`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`203441Orig1s000
`
`
`REMS
`
`

`

`
`
`
`
`
`
`Initial REMS Approved: 12/21/2012
`
`
`
`
`
`NDA 203441 GATTEX®
`
`(Teduglutide [rDNA origin]) for Injection
`
`
`
`
`NPS Pharmaceuticals
`550 Hills Drive, 3rd Floor
`
`Bedminster, NJ07921
`
`RISK EVALUATION AND MITIGATION STRATEGY (REMS)
`
`
` 
`
`
`
`  I. GOAL
`
` To inform prescribers and patients about the risks of possible acceleration of
`
`
`neoplastic growth and enhancement of colon polyp growth, gastrointestinal
`
`
`
`
` obstruction, and biliary and pancreatic disorders associated with GATTEX.
`
`
`
` II. REMS ELEMENTS    
`
`
`
`
`
`
`
`
`
`
` 
` 
`
`
`
`
`
`
`
`  Communication Plan
`
`
`A.
` 
`NPS will implement a communication plan to support implementation of the REMS. The
`
`communication plan materials will comprise:
`
`
`
`
` 1. A Dear Healthcare Professional letter to gastroenterologists, colorectal and
` gastrointestinal tract surgeons. In order to facilitate prescriber training and education,
`
` this initial letter will be distributed within 60 days of approval of GATTEX or at the time
`
` of product launch, whichever is sooner. The letter will be sent again at 12 and 24
`
`
` months after product approval. NPS will also identify and send the DHCP letter to all
`
`
`other GATTEX prescribers within 60 days of the date of initial prescription, and again at
`
`12 and 24 months after their initial prescription. This letter will be distributed via direct
`
`
`
`
`
`mail or electronic delivery and will be accessible via the GATTEX REMS website
`(www.GATTEXREMS.com). A copy of the Full Prescribing Information and a
`Medication Guide will be included in the Dear Healthcare Professional letter.
`
`2. A Dear Professional Society letter to the leadership of the professional
`organizations listed below requesting that the letter be provided to the members of these
`professional organizations. The Dear Professional Society letter will be disseminated via
`direct mail or electronic delivery within 60 days of approval of GATTEX or at the time of
`
`
`
`
`
`Reference ID: 3235717
`
`

`

`
`  B. Elements To Assure Safe Use    
`
`
`
`
`
`
`
`
`product launch, whichever is sooner. The letter will be sent again at 12 and 24 months
`after product approval. A copy of the Full Prescribing Information and a Medication
`Guide will be included in the Dear Professional Society letter.
`
`
`
`i. American Society for Parenteral and Enteral Nutrition
`
`ii. American Gastroenterological Association
`
`
`iii. American College of Gastroenterology
`
`
`iv. Society for Surgery of the Alimentary Tract
`
`
`v. American Society of Colon and Rectal Surgery
`
`
`
`vi. American Board of Physician Nutrition Specialists (ABPNS)
`
`The Dear Healthcare Professional letter and the Dear Professional Society letter are part of
`the REMS and are appended.
`
`The Dear Healthcare Professional letter and the Dear Professional Society letter will be
`
`provided to MedWatch at the same time they are provided to the healthcare professionals and
`
`the professional society leadership.
`
`
`
`
`1. Healthcare providers who prescribe GATTEX will receive training.
`
`
`a. NPS Pharmaceuticals will ensure that training is made available to healthcare
`providers who prescribe GATTEX. Training will consist of the Prescriber
`Education Slide Deck.
`
`b. Each prescriber will be provided with the Prescriber Education Slide Deck
`
`which will include the following information:
`
`i. The risks of possible acceleration of neoplastic growth and enhancement of
`colon polyp growth associated with GATTEX.
`
`ii. The serious risk of gastrointestinal obstruction associated with GATTEX.
`
`iii. The serious risk of biliary and pancreatic disorders associated with
`GATTEX.
`
`iv. The recommended screening colonoscopy, follow-up colonoscopy, and
`monitoring laboratory tests
`
`c. NPS will ensure that the Prescriber Education Slide Deck will be available in
`hard copy and on the GATTEX REMS website.
`
`
`
`
`
`
`
`
`
`
`NPS will ensure that prescribers can report that they have completed the Prescriber
`Education Slide Deck.
`
`
`d. NPS will maintain a list of healthcare providers (HCPs) who have completed the
`Prescriber Education Slide Deck.
`
`Reference ID: 3235717
`
`

