Sandostatin® (octreotide acetate) Injection, a cyclic octapeptide prepared as a clear sterile solution of octreotide, acetate salt, in a buffered lactic acid solution for administration by deep subcutaneous (intrafat) or intravenous injection. Octreotide acetate, known chemically as L-Cysteinamide, D-phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-N-[2-hydroxy-1-(hydroxymethyl)propyl]-, cyclic (2-7)-disulfide; [R-(R*, R*)] acetate salt, is a long-acting octapeptide with pharmacologic actions mimicking those of the natural hormone somatostatin.

Sandostatin Injection is available as: sterile 1-mL ampuls in 3 strengths, containing 50, 100, or 500 mcg octreotide (as acetate), and sterile 5-mL multi-dose vials in 2 strengths, containing 200 and 1000 mcg/mL of octreotide (as acetate).

Each ampul also contains:

lactic acid, USP ..... 3.4 mg
mannitol, USP ..... 45 mg
sodium bicarbonate, USP ..... qs to pH 4.2 ± 0.3
water for injection, USP ..... qs to 1 mL

Each mL of the multi-dose vials also contains:

lactic acid, USP ..... 3.4 mg
mannitol, USP ..... 45 mg
phenol, USP ..... 5.0 mg
sodium bicarbonate, USP ..... qs to pH 4.2 ± 0.3
water for injection, USP ..... qs to 1 mL

Lactic acid and sodium bicarbonate are added to provide a buffered solution, pH to 4.2 ± 0.3.

The molecular weight of octreotide acetate is 1019.3 (free peptide, C₄₉H₆₆N₁₀O₁₀S₂) and its amino acid sequence is:

H-D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol,
xCH₃COOH           where x = 1.4 to 2.5

Last updated on RxList: 10/17/2008

Acromegaly

Sandostatin® (octreotide acetate) is indicated to reduce blood levels of growth hormone and IGF-I (somatomedin C) in acromegaly patients who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses. The goal is to achieve normalization of growth hormone and IGF-I (somatomedin C) levels (See DOSAGE AND ADMINISTRATION). In patients with acromegaly, Sandostatin reduces growth hormone to within normal ranges in 50% of patients and reduces IGF-I (somatomedin C) to within normal ranges in 50%-60% of patients. Since the effects of pituitary irradiation may not become maximal for several years, adjunctive therapy with Sandostatin to reduce blood levels of growth hormone and IGF-I (somatomedin C) offers potential benefit before the effects of irradiation are manifested.

Improvement in clinical signs and symptoms or reduction in tumor size or rate of growth were not shown in clinical trials performed with Sandostatin; these trials were not optimally designed to detect such effects.

Carcinoid Tumors

Sandostatin is indicated for the symptomatic treatment of patients with metastatic carcinoid tumors where it suppresses or inhibits the severe diarrhea and flushing episodes associated with the disease.

Sandostatin studies were not designed to show an effect on the size, rate of growth or development of metastases.

Vasoactive Intestinal Peptide Tumors (VIPomas)

Sandostatin is indicated for the treatment of the profuse watery diarrhea associated with VIP-secreting tumors. Sandostatin studies were not designed to show an effect on the size, rate of growth or development of metastases.

Sandostatin® (octreotide acetate) may be administered subcutaneously or intravenously. Subcutaneous injection is the usual route of administration of Sandostatin for control of symptoms. Pain with subcutaneous administration may be reduced by using the smallest volume that will deliver the desired dose. Multiple subcutaneous injections at the same site within short periods of time should be avoided. Sites should be rotated in a systematic manner.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use if particulates and/or discoloration are observed. Proper sterile technique should be used in the preparation of parenteral admixtures to minimize the possibility of microbial contamination. Sandostatin is not compatible in Total Parenteral Nutrition (TPN) solutions because of the formation of a glycosyl octreotide conjugate which may decrease the efficacy of the product.

