Glucagon is a pancreatic hormone produced by the alpha cells of the pancreas. It is available as injections for intramuscular and intravenous use to treat refractory hypoglycemia, beta-blockers, and calcium-channel blocker toxicity (refractory to epinephrine), and as a diagnostic agent.

Indications of Glucagon:

• Diagnostic aid:

  • During radiologic examinations, it is used as a diagnostic tool as it temporarily inhibits movement of the GI tract in adults.

• Hypoglycemia:

  • Used to treat both adult and paediatric patients with severe hypoglycemia.
  • Note: According to the ADA, all diabetic individuals at risk of level 2 hypoglycemia (less than 54 mg/dl) should be prescribed glucagon. On when and how to administer glucagon, caregivers, educators, or family members of such people should receive training.
  • Restrictions on use: The emergency treatment of hypoglycemia is not suggested for products that are not provided with a syringe and diluent necessary for quick preparation and administration during an emergency outside of a healthcare facility.

• Off Label Use of Glucagon in Adults:

  • Anaphylaxis
  • Beta-blocker overdose
  • Calcium channel blocker overdose

Glucagon dose in adults:

Glucagon dose as a diagnostic aid:

• Relaxation of the stomach, duodenal bulb, duodenum, and small bowel:

  • IM: 1 mg.
  • IV: 0.2 to 0.5 mg.

• Relaxation of colon:

  • IM: 1 to 2 mg.
  • IV: 0.5 to 0.75 mg.

Glucagon dose in the treatment of Hypoglycemia:

• IM, IV, SubQ: 1 mg; may be repeated in 15 minutes as required.
• Intranasal: three milligrammes (one actuation) into one nostril (the dose may be repeated in 15 minutes)
• Note: Administer IV dextrose as soon as it is available; if there is no response to glucagon, must give IV dextrose.

Glucagon dose in the treatment of Anaphylaxis (refractory to epinephrine) in patients on beta-blocker therapy (off-label):

• IV: Initial: 1 to 5 mg bolus, then 5 to 15 mcg/minute of infusion; the infusion rate should be adjusted to produce an appropriate clinical response.

Glucagon dose in the treatment of Beta-blocker overdose (off-label):

• IV: 3 to 10 mg bolus; if no clinical response, repeat the bolus dosage; if there is a clinical response to the bolus dose, start the continuous infusion at 3 to 5 mg/hour; titrate the infusion rate to reach the desired hemodynamic response.

Glucagon dose in the treatment of Calcium channel blocker overdose (off-label):

• IV: 3 to 10 mg bolus; if no clinical response occurs, the bolus dose may be repeated; if a clinical response occurs, the continuous infusion should begin at 3 to 5 mg/hour;

Glucagon Dose in Childrens

Glucagon Dose in the treatment of severe Hypoglycemia:

• Weight-directed dosing:

  • Manufacturer's labeling:

    • Infants, Children, or Adolescents weighing less than 20 kg:
    • Glucagon: IM, IV, SubQ: 0.02-0.03 mg/kg.
    • max dose: 0.5 mg

  • Alternate dosing:

    • Infants, Children, and Adolescents:
      • AAP: IM, IV, Subcutaneous: 0.03 mg/kg; max dose: 1 mg.
      • IDF-ISPAD: IM, Subcutaneous: 0.01-0.03 mg/kg; max dose-dependent on age: <12 years: 0.5 mg; ≥12 years: 1 mg.

• Fixed dosing; age-directed:

  • Manufacturer's labeling: GlucaGen: IM, IV, SubQ:

    • Infants and Children <6 years: 0.5 mg
    • Children and Adolescents ≥6 years: 1 mg

  • Alternate dosing: IM, Subcutaneous:

    • IDF-ISPAD (IDF-ISPAD, 2011):

      • Infants and Children <12 years: 0.5 mg
      • Children and Adolescents ≥12 years: 1 mg

    • CDA (Canadian Diabetes Association, 2013):

      • Infants and Children ≤5 years: 0.5 mg
      • Children and Adolescents >5 years: 1 mg

• Fixed dosing; weight-directed:

  • Infants, Children, and Adolescents:

    • Manufacturer's labeling: IM, IV, SubQ:

      • Glucagon: Patient weight:

        • <20 kg: 0.5 mg
        • ≥20 kg: 1 mg

      • GlucaGen: Patient weight:

        • <25 kg: 0.5 mg
        • ≥25 kg: 1 mg

Glucagon dose for the prevention of Hypoglycemia, during illness (fixed dosing, mini-dose): SubQ:

Note: These doses are lower than those used to treat hypoglycemia, and they have been demonstrated to prevent hypoglycemia for several hours in conditions like gastroenteritis and nausea/vomiting that are linked to hypoglycemia.

• Infants and Children <2 years:

  • 0.02 mg.

• Children and Adolescents 2-15 years:

  • 0.01 mg per year of age.

• Adolescents >15 years:

  • 0.15 mg.

Glucagon dose for the treatment of Beta-blocker or calcium channel blocker toxicity/overdose:

• Infants and Children: Limited data available : IV:

  • Loading dose: 0.03-0.15 mg/kg.
  • Continuous IV infusion: 0.07 mg/kg/hour; max rate: 0.5 mg/hour.

