Dosing & Uses
Dosage Forms & Strengths
injection, powder for reconstitution (GlucaGen, generic)
- 1mg/vial
injectable solution (Gvoke)
- 1mg/0.2mL (single-dose prefilled syringe or HypoPen autoinjector)
Hypoglycemia
Indicated for severe hypoglycemic reactions in patients with diabetes treated with insulin
1 mg (1 unit) IM/SC/IV if no IV for dextrose
Repeat q15min once or twice; give dextrose as soon as it is available and if no response
Administer supplemental carbohydrate to replete glycogen stores
Diagnostic Aid
GlucaGen only
Indicated for use during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract
To inhibit motility of stomach and small bowel: 0.2-0.5 mg IV over 1 min or 1 mg IM
To inhibit motility of colon: 0.5-0.75 mg IV over 1 min or 1-2 mg IM
Bolus doses >1 mg administered IV may cause nausea and vomiting and are not recommended
After completing the diagnostic procedure, give oral carbohydrates to patients who have been fasting, if compatible with the diagnostic procedure applied
Beta-Blocker & Calcium Channel Blocker Toxicity (Off-label)
Indicated off-label for overdose of beta blockers or calcium channel blockers
Load: 50-150 mcg/kg IVP over 1 minute, THEN
3-5 mg/hr or 50-100 mcg/kg/hr IV; titrate infusion to achieve adequate clinical response
Dosage Forms & Strengths
injection, powder (GlucaGen, generic)
- 1mg/vial
injectable solution (Gvoke)
- 0.5mg/0.1mL (single-dose prefilled syringe or HypoPen autoinjector)
- 1mg/0.2mL (single-dose prefilled syringe or HypoPen autoinjector)
Hypoglycemia
Indicated for severe hypoglycemic reactions in patients with diabetes treated with insulin
Administer oral glucose/IV dextrose to replete glycogen stores
GlucaGen
- <6 years: 0.5 mg SC/IM/IV; may repeat in 15 min if necessary
- >6 years: 1 mg SC/IM/IV; may repeat in 15 min if necessary
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Alternatively
- <25 kg: 0.5 mg; may repeat in 15 min if necessary
- ≥25 kg: 1 mg; may repeat in 15 min if necessary
Glucagon Emergency Kit
- <20 kg: 0.5 mg SC/IM/IV q15min PRN, OR 0.02-0.03 mg/kg/dose SC/IM/IV; may repeat in 15 min if necessary
- ≥20 kg: 1 mg SC/IM/IV; may repeat in 15 min if necessary q20min PRN
6 years: 0.5 mg SC/IM/IV; may repeat in 15 min if necessary
>6 years: 1 mg SC/IM/IV; may repeat in 15 min if necessary
Alternatively H5
<25 kg: 0.5 mg; may repeat in 15 min if necessary
≥25 kg: 1 mg; may repeat in 15 min if necessary
Glucagon Emergency Kit H4
<20 kg: 0.5 mg SC/IM/IV q15min PRN, OR 0.02-0.03 mg/kg/dose SC/IM/IV; may repeat in 15 min if necessary
≥20 kg: 1 mg SC/IM/IV; may repeat in 15 min if necessary q20min PRN
Gvoke
- Indicated for severe hypoglycemia in pediatric and adult patients with diabetes aged ≥2 years
- <2 years: Safety and efficacy not established
-
2 to <12 years
- <45 kg: 0.5 mg SC; may repeat in 15 min if necessary
- ≥45 kg: 1 mg SC; may repeat in 15 min if necessary
-
≥12 years
- 1 mg SC; may repeat in 15 min if necessary
Hyperinsulinemic Hypoglycemia (Orphan)
Orphan designation for treatment of hyperinsulinemic hypoglycemia (HH)
Sponsor
- Xeris Pharmaceuticals, Inc; 3208 Red River Street, Suite 300; Austin, TX 78705
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse Effects
>10%
Gvoke
- Nausea (36-54%)
- Hypoglycemia (27-54%)
- Vomiting (14-23%)
- Headache (15%)
- Hyperglycemia (8-14%)
1-10%
GlucaGen
- Nausea (<10%)
Gvoke
- Injection site reaction (9%)
- Abdominal pain (8%)
- Injection site discomfort (8%)
- Urticaria (8%)
<1%
GlucaGen
- Vomiting
- Hypoglycemia
- Hypoglycemia coma
Frequency Not Defined
Nausea and vomiting
