Lanreotide

Lanreotide
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rabin Bista, M.B.B.S. [2]

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Overview

Lanreotide is a somatostatin analog that is FDA approved for the treatment of acromegalic patients who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy. Common adverse reactions include diarrhea, cholelithiasis, abdominal pain, nausea and injection site reactions.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

Somatuline Depot (lanreotide) Injection 60 mg, 90 mg and 120 mg is indicated for the 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 goal of treatment in acromegaly is to reduce growth hormone (GH) and insulin growth factor-1 (IGF-1) levels to normal.

Dosage

Patients should begin treatment with Somatuline Depot 90 mg given via the deep subcutaneous route, at 4 week intervals for 3 months.

After 3 months dosage may be adjusted as follows:

GH >1 to ≤ 2.5 ng/mL, IGF-1 normal and clinical symptoms controlled: maintain Somatuline Depot dose at 90 mg every 4 weeks. GH > 2.5 ng/mL, IGF-1 elevated and/or clinical symptoms uncontrolled, increase Somatuline Depot dose to 120 mg every 4 weeks. GH ≤ 1 ng/mL, IGF-1 normal and clinical symptoms controlled: reduce Somatuline Depot dose to 60 mg every 4 weeks. Thereafter, the dose should be adjusted according to the response of the patient as judged by a reduction in serum GH and /or IGF-1 levels; and/or changes in symptoms of acromegaly.

Somatuline Depot should be injected via the deep subcutaneous route in the superior external quadrant of the buttock. The skin should not be folded and the needle should be inserted perpendicular to the skin, rapidly and to its full length. The injection site should alternate between the right and left side.

The starting dose in patients with moderate and severe renal or moderate and severe hepatic impairment should be 60 mg via the deep subcutaneous route, at 4 week intervals for 3 months followed by dose adjustment as described above

DOSAGE FORMS AND STRENGTHS

60, 90 and 120 mg sterile, single-use, pre-filled syringes. The pre-filled syringes contain a white to pale yellow, semi-solid formulation.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Lanreotide in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Lanreotide in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Lanreotide in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Lanreotide in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Lanreotide in pediatric patients.

Contraindications

• None

Warnings

Cholethiasis and Gallbladder Sludge Lanreotide may reduce gallbladder motility and lead to gallstone formation therefore, patients may need to be monitored periodically [see Adverse Reactions (6.1), Clinical Pharmacology (12.2)].

5.2 Hyperglycemia and Hypoglycemia Pharmacological studies in animals and humans show that lanreotide, like somatostatin and other somatostatin analogs, inhibits the secretion of insulin and glucagon. Hence, patients treated with Somatuline Depot may experience hypoglycemia or hyperglycemia. Blood glucose levels should be monitored when lanreotide treatment is initiated, or when the dose is altered, and antidiabetic treatment should be adjusted accordingly [see Adverse Reactions (6.1)].

5.3 Thyroid function Abnormalities Slight decreases in thyroid function have been seen during treatment with lanreotide in acromegalic patients, though clinical hypothyroidism is rare (<1%). Thyroid function tests are recommended where clinically indicated.

5.4 Cardiovascular Abnormalities The most common overall cardiac adverse reactions observed in three pooled Somatuline Depot Cardiac Studies in patients with acromegaly were sinus bradycardia (12/217, 5.5%), bradycardia (6/217, 2.8%) and hypertension (12/217, 5.6%) [see Adverse Reactions (6.1)].

In patients without underlying cardiac disease, lanreotide may lead to a decrease in heart rate without necessarily reaching the threshold of bradycardia. In patients suffering from cardiac disorders prior to lanreotide treatment, sinus bradycardia may occur. Care should be taken when initiating treatment with lanreotide in patients with bradycardia.

5.5 Drug Interactions The pharmacological gastrointestinal effects of Somatuline Depot may reduce the intestinal absorption of concomitant drugs.

Lanreotide may decrease the relative bioavailability of cyclosporine. Concomitant administration of Somatuline Depot and cyclosporine may necessitate the adjustment of cyclosporine dose to maintain therapeutic levels [see Drug Interactions (7.2)].

