hacin clinical impact: in patients taking indomethacin, glucagon for injection may lose its ability to raise blood glucose or may even produce hypoglycemia. intervention: monitor blood glucose levels during glucagon treatment of patients taking indomethacin. anticholinergic drugs clinical impact: the concomitant use of anticholinergic drugs and glucagon for injection increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. intervention: concomitant use of anticholinergic drugs with glucagon for injection for use as a diagnostic aid is not recommended. 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.

t. patients in states of starvation, with adrenal insufficiency or chronic hypoglycemia may not have adequate levels of hepatic glycogen for glucagon for injection to be effective. patients with these conditions should be treated with glucose. ( 5.4 ) necrolytic migratory erythema (nme): a skin rash, has been reported postmarketing 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 when used as a diagnostic aid: glucagon administered to patients with glucagonoma may cause secondary hypoglycemia. test patients suspected of having glucagonoma for blood levels of glucagon prior to treatment, and monitor blood glucose levels during treatment. if a patient develops hypoglycemia, give glucose orally or intravenously. ( 5.8 ) 5.1 catecholamine release 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 dramatic 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 postmarketing following continuous glucagon infusion. nme lesions may affect the face, groin, perineum and legs or be more widespread. in the reported cases nme resolved with discontinuation of the glucagon, and treatment with corticosteroids was not effective. should nme occur, consider whether the benefits of continuous glucagon infusion outweigh the risks. 5.6 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. glucagon for injection is contraindicated in patients with glucagonoma when used as a diagnostic aid [see contraindications ( 4 )]. test patients suspected of having glucagonoma for blood levels of glucagon prior to treatment, and monitor for changes in blood glucose levels during treatment. if a patient develops symptoms of hypoglycemia after a dose of glucagon for injection, give glucose orally or intravenously.

a new kit while waiting for emergency assistance. important administration instructions for using the glucagon emergency kit for low blood sugar to treat severe hypoglycemia ( 2.1 ) glucagon for injection is for subcutaneous, intramuscular, or intravenous injection. administer intravenously only under medical supervision. see the full prescribing information for administration instructions dosage in adults for using glucagon for injection diagnostic kit and glucagon for injection single-dose vial as a diagnostic aid ( 2.4 ) the recommended diagnostic dose for relaxation of the stomach, duodenal bulb, duodenum, and small bowel is 0.2 mg to 0.5 mg administered intravenously or 1 mg administered intramuscularly; the recommended dose to relax the colon is 0.5 mg to 0.75 mg administered intravenously or 1 mg to 2 mg administered intramuscularly. see the full prescribing information for administration instructions ( 2.3 ) 2.1 important administration instructions for using the glucagon emergency kit for low blood sugar 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. shake the vial gently until the powder is completely dissolved and no particles remain in the fluid. the reconstituted solution should be clear and colorless. 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. immediately after reconstitution, 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. 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 in adults and pediatric patients for using the glucagon emergency kit for low blood sugar to treat severe hypoglycemia adults and pediatric patients weighing more than 25 kg or for pediatric patients with unknown weight 6 years and older the recommended dosage is 1 mg (1 ml) injected subcutaneously or intramuscularly into the upper arm, thigh, or buttocks, or intravenously. if there has been no response after 15 minutes, an additional 1 mg dose (1 ml) of glucagon for injection may be administered using a new kit while waiting for emergency assistance. pediatric patients weighing less than 25 kg or for pediatric patients with unknown weight less than 6 years of age the recommended dosage is 0.5 mg (0.5 ml) injected subcutaneously or intramuscularly into the upper arm, thigh, or buttocks, or 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 using a new kit while waiting for emergency assistance. 2.3 important administration instruction for using glucagon for injection diagnostic kit and glucagon for injection single-dose vial as a diagnostic aid reconstitute glucagon for injection with 1 ml of sterile water for injection. using a syringe, withdraw all of the sterile water for injection (if supplied) or 1 ml sterile water for injection and inject into the glucagon for injection vial. shake the vial gently until the powder is completely dissolved and no particles remain in the fluid. the reconstituted fluid should be clear and colorless. 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. immediately after reconstitution, inject the solution intravenously or intramuscularly into upper arm, thigh, or buttocks. discard any 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 using glucagon for injection diagnostic kit and glucagon for injection single-dose vial as a diagnostic aid the recommended diagnostic dose for relaxation of the stomach, duodenal bulb, duodenum, and small bowel is 0.2 mg to 0.5 mg administered intravenously or 1 mg administered intramuscularly; the recommended dose to relax the colon is 0.5 mg to 0.75 mg administered intravenously or 1 mg to 2 mg administered intramuscularly [see clinical pharmacology ( 12.2 )] . the onset of action after an injection will depend on the organ under examination and route of administration [see clinical pharmacology ( 12.2 )] .

