Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Kit, Injection:
Glucagon Emergency: 1 mg [contains lactose]
Powder, Nasal [preservative free]:
Baqsimi One Pack: 3 mg/dose (1 ea)
Baqsimi Two Pack: 3 mg/dose (1 ea)
Solution Prefilled Syringe, Subcutaneous [preservative free]:
Gvoke PFS: 0.5 mg/0.1 mL (0.1 mL); 1 mg/0.2 mL (0.2 mL)
Solution Reconstituted, Injection:
GlucaGen Diagnostic: 1 mg (1 ea)
GlucaGen HypoKit: 1 mg (1 ea)
Glucagon Emergency: 1 mg/mL (1 ea) [contains lactose monohydrate]
Generic: 1 mg (1 ea)
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: Reported values vary significantly: ~0.25 L/kg (Glucagon Emergency); 137 to 2425 L (Gvoke); 885 L (Baqsimi).
Metabolism
Primarily hepatic; some inactivation occurring renally and in plasma
Onset of Action
Blood glucose concentrations: Note: In general, when used for the treatment of hypoglycemia, the time required to correct hypoglycemia (eg, increase blood glucose concentrations by 20 mg/dL) is similar between formulations and routes of administration (~10 to 15 minutes); clinicians should note that the durability of response may result in blood glucose concentrations that continue to rise for >90 minutes (Baqsimi prescribing information 2019; Gvoke prescribing information 2019; Rickels 2016).
IV: Peak effect: 5 to 20 minutes (GlucaGen prescribing information 2018)
IM:
Onset: 10 minutes.
Peak effect: 30 minutes when used as a diagnostic aid (GlucaGen prescribing information 2018); in patients with type 1 diabetes and insulin-induced hypoglycemia, the peak glucose response was not yet reached during the 90-minute observation window following glucagon administration (Rickels 2016).
Intranasal:
Onset: Slightly delayed compared to IM administration; for example, median response time to reach glucose target in adults was 13 minutes (IM) vs 16 minutes (intranasal), but clinical outcomes/resolution of hypoglycemia at 30 minutes did not differ (Rickels 2016).
Peak effect: Patients with type 1 diabetes:
Children ≥4 years: ~60 minutes (Baqsimi prescribing information 2019).
Adults: A peak glucose responses was not yet reached during the 90-minute observation window following glucagon administration (Baqsimi prescribing information 2019; Rickels 2016).
SubQ:
Onset: ~10 minutes; Gvoke onset is delayed a few minutes compared to Glucagon Emergency, but clinical outcomes/resolution of hypoglycemia at 30 minutes did not differ between SubQ formulations (Gvoke prescribing information 2019).
Peak effect: 30 to 45 minutes in healthy patients (GlucaGen prescribing information 2018; Glucagon Emergency prescribing information 2018); in patients with type 1 diabetes and insulin-induced hypoglycemia, the peak glucose response was not yet reached during the 90-minute observation window following glucagon administration (Gvoke prescribing information 2019).
GI relaxation: IV: 45 seconds; IM: 4 to 10 minutes
Time to Peak
Plasma:
IM: ~10 to 12.5 minutes.
Intranasal:
Pediatric patients 4 to <17 years: 15 to 20 minutes.
Adults: 15 minutes.
SubQ:
Glucagon Emergency: 20 minutes.
Gvoke:
Pediatric patients:
2 to <6 years: 41 minutes.
6 to <12 years: 34 minutes.
12 to <18 years: 51 minutes.
Adults: 50 minutes.
Duration of Action
Blood glucose concentrations: 60 to 90 minutes (GlucaGen prescribing information 2018); other data suggest glucose elevation may persist >90 minutes following intranasal, IM, or SubQ administration in patients with type 1 diabetes (Gvoke prescribing information 2019; Rickels 2016).
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.
Intranasal (apparent): median:
Pediatric patients 4 to <17 years: 21 to 31 minutes.
Adults: ~35 minutes.
SubQ: 32 minutes (Gvoke prescribing information 2019; not reported for other formulations).
Use: Labeled Indications
Diagnostic aid (injection): As a diagnostic aid during radiologic examinations to temporarily inhibit movement of the GI tract in adults.
Hypoglycemia: Note: The American Diabetes Association (ADA) recommends that glucagon be prescribed for all patients with diabetes 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 2019).
Injection, powder for reconstitution (GlucaGen HypoKit or Glucagon Emergency): Treatment of severe hypoglycemia in pediatric and adult patients.
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.
Injection, solution (Gvoke): Treatment of severe hypoglycemia in adult and pediatric patients (≥2 years of age) with diabetes.
Intranasal: Treatment of severe hypoglycemia in adult and pediatric patients (≥4 years of age) with diabetes.
