Octreotide Acetate

Octreotide acetate injection is a somatostatin analogue indicated:

• Acromegaly
  : To reduce blood levels of growth hormone (GH) and insulin growth factor-1 (IGF-1; 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. (
  1.1     Acromegaly

  Octreotide acetate injection is indicated to reduce blood levels of growth hormone (GH) and insulin growth factor-1 (IGF-1; 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.
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• Carcinoid Tumors
  : 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. (
  1.2     Carcinoid Tumors

  Octreotide acetate injection is indicated for treatment of severe diarrhea and flushing episodes associated with metastatic carcinoid tumors.
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• Vasoactive Intestinal Peptide Tumors (VIPomas)
  : For the treatment of profuse watery diarrhea associated with VIP-secreting tumors. (
  1.3     Vasoactive Intestinal Peptide Tumors

  Octreotide acetate injection is indicated for the treatment of the profuse watery diarrhea associated with vasoactive intestinal peptide tumors (VIPomas)-secreting tumors.
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Improvement in clinical signs and symptoms, or reduction in tumor size or rate of growth, were not shown in clinical trials performed with octreotide acetate injection; these trials were not optimally designed to detect such effects. (

• Octreotide acetate injection may be administered subcutaneously or intravenously. (
  2.1     Dosage and Administration Overview

  • Octreotide acetate injection may be administered subcutaneously or intravenously. Pain with subcutaneous administration may be reduced by using the smallest volume that will deliver the desired dose. 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. Octreotide acetate injection is not compatible in Total Parenteral Nutrition solutions because of the formation of a glycosyl octreotide conjugate which may decrease the efficacy of the product.
  • Octreotide acetate injection may be diluted in volumes of 50 mL to 200 mL and infused intravenously over 15 to 30 minutes or administered by intravenous (IV) push over 3 minutes. In emergency situations (e.g., carcinoid crisis), it may be given by rapid bolus.
  • Assess total and/or free T4 levels at baseline and periodically during chronic octreotide acetate injection therapy.
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• Acromegaly
  : Recommended initial octreotide acetate injection dosage is 50 mcg three times daily during the initial 2 weeks of therapy. Maintenance dose 100 mcg to 500 mcg three times daily. (
  2.2     Recommended Dosage and Monitoring for Acromegaly

  The recommended initial dosage of octreotide acetate injection is 50 mcg three times daily to be administered subcutaneously. Increase octreotide acetate injection dose based upon GH or IGF-1 levels. The goal is to achieve GH levels less than 5 ng/mL or IGF-1 levels within normal range. Monitor GH or IGF-1 every two weeks after initiating octreotide acetate injection therapy or with dosage change, and to guide titration.

  The most common dosage is 100 mcg three times daily, but some patients require up to 500 mcg three times daily 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.

  Octreotide acetate injection should be withdrawn yearly for approximately 4 weeks from patients who have received irradiation to assess disease activity. If GH or IGF-1 levels increase and signs and symptoms recur, octreotide acetate injection therapy may be resumed.
  )
• Carcinoid Tumors
  : Recommended dosage range of 100 mcg to 600 mcg daily in two to four divided doses during the initial 2 weeks of therapy. (
  2.3     Recommended Dosage and Monitoring for Carcinoid Tumors

  The recommended daily dosage of octreotide acetate injection during the first 2 weeks of therapy ranges from 100 to 600 mcg/day in two to four divided doses given subcutaneously (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. Measurement of urinary 5-hydroxyindole acetic acid, plasma serotonin, plasma Substance P may be useful in monitoring the progress of therapy.
  )
• VIPomas
  : Recommended dosage range of 200 mcg to 300 mcg daily in two to four divided doses during the initial 2 weeks of therapy. (
  2.4     Recommended Dosage and Monitoring for Vasoactive Intestinal Peptide Tumors

  Daily dosages of 200 mcg to 300 mcg in two to four divided doses given subcutaneously are recommended during the initial 2 weeks of therapy (range, 150 mcg to 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. Measurement of Plasma vasoactive intestinal peptide (VIP) may be useful in monitoring the progress of therapy.
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Injection: 100 mcg/mL of octreotide (as acetate) as a clear solution in a single-dose vial.

