Brand Names

GlucaGen 

Description

Glucagon is a polypeptide hormone identical to naturally-occurring human glucagon. Delivered via a parenteral route, it relaxes the smooth muscle of the stomach, duodenum, small bowel, and colon and temporarily inhibits movement. Glucagon can be used as a diagnostic aid in endoscopic examination of the gastrointestinal tract.  While atropine is usually given to counter vasovagal reactions, glucagon is given to slow intestinal motility. 

Dosing

Notes:

• General instructions
  • The diluent is provided for use only in the preparation of glucagon for subcutaneous, IM, and IV injection and for no other use. The diluent syringe contains 12 mg/ mL of glycerin, water for injection, and hydrochloric acid.
  • Glucagon should not be used at concentrations greater than 1 mg/mL (1 unit).
  • Reconstituted glucagon should be used immediately. Discard any unused portion.
  • Reconstituted glucagon solutions should be used only if they are clear and of a water-like consistency. Do not administer if particulate matter, cloudiness, or discoloration is noted or if solution shows any signs of gel formation.

• Instructions for use as a diagnostic aid
  • Dissolve the lyophilized glucagon using the accompanying diluting solution and use immediately. Discard any unused portion.
  • The doses in table above may be administered for relaxation of the stomach, duodenum, and small bowel, depending on the onset and duration of effect required for the examination.
  • Colon relaxation and reduction of patient discomfort may increase patient satisfaction with the exam.
    

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Overdose

• If overdosage occurs, nausea, vomiting, gastric hypotonicity, and diarrhea would be expected without causing consequential toxicity.
• Intravenous administration of glucagon has been shown to have positive inotropic and chronotropic effects on the heart. A transient increase in both blood pressure and pulse rate may occur following the administration of glucagon.
• Patients taking beta-blockers might be expected to have a greater increase in both pulse and blood pressure, an increase of which will be transient because of glucagon's short half-life.
• The increase in blood pressure and pulse rate may require therapy in patients with pheochromocytoma or coronary artery disease.
• When glucagon was given in large doses to patients with cardiac disease, investigators reported a positive inotropic effect. Side effects included nausea, vomiting, and decreasing serum potassium concentration. Serum potassium concentration could be maintained within normal limits with supplemental potassium.
• The intravenous median lethal dose for glucagon in mice and rats is approximately 300 mg/kg and 38.6 mg/kg, respectively.
• Because glucagon is a polypeptide, it would be rapidly destroyed in the gastrointestinal tract if it were to be accidentally ingested.

Treatment

• In view of the extremely short half-life of glucagon and its prompt destruction and excretion, the treatment of overdosage is symptomatic, primarily for nausea, vomiting, and possible hypokalemia.
• Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of glucagon; it is extremely unlikely that one of these procedures would ever be indicated.

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Reversal Agents

• None

Special Circumstances

• Carcinogenesis, mutagenesis, impairment of fertility:
  
  • Because glucagon is usually given in a single dose and has a very short half-life, no studies have been done regarding carcinogenesis.
  • In a series of studies examining effects on the bacterial mutagenesis (Ames) assay, it was determined that an increase in colony counts was related to technical difficulties in running this assay with peptides and was not due to mutagenic activities of the glucagon.
  • Reproduction studies have been performed in rats at doses up to 2 mg/kg glucagon administered two times a day (up to 40 times the human dose based on body surface area, mg/m2) and have revealed no evidence of impaired fertility.
• Use in pregnancy: Pregnancy Category B. Reproduction studies have not been performed with recombinant glucagon. However, studies with animal-sourced glucagon were performed in rats at doses up to 2 mg/kg glucagon administered two times a day (up to 40 times the human dose based on body surface area, mg/m2), and have revealed no evidence of impaired fertility or harm to the fetus due to glucagon. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
• Use in nursing mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when glucagon is administered to a nursing woman. If the drug is excreted in human milk during its short half-life, it will be hydrolyzed and absorbed like any other polypeptide. Glucagon is not active when taken orally because it is destroyed in the gastrointestinal tract before it can be absorbed.
• Use in pediatric patients: Effectiveness for use as a diagnostic aid has not been established in pediatric patients.
• Use in geriatric patients:
  
  • Clinical studies of glucagon 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.

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Side Effects and Risks

• Severe adverse reactions are very rare.
• Generalized allergic reactions, including urticaria, respiratory distress, and hypotension, have been reported in patients who received glucagon by injection.
• Nausea and vomiting may occur occasionally. These reactions may also occur with hypoglycemia.

Common Issues

Nausea and vomiting can occur especially when used in higher (2 mg) doses 

Warnings

• Glucagon should be administered cautiously to patients with a history suggestive of insulinoma, pheochromocytoma, or both. In patients with insulinoma, intravenous administration of glucagon may produce an initial increase in blood glucose; however, because of glucagon's hyperglycemic effect the insulinoma may release insulin and cause subsequent hypoglycemia. A patient developing symptoms of hypoglycemia after a dose of glucagon should be given glucose orally, intravenously, or by gavage, whichever is most appropriate.
• Exogenous glucagon also stimulates the release of catecholamines. In the presence of pheochromocytoma, glucagon can cause the tumor to release catecholamines, which may result in a sudden and marked increase in blood pressure. If a patient develops a sudden increase in blood pressure, 5 to 10 mg of phentolamine mesylate may be administered intravenously in an attempt to control the blood pressure.
• Generalized allergic reactions, including urticaria, respiratory distress, and hypotension, have been reported in patients who received glucagon by injection.

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Alternative Medications

Anticholinergic drugs (e.g. atropine) can also be used to inhibit the movement of the gastrointestinal tract prior to endoscopic examination, however, carry side effects including dry mouth and urinary retention. Glucagon has been shown to be as effective as these drugs in reducing motility.
 

Contraindications

Glucagon is contraindicated in patients with known hypersensitivity to it or in patients with known pheochromocytoma. 

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Last Updated October 9, 2008