Glucagon [rDNA origin]) for Injection

Name: Glucagon [rDNA origin]) for Injection

Side effects

Side effects may include nausea and vomiting at doses above 1 mg or with rapid injection. Hypotension has been reported up to 2 hours after administration in patients receiving GlucaGen® as premedication for upper GI endoscopy procedures. Glucagon exerts positive inotropic and chronotropic effects and may, therefore, cause tachycardia and hypertension. Adverse reactions indicating toxicity of GlucaGen® have not been reported. A temporary 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 temporary because of glucagon's short half-life [see DRUG INTERACTIONS]. The increase in blood pressure and pulse rate may require therapy in patients with pheochromocytoma or coronary artery disease [see WARNINGS AND PRECAUTIONS]. Anaphylactic reactions may occur in some cases [see WARNINGS AND PRECAUTIONS].

The following adverse reactions have been identified during postapproval use of GlucaGen®. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Table 1: Frequency of Adverse Reactions

Treatment of severe hypoglycemia
Frequency (%) Adverse Reaction
< 10 Nausea
< 1 Vomiting
Use as a diagnostic aid
< 10 Nausea
< 1 Vomiting
< 1 Hypoglycemia
< 1 Hypoglycemic coma

Clinical pharmacology

Mechanism Of Action

Antihypoglycemic Action

Glucagon induces liver glycogen breakdown, releasing glucose from the liver. Hepatic stores of glycogen are necessary for glucagon to produce an antihypoglycemic effect.

Gastrointestinal Motility Inhibition

Extra hepatic effects of glucagon include relaxation of the smooth muscle of the stomach, duodenum, small bowel, and colon.

Pharmacodynamics

For the Treatment of Severe Hypoglycemia

Blood glucose concentration rises within 10 minutes of injection and maximal concentrations are attained at approximately 30 minutes after injection (see Figure 1). The duration of hyperglycemic action after intravenous or intramuscular injection is 60–90 minutes.

Figure 1: Recovery from Insulin Induced Hypoglycemia (mean blood glucose) After Intramuscular Injection of 1 mg GlucaGen® in Type I Diabetic Men

For Use as a Diagnostic Aid

Table 2: Pharmacodynamic Properties of Glucagon

Route of Administration Dose* Time of Maximal Glucose Concentration Time of Onset of Action for GI Smooth Muscle Relaxation Duration of Smooth Muscle Relaxation1
IV 0.25-0.5 mg (0.25-0.5 units) 5-20 minutes 45 seconds 9-17 minutes
2 mg (2 units) 5-20 minutes 45 seconds 22-25 minutes
IM 1 mg (1 unit) 30 minutes 8-10 minutes 12-27 minutes
2 mg (2 units) 30 minutes 4-7 minutes 21-32 minutes
*The usual diagnostic dose for relaxation of the stomach, duodenal bulb, duodenum, and small bowel is 0.2–0.5 mg given intravenously or 1 mg given intramuscularly; the usual dose to relax the colon is 0.5–0.75 mg intravenously and 1–2 mg intramuscularly.
1 Note: The time of maximal glucose concentration for GlucaGen® administered subcutaneously is 30-45 minutes.

Pharmacokinetics

Intramuscular injection of 1 mg GlucaGen® resulted in a mean Cmax (CV%) of 1686 pg/mL (43%) and median Tmax of 12.5 minutes. The mean apparent half-life of 45 minutes after intramuscular injection probably reflects prolonged absorption from the injection site. Glucagon is degraded in the liver, kidney, and plasma.

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