Use: Off Label
Anaphylaxisyes
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 overdoseyes
Based on the American Heart Association (AHA) guideline for cardiopulmonary resuscitation and emergency cardiovascular care and the American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) Guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay, glucagon given for beta-blocker toxicity is a recommended treatment option in patients with cardiovascular instability refractory to standard measures.
Calcium channel blocker overdoseyes
Based on the American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) Guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay, glucagon given for calcium channel blocker toxicity is a recommended treatment option in patients with cardiovascular instability refractory to standard measures.
Contraindications
Known hypersensitivity to glucagon or any component of the formulation (injection contains lactose); pheochromocytoma; insulinoma; use of injection as a diagnostic aid in patients with glucagonoma.
Dosage and Administration
Dosing: Adult
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 overdose (off-label use): IV: 3 to 10 mg bolus; if no clinical response may repeat bolus dose; if clinical response with bolus, start continuous infusion at 3 to 5 mg/hour; titrate infusion rate to achieve adequate hemodynamic response (ACC/AHA/HRS [Kusumoto 2018]; AHA [Vanden Hoek 2010]; Barrueto 2019).
Calcium channel blocker overdose (off-label use): IV: 3 to 10 mg bolus; if no clinical response may repeat bolus dose; if clinical response with bolus, start continuous infusion at 3 to 5 mg/hour; titrate infusion rate to achieve adequate hemodynamic response (ACC/AHA/HRS [Kusumoto 2018]; Barrueto 2019).
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: Note: IV dextrose should be administered as soon as it is available; if patient fails to respond to glucagon, IV dextrose must be given.
Injection:
GlucaGen HypoKit or Glucagon Emergency: IM, IV, SubQ: 1 mg; may repeat in 15 minutes as needed.
Gvoke: SubQ: 1 mg; may repeat in 15 minutes as needed using a new device.
Intranasal: 3 mg (one actuation) into a single nostril; if no response, may repeat in 15 minutes using a new intranasal device.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Hypoglycemia, severe; treatment: Note: 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. Glucagon should be prescribed for all type 1 diabetic patients and type 2 diabetic patients at increased risk of level 2 hypoglycemia (<54 mg/dL); caregivers, school personnel, and family members of these patients should be trained on when and how to administer glucagon (ADA 2019; ADA [Chiang 2018]).
Parenteral:
Weight-based dosing: Infants, Children, and Adolescents: IM, IV, SubQ: 0.02 to 0.03 mg/kg/dose; may repeat every 15 minutes if needed for clinical effect for up to a total of 3 doses; maximum dose: 1 mg/dose (AAP [Shenoi 2020]).
Product-specific dosing:
Glucagon: Infants, Children, and Adolescents: IM, IV, SubQ:
<20 kg: 0.5 mg; if no response in 15 minutes, may repeat dose.
≥20 kg: 1 mg; if no response in 15 minutes, may repeat dose.
GlucaGen: Infants, Children, and Adolescents: IM, IV, SubQ:
Weight-directed dosing:
<25 kg: 0.5 mg; may repeat once if needed.
≥25 kg: 1 mg; may repeat once if needed.
Age-directed dosing: Note: Use when weight is unknown.
Infants and Children <6 years: 0.5 mg; may repeat once if needed.
Children ≥6 years and Adolescents: 1 mg; may repeat once if needed.
Gvoke:
Children 2 to <12 years: SubQ:
<45 kg: 0.5 mg; if no response after 15 minutes, may administer an additional 0.5 mg dose.
≥45 kg: 1 mg; if no response after 15 minutes, may administer an additional 1 mg dose.
Children ≥12 years and Adolescents: SubQ: 1 mg; if no response after 15 minutes, may administer an additional 1 mg dose.
Intranasal (Baqsimi): Children ≥4 years and Adolescents: 3 mg (1 actuation) intranasally into a single nostril; if no response after 15 minutes, may repeat dose using a new device. Note: Inhalation not necessary.
Hypoglycemia, mild (<70 mg/dL) or impending hypoglycemia during illness (mini-dose regimen): Limited data available (Chung 2015; Haymond 2001; ISPAD [Abraham 2018]; ISPAD [Laffel 2018]): Note: These doses are lower than hypoglycemia treatment doses and have been shown to prevent hypoglycemia for several hours during mild hypoglycemia or impending hypoglycemia-associated illness (eg, gastroenteritis, nausea/vomiting) and/or poor oral carbohydrate intake.
Initial dose:
Infants and Children ≤2 years: SubQ: 0.02 mg.
Children >2 years and Adolescents ≤15 years: SubQ: 0.01 mg per year of age.
Adolescents >15 years: SubQ: 0.15 mg.
Subsequent dose: SubQ: If initial dose fails to increase glucose after 30 minutes, may give an additional dose that is twice the initial dose.
