teduglutide 5 MG Injection [Gattex]

INDICATIONS AND USAGE GATTEX ® is indicated for the treatment of adults and pediatric patients 1 year of age and older with Short Bowel Syndrome (SBS) who are dependent on parenteral support . GATTEX ® is a glucagon-like peptide-2 (GLP-2) analog indicated for the treatment of adults and pediatric patients 1 year of age and older with Short Bowel Syndrome (SBS) who are dependent on parenteral support. ( 1 )

DOSAGE AND ADMINISTRATION Important Administration Information GATTEX is for adult self-administration or caregiver administration. Self-administration in pediatric patients has not been tested. Use of the GATTEX 5 mg kit is not recommended in pediatric patients weighing less than 10 kg. ( 2.1 ) Evaluation Testing within 6 Months Prior to Starting GATTEX Adult Patients : Perform a colonoscopy and upper GI endoscopy with removal of polyps. ( 2.1 , 5.1 ) Pediatric Patients : Perform fecal occult blood testing. If new or unexplained blood in the stool, perform colonoscopy/sigmoidoscopy and upper GI endoscopy. ( 2.1 , 5.1 ) Adult and Pediatric Patients : Obtain baseline laboratory assessments (bilirubin, alkaline phosphatase, lipase and amylase). ( 2.1 , 5.3 ) Dosage and Administration For subcutaneous use only. ( 2.2 ) The recommended dosage of GATTEX for both adults and pediatric patients is 0.05 mg/kg once daily by subcutaneous injection. ( 2.2 ) Alternate sites between 1 of the 4 quadrants of the abdomen, or into alternating thighs or alternating arms. ( 2.2 ) Dosage Adjustment for Renal Impairment For adult and pediatric patients with moderate and severe renal impairment and end-stage renal disease (estimated glomerular filtration rate less than 60 mL/min/1.73 m 2 ) the recommended dosage is 0.025 mg/kg once daily. ( 2.3 ) Discontinuation When treatment is discontinued, monitor for fluid and electrolyte imbalances. ( 2.5 , 5.4 ) Preparation See full prescribing information for instructions on reconstitution. ( 2.6 ) 2.1 Important Administration Information GATTEX is for adult self-administration or caregiver administration. Self-administration in pediatric patients has not been tested. Use of the GATTEX 5 mg kit is not recommended in pediatric patients weighing less than 10 kg. Evaluation and testing prior to starting treatment with GATTEX: Within 6 months prior to treatment: Adult patients Perform a colonoscopy and an upper gastrointestinal (GI) endoscopy with removal of polyps [see Warnings and Precautions ( 5.1 )] . Obtain baseline laboratory assessments (bilirubin, alkaline phosphatase, lipase and amylase) [see Warnings and Precautions ( 5.3 )] . Pediatric patients Perform fecal occult blood testing; if there is new or unexplained blood in the stool, perform colonoscopy/sigmoidoscopy and an upper GI endoscopy [see Warnings and Precautions ( 5.1 )] . Obtain baseline laboratory assessments (bilirubin, alkaline phosphatase, lipase and amylase) [see Warnings and Precautions ( 5.3 )] . 2.2 Recommended Dosage and Administration for Adults and Pediatric Patients 1 Year of Age and Older GATTEX is for subcutaneous injection only. Not for intravenous or intramuscular administration. The recommended dosage of GATTEX is 0.05 mg/kg once daily administered by subcutaneous injection. If a dose is missed, that dose should be taken as soon as possible on that day. Do not take 2 doses on the same day. Alternation of sites for subcutaneous injection is recommended, and can include the thighs, upper arms, and the abdomen. 2.3 Dosage Adjustment for Renal Impairment The recommended dosage in adult and pediatric patients with moderate and severe renal impairment and end-stage renal disease (estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m 2 ) is 0.025 mg/kg once daily [see Use in Specific Populations ( 8.6 )] . 2.4 Monitoring to Assess Safety Colonoscopy and Upper GI Endoscopy in Adults A follow-up colonoscopy and upper GI endoscopy (or alternate imaging) is recommended at the end of 1 year of GATTEX. If no polyp is found, subsequent colonoscopies and upper GI endoscopies (or alternate imaging) should be done no less frequently than every 5 years. If a polyp is found, adherence to current polyp follow-up guidelines is recommended [see Warnings and Precautions ( 5.1 )] . Colonoscopy and Upper GI Endoscopy in Pediatric Patients Perform subsequent fecal occult blood testing annually in pediatric patients while they are receiving GATTEX. If there is new or unexplained blood in the stool, perform colonoscopy/sigmoidoscopy and an upper GI endoscopy [see Warnings and Precautions ( 5.1 )] . Colonoscopy/sigmoidoscopy is recommended for all pediatric patients after 1 year of treatment and every 5 years thereafter while on continuous treatment with GATTEX. Consider upper GI endoscopy (or alternate other imaging) during treatment with GATTEX [see Warnings and Precautions ( 5.1 )] . Laboratory Testing Laboratory assessments are recommended every 6 months. If any clinically meaningful elevation is seen, further diagnostic workup is recommended as clinically indicated (i.e., imaging of the biliary tract, liver, or pancreas) [see Warnings and Precautions ( 5.1 ), ( 5.3 )] . 2.5 Discontinuation of Treatment Discontinuation of treatment with GATTEX may result in fluid and electrolyte imbalance. Monitor fluid and electrolyte status in patients who discontinue GATTEX treatment [see Warnings and Precautions ( 5.4 )] . 2.6 Preparation Instructions Reconstitute each vial of GATTEX by slowly injecting the 0.5 mL of preservative-free Sterile Water for Injection provided in the prefilled syringe. A 10 mg/mL sterile solution is obtained after reconstitution. Allow the vial containing GATTEX and water to stand for approximately 30 seconds and then gently roll the vial between the palms for about 15 seconds. Do not shake the vial. Allow the mixed contents to stand for about 2 minutes. Inspect the vial for any undissolved powder. If undissolved powder is observed, gently roll the vial again until all material is dissolved. Do not shake the vial. Reconstituted GATTEX is a sterile, clear, colorless to light straw-colored solution, which should be free from particulates. If there is any discoloration or particulates, discard the solution. A maximum of 0.38 mL of the reconstituted solution, containing 3.8 mg of teduglutide, can be withdrawn from the vial for dosing. If the product remains undissolved after the second attempt, do not use. Storage of the reconstituted solution Administer within 3 hours after reconstitution. Discard any unused portion. Do not shake or freeze the reconstituted solution. For single use only.