Rash
Hypotension
Tachycardia
Increased blood pressure
Increased pulse
Respiratory distress
Urticaria
Hypoglycemic coma
Hypoglycemia
Postmarketing Reports
Necrolytic migratory erythema
Gvoke
- Hypoglycemia and hypoglycemic coma
Warnings
Contraindications
Hypersensitivity
Pheochromocytoma
Insulinoma
Glucagonoma when used as diagnostic tool
Cautions
Contraindicated in patients with pheochromocytoma; glucagon may stimulate the release of catecholamines from the tumor; if the patient develops a dramatic increase in blood pressure, 5-10 mg of phentolamine mesylate has been shown to be effective in lowering blood pressure for the short time that control would be needed
Used as diagnostic aid may increase myocardial oxygen demand, blood pressure, and pulse rate which may be life-threatening in patients with cardiac disease; cardiac monitoring recommended in patients with cardiac disease during use as a diagnostic aid, and an increase in blood pressure and pulse rate may require therapy
Generalized allergic reactions, including urticaria, respiratory distress, and hypotension reported; if symptoms occur discontinue and treat as indicated
Treatment is effective in treating hypoglycemia only if sufficient hepatic glycogen present; patients in states of starvation, with adrenal insufficiency or chronic hypoglycemia may not have adequate levels of hepatic glycogen for therapy to be effective; patients with these conditions should be treated with glucose
Increased blood pressure and heart rate in patients with cardiac disease reported; monitor patients with known cardiac disease
Caution should be observed when used as an adjunct in endoscopic or radiographic procedures to inhibit gastrointestinal motility in patients with known cardiac disease
Consider measuring blood glucose to monitor response
Treatment with in patients with diabetes mellitus may cause hyperglycemia; monitor diabetic patients for changes in blood glucose levels during treatment and treat if indicated
Necrolytic migratory erythema
- Necrolytic migratory erythema (NME), a skin rash commonly associated with glucagonomas (glucagon-producing tumors) and characterized by scaly, pruritic erythematous plaques, bullae, and erosions, reported postmarketing following continuous glucagon infusion
- NME lesions may affect face, groin, perineum and legs or be more widespread
- In reported cases NME resolved with discontinuation of glucagon, and treatment with corticosteroids was not effective
- Should NME occur, consider whether benefits of continuous glucagon infusion outweigh risks
Insulinoma and glucagonoma
- Do not be administered to patients suspected of having insulinoma
- In patients with insulinoma, IV glucagon may directly or indirectly (through an initial rise in blood glucose) stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia
- Administration may directly or indirectly (through an initial rise in blood glucose) stimulate exaggerated insulin release from an insulinoma
- A patient developing symptoms of hypoglycemia after dose should be given glucose PO/IV
- Use contraindicated in patients with glucagonoma when used as diagnostic aid; test patients suspected of having glucagonoma for blood levels of glucagon prior to treatment, and monitor for changes in blood glucose levels during treatment
Drug interaction overview
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Beta-blockers
- Patients taking beta-blockers may have a greater increase in both pulse and blood pressure, an increase of which will be temporary because of glucagon’s short half-life.
