nded. warfarin clinical impact: glucagon for injection may increase the anticoagulant effect of warfarin. intervention: monitor patients for unusual bruising or bleeding, as adjustments in warfarin dosage may be required. insulin clinical impact: insulin acts antagonistically to glucagon. intervention: monitor blood glucose when glucagon for injection is used as a diagnostic aid in patients receiving insulin. beta-blockers : patients taking beta-blockers may have a transient increase in pulse and blood pressure. ( 7 ) indomethacin : in patients taking indomethacin glucagon for injection may lose its ability to raise glucose or may produce hypoglycemia. ( 7 ) anticholinergic drugs : concomitant use of anticholinergic drugs with glucagon for injection for use as a diagnostic aid is not recommended. ( 7 ) warfarin : glucagon for injection may increase the anticoagulant effect of warfarin. ( 7 ) insulin : monitor blood glucose when glucagon for injection is used as a diagnostic aid in patients receiving insulin. ( 7 )

ycemia only if sufficient hepatic glycogen is present. patients in states of starvation, with adrenal insufficiency or chronic hypoglycemia may not have adequate levels of hepatic glycogen for glucagon for injection administration to be effective. patients with these conditions should be treated with glucose. ( 5.4 ) necrolytic migratory erythema (nme): necrolytic migratory erythema (nme), a skin rash, have been reported post marketing following continuous glucagon infusion and resolved with discontinuation of the glucagon. should nme occur, consider whether the benefits of continuous glucagon infusion outweigh the risks. ( 5.5 ) hyperglycemia in patients with diabetes mellitus when used as a diagnostic aid : treatment with glucagon for injection in patients with diabetes mellitus may cause hyperglycemia. monitor diabetic patients for changes in blood glucose levels during treatment and treat if indicated. ( 5.6 ) blood pressure and heart rate increase in patients with cardiac disease when used as a diagnostic aid : glucagon for injection may increase myocardial oxygen demand, blood pressure, and pulse rate. cardiac monitoring is recommended in patients with cardiac disease during use of glucagon for injection as a diagnostic aid, and an increase in blood pressure and pulse rate may require therapy. ( 5.7 ) hypoglycemia in patients with glucagonoma: glucagon administered to patients with glucagonoma may cause secondary hypoglycemia. test patients suspected of having glucagonoma for blood levels of glucagon prior to treatment. ( 4 , 5.8 ) 5.1 substantial increase in blood pressure in patients with pheochromocytoma glucagon for injection is contraindicated in patients with pheochromocytoma because glucagon may stimulate the release of catecholamines from the tumor [see contraindications ( 4 )]. 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. 5.2 hypoglycemia in patients with insulinoma in patients with insulinoma, administration of glucagon may produce an initial increase in blood glucose; however, glucagon for injection administration may directly or indirectly (through an initial rise in blood glucose) stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. glucagon for injection is contraindicated in patients with insulinoma [see contraindications ( 4 )]. if a patient develops symptoms of hypoglycemia after a dose of glucagon for injection, give glucose orally or intravenously. 5.3 hypersensitivity and allergic reactions allergic reactions have been reported with glucagon, these include generalized rash, and in some cases anaphylactic shock with breathing difficulties and hypotension. glucagon for injection is contraindicated in patients with a prior hypersensitivity reaction [see contraindications ( 4 )] . 5.4 lack of efficacy in patients with decreased hepatic glycogen glucagon for injection is effective in treating hypoglycemia only if sufficient hepatic glycogen is present. patients in states of starvation, with adrenal insufficiency or chronic hypoglycemia may not have adequate levels of hepatic glycogen for glucagon for injection administration to be effective. patients with these conditions should be treated with glucose. 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 post marketing 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 hyperglycemia in patients with diabetes mellitus when used as a diagnostic aid treatment with glucagon for injection in patients with diabetes mellitus may cause hyperglycemia. monitor diabetic patients for changes in blood glucose levels during treatment and treat if indicated. 5.7 blood pressure and heart rate increase in patients with cardiac disease when used as a diagnostic aid glucagon for injection may increase myocardial oxygen demand, blood pressure, and pulse rate which may be life-threatening in patients with cardiac disease. cardiac monitoring is recommended in patients with cardiac disease during use of glucagon for injection as a diagnostic aid, and an increase in blood pressure and pulse rate may require therapy. 5.8 hypoglycemia in patients with glucagonoma glucagon administered to patients with glucagonoma may cause secondary hypoglycemia. test patients suspected of having glucagonoma for blood levels of glucagon prior to use as a diagnostic aid as glucagon for injection is contraindicated in this setting [see contraindications ( 4 )].

