If overdose occurs, symptomatic management is indicated.
Up-to-date information about the treatment of overdose can often be obtained from the National Poison Control Center at phone number 1-800-222-1222.
None
The following adverse reactions to SOMATULINE DEPOT (lanreotide) Injection are discussed in greater detail in other sections of the labeling:
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.
AcromegalyThe 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 1The 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 are provided in Table 1.
Table 1: Adverse Reactions at an Incidence > 5%
with Lanreotide Overall and Occurring at Higher Rate in Drug than Placebo:
Placebo-Controlled and Fixed-Dose Phase of Study 1 By Dose
| Body System Preferred Term |
Placebo-Controlled Double-Blind Phase Weeks 0 to 4 | Fixed-Dose Phase Double-Blind + Single-Blind Weeks 0 to 20 | ||||
| Placebo (N=25) N (%) |
Lanreotide Overall (N=83) N (%) |
Lanreotide 60 mg (N=34) N (%) |
Lanreotide 90 mg (N=36) N (%) |
Lanreotide 120 mg (N=37) N (%) |
Lanreotide Overall (N=107) N (%) |
|
| 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 (Injection site mass/ pain/ reaction/ inflammation) | 0 (0%) | 5 (6%) | 3 (9%) | 4 (11%) | 8 (22%) | 15 (14%) |
| 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%) |
| A patient is counted only once for each body system and preferred term. Dictionary = WHOART. |
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 TrialsTable 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.
Table 2: Adverse Reactions at an Incidence > 5.0%
in Overall Group Reported in Studies 1 and 2
| System Organ Class | Number and Percentage of Patients | |||
| Studies 1 & 2 (N = 170) |
Overall Pooled Data (N = 416) |
|||
| N | % | N | % | |
| 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 |
| Dictionary -MedDRA 7.1 |
In addition to the adverse reactions listed in Table 2, the following reactions were also seen:
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.
Pancreatitis was reported in < 1% of patients.
Gallbladder Adverse ReactionsIn 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.
Injection Site ReactionsIn 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 ReactionsIn 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.
Cardiac Adverse ReactionsIn 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.
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 ReactionsFor 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 TumorsThe 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 ≥ 6 months and 72 patients exposed for ≥ 1 year (median duration of exposure 22.1 months). Patients treated with SOMATULINE DEPOT had a median age of 64 years (range 30-83 years), 53% were men and 96% were Caucasian. Eighty-one percent of patients (83/101) in the SOMATULINE DEPOT arm and eighty-two percent 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% in patients receiving SOMATULINE DEPOT 120 mg administered every 4 weeks and reported more commonly than placebo.
Table 3: Adverse Reactions Occurring in > 5% of
Somatuline Depot-Treated Patients and Occurring More Commonly Than in
Placebo-Treated Patients ( > 5% higher incidence) in Study 3
| Adverse Reaction | Somatuline Depot 120 mg N=101 |
Placebo N=103 |
||
| Any (%) | Severe** (%) | Any (%) | Severe** (%) | |
| Any Adverse Reactions | 88 | 26 | 90 | 31 |
| Abdominal pain1 | 34* | 6* | 24* | 4 |
| Musculoskeletal pain2 | 19* | 2* | 13 | 2 |
| Vomiting | 19* | 2* | 9* | 2* |
| Headache | 16 | 0 | 11 | 1 |
| Injection site reaction3 | 15 | 0 | 7 | 0 |
| Hyperglycemia4 | 14* | 0 | 5 | 0 |
| Hypertension5 | 14* | 1* | 5 | 0 |
| Cholelithiasis | 14* | 1* | 7 | 0 |
| Dizziness | 9 | 0 | 2* | 0 |
| Depression6 | 7 | 0 | 1 | 0 |
| Dyspnea | 6 | 0 | 1 | 0 |
| 1 Includes preferred terms of abdominal pain,
abdominal pain upper/lower, abdominal discomfort 2 Includes preferred terms of myalgia, musculoskeletal discomfort, musculoskeletal pain, back pain 3 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. 4 Includes preferred terms of diabetes mellitus, glucose tolerance impaired, hyperglycemia, type 2 diabetes mellitus 5 Includes preferred terms of hypertension, hypertensive crisis 6 Includes preferred terms of depression, depressed mood * 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. ** Defined as hazardous to well-being, significant impairment of function or incapacitation |
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.
