İHALE DÜNYASI
İHALE DÜNYASI
Glucagon for Injection, for intravenous or intramuscular use, is a gastrointestinal motility inhibitor that is produced by solid phase peptide synthesis. Glucagon is a single-chain polypeptide containing 29 amino acid residues. The chemical structure of the glucagon polypeptide is identical to human glucagon and to glucagon extracted from beef and pork pancreas. The structure of glucagon is: C 153 H 225 N 43 O 49 S Molecular Weight = 3483 Glucagon for Injection is a sterile, lyophilized white powder in a 3 mL vial. The reconstituted solution contains 1 mg of glucagon as hydrochloride per mL and lactose monohydrate (107 mg). Glucagon for Injection is supplied at pH 2.5 to 3.5 and is soluble in water. structure
Glucagon for Injection is indicated for use as a diagnostic aid during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract. Limitations of Use : Glucagon for Injection is not indicated for the emergency treatment of hypoglycemia because it is not packaged with a syringe and diluent necessary for rapid preparation and administration during an emergency outside of a healthcare facility. Glucagon for Injection is a gastrointestinal motility inhibitor indicated for use as a diagnostic aid during radiologic examinations to temporarily inhibit movement of the gastrointestinal (GI) tract ( 1 ) Limitations of Use: Glucagon for Injection is not indicated for the emergency treatment of hypoglycemia ( 1 )
Reconstitute lyophilized powder with Sterile Water for Injection before use ( 2.2 , 2.3 ) Determine dose based on diagnostic procedure, route of administration and procedure duration ( 2.1 ): To inhibit stomach and small bowel motility the dose is 0.2 mg to 0.5 mg given intravenously or 1 mg given intramuscularly To inhibit colon motility the dose is 0.5 mg to 0.75 mg given intravenously or 1 mg to 2 mg given intramuscularly 2.1 Recommended Dose Determine the dose based on the type of diagnostic procedure, the route of administration and expected procedure duration [see Clinical Pharmacology ( 12.2 )] . The usual dose to inhibit movement of the: Stomach and small bowel is 0.2 mg to 0.5 mg given intravenously or 1 mg given intramuscularly. Colon is 0.5 mg to 0.75 mg given intravenously or 1 mg to 2 mg given intramuscularly. Bolus doses above 1 mg administered intravenously have caused nausea and vomiting and are not recommended [see Adverse Reactions ( 6 )] . 2.2 Reconstitution of the Lyophilized Powder Glucagon for Injection is a lyophilized powder, which requires reconstitution with Sterile Water for Injection prior to intravenous or intramuscular use. Using a syringe, withdraw 1 mL of Sterile Water for Injection and inject into the vial containing Glucagon for Injection lyophilized powder. Shake the vial gently until the powder is completely dissolved and no particles remain in the reconstituted solution. Visually inspect the reconstituted solution for particulate matter and discoloration prior to administration. The reconstituted solution should be clear and of water-like consistency. Discard the reconstituted solution if there are signs of gel formation or particles. The reconstituted solution has a concentration of approximately 1 mg of glucagon per mL. Use the reconstituted glucagon immediately after reconstitution. 2.3 Important Administration Instructions Glucagon for Injection must be administered by medical personnel. The timing of administration of Glucagon for Injection depends upon the organ under examination and route of administration [see Clinical Pharmacology ( 12.2 )] . If given intravenously, administer Glucagon for Injection as a bolus over a time period of 1 minute. 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. | 2.1 Recommended Dose Determine the dose based on the type of diagnostic procedure, the route of administration and expected procedure duration [see Clinical Pharmacology ( 12.2 )] . The usual dose to inhibit movement of the: Stomach and small bowel is 0.2 mg to 0.5 mg given intravenously or 1 mg given intramuscularly. Colon is 0.5 mg to 0.75 mg given intravenously or 1 mg to 2 mg given intramuscularly. Bolus doses above 1 mg administered intravenously have caused nausea and vomiting and are not recommended [see Adverse Reactions ( 6 )] . | 2.2 Reconstitution of the Lyophilized Powder Glucagon for Injection is a lyophilized powder, which requires reconstitution with Sterile Water for Injection prior to intravenous or intramuscular use. Using a syringe, withdraw 1 mL of Sterile Water for Injection and inject into the vial containing Glucagon for Injection lyophilized powder. Shake the vial gently until the powder is completely dissolved and no particles remain in the reconstituted solution. Visually inspect the reconstituted solution for particulate matter and discoloration prior to administration. The reconstituted solution should be clear and of water-like consistency. Discard the reconstituted solution if there are signs of gel formation or particles. The reconstituted solution has a concentration of approximately 1 mg of glucagon per mL. Use the reconstituted glucagon immediately after reconstitution. | 2.3 Important Administration Instructions Glucagon for Injection must be administered by medical personnel. The timing of administration of Glucagon for Injection depends upon the organ under examination and route of administration [see Clinical Pharmacology ( 12.2 )] . If given intravenously, administer Glucagon for Injection as a bolus over a time period of 1 minute. 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.