-
Indomethacin
- Use with caution
- When used with indomethacin, glucagon may lose its ability to raise blood glucose or may even produce hypoglycemia
-
Anticholinergic drugs
- Coadministration with an anticholinergic drug is not recommended due to increased gastrointestinal side effects
-
Warfarin
- Use with caution
- Glucagon may increase the anticoagulant effect of warfarin
-
Insulin
- Insulin reacts antagonistically towards glucagon
- Use with caution when used as a diagnostic aid in diabetes patients
Pregnancy & Lactation
Pregnancy
Available data from case reports and a small number of observational studies in pregnant women over decades of use have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes; multiple small studies have demonstrated a lack of transfer of pancreatic glucagon across human placental barrier during early gestation
Animal data
- In rat and rabbit reproduction studies, no embryofetal toxicity was observed with glucagon administered by injection during period of organogenesis at doses representing up to 100 and 200 times the human dose, respectively, based on body surface area (mg/m2)
Lactation
There is no information available on presence of glucagon in human or animal milk, effects on breastfed child or on milk production; however, glucagon is a peptide and would be expected to be broken down to its constituent amino acids in infant's digestive tract and is therefore, unlikely to cause harm to an exposed infant
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Insulin antagonist
Stimulates cAMP synthesis to accelerate hepatic glycogenolysis and gluconeogenesis, causing an increase in blood glucose levels
Preexisting hepatic glycogen stores necessary to be effective in treating hypoglycemia
Glucagon also relaxes smooth muscles of GI tract
Absorption
Peak plasma concentration
- GlucaGen IM: 1686 pg/mL
- Gvoke SC: 2481.3 pg/mL
Peak plasma time
- Glucagen IM: 12.5 min
- SC: 30-45 min (GlucaGen); 50 min (Gvoke)
AUC
- Gvoke SC: 3454.6 pg⋅min/mL
Onset
- GlucaGen IV: 45 sec (0.25- to 0.5-mg, 2-mg dose)
- GlucaGen IM: 8-10 min (1-mg dose); 12-27 min (2-mg dose)
Duration of smooth muscle relaxation
- GlucaGen IV: 9-17 min (0.25-0.5 mg-dose); 22-25 min (2-mg dose)
- GlucaGen IM: 12-27 min (1-mg dose); 21-32 min (2-mg dose)
Time of maximal glucose concentration
- GlucaGen IV: 5-20 min
- GlucaGen IM: 30 min
Distribution
Vd
- Gvoke SC: 137-2425 L
Metabolism
- IM: Degraded by the liver, kidney, and plasma
Elimination
Half-life
- Glucagen IM: 45 min
- Gvoke SC: 32 min
Administration
IV Preparation
Reconstitute by adding 1 or 10 mL of sterile diluent to a vial containing 1 or 10 units of drug, respectively, to yield solutions containing 1 mg/mL
If dose <2 mg, use only diluent provided by Mfr
If >2 mg, use SWI
Use immediately after reconstitution
Administration
GlucaGen
- May be give IV, IM, or SC
- Emergency assistance should be sought immediately after SC or IM administration
- IV glucose must be administered if patient fails to respond to glucagon
- Once patient responds to treatment, give fast-acting and long-acting oral carbohydrates to restore the liver glycogen and prevent recurrence of hypoglycemia
Gvoke
- SC administration only
- Severe hypoglycemia requires the help of others to recover, instruct patient to inform those around them about glucagon and its use
- Administer as soon as possible when severe hypoglycemia is recognized
-
Emphasize the following instructions
- Do not open foil pouch until ready to administer; administer according to the printed instructions on the foil pouch label, carton, or instructions for use
- Visually inspect before administration; solution should appear clear and colorless to pale yellow and be free of particles; if the solution is discolored or contains particulate matter, do not use
- Administer injection in the lower abdomen, outer thigh, or outer upper arm
- Call for emergency assistance immediately after administering the dose
- When patient responds to treatment, give oral carbohydrates to restore the liver glycogen and prevent recurrence of hypoglycemia
- Do not attempt to reuse injection; each device contains a single dose of glucagon and cannot be reused
Storage
GlucaGen
- Unopened package: Store at room temperatures (20-25ºC [68-77ºF]); do not freeze; protect from light
- Reconstituted vials: Use immediately; discard any unused portion
Gvoke
Store at room temperatures (20-25ºC [68-77ºF]); excursions permitted between 15-30ºC (59-86ºF)
Do not refrigerate or freeze
Store in original sealed foil pouch until time of use; do not expose to extreme temperatures
Do not use after the expiration date printed on carton and foil pouch
Images
Patient Handout
Formulary
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