`

`
`e. In order to facilitate patient and/or caregiver education about GATTEX, NPS
`will ensure that the Patient and Caregiver Counseling Guide will be available
`for prescribers to use to counsel patients considering GATTEX therapy about the
`possible acceleration of neoplastic growth and enhancement of colon polyp
`growth, gastrointestinal obstruction, and biliary and pancreatic disorders
`associated with GATTEX, as well as the recommended screening colonoscopy,
`follow-up colonoscopy and monitoring laboratory tests.
`
`f. NPS will ensure that all educational materials listed in or appended to the
`GATTEX REMS will be available through the GATTEX REMS website,
`www.GATTEXREMS.com.
`
`
`g. The following materials are part of the GATTEX REMS and are appended:
`
` Prescriber Education Slide Deck
`
`
` Patient and Caregiver Counseling Guide
`
`
` GATTEX REMS Website Screenshots
`
`
`
`These materials will also be available by calling NPS Pharmaceuticals at
`1-855-5GATTEX or 1-855-542-8839.
`
`
`
`
`  C. Timetable for Submission of Assessments        
`
`
`
` 
`
`
`
`
`
` 
`
`
`
` NPS will submit REMS assessments to FDA at 12 months from the date of initial approval of
`
`
`the REMS and annually thereafter. To facilitate inclusion of as much information as possible
`while allowing reasonable time to prepare the submission, the reporting interval covered by
`
`
`
`each assessment should conclude no earlier than 60 days before the submission date for that
`
`assessment. NPS will submit each assessment so that it is received by the FDA on or before
`the due date.
`
`Reference ID: 3235717
`
`

`

`
`
`
` [Date]
`
`
`
`Subject:
`
`
`IMPORTANT DRUG WARNING
`
`Risk of possible acceleration of neoplastic growth and enhancement of colon polyp growth,
`
` GI obstruction, and biliary and pancreatic disorders with GATTEX® (teduglutide)
`
`
`
`Dear Healthcare Professional:
`The purpose of this letter is to inform you that GATTEX® (Teduglutide [rDNA origin]) for Injection has
`been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with
`Short Bowel Syndrome (SBS) who are dependent on parenteral support.
`The FDA has determined that a Risk Evaluation and Mitigation Strategy (REMS) is necessary to ensure that
`the benefits of GATTEX outweigh the potential risks.
`
` Serious Risks of GATTEX
` Possible acceleration of neoplastic growth and enhancement of colon polyp growth
` Acceleration of Neoplastic Growth
`
`Based on the pharmacologic activity and findings in animals, GATTEX has the potential to
`cause hyperplastic changes including neoplasia. 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 with active gastrointestinal malignancy (GI tract, hepatobiliary, pancreatic),
`GATTEX therapy should be discontinued. In patients with active non-gastrointestinal
`
`malignancy, the clinical decision to continue GATTEX should be made based on risk-benefit
`considerations.
`
`  Colorectal Polyps
`
`Colorectal polyps were identified during the clinical trials. Colonoscopy of the entire colon
`with removal of polyps must be done within 6 months prior to starting treatment with
`GATTEX. A follow-up colonoscopy (or alternate imaging) is recommended at the end of 1
`year of GATTEX. Subsequent colonoscopies should be done every 5 years or more often as
`needed. If a polyp is found, adherence to current polyp follow-up guidelines is recommended.
`In case of diagnosis of colorectal cancer, GATTEX therapy should be discontinued.
`
` Small Bowel Neoplasia
`Based on benign tumor findings in the rat carcinogenicity study, patients should be monitored
`clinically for small bowel neoplasia. If a benign neoplasm is found, it should be removed. In
`case of small bowel cancer, GATTEX therapy should be discontinued.
`
`Gastrointestinal obstruction
`
`Intestinal obstruction has been reported in clinical trials. In patients who develop intestinal
`
`
`or stomal obstruction, GATTEX should be temporarily discontinued while the patient is
`clinically managed. GATTEX may be restarted when the obstructive presentation resolves, if
`clinically indicated.
`
`
`
`
`
`
`
`
`
` Final V 5 .0
`
`Reference ID: 3235717
`
`
`
` 1
`
`

