GLUCAGON

Glucagon is an antihypoglycemic agent and a gastrointestinal motility inhibitor. It is produced by solid phase peptide synthesis. The chemical structure of the glucagon is identical to human glucagon. Glucagon is a single-chain polypeptide containing 29 amino acid residues. The structure of glucagon is: Glucagon for Injection is a sterile, lyophilized white powder in a 3 mL vial for subcutaneous, intramuscular or intravenous use. The reconstituted solution contains glucagon as hydrochloride 1 mg per mL and lactose monohydrate (107 mg). Glucagon for Injection is supplied at pH 2.5 to 3.5 and is soluble in water. DESCRIPTION

INDICATIONS & USAGE 1.1 Severe Hypoglycemia Glucagon for Injection is indicated for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes. 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.

DOSAGE & ADMINISTRATION 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- 12.2)]. The onset of action after an injection will depend on the organ under examination and route of administration [see Clinical Pharmacology ( 12- 12.2)].

Glucagon for Injection is contraindicated in patients with: Pheochromocytoma [see Warnings and Precautions ( 5- 5.1)] Insulinoma [see Warnings and Precautions ( 5- 5.2)] because of the risk of hypoglycemia Known hypersensitivity to glucagon or any of the excipients in Glucagon for Injection. Allergic reactions have been reported with glucagon and include anaphylactic shock with breathing difficulties and hypotension [see Warnings and Precautions ( 5- 5.3)] Glucagonoma [see Warnings and Precautions ( 5- 5.8)] because of risk of hypoglycemia when used as a diagnostic aid

The following important adverse reactions are described below and elsewhere in the labeling: Hypersensitivity and Allergic Reactions [see Warnings and Precautions ( 5- 5.3)] Necrolytic Migratory Erythema [see Warnings and Precautions ( 5- 5.5)] Hyperglycemia in Patients with Diabetes Mellitus when Used as a Diagnostic Aid [see Warnings and Precautions ( 5- 5.6)] Blood Pressure and Heart Rate Increase in Patients with Cardiac Disease when Used as a Diagnostic Aid [see Warnings and Precautions ( 5- 5.7)] 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates 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 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. ADVERSE

7.1 DRUG INTERACTIONS