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Octreotide (Systemic)


VA CLASSIFICATION
Primary: GA208
Secondary: BL116; CV900; HS900

Commonly used brand name(s): Sandostatin; Sandostatin LAR Depot.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antidiarrheal (gastrointestinal tumor; acquired immunodeficiency syndrome [AIDS])—

growth hormone suppressant (acromegaly)—

antihemorrhagic (bleeding gastroesophageal varices)—

antihypotensive (carcinoid crisis)—

antihypoglycemic (pancreatic tumor)—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Tumors, gastrointestinal (treatment adjunct)—Octreotide is indicated for palliative management of gastrointestinal endocrine tumors, such as:

• Carcinoid tumors—To suppress or inhibit the associated severe diarrhea and facial flushing episodes. {01} {02} {05}


• Vasoactive intestinal polypeptide–secreting tumors (VIPomas)—For the treatment of the profuse watery diarrhea associated with VIPomas. {01} {02}


Acromegaly (treatment)—Octreotide is indicated to suppress secretion of growth hormone from pituitary tumors and decrease blood concentrations of insulin-like growth factor-I (IGF-I; somatomedin C) in patients with acromegaly who have not optimally responded to or cannot be treated with surgical resection or pituitary irradiation or have been unable to tolerate bromocriptine. Octreotide may be used as adjunctive therapy with irradiation to help relieve symptoms of acromegaly and possibly slow the rate of tumor growth. {01} {02} {04} {07} {10} {13}

[Pancreatic surgery, complications of (prophylaxis) ]—Octreotide is indicated to reduce the incidence and severity of the postoperative complications of high-risk pancreatic surgery. These complications may include abscess formation and subsequent sepsis, acute pancreatitis, pancreatic fistula, and peripancreatic fluid collection. {07}

[Varices, gastroesophageal, bleeding (treatment) ]—Octreotide, with an appropriate adjunctive therapeutic intervention such as sclerotherapy, is indicated to control bleeding and early rebleeding and to reduce transfusion requirements in patients with bleeding gastroesophageal varices associated with cirrhosis. Octreotide has been shown to improve the 5-day survival rate in these patients. {07}

[Hypotension (treatment)]1—Octreotide is indicated to reverse life-threatening hypotension due to carcinoid crisis during induction of anesthesia. {03}

[Tumors, pancreatic (treatment adjunct) ]1—Octreotide is indicated for use as palliative treatment of the symptoms resulting from hyperinsulinemia from severe refractory metastatic insulinoma. {20} {21} {22} {25}

[Diarrhea, acquired immunodeficiency syndrome (AIDS)–associated (treatment)]1—Octreotide is indicated in AIDS patients with severe secretory diarrhea who have failed to respond to antimicrobial or antimotility agents. {09} {16} {17} {18} {19} {25}

[Diarrhea, chemotherapy–induced (treatment)]1—Octreotide is indicated for the treatment of chemotherapy–induced diarrhea.{26}{27}{28}{29}{30}{31}{32}{33}

Acceptance not established
Use of octreotide for the treatment of hepatocellular carcinoma has not been established, due to insufficient reliable data supporting efficacy.{34}{35}{36}{37}{38}{39}{40}{41}{42}{43}{44}{45}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Octreotide (base): 1019.26 {23}


pH
    4 to 4.6. {15}

Mechanism of action/Effect:

Gastrointestinal tumors—The action of octreotide is similar to that of naturally occurring somatostatin, but with a prolonged duration. {07} {20} Like the naturally occurring hormone, octreotide suppresses secretion of serotonin and the gastroenteropancreatic peptides including gastrin, motilin, and secretin, {01} {02} stimulates fluid and electrolyte absorption from the gastrointestinal tract, and prolongs intestinal transit time. It blocks the carcinoid flush, decreases circulating concentrations of serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), and controls other symptoms associated with the carcinoid syndrome. {01} {05} {07}

Acromegaly—Octreotide suppresses secretion of growth hormone and insulin-like growth factor-I (IGF-I; somatomedin C). {01} {02} {07}