`

`
`
`
`
` Biliary and pancreatic disorders
`
`
` Gallbladder and Biliary Tract Disease
`Cholecystitis, cholangitis, and cholelithiasis, have been reported in clinical studies. For
`identification of the onset or worsening of gallbladder/biliary disease, patients must undergo
`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 the need for continued GATTEX treatment should be
`reassessed
`
` Pancreatic Disease
`Pancreatitis has been reported in clinical studies. For identification of onset or worsening of
`pancreatic disease, patients must undergo laboratory assessment 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 the need for continued GATTEX treatment
`
`should be reassessed.
`
`
`
`
` Appropriate Patient Selection, Counseling, and Monitoring
`
`Prescribers should select the appropriate patients to receive GATTEX in accordance with the approved
`prescribing information, discuss the benefits and risks of GATTEX with patients, and monitor patients as
`specified in the approved prescribing information. A Patient and Caregiver Counseling Guide is available for
`your use in discussing GATTEX with patients. The guide can be accessed via www.GATTEXREMS.com
`
`or by contacting 1-855-5GATTEX (1-855-542-8839).
`
`
`GATTEX Healthcare Provider Training
`
`It is important that healthcare providers understand the serious risks associated with GATTEX. As part of
`the REMS, healthcare providers should access www.GATTEXREMS.com to review the Prescriber
`Education Slide Deck and complete a Post-training Knowledge Assessment. The Prescriber Education Slide
`Deck and the Post-training Knowledge Assessment can also be obtained in hard copy by contacting 1-855­
`
`5GATTEX (1-855-542-8839).
`
`
` Reporting Adverse Events
`
`To report all suspected adverse events associated with the use of GATTEX, contact
` NPS Pharmaceuticals, toll-free GATTEX Support Line at 1-855-5GATTEX (1-855-542-8839) or
`
`Event/Product Complaint Line at 1-855-215-5550,
` FDA MedWatch program at 1-800-FDA-1088 (1-800-332-1088), or via the FDA website at
`
`
`www.fda.gov/medwatch./report.htm
`
`A copy of the letter is available at www. GATTEXREMS.com and through NPS Medical Information
`(1-855-5GATTEX or 1-855-542-8839). For more information regarding GATTEX, please contact the toll-
`free GATTEX Support Line at 1-855-5GATTEX (1-855-542-8839) or visit the product website at
`www.GATTEX.com.
`This letter is not a complete description of the risks associated with GATTEX. Please see the enclosed full
`Prescribing Information for GATTEX for additional safety information.
`
`
`
` Final V 5 .0
`
`Reference ID: 3235717
`
`
`
` 2
`
`

`

`
`
`
`
`Sincerely,
`
`
`
`Roger Garceau, M.D.
`Chief Medical Officer
`NPS Pharmaceuticals
`
`Enclosures:
`
` GATTEX Full Prescribing Information
`
` Medication Guide
`
`
`
`
`
`
` Final V 5 .0
`
`Reference ID: 3235717
`
`
`
` 3
`
`