Sandostatin is stable in sterile isotonic saline solutions or sterile solutions of dextrose 5% in water for 24 hours. It may be diluted in volumes of 50-200 mL and infused intravenously over 15-30 minutes or administered by IV push over 3 minutes. In emergency situations (e.g., carcinoid crisis) it may be given by rapid bolus.

The initial dosage is usually 50 mcg administered twice or three times daily. Upward dose titration is frequently required. Dosage information for patients with specific tumors follows.

Acromegaly

Dosage may be initiated at 50 mcg t.i.d. Beginning with this low dose may permit adaptation to adverse gastrointestinal effects for patients who will require higher doses. IGF-I (somatomedin C) levels every 2 weeks can be used to guide titration. Alternatively, multiple growth hormone levels at 0-8 hours after Sandostatin® (octreotide acetate) administration permit more rapid titration of dose. The goal is to achieve growth hormone levels less than 5 ng/mL or IGF-I (somatomedin C) levels less than 1.9 U/mL in males and less than 2.2 U/mL in females. The dose most commonly found to be effective is 100 mcg t.i.d., but some patients require up to 500 mcg t.i.d. for maximum effectiveness. Doses greater than 300 mcg/day seldom result in additional biochemical benefit, and if an increase in dose fails to provide additional benefit, the dose should be reduced. IGF-I (somatomedin C) or growth hormone levels should be re-evaluated at 6-month intervals.

Sandostatin should be withdrawn yearly for approximately 4 weeks from patients who have received irradiation to assess disease activity. If growth hormone or IGF-I (somatomedin C) levels increase and signs and symptoms recur, Sandostatin therapy may be resumed.

Carcinoid Tumors

The suggested daily dosage of Sandostatin during the first 2 weeks of therapy ranges from 100-600 mcg/day in 2-4 divided doses (mean daily dosage is 300 mcg). In the clinical studies, the median daily maintenance dosage was approximately 450 mcg, but clinical and biochemical benefits were obtained in some patients with as little as 50 mcg, while others required doses up to 1500 mcg/day. However, experience with doses above 750 mcg/day is limited.

VIPomas

Daily dosages of 200-300 mcg in 2-4 divided doses are recommended during the initial 2 weeks of therapy (range 150-750 mcg) to control symptoms of the disease. On an individual basis, dosage may be adjusted to achieve a therapeutic response, but usually doses above 450 mcg/day are not required.

Sandostatin® (octreotide acetate) Injection is available in 1-mL ampuls and 5-mL multi-dose vials as follows:

Ampuls

50 mcg/mL octreotide (as acetate)

Package of 10 ampuls NDC 0078-0180-01

100 mcg/mL octreotide (as acetate)

Package of 10 ampuls NDC 0078-0181-01

500 mcg/mL octreotide (as acetate)

Package of 10 ampuls NDC 0078-0182-01

Multi-Dose Vials

200 mcg/mL octreotide (as acetate)

Box of one NDC 0078-0183-25

1000 mcg/mL octreotide (as acetate)

Box of one NDC 0078-0184-25

Storage

For prolonged storage, Sandostatin ampuls and multi-dose vials should be stored at refrigerated temperatures 2°C-8°C (36°F-46°F) and store in outer carton in order to protect from light. At room temperature, (20°C-30°C or 70°F-86°F), Sandostatin is stable for 14 days if protected from light. The solution can be allowed to come to room temperature prior to administration. Do not warm artificially. After initial use, multiple-dose vials should be discarded within 14 days. Ampuls should be opened just prior to administration and the unused portion discarded. Dispose unused product or waste properly.

REV: August 2008. Manufactured by: Novartis Pharma Stein AG Stein, Switzerland. Distributed by: Novartis Pharmaceuticals Corporation East Hanover, NJ 07936. FDA rev date: 8/26/2008

Last updated on RxList: 10/17/2008

Gallbladder Abnormalities

Gallbladder abnormalities, especially stones and/or biliary sludge, frequently develop in patients on chronic Sandostatin® (octreotide acetate) therapy (see WARNINGS).