WARNINGS AND PRECAUTIONS Acceleration of Neoplastic Growth : In case of intestinal malignancy, discontinue GATTEX. The decision to continue GATTEX in patients with non-gastrointestinal malignancy should be made based on benefit risk considerations. ( 5.1 ) In adult patients, colonoscopy and upper GI endoscopy (or alternate imaging) is recommended after 1 year of treatment. Perform subsequent colonoscopies and upper GI endoscopes (or alternate imaging) no less frequently than every 5 years. ( 5.1 ) In pediatric patients, perform fecal occult blood testing annually. Colonoscopy/sigmoidoscopy is recommended after 1 year of treatment and every 5 years thereafter on treatment. Consider upper GI endoscopy (or alternate imaging) during treatment with GATTEX. ( 5.1 ) Intestinal Obstruction : In patients who develop intestinal or stomal obstruction, temporarily discontinue GATTEX pending further clinical evaluation and management. ( 5.2 ) Biliary and Pancreatic Disease : Obtain bilirubin, alkaline phosphatase, lipase, amylase every 6 months. If clinically meaningful changes are seen, further evaluation is recommended including imaging, and reassess continued GATTEX treatment. ( 5.3 ) Fluid Overload, Including Congestive Heart Failure : If fluid overload occurs, adjust parenteral support, and reassess continued GATTEX treatment. ( 5.4 ) Potential for Increased Absorption of Oral Medications : Monitor patients on concomitant oral medications (e.g., benzodiazepines) for adverse reactions related to the concomitant drug; dosage reduction of the other drug may be required. ( 5.5 , 7.1 ) 5.1 Acceleration of Neoplastic Growth Based on the pharmacologic activity and tumor findings in the rat and mouse carcinogenicity studies, GATTEX has the potential to cause hyperplastic changes including neoplasia [see Clinical Pharmacology ( 12.1 ), Nonclinical Toxicology ( 13.1 )] . In patients at increased risk for malignancy, the clinical decision to use GATTEX should be considered only if the benefits outweigh the risks. In patients who develop active gastrointestinal malignancy (GI tract, hepatobiliary, pancreatic) while on GATTEX, discontinue GATTEX treatment. In patients who develop active non-gastrointestinal malignancy while on GATTEX, the clinical decision to continue GATTEX should be made based on benefit-risk considerations. Gastrointestinal Polyps Intestinal polyps were identified during the clinical studies. Postmarketing cases of colorectal, gastric, and small intestinal (duodenum, ileum, and jejunum) polyps have been reported postmarketing [see Adverse Reactions ( 6.1 , 6.2 )] . Adult Patients Within 6 months prior to starting treatment with GATTEX, perform colonoscopy and upper GI endoscopy with removal of polyps. A follow-up colonoscopy and upper GI endoscopy (or alternate imaging) is recommended at the end of 1 year of GATTEX. Perform subsequent colonoscopies and upper GI endoscopies (or alternate imaging) every 5 years or more often as needed. If a polyp is found, adherence to current polyp follow-up guidelines is recommended. If gastrointestinal cancer is diagnosed, discontinue GATTEX therapy. Pediatric Patients Within 6 months prior to starting treatment with GATTEX, perform fecal occult blood testing; if there is new or unexplained blood in the stool, perform colonoscopy/sigmoidoscopy and an upper GI endoscopy. Perform subsequent fecal occult blood testing annually in pediatric patients while they are receiving GATTEX. If there is new or unexplained blood in the stool, perform colonoscopy/sigmoidoscopy and an upper GI endoscopy. Colonoscopy/sigmoidoscopy is recommended for all pediatric patients after 1 year of treatment and every 5 years thereafter while on continuous treatment with GATTEX [see Dosage and Administration ( 2.1 )] . Consider upper GI endoscopy (or alternate other imaging) during treatment with GATTEX. If gastrointestinal cancer is diagnosed, discontinue GATTEX therapy. 