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  • CLASSES

    Diagnostic Hormonal Agents
    Glucagon

    DEA CLASS

    Rx

    DESCRIPTION

    Recombinant glucagon identical to native glucagon; injections are expressed in either a Saccharoyces cervisiae (GlucaGen) or Escherichia coli strain (Glucagon, Lilly); nasal powder (Baqsimi) is also available
    Most commonly used in the emergency treatment of severe hypoglycemia in diabetes mellitus or as a diagnostic aid in endoscopic or radiologic examination of GI tract
    Also used adjunctively as a cardiac stimulant in beta-blocker overdose

    COMMON BRAND NAMES

    BAQSIMI, GlucaGen, Glucagon, Gvoke

    HOW SUPPLIED

    BAQSIMI Nasal Pwd: 3mg
    GlucaGen/Glucagon Intramuscular Inj Pwd F/Sol: 1mg
    GlucaGen/Glucagon Intravenous Inj Pwd F/Sol: 1mg
    GlucaGen/Glucagon Subcutaneous Inj Pwd F/Sol: 1mg
    Glucagon/Gvoke HypoPen Subcutaneous Inj Sol: 0.1mL, 0.2mL, 0.5mg, 1mg

    DOSAGE & INDICATIONS

    For the treatment of severe hypoglycemia.
    Patients with diabetes mellitus.
    Intramuscular, Intravenous, or Subcutaneous dosage (guideline dosing)
    Children and Adolescents 12 years and older

    0.01 to 0.03 mg/kg/dose IM, IV, or subcutaneously once (Max: 1 mg/dose). If no response seen in 15 minutes, may repeat dose up to a total of 3 doses; IV dextrose must be administered to a patient who fails to respond to initial dose. Once the patient has responded to treatment, give oral carbohydrates to prevent recurrence of hypoglycemia.

    Infants and Children 11 years and younger

    0.01 to 0.03 mg/kg/dose IM, IV, or subcutaneously once (Max: 0.5 mg/dose). If no response seen in 15 minutes, may repeat dose up to a total of 3 doses; IV dextrose must be administered to a patient who fails to respond to initial dose.

    Intramuscular, Intravenous, or Subcutaneous dosage (GlucaGen)
    Adults

    1 mg administered IM, IV, or subcutaneously. Additional doses may be given while waiting for emergency assistance. IV dextrose must be administered if the patient fails to respond to glucagon. Once the patient has responded to treatment, give oral carbohydrates to prevent recurrence of hypoglycemia.

    Children and Adolescents weighing 25 kg or more and Children 6 years and older with unknown weight

    1 mg IM, IV, or subcutaneously once. If no response is seen within 15 minutes, may repeat dose up to a total of 3 doses. IV dextrose must be administered if the patient fails to respond to glucagon. Once the patient has responded to treatment, give oral carbohydrates to prevent recurrence of hypoglycemia.

    Infants and Children weighing less than 25 kg and Children younger than 6 years with unknown weight

    0.5 mg IM, IV, or subcutaneously once. If no response is seen within 15 minutes, may repeat dose up to a total of 3 doses. IV dextrose must be administered if the patient fails to respond to glucagon. Once the patient has responded to treatment, give oral carbohydrates to prevent recurrence of hypoglycemia.

    Intramuscular, Intravenous, or Subcutaneous dosage (glucagon, recombinant by Eli Lilly)
    Adults

    1 mg IM, IV, or subcutaneously. Additional doses may be given while waiting for emergency assistance. IV dextrose must be administered if the patient fails to respond to glucagon. Once the patient has responded to treatment, give oral carbohydrates to prevent recurrence of hypoglycemia.

    Children and Adolescents weighing 20 kg or more

    1 mg IM, IV, or subcutaneously once. If no response is seen within 15 minutes, may repeat dose up to a total of 3 doses. IV dextrose must be administered if the patient fails to respond to glucagon. Once the patient has responded to treatment, give oral carbohydrates to prevent recurrence of hypoglycemia.

