Action And Clinical Pharmacology: Glucagon causes an increase in blood glucose concentration. Glucagon acts only on liver glycogen, converting it to glucose.
Parenteral administration of glucagon produces relaxation of the smooth muscle of the stomach, duodenum, small bowel and colon.
The half-life of glucagon in plasma is approximately 3 to 6 minutes.
Indications And Clinical Uses: Hypoglycemia: Glucagon is useful in counteracting severe hypoglycemic reactions.
The patient with type I diabetes does not have as great a response in blood glucose levels as does the stable type II diabetic. Therefore, supplementary carbohydrate should be given as soon as possible, especially to a child or adolescent patient.
Diagnostic Aid: As a diagnostic aid in the radiologic examination of the stomach, duodenum, small bowel and colon when a hypotonic state would be advantageous.
Contra-Indications: In patients with known hypersensitivity to glucagon or patients with pheochromocytoma.
Manufacturers’ Warnings In Clinical States: Glucagon should be administered cautiously to patients with a history suggestive of insulinoma and/or pheochromocytoma. In patients with insulinoma, i.v. administration of glucagon will produce an initial increase in blood glucose however, because of glucagon’s insulin releasing effect, it may cause the insulinoma to release its insulin and subsequently cause hypoglycemia. A patient developing symptoms of hypoglycemia after a dose of glucagon should be given glucose orally, i.v., or by gavage, whichever is more appropriate.
Exogenous glucagon also stimulates the release of catecholamines. In the presence of pheochromocytoma, glucagon can cause the tumor to release catecholamines which results in a sudden and marked increase in blood pressure. If a patient suddenly develops a marked increase in blood pressure, 5 to 10 mg of phentolamine mesylate may be administered i.v. 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.
Precautions: Glucagon is helpful in hypoglycemia only if liver glycogen is available. Because glucagon is of little or no help in states of starvation, adrenal insufficiency, or chronic hypoglycemia, glucose should be considered for the treatment of hypoglycemia.
Laboratory Tests: Blood glucose determinations may be obtained to follow the patient in hypoglycemic shock until he or she is asymptomatic.
Pregnancy: Reproduction studies have been performed in rats at doses up to 2 mg/kg b.i.d., (up to 120 times the human dose), and have revealed no evidence of 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.
Lactation: It is not known whether this drug is excreted in human milk. Glucagon is not active when taken orally because it is destroyed in the gastrointestinal tract before it can be absorbed.
Adverse Reactions: Nausea, vomiting, and hypokalemia may occur occasionally. Generalized allergic reactions have been reported.
Symptoms And Treatment Of Overdose: Symptoms: No cases of human overdosage of glucagon have been reported. Glucagon is generally well tolerated. If overdosage occurred, it would not be expected to cause consequential toxicity, but would be expected to be associated with nausea, vomiting, gastric hypotonicity, and diarrhea.
I.V. administration of glucagon has been shown to have a positive inotropic and chronotropic effect. A transient increment in both blood pressure and pulse rate may occur following the administration of glucagon. Patients taking b-blockers might be expected to have a greater increment in both pulse rate and blood pressure. This increase 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 cardiac patients, investigators reported a positive inotropic effect. These investigators administered glucagon in doses of 0.5 to 16 mg/hour by continuous infusion for periods of 5 to 166 hours. Total doses ranged from 25 to 996 mg, and a 21-month-old child received approximately 8.25 mg in 165 hours. Side effects included nausea, vomiting, and decreasing serum potassium concentration. Serum potassium concentration could be maintained within normal limits with supplemental potassium. The i.v. median lethal dose for glucagon in rats and mice is approximately 300 mg/kg.
Because glucagon is a polypeptide, it would be rapidly destroyed in the gastrointestinal tract if it were to be accidentally ingested.
Treatment: In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.
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.
If the patient develops a dramatic increase in blood pressure, 5 to 10 mg of phentolamine has been shown to be effective in lowering blood pressure for the short time that control would be needed.
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.