Cardiac

In acromegalics, sinus bradycardia ( < 50 bpm) developed in 25%; conduction abnormalities occurred in 10% and arrhythmias developed in 9% of patients during Sandostatin therapy (see PRECAUTIONS - General).

Gastrointestinal

Diarrhea, loose stools, nausea and abdominal discomfort were each seen in 34%-61% of acromegalic patients in U.S. studies although only 2.6% of the patients discontinued therapy due to these symptoms. These symptoms were seen in 5%-10% of patients with other disorders.

The frequency of these symptoms was not dose-related, but diarrhea and abdominal discomfort generally resolved more quickly in patients treated with 300 mcg/day than in those treated with 750 mcg/day. Vomiting, flatulence, abnormal stools, abdominal distention, and constipation were each seen in less than 10% of patients.

In rare instances, gastrointestinal side effects may resemble acute intestinal obstruction, with progressive abdominal distension, severe epigastric pain, abdominal tenderness and guarding.

Hypo/Hyperglycemia

Hypoglycemia and hyperglycemia occurred in 3% and 16% of acromegalic patients, respectively, but only in about 1.5% of other patients. Symptoms of hypoglycemia were noted in approximately 2% of patients.

Hypothyroidism

In acromegalics, biochemical hypothyroidism alone occurred in 12% while goiter occurred in 6% during Sandostatin therapy (see PRECAUTIONS - General). In patients without acromegaly, hypothyroidism has only been reported in several isolated patients and goiter has not been reported.

Other Adverse Events

Pain on injection was reported in 7.7%, headache in 6% and dizziness in 5%. Pancreatitis was also observed (see WARNINGS and PRECAUTIONS).

Other Adverse Events 1%-4%

Other events (relationship to drug not established), each observed in 1%-4% of patients, included fatigue, weakness, pruritus, joint pain, backache, urinary tract infection, cold symptoms, flu symptoms, injection site hematoma, bruise, edema, flushing, blurred vision, pollakiuria, fat malabsorption, hair loss, visual disturbance and depression.

Other Adverse Events < 1%

Events reported in less than 1% of patients and for which relationship to drug is not established are listed: Gastrointestinal: hepatitis, jaundice, increase in liver enzymes, GI bleeding, hemorrhoids, appendicitis, gastric/peptic ulcer, gallbladder polyp; Integumentary: rash, cellulitis, petechiae, urticaria, basal cell carcinoma; Musculoskeletal: arthritis, joint effusion, muscle pain, Raynaud's phenomenon; Cardiovascular: chest pain, shortness of breath, thrombophlebitis, ischemia, congestive heart failure, hypertension, hypertensive reaction, palpitations, orthostatic BP decrease, tachycardia; CNS: anxiety, libido decrease, syncope, tremor, seizure, vertigo, Bell's Palsy, paranoia, pituitary apoplexy, increased intraocular pressure, amnesia, hearing loss, neuritis; Respiratory: pneumonia, pulmonary nodule, status asthmaticus; Endocrine: galactorrhea, hypoadrenalism, diabetes insipidus, gynecomastia, amenorrhea, polymenorrhea, oligomenorrhea, vaginitis; Urogenital: nephrolithiasis, hematuria; Hematologic: anemia, iron deficiency, epistaxis; Miscellaneous: otitis, allergic reaction, increased CK, weight loss.

Evaluation of 20 patients treated for at least 6 months has failed to demonstrate titers of antibodies exceeding background levels. However, antibody titers to Sandostatin were subsequently reported in three patients and resulted in prolonged duration of drug action in two patients. Anaphylactoid reactions, including anaphylactic shock, have been reported in several patients receiving Sandostatin.

Drug Abuse and Dependence

There is no indication that Sandostatin has potential for drug abuse or dependence. Sandostatin levels in the central nervous system are negligible, even after doses up to 30,000 mcg.

Sandostatin has been associated with alterations in nutrient absorption, so it may have an effect on absorption of orally administered drugs. Concomitant administration of Sandostatin with cyclosporine may decrease blood levels of cyclosporine and result in transplant rejection.