`

`
`
`
` [Date]
`
`
`
`Subject:
`
`
`IMPORTANT DRUG WARNING
`
`Risk of possible acceleration of neoplastic growth and enhancement of colon polyp growth,
`
` GI obstruction, and biliary and pancreatic disorders with GATTEX® (teduglutide)
`
`
`
`
`Dear Professional Society Leader:
`The purpose of this letter is to inform you that GATTEX® (Teduglutide [rDNA origin]) for Injection has
`been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with
`Short Bowel Syndrome (SBS) who are dependent on parenteral support.
`The FDA has determined that a Risk Evaluation and Mitigation Strategy (REMS) is necessary to ensure that
`the benefits of GATTEX outweigh the potential risks. The REMS includes a healthcare provider education
`and training.
`We are sending your organization this communication to distribute to members of your organization
`who may be appropriate prescribers of Gattex.
`
` Serious Risks of Gattex
` Possible acceleration of neoplastic growth and enhancement of colon polyp growth
` Acceleration of Neoplastic Growth
`
`Based on the pharmacologic activity and findings in animals, GATTEX has the potential to
`cause hyperplastic changes including neoplasia. 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 with active gastrointestinal malignancy (GI tract, hepatobiliary, pancreatic),
`GATTEX therapy should be discontinued. In patients with active non-gastrointestinal
`
`malignancy, the clinical decision to continue GATTEX should be made based on risk-benefit
`considerations.
`
`  Colorectal Polyps
`
`Colorectal polyps were identified during the clinical trials. Colonoscopy of the entire colon
`with removal of polyps must be done within 6 months prior to starting treatment with
`GATTEX. A follow-up colonoscopy (or alternate imaging) is recommended at the end of 1
`year of GATTEX. Subsequent colonoscopies should be done every 5 years or more often as
`needed. If a polyp is found, adherence to current polyp follow-up guidelines is recommended.
`In case of diagnosis of colorectal cancer, GATTEX therapy should be discontinued.
`
` Small Bowel Neoplasia
`Based on benign tumor findings in the rat carcinogenicity study, patients should be monitored
`clinically for small bowel neoplasia. If a benign neoplasm is found, it should be removed. In
`case of small bowel cancer, GATTEX therapy should be discontinued.
`
`
`
`
`Gastrointestinal obstruction
`
`
` Intestinal obstruction has been reported in clinical trials. In patients who develop intestinal
`or stomal obstruction, GATTEX should be temporarily discontinued while the patient is
`clinically managed. GATTEX may be restarted when the obstructive presentation resolves, if
`clinically indicated.
`
`
`
` Final V3 .0
`
`Reference ID: 3235717
`
`
`
` 1
`
`

`

`
`
`
`
`Biliary and pancreatic disorders
`
` Gallbladder and Biliary Tract Disease
`Cholecystitis, cholangitis, and cholelithiasis, have been reported in clinical studies. For
`identification of the onset or worsening of gallbladder/biliary disease, patients must undergo
`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 the need for continued GATTEX treatment should be
`reassessed
`
` Pancreatic Disease
`Pancreatitis has been reported in clinical studies. For identification of onset or worsening of
`pancreatic disease, patients must undergo laboratory assessment 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 the need for continued GATTEX treatment
`should be reassessed.
`
`
` Appropriate Patient Selection, Counseling, and Monitoring
`
`Prescribers should select the appropriate patients to receive GATTEX in accordance with the approved
`prescribing information, discuss the benefits and risks of GATTEX with patients, monitor patients as
`specified in the approved prescribing information and report adverse events to NPS Pharmaceuticals.
`
` GATTEX Healthcare Provider Training
`
`It is important that healthcare providers understand the serious risks associated with GATTEX. As part of
`the REMS, healthcare providers should access www.GATTEXREMS.com to review the Prescriber
`Education Slide Deck and complete a Post-training Knowledge Assessment. The Prescriber Education Slide
`Deck and the Post-training Knowledge Assessment can also be obtained in hard copy by contacting
`
`1-855-5GATTEX (1-855-542-8839).
`
` Reporting Adverse Events
`
`To report all suspected adverse events associated with the use of GATTEX, contact
` NPS Pharmaceuticals, toll-free GATTEX Support Line at 1-855-5GATTEX (1-855-542-8839) or
`
`Event/Product Complaint Line at 1-855-215-5550,
` FDA MedWatch program at 1-800-FDA-1088 (1-800-332-1088) or via the FDA website at
`
`
`www.fda.gov/medwatch./report.htm
`
`A copy of the letter is available at www. GATTEXREMS.com or via NPS Medical Information
`(1-855-5GATTEX).
`Should your members require additional information about GATTEX, please direct them to contact the toll-
`free GATTEX Support Line at 1-855-5GATTEX (1-855-542-8839) or visit the product website at
`www.GATTEX.com.
`This letter is not a complete description of the risks associated with GATTEX. Please see the enclosed full
`Prescribing Information for GATTEX for additional safety information.
`
`
`
` Final V3 .0
`
`Reference ID: 3235717
`
`
`
` 2
`
`