In Study 3, development of anti-lanreotide antibodies was assessed using a radioimmunoprecipitation assay. In patients with GEP NETs receiving SOMATULINE DEPOT, the incidence of anti-lanreotide antibodies was 3.7% (3 of 82) at 24 weeks, 10.4% (7 of 67) at 48 weeks, 10.5% (6 of 57) at 72 weeks, and 9.5% (8 of 84) at 96 weeks. Assessment for neutralizing antibodies was not conducted.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to SOMATULINE DEPOT with the incidence of antibodies to other products may be misleading.
Postmarketing ExperienceAs 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, diarrhea, and steatorrhea), hepatobiliary disorders (cholecystitis), and general disorders and administration site conditions (injection site reactions). Occasional cases of pancreatitis have also been observed.
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.
Gastroenteropancreatic Neuroendocrine TumorsSOMATULINE DEPOT Injection 120 mg is indicated for the treatment of patients with unresectable, well-or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival.
Lanreotide has a high affinity for human somatostatin receptors (SSTR) 2 and 5 and a reduced binding affinity for human SSTR1, 3, and 4. Activity at human SSTR2 and 5 is the primary mechanism believed responsible for GH inhibition. Like somatostatin, lanreotide is an inhibitor of various endocrine, neuroendocrine, exocrine, and paracrine functions.
The primary pharmacodynamic effect of lanreotide is a reduction of GH and/or IGF-1 levels enabling normalization of levels in acromegalic patients. In acromegalic patients, lanreotide reduces GH levels in a dose-dependent way. After a single injection of SOMATULINE DEPOT, plasma GH levels fall rapidly and are maintained for at least 28 days.
Lanreotide inhibits the basal secretion of motilin, gastric inhibitory peptide, and pancreatic polypeptide, but has no significant effect on the secretion of secretin. Lanreotide inhibits postprandial secretion of pancreatic polypeptide, gastrin, and cholecystokinin (CCK). In healthy subjects, lanreotide produces a reduction and a delay in postprandial insulin secretion, resulting in transient, mild glucose intolerance.
Lanreotide inhibits meal-stimulated pancreatic secretions, and reduces duodenal bicarbonate and amylase concentrations, and produces a transient reduction in gastric acidity.
Lanreotide has been shown to inhibit gallbladder contractility and bile secretion in healthy subjects.
In healthy subjects, lanreotide inhibits meal-induced increases in superior mesenteric artery and portal venous blood flow, but has no effect on basal or meal-stimulated renal blood flow. Lanreotide has no effect on renal plasma flow or renal vascular resistance. However, a transient decrease in glomerular filtration rate (GFR) and filtration fraction has been observed after a single injection of lanreotide.
In healthy subjects, non-significant reductions in glucagon levels were seen after lanreotide administration. In diabetic non-acromegalic subjects receiving a continuous infusion (21-day) of lanreotide, serum glucose concentrations were temporarily decreased by 20-30% after the start and end of the infusion. Serum glucose concentrations returned to normal levels within 24 hours. A significant decrease in insulin concentrations was recorded between baseline and Day 1 only.
Lanreotide inhibits the nocturnal increase in thyroid-stimulating hormone (TSH) seen in healthy subjects. Lanreotide reduces prolactin levels in acromegalic patients treated on a long-term basis.
SOMATULINE DEPOT is thought to form a drug depot at the injection site due to the interaction of the formulation with physiological fluids. The most likely mechanism of drug release is a passive diffusion of the precipitated drug from the depot towards the surrounding tissues, followed by the absorption to the bloodstream.