minister intravenously only under medical supervision. see the full prescribing information for administration instructions dosage in adults for using glucagon for injection as a diagnostic aid ( 2.4 ) doses required for relaxation of the stomach, duodenum, and small bowel, depend on the onset and duration of effect required for the examination. the dose for relaxation of the duodenum and small bowel is 0.25 mg to 0.5 mg given intravenously or 1 mg given intramuscularly. for the stomach 0.5 mg intravenous or 2 mg intramuscular doses are recommended. for the colon, it is recommended that a 2 mg dose be administered intramuscularly approximately 10 minutes prior to the procedure. see the full prescribing information for administration instructions ( 2.3 ) 2.1 important administration instructions for using glucagon for injection to treat severe hypoglycemia glucagon for injection is for subcutaneous, intramuscular, or intravenous injection. administer intravenously only under medical supervision. instruct patients and their caregivers on the signs and symptoms of severe hypoglycemia. because severe hypoglycemia requires the help of others to recover, instruct the patient to inform those around them about glucagon for injection and its instructions for use. administer glucagon for injection as soon as possible when severe hypoglycemia is recognized. instruct the patient or caregiver to read the instructions for use at the time they receive a prescription for glucagon for injection. emphasize the following instructions to the patient or caregiver: using the supplied prefilled syringe, carefully insert the needle through the rubber stopper of the vial containing glucagon for injection powder and inject all the liquid from the syringe into the vial. swirl the vial gently until the powder is completely dissolved and no particles remain in the fluid. the reconstituted solution should be clear and of a water-like consistency at time of use. inspect visually for particulate matter and discoloration. if the resulting solution is cloudy or contains particulate matter do not use. the reconstituted solution is 1 mg per ml glucagon. use immediately after reconstitution. immediately after reconstitution, use the same syringe to withdraw the correct dose of glucagon for injection. inject the solution subcutaneously or intramuscularly in the upper arm, thigh, or buttocks. in addition, healthcare providers may administer intravenously. call for emergency assistance immediately after administering the dose. if there has been no response after 15 minutes, an additional dose of glucagon for injection may be administered while waiting for emergency assistance. when the patient has responded to the treatment and is able to swallow, give oral carbohydrates to restore the liver glycogen and prevent recurrence of hypoglycemia. discard any unused portion. 2.2 dosage for treatment of severe hypoglycemia adults and pediatric patients weighing 20 kg or more the recommended dosage is 1 mg (1 ml) injected subcutaneously or intramuscularly into the upper arm, thigh, or buttocks. alternatively, healthcare providers may administer the dose intravenously. if there has been no response after 15 minutes, an additional 1 mg dose (1 ml) of glucagon for injection may be administered while waiting for emergency assistance. pediatric patients weighing less than 20 kg the recommended dosage is 0.5 mg (0.5 ml) or dose equivalent to 20 to 30 mcg/kg injected subcutaneously or intramuscularly into the upper arm, thigh, or buttocks. alternatively, healthcare providers may administer the dose intravenously. if there has been no response after 15 minutes, an additional 0.5 mg dose (0.5 ml) of glucagon for injection may be administered while waiting for emergency assistance. 2.3 important administration instructions for using glucagon for injection as a diagnostic aid reconstitute glucagon for injection with 1 ml of diluent. swirl the vial gently until the powder is completely dissolved and no particles remain in the fluid. the reconstituted solution should be clear and of a water-like consistency at time of use. inspect visually for particulate matter and discoloration. if the resulting solution is cloudy or contains particulate matter do not use. withdraw the correct dose of glucagon for injection. the reconstituted solution is 1 mg per ml glucagon. immediately after reconstitution, inject the solution intravenously or intramuscularly into upper arm, thigh, or buttocks. discard unused portion. after the end of the diagnostic procedure, give oral carbohydrates to patients who have been fasting, if this is compatible with the diagnostic procedure. 2.4 dosage in adults for use as a diagnostic aid doses required for relaxation of the stomach, duodenum, and small bowel, depend on the onset and duration of effect required for the examination [see pharmacodynamics ( 12.2 )] . the usual dose for relaxation of the stomach, duodenum and small bowel is 0.25 mg to 0.5 mg given intravenously or 1 mg given intramuscularly, but up to 2 mg intravenously or intramuscularly may be used if required (2 mg doses produce a higher rate of nausea and vomiting than lower doses) [see adverse reactions ( 6 )] . for the stomach because it is less sensitive to the effect of glucagon, 0.5 mg intravenous or 2 mg intramuscular doses are recommended. for the examination of the colon, it is recommended that a 2 mg dose be administered intramuscularly approximately 10 minutes prior to the procedure.

