%), depression (7%)

Gastrointestinal: Loose stools (6% to 9%), constipation (5% to 8%)

Neuromuscular & skeletal: Arthralgia (7% to 10%), muscle spasm (5%)

Respiratory: Dyspnea (6%)

<1%, postmarketing, and/or case reports: Abscess at injection site, anaphylaxis, angioedema, aortic insufficiency, cholecystitis, hypothyroidism, mitral valve insufficiency, pancreatitis, steatorrhea

Warnings/Precautions

Concerns related to adverse effects:

• Cholelithiasis: May reduce gall bladder motility, leading to gall stone formation (may be dose- or duration-related); may require periodic monitoring. Cholelithiasis and complications of cholelithiasis (eg, cholecystitis, cholangitis, pancreatitis) requiring cholecystectomy have been reported; discontinue and treat appropriately if suspected.
• Gastrointestinal effects: Diarrhea and loose stools may occur (may affect intestinal absorption of concurrently-administered medication); abdominal pain may also occur.
• Hyper-/hypoglycemia: Inhibition of insulin and glucagon secretion may affect glucose regulation, leading to hyper-/hypoglycemia. Carefully monitor blood glucose levels with the initiation of therapy and with dosage alterations. Use with caution in patients with diabetes; may require dosage adjustments in antidiabetic therapy.
• Hypersensitivity: Allergic reactions, including angioedema and anaphylaxis, have been reported.
• Thyroid disorders: Decreases (slight) in thyroid function have been observed during treatment for acromegaly; monitor thyroid function tests if clinically indicated. The incidence of clinical hypothyroidism is rare.

Disease-related concerns:

• Cardiac disorders: Bradycardia, sinus bradycardia, and hypertension have been observed with therapy. Use with caution in patients with preexisting cardiac disease; monitor heart rate. Patients without preexisting cardiac disease may experience a decrease in heart rate though not to the level of bradycardia. Appropriate medical therapy should be initiated if patients develop symptomatic bradycardia.
• Hepatic impairment: Use with caution in patients with acromegaly with moderate to severe hepatic impairment (systemic exposure may be increased); lower doses are recommended at therapy initiation. Lanreotide has not been studied in patients with neuroendocrine tumors with hepatic impairment.
• Renal impairment: Use with caution in patients with acromegaly with moderate to severe renal impairment; lower initial doses are recommended.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

Serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1) at 3 months and as clinically indicated in acromegaly patients (obtain levels 6 weeks after dose adjustment when switching to extended-interval dosing); blood glucose, glycemic control and antidiabetic regimen (patients with diabetes mellitus) should be assessed following initiation, then periodically or following dosage adjustments; thyroid function (where clinically indicated); heart rate, gallbladder monitoring if clinically indicated; routine gallbladder ultrasound is not considered necessary (Endocrine Society [Katznelson 2014]).

Pregnancy

Pregnancy Considerations

Information related to the use of lanreotide in pregnancy is limited (de Menis 1999; Teltayev 2017) and it is recommended to discontinue therapy during pregnancy (Endocrine Society [Katznelson 2014]). If treatment for acromegaly is required during pregnancy for worsening symptoms (eg, headaches or evidence of tumor growth), alternative agents are recommended. Monitoring of insulin-like growth factor 1 (IGF-1) and/or growth hormone (GH) is not recommended during pregnancy, as an active placental GH variant present in maternal blood limits the usefulness of the results (Endocrine Society [Katznelson 2014]).

Because normalization of IGF-1 and GH may restore fertility in women with acromegaly, women of childbearing potential should use adequate contraception during treatment. The Endocrine Society suggests discontinuing long-acting formulations of somatostatin analogs approximately 2 months prior to a planned pregnancy; short-acting octreotide may be used until conception if needed (Endocrine Society [Katznelson 2014]).

Patient Education

What is this drug used for?

• It is used to treat acromegaly.
• It is used to treat a certain type of cancer called neuroendocrine tumor from the gastrointestinal tract or the pancreas (GEP-NETs).
• It is used to treat carcinoid syndrome.

Frequently reported side effects of this drug

• Abdominal pain
• Passing gas
• Nausea
• Vomiting
• Diarrhea
• Constipation
• Joint pain
• Muscle pain
• Muscle spasm
• Injection site irritation
• Weight loss

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit.
• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating.
• Gallstones like pain in the upper right abdominal area, right shoulder area, or between the shoulder blades; yellow skin; or fever with chills.
• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting.
• Severe dizziness
• Passing out
• Severe headache
• Vision changes
• Thyroid problems like change in weight without trying, anxiety, agitation, feeling very weak, hair thinning, depression, neck swelling, trouble focusing, inability handling heat or cold, menstrual changes, tremors, or sweating.
• Chest pain
• Confusion
• Trouble with memory
• Slow heartbeat
• Depression
• Shortness of breath
• Flushing
• Severe loss of strength and energy
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.