    Infants and Children weighing less than 20 kg

    0.02 to 0.03 mg/kg/dose or 0.5 mg/dose IM, IV, or subcutaneously once. If no response is seen within 15 minutes, may repeat dose up to a total of 3 doses. IV dextrose must be administered if the patient fails to respond to glucagon. Once the patient has responded to treatment, give oral carbohydrates to prevent recurrence of hypoglycemia.

    Subcutaneous dosage (Gvoke)
    Adults

    1 mg subcutaneously. Instruct patients to seek medical attention immediately after administration of the first dose. May repeat 1 mg dose if there has been no response after 15 minutes; the patient should not administer more than 2 sequential doses unless under direct medical supervision.

    Children 2 to 12 years weighing 45 kg or more and Adolescents

    1 mg subcutaneously. Instruct patients to seek medical attention immediately after administration of the first dose. May repeat 1 mg dose if there has been no response after 15 minutes; the patient should not administer more than 2 sequential doses unless under direct medical supervision.

    Children 2 to 12 years weighing less than 45 kg

    0.5 mg subcutaneously. Instruct patients to seek medical attention immediately after administration of the first dose. May repeat 0.5 mg dose if there has been no response after 15 minutes; the patient should not administer more than 2 sequential doses unless under direct medical supervision.

    Nasal dosage (Baqsimi)
    Adults

    1 actuation (3 mg/dose) into 1 nostril. Instruct patients to seek medical attention immediately after administration of the first dose. May repeat 3 mg dose if there has been no response after 15 minutes; the patient should not administer more than 2 sequential doses unless under direct medical supervision.[64497]

    Children and Adolescents 4 to 17 years

    1 actuation (3 mg/dose) into 1 nostril. Instruct patients to seek medical attention immediately after administration of the first dose. May repeat 3 mg dose if there has been no response after 15 minutes; the patient should not administer more than 2 sequential doses unless under direct medical supervision.[64497]

    Psychotic patients receiving insulin shock therapy.
    Intramuscular or Intravenous dosage
    Adults

    0.5 to 1 mg of glucagon IM or IV after 1 hour of coma. If patient does not awaken after 10 to 25 minutes, the dose may be repeated. For patients in a deep state of coma, IV dextrose should be administered in addition to glucagon for a more immediate response.

    For the treatment of severe hypoglycemia in neonates.
    Intermittent Intramuscular, Intravenous, or Subcutaneous dosage
    Neonates


    0.2 mg/kg/dose IM, IV, or subcutaneously (Max: 1 mg/dose) is commonly used although there is variability in clinical practice; doses of 0.003 to 0.3 mg/kg/dose have been reported in the literature. If no response within 15 minutes, the dose may be repeated.[44772] [52416] [52418] Of note, FDA-approved product labeling does not provide specific recommendations for neonatal dosing, and there is wide variance between the doses reported in the literature and pediatric doses recommended by the product labeling. In addition, recommendations from product labeling vary by specific product. For glucagon (recombinant by Eli Lilly), 0.02 to 0.03 mg/kg/dose or 0.5 mg/dose for patients weighing less than 20 kg is the recommended dose.[52413] For GlucaGen, 0.5 mg/dose for patients weighing less than 25 kg is recommended.[28627]

    Continuous Intravenous Infusion†
    Neonates

    0.5 to 1 mg/day given as a continuous IV infusion regardless of age or weight (usual dose = 0.01 to 0.02 mg/kg/hour) is recommended by some experts. Administer IV dextrose concurrently. Continue glucagon infusion until blood glucose is stable then wean over 24 to 72 hours.