5.6 Monitoring: Laboratory Tests Serum GH and IGF-1 levels are useful markers of the disease and the effectiveness of treatment

Adverse Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

6.1 Clinical Studies Experience The data described below reflect exposure to Somatuline Depot in 416 acromegalic patients in seven studies. One study was a fixed-dose pharmacokinetic study. The other six studies were open-label or extension studies, one had a placebo controlled run-in period and another had an active control. The population was mainly Caucasian (329/353, 93%) with a median age of 53.0 years of age (range 19-84 years). Fifty-four subjects (13%) were age 66-74 and eighteen subjects (4.3%) were ≥ 75 years of age. Patients were evenly matched for gender (205 males and 211 females). The median average monthly dose was 91.2 mg (e.g., 90 mg injected via the deep subcutaneous route every 4 weeks) over 385 days with a median cumulative dose of 1290 mg. Of the patients reporting acromegaly severity at baseline (N=265), serum GH levels were < 10 ng/mL for 69% (183/265) of the patients and ≥ 10 ng/mL for 31% (82/265) of the patients.

The most commonly reported adverse reactions reported by > 5% of patients who received Somatuline Depot (N=416) in the overall pooled safety studies in acromegaly patients were gastrointestinal disorders (diarrhea, abdominal pain, nausea, constipation, flatulence, vomiting, loose stools), cholelithiasis and injection site reactions.

TABLES 1 and 2 present adverse reaction data from clinical studies with Somatuline Depot in acromegalic patients. The tables include data from a single clinical study and pooled data from seven clinical studies.

Adverse Reactions in Parallel Fixed-Dose Phase of Study 1:

The incidence of treatment-emergent adverse reactions for Somatuline Depot 60 mg, 90 mg, and 120 mg by dose as reported during the first 4 months (fixed-dose phase) of Study 1 [see Clinical Studies (14)], are provided in TABLE 1.

In Study 1, the adverse reactions of diarrhea, abdominal pain and flatulence increased in incidence with increasing dose of Somatuline Depot.

Adverse Reactions in Long-Term Clinical Trials:

TABLE 2 provides the most common adverse reactions that occurred in 416 acromegalic patients treated with Somatuline Depot in seven studies. The analysis of safety compares adverse reaction rates of patients at baseline from the two efficacy studies, to the overall pooled data from seven studies. Patients with elevated GH and IGF-1 levels were either naive to somatostatin analog therapy or had undergone a 3-month washout

In addition to the adverse reactions listed in TABLE 2, the following reactions were also seen:

Sinus bradycardia occurred in 7% (12) of patients in the pooled Study 1 and 2 and in 3% (13) of patients in the overall pooled studies. Hypertension occurred in 7% (11) of patients in the pooled Study 1 and 2 and in 5% (20) of patients in the overall pooled studies. Anemia occurred in 7% (12) of patients in the pooled Study 1 and 2 and in 3% (14) of patients in the overall pooled studies. Gastrointestinal Adverse Reactions

In the pooled clinical studies of Somatuline Depot therapy, a variety of gastrointestinal reactions occurred, the majority of which were mild to moderate in severity. One percent of acromegalic patients treated with Somatuline Depot in the pooled clinical studies discontinued treatment because of gastrointestinal reactions.

Gallbladder Adverse Reactions

In clinical studies involving 416 acromegalic patients treated with Somatuline Depot, cholelithiasis and gallbladder sludge were reported in 20% of the patients. Among 167 acromegalic patients treated with Somatuline Depot who underwent routine evaluation with gallbladder ultrasound, 17.4% had gallstones at baseline. New cholelithiasis was reported in 12.0% of patients. Cholelithiasis may be related to dose or duration of exposure [see Cholelithiasis and Gallbladder Sludge (5.1)].

Injection Site Reactions

In the pooled clinical studies, injection site pain (4.1%) and injection site mass (1.7%) were the most frequently reported local adverse drug reactions that occurred with the administration of Somatuline Depot. In a specific analysis 20 of 413 patients (4.8%) presented indurations at the injection site. Injection site adverse reactions were more commonly reported soon after the start of treatment and were less commonly reported as treatment continued. Such adverse reactions were usually mild or moderate but did lead to withdrawal from clinical studies in two subjects.