Prophylaxis of complications of high-risk pancreatic surgery—Complications of high-risk pancreatic surgery, such as abscess formation and subsequent sepsis, acute pancreatitis, pancreatic fistula, and peripancreatic fluid collection, occur as a result of fluid leaking from the pancreatic remnant into the surrounding tissues. This fluid contains digestive enzymes that cause inflammation and destruction of the surrounding intestinal organs and vessels. When administered perioperatively, octreotide suppresses secretion of pancreatic fluid. {07}

Bleeding gastroesophageal varices—The exact mechanism of action is unknown but is believed to be related to the suppression of vasoactive gastrointestinal hormones and exertion of a direct vasomotor effect on the splanchnic vessels, resulting in a reduction of splanchnic blood flow. {07}


Other actions/effects:

Octreotide suppresses secretion of glucagon, insulin, and thyroid stimulating hormone, {01} {02} {07} and suppresses the luteinizing hormone response to gonadotropin-releasing hormone. {01} {02} {07} Octreotide also inhibits gallbladder contractions {01} {02} {09} {10} {13} {14} and decreases bile secretion. {01} {02}

Absorption:

Immediate-release dosage form—Absorbed rapidly and completely from the injection site. {01} {02} {07}

Protein binding:

In patients with acromegaly—Moderate (41.2%). {02}

In all other patients—High (65%, {01} {02} {07} to lipoproteins and to a lesser extent to albumin). {01} {02}

Half-life:


Immediate-release dosage form:


Elimination—


Subcutaneous—

1.7 hours. {01} {02}



Intravenous—

Alpha phase: Approximately 10 minutes. {07}

Beta phase: Approximately 90 minutes. {07}




May be increased in elderly patients (by up to 46%) {01} {02} and in patients with renal function impairment requiring dialysis. {01} {02} {07}


Time to peak concentration:



Immediate-release dosage form—Approximately 30 minutes. {01} {02} {07}


Long-acting dosage form:

Initial: 60 minutes. {02}

Plateau: 2 to 3 weeks. {02}


Peak serum concentration:


Immediate-release dosage form:

5.2 nanograms/mL with a 100-mcg dose. {01} {02}



Long-acting dosage form:

Initial: 0.03 nanogram/mL/mg. {02}

Plateau: 0.07 nanogram/mL/mg. {02}


Duration of action:

Immediate-release dosage form—Up to 12 hours (depending on the type of tumor). {01} {02}

Elimination:
    Renal (32% of dose). {01} {02}


Precautions to Consider

Carcinogenicity

Lifetime carcinogenicity studies in male and female mice receiving octreotide at subcutaneous doses of 0.4 mg, 1.2 mg, and 2 mg per kg of body weight (mg/kg) per day demonstrated an increase in the incidence of duodenal mucosal hyperplasia in the females. {07}

Studies in male and female Wistar rats administered octreotide subcutaneously for up to 116 weeks demonstrated an increased incidence of subcutaneous sarcomata in males receiving 0.24 and 1.25 mg/kg per day. Additionally, in the females, there were dose-related increases in ovarian sections without corpora lutea and uterine glandular and luminal dilatation; endometriosis was seen in all treated groups, particularly the 1.25-mg/kg-per-day group. There was a marginal but statistically significant increase in the relative proportion of lymphocytes in males receiving 0.8 and 1.25 mg/kg per day (8 to 10% increase) and in females receiving 1.25 mg/kg per day (16% increase). {07} All groups of treated males and females receiving 0.8 and 1.25 mg/kg per day experienced dose-related weight loss. {07}

Mutagenicity

No evidence of mutagenicity was demonstrated in vitro with the Ames test or in vivo with the micronucleus test or unscheduled DNA synthesis (UDS) assay. {07}

Pregnancy/Reproduction
Fertility—
Studies in rats at doses of up to 1000 mcg per kg of body weight (seven times the human exposure based on body surface area) a day have not shown that octreotide causes impaired fertility. {01} {02} {07}

Pregnancy—
Adequate and well-controlled studies in humans have not been done. {01} {02} {07}

Studies in rats and rabbits at doses of up to 30 times the maximum human dose have not shown that octreotide causes adverse effects in the fetus. {07}

FDA Pregnancy Category B. {01} {02}

Breast-feeding

It is not known whether octreotide is distributed into breast milk. {01} {02} {07}

Pediatrics

Appropriate studies with immediate-release octreotide have not been performed in the pediatric population. However, doses of 1 to 10 mcg per kg of body weight, given to children as young as 1 month old, were well tolerated. One case in which an infant (a case of nesidioblastosis) suffered a seizure while undergoing octreotide therapy was thought to be unrelated to octreotide administration. {01} {07}

Safety and efficacy of long-acting octreotide in pediatric patients have not been established. {02}


Geriatrics


Studies performed to date in patients as old as 83 years of age have not demonstrated geriatrics-specific problems that would limit the usefulness of this medication in the elderly. However, the half-life may be significantly increased (by up to 46%) and the clearance significantly decreased (by as much as 26%), which may require adjustment of dosage in elderly patients receiving octreotide. {01} {02}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Antidiabetic agents, sulfonylurea{07} or
» Diazoxide, oral{07} or
» Glucagon or
» Growth hormone or
» Insulin{01}{02}{07}    (use of these medications during octreotide therapy may result in hypoglycemia or hyperglycemia; patient monitoring and dosage adjustment of these medications may be necessary {01} {02} {07})


Beta-adrenergic blocking agents{01}{02}    (because of the bradycardic effect of octreotide, dosage adjustment may be required {01} {02})


Cyclosporine{01}{02}{07}    (a single case of transplant rejection [renal/whole pancreas] in a patient who was receiving octreotide and who was immunosuppressed with cyclosporine has been reported; the use of octreotide to reduce exocrine secretion and close a fistula in this patient resulted in a decrease in the blood concentrations of cyclosporine, thus possibly contributing to the rejection episode {07} {09})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Schilling test{01}{02}    (abnormal results have been seen {01} {02})

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]){07} and
Alkaline phosphatase{07} and
Aspartate aminotransferase (AST [SGOT]){07} and
Gamma-glutamyltransferase (GGT), serum{07}    (values may be increased if hyperbilirubinemia develops {07})


Electrocardiogram{01}{02}    (changes such as QT prolongation, axis shifts, early repolarization, low voltage, R/S transition, R-wave progression, and nonspecific ST-T wave changes have been seen in patients with acromegaly {01} {02})


Thyroid hormones    (serum concentration of thyroxine [T 4] may be decreased; hypothyroidism occurred in one clinical trial patient [with a carcinoid tumor] after 19 months of receiving 1.5 mg of octreotide daily {07})


Vitamin B 12, serum{01}{02}    (concentrations may be decreased {01} {02})


Zinc, serum{02}    (concentrations may increase excessively in patients receiving total parenteral nutrition [TPN] when fluid loss is corrected {02})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Diabetes mellitus    (therapy used to control glycemic states may need to be adjusted {01} {02} {07})


» Gallbladder disease or gallstones, or history of    (increased risk of cholelithiasis possibly due to alteration of fat absorption and decrease in gallbladder motility caused by octreotide {01} {07} {13} {14} {24})


Renal function impairment, severe    (half-life of octreotide may be increased; dosage adjustment may be necessary {01} {02} {07})


Sensitivity to octreotide{01}{02}{07}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Carotene, serum concentrations and
Fecal fat, quantitative{07}    (octreotide therapy may alter absorption of dietary fats; periodic 72-hour fecal fat and serum carotene determinations are recommended to assess possible aggravation of fat malabsorption {07})


Glucose    (measurement of blood concentrations is recommended at the beginning of octreotide therapy and at each change of dosage if clinical signs of increase or decrease occur {01} {07} {12} {13} {14})


» Growth hormone{01}{02}{07}    (recommended at 1- to 4-hour intervals for 8 to 12 hours following a dose of immediate-release octreotide and at 6-month intervals thereafter to assess response in patients with acromegaly; {01} {02} {07} after transfer to the long-acting dosage form, monitoring is recommended at 3-month intervals {02})


» 5-hydroxyindoleacetic acid (5-HIAA), quantitative, urine{01}{02}{07} and
Serotonin{01}{02} and
Substance P, plasma{01}{02}{07}    (periodic determinations are recommended during therapy in patients with carcinoid tumors to assess patient response {01} {02})


Insulin-like growth factor-I (IGF-I; somatomedin C){01}{02}{07}    (an alternative to measurement of growth hormone; may be measured one time 2 weeks after immediate-release octreotide initiation or change of dosage and at 6-month intervals thereafter to assess response in patients with acromegaly; {01} {02} {07} after transfer to the long-acting dosage form, monitoring is recommended at 3-month intervals {02})


Thyroid function determinations{01}{02}    (baseline and periodic thyroid function tests using total and free serum thyroxine [T 4] are recommended during chronic therapy {01} {02} {07})


» Ultrasonograms    (therapy with octreotide, as with the natural hormone somatostatin, may be associated with cholelithiasis, presumably due to an alteration of fat absorption and possibly to decreased motility of the gallbladder; baseline and periodic ultrasonograms may be required to assess the presence of gallstones {11} {13})


Vasoactive intestinal polypeptide (VIP){01}{02}{07}    (periodic determinations are recommended in patients with VIP-secreting tumors [VIPomas] to assess patient response {01} {02})


Vitamin B 12, serum{01}{02}    (periodic determinations are recommended during chronic therapy {01} {02})


Zinc, serum{02}    (periodic determinations are recommended in patients receiving TPN {02})




Side/Adverse Effects

Note: Isolated reports of hepatic dysfunctions associated with octreotide administration include acute hepatitis without cholestasis, slow development of hyperbilirubinemia, and gallstone formation. {07} The risk of gallstone formation increases with long-term therapy, which usually is required in the treatment of acromegaly. {07} {11} {13}
Development of antibodies has been seen in up to 25% of patients treated with octreotide. In most of these cases, therapeutic response to octreotide has not been affected. However, in two patients with acromegaly, the duration of growth hormone suppression following an injection of immediate-release octreotide was doubled as compared with that in patients without antibodies. {02}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Arrhythmias (irregular heartbeat)—incidence 9% in patients with acromegaly,{01}{02} 3% in patients with carcinoid tumors{02}
    
bradycardia (slow heartbeat)—incidence 25% in patients with acromegaly,{01} 19% in patients with carcinoid tumors{02}

Incidence less frequent or rare
    
Hyperglycemia (blurred vision; drowsiness; dry mouth; flushed, dry skin; fruit-like breath odor; increased urination [frequency and volume]; ketones in urine; loss of appetite; stomachache, nausea, or vomiting; tiredness; troubled breathing [rapid and deep]; unconsciousness; unusual thirst){01}{02}{07}
    
hypoglycemia (anxiety; behavior change similar to drunkenness; blurred vision; cold sweats; coma; confusion; cool, pale skin; difficulty in concentrating; drowsiness; excessive hunger; fast heartbeat; headache; nausea; nervousness; nightmares; restless sleep; seizures; shakiness; slurred speech; unusual tiredness or weakness){01}{02}{07}
    
pancreatitis, acute (abdominal pain or distension; nausea; vomiting){01}{07}

Note: Octreotide therapy is occasionally associated with mild transient hypoglycemia or hyperglycemia due to an alteration in the balance between the counterregulatory hormones, insulin, glucagon, and growth hormone. {01} {02} {09} {12} {13}
Acute pancreatitis generally is seen within the first hours or days of octreotide administration and resolves when therapy is discontinued. {07}




Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Gastrointestinal symptoms (abdominal or stomach pain or discomfort; constipation; diarrhea; flatulence; nausea and vomiting){01}{02}{07}
    
pain, stinging, tingling, or burning sensation at injection site, with redness and swelling {01}{02}{07}

Note: Gastrointestinal symptoms usually are self-limiting and usually are resolved after 2 to 3 weeks of therapy. {13} {25}


Incidence less frequent or rare
    
Alopecia {01}{07}
    
dizziness or lightheadedness {01}{02}{07}
    
edema (swelling of feet or lower legs)
    
fatigue {01}{02}
    
fever {02}{07}
    
headache {01}{02}
    
redness or flushing of face {01}{07}
    
unusual weakness {01}{07}





Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
    
Abdominal cramps {07}
    
decrease in heart rate {07}
    
diarrhea {07}
    
dizziness {02}
    
empty feeling in stomach {07}
    
flushing of face {02}{07}
    
nausea {02}{07}


Treatment of overdose
Supportive care—Recommended treatment consists of temporary withdrawal of octreotide and symptomatic treatment of the clinical effects. {07}


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Octreotide (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to octreotide
Other medications, especially glucagon, growth hormone, insulin, oral diazoxide, or sulfonylurea antidiabetic agents
Other medical problems, especially diabetes mellitus or gallbladder disease or gallstones

Proper use of this medication
» Taking medication only as directed by physician

» Reading directions in starter kit before using

» Carefully selecting and rotating injection sites

Allowing medication to reach room temperature if pain, stinging, tingling, or burning sensation occurs upon injection

» Safe handling and disposal of needles and syringes; not reusing needles and syringes {07}

» Proper dosing
Missed dose:

• Long-acting dosage form—Contacting physician


• Immediate-release dosage form—Using as soon as possible unless almost time for next dose, then going back to regular dosing schedule; {07} not doubling doses


» Proper storage

Precautions while using this medication
» Importance of close monitoring by physician


Side/adverse effects
Signs of potential side effects, especially arrhythmias, bradycardia, hyperglycemia, hypoglycemia, and acute pancreatitis


General Dosing Information
Preferred sites for subcutaneous administration of octreotide injection (immediate-release dosage form) are the hip, thigh, and abdomen. {07}

Octreotide suspension (long-acting dosage form) is recommended for intragluteal administration only. Injection into the deltoid muscle causes significant discomfort at the site. {02} Intravenous or subcutaneous administration is not recommended. {02}

Multiple injections at the same injection site within short periods of time are not recommended. {01} {02} {07} {15} This is to avoid irritating the area. {02} {07}

Local reactions at the injection site may be minimized by allowing the medication to reach room temperature before injection and by administering slowly. {07}

Periodic exacerbation of symptoms may occur despite good overall control. During these times, if the patient is receiving octreotide injection, the dosage should be adjusted. {07} If the patient is receiving octreotide suspension, octreotide injection, at the previous dosage, should be administered concurrently with octreotide suspension until symptoms are again controlled. Administration of octreotide injection may then be discontinued. {02}

For gastrointestinal tumors
When initiating therapy with octreotide suspension, octreotide injection, at the current dosage, should be administered concurrently for at least 2 weeks (up to 4 weeks may be required in some patients) to allow octreotide suspension to reach therapeutic concentrations. Failure to do so may result in exacerbation of symptoms. {02}

For acromegaly
If after 3 months there is no significant decrease in growth hormone concentration and no appreciable improvement in clinical symptoms, octreotide therapy should be discontinued. {07}

Octreotide therapy should be withheld for approximately 8 weeks each year from patients who have received irradiation, to assess disease activity. During this time, if growth hormone or insulin-like growth factor-I (IGF-I) concentration increases or if clinical signs and symptoms recur, octreotide therapy should be reinstated. {01}

Diet/Nutrition
To avoid the occurrence of gastrointestinal side effects, injections of octreotide should be scheduled between meals and at bedtime. {07}


Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

OCTREOTIDE ACETATE FOR INJECTABLE SUSPENSION

Usual adult and adolescent dose
Gastrointestinal tumors
Patients not currently receiving octreotide—To ascertain responsiveness to octreotide, it is recommended that therapy be initiated and maintained for at least two weeks with the immediate-release dosage form (see Octreotide Acetate Injection ). {02}

Patients currently receiving octreotide injection: Intragluteal, 20 mg every four weeks for two months. Dosage may then be increased to 30 mg every four weeks or decreased to 10 mg every four weeks, based on patient response. {02}

Note: Administration of octreotide injection at the current dosage should be maintained for at least two weeks to allow octreotide suspension to reach therapeutic concentrations. {02}