es observed in the clinical trials of a drug cannot be directly compared to the rates in clinical trials of another drug and may not reflect the rates observed in practice. in a randomized single-blind clinical study of glucagon for injection, 29 healthy subjects received a single dose of 1 mg glucagon for injection intramuscularly. table 1 shows the most common adverse reactions that were not present at baseline and occurred in at least 5% of patients. table 1: adverse reactions occurring in ≥ 5% of healthy subjects who received glucagon for injection intramuscularly glucagon for injection (n=29) % of patients nausea 17 vomiting 7 in a randomized, single-blind clinical study of glucagon for injection, 31 healthy subjects received a single dose of 1 mg glucagon for injection subcutaneously. table 2 shows the most common adverse reactions that were not present at baseline and occurred in at least 5% of patients. ( 2.1 )]. table 2: adverse reactions occurring ≥5% in healthy subjects who received glucagon for injection subcutaneously glucagon for injection (n=31) % of patients injection site swelling 58 injection site erythema 55 vomiting 36 nausea 32 decreased blood pressure 23 asthenia 23 headache 13 dizziness 10 pallor 10 diarrhea 7 somnolence 7 other adverse reactions hypertension and tachycardia have occurred with glucagon treatment. 6.2 postmarketing experience additional adverse reactions have been identified during post-approval use of glucagon. because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. 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 postmarketing in patients receiving continuous infusion of glucagon.

hacin clinical impact: in patients taking indomethacin, glucagon for injection may lose its ability to raise blood glucose or may even produce hypoglycemia. intervention: monitor blood glucose levels during glucagon treatment of patients taking indomethacin. anticholinergic drugs clinical impact: the concomitant use of anticholinergic drugs and glucagon for injection increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. intervention: concomitant use of anticholinergic drugs with glucagon for injection for use as a diagnostic aid is not recommended. 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.

spectively. data animal data in rats and rabbits given glucagon by injection at doses of 0.4, 2.0, and 10 mg/kg (up to 100 and 200 times the human dose based on mg/m 2 for rats and rabbits, respectively) 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.

n rats and rabbits given glucagon by injection at doses of 0.4, 2.0, and 10 mg/kg (up to 100 and 200 times the human dose based on mg/m 2 for rats and rabbits, respectively) there was no evidence of increased malformations or embryofetal lethality.

r glucagon for injection product for intravenous route a dose is determined based on the length of the procedure. route of administration dose a time of maximal glucose concentration time of onset of action for gi smooth muscle relaxation duration of smooth muscle relaxation intravenous 0.25 to 0.5 mg 5 to 20 minutes 45 seconds 9 to 17 minutes table 5 pharmacodynamic properties of another glucagon for injection product for intramuscular route a dose is determined based on the length of the procedure. route of administration dose a time of maximal glucose concentration time of onset of action for gi smooth muscle relaxation duration of smooth muscle relaxation intramuscular 1 mg 30 minutes 8 to 10 minutes 12 to 27 minutes 2 mg 30 minutes 4 to 7 minutes 21 to 32 minutes in a study in healthy subjects, a subcutaneous dose of 1 mg glucagon for injection resulted on average a peak blood glucose concentration of 79.3 mg/dl with a median time of 50 minutes after injection. 12.3 pharmacokinetics absorption following subcutaneous administration of glucagon for injection, the median time to reach the maximum baseline uncorrected plasma glucagon concentrations of 3533 pg/ml was approximately 10 to 13 minutes after dosing following intramuscular administration of 1 mg dose, the maximum baseline uncorrected plasma glucagon concentrations of 3391 pg/ml were attained approximately 10 minutes after dosing. elimination the mean apparent half-life of glucagon was about 42 minutes after subcutaneous administration. the mean apparent half-life of glucagon was 26 minutes after intramuscular administration. metabolism glucagon is degraded in the liver, kidney, and plasma.

itution. do not freeze. keep in the original package to protect from light. after reconstitution use reconstituted glucagon solution immediately. discard any unused portion [see dosage and administration ( 2.3 )] .

lucagon? before using glucagon, tell your doctor about all of your medical conditions, including if you: have kidney problems. have pancreas problems. have not had food or 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 doctor 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 doctor and pharmacist when you get a new medicine. how should i use glucagon? read the detailed instructions for use that come with glucagon. use glucagon exactly as your doctor tells you to. make sure that you and your family know how to use glucagon the right way before you need it. act quickly. having very low blood sugar for a period of time may be harmful. call for emergency medical help right after you use glucagon. if the person does not respond after 15 minutes, another dose may be given, if available. 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 doctor each time you use glucagon. your doctor may need to change the dose of your diabetes medicines. what are the possible side effects of glucagon? 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. low blood sugar . glucagon can cause low blood sugar in patients with tumors in their pancreas called insulinomas and glucagonomas by making too much insulin in their bodies. serious allergic reactions. call your doctor 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 before your radiology exam it can cause high blood sugar. your doctor will monitor your blood sugar levels during your treatment. heart problems. if you have heart problems and receive glucagon before your radiology exam, you may have an increase in your blood pressure and pulse while using glucagon which could be life threatening.your doctor will monitor your heart during treatment. the most common side effects of glucagon 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 doctor 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. 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? before you mix the glucagon powder and liquid: store glucagon at room temperature between 68°f to 77°f (20°c to 25°c) for up to 24 months (2 years). do not freeze glucagon. keep glucagon in its original package glucagon and out of light. after you mix the glucagon powder and liquid: use glucagon right away. throw away any unused glucagon. glucagon should be clear and colorless. do not use glucagon if it is cloudy or if you see particles in the solution. keep glucagon and all medicines out of the reach of children . general information about the safe and effective use of glucagon: medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. do not use glucagon for a condition for which it was not prescribed. do not give glucagon 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 that is written for health professionals. what are the ingredients in the glucagon? active ingredient: glucagon inactive ingredients: lactose monohydrate and sterile water for reconstitution for more information, go to www.fresenius-kabi.com/us or call 1-800-551-7176.