After a single, deep subcutaneous administration, the mean absolute bioavailability of SOMATULINE DEPOT in healthy subjects was 73.4, 69.0, and 78.4% for the 60 mg, 90 mg, and 120 mg doses, respectively. Mean C max values ranged from 4.3 to 8.4 ng/mL during the first day. Single-dose linearity was demonstrated with respect to AUC and Cmax , and showed high inter-subject variability. SOMATULINE DEPOT showed sustained release of lanreotide with a half-life of 23 to 30 days. Mean serum concentrations were > 1 ng/mL throughout 28 days at 90 mg and 120 mg and > 0.9 ng/mL at 60 mg.
In studies evaluating excretion, < 5% of lanreotide was excreted in urine and less than 0.5% was recovered unchanged in feces, indicative of some biliary excretion.
AcromegalyIn a repeat-dose administration pharmacokinetics (PK) study in acromegalic patients, rapid initial release was seen giving peak levels during the first day after administration. At doses of SOMATULINE DEPOT between 60 and 120 mg, linear pharmacokinetics were observed in acromegalic patients. At steady state, mean C max values were 3.8 ± 0.5, 5.7 ± 1.7, and 7.7 ± 2.5 ng/mL, increasing linearly with dose. The mean accumulation ratio index was 2.7, which is in line with the range of values for the half-life of SOMATULINE DEPOT. The steady-state trough serum lanreotide concentrations in patients receiving SOMATULINE DEPOT every 28 days were 1.8 ± 0.3; 2.5 ± 0.9 and 3.8 ± 1.0 ng/mL at 60 mg, 90 mg, and 120 mg doses, respectively. A limited initial burst effect and a low peak-to-trough fluctuation (81% to 108%) of the serum concentration at the plateau were observed.
For the same doses, similar values were obtained in clinical studies after at least four administrations (2.3 ± 0.9, 3.2 ± 1.1, and 4.0 ± 1.4 ng/mL, respectively).
Pharmacokinetic data from studies evaluating extended dosing use of SOMATULINE DEPOT 120 mg demonstrated mean steady-state, C min values between 1.6 and 2.3 ng/mL for the 8-and 6-week treatment interval, respectively.
Gastroenteropancreatic Neuroendocrine TumorsIn patients with GEP-NETs treated with SOMATULINE DEPOT 120 mg every 4 weeks, steady state concentrations were reached after 4 to 5 injections and the mean trough serum lanreotide concentrations at steady state ranged from 5.3 to 8.6 ng/mL.
Lanreotide has been shown to have an embryocidal effect in rats and rabbits. There are no adequate and well-controlled studies in pregnant women. SOMATULINE DEPOT should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Reproductive studies in pregnant rats given 30 mg/kg by subcutaneous injection every 2 weeks (five times the human dose, based on body surface area comparisons) resulted in decreased embryo/fetal survival. Studies in pregnant rabbits given subcutaneous injections of 0.45 mg/kg/day (two times the human therapeutic exposures at the maximum recommended dose of 120 mg, based on comparisons of relative body surface area) shows decreased fetal survival and increased fetal skeletal/soft tissue abnormalities.
Injection: 60 mg/0.2 mL, 90 mg/0.3 mL and 120 mg/0.5 mL sterile, single-use, prefilled syringes fitted with an automatic needle guard. The prefilled syringes contain a white to pale yellow, semi-solid formulation.
SOMATULINE DEPOT is supplied in strengths of 60 mg/0.2 mL, 90 mg/0.3 mL, and 120 mg/0.5 mL in a single, sterile, prefilled, ready-to-use, polypropylene syringe (fitted with an automatic needle guard) fitted with a 20 mm needle covered by a low density polythylene sheath.
Each prefilled syringe is sealed in a laminated pouch and packed in a carton.
