Prescription Drug Information: SOMATULINE DEPOT

SOMATULINE DEPOT- lanreotide acetate injection
Ipsen Biopharmaceuticals, Inc.

1 INDICATIONS AND USAGE

1.1 Acromegaly

SOMATULINE DEPOT 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.

1.2 Gastroenteropancreatic Neuroendocrine Tumors

SOMATULINE DEPOT is indicated for 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.

1.3 Carcinoid Syndrome

SOMATULINE DEPOT is indicated for the treatment of adults with carcinoid syndrome; when used, it reduces the frequency of short-acting somatostatin analog rescue therapy.

2 DOSAGE AND ADMINISTRATION

2.1 Important Administration Instructions

  • For deep subcutaneous injection only.
  • SOMATULINE DEPOT is intended for administration by a healthcare provider.
  • Refer to the Instructions For Use (IFU) for complete administration instructions with illustrations.

Preparation

  1. Remove SOMATULINE DEPOT from the refrigerator 30 minutes prior to administration and allow to come to room temperature.
  2. Keep pouch sealed until just prior to injection.
  3. Product left in its sealed pouch at room temperature (not to exceed 104°F or 40°C) for up to 72 hours may be returned to the refrigerator for continued storage and use at a later time.
  4. Prior to administration, inspect the SOMATULINE DEPOT syringe visually for particulate matter and discoloration. Do not administer if particulate matter or discoloration is observed. The content of the prefilled syringe is a semi-solid phase having a gel-like appearance, with viscous characteristics and a color varying from white to pale yellow. The supersaturated solution can also contain micro bubbles that can clear up during injection. These differences are normal and do not interfere with the quality of the product.

Administration

  1. Slowly administer for 20 seconds as a deep subcutaneous injection in the superior external quadrant of the buttock.
  2. Alternate the injection site between the right and left sides from one injection to the next.

2.2 Recommended Dosage

Acromegaly

The recommended starting dosage of SOMATULINE DEPOT is 90 mg given via the deep subcutaneous route, at 4-week intervals for 3 months.

After 3 months, the dosage may be adjusted as follows:

  • GH greater than 1 ng/mL to less than or equal to 2.5 ng/mL, IGF-1 normal, and clinical symptoms controlled: maintain SOMATULINE DEPOT dosage at 90 mg every 4 weeks.
  • GH greater than 2.5 ng/mL, IGF-1 elevated, and/or clinical symptoms uncontrolled: increase SOMATULINE DEPOT dosage to 120 mg every 4 weeks.
  • GH less than or equal to 1 ng/mL, IGF-1 normal, and clinical symptoms controlled: reduce SOMATULINE DEPOT dosage to 60 mg every 4 weeks.

Thereafter, the dosage 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.

Patients who are controlled on SOMATULINE DEPOT 60 or 90 mg may be considered for an extended dosing interval of SOMATULINE DEPOT 120 mg every 6 or 8 weeks. GH and IGF-1 levels should be obtained 6 weeks after this change in dosing regimen to evaluate persistence of patient response.

Continued monitoring of patient response with dosage adjustments for biochemical and clinical symptom control, as necessary, is recommended.

Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

The recommended dosage of SOMATULINE DEPOT is 120 mg administered every 4 weeks by deep subcutaneous injection.

Carcinoid Syndrome

The recommended dosage of SOMATULINE DEPOT is 120 mg administered every 4 weeks by deep subcutaneous injection.

If patients are already being treated with SOMATULINE DEPOT for GEP-NETs, do not administer an additional dose for the treatment of carcinoid syndrome.

2.3 Dosage Adjustment in Renal Impairment

Acromegaly

The recommended starting dosage of SOMATULINE DEPOT in acromegalic patients with moderate or severe renal impairment (creatinine clearance less than 60 mL/min) is 60 mg via the deep subcutaneous route at 4-week intervals for 3 months followed by dosage adjustment [see Dosage and Administration (2.2), Use in Specific Populations (8.6)].

