GlucaGen®(glucagon) for injection 2
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
1.1 Treatment of severe hypoglycemia
GlucaGen®is used to treat severe hypoglycemic (low blood sugar) reactions which may occur in
patients with diabetes mellitus treated with insulin. Because GlucaGen®depletes glycogen stores, the
patient should be given supplemental carbohydrates as soon as he/she awakens and is able to swallow,
especially children or adolescents. Medical evaluation is recommended for all patients who experience
severe hypoglycemia.
1.2 Use as a diagnostic aid
GlucaGen®is indicated for use during radiologic examinations to temporarily inhibit movement of
the gastrointestinal tract. GlucaGen®is not recommended in combination with anticholinergic agents
due to the possibility of increased side effects. After the end of the diagnostic procedure, give oral
carbohydrates to patients who have been fasting, if this is compatible with the diagnostic procedure
applied.
2 DOSAGE AND ADMINISTRATION
For GlucaGen®HypoKit®:
2.1 Treatment of severe hypoglycemia
1. Using the supplied prefilled syringe, carefully insert the needle through the rubber stopper of the
vial containing GlucaGen®powder and inject all the liquid from the syringe into the vial.
2. Shake the vial gently until the powder is completely dissolved and no particles remain in the
fluid. The reconstituted fluid should be clear and of water-like consistency.
3. The reconstituted GlucaGen®gives a concentration of approximately 1 mg/mL glucagon.
4. The reconstituted GlucaGen®should be used immediately after reconstitution.
5. Inject 1 mL (adults and children, weighing more than 55 lbs (25 kg)) or 0.5 mL (children
weighing less than 55 lbs (25 kg)) subcutaneously, intramuscularly, or intravenously. Common
injection sites for GlucaGen®are upper arms, thighs, or buttocks. If the weight is not known:
children younger than 6 years should be given a 0.5 mL and children 6 years and older should
be given 1 mL.
6. Discard any unused portion.
7. Emergency assistance should be sought immediately after subcutaneous or intramuscular
injection of glucagon.
8. The glucagon injection may be repeated using a new kit while waiting for emergency assistance.
9. Intravenous glucose MUST be administered if the patient fails to respond to glucagon.
10. When the patient has responded to the treatment, give fast-acting and long-acting oral
carbohydrates to restore the liver glycogen and prevent recurrence of hypoglycemia.
For GlucaGen®Diagnostic Kit and the GlucaGen®10-pack:
2.2 Use as a diagnostic aid
1. GlucaGen®should be reconstituted with 1 mL of Sterile Water for Reconstitution (if supplied)
or 1 mL of Sterile Water for Injection, USP. Using a syringe, withdraw all of the Sterile Water
for Reconstitution (if supplied) or 1 mL Sterile Water for Injection, USP and inject into the
GlucaGen®vial.
2. Shake the vial gently until the powder is completely dissolved and no particles remain in the
fluid. The reconstituted fluid should be clear and of water-like consistency.
3. The reconstituted GlucaGen®gives a concentration of approximately 1 mg/mL glucagon.
4. The reconstituted GlucaGen®should be used immediately after reconstitution.
5. GlucaGen®must be administered by medical personnel.
6. Discard any unused portion.
7. Onset of action after an injection will depend on the organ under examination and route of
administration
[see Pharmacodynamics (12.2)]
.
8. The usual diagnostic dose for relaxation of the stomach, duodenal bulb, duodenum, and small
bowel is 0.2 mg to 0.5 mg given intravenously or 1 mg given intramuscularly; the usual dose
to relax the colon is 0.5 mg to 0.75 mg intravenously and 1 mg to 2 mg intramuscularly
[see
Pharmacodynamics (12.2)]
.
9. After the end of the diagnostic procedure, give oral carbohydrates to patients who have been
fasting, if this is compatible with the diagnostic procedure applied.
The GlucaGen®Diagnostic Kit and the GlucaGen®10-pack presentations are
intended only for use by healthcare providers as a diagnostic aid. The GlucaGen®
Diagnostic Kit and the GlucaGen®10-pack presentations are not intended for use
by patients to treat severe hypoglycemia because they are not packaged with a
syringe and diluent necessary for rapid preparation and administration during an
emergency outside of a healthcare facility.
