Glucagon 1 mg/ ml

1 INDICATIONS AND USAGE GLUCAGON for Injection is an antihypoglycemic agent and a gastrointestinal motility inhibitor indicated: for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes. ( 1.1 ) as a diagnostic aid for use during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract in adult patients. ( 1.2 ) 1.1 Severe Hypoglycemia Glucagon for Injection is indicated for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes mellitus. 1.2 Diagnostic Aid Glucagon for Injection is indicated as a diagnostic aid for use during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract in adult patients.

2 DOSAGE AND ADMINISTRATION Dosage in adult and pediatric patients to treat severe hypoglycemia ( 2.2 ) 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, or intravenously. ■ If there has been no response after 15 minutes, an additional 1 mg dose (1 mL) 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, or intravenously. ■ If there has been no response after 15 minutes, an additional 0.5 mg dose (0.5 mL) may be administered while waiting for emergency assistance Important Administration Instructions for Using Glucagon for Injection 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 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.

5 WARNINGS AND PRECAUTIONS Substantial Increase in Blood Pressure in Patients with Pheochromocytoma : Contraindicated in patients with pheochromocytoma because Glucagon for Injection may stimulate the release of catecholamines from the tumor. ( 4 , 5.1 ) Hypoglycemia in Patients with Insulinoma : In patients with insulinoma, glucagon administration may produce an initial increase in blood glucose; however, Glucagon for Injection may stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. If a patient develops symptoms of hypoglycemia after a dose of Glucagon for Injection, give glucose orally or intravenously. ( 4 , 5.2 ) Hypersensitivity and Allergic Reactions : Allergic reactions, which have been reported with glucagon, may occur and include generalized rash, and in some cases anaphylactic shock with breathing difficulties, and hypotension. ( 4 , 5.3 ) Lack of Efficacy in Patients with Decreased 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. ( 5.4 ) 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) ] .

6 ADVERSE REACTIONS The following important adverse reactions are described below and elsewhere in the labeling: Hypersensitivity and Allergic Reactions [see Warnings and Precautions (5.3)] Necrolytic Migratory Erythema [ see Warnings and Precautions (5.5) ] Hyperglycemia in Patients with Diabetes Mellitus when Used as a Diagnostic Aid [ see Warnings and Precautions (5.6) ] Blood Pressure and Heart Rate Increase in Patients with Cardiac Disease when used as a Diagnostic Aid [ see Warnings and Precautions (5.7) ] The following 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. Injection site reactions including erythema and swelling Nausea Vomiting Headache Dizziness Asthenia Pallor Diarrhea Somnolence Generalized allergic reactions including anaphylactic shock 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. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Amphastar Pharmaceuticals, Inc. at 1-800-423-4136 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .