Octreotide Acetate

Pronunciation

Pronunciation: ok-TREE-oh-tide AS-e-tate
Class: Endocrine and metabolic agent

Trade Names

Sandostatin
- Injection 0.05 mg/mL
- Injection 0.1 mg/mL
- Injection 0.2 mg/mL
- Injection 0.5 mg/mL
- Injection 1 mg/mL

Sandostatin LAR Depot
- Injection 10 mg per 5 mL
- Injection 20 mg per 5 mL
- Injection 30 mg per 5 mL

Pharmacology

Actions mimic those of the natural hormone somatostatin. Suppresses secretion of serotonin and gastroenteropancreatic peptides (eg, gastrin, insulin, glucagon, secretin, motilin). Also suppresses growth hormone.

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Pharmacokinetics

Absorption

Octreotide is rapidly and completely absorbed (subcutaneous).

The bioavailability is 100% (subcutaneous). C max is 5.2 ng/mL, and T max is 0.4 h.

Distribution

Vd is 13.6 L. Protein binding is 65% and is bound mainly to lipoprotein, and, to a lesser extent, albumin.

Elimination

The t ½ is 1.7 h. 32% is eliminated unchanged through the urine. Cl is 10 L/h.

Special Populations

Renal Function Impairment

Elimination and Cl is prolonged; Cl may be reduced by about 50% in patients with severe renal failure.

Hepatic Function Impairment

Patients with liver cirrhosis showed prolonged elimination of the drug with t ½ increasing and Cl decreasing.

Elderly

There is a 46% increase in the half-life of the drug, and a 26% decrease in Cl. Dosage adjustment may be necessary.

Indications and Usage

Symptomatic treatment of diarrhea and flushing episodes associated with carcinoid tumors; treatment of profuse watery diarrhea associated with vasoactive intestinal peptide tumors (VIPoma); to reduce blood levels of growth hormone (GH) and insulin-like growth factor (IGF-1) in acromegaly patients who have had inadequate response to or cannot be treated with resection, pituitary irradiation, and bromocriptine at maximally tolerated doses.

Unlabeled Uses

To reduce output from GI fistulas; for variceal bleeding; for relief of diarrhea associated with a variety of conditions; to reduce output from pancreatic fistulas; to treat irritable bowel syndrome; to treat dumping syndrome; to treat the following conditions: antineoplastic therapy, chronic pain management, decreased insulin requirements in diabetes mellitus, enteric fistula, gastrinoma (Zollinger-Ellison syndrome), glucagonoma, insulinoma, intestinal obstruction, local radiotherapy, pancreatic surgery, pancreatitis, thyrotropin- and TSH-secreting tumors.

Contraindications

Standard considerations.

Dosage and Administration

Acromegaly

Withdraw octreotide yearly for approximately 4 wk from patients who received irradiation to assess disease activity. If GH or IGF-1 levels increase and signs and symptoms recur, therapy may be resumed.

Adults

IV / Subcutaneous 50 mcg 3 times daily. Although 100 mcg 3 times daily is the most commonly effective dosage, some patients require up to 500 mcg 3 times daily.

Adults

IM (intragluteally)

Patients not currently receiving octreotide

Before administering the octreotide long-acting depot formulation ( Sandostatin LAR Depot ), patients not currently receiving octreotide should begin therapy with octreotide immediate-release formulation ( Sandostatin injection) given subcutaneously in an initial dosage of 50 mcg 3 times daily. Most patients require 100 to 200 mcg 3 times daily, but some patients require 500 mcg 3 times daily. After maintaining patients on subcutaneous octreotide for at least 2 wk to determine tolerance, patients who are considered responders can be switched to administration of the intragluteal long-acting depot formulation in a dose of 20 mg given IM intragluteally at 4-wk intervals for 3 months; dosage may be adjusted as follows:

GH 2.5 ng/mL or less, IGF-1 normal and clinical symptoms controlled

Maintain octreotide depot dosage at 20 mg every 4 wk.

GH greater than 2.5 ng/mL, IGF-1 elevated and/or clinical symptoms uncontrolled

Increase the octreotide depot dosage to 30 mg every 4 wk.

GH 1 ng/mL or less, IGF-1 normal and clinical symptoms controlled

Reduce the octreotide depot dosage to 10 mg every 4 wk.

GH, IGF-1, or symptoms are not adequately controlled at a dose of 30 mg

The dosage may be increased to 40 mg every 4 wk. Higher doses are not recommended.

Carcinoid Tumors and VIPomas
Adults

IV / Subcutaneous

Carcinoid tumors

Suggested dosage ranges from 100 to 600 mcg/day in 2 to 4 divided doses during the first 2 wk of therapy. Clinically, some patients require as little as 50 mcg/day while others require up to 1,500 mcg/day. Experience with dosages above 750 mcg/day is limited.

VIPomas

200 to 300 mcg/day in 2 to 4 divided doses are recommended during the initial 2 wk of therapy (range, 150 to 750 mcg/day) to control symptoms. Usually, dosages above 450 mcg/day are not required.

Adults

IM (intragluteally)

Patients not currently receiving octreotide immediate-release formulation

Patients should begin therapy with octreotide immediate-release formulation subcutaneously with 100 to 600 mcg/day in 2 to 4 divided doses. Some patients may require doses up to 1,500 mcg/day. Continue treatment for at least 2 wk. Thereafter, patients who are considered responders may be switched to the octreotide long-acting depot formulation in a dosage of 20 mg IM intragluteally at 4 wk intervals for 2 months. Because of the need for serum octreotide to reach therapeutic levels following the initial injection of the depot formulation, carcinoid tumor patients and VIPoma patients should continue receiving the immediate-release formulation subcutaneously for at least 2 wk in the same dosage as before the switch. Failure to continue subcutaneous injections for this period may result in exacerbation of symptoms.

Dosage adjustments after 2 months

If symptoms are adequately controlled, consider a dose reduction to 10 mg for a trial period. If symptoms recur, dosage should be increased to 20 mg every 4 wk. If symptoms are not adequately controlled, increase the octreotide long-acting depot dose to 30 mg every 4 wk. 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, increase the dosage to 20 mg every 4 wk. Doses higher than 30 mg are not recommended. Patients with carcinoid tumors and VIPomas who experience periodic exacerbation of symptoms, whether they are being maintained on the immediate-release or long-acting depot formulation, may be given subcutaneous immediate-release injections for a few days at the dosage they were receiving prior to switching to the depot formulation. When symptoms are controlled, the subcutaneous injections may be discontinued.

Hepatic function impairment

In patients with liver cirrhosis, start with 10 mg every 4 wk.

Renal function impairment

In patients with renal function impairment requiring dialysis, the starting dosage should be 10 mg every 4 wk. In other patients with renal function impairment, the starting dosage should be 20 mg every 4 wk.

General Advice

  • Octreotide long-acting depot formulation should be administered IM intragluteally and never be given IV or subcutaneously. Avoid deltoid injection.
  • Octreotide immediate-release formulation is for IV or subcutaneous administration only.
  • Rotate subcutaneous administration sites.
  • Octreotide is not compatible in total parenteral nutrition solutions.
  • Dilute octreotide in sterile isotonic saline solutions or sterile solutions of dextrose 5% in water in volumes of 50 to 200 mL and infuse over 15 to 30 min or administer by IV push over 3 min. In emergency situations, it may be given by rapid bolus.

Storage/Stability

Sandostatin

Store at 36° to 46°F. Protect from light. May be stored at room temperature (70° to 86°F) for 14 days. Protect from light. Allow to come to room temperature before administration. Do not warm artificially. After initial use, multiple-dose vials should be discarded within 14 days. Octreotide is stable in sterile isotonic solutions or sterile solutions of dextrose 5% in water for 24 h.

Sandostatin LAR Depot

Store at 36° to 46°F. Protect from light. The kit should remain at room temperature for 30 to 60 minutes prior to preparation of the suspension. Use immediately after preparation.

Drug Interactions

Beta-blockers and other bradycardia-inducing drugs

Octreotide has additive effect on heart rate reduction.

Bromocriptine

Availability may be increased by octreotide.

Cyclosporine

May decrease plasma levels of cyclosporine.

Hypoglycemic agents, insulin

Insulin and glucagon secretion may be inhibited by octreotide; monitor blood glucose when starting, stopping or changing the dose of octreotide and adjust antidiabetic treatment as needed.

Incompatibility

Parenteral nutrition solutions.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Sinus bradycardia (25%); hypertension (13%); conduction abnormalities (10%); arrhythmias (9%); arterial thrombosis of the arm; atrial fibrillation, cardiac arrest, orthostatic hypotension, retinal vein thrombosis (postmarketing).

CNS

Fatigue (32%); headache (30%); dizziness (20%); depression, weakness (1% to 4%); aphasia, Bell palsy, convulsions, decreased libido, intracranial hemorrhage, migraines, paranoia (postmarketing).

Dermatologic

Pruritus (18%); rash (15%); alopecia (13%); bruise, flushing (1% to 4%); facial edema, petechiae, urticaria (postmarketing).

EENT

Blurred vision, visual disturbances (1% to 4%); deafness, glaucoma, scotoma, visual field defect (postmarketing).

GI

Diarrhea (58%); abdominal pain or discomfort (44%); nausea (41%); abdominal pain (35%); nausea (30%); flatulence (26%); constipation (19%); vomiting (16%); appendicitis, gallbladder polyp, GI hemorrhage, intestinal obstruction; pancreatitis, peptic/gastric ulcer (postmarketing).

Genitourinary

Pollakiuria, UTI (1% to 4%); breast carcinoma, gynecomastia, hematuria, renal failure, renal insufficiency (postmarketing).

Hematologic-Lymphatic

Anemia (15%); pancytopenia, thrombocytopenia (postmarketing).

Hepatic

Cholelithiasis (38%); decreased liver enzymes, fatty liver, hepatitis (postmarketing).

Hypersensitivity

Octreotide antibodies (25%); anaphylactic shock (postmarketing).

Lab Tests

Increased creatine kinase, increased creatinine (postmarketing)

Local

Injection-site pain (30% to 50%); injection-site hematoma (1% to 4%).

Metabolic-Nutritional

Hyperglycemia (27%); hypothyroidism (12%); hypoglycemia (4%); fat metabolism (1% to 4%); diabetes insipidus, diabetes mellitus, galactorrhea (postmarketing).

Musculoskeletal

Back pain (27%); arthropathy (19%); myalgia (18%); musculoskeletal pain (15%); joint pain (1% to 4%); arthritis, joint effusion (postmarketing).

Respiratory

Upper respiratory tract infection (23%); sinusitis (15%); aggravated pneumothorax, pulmonary hypertension, pulmonary nodule, status asthmaticus (postmarketing).

Miscellaneous

Influenza-like symptoms (20%); generalized pain (15%); upper abdominal pain (11%); goiter (8%); cold symptoms, edema (1% to 4%); aneurysm, enlarged abdomen, hemiparesis, paresis, pituitary apoplexy, Raynaud syndrome, suicide attempt (postmarketing).

Precautions

Monitor

Monitor blood glucose levels when starting or changing the octreotide dose in diabetic patients. Measure baseline and periodically assess thyroid function. Monitor vitamin B 12 levels. Based on diagnosis, lab tests may be helpful in determining response to therapy (eg, GH and IGF-1 for acromegaly, urinary 5-hydroxyindole acetic acid for carcinoid tumors, and baseline and periodic total and/or free T4 for VIPoma).


Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy experience in children is limited.

Elderly

Use with caution, usually starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Renal Function

Dosage reduction may be necessary.

Cardiac effects

In acromegalics, bradycardia, conduction abnormalities, and arrhythmias have occurred. Other ECG changes observed include QT prolongation, axis shifts, early repolarization, low voltage, R/S transition, and early wave progression. Dose adjustments in drugs, such as beta-blockers that have bradycardia effects, may be necessary.

Cholelithiasis

Cholelithiasis may occur; periodically monitor gallbladder function.

Hypoglycemia or hyperglycemia

Serum glucose control may be altered; carefully monitor patient and adjust insulin requirements accordingly.

Nutrition

Dietary fat absorption may be altered. Vitamin B 12 levels and abnormal Schilling tests may occur.

Pancreatitis

Several cases have occurred in patients receiving octreotide.

Pituitary irradiation

In patients who have received pituitary irradiation, withdraw octreotide long-acting depot formulation for approximately 8 wk to assess disease activity. If GH or IGF-1 levels increase and signs and symptoms recur, therapy may be resumed.

Thyroid function

TSH may be suppressed, resulting in hypothyroidism.

Overdosage

Symptoms

Dizziness, flushing, hypoglycemia, nausea.

Patient Information

  • Instruct and observe return demonstration of correct technique for subcutaneous injection. Explain that preferred sites for injection are abdomen, thigh, and hip.
  • Caution patient to report the following symptoms to health care provider: clay-colored stools, dark urine, icterus, jaundice.
  • Advise patient to notify health care provider of abdominal pain, chest pain, dry mouth, edema, fainting, or shortness of breath.

Copyright © 2009 Wolters Kluwer Health.

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