`

`
`
`
`
`Sincerely,
`
`
`
`Roger Garceau, M.D.
`Chief Medical Officer
`NPS Pharmaceuticals
`
`Enclosures:
`
` GATTEX full Prescribing Information
`
` Medication Guide
`
`
`
`
`
`
` Final V3 .0
`
`Reference ID: 3235717
`
`
`
` 3
`
`

`

`GATTEX® (Teduglutide [rDNA origin]) for Injection
`
`For subcutaneous use only
`
`
`
` NPS Pharmaceuticals, Inc.
`    
`
`
` 550 Hills Drive, Bedminster, NJ 07921
`        
`
`
`
`
`
`
`
`Reference ID: 3235717
`
`

`

`Table of Contents
`
`
`
`Topic
`Indication
` Overview: Important Adverse Reactions of Special Interest          
`
`
`
`
`
`Possible Acceleration of Neoplastic Growth
` 
` 
` 
` 
` 
`Possible Enhanced Growth of Colorectal Polyps
` 
` 
` 
` 
` 
`Gastrointestinal Obstruction
` 
` 
`Gallbladder and Biliary Tract Disease
` 
` 
` 
` 
` 
`Pancreatic Disease
` 
`Fluid Overload
` 
`Increased Absorption of Concomitant Oral Medication
` 
` 
` 
` 
` 
`
`Reference ID: 3235717
`
`Slide
`3
`4
`5
`7
`9
`11
`13
`15
`18
`
`2
`
`

`

`Indication
`
`
`
`  GATTEX® (teduglutide [rDNA origin]) for injection is indicated for              
`
`
`
`
`
`
`
` the treatment of adult patients with Short Bowel Syndrome (SBS)                  
`
`
`
`
`
`
`
`
`
` who are dependent on parenteral support.        
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`    Teduglutide is a recombinant analog of GLP‐2      
`
`
`
` GLP‐2, glucagon‐like peptide‐2  
`
`
`
`Reference ID: 3235717
`
`3
`
`

`

`Overview
`
`Important Adverse Reactions of Special Interest
`
` 
` 
` 
` 
` 
`
` Possible safety risks with GATTEX
` 
` 
` 
` 
`– Possible acceleration of neoplastic growth and
`
` 
` 
` 
` 
` 
` 
`enhanced growth of colorectal polyps
`
` 
` 
` 
` 
` 
`– Gastrointestinal obstruction
` 
` 
`– Gallbladder, biliary tract and pancreatic disease
` 
` 
` 
` 
` 
` 
`– Increased absorption of fluids leading to fluid overload
` 
` 
` 
` 
` 
` 
` 
` 
`in patients with cardiovascular disease
` 
` 
` 
` 
` 
`– Increased absorption of oral medications with narrow
` 
` 
` 
` 
` 
` 
` 
`therapeutic index
` 
`
`Reference ID: 3235717
`
`4
`
`