    For use as a diagnostic aide in radiographic examination and magnetic resonance imaging (MRI) of the GI tract.
    Intravenous or Intramuscular dosage
    Adults

    The dose ranges from 0.2 mg to 2 mg depending on the diagnostic technique and the route of glucagon administration. The usual diagnostic dose for relaxation of the stomach, duodenal bulb, duodenum, and small bowel is 0.2 mg to 0.5 mg IV OR 1 mg IM; the usual dose to relax the colon is 0.5 mg to 0.75 mg IV OR 1 mg to 2 mg IM. 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. Because the stomach and colon are less sensitive to glucagon's effects, one manufacturer recommends the 2 mg IM dose to inhibit movement of these organs. 1 mg IM has an approximate onset of action of 8 to 10 minutes and a duration of 12 to 27 minutes. 2 mg IM has an approximate onset of action of 4 to 7 minutes and a duration of 21 to 32 minutes. If examining the colon, administer IM approximately 10 minutes prior to the procedure.

    Children† and Adolescents†

    Dosage not established; not FDA-approved. However, off-label intravenous use for GI radiologic procedures is widely reported. Doses in literature are similar to those used in adults as listed in diagnostic glucagon package inserts. One publication used a weight-based protocol in their institution for MRI enterography in non-sedated children and adolescents: Patients weighing less than 24.9 kg are administered 0.5 mg IV. Patients weighing 24.9 kg or more receive 1 mg IV. Administered as a slow IV push over 5 minutes while IV saline is simultaneously administered via the same IV tubing. IV glucagon improves visualization of both the small- and large-bowel, but adds time to the diagnostic procedure and many patients experience nausea (48%). Emesis occurs in about 10% of patients. After the procedure, give oral carbohydrates to patients who have been fasting, if this is compatible with the diagnostic procedure applied.

    For the treatment of congenital hyperinsulinemia† (e.g., hyperinsulinemic hypoglycemia).
    Intravenous or Subcutaneous dosage
    Neonates

    0.001 to 0.02 mg/kg/hour IV or subcutaneously may reduce the infusion rate of glucose needed to maintain normoglycemia. Some experts recommend glucagon infusion with concurrent administration of octreotide; if administered concurrently, the lower initial rate of glucagon 0.001 mg/kg/hour is recommended. Monitor blood glucose closely.

    For the treatment of beta-blocker toxicity† or calcium channel blocker toxicity† (e.g., verapamil toxicity†).
    Intravenous dosage
    Adults

    3 to 10 mg IV followed by 1 to 10 mg/hour continuous IV infusion.[59357] [63131] [63867]

    Adolescents

    5 to 10 mg IV; repeat dose every 3 to 5 minutes as needed. May be followed by 1 to 5 mg/hour continuous IV infusion if required. Initial max rate: 5 mg/hour. Titrate to clinical effect.[44772] [52428]

    Infants and Children

    0.03 to 0.15 mg/kg/dose IV (Max: 10 mg/dose); may repeat every 3 to 5 minutes as needed. May be followed by 0.05 to 0.1 mg/kg/hour continuous IV infusion if required. Initial max rate: 5 mg/hour. Titrate to clinical effect.

    Neonates

    Safety and efficacy have not been established; very limited data are available. There have been case reports of using glucagon for neonatal beta-blocker toxicity due to maternal receipt before delivery; however, doses reported are not consistent. One report describes a dose of 0.25 mg IM in a 35-week gestational age neonate (birth weight 2,250 grams); repeated doses were required for recurrence of hypoglycemia.[52438] In another case, a 32-week gestational age neonate (birth weight 1,805 grams) was given an initial dose of glucagon 0.3 mg/kg IV, which resulted in an immediate improvement in heart rate and blood pressure. Five additional doses were required and ranged from 0.3 to 0.6 mg/kg/dose IV.[52519]

    For the emergency treatment of choking due to esophageal foreign body impaction†.
    Intravenous dosage
    Adults

    1 mg (dose range: 0.5 to 2 mg) IV has been used with some success. A second dose administered 5 to 10 minutes later is appropriate if needed. Limited data exist on the clinical application of this treatment, and although considered safe, its efficacy is variable. Glucagon is less effective in patients with structural abnormalities (i.e., strictures or rings) of the esophagus. In some patients, glucagon may promote spontaneous passage of an impacted foreign body by relaxing the lower esophageal sphincter; however, its use should not delay definitive endoscopic removal.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Dependent on route of administration and indication for therapy.