ock with breathing difficulties and hypotension hypertension and tachycardia decreased blood pressure. hypotension has been reported up to 2 hours after administration in patients receiving glucagon as premedication for upper gastrointestinal endoscopy procedures. hypoglycemia and hypoglycemic coma. patients taking indomethacin may be more likely to experience hypoglycemia following glucagon administration [see drug interactions ( 7 )] . necrolytic migratory erythema (nme) cases have been reported post marketing in patients receiving continuous infusion of glucagon. glucagon adverse reactions include: injection site reactions, nausea, vomiting, headache, dizziness, asthenia, pallor, diarrhea, somnolence, and decreased blood pressure, to report suspected adverse reactions, contact eli lilly and company at 1-800-lillyrx (1-800-545-5979) or fda at 1-800-fda-1088 or www.fda.gov/medwatch .

nded. warfarin clinical impact: glucagon for injection may increase the anticoagulant effect of warfarin. intervention: monitor patients for unusual bruising or bleeding, as adjustments in warfarin dosage may be required. insulin clinical impact: insulin acts antagonistically to glucagon. intervention: monitor blood glucose when glucagon for injection is used as a diagnostic aid in patients receiving insulin. beta-blockers : patients taking beta-blockers may have a transient increase in pulse and blood pressure. ( 7 ) indomethacin : in patients taking indomethacin glucagon for injection may lose its ability to raise glucose or may produce hypoglycemia. ( 7 ) anticholinergic drugs : concomitant use of anticholinergic drugs with glucagon for injection for use as a diagnostic aid is not recommended. ( 7 ) warfarin : glucagon for injection may increase the anticoagulant effect of warfarin. ( 7 ) insulin : monitor blood glucose when glucagon for injection is used as a diagnostic aid in patients receiving insulin. ( 7 )

egnant rats given animal sourced glucagon twice-daily by injection at doses up to 2 mg/kg (up to 40 times the human dose based on body surface area extrapolation, mg/m 2 ) during the period of organogenesis, there was no evidence of increased malformations or embryofetal lethality. 8.2 lactation risk summary 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. however, glucagon is a peptide and would be expected to be broken down to its constituent amino acids in the infant's digestive tract and is therefore, unlikely to cause harm to an exposed infant. 8.4 pediatric use the safety and effectiveness of glucagon for injection for the treatment of severe hypoglycemia in pediatric patients with diabetes have been established. safety and effectiveness for use as a diagnostic aid during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract in pediatric patients have not been established. 8.5 geriatric use clinical studies of glucagon did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient when used as a diagnostic aid should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

ed glucagon twice-daily by injection at doses up to 2 mg/kg (up to 40 times the human dose based on body surface area extrapolation, mg/m 2 ) during the period of organogenesis, there was no evidence of increased malformations or embryofetal lethality.

es of glucagon for injection as a diagnostic aid during radiological examination. table 2: dose and pharmacodynamic properties of glucagon for injection as a diagnostic aid * administration of 2 mg doses produces a higher incidence of nausea and vomiting than do lower doses. dose route of administration time of onset of action approximate duration of effect 0.25 – 0.5 mg intravenous 1 minute 9 – 17 minutes 1 mg intramuscular 8 – 10 minutes 12 – 27 minutes 2 mg* intravenous 1 minute 22 – 25 minutes 2 mg* intramuscular 4 – 7 minutes 21 – 32 minutes 12.3 pharmacokinetics absorption glucagon injected through the intramuscular route achieved mean peak plasma levels of 6.9 ng/ml at approximately 13 minutes after dosing; and 7.9 ng/ml at approximately 20 minutes after subcutaneous dosing. administration of the intravenous glucagon showed dose proportionality of the pharmacokinetics between 0.25 and 2 mg. figure 2 mean (se) serum glucagon concentrations after subcutaneous injection of glucagon (1 mg) in 25 normal volunteers figure 2 distribution the mean volume of distribution was 0.25 l/kg. elimination the mean clearance was 13.5 ml/min/kg. the mean half-life ranged from 8 to 18 minutes. metabolism glucagon is degraded in the liver, kidney and plasma.