Acromegaly


Patients not currently receiving octreotide:
To ascertain responsiveness to octreotide, it is recommended that therapy be initiated and maintained for at least two weeks with the immediate-release dosage form (see Octreotide Acetate Injection ). {02}



Patients currently receiving octreotide injection:
Intragluteal, 20 mg every four weeks for three months. Dosage should then be titrated based on the following criteria:

• If growth hormone concentrations are less than 2.5 nanograms per mL, IGF-I concentrations are normal, and clinical symptoms are controlled—Intragluteal, 20 mg every four weeks. {02}


• If growth hormone concentrations are greater than 2.5 nanograms per mL, IFG-I concentrations are elevated, and/or clinical symptoms are uncontrolled—Intragluteal, 30 mg every four weeks. {02}


• If growth hormone concentrations are less than or equal to 1 nanogram per mL, IFG-I concentrations are normal and clinical symptoms are controlled—Intragluteal, 10 mg every four weeks. {02}


• If growth hormone concentrations, IGF-I concentrations, and clinical symptoms are not controlled with 30 mg—Intragluteal, 40 mg every four weeks. {02}




Note: Administration at dosing intervals greater than every four weeks is not recommended; efficacy at this schedule has not been determined. {02}
Because of the increase in the half-life of octreotide, patients with renal failure requiring dialysis may need an adjustment in the dosage. {02}


Usual adult prescribing limits
Gastrointestinal tumors—30 mg every four weeks. {02}

Acromegaly—40 mg every four weeks. {02}

Usual pediatric dose
Safety and efficacy have not been established. {02}

Usual geriatric dose
See Usual adult and adolescent dose .

Note: Because of the significant increase in the half-life of octreotide and the decrease in clearance seen in geriatric patients, dosage adjustment may be required. {02}


Size(s) usually available:
U.S.—


10 mg (base) per vial (Rx) [Sandostatin LAR Depot{02}]


20 mg (base) per vial (Rx) [Sandostatin LAR Depot{02}]


30 mg (base) per vial (Rx) [Sandostatin LAR Depot{02}]

Canada—
Not commercially available.

Packaging and storage:
Store at 2 to 8 °C (36 to 46 °F), {02} unless otherwise specified by manufacturer. Protect from light. {02}

Note: Octreotide for injectable suspension vial and diluent should be taken from the refrigerator 30 to 60 minutes before administration to allow them to warm to room temperature. {02}


Preparation of dosage form:
The manufacturer's instructions for preparation should be followed. {02}

Stability:
Octreotide suspension should be administered immediately after preparation. {02}

Auxiliary labeling:
   • Refrigerate.

Note: Injection sites should be rotated. {02}



OCTREOTIDE ACETATE INJECTION

Usual adult and adolescent dose
Gastrointestinal tumors
Subcutaneous, 50 mcg initially, administered two or three times a day, the dose being increased gradually according to patient tolerance and response. {01} The following dosages are recommended for specific tumors:


Carcinoid tumors—
Initial: Subcutaneous, 100 to 600 mcg per day, administered in two to four divided doses, for the first two weeks of therapy. {01} {02} {07}

Maintenance: Subcutaneous, 50 to 1500 mcg per day. In clinical trials, the median maintenance dosage was 450 mcg per day. {01} {07}



Vasoactive intestinal polypeptide–secreting tumors (VIPomas)—
Subcutaneous, 200 to 300 mcg per day, administered in two to four divided doses, for the first two weeks of therapy. Dosage may then be increased based on patient response. {01} {07}



Acromegaly
Subcutaneous or intravenous, initially 50 mcg three times a day. Dosage is titrated every two weeks as needed, according to IGF-I concentrations, to a dose of 100 {01} {02} {13} to 200 {02} mcg three times a day; or, for rapid titration, dosage increase may be based on multiple serum growth hormone concentrations taken at one- to four-hour intervals over eight to twelve hours. {13} Doses of up to 500 mcg three times a day have been used rarely. {01} {13}

Note: Octreotide injection may be administered subcutaneously (the preferred route) or intravenously. To help prevent pain at the injection site, octreotide should be given in the smallest volume needed to achieve the proper dose. In emergencies, intravenous injections may be used cautiously. {01}
If an increase in dose fails to provide additional benefit, the dose should be reduced. {01}


