Glucag0n

Overdose

If overdosage occurs, the patient may experience nausea, vomiting, inhibition of GI tract motility, increase in blood pressure and heart rate, and decrease in serum potassium. In case of suspected overdosage, monitor and correct hypokalemia. If the patient develops a severe increase in blood pressure, phentolamine mesylate may be effective in lowering blood pressure for the short time that control would be needed.

Contraindications

Glucag0N for Injection is contraindicated in patients with:

• Pheochromocytoma because of the risk of increased blood pressure
• Insulinoma because of the risk of hypoglycemia
• Glucag0Noma because of the risk of hypoglycemia

Pharmaceutical form

Undesirable effects

The following serious adverse reactions are described below and elsewhere in the labeling:

• Hypertension in patients with Pheochromocytoma
• Hypoglycemia in Patients with Insulinoma and Glucag0Noma
• Hyperglycemia in Patients with Diabetes Mellitus
• Hypersensitivity and Allergic Reactions; generalized allergic reactions including generalized rash, and in some cases anaphylactic shock with breathing difficulties, and hypotension

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in clinical trials of another drug and may not reflect the rates observed in practice.

In an open-label clinical study of Glucag0N for Injection, 29 healthy volunteers received a single dose of 1 mg Glucag0N for Injection intramuscularly. Table 1 shows the most common adverse reactions that were not present at baseline and occurred in at least 5% of patients.

Table 1: Adverse Reactions in Healthy Volunteers Who Received Glucag0N for Injection, 1 mg Administered Intramuscularly

The following adverse reactions have been identified from the literature and clinical studies with the use of Glucag0N. Therefore, it is not possible to reliably estimate their frequency.

• Nausea and vomiting occurred with doses above 1 mg administered by rapid intravenous injection (within 1 to 2 seconds). Doses above 1 mg are not recommended for intravenous use.
• Hypotension was reported up to 2 hours after administration in patients receiving Glucag0N as premedication for upper GI endoscopy procedures.
• A temporary increase in both blood pressure and pulse rate occurred following the administration of Glucag0N. Patients taking beta-blockers experienced a temporary increase in both pulse and blood pressure that was greater than normal.
• Other adverse reactions included hypoglycemia and hypoglycemic coma, as described in postmarketing reports. Patients taking indomethacin may be more likely to experience hypoglycemia following Glucag0N administration.

Therapeutic indications

Glucag0N for Injection is indicated for use as a diagnostic aid during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract.

Glucag0N for Injection is not indicated for the emergency treatment of hypoglycemia because it is not packaged with a syringe and diluent necessary for rapid preparation and administration during an emergency outside of a healthcare facility.

Pharmacodynamic properties

Table 3 displays the pharmacodynamics properties of Glucag0N for Injection as a diagnostic aid during radiologic examination.

Table 3: Pharmacodynamic Properties of Glucag0N for Injection as a Diagnostic Aid

Name of the medicinal product

Special warnings and precautions for use

Included as part of the PRECAUTIONS section.

Glucag0N for Injection is contraindicated in patients with pheochromocytoma because Glucag0N may stimulate the release of catecholamines from the tumor, which may result in a sudden and marked increase in blood pressure.

Glucag0N for Injection is contraindicated in patients with insulinoma or Glucag0Noma as it may cause secondary hypoglycemia. Test patients suspected of having Glucag0Noma for blood levels of Glucag0N prior to treatment, and monitor for changes in blood glucose levels during treatment. If a patient develops symptoms of hypoglycemia after a dose of Glucag0N for Injection, administer glucose orally or intravenously.

Treatment with Glucag0N for Injection in patients with diabetes mellitus may cause hyperglycemia. Monitor diabetic patients for changes in blood glucose levels during treatment. If patients develop symptoms of hyperglycemia after a dose of Glucag0N for Injection, administer insulin.

Glucag0N for Injection may increase myocardial oxygen demand, blood pressure, and pulse rate which may be life-threatening in patients with cardiac disease. Cardiac monitoring is recommended in patients with cardiac disease during Glucag0N treatment, and an increase in blood pressure and pulse rate may require therapy.

Generalized allergic reactions and hypersensitivity, including generalized rash, and anaphylactic shock with breathing difficulties, and hypotension, have been reported with Glucag0N treatment or lactose. Discontinue Glucag0N for Injection and administer standard treatment for anaphylaxis if needed.

Long term studies in animals to evaluate carcinogenic potential have not been performed.

Synthetic Glucag0N was negative in the bacterial reverse mutation assay (Ames test). The clastogenic potential of synthetic Glucag0N in the Chinese Hamster Ovary (CHO) assay was positive in the absence of metabolic activation. Doses of 100 and 200 mg/kg of Glucag0N of both pancreatic and recombinant origins gave slightly higher incidences of micronucleus formation in male mice but there was no effect in females. The weight of evidence indicates that synthetic and recombinant Glucag0N are not different and do not pose a genotoxic risk to humans.

Glucag0N (rDNA and synthetic origin) was not tested in animal fertility studies. Studies in rats have shown that pancreatic Glucag0N does not cause impaired fertility.

Reproduction studies were performed in rats and rabbits with another Glucag0N product at doses of 0.4, 2, and 10 mg per kg. These doses represent exposures of up to 100 and 200 times the human dose based on mg/m² for rats and rabbits, respectively, and revealed no evidence of harm to the fetus. There are, however, no adequate and well-controlled studies in pregnant women. Glucag0N does not cross the human placental barrier.

It is not known whether Glucag0N is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Glucag0N is administered to a nursing woman. No clinical studies have been performed in nursing mothers, however, Glucag0N is a peptide and intact Glucag0N is not absorbed from the GI tract. Therefore, even if the infant ingested Glucag0N it would be unlikely to have any effect on the infant. Additionally, Glucag0N has a short plasma half-life thus limiting amounts available to the child.

Safety and effectiveness of Glucag0N for Injection have not been established in pediatric patients for use as a diagnostic aid during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract.

Dosage (Posology) and method of administration

Determine the dose based on the type of diagnostic procedure, the route of administration and expected procedure duration.

The usual dose to inhibit movement of the:

• Stomach and small bowel is 0.2 mg to 0.5 mg given intravenously or 1 mg given intramuscularly.
• Colon is 0.5 mg to 0.75 mg given intravenously or 1 mg to 2 mg given intramuscularly.

Bolus doses above 1 mg administered intravenously have caused nausea and vomiting and are not recommended.

Glucag0N for Injection is a lyophilized powder, which requires reconstitution with Sterile Water for Injection prior to intravenous or intramuscular use.

• Using a syringe, withdraw 1 mL of Sterile Water for Injection and inject into the vial containing Glucag0N for Injection lyophilized powder.
• Shake the vial gently until the powder is completely dissolved and no particles remain in the reconstituted solution.
• Visually inspect the reconstituted solution for particulate matter and discoloration prior to administration. The reconstituted solution should be clear and of water-like consistency. Discard the reconstituted solution if there are signs of gel formation or particles.
• The reconstituted solution has a concentration of approximately 1 mg of Glucag0N per mL.
• Use the reconstituted Glucag0N immediately after reconstitution.

• Glucag0N for Injection must be administered by medical personnel.
• The timing of administration of Glucag0N for Injection depends upon the organ under examination and route of administration.
• If given intravenously, administer Glucag0N for Injection as a bolus over a time period of 1 minute.
• Discard any unused portion.
• After the end of the diagnostic procedure, give oral carbohydrates to patients who have been fasting, if this is compatible with the diagnostic procedure.