In this section, you will find the following information about
Sandostatin® LAR Depot:
- Clinical Effectiveness
- Pharmacokinetics of Sandostatin® LAR Depot
- Clinical Study Design for Sandostatin® LAR Depot Efficacy Determinations
- Patients Reporting Clinical Symptoms
- Conclusions: Efficacy Profile for Sandostatin® LAR Depot in Carcinoid Syndrome
Clinical Effectiveness1
Sandostatin® LAR Depot (octreotide acetate for injectable suspension) is a 28-day long-acting formulation of a proven medication, subcutaneously injected immediate-release Sandostatin® (octreotide acetate) Injection. How can a 28-day long-acting formulation maintain the clinical effectiveness of a daily-injected formulation?
Sandostatin® LAR Depot:
- Incorporates octreotide into microspheres of the biodegradable glucose star polymer, D,L-lactic, and glycolic acids copolymer
- Releases octreotide slowly over time
- Maintains all of the clinical and pharmacological characteristics of the immediate-release dosage form (immediate-release Sandostatin® Injection)
- Has a different pharmacokinetic profile than immediate-release Sandostatin® Injection, allowing for once-monthly injections
Blood glucose levels should be monitored when Sandostatin® LAR Depot treatment is initiated or when the dose is altered. Hypoglycemia or hyperglycemia may occur.
Pharmacokinetics of Sandostatin® LAR Depot1
In patients with carcinoid tumors, the mean octreotide concentrations after 6 doses of 10 mg, 20 mg, and 30 mg Sandostatin® LAR Depot administered by IM injection every four weeks were 1.2 ng/mL, 2.5 ng/mL, and 4.2 ng/mL, respectively. Concentrations were dose proportional and steady-state concentrations were reached after 2 injections of 20 mg and 30 mg and after 3 injections of 10 mg.
Sandostatin® LAR Depot has not been studied in patients with renal or hepatic impairment.
Clinical Study Design for Sandostatin® LAR Depot Efficacy Evaluation1
The efficacy of Sandostatin® LAR Depot for treatment of carcinoid tumors and VIPomas has been evaluated in one phase 3 study.
Because Sandostatin® LAR Depot is appropriate and tolerated for patients who have been shown to respond to and tolerate immediate-release Sandostatin® Injection, clinical trials of Sandostatin® LAR Depot were performed in patients who had been receiving immediate-release Sandostatin® Injection. These were patients with carcinoid tumors and VIPomas that had responded to and tolerated Sandostatin® Injection. Adverse events were also monitored.
A total of 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. Treatment was monitored for 6 months.
A 12-month extension study enrolled 78 patients with malignant carcinoid syndrome who had participated in this 6-month trial. In the extension study, patients received 12 injections of Sandostatin® LAR Depot at 4-week intervals.
Patients Reporting Clinical Symptoms1
Over the 6-month treatment period approximately 50%-70% of patients required supplemental Sandostatin® Injection to control severe carcinoid symptoms even though steady-state serum Sandostatin® LAR Depot levels had been reached.
The table below presents the average number of daily stools and flushing episodes in malignant carcinoid patients. Overall, mean daily stool frequency was well controlled on Sandostatin® LAR Depot as on Sandostatin® Injection (approximately 2 to 2.5 stools/day). Mean daily flushing episodes were similar at all doses of Sandostatin® LAR Depot and on Sandostatin® Injection (approximately 0.5 to 1 episode/day).
Average No. of Daily Stools and Flushing Episodes in Patients With Malignant Carcinoid Syndrome |
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Conclusions: Efficacy Profile for Sandostatin® LAR Depot in Carcinoid Syndrome
- Powerful control of severe diarrhea and flushing episodes
associated with carcinoid syndrome1 - Powerful control of severe watery diarrhea associated with VIP-secreting tumors1
- Consistent drug exposure, dose to dose1
- Proven strength and a more than 20-year heritage of success1,2
- Convenient dosing for continuing therapy1
- The immediate-release formulation can be used for additional control for symptom flare-ups 1
Gallbladder abnormalities may occur. Patients should be monitored periodically
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%).