Anaphylaxis (refractory to epinephrine) in patients on beta-blocker therapy: Limited data available (AAAAI/ACAAI [Campbell 2014]; AAP [Shenoi 2020]; Canadian Paediatric Society [Cheng 2011]):
Infants, Children, and Adolescents: IV:
Initial: 0.02 to 0.03 mg/kg slow IV; maximum dose: 1 mg/dose.
Continuous infusion: Follow initial dose with a continuous infusion of 5 to 15 mcg/minute; titrate to effect.
Beta-blocker or calcium channel blocker toxicity/overdose: Limited data available:
Infants and Children:
Loading dose: IV: 0.05 mg/kg as a single dose (AAP [Shenoi 2020]; Arroyo 2009; Nelson 2019); if no response, may repeat dose (Nelson 2019).
Continuous IV infusion: 0.05 to 0.1 mg/kg/hour; titrate to effect (Arroyo 2009); usual adolescent dose: 1 to 5 mg/hour (PALS [Kleinman 2010]); some experts recommend initiating the infusion at the "response dose" (cumulative loading dose) per hour (Nelson 2019).
Adolescents:
Loading dose: IV: 5 to 10 mg (PALS [Kleinman 2010]).
Continuous IV infusion: 1 to 5 mg/hour (PALS [Kleinman 2010]); some experts recommend initiating the infusion at the "response dose" (cumulative loading dose) per hour (Nelson 2019).
Reconstitution
Injection, powder for reconstitution: Reconstitute powder for injection by adding 1 mL of manufacturer-supplied sterile diluent or sterile water for injection to a vial containing 1 mg of the drug, to provide solutions containing 1 mg/mL. Shake vial gently to dissolve. A solution for continuous infusion may be prepared by further dilution in D5W (Shepherd 2006); also refer to institution-specific policies and procedures.
Administration
Note: For the treatment of hypoglycemia, administer fast-acting and long-acting oral carbohydrates to patient as soon as possible after response to glucagon treatment. If patient is unconscious, place in lateral recumbent position to prevent choking when consciousness returns.
IM: For treatment of hypoglycemia, may administer reconstituted solution for injection as an IM injection in the upper arms, thighs, or buttocks. For use as a diagnostic aid, may administer IM. After the diagnostic procedure, administer oral carbohydrates to patients who have been fasting, if this is compatible with the diagnostic procedure applied.
Intranasal: Insert the tip of the intranasal device into one nostril and fully depress plunger until the green line is no longer visible. Inhalation of the dose is not necessary. Do not reuse the device after administration.
IV: Rapid injection may be associated with increased nausea and vomiting.
Anaphylaxis (refractory to epinephrine) in patients on beta-blocker therapy: Administer IV bolus over 5 minutes; continuous infusions may be used (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]).
Diagnostic aid: May administer IV 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.
Subcutaneous:
Injection, powder for reconstitution: For treatment of hypoglycemia, may administer reconstituted solution in the upper arms, thighs, or buttocks.
Injection, solution (Gvoke): Administer in the lower abdomen, outer thigh, or outer upper arm; inject rapidly to reduce injection-site pain.
Dietary Considerations
Administer oral carbohydrates to patient as soon as possible after response to treatment.
Storage
Injection, powder for reconstitution: 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.
Injection, solution (Gvoke): Store at 20°C to 25°C (68°F to 77°F) in original sealed foil pouch until time of use; excursions permitted between 15°C and 30°C (59°F and 86°F). Do not refrigerate, freeze, or expose to extreme temperatures.
Intranasal: Store at ≤30°C (86°F). Do not remove intranasal device from the provided shrink-wrapped tube until ready to use. For single use only; discard after use.
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; hepatic glycogen levels may be inadequate for glucagon to effectively increase blood glucose.
- Cardiac disease: Use with caution in patients with cardiac disease.
- Chronic hypoglycemia: Use with caution in patients with chronic hypoglycemia; hepatic glycogen levels may be inadequate for glucagon to effectively increase blood glucose.
- 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; may cause secondary hypoglycemia. The use of injectable glucagon as a diagnostic aid is contraindicated in patients with this condition.
- 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; hepatic glycogen levels may be inadequate for glucagon to effectively increase blood glucose.
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
Pregnancy Considerations
Glucagon may be used for the treatment of severe hypoglycemia during pregnancy (Alexopoulos 2019). In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant females if there is a clear indication for use and should not be withheld because of concerns of teratogenicity (Bailey 2003a).
Patient Education
What is this drug used for?
- It is used to treat low blood sugar.
- It is used to quiet the GI (gastrointestinal) tract so it may be x-rayed.
- It may be given to you for other reasons. Talk with the doctor.
Frequently reported side effects of this drug
- Nausea
- Vomiting
- Common cold symptoms
- Nose irritation
- Sore throat
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating
- High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit
- Skin blister
- Skin breakdown
- Painful skin
- Severe dizziness
- Passing out
- Severe headache
- Vision changes
- Fast heartbeat
- Signs of a significant reaction like 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. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