Glucagon for Injection is contraindicated in patients with: Pheochromocytoma [see Warnings and Precautions ( 5.1 )] because of the risk of increased blood pressure Insulinoma [see Warnings and Precautions ( 5.2 )] because of the risk of hypoglycemia Glucagonoma [see Warnings and Precautions ( 5.2 )] because of the risk of hypoglycemia Pheochromocytoma ( 4 , 5.1 ) Insulinoma ( 4 , 5.2 ) Glucagonoma ( 4 , 5.2 )
The following serious adverse reactions are described below and elsewhere in the labeling: Hypertension in patients with Pheochromocytoma [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )] Hypoglycemia in Patients with Insulinoma and Glucagonoma [see Contraindications ( 4 ) and Warnings and Precautions ( 5.2 )] Hyperglycemia in Patients with Diabetes Mellitus [see Warnings and Precautions ( 5.3 )] Hypersensitivity and Allergic Reactions; generalized allergic reactions including generalized rash, and in some cases anaphylactic shock with breathing difficulties, and hypotension [see Warnings and Precautions ( 5.5 )] Adverse Reactions from Clinical Trials 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 an open-label clinical study of Glucagon for Injection, 29 healthy volunteers 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 in Healthy Volunteers Who Received Glucagon for Injection, 1 mg Administered Intramuscularly (N=29) % of Patients Vomiting 17 Nausea 7 Adverse Reactions from the Literature and Other Clinical Studies The following adverse reactions have been identified from the literature and clinical studies with the use of glucagon. Therefore, it is not possible to reliably estimate their frequency. Nausea and vomiting occurred with doses above 1 mg administered by rapid intravenous injection (within 1 to 2 seconds) . Doses above 1 mg are not recommended for intravenous use [see Dosage and Administration ( 2.1 )]. Hypotension was reported up to 2 hours after administration in patients receiving glucagon as premedication for upper GI endoscopy procedures. A temporary increase in both blood pressure and pulse rate occurred following the administration of glucagon. Patients taking beta-blockers experienced a temporary increase in both pulse and blood pressure that was greater than normal [see Drug Interactions ( 7 )] . Other adverse reactions included hypoglycemia and hypoglycemic coma, as described in postmarketing reports. Patients taking indomethacin may be more likely to experience hypoglycemia following glucagon administration [see Drug Interactions ( 7 )] . Adverse reactions seen with glucagon are transient changes in blood pressure, increase in heart rate, hypersensitivity reactions, nausea and vomiting, and hypoglycemia ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Hyperglycemia in patients with diabetes : Monitor blood glucose and treat with insulin if indicated ( 5.3 ) Increased blood pressure and heart rate in patients with cardiac disease : Monitor patients with known cardiac disease ( 5.4 ) Allergic reactions including anaphylactic shock with breathing difficulties, and hypotension, generalized rash : Discontinue and treat as indicated ( 5.5 ) 5.1 Hypertension in Patients with Pheochromocytoma Glucagon for Injection is contraindicated in patients with pheochromocytoma because glucagon may stimulate the release of catecholamines from the tumor, which may result in a sudden and marked increase in blood pressure. 5.2 Hypoglycemia in Patients with Insulinoma or Glucagonoma Glucagon for Injection is contraindicated in patients with insulinoma or glucagonoma as it may cause secondary hypoglycemia. 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, administer glucose orally or intravenously. 