In this section, you'll find the following information about the safety of Sandostatin® LAR Depot:
Safety Profile of Sandostatin® LAR Depot
Safety data were obtained from one study with the following results:
- The most common adverse events were nausea, headache, back pain, and abdominal pain
- Patient-reported pain at the injection site was noted by about 20% to 25% at a 10-mg dose and about 30% to 50% at the 20-mg and 30-mg dose
Adverse Reactions1
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 VIPomas1
The safety of Sandostatin® LAR Depot in the treatment of carcinoid tumors and VIPomas has been evaluated in one phase 3 study; 93 patients with carcinoid syndrome were randomized to Sandostatin® LAR Depot 10 mg, 20 mg, or 30 mg in a blind fashion or to open-label Sandostatin® Injection subcutaneously (SC). The population age range was between 25-78 years old and 44% were female, 95% were Caucasian and 3% black. All the patients had symptom control on their previous Sandostatin® subcutaneous treatment. Eighty patients finished the initial 24 weeks of Sandostatin® exposure; comparable numbers of patients were randomized to each dose. The table below reflects the adverse events occurring in ≥15% of patients regardless of presumed causality to study drug.
Adverse Events Occurring in ≥15% of Carcinoid Tumor and VIPoma Patients
| Adverse Event |
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.
Postmarketing 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 postmarketing 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 postmarketing 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.
INDICATIONS AND USAGE
Sandostatin® LAR Depot (octreotide acetate for injectable suspension) is indicated for patients in whom initial treatment with immediate release Sandostatin® (octreotide acetate) Injection has been shown to be effective and tolerated for:
- Long-term maintenance therapy in acromegalic patients who have had 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).
- Long-term treatment of the severe diarrhea and flushing episodes associated with metastatic carcinoid tumors.
- Long-term treatment of the profuse watery diarrhea associated with VIP-secreting tumors.
In patients with carcinoid syndrome and VIPomas, the effect of Sandostatin Injection and Sandostatin LAR Depot on tumor size, rate of growth and development of metastases has not been determined.
IMPORTANT SAFETY INFORMATION
Warnings and Precautions:
- Gallbladder abnormalities may occur: Patients should be monitored periodically.
- Glucose Metabolism: Hypoglycemia or hyperglycemia may occur. Blood glucose levels should be monitored when Sandostatin LAR Depot treatment is initiated or when the dose is altered. Antidiabetic treatment should be adjusted accordingly.
- Thyroid Function: Hypothyroidism may occur. Baseline and periodic assessment of thyroid function (TSH, total and/or free T4) is recommended.
- Cardiac Function: Bradycardia, arrhythmia, conduction abnormalities, and other EKG changes may occur. The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac disease. Use with caution in at-risk patients.
- Nutrition: Octreotide may alter absorption of dietary fats. Monitoring of vitamin B12 levels is recommended during therapy with Sandostatin LAR Depot. Patients on total parenteral nutrition (TPN) and octreotide should have periodic monitoring of zinc levels.
Drug Interactions: The following drugs require monitoring and possible dose adjustment when used with Sandostatin LAR Depot: cyclosporine, insulin, oral hypoglycemic agents, beta-blockers, bromocriptine. Octreotide has been associated with alterations in nutrient absorption, so it may have an effect on absorption of orally administered drugs. Drugs mainly metabolized by CYP3A4 and which have a low therapeutic index should be used with caution.
Adverse Reactions: The most common adverse reactions occurring in patients receiving Sandostatin LAR Depot are:
- Acromegaly: biliary abnormalities (52%), diarrhea (36-48%), cholelithiasis (13-38%), abdominal pain or discomfort (11-29%), flatulence (26%), influenza-like symptoms (20%), constipation (19%), headache (15%), anemia (15%), hyperglycemia (15%), injection site pain (2-14%), hypertension (13%), dizziness (12%), fatigue (11%), nausea (10%), vomiting (7%), hypothyroidism (2%), hypoglycemia (2%), and goiter (2%).
- Carcinoid Tumors and VIPomas: biliary abnormalities (62%), injection site pain (20-50%), nausea (24-41%), abdominal pain (10-35%), fatigue (8-32%), headache (16-30%), hyperglycemia (27%), back pain (8-27%), constipation or vomiting (15-21%), dizziness (18-20%), sinus bradycardia (19%), pruritus (18%), URTI (10-18%), myalgia (4-18%), flatulence (9-16%), arthropathy (8-15%), rash (15%), generalized pain (4-15%), sinusitis (5-12%), conduction abnormalities (9%), hypoglycemia (4%), and arrhythmia (3%).
