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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 weighing 25 kg or more

    0.03 mg/kg/dose IM, IV, or subcutaneously once (Max: 1 mg/dose); may repeat every 15 minutes for up to 3 doses. Administer in conjunction with glucose/dextrose.

    Infants and Children weighing less than 25 kg

    0.03 mg/kg/dose IM, IV, or subcutaneously once (Max: 0.5 mg/dose); may repeat every 15 minutes for up to 3 doses. Administer in conjunction with glucose/dextrose.

    Intramuscular, Intravenous, or Subcutaneous dosage (GlucaGen)
    Adults

    1 mg administered IM, IV, or subcutaneously. Call for emergency assistance immediately after administering the dose. If there has been no response after 15 minutes, an additional dose may be administered 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 there has been no response after 15 minutes, an additional 1 mg dose may be administered using a new kit while waiting for emergency assistance. Administer in conjunction with glucose/dextrose.

    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 there has been no response after 15 minutes, an additional 0.5 mg dose may be administered using a new kit while waiting for emergency assistance. Administer in conjunction with glucose/dextrose.

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

    1 mg IM, IV, or subcutaneously; if there has been no response after 15 minutes, an additional 1 mg dose may be administered using a new kit while waiting for emergency assistance. 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 there has been no response after 15 minutes, an additional 0.5 mg dose may be administered using a new kit while waiting for emergency assistance. Administer in conjunction with glucose/dextrose.

    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 there has been no response after 15 minutes, an additional 0.5 mg dose may be administered using a new kit while waiting for emergency assistance. Administer in conjunction with glucose/dextrose.

    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 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. May repeat every 15 minutes for up to 3 doses. Of note, FDA-approved product labeling does not provide specific recommendations for neonatal dosing, and there is a 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. For GlucaGen, 0.5 mg/dose for patients weighing less than 25 kg is recommended.

    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. Some products (e.g., Gvoke) are only for subcutaneous use.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
     
    Reconstitution of Lyophilized Glucagon injection 1 mg vial:
    Using a syringe, withdraw 1 mL of Sterile Water for Injection and inject into the vial of lyophilized injection powder.
    Shake gently until the powder is completely dissolved and no particles remain.
    The reconstituted solution should be clear and of water-like consistency. Discard if there are signs of gel formation or particles.
    The final concentration is approximately 1 mg/mL.
    Use immediately after reconstitution. Discard any unused portion.

    Intravenous Administration

    IV Push
    Must be administered by a health care professional only.
    After reconstitution, administer the dose IV as a bolus over a time period of 1 minute.
    Single bolus doses above 1 mg IV have caused nausea and vomiting and are not recommended.

    Intramuscular Administration

    See the manufacturer's "Instructions for Use" for the specific product prescribed.
    Reconstitute as directed. Withdraw the correct patient dose.
    Inject IM into the upper arm, thigh, or buttocks.
    Discard any unused portion.

    Subcutaneous Administration

    Train patients and/or caregivers in the proper injection technique.
    See the manufacturer's "Instructions for Use" for the specific product prescribed.
     
    GlucaGen Subcutaneous Administration (e.g., GlucaGen, GlucaGen Hypokit)
    Reconstitute as directed. Withdraw the correct dose from the vial.
    Inject subcutaneously in the upper arm, thigh, or buttocks.
    If used as an outpatient: 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.
    Discard any unused portion. Put used syringes in an FDA-cleared sharps disposal container right away after use.
     
    Gvoke Subcutaneous Administration (i.e., auto-injector, pre-filled syringe, and vial and syringe kit)
    For subcutaneous use only.
    For the auto-injector or pre-filled syringe: Do not open foil pouch until it is ready to be used.
    For the vial and syringe kit: Store in original carton until ready to administer. Reconstitute as directed.
    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.
    Withdraw the correct dose (if required).
    Administer in the lower abdomen, outer thigh, or outer upper arm.
    If used as an outpatient: Call for emergency assistance immediately after administering the dose.
    If there has been no response after 15 minutes, administer an additional dose from a new device (or vial and syringe kit).
    Once patient responds to treatment, give oral carbohydrates to restore the liver glycogen and prevent recurrence of hypoglycemia.
    Do not reuse injectors or syringes. Each injection or vial contains 1 dose of glucagon and cannot be reused; discard any unused portion. Dispose of used auto-injector or syringes properly in an FDA-cleared sharps disposal container right away after use.