`

`
`
` Possible Acceleration of Neoplastic Growth
`        
`
`
`
`
`
`
`
`
`
`
`  GLP‐2 receptors are localized mainly in the GI tract1              
`
`
`
`
`
`
`
` GATTEX promotes growth of intestinal epithelial cells in the GI
` 
` 
` 
` 
` 
` 
` 
` 
` 
` 
`tract
` It can not be excluded that GATTEX promotes growth of
` 
` 
` 
` 
` 
` 
` 
` 
` 
` 
`existing neoplasms in the GI tract
` 
` 
` 
` 
` 
` 
` 3 patients on GATTEX were reported with neoplasms*:
` 
` 
` 
` 
` 
` 
` 
`– 2 cases of lung cancer with smoking history
` 
` 
` 
` 
` 
` 
` 
`– 1 case of GI metastatic adenocarcinoma (unknown origin)
` 
` 
` 
` 
` 
` 
` 
` 
`following abdominal radiation for Hodgkin’s disease
` 
` 
` 
` 
` 
` 
`
`
`
`
`
`     1. Munroe DG et al. Proc Natl Acad Sci. 1999; 96:1569‐1573.            
`
`   * As of October 30th, 2011    
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`5
`
`Reference ID: 3235717
`
`

`

`
` Possible Acceleration of Neoplastic Growth      
`
`
`
`
` GATTEX Label – Warnings and Precautions      
`
`
`
`
` Possible Acceleration of Neoplastic Growth      
`
`
`
`
`
`
`  – Based on the pharmacologic activity and findings in animals,              
`
`
`
`
`
`
`
` GATTEX has the potential to cause hyperplastic changes including              
`
`
`
`
`
`
`
`
`neoplasia.
`– Based on benign tumor findings in the rat carcinogenicity study,
` 
` 
` 
` 
` 
` 
` 
` 
` 
`patients should be monitored clinically for small bowel neoplasia. If
` 
` 
` 
` 
` 
` 
` 
` 
` 
` 
`a benign neoplasm is found, it should be removed. In case of small
` 
` 
` 
` 
` 
` 
` 
` 
` 
` 
` 
` 
` 
`bowel cancer, GATTEX therapy should be discontinued.
` 
` 
` 
` 
` 
` 
`In patients with active gastrointestinal malignancy (GI tract,
` 
` 
` 
` 
` 
` 
` 
` 
`hepatobiliary, pancreatic), GATTEX therapy should be discontinued.
` 
` 
` 
` 
` 
` 
`In patients with active non‐gastrointestinal malignancy, the clinical
` 
` 
` 
` 
` 
` 
` 
` 
`decision to continue GATTEX should be made based on risk‐benefit
` 
` 
` 
` 
` 
` 
` 
` 
` 
` 
`considerations.
`In patients at increased risk for malignancy, the clinical decision to
` 
` 
` 
` 
` 
` 
` 
` 
` 
` 
` 
`use GATTEX should be considered only if the benefits outweigh the
` 
` 
` 
` 
` 
` 
` 
` 
` 
` 
` 
`risks.
`
`–
`
`–
`
`–
`
`Reference ID: 3235717
`
`6
`
`

`

`Possible Enhanced Growth of Colorectal Polyps
`
` 
` 
` 
` 
` 
`
`
`
`
`  4/173 (2.3%) GATTEX‐treated patients developed GI polyps in              
`
`
` pooled Phase III SBS studies*        
`
`
`
`
`
` – 2 villous adenomas  
`
`
`
` – 2 hyperplastic
`  GATTEX mechanism of action and nonclinical data are               
`
`
`
`
`
`
`
`
` consistent with a potential to enhance growth of polyps              
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`  * As of October 30th, 2011      
`
`
`
`
`
`Reference ID: 3235717
`
`7
`
`