Glucose Metabolism Adverse Reactions

In the clinical studies in acromegalic patients treated with Somatuline Depot, adverse reactions of dysglycemia (hypoglycemia, hyperglycemia, diabetes) were reported by 14% (47/332) of patients and were considered related to study drug in 7% (24/332) of patients [see Hyperglycemia and Hypoglycemia (5.2)].

Cardiac Adverse Reactions

In the pooled clinical studies, sinus bradycardia (3.1%) was the most frequently observed heart rate and rhythm disorder. All other cardiac adverse drug reactions were observed in < 1% of patients. The relationship of these events to Somatuline Depot could not be established because many of these patients had underlying cardiac disease [see Cardiovascular Abnormalities (5.4)].

A comparative echocardiography study of lanreotide and another somatostatin analog demonstrated no difference in the development of new or worsening valvular regurgitation between the two treatments over one year. The occurrence of clinically significant mitral regurgitation (i.e., moderate or severe in intensity) or of clinically significant aortic regurgitation (i.e., at least mild in intensity) was low in both groups of patients throughout the study.

Other Adverse Reactions

For the most commonly occurring adverse reactions in the pooled analysis, diarrhea, abdominal pain and cholelithiasis, there was no apparent trend for increasing incidence with age. GI disorders and renal and urinary disorders were more common in patients with documented hepatic impairment; however, the incidence of cholelithiasis was similar between groups.

Laboratory investigations of acromegalic patients treated with Somatuline Depot in clinical studies show that the percentage of patients with putative antibodies at any time point after treatment is low (<1% to 4% of patients in specific studies whose antibodies were tested). The antibodies did not appear to affect the efficacy or safety of Somatuline Depot.

Postmarketing Experience

• As adverse reactions experienced post approval use are reported voluntarily from a population of uncertain size it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The profile of reported adverse reactions for Somatuline Depot was consistent with that observed for treatment-related adverse reactions in the clinical studies. Those reported most frequently being gastrointestinal disorders (abdominal pain and diarrhea) and general disorders and administration site conditions (injection site reactions).

Drug Interactions

Insulin and Oral Hypoglycemic Drugs Lanreotide, like somatostatin and other somatostatin analogs, inhibits the secretion of insulin and glucagon. Therefore, blood glucose levels should be monitored when lanreotide treatment is initiated or when the dose is altered and antidiabetic treatment should be adjusted accordingly.

7.2 Cyclosporine Concomitant administration of cyclosporine with lanreotide may decrease the relative bioavailability of cyclosporine and, therefore, may necessitate adjustment of cyclosporine dose to maintain therapeutic levels.

7.3 Other Concomitant Drug Therapy The pharmacological gastrointestinal effects of Somatuline Depot may reduce the intestinal absorption of concomitant drugs. Limited published data indicate that concomitant administration of a somatostatin analog and bromocriptine may increase the availability of bromocriptine.

Concomitant administration of bradycardia inducing drugs (e.g. beta-blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Dose adjustments of concomitant medication may be necessary.

Vitamin K absorption was not affected when concomitantly administered with lanreotide.

7.4 Drug Metabolism Interactions The limited published data available indicate that somatostatin analogs may decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes, which may be due to the suppression of growth hormone. Since it cannot be excluded that lanreotide may have this effect, other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (e.g. quinidine, terfenadine) should therefore be used with caution. Drugs metabolized by the liver may be metabolized more slowly during lanreotide treatment and dose reductions of the concomitantly administered medications should be considered.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Lanreotide in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Lanreotide during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Lanreotide with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Lanreotide with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Lanreotide with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Lanreotide with respect to specific gender populations.

Race

There is no FDA guidance on the use of Lanreotide with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Lanreotide in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Lanreotide in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Lanreotide in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Lanreotide in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

• Intravenous

Monitoring

There is limited information regarding Monitoring of Lanreotide in the drug label.

• Description

IV Compatibility

There is limited information regarding IV Compatibility of Lanreotide in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Description

Management

• Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Lanreotide in the drug label.

Pharmacology

There is limited information regarding Lanreotide Pharmacology in the drug label.

Mechanism of Action

Structure

File:Lanreotide01.png

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Lanreotide in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Lanreotide in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Lanreotide in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Lanreotide in the drug label.

How Supplied

Storage

There is limited information regarding Lanreotide Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Lanreotide in the drug label.

Precautions with Alcohol

• Alcohol-Lanreotide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• ®

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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