2.4 Dosage Adjustment in Hepatic Impairment

Acromegaly

The recommended starting dosage of SOMATULINE DEPOT in acromegalic patients with moderate or severe hepatic impairment (Child-Pugh Class B or C) is 60 mg via the deep subcutaneous route at 4-week intervals for 3 months followed by dosage adjustment [see Dosage and Administration (2.2), Use in Specific Populations (8.7)].

3 DOSAGE FORMS AND STRENGTHS

Injection: 60 mg/0.2 mL, 90 mg/0.3 mL, and 120 mg/0.5 mL sterile, single-dose, prefilled syringes fitted with an automatic safety system (attached retractable needle and needle guard). The prefilled syringes contain a white to pale yellow, semi-solid formulation.

4 CONTRAINDICATIONS

SOMATULINE DEPOT is contraindicated in patients with history of a hypersensitivity to lanreotide. Allergic reactions (including angioedema and anaphylaxis) have been reported following administration of lanreotide [see Adverse Reactions (6.3)].

5 WARNINGS AND PRECAUTIONS

5.1 Cholelithiasis and Complications of Cholelithiasis

SOMATULINE DEPOT 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)]. There have been postmarketing reports of cholelithiasis (gallstones) resulting in complications, including cholecystitis, cholangitis, and pancreatitis, and requiring cholecystectomy in patients taking SOMATULINE DEPOT. If complications of cholelithiasis are suspected, discontinue SOMATULINE DEPOT and treat appropriately.

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 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, 5.5%) [see Adverse Reactions (6.1)].

In 81 patients with baseline heart rates of 60 beats per minute (bpm) or greater treated with SOMATULINE DEPOT in Study 3, the incidence of heart rate less than 60 bpm was 23% (19/81) as compared to 16% (15/94) of placebo treated patients; 10 patients (12%) had documented heart rates less than 60 bpm on more than one visit. The incidence of documented episodes of heart rate less than 50 bpm as well as the incidence of bradycardia reported as an adverse event was 1% in each treatment group. Initiate appropriate medical management in patients who develop symptomatic bradycardia.

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

5.4 Thyroid Function Abnormalities

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

5.5 Monitoring: Laboratory Tests

Acromegaly: Serum GH and IGF-1 levels are useful markers of the disease and the effectiveness of treatment [see Dosage and Administration (2.2)].

6 ADVERSE REACTIONS

The following adverse reactions to SOMATULINE DEPOT are discussed in greater detail in other sections of the labeling:

6.1 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.

Acromegaly

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 years of age (range 19 to 84 years). Fifty-four subjects (13%) were age 66 to 74 and 18 subjects (4.3%) were 75 years of age and older.

Patients were evenly matched for sex (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 less than 10 ng/mL for 69% (183/265) of the patients and 10 ng/mL or greater for 31% (82/265) of the patients.

The most commonly reported adverse reactions reported by greater than 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, 90, and 120 mg by dose as reported during the first 4 months (fixed-dose phase) of Study 1 [see Clinical Studies (14.1)] are provided in Table 1.