• Females and Males of Reproductive Potential
  : Advise premenopausal females of the potential for an unintended pregnancy. (
  8.3     Females and Males of Reproductive Potential

  Discuss the potential for unintended pregnancy with premenopausal women as the therapeutic benefits of a reduction in GH levels and normalization of insulin-like growth factor 1 (IGF-1) concentration in acromegalic females treated with octreotide may lead to improved fertility.
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• Cardiac Function Abnormalities
  : Increased risk for higher degree of atrioventricular blocks. Consider cardiac monitoring in patients receiving octreotide acetate injection intravenously. Bradycardia, arrhythmias, or conduction abnormalities may occur. Use with caution in at-risk patients. Dosage adjustment of cardiac medications may be necessary. (
  5.1     Cardiac Function Abnormalities

  Complete Atrioventricular Block

  Patients who receive octreotide acetate injection intravenously may be at increased risk for higher degree atrioventricular blocks. In postmarketing reports, complete atrioventricular block was reported in patients receiving IV octreotide acetate injection during surgical procedures. In the majority of patients, octreotide acetate injection was given at higher than recommended doses and/or as a continuous IV infusion. The safety of continuous IV infusion has not been established in patients receiving octreotide acetate injection for the approved indications. Consider cardiac monitoring in patients receiving octreotide acetate injection intravenously.

  Other Cardiac Conduction Abnormalities

  Other cardiac conduction abnormalities have occurred during treatment with octreotide acetate injection. In acromegalic patients, bradycardia (< 50 bpm) developed in 25%; conduction abnormalities occurred in 10% and arrhythmias occurred in 9% of patients during octreotide acetate injection therapy

  [see Adverse Reactions (6)]

  . Other electrocardiogram (ECG) 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 (CHF), initiation of octreotide acetate injection therapy resulted in worsening of CHF with improvement when drug was discontinued. Confirmation of a drug effect was obtained with a positive rechallenge.
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• Cholelithiasis and Complications of Cholelithiasis
  : Monitor periodically. Discontinue if complications of cholelithiasis are suspected. (
  5.2     Cholelithiasis and Complications of Cholelithiasis

  Octreotide acetate injection may inhibit gallbladder contractility and decrease bile secretion, which may lead to gallbladder abnormalities or sludge. Acute cholecystitis, ascending cholangitis, biliary obstruction, cholestatic hepatitis, or pancreatitis have been reported with octreotide acetate injection therapy. 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 octreotide acetate injection for 12 months or longer was 52%. Less than 2% of patients treated with octreotide acetate injection for 1 month or less developed gallstones. One patient developed ascending cholangitis during octreotide acetate injection therapy and died. If complications of cholelithiasis are suspected, discontinue octreotide acetate injection and treat appropriately.
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• Glucose Metabolism
  : Hypoglycemia or hyperglycemia may occur. Glucose monitoring is recommended and anti-diabetic treatment may need adjustment. (
  5.3     Hyperglycemia and Hypoglycemia

  Octreotide acetate injection alters the balance between the counter-regulatory hormones, insulin, glucagon and GH, which may result in hypoglycemia or hyperglycemia. The hypoglycemia or hyperglycemia which occurs during octreotide acetate injection therapy is usually mild but may result in overt diabetes mellitus or necessitate dose changes in insulin or other anti-diabetic agents. Hypoglycemia and hyperglycemia occurred on octreotide acetate injection in 3% and 16% of acromegalic patients, respectively

  [see Adverse Reactions (6)]

  . Severe hyperglycemia, subsequent pneumonia, and death following initiation of octreotide acetate injection therapy was reported in one patient with no history of hyperglycemia.

  Monitor glucose levels during octreotide acetate injection therapy. Adjust dosing of insulin or other anti-diabetic therapy accordingly.
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• Thyroid Function
  : Hypothyroidism may occur. Monitor thyroid levels periodically. (
  5.4     Thyroid Function Abnormalities

  Octreotide suppresses secretion of thyroid stimulating hormone (TSH), which may result in hypothyroidism. Baseline and periodic assessment of thyroid function (TSH, total, and/or free T₄) is recommended during chronic therapy

  [see Adverse Reactions (6)]

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