    Geriatric

    Dependent on route of administration and indication for therapy.

    Adolescents

    3 mg/dose for intranasal use and 1 mg/dose IV, IM, or subcutaneously is the maximum dose typically used; however, indication and clinical response determine dosage titration.

    Children

    Children 4 to 12 years: 3 mg/dose for intranasal use and 1 mg/dose IV, IM, or subcutaneously is the maximum dose typically used; however, indication and clinical response determine dosage titration.
    Children 1 to 3 years: 1 mg/dose IV, IM, or subcutaneously is the maximum dose typically used; however, indication and clinical response determine dosage titration. Safety and efficacy of intranasal administration have not been established.

    Infants

    1 mg/dose IV, IM, or subcutaneously is the maximum dose typically used; however, indication and clinical response determine dosage titration. Safety and efficacy of intranasal administration have not been established.

    Neonates

    1 mg/dose IV, IM, or subcutaneously is the maximum dose typically used; however, indication and clinical response determine dosage titration. Safety and efficacy of intranasal administration have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    For storage information, see specific product information within the How Supplied section.

    Injectable Administration

    Glucagon is administered by subcutaneous, intramuscular, or intravenous injection.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
     
    Reconstitution:
    Reconstitute with 1 mL of sterile water for injection or with diluent supplied by the manufacturer. 
    Shake the vial gently until the powder is completely dissolved.
    The reconstituted injection should be clear and of water-like consistency. The concentration is approximately 1 mg/mL glucagon.
    Use reconstituted injection immediately. Discard any unused portion.

    Intravenous Administration

    Inject glucagon directly into a vein at a rate not to exceed 1 mg/minute. May be administered through a line running Dextrose 5% Injection or given at the same time as a bolus of dextrose.

    Intramuscular Administration

    Inject glucagon into a large muscle mass.

    Subcutaneous Administration

    Inject glucagon subcutaneously taking care not to inject intradermally.
     
    Subcutaneous auto-injector and pre-filled syringe (Gvoke)
    For subcutaneous use only.
    Do not open foil pouch until it is ready to be used.
    Inspect prior to use. The solution should be clear and colorless to pale yellow and free of particles. Do not use if the solution is discolored or contains particulate matter.
    When ready to use, administer the injection in the lower abdomen, outer thigh, or outer upper arm.
    Call for emergency assistance immediately after administering the dose.
    Once patient responds to treatment, give oral carbohydrates to restore the liver glycogen and prevent recurrence of hypoglycemia.
    Do not reuse glucagon injection. Each injection contains 1 dose of glucagon and cannot be reused.

    Inhalation Administration
    Intranasal Inhalation Administration

    Intranasal powder (Baqsimi)
    For intranasal use only.
    Do not remove the shrink wrap or open the tube until it is ready to be used. Opening the tube could expose it to moisture causing it to not work as expected.
    Do not push the plunger or test the device prior to administration.
    When ready to use, remove the shrink wrap by pulling on the red stripe. Open the lid and remove the device from the tube without pressing the plunger.
    Hold device between fingers and thumb and administer the dose by inserting the tip into 1 nostril and pressing the device plunger all the way in until the green line is no longer showing. The dose does not need to be inhaled.
    Call for emergency assistance immediately after administering the dose.
    Once patient responds to treatment, give oral carbohydrates to restore the liver glycogen and prevent recurrence of hypoglycemia.
    Do not reuse glucagon device. Each device contains 1 dose of glucagon and cannot be reused.[64497]

    STORAGE

    BAQSIMI:
    - Protect from moisture
    - Store at room temperature not exceeding 86 degrees F
    - Store in original package until time of use
    GlucaGen:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Protect from light
    - Reconstituted product should be used immediately. Discard unused portion
    - Store in original container
    - Store unreconstituted product at 68 to 77 degrees F
    Glucagon:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Protect from light
    - Reconstituted product should be used immediately. Discard unused portion
    - Store in original container
    - Store unreconstituted product at 68 to 77 degrees F
    Gvoke:
    - Avoid extreme temperatures
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Do not refrigerate
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in original package until time of use

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Glucagon is contraindicated in patients with a known hypersensitivity to glucagon, lactose, or any other constituent of the formulations. 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 glucagon injection.