Table 1: Adverse Reactions at an Incidence of Greater than 5% with SOMATULINE DEPOT Overall and Occurring at Higher Rate than Placebo: Placebo-Controlled and Fixed-Dose Phase of Study 1 By Dose
Placebo-Controlled Double-Blind PhaseWeeks 0 to 4 Fixed-Dose Phase Double-Blind + Single-Blind Weeks 0 to 20
Body System Preferred Term Placebo (N=25) SOMATULINE DEPOT Overall(N=83) SOMATULINE DEPOT 60 mg(N=34) SOMATULINE DEPOT 90 mg(N=36) SOMATULINE DEPOT 120 mg(N=37) SOMATULINE DEPOT Overall(N=107)
N (%) N (%) N (%) N (%) N (%) N (%)
A patient is counted only once for each body system and preferred term.
Dictionary = WHOART.
Gastrointestinal System Disorders 1 (4%) 30 (36%) 12 (35%) 21 (58%) 27 (73%) 60 (56%)
Diarrhea 0 26 (31%) 9 (26%) 15 (42%) 24 (65%) 48 (45%)
Abdominal pain 1 (4%) 6 (7%) 3 (9%) 6 (17%) 7 (19%) 16 (15%)
Flatulence 0 5 (6%) 0 (0%) 3 (8%) 5 (14%) 8 (7%)
Application Site Disorders 0 (0%) 5 (6%) 3 (9%) 4 (11%) 8 (22%) 15 (14%)
(Injection site mass/ pain/ reaction/ inflammation)
Liver and Biliary System Disorders 1 (4%) 3 (4%) 9 (26%) 7 (19%) 4 (11%) 20 (19%)
Cholelithiasis 0 2 (2%) 5 (15%) 6 (17%) 3 (8%) 14 (13%)
Heart Rate & Rhythm Disorders 0 8 (10%) 7 (21%) 2 (6%) 5 (14%) 14 (13%)
Bradycardia 0 7 (8%) 6 (18%) 2 (6%) 2 (5%) 10 (9%)
Red Blood Cell Disorders 0 6 (7%) 2 (6%) 5 (14%) 2 (5%) 9 (8%)
Anemia 0 6 (7%) 2 (6%) 5 (14%) 2 (5%) 9 (8%)
Metabolic & Nutritional Disorders 3 (12%) 13 (16%) 8 (24%) 9 (25%) 4 (11%) 21 (20%)
Weight decrease 0 7 (8%) 3 (9%) 4 (11%) 2 (5%) 9 (8%)

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 (greater than 5%) that occurred in 416 acromegalic patients treated with SOMATULINE DEPOT pooled from 7 studies compared to those patients from the 2 efficacy studies (Studies 1 and 2). Patients with elevated GH and IGF-1 levels were either naive to somatostatin analog therapy or had undergone a 3-month washout [see Clinical Studies (14.1)].

Table 2: Adverse Reactions in SOMATULINE DEPOT-Treated Patients at an Incidence Greater than 5% in Overall Group Versus Adverse Reactions Reported in Studies 1 and 2
System Organ Class Number and Percentage of Patients
Studies 1 & 2 Overall Pooled Data
(N=170) (N=416)
N % N %
Dictionary = MedDRA 7.1
Patients with any Adverse Reactions 157 92 356 86
Gastrointestinal disorders 121 71 235 57
Diarrhea 81 48 155 37
Abdominal pain 34 20 79 19
Nausea 15 9 46 11
Constipation 9 5 33 8
Flatulence 12 7 30 7
Vomiting 8 5 28 7
Loose stools 16 9 23 6
Hepatobiliary disorders 53 31 99 24
Cholelithiasis 45 27 85 20
General disorders and administration site conditions 51 30 91 22
(Injection site pain /mass /induration/ nodule/pruritus) 28 17 37 9
Musculoskeletal and connective tissue disorders 44 26 70 17
Arthralgia 17 10 30 7
Nervous system disorders 34 20 80 19
Headache 9 5 30 7

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 (GI) 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.

Pancreatitis was reported in less than 1% of patients.

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% had gallstones at baseline. New cholelithiasis was reported in 12% of patients. Cholelithiasis may be related to dose or duration of exposure [see Warnings and Precautions (5.1)].

Injection Site Reactions

In the pooled clinical studies, injection site pain (4%) and injection site mass (2%) 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 (5%) 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 Warnings and Precautions (5.2)].

Cardiac Adverse Reactions

In the pooled clinical studies, sinus bradycardia (3%) was the most frequently observed heart rate and rhythm disorder. All other cardiac adverse drug reactions were observed in less than 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 Warnings and Precautions (5.3)].

A comparative echocardiography study of lanreotide and another somatostatin analog demonstrated no difference in the development of new or worsening valvular regurgitation between the 2 treatments over 1 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.

