DOSAGE AND ADMINISTRATION
Sandostatin LAR® Depot (octreotide acetate for injectable suspension) must be administered under the supervision of a physician. Do not directly inject diluent without preparing suspension. It is important to closely follow the mixing instructions included in the packaging. Sandostatin LAR® Depot must be administered immediately after mixing. Sandostatin LAR® Depot should be administered intragluteally at four-week intervals. Administration of Sandostatin LAR® Depot at intervals greater than 4 weeks is not recommended because there is no adequate information on whether such patients could be satisfactorily controlled. Deltoid injections are to be avoided because of significant discomfort at the injection site when given in that area. Sandostatin LAR® Depot should never be administered by the IV or S.C. routes. The following dosage regimens are recommended.
ACROMEGALY
1. PATIENTS NOT CURRENTLY RECEIVING OCTREOTIDE ACETATE
Patients not currently receiving octreotide acetate should begin therapy with Sandostatin® (octreotide acetate) Injection given subcutaneously in an initial dose of 50 mcg t.i.d. Beginning with this low dose may permit adaptation to adverse gastrointestinal effects for patients who require higher doses. Multiple growth hormone (GH) determinations at 0-8 hours after a subcutaneous Sandostatin® Injection will guide dosage titration. The goal is to attempt to normalize GH and IGF-1 (somatomedin C) levels. Most patients require doses of 100 mcg to 200 mcg t.i.d. for maximum effect but some patients require up to 500 mcg t.i.d. Injection sites should be rotated in a systematic manner to avoid irritation.
Although responsiveness of GH to octreotide acetate can be ascertained quickly, patients should be maintained on Sandostatin® Injection s.c. for at least 2 weeks to determine tolerance to octreotide.
The most common adverse events are gastrointestinal, which usually begin within the first few days of administration and usually subside within 2 to 8 weeks. In clinical trials, <3% of patients discontinued Sandostatin® Injection because of G.I. symptoms.
Patients who are considered to be "responders" to the drug, based on GH and IGF-1 levels, and who tolerate the drug, can then be switched to Sandostatin LAR® Depot in the dosage scheme described under 2, below (Patients Currently Receiving Sandostatin® Injection).
2. PATIENTS CURRENTLY RECEIVING SANDOSTATIN®(OCTREOTIDE ACETATE) INJECTION
Patients currently receiving Sandostatin® Injection can be switched directly to Sandostatin LAR® Depot in a dose of 20 mg given IM intragluteally at 4-week intervals for 3 months. (Deltoid injections are to be avoided because of significant discomfort at the injection site when given in that area.) Gluteal injection sites should be alternated to avoid irritation.
At the end of 3 months Sandostatin LAR® Depot dosage may be continued at the same level or increased or decreased based on the following regimen:
GH
GH >2.5 ng/mL, IGF-1 elevated, and/or clinical symptoms uncontrolled, increase Sandostatin LAR® Depot dosage to 30 mg every 4 weeks.
GH
Patients whose GH, IGF-1, and symptoms are not adequately controlled at a dose of 30 mg may have the dose increased to 40 mg every 4 weeks. Doses higher than 40 mg are not recommended.
Administration of Sandostatin LAR® Depot at intervals greater than 4 weeks is not recommended because there is no adequate information on whether such patients could be satisfactorily controlled.
In patients who have received pituitary irradiation, Sandostatin LAR® Depot should be withdrawn yearly for approximately 8 weeks to assess disease activity. If GH or IGF-1 levels increase and signs and symptoms recur, Sandostatin LAR® Depot therapy may be resumed.
3. SPECIAL POPULATIONS: RENAL FAILURE
In patients with renal failure requiring dialysis, the half-life of octreotide may be increased, necessitating adjustment of the maintenance dosage (see CLINICAL PHARMACOLOGY and Pharmacokinetics of Octreotide Acetate).
CARCINOID TUMORS AND VIPOMAS
1. PATIENTS NOT CURRENTLY RECEIVING OCTREOTIDE ACETATE
Patients not currently receiving octreotide acetate should begin therapy with Sandostatin® Injection given subcutaneously. The suggested daily dosage for carcinoid tumors during the first 2 weeks of therapy ranges from 100-600 mcg/day in 2-4 divided doses (mean daily dosage is 300 mcg). Some patients may require doses up to 1500 mcg/day. The suggested daily dosage for VIPomas is 200-300 mcg in 2-4 divided doses (range 150-750 mcg); dosage may be adjusted on an individual basis to control symptoms but usually doses above 450 mcg/day are not required.
Sandostatin® Injection should be continued for at least 2 weeks. Thereafter, patients who are considered "responders" to octreotide acetate and who tolerate the drug may be switched to Sandostatin LAR® Depot in the dosage regimen described under 2, below (Patients Currently Receiving Sandostatin® Injection).
2. PATIENTS CURRENTLY RECEIVING SANDOSTATIN®(OCTREOTIDE ACETATE) INJECTION
Patients currently receiving Sandostatin® Injection can be switched to Sandostatin LAR® Depot in a dosage of 20 mg given IM intragluteally at 4-week intervals for 2 months. Deltoid injections are to be avoided because of significant discomfort at the injection site when given in that area. Gluteal injection sites should be alternated to avoid irritation. Because of the need for serum octreotide to reach therapeutically effective levels following initial injection of Sandostatin LAR® Depot, carcinoid tumor and VIPoma patients should continue to receive Sandostatin® Injection s.c. for at least 2 weeks in the same dosage they were taking before the switch. Failure to continue subcutaneous injections for this period may result in exacerbation of symptoms. (Some patients may require 3 or 4 weeks of such therapy.)
After two months of a 20-mg dosage of Sandostatin LAR® Depot, dosage may be increased to 30 mg every 4 weeks if symptoms are not adequately controlled. Patients who achieve good control on a 20-mg dose may have their dose lowered to 10 mg for a trial period. If symptoms recur, dosage should then be increased to 20 mg every 4 weeks. Many patients can, however, be satisfactorily maintained at a 10-mg dosage every 4 weeks. A dose of 10 mg is not recommended as a starting dose, however, because therapeutically effective levels of octreotide are reached more rapidly with a 20-mg dose.
Dosages higher than 30 mg are not recommended because there is no information on their usefulness.
Despite good overall control of symptoms, patients with carcinoid tumors and VIPomas often experience periodic exacerbation of symptoms (regardless of whether they are being maintained on Sandostatin® Injection or Sandostatin LAR® Depot). During these periods they may be given Sandostatin® Injection s.c. for a few days at the dosage they were receiving prior to switch to Sandostatin LAR® Depot. When symptoms are again controlled, the Sandostatin® Injection s.c. can be discontinued.
Administration of Sandostatin LAR® Depot at intervals greater than 4 weeks is not recommended because there is no adequate information on whether such patients could be adequately controlled.
3. SPECIAL POPULATIONS: RENAL FAILURE
In patients with renal failure requiring dialysis, the half-life of octreotide may be increased, necessitating adjustment of the maintenance dosage (see CLINICAL PHARMACOLOGY and Pharmacokinetics of Octreotide Acetate).
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