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Somatuline Depot (Lanreotide Acetate) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

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.

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 ], are provided in Table 1.

Table 1 Adverse Reactions at an Incidence > 5% Lanreotide Overall and Occurring at Higher Rate in Drug than Placebo: Placebo-Controlled and Fixed-Dose Phase of Study 1 by Dose
Placebo-Controlled Double-Blind Phase
Weeks 0 to 4
Fixed-Dose Phase
Double-Blind + Single-Blind
Weeks 0 to 20
Body System
  Preferred Term
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 (%)

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 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 [see Clinical Studies ].

Table 2 Adverse Reactions at an Incidence > 5.0% in Overall Group Reported in Clinical Studies
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 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 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 ].

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 ].

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 ].

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, diarrhea, and steatorrhea), hepatobiliary disorders (cholecystitis), and general disorders and administration site conditions (injection site reactions). Occasional cases of pancreatitis have also been observed.

A small number of allergic reactions associated with lanreotide (including angioedema, anaphylaxis, and hypersensitivity) have been reported in the postmarketing environment.



REPORTS OF SUSPECTED SOMATULINE DEPOT SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Somatuline Depot. The information is not vetted and should not be considered as verified clinical evidence.

Possible Somatuline Depot side effects / adverse reactions in 30 year old male

Reported by a health professional (non-physician/pharmacist) from Netherlands on 2011-10-07

Patient: 30 year old male weighing 106.0 kg (233.2 pounds)

Reactions: Injection Site Abscess

Suspect drug(s):
Somatuline Depot

Other drugs received by patient: Somavert; Lantus; Novolog



Possible Somatuline Depot side effects / adverse reactions in 59 year old male

Reported by a health professional (non-physician/pharmacist) from Netherlands on 2011-10-21

Patient: 59 year old male weighing 81.0 kg (178.2 pounds)

Reactions: Injection Site Extravasation, Injection Site Pruritus

Suspect drug(s):
Somatuline Depot
    Dosage: 120mg (120 mg, 1 in 28 d), intramuscular
    Indication: Acromegaly
    Start date: 2011-09-16
    End date: 2011-09-16

Somatuline Depot
    Dosage: 120mg (120 mg, 1 in 28 d), intramuscular
    Indication: Acromegaly
    Start date: 2011-06-30
    End date: 2011-06-30

Other drugs received by patient: Amlodipine; Lantus; Metformin HCL; Novolog



Possible Somatuline Depot side effects / adverse reactions in 21 year old male

Reported by a individual with unspecified qualification from United States on 2011-10-21

Patient: 21 year old male

Reactions: Pituitary Tumour Removal, Balance Disorder, Abasia

Adverse event resulted in: hospitalization

Suspect drug(s):
Somatuline Depot



See index of all Somatuline Depot side effect reports >>

Drug label data at the top of this Page last updated: 2014-06-18

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