Dosage And Administration: Hypoglycemia: The diluent is provided for use only in the preparation of glucagon for intermittent parenteral injection and for no other use.
If glucagon is to be given at doses higher than 2 mg, it should be reconstituted with Sterile Water for Injection instead of the supplied diluting solution and used immediately.
Directions for use of Glucagon: 1. Dissolve the lyophilized glucagon in the accompanying diluent.
2. Glucagon should not be used at concentrations greater than 1 mg/mL (1 unit/mL).
3. Glucagon solutions should not be used unless they are clear and of a water-like consistency.
4. For adults and for children weighing more than 20 kg, give 1 mg (1 unit) by s.c., i.m., or i.v. injection.
5. For children weighing less than 20 kg, give 0.5 mg (0.5 unit) or a dose equivalent to 20 to 30 g/kg.
6. The patient will usually awaken within 15 minutes. If the response is delayed, there is no contraindication to the administration of 1 or 2 additional doses of glucagon; however, in view of the deleterious effects of cerebral hypoglycemia and depending on the duration and depth of coma, the use of parenteral glucose must be considered by the physician.
7. I.V. glucose must be given if the patient fails to respond to glucagon.
8. When the patient responds, give supplemental carbohydrate to restore the liver glycogen and prevent secondary hypoglycemia.
Instructions to the Family: Instructions describing the method of using glucagon are included in the literature which accompanies the patient’s package. It is advisable for the patient and family members to become familiar with the technique of preparing Glucagon for Injection before an emergency arises. Patients are instructed to use 1 mg (1 unit) for adults and, if recommended by a doctor, 1/2 the adult dose (0.5 mg [0.5 unit]) for children weighing less than 20 kg.
General Management of Hypoglycemia: The following are helpful measures in the prevention of hypoglycemic reactions due to insulin: 1. Reasonable uniformity from day to day with regard to diet, insulin, and exercise.
2. 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.
3. Frequent testing of the urine so that a change in insulin requirements can be foreseen.
4. 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.
If the patient is unaware of the symptoms of hypoglycemia, he may lapse into insulin shock; therefore, the physician should instruct the patient in this regard when feasible.
It is important that the patient be aroused as quickly as possible, because prolonged hypoglycemic reactions may result in cortical damage. Glucagon or i.v. glucose will awaken the patient sufficiently so that oral carbohydrates may be taken.
Caution: Although glucagon may be used for the treatment of hypoglycemia by the patient during an emergency, the physician must still be notified when hypoglycemic reactions occur so that the dose of insulin may be adjusted more accurately.
Diagnostic Aid: Dissolve the lyophilized glucagon in the accompanying diluting solution. Glucagon should not be used at concentrations greater than 1 mg/mL (1 unit/mL).
The doses in Table I may be administered for relaxation of the stomach, duodenum, and small bowel, depending on the time of onset of action and the duration of effect required for the examination. Since the stomach is less sensitive to the effect of glucagon, 0.5 mg (0.5 unit) i.v. or 2 mg (2 units) i.m. are recommended.
For examination of the colon, it is recommended that a 2 mg (2 units) dose be administered i.m. approximately 10 minutes prior to initiation of the procedure. Relaxation of the colon and reduction of discomfort to the patient will allow the radiologist to perform a more satisfactory examination.
Prior to reconstitution, the vials may be stored at controlled room temperature, 15 to 30°C.
Glucagon should be used immediately after reconstitution. Discard any unused portion.
Availability And Storage: Each rubber-stoppered vial of lyophilized powder contains: glucagon for injection USP 1 unit (1 mg) (as the hydrochloride). Nonmedicinal ingredients: vial of lyophilized glucagon: lactose 49 mg; diluting solution: glycerin and phenol. May contain sodium hydroxide and/or hydrochloric acid for pH adjustment. Vials of 1 mL.
Glucagon Emergency Kit: Each kit contains: 1 vial of glucagon 1 unit (1 mg) and a prefilled Hyporet of diluting solution.
GLUCAGON INJECTION Lilly Glucagon HCl Hyperglycemic Agent