Glucagon

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 Cipla Ltd. at 1-866-604-3268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.