Medically reviewed on Nov 22, 2018

Pronunciation

(GLOO ka gon)

Index Terms

• Glucagon HCl
• Glucagon Hydrochloride

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Kit, Injection:

Glucagon Emergency: 1 mg [contains lactose]

Solution Reconstituted, Injection:

GlucaGen Diagnostic: 1 mg (1 ea)

GlucaGen HypoKit: 1 mg (1 ea)

Generic: 1 mg (1 ea)

Brand Names: U.S.

• GlucaGen Diagnostic
• GlucaGen HypoKit
• Glucagon Emergency

Pharmacologic Category

• Antidote
• Antidote, Hypoglycemia
• Diagnostic Agent

Pharmacology

Stimulates adenylate cyclase to produce increased cyclic AMP, which promotes hepatic glycogenolysis and gluconeogenesis, causing a raise in blood glucose levels; antihypoglycemic effect requires preexisting hepatic glycogen stores. Extra hepatic effects of glucagon include relaxation of the smooth muscle of the stomach, duodenum, small bowel, and colon.

Distribution

V_d: ~0.25 L/kg

Metabolism

Primarily hepatic; some inactivation occurring renally and in plasma

Onset of Action

Blood glucose levels: Peak effect: IV: 5 to 20 minutes; IM: 30 minutes; SubQ: 30 to 45 minutes

GI relaxation: IV: 45 seconds; IM: 4 to 10 minutes

Time to Peak

IM: ~10 to 12.5 minutes; SubQ: 20 minutes

Duration of Action

Glucose elevation: IV, IM, SubQ: 60 to 90 minutes

GI relaxation: IV: 9 to 25 minutes; IM: 12 to 32 minutes

Half-Life Elimination

Plasma: IV: 8 to 18 minutes; IM (apparent): 26 to 45 minutes

Use: Labeled Indications

Diagnostic aid: As a diagnostic aid during radiologic examinations to temporarily inhibit movement of the GI tract in adults.

Hypoglycemia: Treatment of severe hypoglycemia in pediatric and adult patients. Note: The American Diabetes Association (ADA) recommends that glucagon be prescribed for all diabetic patients at increased risk of level 2 hypoglycemia (<54 mg/dL); caregivers, school personnel, or family members of these patients should be trained on when and how to administer glucagon (ADA 2018).

Limitations of use: Products not packaged with a syringe and diluent necessary for rapid preparation and administration during an emergency outside of a health care facility are not indicated for the emergency treatment of hypoglycemia.

Off Label Uses

Anaphylaxis

Based on the American Academy of Allergy, Asthma & Immunology (AAAAI), the American College of Allergy, Asthma & Immunology (ACAAI), and the Joint Council of Allergy, Asthma, and Immunology (JCAAI) guidelines for management of anaphylaxis, glucagon is recommended for the treatment of anaphylaxis in patients on beta-blocker therapy who are refractory to epinephrine.

Beta-blocker-induced myocardial depression

Based on the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care, glucagon given for beta-blocker-induced myocardial depression is effective and recommended in patients with severe cardiovascular instability refractory to standard measures, including vasopressors.

Calcium channel blocker-induced myocardial depression

Clinical experience suggests the utility of glucagon in the treatment of severe cardiovascular instability refractory to standard measures, including vasopressors ^{[Bailey 2003]}. However, the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care suggest that the use of glucagon for calcium channel blocker overdose is not well-established due to insufficient and conflicting evidence.

Contraindications

Known hypersensitivity to glucagon, lactose, or any component of the formulation; pheochromocytoma; insulinoma; glucagonoma (excluding GlucaGen)

Dosing: Adult

Diagnostic aid:

Relaxation of 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

Hypoglycemia: IM, IV, SubQ: 1 mg; may repeat in 15 minutes as needed. Note: IV dextrose should be administered as soon as it is available; if patient fails to respond to glucagon, IV dextrose must be given.

Anaphylaxis (refractory to epinephrine) in patients on beta-blocker therapy (off-label use): IV: Initial: 1 to 5 mg bolus; followed by an infusion of 5 to 15 mcg/minute; titrate the infusion rate to achieve an adequate clinical response (Lieberman 2015).

Beta-blocker- or calcium channel blocker-induced myocardial depression (with or without hypotension) unresponsive to standard measures (off-label use; AHA [Vanden Hoek 2010]; Bailey 2003): IV: 3 to 10 mg (or 0.05 to 0.15 mg/kg) bolus followed by an infusion of 3 to 5 mg/hour (or 0.05 to 0.1 mg/kg/hour); titrate infusion rate to achieve adequate clinical response (AHA [Vanden Hoek 2010])

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Hypoglycemia, severe; treatment:

Weight-directed dosing:

Manufacturer's labeling: Infants, Children, or Adolescents weighing <20 kg: Glucagon: IM, IV, SubQ: 0.02-0.03 mg/kg; maximum dose: 0.5 mg

Alternate dosing: Infants, Children, and Adolescents:

AAP: IM, IV, SubQ: 0.03 mg/kg; maximum dose: 1 mg (Hegenbarth, 2008)

IDF-ISPAD: IM, SubQ: 0.01-0.03 mg/kg; maximum dose dependent on age: <12 years: 0.5 mg; ≥12 years: 1 mg (IDF-ISPAD, 2011)

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, SubQ:

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

Hypoglycemia, prevention during illness (fixed dosing, mini-dose): Limited data available (Haymond, 2001; IDF-ISPAD, 2011): SubQ: Note: These doses are lower than hypoglycemia treatment doses and have been shown to prevent hypoglycemia for several hours during hypoglycemia-associated illness (eg, gastroenteritis, nausea/vomiting).