NDC 15054-1060-3 60 mg/0.2 mL, sterile, prefilled syringe
NDC 15054-1090-3 90 mg/0.3 mL, sterile, prefilled syringe
NDC 15054-1120-3 120 mg/0.5 mL, sterile, prefilled
syringe
SOMATULINE DEPOT must be stored in a refrigerator at 2°C to 8°C (36°F to 46°F) and protected from light in its original package. Thirty (30) minutes prior to injection, remove sealed pouch of SOMATULINE DEPOT from refrigerator and allow it to come to room temperature. Keep pouch sealed until injection.
Each syringe is intended for single use. Do not use beyond the expiration date on the packaging.
SOMATULINE DEPOT is manufactured by Ipsen Pharma Biotech, Parc d'Activities du Plateau de Signes, 83870 Signes, France for Ipsen Biopharmaceuticals, Inc., 106 Allen Road, Basking Ridge, NJ 07920 USA. Revised: December 2014.
Included as part of the PRECAUTIONS section.
PRECAUTIONS Cholelithiasis And Gallbladder SludgeLanreotide may reduce gallbladder motility and lead to gallstone formation; therefore, patients may need to be monitored periodically .
Hyperglycemia And HypoglycemiaPharmacological 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.
Thyroid Function AbnormalitiesSlight 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.
Cardiovascular AbnormalitiesThe 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%).
In 81 patients with baseline heart rates of ≥ 60 beats per minute (bpm) treated with SOMATULINE DEPOT in Study 3, the incidence of heart rate < 60 bpm was 23% (19/81) as compared to 16 % (15/94) of placebo treated patients; ten patients (12%) had documented heart rates < 60 bpm on more than one visit. The incidence of documented episodes of heart rate < 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.
Drug InteractionsThe 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.
Monitoring: Laboratory TestsAcromegaly: Serum GH and IGF-1 levels are useful markers of the disease and the effectiveness of treatment.
Patient Counseling InformationAdvise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION).
Advise patients to inform their doctor or pharmacist if they develop any unusual symptoms, or if any known symptom persists or worsens.
Advise patients with acromegaly that response to SOMATULINE DEPOT should be monitored by periodic measurements of GH and IGF-1 levels, with a goal of decreasing these levels to the normal range.
Advise patients experiencing dizziness not to drive or operate machinery.
Nonclinical Toxicology Carcinogenicity, Mutagenicity, Impairment Of FertilityStandard lifetime carcinogenicity bioassays were conducted in mice and rats. Mice were given daily subcutaneous doses of lanreotide acetate at 0.5, 1.5, 5, 10 and 30 mg/kg for 104 weeks. Cutaneous and subcutaneous tumors of fibrous connective tissues at the injection sites were observed at the high dose of 30 mg/kg/day. Fibrosarcomas in both genders and malignant fibrous histiocytomas were observed in males at 30 mg/kg/day resulting in exposures 3-times higher than the clinical therapeutic exposure at the maximum therapeutic dose of 120 mg given by monthly subcutaneous injection based on the AUC values. Rats were given daily subcutaneous doses of lanreotide acetate at 0.1, 0.2, and 0.5 mg/kg for 104 weeks. Increased cutaneous and subcutaneous tumors of fibrous connective tissues at the injection sites were observed at the dose of 0.5 mg/kg/day resulting in exposures less than the clinical therapeutic exposure at 120 mg given by monthly subcutaneous injection. The increased incidence of injection site tumors in rodents is likely related to the increased dosing frequency (daily) in animals compared to monthly dosing in humans and therefore may not be clinically relevant.
Lanreotide was not genotoxic in tests for gene mutations in a bacterial mutagenicity (Ames) assay, or mouse lymphoma cell assay with or without metabolic activation. Lanreotide was not genotoxic in tests for the detection of chromosomal aberrations in a human lymphocyte and in vivo mouse micronucleus assay.
Subcutaneous dosing (30mg/kg/2 wks) before mating and continuing into gestation in rats at doses five times the human clinical exposure (120 mg every 4 weeks) based on mg/m² had reduced fertility. Gestation length was statistically significantly increased suggesting some delay in parturition at three times the human exposure. The reduction in fertility in non-acromegalic animals is likely related to the pharmacologic activity (decreased growth hormone secretion) of lanreotide acetate.