5.3 Hyperglycemia in Patients with Diabetes Mellitus Treatment with Glucagon for Injection in patients with diabetes mellitus may cause hyperglycemia. Monitor diabetic patients for changes in blood glucose levels during treatment. If patients develop symptoms of hyperglycemia after a dose of Glucagon for Injection, administer insulin. 5.4 Blood Pressure and Heart Rate Increase in Patients with Cardiac Disease 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 glucagon treatment, and an increase in blood pressure and pulse rate may require therapy. 5.5 Hypersensitivity and Allergic Reactions Generalized allergic reactions and hypersensitivity, including generalized rash, and anaphylactic shock with breathing difficulties, and hypotension, have been reported with glucagon treatment or lactose. Discontinue Glucagon for Injection and administer standard treatment for anaphylaxis if needed. | 5.1 Hypertension in Patients with Pheochromocytoma Glucagon for Injection is contraindicated in patients with pheochromocytoma because glucagon may stimulate the release of catecholamines from the tumor, which may result in a sudden and marked increase in blood pressure. | 5.2 Hypoglycemia in Patients with Insulinoma or Glucagonoma Glucagon for Injection is contraindicated in patients with insulinoma or glucagonoma as it may cause secondary hypoglycemia. 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, administer glucose orally or intravenously. | 5.3 Hyperglycemia in Patients with Diabetes Mellitus Treatment with Glucagon for Injection in patients with diabetes mellitus may cause hyperglycemia. Monitor diabetic patients for changes in blood glucose levels during treatment. If patients develop symptoms of hyperglycemia after a dose of Glucagon for Injection, administer insulin. | 5.4 Blood Pressure and Heart Rate Increase in Patients with Cardiac Disease 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 glucagon treatment, and an increase in blood pressure and pulse rate may require therapy. | 5.5 Hypersensitivity and Allergic Reactions Generalized allergic reactions and hypersensitivity, including generalized rash, and anaphylactic shock with breathing difficulties, and hypotension, have been reported with glucagon treatment or lactose. Discontinue Glucagon for Injection and administer standard treatment for anaphylaxis if needed.
Table 2 includes clinically significant drug interactions with Glucagon for Injection. Table 2: Clinically Significant Drug Interactions with Glucagon for Injection Beta-Blockers Clinical Impact: The concomitant use of beta-blockers and Glucagon for Injection may increase the risk of a temporary increase in heart rate and blood pressure. Intervention: The increase in blood pressure and heart rate may require therapy in patients with coronary artery disease. Insulin Clinical Impact: Insulin reacts antagonistically towards glucagon. Intervention: Monitor blood glucose when Glucagon for Injection is used as a diagnostic aid in diabetes patients. Indomethacin Clinical Impact: The concomitant use of indomethacin and Glucagon for Injection may lead to 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 increase the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Intervention: Concomitant use is not recommended. Warfarin Clinical Impact: Glucagon may increase the anticoagulant effect of warfarin. Intervention: Monitor patients for unusual bruising or bleeding, as adjustments in warfarin dosage may be required. Beta-blockers : May cause a greater increase in both heart rate and blood pressure ( 7 ) Insulin : Reacts antagonistically towards glucagon; monitor glucose ( 7 ) Indomethacin : May produce hypoglycemia; monitor glucose ( 7 ) Anticholinergic Drugs : Concomitant use not recommended due to increased gastrointestinal adverse reactions ( 7 ) Warfarin : May increase anticoagulant effect of warfarin; may require an adjustment in warfarin dosage ( 7 )
