Lanreotide (Monograph)

Brand name: Somatuline Depot
Drug class: Somatostatin Agonists
- Somatostatin Analogs
Chemical name: [cyclo S-S]-3-(2-naphthyl)-d-alanyl-l-cysteinyl-l-tyrosyl-d-tryptophyl-l-lysyl-l-valyl-l-cysteinyl-l-threoninamide acetate (salt)
CAS number: 127984-74-1

Medically reviewed by Drugs.com on Jul 25, 2022. Written by ASHP.

Introduction

Synthetic octapeptide pharmacologically related to somatostatin.^{1 6 8}

Uses for Lanreotide

Acromegaly

Long-term treatment of acromegaly in patients who have had inadequate responses to or are not candidates for surgical resection and/or radiotherapy (designated an orphan drug by FDA for this use).^{1 2}

Goal of therapy is to normalize concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1).¹

Improves certain manifestations of acromegaly (asthenia, joint pain, swelling of extremities, excessive perspiration, headache).⁴

Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

Treatment of unresectable, well- or moderately differentiated, locally advanced or metastatic GEP-NETs to improve progression-free survival (designated an orphan drug by FDA for this use).^{1 2 11}

Carcinoid Syndrome

Treatment of carcinoid syndrome.^{1 12} (designated an orphan drug by FDA for this use).^{1 2 12}

Lanreotide Dosage and Administration

General

Pretreatment Screening

• Evaluate patient for bradycardia.¹ In patients with preexisting bradycardia, initiate lanreotide with caution.¹

• Monitor blood glucose concentrations when initiating treatment.¹

Patient Monitoring

• Acromegaly: Monitor serum GH and IGF-1 concentrations to assess response to therapy and adjust dosage accordingly.^{1 9}

• Monitor blood glucose concentrations when lanreotide dosage is altered; adjust antidiabetic treatment accordingly.¹

• Periodically monitor for gallstones or complications of gallstones.¹

• Monitor thyroid function as clinically indicated.¹

Administration

Administer by deep subcutaneous injection only by a healthcare provider.¹

Sub-Q Administration

Administer by deep sub-Q injection into the upper outer quadrant of the buttock; alternate injection sites every 4 weeks between the right and left buttock.¹

Commercially available as a prefilled syringe.¹

Allow product to reach room temperature by removing sealed pouch from refrigerator 30 minutes prior to administration.¹ Keep pouch sealed until time of administration.¹

Insert the needle rapidly to its full length at an angle perpendicular to the skin; the skin should not be pinched prior to administration.¹

Prefilled syringes are for single-use only; discard after use.¹

Dosage

Available as lanreotide acetate; dosage expressed in terms of lanreotide.¹

Adults

Acromegaly

Sub-Q

Initially, 90 mg once every 4 weeks for 3 months.¹

After 3 months, adjust subsequent dosages based on response (GH and IGF-1 concentrations and clinical response) (see Table 1).¹

In patients who are controlled on a lanreotide dosage of 60 or 90 mg once every 4 weeks, may consider extending the dosing interval to 120 mg once every 6 or 8 weeks.¹ Determine GH and IGF-I concentrations at 6 weeks after this change in dosing regimen to evaluate for continued patient response.¹

Continue to monitor patient response (biochemical and clinical control) and adjust dosage as necessary.¹

Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

Sub-Q

120 mg once every 4 weeks.¹

Carcinoid Syndrome

Sub-Q

120 mg once every 4 weeks.¹

Patients receiving lanreotide for treatment of GEP-NETs should not receive an additional dose of lanreotide for treatment of carcinoid syndrome.¹

Special Populations

Hepatic Impairment

Acromegaly

Sub-Q

In patients with moderate to severe hepatic impairment (Child-Pugh class B or C), initially, 60 mg once every 4 weeks for 3 months.¹ Adjust subsequent dosage based on GH and IGF-1 concentrations and clinical response.¹ Caution is advised when considering an extended dosing interval of 120 mg every 6 or 8 weeks in patients with moderate or severe hepatic impairment.¹

Renal Impairment

Acromegaly

Sub-Q

In patients with moderate to severe hepatic impairment, initially, 60 mg once every 4 weeks for 3 months.¹ Adjust subsequent dosage based on GH and IGF-1 concentrations and clinical response.¹ Caution is advised when considering an extended dosing interval of 120 mg every 6 or 8 weeks in patients with moderate or severe renal impairment.¹

Geriatric Patients

Cautious dosage selection because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹

Cautions for Lanreotide

Contraindications

• None.¹

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis and angioedema reactions reported.¹

Biliary Effects

Biliary abnormalities (e.g., cholelithiasis, biliary sludge) occur commonly,¹ due to decreased gallbladder motility, inhibited gallbladder contractility, and decreased bile secretion.¹ Incidence may be related to dose and duration of therapy.¹ Perform gallbladder studies periodically.¹

Cholelithiasis resulting in complications (e.g., cholecystitis, cholangitis, pancreatitis) and requiring cholecystectomy reported in postmarketing experience.¹ If complications of cholelithiasis suspected, discontinue therapy and initiate appropriate medical therapy.¹

Endocrine Effects

Hypoglycemia or hyperglycemia can occur as a result of inhibition of insulin and glucagon secretion.¹ Monitor blood glucose concentrations when lanreotide therapy is initiated or dosage adjusted in patients with diabetes mellitus.^{1 10} Adjust dose of antidiabetic agents as necessary.¹