Patients receiving insulin, oral hypoglycemic agents, beta blockers, calcium channel blockers, or agents to control fluid and electrolyte balance, may require dose adjustments of these therapeutic agents.

Concomitant administration of octreotide and bromocriptine increases the availability of bromocriptine. Limited published data indicate that somatostatin analogs might decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes, which may be due to the suppression of growth hormones. Since it cannot be excluded that octreotide may have this effect, other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (e.g., quinidine, terfenadine) should therefore be used with caution.

Drug Laboratory Test Interactions

No known interference exists with clinical laboratory tests, including amine or peptide determinations.

Last updated on RxList: 10/17/2008

Single doses of Sandostatin® (octreotide acetate) have been shown to inhibit gallbladder contractility and decrease bile secretion in normal volunteers. In clinical trials (primarily patients with acromegaly or psoriasis), the incidence of biliary tract abnormalities was 63% (27% gallstones, 24% sludge without stones, 12% biliary duct dilatation). The incidence of stones or sludge in patients who received Sandostatin for 12 months or longer was 52%. Less than 2% of patients treated with Sandostatin for 1 month or less developed gallstones. The incidence of gallstones did not appear related to age, sex or dose. Like patients without gallbladder abnormalities, the majority of patients developing gallbladder abnormalities on ultrasound had gastrointestinal symptoms. The symptoms were not specific for gallbladder disease. A few patients developed acute cholecystitis, ascending cholangitis, biliary obstruction, cholestatic hepatitis, or pancreatitis during Sandostatin therapy or following its withdrawal. One patient developed ascending cholangitis during Sandostatin therapy and died.

General

Sandostatin® (octreotide acetate) alters the balance between the counter-regulatory hormones, insulin, glucagon and growth hormone, which may result in hypoglycemia or hyperglycemia. Sandostatin also suppresses secretion of thyroid stimulating hormone, which may result in hypothyroidism. Cardiac conduction abnormalities have also occurred during treatment with Sandostatin. However, the incidence of these adverse events during long-term therapy was determined vigorously only in acromegaly patients who, due to their underlying disease and/or the subsequent treatment they receive, are at an increased risk for the development of diabetes mellitus, hypothyroidism, and cardiovascular disease. Although the degree to which these abnormalities are related to Sandostatin therapy is not clear, new abnormalities of glycemic control, thyroid function and ECG developed during Sandostatin therapy as described below.

Risk of Pregnancy with Normalization of IGF-1 and GH

Although acromegaly may lead to infertility, there are reports of pregnancy in acromegalic women. In women with active acromegaly who have been unable to become pregnant, normalization of GH and IGF-1 may restore fertility. Female patients of childbearing potential should be advised to use adequate contraception during treatment with octreotide.

The hypoglycemia or hyperglycemia which occurs during Sandostatin therapy is usually mild, but may result in overt diabetes mellitus or necessitate dose changes in insulin or other hypoglycemic agents. Hypoglycemia and hyperglycemia occurred on Sandostatin in 3% and 16% of acromegalic patients, respectively. Severe hyperglycemia, subsequent pneumonia, and death following initiation of Sandostatin therapy was reported in one patient with no history of hyperglycemia.

In patients with concomitant Type I diabetes mellitus, Sandostatin Injection and Sandostatin LAR® Depot (octreotide acetate for injectable suspension) are likely to affect glucose regulation, and insulin requirements may be reduced. Symptomatic hypoglycemia, which may be severe, has been reported in these patients. In non-diabetics and Type II diabetics with partially intact insulin reserves, Sandostatin Injection or Sandostatin LAR Depot administration may result in decreases in plasma insulin levels and hyperglycemia. It is therefore recommended that glucose tolerance and antidiabetic treatment be periodically monitored during therapy with these drugs.

In acromegalic patients, 12% developed biochemical hypothyroidism only, 8% developed goiter, and 4% required initiation of thyroid replacement therapy while receiving Sandostatin. Baseline and periodic assessment of thyroid function (TSH, total and/or free T4) is recommended during chronic therapy.

