In this section, you will find the following information about
Sandostatin® LAR Depot (octreotide acetate for injectable suspension):
- 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 maintains all of the clinical and pharmacological characteristics of the immediate-release dosage form (immediate release Sandostatin® Injection)
- Sandostatin® LAR Depot incorporates octreotide into microspheres of the biodegradable glucose star polymer, D,L-lactic, and glycolic acids copolymer
- Slow drug release accompanies the biodegradation of the polymer ester bond through hydrolysis
- Sandostatin® LAR Depot has a different pharmacokinetic profile than immediate release Sandostatin® Injection, allowing for once-monthly injections
- Sandostatin® LAR Depot formulation releases octreotide slowly over time
Pharmacokinetics of Sandostatin® LAR Depot
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 two injections of 20 mg and 30 mg and after three 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 Determination1
The efficacy of Sandostatin® LAR Depot for treatment of carcinoid tumors and VIPomas has been evaluated in one phase 3 study.
- In Study 1, 93 patients were enrolled. Treatment was monitored for 6 months
- A 12-month extension enrolled 78 patients who had participated in Study 1
Study 1 evaluates the safety of Sandostatin® LAR Depot in the treatment of carcinoid tumors and VIPomas who had previously been responsive to Sandostatin® Injection. Adverse events were also monitored.
Because Sandostatin® LAR Depot is appropriate 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.
Ninety-three 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.
Seventy-eight patients with malignant carcinoid syndrome who had participated in this 6-month trial went on to participate in a 12-month extension study. In the extension study, patients received 12 injections of Sandostatin® LAR Depot at 4-week intervals.
Patients Reporting Clinical Symptoms
In Study 1, over the 6-month treatment period approximately 50% to 70% of patients required supplemental Sandostatin® Injection to control severe carcinoid symptoms even though steady-state serum Sandostatin® LAR Depot levels had been reached.
Table 1 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).
Table 1. Average Number 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 metastatic carcinoid tumors - Powerful control of severe watery diarrhea associated with VIP-secreting tumor1
- Consistent drug exposure, dose to dose1
- Proven strength and a 20-year heritage of success2,3
- Convenient dosing for continuing therapy1
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.
