Safety Profile of Sandostatin® LAR Depot (octreotide acetate for injectable suspension)
Safety data were obtained from one study with the following results:
- Clinical symptoms of carcinoid syndrome were reduced during treatment1
- The most common adverse events were nausea, headache, back pain, and abdominal pain
- Local tolerability at the injection site was demonstrated; injection-site reactions were generally mild to moderate and dose related1
- Short-lived injection-site pain after IM administration—discomfort lasting usually less than 1 hour—was reported in 2%, 9%, and 11% of patients, respectively, receiving 10 mg, 20 mg, and 30 mg of Sandostatin® LAR Depot1
Adverse Reactions
Clinical Studies 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 trial of another drug and may not reflect the rates observed in practice.
Carcinoid and VIPomas
The safety of Sandostatin® LAR Depot in the treatment of carcinoid tumors and VIPomas has been evaluated in one phase 3 study. Study 1 randomized 93 patients with carcinoid syndrome to Sandostatin® LAR Depot 10 mg, 20 mg or 30 mg in a blind fashion or to open label Sandostatin® Injection subcutaneously. The population age range was between 25-78 years old and 44% were female, 95% were Caucasian and 3% African American. All the patients had symptom control on their previous Sandostatin® subcutaneous treatment. Eighty patients finished the initial 24 weeks of Sandostatin® exposure in study 1. In study 1, comparable numbers of patients were randomized to each dose. Table 4 below reflects the adverse events occurring in ≥15% of patients regardless of presumed causality to study drug.
Table 1. Adverse Events Occurring in ≥15% of
Carcinoid Tumor and VIPoma Patients in Study 1
| WHO Preferred Term |
Study 1 Number (%) of Subjects with AEs (n=93) |
|||
|---|---|---|---|---|
| Sc N=26 |
10 mg N=22 |
20 mg N=20 |
30 mg N=25 |
|
| Abdominal Pain | 8 (30.8) | 8 (35.4) | 2 (10.0) | 5 (20.0) |
| Arthropathy | 5 (19.2) | 2 (9.1) | 3 (15.0) | 2 (8.0) |
| Back Pain | 7 (26.9) | 6 (27.3) | 2 (10.0) | 2 (8.0) |
| Dizziness | 4 (15.4) | 4 (18.2) | 4 (20.0) | 5 (20.0) |
| Fatigue | 3 (11.5) | 7 (31.8) | 2 (10.0) | 2 (8.0) |
| Flatulence | 3 (11.5) | 2 (9.1) | 2 (10.0) | 4 (16.0) |
| Generalized Pain | 4 (15.4) | 2 (9.1) | 3 (15.0) | 1 (4.0) |
| Headache | 5 (19.2) | 4 (18.2) | 6 (30.0) | 4 (16.0) |
| Musculoskeletal Pain |
4 (15.4) | 0 | 1 (5.0) | 0 |
| Myalgia | 0 | 4 (18.2) | 1 (5.0) | 1 (4.0) |
| Nausea | 8 (30.8) | 9 (40.9) | 6 (30.0) | 6 (24.0) |
| Pruritus | 0 | 4 (18.2) | 0 | 0 |
| Rash | 1 (3.8) | 0 | 3 (15.0) | 0 |
| Sinusitis | 4 (15.4) | 0 | 1 (5.0) | 3 (12.0) |
| URTI | 6 (23.1) | 4 (18.2) | 2 (10.0) | 3 (12.0) |
| Vomiting | 3 (11.5) | 0 | 0 | 4 (16.0) |
Gallbladder Abnormalities
In clinical trials 62% of malignant carcinoid patients who received Sandostatin® LAR Depot for up to 18 months developed new biliary abnormalities including jaundice, gallstones, sludge and dilatation. New gallstones occurred in a total of 24% of patients.
Glucose Metabolism - Hypoglycemia/Hyperglycemia
In carcinoid patients, hypoglycemia occurred in 4% and hyperglycemia in 27% of patients treated with Sandostatin® LAR Depot.