In acromegalics, bradycardia ( < 50 bpm) developed in 25%; conduction abnormalities occurred in 10% and arrhythmias occurred in 9% of patients during Sandostatin therapy. Other EKG changes observed included QT prolongation, axis shifts, early repolarization, low voltage, R/S transition, and early R wave progression. These ECG changes are not uncommon in acromegalic patients. Dose adjustments in drugs such as beta-blockers that have bradycardia effects may be necessary. In one acromegalic patient with severe congestive heart failure, initiation of Sandostatin therapy resulted in worsening of CHF with improvement when drug was discontinued. Confirmation of a drug effect was obtained with a positive rechallenge.

Several cases of pancreatitis have been reported in patients receiving Sandostatin therapy.

Sandostatin may alter absorption of dietary fats in some patients.

In patients with severe renal failure requiring dialysis, the half-life of Sandostatin may be increased, necessitating adjustment of the maintenance dosage.

Depressed vitamin B12 levels and abnormal Schilling's tests have been observed in some patients receiving Sandostatin therapy, and monitoring of vitamin B12 levels is recommended during chronic Sandostatin therapy.

Laboratory Tests

Laboratory tests that may be helpful as biochemical markers in determining and following patient response depend on the specific tumor. Based on diagnosis, measurement of the following substances may be useful in monitoring the progress of therapy:

Acromegaly: Growth Hormone, IGF-I (somatomedin C) Responsiveness to Sandostatin may be evaluated by determining growth hormone levels at 1-4 hour intervals for 8-12 hours post dose. Alternatively, a single measurement of IGF-I (somatomedin C) level may be made two weeks after drug initiation or dosage change.

Carcinoid: 5-HIAA (urinary 5-hydroxyindole acetic acid), plasma serotonin, plasma Substance P

VIPoma: VIP (plasma vasoactive intestinal peptide)

Baseline and periodic total and/or free T4 measurements should be performed during chronic therapy (see PRECAUTIONS - General).

Carcinogenesis/Mutagenesis/Impairment of Fertility

Studies in laboratory animals have demonstrated no mutagenic potential of Sandostatin.

No carcinogenic potential was demonstrated in mice treated subcutaneously for 85-99 weeks at doses up to 2000 mcg/kg/day (8x the human exposure based on body surface area). In a 116-week subcutaneous study in rats, a 27% and 12% incidence of injection site sarcomas or squamous cell carcinomas was observed in males and females, respectively, at the highest dose level of 1250 mcg/kg/day (10x the human exposure based on body surface area) compared to an incidence of 8%-10% in the vehicle-control groups. The increased incidence of injection site tumors was most probably caused by irritation and the high sensitivity of the rat to repeated subcutaneous injections at the same site. Rotating injection sites would prevent chronic irritation in humans. There have been no reports of injection site tumors in patients treated with Sandostatin for up to 5 years. There was also a 15% incidence of uterine adenocarcinomas in the 1250 mcg/kg/day females compared to 7% in the saline-control females and 0% in the vehicle-control females. The presence of endometritis coupled with the absence of corpora lutea, the reduction in mammary fibroadenomas, and the presence of uterine dilatation suggest that the uterine tumors were associated with estrogen dominance in the aged female rats which does not occur in humans.

Sandostatin did not impair fertility in rats at doses up to 1000 mcg/kg/day, which represents 7x the human exposure based on body surface area.

Pregnancy Category B

There are no adequate and well-controlled studies of octreotide use in pregnant women. Reproduction studies have been performed in rats and rabbits at doses up to 16 times the highest recommended human dose based on body surface area and revealed no evidence of harm to the fetus due to octreotide. However, because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

In postmarketing data, a limited number of exposed pregnancies have been reported in patients with acromegaly. Most women were exposed to octreotide during the first trimester of pregnancy at doses ranging from 100-300 mcg/day of Sandostatin s.c. or 20-30 mg/month of Sandostatin LAR, however some women elected to continue octreotide therapy throughout pregnancy. In cases with a known outcome, no congenital malformations were reported.