    Insulinoma

    Glucagon is contraindicated in patients who have been diagnosed with or suspected of having an insulinoma. In patients with insulinoma, glucagon may produce an initial increase in blood glucose; however, glucagon administration may directly or indirectly (through an initial rise in blood glucose) stimulate exaggerated insulin release from the insulinoma. Any patient developing symptoms of hypoglycemia after a dose of glucagon should be given glucose orally or intravenously, whichever is most appropriate. Caution should be observed in administering glucagon to patients with glucagonoma.

    Pheochromocytoma

    Glucagon is contraindicated in patients with pheochromocytoma because the drug may stimulate the release of catecholamines from the tumor. Stimulation of catecholamine release by exogenous glucagon can cause a substantial increase in blood pressure. 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.

    Adrenal insufficiency, anorexia nervosa, malnutrition

    In order for glucagon treatment to reverse hypoglycemia, adequate amounts of glucose must be stored in the liver (as glycogen). Therefore, glucagon should be used with caution in patients with conditions such as prolonged fasting, starvation (e.g., anorexia nervosa), malnutrition, 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 glucagon treatment. After the end of a diagnostic procedure where glucagon has been administered, oral carbohydrates should be administered to patients who have been fasting, if this is compatible with the diagnostic procedure applied.

    Cardiac disease, coronary artery disease

    Caution should be observed when glucagon is used as an adjunct in endoscopic or radiologic procedures to inhibit gastrointestinal motility in patients with known cardiac disease or coronary artery disease. A temporary increase in both blood pressure and pulse rate may occur following the administration of glucagon, due to the short half-life of the drug. In some patients, however, treatment may be needed. 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.

    Driving or operating machinery

    No studies of glucagon administration regarding the effects on the ability to drive and use machines have been performed. After diagnostic procedures, hypoglycemia has been reported infrequently. The patient’s ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating machinery. Therefore, these activities should be avoided until the patient has had intake of oral carbohydrates.

    Pregnancy

    There are no adequate and well-controlled studies in pregnant women; however limited clinical data in humans have revealed that there is very low or even negligible embryo and/or fetal risk from glucagon administered during pregnancy. Only doses of up to 1 mg have been reported in pregnant women. Because appropriate care of pregnant women is essential, pregnant women suffering from severe hypoglycemia should be administered glucagon when clinically indicated without concern for fetal safety; withholding therapy may place the fetus at greater risk than the minimal, if any, risk of glucagon exposure. Animal studies have not revealed any teratogenic effects associated with glucagon. Limited human and animal data both indicate that glucagon does not cross the placenta.

    Breast-feeding

    While caution should be exercised when glucagon is administered to breast-feeding women, there appears to be little risk to the nursing infant if the drug is clinically necessary for treatment of the lactating woman. No clinical studies have been performed in nursing mothers and it is not known if glucagon is excreted in human milk. However, glucagon is a peptide and is not absorbed intact from the GI tract. Therefore, it would be unlikely to have any effect on the infant if ingested by the infant via breast milk. Further, glucagon has a high molecular weight and a short plasma half-life thus likely limiting amounts excreted into human milk and available to the nursing infant.

    Infants

    Glucagon is reported safe and effective for treatment of severe hypoglycemia in pediatric patients. Glucagon depletes glycogen stores, thus pediatric patients should be given supplemental carbohydrates as soon as possible after administration for hypoglycemia. Safety and effectiveness for use as a diagnostic aid have not been established in infants or other pediatric patients. However, off-label use of glucagon for radiologic examination of the GI tract has been commonly reported in pediatric patients (children and adolescents). After the end of the diagnostic procedure, oral carbohydrates should be administered to patients administered glucagon who have been fasting, if this is compatible with the diagnostic procedure applied.