• Adolescents: IV:

  • Loading dose: 5-10 mg over several minutes.
  • Continuous IV infusion: 1-5 mg/hour.

Pregnancy Risk Category: B

• During animal reproduction studies, there were no adverse events.

Glucagon use during breastfeeding:

• Breastfeeding infants are less likely to experience side effects because glucagon is not absorbed through the GI tract.

Dose adjustment in renal disease:

No dosage adjustments are provided in the manufacturer’s labeling.

Dose adjustment in liver disease:

No dosage adjustments are provided in the manufacturer’s labeling.

Side Effects of Glucagon:

• Gastrointestinal:

  • Nausea (With Rapid Administration Of High Doses)
  • Vomiting (With Rapid Administration Of High Doses)

• Cardiovascular:

  • Hypotension (Up To 2 Hours After GI Procedures)
  • Increased Blood Pressure
  • Increased Pulse

• Dermatologic:

  • Skin Rash

• Hypersensitivity:

  • Anaphylactic Shock
  • Hypersensitivity Reaction

• Respiratory:

  • Dyspnea

Contraindications to Glucagon:

• Hypersensitivity to glucagon, lactose or any other component of the formulation
• Pheochromocytoma
• Insulinoma
• Glucagonoma (excluding GlucaGen)

Warnings and precautions

• Hypersensitivity reactions

  • Allergic reactions to glucagon have been reported and are usually associated with endoscopic patients
  • These reactions include anaphylactic shock and skin rash (with hypotension or respiratory problems).

• Necrolytic migratory Erythema:

  • Necrolytic migratory Erythema (NME) is rarely reported after continuous glucagon injections.
  • This cutaneous disease is frequently linked to glucagonomas (glucagon producing tumors). Erythematous bullae and plaques are its defining features.
  • It can affect the face, legs, groin, perineum and legs.
  • NME can lead to serious side effects. You should consider all options.

• Insufficiency of the adrenals:

  • Patients with adrenal insufficiency should be cautious as the glucose stores in their liver may be reduced.

• Cardiac disease

  • Be careful.

• Hypoglycemia chronic:

  • Patients with hypoglycemia should be cautious as the liver glucose stores can be reduced.

• Diabetes:

  • Use it as a diagnostic tool for diabetics on insulin.

• Glucagonoma

  • Be careful.
  • Patients with this condition (except GlucaGen) are not advised to use glucagon.

• Insulinoma

  • Blood sugar levels may increase as a result of exogenous glucagon, followed by rebound hypoglycemia.
  • Patients with this condition should not take glucagon.

• Pheochromocytoma:

  • Catecholamines may be released by exogenous glucagon, raising blood pressure.
  • Patients with this condition should not take glucagon.

• Fasting and starvation:

  • Keep in mind that prolonged fasting or starvation may result in the depletion of hepatic glycogen.

Glucagon: Drug Interaction

Monitoring parameters:

• Bp
• Heart rate
• Blood glucose levels
• Electrocardiogram
• Mentation
• Signs or symptoms of a hypersensitivity reaction.

How to administer Glucagon?

Diagnostic aid:

• For administration by IM or IV. Administering intravenously should take more than a minute.
• If it is appropriate given the diagnostic process used, patients who have been fasting should be given oral carbohydrates after the diagnostic procedure. Bolus intravenous dosages more than 1 mg are not advised.

Hypoglycemia:

• Upper arms, thighs, or buttocks may be used as injection sites for intravenous, subcutaneous, or intramuscular injections. Fast and long-acting oral carbohydrates should be administered to the patient as soon as feasible following the response to treatment.

IV:

• Rapid intravenous injection may cause nausea and vomiting; the patient should be positioned in a lateral recumbent position to protect the airway and prevent choking when consciousness returns.
• Patients on beta-blockers should get an IV bolus over a 5-minute period if they experience epinephrine-refractory anaphylaxis.

Beta-blocker/calcium channel blocker toxicity:

• Give a IV bolus over 3 to 5 minutes; consider using continuous infusions.

Mechanism of action of Glucagon:

• Stimulation of adenylate cyclase results in an increased production of cyclic AMP.
• This causes hepatic glucose to rise and gluconeogenesis.
• The stomach, duodenum, and small bowel's smooth muscles can relax as an extrahepatic impact.

The onset of action: Blood glucose levels:

• Peak effect seen with IV administration is 5 to 20 minutes with IM is 30 minutes and with subcutaneous administration, it is 30 to 45 minutes.

Duration:

• It takes 60-90 minutes for glucose elevation with IV, IM, SubQ injection.
• GI relaxation occurs in 9-25 minutes with IV and in 12-32 mins in case of IM injection.

Metabolism:

• The liver is the primary site, with kidneys and plasma also experiencing some inactivation.

Half-life elimination,

• The plasma half-life is 8-18 mins in case of IV and 26-45mins in case of IM injection

Time to peak:

• Almost 10-12.5 mins in IM and 20 mins in case of subcutaneous injection.

International Brand Names of Glucagon:

• GlucaGen Diagnostic
• GlucaGen HypoKit
• Glucagon Emergency
• Garcon
• Glucagen
• GlucaGen
• Glucagen G
• Glucagen Novo
• Glucagon Novo Nordisk
• R-Glucagon Lil

Glucagon Brand Names in Pakistan:

No Brands Available in Pakistan.