Nursing Mothers

It is not known whether octreotide is excreted into human milk. Because many drugs are excreted in human milk, caution should be exercised when octreotide is administered to a nursing woman.

Pediatric Use

Experience with Sandostatin in the pediatric population is limited. Although formal controlled clinical trials have not been performed to evaluate safety and effectiveness in this age group, there are reports of 49 cases in the literature of neonates and infants with congenital hyperinsulinism [also called familial hyperinsulinism (HI), persistent hyperinsulinemic hypoglycemia of infancy (PHHI), or nesidioblastosis] who have received Sandostatin as an inhibitor of insulin release. The following efficacy and safety information is derived from these 49 patients.

Sandostatin has been used to stabilize plasma glucose levels prior to pancreatectomy and to treat recurrent post-operative hypoglycemia. Although most use of octreotide in this setting is short-term, a few reports in the literature have documented longer-term therapy in pediatric patients (2.2-5.5 years). Octreotide is an alternative medical treatment to diazoxide for control of hypoglycemia in this disorder. Of 31 pediatric patients who received Sandostatin as prescribed for congenital hyperinsulinism and for which long-term follow-up was available, octreotide obviated the need for surgery in 3 patients (10%) and was replaced by diazoxide in 4 patients (13%) due to uncontrolled hypoglycemia. Although the remainder of these patients required surgery, there have been a few reports in the literature of patients who have responded to octreotide after failing treatment with surgery and/or diazoxide. Doses of 3-40 mcg/kg/day have been used. At these doses, the majority of side effects were gastrointestinal: diarrhea, steatorrhea, vomiting, and abdominal distention, each reported in 22%-35% (n = 1117) of patients. However, they were generally short-lived - with resolution of vomiting and distention in 2-4 days, and diarrhea/steatorrhea, within 2-4 weeks. Steatorrhea was controlled in most patients with pancreatic enzyme supplements. Poor growth was reported in 37% of patients (n = 7) who received Sandostatin for 1-4.33 years. It was associated with low serum growth hormone and/or IGF-1 levels in 4/6 patients in whom these parameters were measured. Catch-up growth occurred in 3/3 patients who were followed after Sandostatin was discontinued. Poor weight gain was reported in 32% of patients (n = 6). Tachyphylaxis was reported in 35% (n = 17) of patients. Asymptomatic gallstones with sludge was reported in one infant after one year of therapy and was treated with ursodeoxycholic acid. There has been a single report of an infant with nesidioblastosis who experienced a seizure thought to be independent of Sandostatin therapy. A single death has been reported in a 16-month-old male with enterocutaneous fistula who developed sudden abdominal pain and increased nasogastric drainage and expired 8 hours after receiving a single 100 mcg subcutaneous dose of Sandostatin.

Geriatric Use

Clinical studies of Sandostatin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Last updated on RxList: 10/17/2008

A limited number of accidental overdoses of Sandostatin® in adults have been reported. In adults, the doses ranged from 2,400-6,000 micrograms/day administered by continuous infusion (100-250 micrograms/hour) or subcutaneously (1,500 micrograms t.i.d.). Adverse events in some patients included arrhythmia, hypotension, cardiac arrest, brain hypoxia, pancreatitis, hepatitis steatosis, hepatomegaly, lactic acidosis, flushing, diarrhea, lethargy, weakness, and weight loss.

Sandostatin Injection given in intravenous boluses of 1 mg (1000 mcg) to healthy volunteers did not result in serious ill effects, nor did doses of 30 mg (30,000 mcg) given intravenously over 20 minutes and of 120 mg (120,000 mcg) given intravenously over 8 hours to research patients.

If overdose occurs, symptomatic management is indicated. Up-to-date information about the treatment of overdose can often be obtained from the National Poison Control Center at 1-800222-1222.

Sensitivity to this drug or any of its components.

Last updated on RxList: 10/17/2008

Sandostatin® (octreotide acetate) exerts pharmacologic actions similar to the natural hormone, somatostatin. It is an even more potent inhibitor of growth hormone, glucagon, and insulin than somatostatin. Like somatostatin, it also suppresses LH response to GnRH, decreases splanchnic blood flow, and inhibits release of serotonin, gastrin, vasoactive intestinal peptide, secretin, motilin, and pancreatic polypeptide.

