DailyMed Label: GlucaGen

DailyMed Label: GlucaGen

2021

DailyMed Prescription

GlucaGen

glucagon hydrochloride

Boehringer Ingelheim Pharmaceuticals, Inc.

NDC: 0597-0260

NDC: 0597-0053

NDC: 0597-0053

NDC: 0597-0265

NDC: 0597-0260

NDC: 0597-0053

NDC: 0597-0053

NDC: 0597-0265

NDC: 0597-0260

NDC: 0597-0053

NDC: 0597-0265

NDC: 0597-0053

NDC: 0597-0260

NDC: 0597-0053

NDC: 0597-0265

NDC: 0597-0053

NDC: 0597-0260

NDC: 0597-0053

NDC: 0597-0265

NDC: 0597-0053

NDC: 0597-0260

NDC: 0597-0260

NDC: 0597-0053

NDC: 0597-0053

Glucagon is an antihypoglycemic agent and a gastrointestinal motility inhibitor. It is produced by expression of recombinant DNA in a Saccharomyces cerevisiae vector with subsequent purification. The chemical structure of the glucagon is identical to human glucagon. Glucagon with the empirical formula of C 153 H 225 N 43 O 49 S, and a molecular weight of 3483, is a single-chain polypeptide containing 29 amino acid residues. The structure of glucagon is: GlucaGen is a sterile, lyophilized white powder for reconstitution for subcutaneous, intramuscular or intravenous use, supplied in a 2 mL vial (appearance of the powder may vary, and occasionally the powder may appear compacted). Each vial for reconstitution contains 1 mg of glucagon, 107 mg of lactose monohydrate, hydrochloric acid and sodium hydroxide. Hydrochloric acid and/or sodium hydroxide may be used to adjust the pH before lyophilization. The reconstituted solution of GlucaGen contains glucagon 1 mg/mL at pH 2.5-3.5, and is soluble in water.

GlucaGen 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 )

Dosage in adults and pediatric patients using the GlucaGen HypoKit to treat severe hypoglycemia ( 2.2 ) • Adults and Pediatric Patients Weighing 25 kg or More 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 GlucaGen 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 GlucaGen may be administered using a new kit while waiting for emergency assistance. Important Administration Instructions for Using the GlucaGen HypoKit to Treat Severe Hypoglycemia ( 2.1 ) • GlucaGen 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 GlucaGen Diagnostic Kit and GlucaGen 10-pack 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 )

GlucaGen for injection is a white lyophilized powder supplied as follows: Treatment of Severe Hypoglycemia • 1 mg single-dose vial of GlucaGen with a 1 mL single-dose syringe of Sterile Water for Injection, USP (GlucaGen HypoKit ® ) Use as a Diagnostic Aid • 1 mg single-dose vial of GlucaGen • 1 mg single-dose vial of GlucaGen with a 1 mL single-dose vial of Sterile Water for Injection, USP (Diagnostic Kit)

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

Substantial Increase in Blood Pressure in Patients with Pheochromocytoma : Contraindicated in patients with pheochromocytoma because GlucaGen may stimulate the release of catecholamines from the tumor. ( 4 , 5.1 )   Hypoglycemia in Patients with Insulinoma: In patients with insulinoma, administration may produce an initial increase in blood glucose; however, GlucaGen may stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. If a patient develops symptoms of hypoglycemia after a dose of GlucaGen, give glucose orally or intravenously. ( 4 , 5.2 )   Hypersensitivity and Allergic Reactions: Allergic reactions have been reported 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 Hepatic Glycogen: GlucaGen 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 GlucaGen 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 GlucaGen 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: GlucaGen may increase myocardial oxygen demand, blood pressure, and pulse rate. Cardiac monitoring is recommended in patients with cardiac disease during use of GlucaGen 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. ( 5.8 )

The following important adverse reactions are described below and elsewhere in the labeling:

Table 1: Clinically Significant Drug Interactions with GlucaGen Beta-Blockers Clinical Impact: Patients taking beta-blockers may have a transient increase in pulse and blood pressure when given GlucaGen. Intervention: The increase in blood pressure and heart rate may require therapy in patients with coronary artery disease. Indomethacin Clinical Impact: In patients taking indomethacin, GlucaGen may lose its ability to raise blood glucose or may even produce hypoglycemia. Intervention: Monitor blood glucose levels during GlucaGen treatment of patients taking indomethacin. Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs and GlucaGen increase the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Intervention: Concomitant use of anticholinergic drugs with GlucaGen for use as a diagnostic aid is not recommended. Warfarin Clinical Impact: GlucaGen 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 GlucaGen is used as a diagnostic aid in patients receiving insulin.

Risk Summary Available data from case reports and a small number of observational studies with glucagon use in pregnant women over decades of use have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Multiple small studies have demonstrated a lack of transfer of pancreatic glucagon across the human placental barrier during early gestation. In rat and rabbit reproduction studies, no embryofetal toxicity was observed with glucagon administered by injection during the period of organogenesis at doses representing up to 100 and 200 times the human dose, respectively, based on body surface area (mg/m 2 ) (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Data Animal Data In rats and rabbits given glucagon by injection at doses of 0.4, 2, 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.

GlucaGen for injection is supplied as a lyophilized white powder available as follows: Presentation NDC Strength Description Treatment of Severe Hypoglycemia GlucaGen HypoKit 0169-7065-15 1 mg per vial 1 mL single-dose vial of GlucaGen with 1 mL single-dose syringe of Sterile Water for Injection, USP for reconstitution Use as a Diagnostic Aid GlucaGen 10-pack: 10 Single-dose vials 0597-0053-45 1 mg per vial 1 mL single-dose vial of GlucaGen GlucaGen Diagnostic Kit 0597-0260-10 1 mg per vial 1 mL single-dose vial of GlucaGen with 1 mL single-dose vial of Sterile Water for Injection, USP for reconstitution

Glucagon increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver. Hepatic stores of glycogen are necessary for glucagon to produce an antihypoglycemic effect. Extrahepatic effects of glucagon include relaxation of the smooth muscle of the stomach, duodenum, small bowel, and colon.

Carcinogenesis Long term studies in animals to evaluate carcinogenic potential have not been performed. Mutagenesis The mutagenic potential tested in the Ames and human lymphocyte assays, was borderline positive under certain conditions for both glucagon (pancreatic) and glucagon (rDNA) origin. Doses of 100 and 200 mg/kg of glucagon of both pancreatic and recombinant origins gave slightly higher incidences of micronucleus formation in male mice but there was no effect in females. The weight of evidence indicates that synthetic and recombinant glucagon are not different and do not pose a genotoxic risk to humans. Impairment of Fertility Glucagon was not tested in animal fertility studies. Studies in rats have shown that pancreatic glucagon does not cause impaired fertility.

NDC 0597-0260-10 GlucaGen ® (glucagon) for injection 1 mg per vial For intramuscular or intravenous injection GlucaGen ® should be reconstituted with Sterile Water for Reconstitution immediately before use Single dose. Discard unused portion. Protect from Light. See package insert for complete product information. FOR DIAGNOSTIC USE ONLY - NOT INTENDED FOR USE BY PATIENTS TO TREAT SEVERE HYPOGLYCEMIA Rx ONLY Boehringer Ingelheim