Slight decreases in thyroid function possible; hypothyroidism reported rarely.¹ Assess thyroid function when indicated.¹

Cardiovascular Effects

Sinus bradycardia, bradycardia, and hypertension reported.¹ Exercise care when initiating therapy in patients with bradycardia.¹ If symptomatic bradycardia occurs, initiate appropriate therapy.¹

Immunogenicity

Potential for immunogenicity with use of therapeutic proteins, such as lanreotide.¹ Development of antibodies to lanreotide reported infrequently in clinical trials; however, safety and efficacy not affected.¹

Specific Populations

Pregnancy

No adequate and well-controlled studies using lanreotide in pregnant women.¹ In animal studies, embryofetal toxicity (e.g., decreased embryofetal survival, fetal skeletal/soft tissue abnormalities) observed.¹

Lactation

Not known whether lanreotide is distributed into milk, affects milk production, or has any effects on breast-fed infants. ¹ Discontinue nursing during therapy and for 6 months after the last dose. ¹

Pediatric Use

Safety and efficacy not established.¹

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.¹

Hepatic Impairment

Patients with acromegaly: Clearance is decreased in patients with moderate to severe hepatic impairment.¹ Dosage adjustment recommended for such patients.¹

Patients with GEP-NETs: Effect of hepatic impairment on pharmacokinetics of lanreotide not established.¹

Renal Impairment

Patients with acromegaly: Clearance may be decreased and half-life and AUC may be increased in patients with end-stage renal function on dialysis.¹ Dosage adjustment recommended for patients with moderate to severe renal impairment (Cl_cr < 60 mL/minute).¹

Patients with GEP-NETs: Pharmacokinetics of lanreotide not substantially altered in patients with mild to moderate renal impairment (Cl_cr 30–89 mL/minute).¹ Effect of severe renal impairment (Cl_cr <30 mL/minute) on pharmacokinetics of lanreotide not established.¹

Common Adverse Effects

Diarrhea, abdominal pain, nausea, constipation, flatulence, vomiting, cholelithiasis, injection site reactions, arthralgia, headache, musculoskeletal pain, hyperglycemia, hypertension, dizziness, and muscle spasm.¹

Drug Interactions

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP isoenzyymes: Potential pharmacokinetic interaction (decreased substrate clearance).¹ Caution advised if used concomitantly with CYP3A4 substrates with a low therapeutic index.¹

Drugs Associated with Bradycardia

Possible additive effect on heart rate reduction; dosage adjustment of the concomitantly administered drug may be necessary.¹

Effects on GI Absorption of Drugs

Possible decreased absorption of concomitant drugs.¹

Specific Drugs

Lanreotide Pharmacokinetics

Absorption

Bioavailability

Mean bioavailability was 73.4, 69, and 78.4% following sub-Q administration of single 60-, 90-, and 120-mg dosages, respectively.¹ A drug depot is formed at the injection site allowing for sustained release.¹

Peak levels obtained during the first day following sub-Q administration.¹

Duration

Serum concentrations slowly decline over 28 days with low peak to trough fluctuation noted at steady state.¹

Distribution

Extent

Not known whether lanreotide is distributed into milk. ¹

Elimination

Elimination Route

<5% excreted in urine; <0.5% recovered unchanged in feces, indicating some biliary excretion.¹

Half-life

23–30 days following single-dose administration to healthy subjects.¹

Special Populations

In healthy geriatric individuals, half-life was increased by 85%.¹

End-stage renal disease requiring dialysis decreases clearance twofold and increases half-life and AUC twofold.¹

Moderate to severe hepatic impairment reduces clearance by 30%.¹

Stability

Storage

Parenteral

Injection

2–8°C in original package; protect from light.¹

Actions

• Decreases the concentration of GH and IGF-1.^{1 8}

• Inhibits basal secretion of several gastric enzymes (e.g., motilin, gastric inhibitory peptide, pancreatic polypeptide) and postprandial secretion of pancreatic polypeptide, gastrin, and cholecystokinin.^{1 8}

• Has high affinity for somatostatin receptors (SSTR) 2 and 5 in the anterior pituitary and pancreas.^{1 6 8}

Advice to Patients

• Advise patient to read manufacturer’s patient information.¹

• Risk of cholelithiasis or complications of gallstones; importance of patients contacting a clinician immediately if they experience sudden abdominal or shoulder pain, fever, chills, nausea, or yellowing of eyes or skin.¹

• Risk of bradycardia; importance of patients contacting a clinician immediately if they experience bradycardia.¹

• Risk of hyperglycemia or hypoglycemia; importance of monitoring for signs and symptoms of hyperglycemia (e.g., excessive thirst, increased appetite with weight loss, high urine output, fatigue) or hypoglycemia (e.g., dizziness, confusion, headache, hunger, shakiness).¹ Importance of monitoring blood glucose concentration during therapy.¹

• Risk of thyroid function abnormalities; importance of patients contacting a clinician immediately if they experience signs and symptoms of hypothyroidism (chest pain, shortness of breath, weakness, dizziness, or fainting.¹

• Risk of hypersensitivity reactions; importance of immediately contacting a clinician if a serious hypersensitivity reaction (e.g., angioedema, anaphylaxis) occurs.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

• Importance of women informing clinicians if they are or plan to become pregnant. ¹

• Importance of advising women to discontinue nursing during therapy and for 6 months after the last dose.¹

• Importance of advising women that lanreotide may reduce fertility.¹

• Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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