    ADVERSE REACTIONS

    Severe

    coma / Early / 0-1.0
    anaphylactoid reactions / Rapid / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    necrolytic migratory erythema / Delayed / Incidence not known

    Moderate

    hypoglycemia / Early / 0-39.0
    hyperglycemia / Delayed / 7.0-7.0
    antibody formation / Delayed / 2.0-2.0
    hypotension / Rapid / 0-1.0
    sinus tachycardia / Rapid / 0-1.0
    hypertension / Early / 0-1.0
    chest pain (unspecified) / Early / 0-1.0
    bullous rash / Early / Incidence not known

    Mild

    nausea / Early / 0-45.0
    nasal congestion / Early / 41.7-42.5
    rhinorrhea / Early / 25.0-34.6
    vomiting / Early / 0-30.6
    headache / Early / 5.0-25.0
    sneezing / Early / 19.4-19.6
    injection site reaction / Rapid / 3.0-7.0
    abdominal pain / Early / 3.0-3.0
    urticaria / Rapid / 3.0-3.0
    rash / Early / Incidence not known
    pruritus / Early / Incidence not known
    cough / Delayed / Incidence not known
    dysgeusia / Early / Incidence not known
    throat irritation / Early / Incidence not known
    epistaxis / Delayed / Incidence not known
    parosmia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Anticholinergics: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Atropine: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Atropine; Difenoxin: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Atropine; Diphenoxylate: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Atropine; Edrophonium: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Belladonna; Opium: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Benztropine: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Beta-blockers: (Minor) A temporary increase in both blood pressure and pulse rate may occur following the administration of glucagon. Patients taking beta-blockers might be expected to have a greater increase in both pulse and blood pressure. Glucagon exerts positive inotropic and chronotropic effects and may, therefore, cause tachycardia and hypertension in some patients. The increase in blood pressure and pulse rate may require therapy in some patients with coronary artery disease.
    Chlordiazepoxide; Clidinium: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Dicyclomine: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Flavoxate: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Glycopyrrolate: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Glycopyrrolate; Formoterol: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Homatropine; Hydrocodone: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Hyoscyamine: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Indacaterol; Glycopyrrolate: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Indomethacin: (Moderate) 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.
    Insulins: (Minor) Caution should be exercised when glucagon is used as a diagnostic aid for radiologic examination in patients taking insulin. Insulin reacts antagonistically towards glucagon. Monitor the patient receiving glucagon for a diagnostic procedure for the desired clinical effects. There is no concern when glucagon is used to treat severe hypoglycemia. If a patient receives glucagon due to severe hypoglycemia by a family member or caregiver, they should alert their health care provider so that insulin treatment may be adjusted, if needed.
    Mepenzolate: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Methscopolamine: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Oxybutynin: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Propantheline: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Scopolamine: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Trihexyphenidyl: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Warfarin: (Moderate) Caution should be exercised for patients taking warfarin when glucagon will be administered. Monitor the INR as clinically indicated and monitor for evidence of bleeding. Glucagon has been reported to enhance the hypoprothrombinemic response in 8 out of 13 patients receiving warfarin. Clinical bleeding also was reported in 3 patients. These findings - based on data from only 13 patients - were published in 1970 and no subsequent reports have been identified. The mechanism of this interaction is uncertain.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies in pregnant women; however limited clinical data in humans have revealed that there is very low or even negligible embryo and/or fetal risk from glucagon administered during pregnancy. Only doses of up to 1 mg have been reported in pregnant women. Because appropriate care of pregnant women is essential, pregnant women suffering from severe hypoglycemia should be administered glucagon when clinically indicated without concern for fetal safety; withholding therapy may place the fetus at greater risk than the minimal, if any, risk of glucagon exposure. Animal studies have not revealed any teratogenic effects associated with glucagon. Limited human and animal data both indicate that glucagon does not cross the placenta.