Use In Specific Populations Pregnancy Pregnancy Category CLanreotide has been shown to have an embryocidal effect in rats and rabbits. There are no adequate and well-controlled studies in pregnant women. SOMATULINE DEPOT should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Reproductive studies in pregnant rats given 30 mg/kg by subcutaneous injection every 2 weeks (five times the human dose, based on body surface area comparisons) resulted in decreased embryo/fetal survival. Studies in pregnant rabbits given subcutaneous injections of 0.45 mg/kg/day (two times the human therapeutic exposures at the maximum recommended dose of 120 mg, based on comparisons of relative body surface area) shows decreased fetal survival and increased fetal skeletal/soft tissue abnormalities.
Nursing MothersIt is not known whether lanreotide is excreted in human milk. Many drugs are excreted in human milk. As a result of serious adverse reactions from SOMATULINE DEPOT in animals and, potentially in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, after taking into account the importance of the drug to the mother.
Pediatric UseSafety and effectiveness in pediatric patients have not been established.
Geriatric UseNo overall differences in safety or effectiveness were observed between elderly patients with acromegaly compared with younger patients and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Study 3, conducted in patients with GEP-NET, did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
AcromegalyIt is not necessary to alter the starting dose in elderly patients; lanreotide serum concentrations in the elderly are well within the range of serum concentrations safely tolerated in healthy young subjects. Similarly, it is not necessary to alter the titration or maintenance doses of SOMATULINE DEPOT, as dose selection is based on therapeutic response.
Gastroenteropancreatic Neuroendocrine TumorsNo dose adjustment required..
Renal Impairment AcromegalyLanreotide has been studied in patients with end-stage renal function on dialysis, but has not been studied in patients with mild, moderate, or severe renal impairment. It is recommended that patients with moderate or severe renal impairment receive a starting dose of lanreotide of 60 mg. Caution should be exercised when considering patients with moderate or severe renal impairment for an extended dosing interval of SOMATULINE DEPOT 120 mg every 6 or 8 weeks.
Gastroenteropancreatic Neuroendocrine TumorsNo effect was observed in total clearance of lanreotide in patients with mild to moderate renal impairment receiving SOMATULINE DEPOT 120 mg. Patients with severe renal impairment were not studied.
Hepatic Impairment AcromegalyIt is recommended that patients with moderate or severe hepatic impairment receive a starting dose of lanreotide of 60 mg. Caution should be exercised when considering patients with moderate or severe hepatic impairment for an extended dosing interval of SOMATULINE DEPOT 120 mg every 6 or 8 weeks.
Gastroenteropancreatic Neuroendocrine TumorsSOMATULINE DEPOT has not been studied in patients with hepatic impairment.
Somatuline Depot should be administered by healthcare professionals. Please see enclosed Instructions for Use Leaflet for administration of Somatuline Depot.
AcromegalyPatients 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:
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.
Patients who are controlled on SOMATULINE DEPOT 60 mg 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 dose adjustments for biochemical and clinical symptom control, as necessary, is recommended.
The starting dose in patients with moderate or severe renal impairment or moderate or 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.
Gastroenteropancreatic Neuroendocrine TumorsThe recommended dose of SOMATULINE DEPOT is 120 mg administered every 4 weeks by deep subcutaneous injection. There is no recommended dose adjustment for mild or moderate renal impairment. There is insufficient information to recommend a dose for patients with severe renal impairment or with hepatic impairment of any severity.
AdministrationSOMATULINE DEPOT is provided in a single-dose, prefilled syringe affixed with an automatic needle protection system. Inject SOMATULINE DEPOT via the deep subcutaneous route in the superior external quadrant of the buttock. Alternate the injection site between the right and left sides from one injection to the next. Remove SOMATULINE DEPOT from the refrigerator 30 minutes prior to administration. Keep pouch sealed until just prior to injection.
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.