    Inhalation Administration
    Intranasal Inhalation Administration

    Nasal powder (Baqsimi)
    For nasal 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 or 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.

    Glucagonoma, 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. Glucagon is contraindicated in patients with glucagonoma when used as a diagnostic aid. Test patients suspected of having glucagonoma for blood levels of glucagon prior to diagnostic use, and monitor for changes in blood glucose levels during treatment. If a patient develops symptoms of hypoglycemia after a diagnostic dosage, administer glucose orallyor intravenously.

    Pheochromocytoma

    Glucagon is contraindicated in patients with pheochromocytoma because glucagon may stimulate the release of catecholamines from the tumor. If the patient develops a substantial increase in blood pressure and a previously undiagnosed pheochromocytoma is suspected, 5 to 10 mg of phentolamine mesylate, administered intravenously, has been shown to be effective in lowering blood pressure for the short time that control would be needed.

    Adrenal insufficiency, anorexia nervosa, malnutrition

    Glucagon is effective in treating hypoglycemia only if sufficient hepatic glycogen is present. Patients in states of starvation (e.g., anorexia nervosa), malnutrition, adrenal insufficiency, or chronic hypoglycemia may not have adequate levels of hepatic glycogen for glucagon administration to be effective. Patients with these conditions should be treated with glucose. 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

    Glucagon may increase myocardial oxygen demand, blood pressure, and pulse rate which may be life-threatening in patients with cardiac disease or coronary artery disease. Cardiac monitoring is recommended in patients with cardiac disease during use of glucagon as a diagnostic aid, and an increase in blood pressure and pulse rate may require therapy.

    Driving or operating machinery, hyperglycemia

    Inform patients that hypoglycemia has occurred when glucagon has been used for diagnostic purposes. Inform patients of the symptoms of hypoglycemia and how to treat it. Advise patients to avoid driving or operating machinery until ingesting a meal. Advise patients to inform their health care provider if hypoglycemia occurs so that treatment may be given if necessary. When used as a diagnostic aid in patients with diabetes mellitus, glucagon may cause hyperglycemia; monitor such patients for changes in blood glucose levels during treatment.

    Pregnancy

    Available data from case reports and a few observational studies with glucagon use 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 from use during pregnancy. Glucagon does not cross the human placental barrier. 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.

    Breast-feeding

    There is no information available on the presence of glucagon in human or animal milk, the effects of glucagon on the breastfed child or the effects of glucagon on milk production in a breast-feeding woman. However, glucagon is a peptide and intact glucagon is not absorbed from the GI tract. Therefore, even if the infant ingested glucagon it would be unlikely to have any effect on the infant. Additionally, glucagon has a short plasma half-life thus limiting amounts available to the child.

    ADVERSE REACTIONS

    Severe

    coma / Early / 0-1.0
    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
    sinus tachycardia / Rapid / 0-1.0
    hypotension / Rapid / 0-1.0
    hypertension / 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
    asthenia / Delayed / Incidence not known
    dizziness / Early / Incidence not known
    pallor / Early / Incidence not known
    diarrhea / Early / Incidence not known
    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; 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.
    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.
    Budesonide; 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.
    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.
    Diphenoxylate; 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.
    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.
    Phenobarbital; Hyoscyamine; Atropine; 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.
    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

    Available data from case reports and a few observational studies with glucagon use 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 from use during pregnancy. Glucagon does not cross the human placental barrier. 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.

    There is no information available on the presence of glucagon in human or animal milk, the effects of glucagon on the breastfed child or the effects of glucagon on milk production in a breast-feeding woman. However, glucagon is a peptide and intact glucagon is not absorbed from the GI tract. Therefore, even if the infant ingested glucagon it would be unlikely to have any effect on the infant. Additionally, glucagon has a short plasma half-life thus limiting amounts available to the child.

    MECHANISM OF ACTION

    Glucagon injections produce 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 increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver. Hepatic stores of glycogen are necessary for glucagon to produce an antihypoglycemic effect. 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.
     
    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 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.