of ingredients in glucagon for injection. before using glucagon for injection, tell your healthcare provider about all of your medical conditions, including if you: have adrenal problems. have pancreas problems. have not had anything to eat or have not had a drink of water for a long time (prolonged fasting or starvation). have low blood sugar that does not go away (chronic hypoglycemia). have heart problems. are pregnant or plan to become pregnant. it is not known if glucagon will harm your unborn baby. are breastfeeding or plan to breastfeed. it is not known if glucagon passes into your breast milk. tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. glucagon may affect the way other medicines work, and other medicines may affect how glucagon works. know the medicines you take. keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. how should i use glucagon for injection? read the detailed instructions for use that come with glucagon for injection. use glucagon for injection exactly how and when your healthcare provider tells you to use it. make sure you and your caregiver knows where you keep your glucagon for injection and how to use glucagon for injection the right way before you need their help. act quickly. having very low blood sugar for a period of time may be harmful. after glucagon is mixed, make sure it is clear and of water-like consistency. do not use if it has particles or is discolored. after giving glucagon for injection the caregiver should call for emergency medical help right away. turn the person on their side to prevent them from choking. if the person does not respond after 15 minutes, another dose may be given, if available while waiting for emergency medical help. eat sugar or a sugar sweetened product such as a regular soft drink or fruit juice as soon as you are able to swallow. tell your healthcare provider each time you use glucagon for injection. your healthcare provider may need to change the dose of your diabetes medicines. what are the possible side effects of glucagon for injection? glucagon may cause serious side effects, including: high blood pressure . glucagon can cause high blood pressure in certain people with tumors in their adrenal glands called pheochromocytoma. low blood sugar . glucagon can cause low blood sugar in people with tumors in their pancreas called insulinomas and glucagonomas . signs and symptoms of low blood sugar may include: sweating drowsiness dizziness sleep disturbances irregular heartbeat anxiety tremor blurred vision hunger slurred speech restlessness depressed mood tingling in the hands, feet, lips or tongue irritability abnormal behavior lightheadedness unsteady movement inability to concentrate personality changes headache very low blood sugar can cause confusion, seizures, passing out (loss of consciousness) and death. talk to your healthcare provider about how to tell if you have low blood sugar and what to do if this happens while using glucagon for injection. know your symptoms of low blood sugar. follow your healthcare provider's instructions for treat low blood sugar. serious allergic reactions. call your healthcare provider or get medical help right away if you have a serious allergic reaction including: rash difficulty breathing low blood pressure high blood sugar. if you receive glucagon for injection before your radiology exam, it can cause high blood sugar. your healthcare provider will monitor your blood sugar levels during your treatment. heart problems. if you have heart problems and receive glucagon for injection before your radiology exam, you may have an increase in your blood pressure and pulse while using glucagon for injection which could be life threatening.your healthcare provider will monitor your heart during treatment. the most common side effects of glucagon for injection include: swelling at the injection site redness at the injection site vomiting nausea decreased blood pressure weakness headache dizziness pale skin diarrhea sleepiness or drowsiness tell your healthcare provider if you have any side effect that bothers you or that does not go away. these are not all the possible side effects of glucagon for injection. for more information, ask your healthcare provider. call your doctor for medical advice about side effects. you may report side effects to fda at 1-800-fda-1088. how should i store glucagon for injection? before you mix the glucagon powder and liquid: do not use glucagon for injection if the expiration date has passed. store glucagon for injection at room temperature between 68°f to 77°f (20°c to 25°c). do not freeze glucagon. keep glucagon for injection in its original package and away from light. after you mix the glucagon powder and liquid: use glucagon for injection right away. throw away unused glucagon for injection. keep glucagon for injection and all medicines out of the reach of children . general information about the safe and effective use of glucagon for injection. medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. do not use glucagon for injection for a condition for which it was not prescribed. do not give glucagon for injection to other people, even if they have the same symptoms that you have. it may harm them. you can ask your pharmacist or healthcare provider for information about glucagon for injection that is written for health professionals. what are the ingredients in the glucagon for injection? active ingredient: glucagon inactive ingredients: lactose monohydrate, hydrochloric acid, and water for injection marketed by: lilly usa, llc, indianapolis , in 46285, usa copyright © 1999, 2021, eli lilly and company. all rights reserved.