By virtue of these pharmacological actions, Sandostatin has been used to treat the symptoms associated with metastatic carcinoid tumors (flushing and diarrhea), and Vasoactive Intestinal Peptide (VIP) secreting adenomas (watery diarrhea).

Sandostatin substantially reduces growth hormone and/or IGF-I (somatomedin C) levels in patients with acromegaly.

Single doses of Sandostatin have been shown to inhibit gallbladder contractility and to decrease bile secretion in normal volunteers. In controlled clinical trials the incidence of gallstone or biliary sludge formation was markedly increased (see WARNINGS.)

Sandostatin suppresses secretion of thyroid stimulating hormone (TSH).

Pharmacokinetics

After subcutaneous injection, octreotide is absorbed rapidly and completely from the injection site. Peak concentrations of 5.2 ng/mL (100-mcg dose) were reached 0.4 hours after dosing. Using a specific radioimmunoassay, intravenous and subcutaneous doses were found to be bioequivalent. Peak concentrations and area under the curve values were dose proportional after intravenous single doses up to 200 mcg and subcutaneous single doses up to 500 mcg and after subcutaneous multiple doses up to 500 mcg t.i.d. (1500 mcg/day).

In healthy volunteers the distribution of octreotide from plasma was rapid (ta½ = 0.2 h), the volume of distribution (Vdss) was estimated to be 13.6 L, and the total body clearance ranged from 7 L/hr to 10 L/hr. In blood, the distribution into the erythrocytes was found to be negligible and about 65% was bound in the plasma in a concentration-independent manner. Binding was mainly to lipoprotein and, to a lesser extent, to albumin.

The elimination of octreotide from plasma had an apparent half-life of 1.7 to 1.9 hours compared with 1-3 minutes with the natural hormone. The duration of action of Sandostatin is variable but extends up to 12 hours depending upon the type of tumor. About 32% of the dose is excreted unchanged into the urine. In an elderly population, dose adjustments may be necessary due to a significant increase in the half-life (46%) and a significant decrease in the clearance (26%) of the drug.

In patients with acromegaly, the pharmacokinetics differ somewhat from those in healthy volunteers. A mean peak concentration of 2.8 ng/mL (100-mcg dose) was reached in 0.7 hours after subcutaneous dosing. The volume of distribution (Vdss) was estimated to be 21.6 ± 8.5 L and the total body clearance was increased to 18 L/h. The mean percent of the drug bound was 41.2%. The disposition and elimination half-lives were similar to normals.

In patients with renal impairment the elimination of octreotide from plasma was prolonged and total body clearance reduced. In mild renal impairment (CL_CR 40-60 mL/min) octreotide t½ was 2.4 hours and total body clearance was 8.8 L/hr, in moderate impairment (CL_CR 10-39 mL/min) t½ was 3.0 hours and total body clearance 7.3 L/hr, and in severely renally impaired patients not requiring dialysis (CL_CR < 10 mL/min) t½ was 3.1 hours and total body clearance was 7.6 L/hr. In patients with severe renal failure requiring dialysis, total body clearance was reduced to about half that found in healthy subjects (from approximately 10 L/hr to 4.5 L/hr).

Patients with liver cirrhosis showed prolonged elimination of drug, with octreotide t½ increasing to 3.7 hr and total body clearance decreasing to 5.9 L/hr, whereas patients with fatty liver disease showed t½ increased to 3.4 hr and total body clearance of 8.2 L/hr.

Last updated on RxList: 10/17/2008

Careful instruction in sterile subcutaneous injection technique should be given to the patients and to other persons who may administer Sandostatin Injection.