Gastroenteropancreatic Neuroendocrine Tumors

The safety of SOMATULINE DEPOT 120 mg for the treatment of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) was evaluated in Study 3, a double-blind, placebo-controlled trial. Patients in Study 3 were randomized to receive SOMATULINE DEPOT (N=101) or placebo (N=103) administered by deep subcutaneous injection once every 4 weeks. The data below reflect exposure to SOMATULINE DEPOT in 101 patients with GEP-NETs, including 87 patients exposed for at least 6 months and 72 patients exposed for at least 1 year (median duration of exposure 22 months). Patients treated with SOMATULINE DEPOT had a median age of 64 years (range 30 to 83 years), 53% were men and 96% were Caucasian. Eighty-one percent of patients (83/101) in the SOMATULINE DEPOT arm and 82% of patients (82/103) in the placebo arm did not have disease progression within 6 months of enrollment and had not received prior therapy for GEP-NETs. The rates of discontinuation due to treatment-emergent adverse reactions were 5% (5/101 patients) in the SOMATULINE DEPOT arm and 3% (3/103 patients) in the placebo arm.

Table 3 compares the adverse reactions reported with an incidence of 5% and greater in patients receiving SOMATULINE DEPOT 120 mg administered every 4 weeks and reported more commonly than placebo.

Table 3: Adverse Reactions Occurring in 5% and Greater of SOMATULINE DEPOT-Treated Patients and at a Higher Rate Than in Placebo-Treated Patients in Study 3
Adverse Reaction SOMATULINE DEPOT 120 mgN=101 PlaceboN=103
Any (%) Severe * (%) Any (%) Severe * (%)
*
Defined as hazardous to well-being, significant impairment of function or incapacitation
Includes preferred terms of abdominal pain, abdominal pain upper/lower, abdominal discomfort
Includes one or more serious adverse events (SAEs) defined as any event that results in death, is life threatening, results in hospitalization or prolongation of hospitalization, results in persistent or significant disability, results in congenital anomaly/birth defect, or may jeopardize the patient and may require medical or surgical intervention to prevent one of the outcomes listed.
§
Includes preferred terms of myalgia, musculoskeletal discomfort, musculoskeletal pain, back pain
Includes preferred terms of infusion site extravasation, injection site discomfort, injection site granuloma, injections site hematoma, injection site hemorrhage, injection site induration, injection site mass, injections site nodule, injection site pain, injection site pruritus, injection site rash, injection site reaction, injection site swelling
#
Includes preferred terms of diabetes mellitus, glucose tolerance impaired, hyperglycemia, type 2 diabetes mellitus
Þ
Includes preferred terms of hypertension, hypertensive crisis
ß
Includes preferred terms of depression, depressed mood
Any Adverse Reactions 88 26 90 31
Abdominal pain 34 6 24 4
Musculoskeletal pain § 19 2 13 2
Vomiting 19 2 9 2
Headache 16 0 11 1
Injection site reaction 15 0 7 0
Hyperglycemia # 14 0 5 0
Hypertension Þ 14 1 5 0
Cholelithiasis 14 1 7 0
Dizziness 9 0 2 0
Depression ß 7 0 1 0
Dyspnea 6 0 1 0

Carcinoid Syndrome

The safety of SOMATULINE DEPOT 120 mg in patients with histopathologically confirmed neuroendocrine tumors and a history of carcinoid syndrome (flushing and/or diarrhea) was evaluated in Study 4, a double-blind, placebo-controlled trial. Patients were randomized to receive SOMATULINE DEPOT (N=59) or placebo (N=56) administered by deep subcutaneous injection once every 4 weeks. Patients in both arms of Study 4 had access to subcutaneous octreotide as rescue medication for symptom control.

Adverse reactions reported in Study 4 were generally similar to those reported in Study 3 for the GEP-NETs population shown in Table 3 above. Adverse reactions occurring in Study 4 in 5% and greater of SOMATULINE DEPOT-treated patients and occurring at least 5% more than in placebo-treated patients were headache (12% vs 5%, respectively), dizziness (7% vs 0%, respectively), and muscle spasm (5% vs 0%, respectively) by week 16.

RxDrugLabels.com provides trustworthy package insert and label information about marketed prescription drugs as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by RxDrugLabels.com. Every individual prescription drug label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.

As a leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. RxDrugLabels.com provides the full prescription-only subset of the FDA's repository. Medication information provided here is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2024. All Rights Reserved.