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.
Glucagon is effective in treating hypoglycemia only if sufficient liver glycogen is present. Because glucagon is of little or no help in states of starvation, adrenal insufficiency, or chronic hypoglycemia, hypoglycemia in these conditions should be treated with glucose.
Information for Patients
Refer patients and family members to the attached Information for the User for instructions describing the method of preparing and injecting glucagon. Advise the patient and family members to become familiar with the technique of preparing glucagon before an emergency arises. Instruct patients to use 1 mg (1 unit) for adults and 1/2 the adult dose (0.5 mg) [0.5 unit] for pediatric patients weighing less than 44 lb (20 kg).
Patients and family members should be informed of the following measures to prevent hypoglycemic reactions due to insulin:
- Reasonable uniformity from day to day with regard to diet, insulin, and exercise.
- Careful adjustment of the insulin program so that the type (or types) of insulin, dose, and time (or times) of administration are suited to the individual patient.
- Frequent testing of the blood or urine for glucose so that a change in insulin requirements can be foreseen.
- Routine carrying of sugar, candy, or other readily absorbable carbohydrate by the patient so that it may be taken at the first warning of an oncoming reaction.
To prevent severe hypoglycemia, patients and family members should be informed of the symptoms of mild hypoglycemia and how to treat it appropriately.
Family members should be informed to arouse the patient as quickly as possible because prolonged hypoglycemia may result in damage to the central nervous system. Glucagon or intravenous glucose should awaken the patient sufficiently so that oral carbohydrates may be taken.
Patients should be advised to inform their physician when hypoglycemic reactions occur so that the treatment regimen may be adjusted if necessary.
Blood glucose determinations should be obtained to follow the patient with hypoglycemia until patient is asymptomatic.
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.
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.
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.
For the treatment of hypoglycemia: The use of glucagon in pediatric patients has been reported to be safe and effective.2-6
For use as a diagnostic aid: Effectiveness has not been established in pediatric 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.