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

Beta-blocker or calcium channel blocker toxicity/overdose:

Infants and Children: Limited data available (Hegenbarth, 2008): IV:

Loading dose: 0.03-0.15 mg/kg

Continuous IV infusion: 0.07 mg/kg/hour; maximum rate: 5 mg/hour

Adolescents [Hegenbarth, 2008; PALS guidelines (Kleinman, 2010)]: IV:

Loading dose: 5-10 mg over several minutes

Continuous IV infusion: 1-5 mg/hour

Reconstitution

Reconstitute powder for injection by adding 1 mL of manufacturer-supplied sterile diluent or sterile water for injection to a vial containing 1 unit of the drug, to provide solutions containing 1 mg of glucagon/mL. Shake vial gently to dissolve. Solution for infusion may be prepared by reconstitution with and further dilution in NS or D₅W (Love, 1998).

Administration

Diagnostic aid: For IM or IV administration. If given IV, administer over 1 minute. After the diagnostic procedure, administer oral carbohydrates to patients who have been fasting, if this is compatible with the diagnostic procedure applied. Bolus IV doses >1 mg are not recommended.

Hypoglycemia: May administer IV or as a SubQ or IM injection in the upper arms, thighs, or buttocks. Administer fast-acting and long-acting oral carbohydrates to patient as soon as possible after response to treatment.

IV: Rapid injection may be associated with increased nausea and vomiting; place patient in lateral recumbent position to protect airway (Lieberman 2010) and to prevent choking when consciousness returns.

Anaphylaxis (refractory to epinephrine) in patients on beta-blocker therapy: Administer IV bolus over 5 minutes (Lieberman 2015).

Beta-blocker/calcium channel blocker toxicity: Administer IV bolus over 3 to 5 minutes; continuous infusions may be used. Ensure adequate supply available to continue therapy (AHA [Vanden Hoek 2010]).

Dietary Considerations

Administer oral carbohydrates to patient as soon as possible after response to treatment.

Storage

Prior to reconstitution, store at 20°C to 25°C (69°F to 77°F) for up to 24 months. Do not freeze. Protect from light. Use reconstituted solution immediately; discard unused portion.

Drug Interactions

Anticholinergic Agents: May enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Indomethacin: May diminish the therapeutic effect of Glucagon. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Glucagon may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Adverse Reactions

1% to 10%:

Gastrointestinal: Nausea (with rapid administration of high doses)

Frequency not defined.

Cardiovascular: Hypotension (up to 2 hours after GI procedures), increased blood pressure, increased pulse

Dermatologic: Skin rash

Gastrointestinal: Vomiting (with rapid administration of high doses)

Hypersensitivity: Anaphylactic shock, hypersensitivity reaction

Respiratory: Dyspnea

<1%, postmarketing, and/or case reports: Hypoglycemia, hypoglycemic coma, necrolytic migratory erythema, respiratory distress, urticaria

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Allergic reactions including skin rash and anaphylactic shock (with hypotension and respiratory difficulties) have been reported; reactions have generally been associated with endoscopic patients.

• Necrolytic migratory erythema: Necrolytic migratory erythema (NME), a skin rash associated with glucagonomas (glucagon-producing tumors) and characterized by scaly, pruritic, erythematous plaques, bullae, and erosions, has been reported (rarely) following continuous glucagon infusion. Rash may occur on face, groin, perineum, and legs or may be more widespread; rash generally resolves with discontinuation of treatment. Consider the risks versus benefits of continuing the glucagon infusion if NME occurs.

Disease-related concerns:

• Adrenal insufficiency: Use with caution in patients with adrenal insufficiency; levels of glucose stores in liver may be decreased.

• Cardiac disease: Use with caution in patients with cardiac disease.

• Chronic hypoglycemia: Use with caution in patients with chronic hypoglycemia; levels of glucose stores in liver may be decreased.

• Diabetes: Use caution if using as diagnostic aid in patients with diabetes on insulin; may cause hyperglycemia.

• Glucagonoma: Use with caution in patients with glucagonoma. The use of glucagon is contraindicated in patients with this condition (excluding GlucaGen).

• Insulinoma: Exogenous glucagon may cause an initial rise in blood glucose followed by rebound hypoglycemia. The use of glucagon is contraindicated in patients with this condition.

• Pheochromocytoma: Exogenous glucagon may cause the release of catecholamines, resulting in an increase in blood pressure. The use of glucagon is contraindicated in patients with this condition.

• Starvation/fasting: Use caution with prolonged fasting and/or starvation; levels of glycogen stores in liver may be decreased.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Lactose: May contain lactose; avoid administration in hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

Other warnings/precautions:

• Appropriate use: Insulin or sulfonylurea overdose: Patients with hypoglycemia should immediately be treated with dextrose. If IV access cannot be established or if dextrose is not available, glucagon may be considered as alternative acute treatment until dextrose can be administered.

• Secondary hypoglycemia: Supplemental carbohydrates should be given to patients who respond to glucagon for severe hypoglycemia to prevent secondary hypoglycemia.

Monitoring Parameters

Blood pressure, blood glucose, ECG, heart rate, mentation; signs or symptoms of a hypersensitivity reaction.

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea or vomiting. Have patient report immediately to prescriber signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating), signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), skin blister, skin breakdown, painful skin, severe dizziness, passing out, severe headache, vision changes, or tachycardia (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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