Lanreotide Acetate

Pronunciation: lan-REE-oh-tide AS-e-tate
Class: Somatostatin analog

Trade Names

Somatuline Depot
- Injection, solution, ER 60 mg per 0.2 mL
- Injection, solution, ER 90 mg per 0.3 mL
- Injection, solution, ER 120 mg per 0.5 mL

Pharmacology

Similar to the natural hormone somatostatin. Suppresses secretion of serotonin and gastroenteropancreatic peptides (eg, gastrin, glucagon, insulin, motilin, secretin). Also suppresses growth hormone (GH).

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Pharmacokinetics

Absorption

After subcutaneous administration, bioavailability ranges from approximately 69% to 78%, depending on the dose. C max ranges from 4.3 to 8.4 ng/mL during the first day. At steady state, C max ranges from 3.8 to 7.7 ng/mL, increasing linearly with the dose. The steady-state trough serum concentration ranges from 1.8 to 3.8 ng/mL, depending on the dose. Mean serum concentration is greater than 1 ng/mL throughout 28 days with the 90 mg dose and greater than 0.9 ng/mL with the 60 mg.

Elimination

The half-life is 23 to 30 days. Less than 5% is excreted in urine and less than 0.5% is recovered unchanged in feces, indicating some biliary excretion.

Special Populations

Renal Function Impairment

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

Hepatic Function Impairment

A 30% reduction in Cl is observed in patients with moderate to severe hepatic impairment.

Elderly

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

Indications and Usage

Long-term treatment of acromegaly in patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option.

Contraindications

None well documented.

Dosage and Administration

Acromegaly
Adults

Subcutaneous Start with 90 mg subcutaneously at 4-wk intervals for 3 mo. After 3 mo, the dosage may be adjusted as follows: If GH greater than 1 to 2.5 ng/mL or less with insulin-like growth factor-1 (IGF-1) normal and clinical symptoms controlled, maintain dosage at 90 mg every 4 wk. If GH greater than 2.5 ng/mL with IGF-1 elevated and/or clinical symptoms uncontrolled, increase dosage to 120 mg every 4 wk. If GH 1 ng/mL or less with IGF-1 normal and clinical symptoms controlled, reduce dosage to 60 mg every 4 wk. Thereafter, adjust dosage according to response of patient as judged by reduction in serum GH and/or IGF-1 levels, and/or changes in acromegaly symptoms.

Hepatic/Renal Function Impairment

Subcutaneous In patients with moderate to severe hepatic or renal impairment, start with 60 mg at 4-wk intervals for 3 mo then adjust dosage as described above.

General Advice

  • Administer via deep subcutaneous injection in the superior external quadrant of the buttock.
  • Insert needle perpendicular to the skin, rapidly and to its full length; do not fold skin. Alternate between right and left side.
  • Remove from refrigerator 30 min prior to administration and allow to come to room temperature.
  • Patients who are controlled on lanreotide 60 or 90 mg may be considered for an extended dosing interval of lanreotide 120 mg every 6 or 8 wk. GH and IGF-1 levels should be obtained 6 wks after this change in dosing regimen to evaluate persistence of patient response. Caution should be exercised when considering this dose in patients with renal and/or hepatic impairment.
  • Continued monitoring of patient's response with dose adjustments for biochemical and clinical symptom control, as necessary, is recommended.

Storage/Stability

Store under refrigeration between 36° and 46°F. Protect from light.

Drug Interactions

Bradycardia-inducing drugs (eg, beta-blockers)

There may be an additive effect on reduction of heart rate associated with lanreotide, necessitating dosage adjustment of concurrent medication.

Bromocriptine

Coadministration may increase availability of bromocriptine. Clinical monitoring is warranted. If an interaction is suspected, adjust the bromocriptine dose as needed.

Cyclosporine

Cyclosporine bioavailability may be reduced, necessitating cyclosporine dosage adjustments.

Drugs metabolized by CYP3A4

Cl may be reduced by lanreotide. Use drugs that have a low therapeutic index (eg, quinidine) with caution.

Insulin, oral hypoglycemic agents

Insulin and glucagon secretion may be inhibited, necessitating adjustments in antidiabetic treatment.

Adverse Reactions

Cardiovascular

Bradycardia (18%); hypertension, sinus bradycardia (7%).

GI

Diarrhea (65%); abdominal pain (20%); flatulence (14%); nausea (11%); loose stools (9%); constipation (8%); vomiting (7%).

Hepatic

Cholelithiasis (27%); gallbladder sledge (20%).

Local

Injection-site induration, inflammation, mass, nodule, pain, pruritus, or reaction (22%).

Metabolic-Nutritional

Diabetes/hyperglycemia/hypoglycemia (14%); decreased weight (11%).

Miscellaneous

Anemia (14%); arthralgia (10%); headache (7%); antibody formation (4% to less than 1%).

Precautions

Monitor

Monitor blood glucose levels when treatment is started or when the dose is altered. Serum GH and IGF-1 levels are useful markers of the disease and the effectiveness of treatment. Periodically monitor gallbladder motility and thyroid function.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

Reduce starting dose in patients with moderate to severe renal impairment.

Hepatic Function

Reduce starting dose in patients with moderate to severe hepatic impairment.

CV abnormalities

In patients with acromegaly, the most common adverse reactions are bradycardia, sinus bradycardia, and hypertension. In patients suffering from cardiac disorders prior to treatment, sinus bradycardia may occur. Use with caution in patients with bradycardia.

Cholelithiasis

Gallbladder motility may be reduced, leading to gallstone formation.

Hyperglycemia or hypoglycemia

Serum glucose control may be altered because of inhibition of insulin and glucagon secretion.

Thyroid function

Slight decreases in thyroid function have been seen during treatment in patients with acromegaly.

Overdosage

Symptoms

None well documented.

Patient Information

  • Advise patient to read the patient information leaflet.
  • Advise patients to consult with health care provider as soon as possible if an injection is missed.
  • Instruct patients to report severe pain in the right upper area of the stomach (abdomen), along with nausea and vomiting, or any other bothersome or persistent adverse reactions to health care provider.
  • Advise patients that response to lanreotide should be monitored by periodic measurements of GH and IGF-1 levels, with a goal of decreasing these levels to the normal range.

Copyright © 2009 Wolters Kluwer Health.

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