[Complications of pancreatic surgery (prophylaxis of)]
Subcutaneous, 100 mcg three times a day for seven days beginning on the day of surgery at least one hour before laparotomy. {07}

[Bleeding gastroesophageal varices]
Intravenous infusion, 25 mcg per hour for forty-eight hours. Infusion should continue for up to five days in patients at high risk for rebleeding. {07}

[Pancreatic tumors]1
Subcutaneous, 50 to 150 mcg initially, administered two times a day thirty minutes before meals, the dose being increased gradually according to patient tolerance and response. {20} {21}

[Acquired immunodeficiency syndrome (AIDS)–associated diarrhea]1
Subcutaneous, 100 to 1800 mcg per day. {16} {17} {18} {19} {25}

[Chemotherapy–induced diarrhea]1
Subcutaneous, 100 to 150 mcg three times a day as a starting dose. Dosage may be increased up to 2000 mcg three times a day if needed. Treatment may last three to five days or until diarrhea resolves.{26}{27}{28}{29}{30}{31}{32}{33}


Usual adult prescribing limits
Acromegaly—1500 mcg daily. {07}

Usual pediatric dose
Gastrointestinal tumors
Subcutaneous, 1 to 10 mcg per kg of body weight per day. {01}


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Because of the significant increase in the half-life of octreotide and the decrease in clearance seen in geriatric patients, dosage adjustment may be required. {01}


Strength(s) usually available
U.S.—


50 mcg per mL (Rx) [Sandostatin{01}]


100 mcg per mL (Rx) [Sandostatin{01}]


200 mcg per mL (Rx) [Sandostatin{01}]


500 mcg per mL (Rx) [Sandostatin{01}]


1000 mcg per mL (Rx) [Sandostatin{01}]

Note: The 50 mcg per mL, 100 mcg per mL, and 500 mcg per mL strengths are packaged as single-use ampuls; the remaining strengths are packaged as multiple-dose vials. {01}


Canada—


50 mcg per mL (Rx) [Sandostatin{07}]


100 mcg per mL (Rx) [Sandostatin{07}]


200 mcg per mL (Rx) [Sandostatin{07}]


500 mcg per mL (Rx) [Sandostatin{07}]

Note: The 50 mcg per mL, 100 mcg per mL, and 500 mcg per mL strengths are packaged as single-use ampuls; the 200 mcg per mL strength is packaged as a multiple-dose vial. {07}


Packaging and storage:
Octreotide may be stored at room temperature protected from light for up to 14 days. {01} {07} {15} However, for prolonged periods, store at 2 to 8 °C (36 to 46 °F), {07} unless otherwise specified by manufacturer. Protect from freezing. {07} Protect from light. {01} {07}

Note: Solution should be allowed to warm to room temperature before administration. Do not warm artificially before injection. Single-use ampuls should be opened just prior to use and any unused portion discarded. {01} {07}


Preparation of dosage form:
Octreotide is stable when diluted in 50 to 200 mL of either sterile 0.9% sodium chloride injection or 5% dextrose injection. The diluted solution can be infused intravenously over a 15- to 30-minute period or administered via a direct intravenous injection over a 3-minute period. {01} {15} In emergencies, rapid intravenous injections may be used cautiously. {01}

Stability:
If protected from light, octreotide injection is stable at room temperature, preferably between 15 and 30 °C (59 and 86 °F), for 14 days. When diluted in 0.9% sodium chloride injection, octreotide injection is stable at room temperature for 24 hours. {07} Octreotide should not be used if it is discolored or if particulate matter forms in the solution. {01} {07}

Incompatibilities:
Octreotide is not compatible with fat emulsions {15} or with total parenteral nutrition (TPN) solutions because decreased efficacy may result if glycosyloctreotide conjugates form. {01}

Note: Subcutaneous injection sites should be rotated. {07} {15}




Revised: 01/07/2003



References
  1. Sandostatin package insert (Novartis—US), Rev 01/97, Rec 02/23/99.
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