    While caution should be exercised when glucagon is administered to breast-feeding women, there appears to be little risk to the nursing infant if the drug is clinically necessary for treatment of the lactating woman. No clinical studies have been performed in nursing mothers and it is not known if glucagon is excreted in human milk. However, glucagon is a peptide and is not absorbed intact from the GI tract. Therefore, it would be unlikely to have any effect on the infant if ingested by the infant via breast milk. Further, glucagon has a high molecular weight and a short plasma half-life thus likely limiting amounts excreted into human milk and available to the nursing infant.

    MECHANISM OF ACTION

    Exogenous administration of glucagon produces the same pharmacologic effects as endogenous glucagon. Native human glucagon is a hormone synthesized by the alpha-2 cells of the pancreatic islets of Langerhans and acts to increase blood glucose. Glucagon induces glycogenolysis to increase blood glucose. Hepatic stores of glycogen are necessary for glucagon to increase blood glucose. In liver and adipose tissue, glucagon increases the production of adenylate cyclase, which catalyzes the conversion of ATP to cAMP. Cyclic AMP then initiates a series of enzymatic reactions that include activation of phosphorylase, which promotes the breakdown of glycogen to glucose. As a result, blood glucose levels are increased within minutes of glucagon administration. Blood glucose concentration increase within 10 minutes of injection, with maximal blood glucose levels occurring 30 to 45 minutes after injection, depending on the route of administration. The duration of hyperglycemic action after intravenous or intramuscular injection is 60 to 90 minutes. The effects of glucagon also include relaxation of smooth muscle of the GI tract, and a positive inotropic and chronotropic effect on the heart. Extra hepatic effects of glucagon include relaxation of the smooth muscle of the stomach, duodenum, small bowel, and colon. The exact mechanism by which glucagon exerts its effects on GI smooth muscle and cardiac muscle are unknown.

    PHARMACOKINETICS

    Glucagon is administered intranasally and parenterally. Similar to other polypeptides, parenteral administration avoids rapid and complete degradation in the GI tract. The time to maximum hyperglycemic activity is dependent upon the route of administration. The onset and duration of GI smooth muscle effects depends on dose and route of administration. The metabolism of glucagon has not been clearly defined, but it is extensively degraded by the liver, kidneys, and plasma. The plasma half-life of IV glucagon is approximately 8 to 18 minutes.[52413] The half-life of intranasal glucagon is 35 minutes and 45 minutes for intramuscular injection.[28627] [64497]
     
    Affected cytochrome P450 isoenzymes: none

    Intravenous Route

    The maximal glucose concentrations occur 5 to 20 minutes after intravenous administration of glucagon. Blood glucose concentrations return to normal or hypoglycemic levels within 1 to 2 hours. The onset of GI smooth muscle effects is within 1 minute after intravenous administration. The duration of GI smooth muscle effects after intravenous administration varies between 9 to 25 minutes.

    Intramuscular Route

    The maximal glucose concentrations occur 30 minutes after an intramuscular dose of glucagon. Blood glucose concentrations return to normal or hypoglycemic levels within 1 to 2 hours. The onset of GI smooth muscle effects is within 8 to 10 minutes or 4 to 7 minutes after 1 mg or 2 mg intramuscular doses, respectively. The duration of GI smooth muscle effects after intramuscular administration varies between 12 to 32 minutes. A mean apparent half-life of 45 minutes after intramuscular injection is observed and probably reflects prolonged absorption from the injection site.[28627]

    Subcutaneous Route

    The maximal glucose concentrations occur 30 to 45 minutes after a subcutaneous dose of glucagon. Blood glucose concentrations return to normal or hypoglycemic levels within 1 to 2 hours.

    Other Route(s)

    Intranasal Route
    Mean peak plasma concentrations occur approximately 15 minutes after an intranasal dose of glucagon.