5.2 Intestinal Obstruction Intestinal obstruction has been reported in clinical studies [see Adverse Reactions ( 6.1 )] and postmarketing. In patients who develop intestinal or stomal obstruction, temporarily discontinue GATTEX while the patient is clinically managed. GATTEX may be restarted when the obstructive presentation resolves, if clinically indicated. 5.3 Biliary and Pancreatic Disease Gallbladder and Biliary Tract Disease Cholecystitis, cholangitis, and cholelithiasis have been reported in clinical studies [see Adverse Reactions ( 6.1 )] and postmarketing. For identification of the onset or worsening of gallbladder/biliary disease, obtain laboratory assessment of bilirubin and alkaline phosphatase within 6 months prior to starting GATTEX, and at least every 6 months while on GATTEX; or more frequently if needed. If clinically meaningful changes are seen, further evaluation including imaging of the gallbladder and/or biliary tract is recommended; and reassess the need for continued GATTEX treatment. Pancreatic Disease Pancreatitis has been reported in clinical studies [see Adverse Reactions ( 6.1 )] . For identification of onset or worsening of pancreatic disease, obtain laboratory assessments of lipase and amylase within 6 months prior to starting GATTEX, and at least every 6 months while on GATTEX; or more frequently if needed. If clinically meaningful changes are seen, further evaluation such as imaging of the pancreas is recommended; and reassess the need for continued GATTEX treatment. 5.4 Fluid Imbalance and Fluid Overload Fluid Overload Fluid overload and congestive heart failure have been observed in clinical studies, which were deemed to be related to enhanced fluid absorption associated with GATTEX [see Adverse Reactions ( 6.1 )] . If fluid overload occurs, adjust parenteral support and reassess GATTEX treatment, especially in patients with underlying cardiovascular disease. If significant cardiac deterioration develops while on GATTEX, reassess the need for continued GATTEX treatment. Fluid and Electrolyte Imbalance Discontinuation of treatment with GATTEX may also result in fluid and electrolyte imbalance. Monitor fluid and electrolyte status in patients who discontinue treatment with GATTEX [see Dosage and Administration ( 2.5 )]. 5.5 Increased Absorption of Concomitant Oral Medication In the adult placebo-controlled studies, an analysis of episodes of cognition and attention disturbances was performed for patients on benzodiazepines. One patient receiving prazepam concomitantly with GATTEX 0.05 mg/kg once daily experienced a dramatic deterioration in mental status progressing to coma during the first week of GATTEX therapy. The patient was admitted to the ICU and the prazepam blood concentration was >300 mcg/L. GATTEX and prazepam were discontinued, and coma resolved 5 days later. Monitor patients receiving concomitant oral drugs requiring titration or with a narrow therapeutic index, for adverse reactions due to potential increased absorption of the concomitant drug. The concomitant drug may require a reduction in dosage [see Drug Interactions ( 7.1 )] .

CONTRAINDICATIONS None. None. ( 4 )

Mechanism of Action Teduglutide is an analog of naturally occurring human glucagon-like peptide-2 (GLP-2), a peptide secreted by L-cells of the distal intestine. GLP-2 is known to increase intestinal and portal blood flow and inhibit gastric acid secretion. Teduglutide binds to the glucagon-like peptide-2 receptors located in intestinal subpopulations of enteroendocrine cells, subepithelial myofibroblasts and enteric neurons of the submucosal and myenteric plexus. Activation of these receptors results in the local release of multiple mediators including insulin-like growth factor (IGF)-1, nitric oxide and keratinocyte growth factor (KGF).