3 DOSAGE FORMS AND STRENGTHS
GlucaGen®is supplied in a vial, alone, or accompanied by Sterile Water for Reconstitution (1 mL) also
in a vial (10 pack or diagnostic kit). It is also supplied as GlucaGen®HypoKit®, a presentation with
a disposable prefilled syringe containing 1 mL Sterile Water for Reconstitution. When the glucagon
powder is reconstituted with Sterile Water for Reconstitution (if supplied) or with Sterile Water for
Injection, USP, it forms a solution of 1 mg/mL glucagon for subcutaneous, intramuscular, or intravenous
injection (appearance of the powder may vary, and occasionally the powder may appear compacted).
4 CONTRAINDICATIONS
GlucaGen®is contraindicated in patients with:
• Known hypersensitivity to glucagon, lactose or any other constituent in GlucaGen®
• Pheochromocytoma
[see Warnings and Precautions (5.1)]
• Insulinoma
[see Warnings and Precautions (5.2)]
5 WARNINGS AND PRECAUTIONS
5.1 Pheochromocytoma
GlucaGen®is contraindicated in patients with pheochromocytoma because GlucaGen®may stimulate
the release of catecholamines from the tumor. If the patient develops a dramatic increase in blood
pressure, 5 to 10 mg of phentolamine mesylate has been shown to be effective in lowering blood
pressure for the short time that control would be needed.
5.2 Insulinoma and Glucagonoma
GlucaGen®should not be administered to patients suspected of having insulinoma. In patients
with insulinoma, intravenous administration of glucagon may produce an initial increase in blood
glucose; however, GlucaGen®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 a dose of GlucaGen®should be given glucose orally or intravenously, whichever
is most appropriate. Caution should be observed in administering GlucaGen®to patients with
glucagonoma.
5.3 Hypersensitivity and Allergic Reactions
Allergic reactions may occur and include generalized rash, and in some cases anaphylactic shock
with breathing difficulties, and hypotension. The anaphylactic reactions have generally occurred in
association with endoscopic examination during which patients often received other agents including
contrast media and local anesthetics. The patients should be given standard treatment for anaphylaxis
including an injection of epinephrine if they encounter respiratory difficulties after GlucaGen®injection.
5.4 Glycogen Stores and Hypoglycemia
In order for GlucaGen®treatment to reverse hypoglycemia, adequate amounts of glucose must be
stored in the liver (as glycogen). Therefore, GlucaGen®should be used with caution in patients with
conditions such as prolonged fasting, starvation, adrenal insufficiency, or chronic hypoglycemia
because these conditions result in low levels of releasable glucose in the liver and an inadequate
reversal of hypoglycemia by GlucaGen®treatment.
5.5 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, has been reported postmarketing following continuous glucagon infusion. NME lesions may
affect the face, groin, perineum and legs or be more widespread. In the reported cases NME resolved
with discontinuation of the glucagon, and treatment with corticosteroids was not effective. Should
NME occur, consider whether the benefits of continuous glucagon infusion outweigh the risks.
5.6 Cardiac Disease
Caution should be observed when GlucaGen®is used as an adjunct in endoscopic or radiographic
procedures to inhibit gastrointestinal motility in patients with known cardiac disease.
5.7 Laboratory Tests
Blood glucose measurements may be considered to monitor the patient’s response.
6 ADVERSE REACTIONS
The following important adverse reactions are described below and elsewhere in the labeling:
• Hypersensitivity and Allergic Reactions
[see Warnings and Precautions (5.3)]
• Necrolytic Migratory Erythema
[see Warnings and Precautions (5.5)]
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. GlucaGen®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 GlucaGen®. 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
GlucaGen®’s short half-life
[see Drug Interactions (7.1)]
. The increase in blood pressure and pulse rate
may require therapy in patients with pheochromocytoma or coronary artery disease
[see Warnings and
Precautions (5.1)]
. Anaphylactic reactions may occur in some cases.
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
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.
Necrolytic migratory erythema (NME) cases have been reported postmarketing in patients receiving
continuous infusion of glucagon.
7 DRUG INTERACTIONS
7.1 Beta-blockers
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. The increase
in blood pressure and pulse rate may require therapy in patients with pheochromocytoma or coronary
artery disease.
7.2 Indomethacin
When used with indomethacin, glucagon may lose its ability to raise blood glucose or may even
produce hypoglycemia. Therefore, caution should be exercised for patients taking indomethacin when
glucagon will be administered.
7.3 Anticholinergic Drugs
Coadministration with an anticholinergic drug is not recommended due to increased gastrointestinal
side effects.
7.4 Warfarin
Glucagon may increase the anticoagulant effect of warfarin. Therefore, caution should be exercised for
patients taking warfarin when glucagon will be administered.