Last updated on RxList: 10/17/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

OCTREOTIDE - INJECTION

(ok-TREE-oh-tide)

COMMON BRAND NAME(S): Sandostatin

USES: Octreotide is used to treat severe watery diarrhea and sudden reddening of the face and neck caused by certain types of tumors (e.g., carcinoid tumors, vasoactive intestinal peptide tumors) that are found usually in the intestines and pancreas. The symptoms occur when these tumors make too much of certain natural substances (hormones). This medication works by blocking the production of these hormones. By decreasing watery diarrhea, octreotide helps to reduce the loss of body fluids and minerals.

Octreotide is also used to treat a certain condition (acromegaly) that occurs when the body makes too much of a certain natural substance called growth hormone. Treating acromegaly helps reduce the risk of serious problems such as diabetes and heart disease. Octreotide works by decreasing the amount of growth hormone to normal levels.

This drug is not a cure for these conditions. This medication is usually used with other treatment (e.g., surgery, radiation, other drugs).

HOW TO USE: This medication is usually given by injection under the skin, usually 2 to 3 times a day or as directed by your doctor. Depending on your condition, it may be given by injection into a vein by a health care professional.

If your doctor directs you to inject this medication under the skin yourself, learn all preparation and usage instructions from your health care professional. Learn how to store and discard needles and medical supplies safely. If you have questions, ask your health care professional.

Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Before injecting each dose, clean the injection site with rubbing alcohol. Change the location of the injection site each time to avoid problem areas under the skin.

Dosage is based on your medical condition and response to treatment.

Use this medication regularly to get the most benefit from it. To help you remember, use it at the same times each day.

Tell your doctor if your condition does not improve or if it worsens.

SIDE EFFECTS: Nausea, vomiting, loose/oily stools, constipation, stomach upset, gas, bloating, dizziness, or headache may occur. Pain and irritation at the injection site may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: signs of gallbladder problems (e.g., fever, stomach/abdominal pain, severe nausea/vomiting, yellowing eyes/skin, unexplained pain in the back/right shoulder), signs of underactive thyroid (e.g., unexplained weight gain, cold intolerance, slow heartbeat, severe constipation, unusual/extreme tiredness, growth/lump/swelling on the front of the neck), worsening heart condition symptoms (e.g., trouble breathing, slow/fast/irregular heartbeat), numbness/tingling of the arms/legs.

This medication may infrequently cause changes in blood sugar, especially if you have diabetes. Symptoms of high blood sugar include increased thirst and urination. Symptoms of low blood sugar include nervousness, shakiness, sweating, fast heartbeat, and hunger. Follow your doctor's instructions to treat low blood sugar (e.g., eat a quick source of sugar such as glucose gel/tablets, table sugar, or honey, or drink fruit juice or non-diet soda). Tell your doctor immediately if you experience symptoms of high or low blood sugar while taking this medication. Monitor your blood sugar levels as directed by your doctor.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using octreotide, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, diabetes, thyroid problems, gallbladder problems (e.g., gallstones), nutrition problems (e.g., decreased fat absorption, vitamin B12 deficiency).

This drug may make you dizzy. Use caution while driving, using machinery, or doing any activity that requires alertness. Limit alcoholic beverages.

Caution is advised when using this drug in children. Use of this medication for long periods (e.g., longer than 1 year) may slow a child's growth rate. However, the growth rate catches up after treatment with the drug is stopped. Consult your doctor for more information.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: beta-blockers (e.g., metoprolol, propranolol), calcium channel blockers (e.g., diltiazem, verapamil), cyclosporine, drugs to treat diabetes (e.g., glyburide, insulin), nutritional solutions given by vein (e.g., total parenteral nutrition-TPN), pegvisomant, "water pills" (diuretics such as furosemide, hydrochlorothiazide).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., blood glucose tests, thyroid function tests, hormone levels, vitamin B12 levels) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store this medication in the refrigerator between 36-46 degrees F (2-8 degrees C) away from light. Allow the medication to come to room temperature before using. This medication is good for 2 weeks if stored at room temperature between 68-86 degrees F (20-30 degrees C) away from light. Multi-use vials should be discarded 2 weeks after opening. Ampules should be opened just before each dose, and any unused portion should be discarded. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.