Hypothyroidism
In carcinoid patients, hypothyroidism has only been reported in isolated patients and goiter has not been reported.
Cardiac
Electrocardiograms were performed only in carcinoid patients receiving Sandostatin® LAR Depot. In carcinoid syndrome patients sinus bradycardia developed in 19%, conduction abnormalities occurred in 9%, and arrhythmias developed in 3%. The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac disease.
Other Clinical Studies Adverse Events
Other clinically significant adverse events (relationship to drug not established) in acromegalic and/or carcinoid syndrome patients receiving Sandostatin® LAR Depot were malignant hyperpyrexia, cerebral vascular disorder, rectal bleeding, ascites, pulmonary embolism, pneumonia, and pleural effusion.
Post-Marketing Experience
The following adverse reactions have been identified during the post-approval use of Sandostatin®. Because these reactions 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.
Myocardial infarction has been observed in the post-marketing setting, mainly in patients with cardiovascular risk factors. Hypoadrenalism has been reported in some reports in patients 18 months of age and under.
Additional events reported in the post-marketing setting include anaphylactoid reactions, including anaphylactic shock, cardiac arrest, renal failure, renal insufficiency, convulsions, atrial fibrillation, aneurysm, hepatitis, increased liver enzymes, gastrointestinal hemorrhage, pancreatitis, pancytopenia, thrombocytopenia, arterial thrombosis of the arm, retinal vein thrombosis, intracranial hemorrhage, hemiparesis, paresis, deafness, visual field defect, aphasia, scotoma, status asthmaticus, pulmonary hypertension, diabetes mellitus, intestinal obstruction, peptic/gastric ulcer, appendicitis, creatinine increased, CK increased, arthritis, joint effusion, pituitary apoplexy, breast carcinoma, suicide attempt, paranoia, migraines, urticaria, facial edema, generalized edema, hematuria, orthostatic hypotension, Raynaud's syndrome, glaucoma, pulmonary nodule, pneumothorax aggravated, cellulitis, Bell's palsy, diabetes insipidus, gynecomastia, galactorrhea, gallbladder polyp, fatty liver, abdomen enlarged, libido decrease, and petechiae.
Important Safety Information
Carcinoid Syndrome:
Sandostatin® LAR Depot (octreotide acetate for injectable suspension) is indicated for long-term treatment of the severe diarrhea and flushing episodes associated with metastatic carcinoid tumors and for the long-term treatment of the profuse watery diarrhea associated with VIP-secreting tumors in patients in whom initial treatment with immediate release Sandostatin® (octreotide acetate) Injection has been shown to be effective and tolerated.
Important Safety Information:
As with immediate release Sandostatin® Injection, the most frequently reported drug-related adverse events were biliary disorders (62%), gastrointestinal disorders (14% to 38%), and injection-site pain (20% to 50%). Hypoglycemia (4%), hyperglycemia (27%), sinus bradycardia (19%), conduction abnormalities (9%), and arrhythmias (3%) have been reported.
The controlled clinical trials that support the marketing clearance for Sandostatin® LAR Depot did not include determination of effect on tumor size or rate of growth. Sandostatin® LAR Depot is not indicated for tumor shrinkage.
Acromegaly
Sandostatin® LAR Depot (octreotide acetate for injectable suspension) is indicated for long-term maintenance therapy in 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 GH and IGF-1 levels to normal.
Important Safety Information:
As with immediate release Sandostatin® Injection, the most frequently reported drug-related adverse events were biliary disorders (52%), gastrointestinal disorders (7% to 36%), and injection-site pain (2% to 11%). Hypoglycemia (2%), hyperglycemia (15%), and hypothyroidism (2%) have been reported. While not measured in acromegalic patients receiving Sandostatin® LAR Depot, ECG changes have been reported in patients receiving immediate release Sandostatin® Injection; the degree to which these abnormalities are related to octreotide acetate is not clear, as many acromegalics have cardiovascular disease. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