`

`
` Possible Enhanced Growth of Colorectal Polyps
`        
`
`
`
`
`
` GATTEX Label – Warnings and Precautions
`      
`
`
`
`
`Colorectal Polyps
` 
`– Colonoscopy of the entire colon with removal of polyps
` 
` 
` 
` 
` 
` 
` 
` 
` 
`must be done within 6 months prior to starting treatment
` 
` 
` 
` 
` 
` 
` 
` 
` 
` 
`with GATTEX.
` 
`– A follow‐up colonoscopy (or alternate imaging) is
`
` 
` 
` 
` 
` 
` 
` 
`recommended at the end of 1 year of GATTEX.
`
` 
` 
` 
` 
` 
` 
` 
` 
`– Subsequent colonoscopies should be done every 5 years or
` 
` 
` 
` 
` 
` 
` 
` 
` 
`more often as needed. If a polyp is found, adherence to
` 
` 
` 
` 
` 
` 
` 
` 
` 
` 
` 
`current polyp follow‐up guidelines is recommended.
` 
` 
` 
` 
` 
`In case of diagnosis of colorectal cancer, GATTEX therapy
` 
` 
` 
` 
` 
` 
` 
` 
` 
`should be discontinued.
` 
` 
`
`–
`
`Reference ID: 3235717
`
`8
`
`

`

`
`
` Gastrointestinal Obstruction
`  
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`  12 patients experienced one or more episodes of intestinal                
`
`
`
` obstruction/stenosis*
`  – 6 in SBS placebo‐controlled studies    
`
`
`
`
`
` • 3/77 (3.9%) on GATTEX, 0.05 mg/kg/day        
`
`
`
`
`
` • 3/32 (9.4%) on GATTEX, 0.05 mg/kg/day        
`
`
`
`
`  • None in placebo‐group
`
`
`
`  • Onset 1 day to 6 months      
`
`
`
`
`  – 6 in the extension studies (all on GATTEX, 0.05 mg/kg/day)
`              
`
`
`
`
`  • Onset 6 days to 7 months      
`
`
`
`
`
` – Of all of these patients, 1 patient required endoscopic
`                
`
`
`
`
`
`
`
`
`  dilatation; and none required surgical intervention
`      
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`  * As of October 30th, 2011      
`
`
`
`Reference ID: 3235717
`
`9
`
`

`

`Gastrointestinal Obstruction
` 
` 
`GATTEX Label – Warnings and Precautions
` 
` 
` 
` 
`
`Intestinal Obstruction
` 
` 
`–
`Intestinal obstruction has been reported in clinical trials.
` 
` 
` 
` 
` 
` 
` 
`–
`In patients who develop intestinal or stomal obstruction,
` 
` 
` 
` 
` 
` 
` 
` 
`GATTEX should be temporarily discontinued while the
` 
` 
` 
` 
` 
` 
` 
`patient is clinically managed.
` 
` 
` 
`– GATTEX may be restarted when the obstructive
`
` 
` 
` 
` 
` 
` 
` 
`presentation resolves, if clinically indicated.
`
` 
` 
` 
` 
`
`Reference ID: 3235717
`
`10
`
`

`

`
`
`
`
`
`
`
`
` Gallbladder and Biliary Tract Disease
`        
`
`
`
`
`  11/173 (6.4%) of GATTEX‐treated patients reported biliary events,              
`
`
`
`
`
`
` including cholecystitis and gallstones/sludge in pooled Phase III              
`
`
`
`
`
`
`
`
` SBS studies*  
`
`
` – 5 patients had a history of biliary disease            
`
`
`
`
`
`
`
`  – None of these events resulted in study withdrawal          
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`  * As of October 30th, 2011      
`
`
`
`Reference ID: 3235717
`
`11
`
`

`

`Gallbladder and Biliary Tract Disease
` 
` 
` 
` 
`GATTEX Label – Warnings and Precautions
` 
` 
` 
` 
` 
`
`Gallbladder and Biliary Tract Disease
` 
` 
` 
` 
`– Cholecystitis, cholangitis, and cholelithiasis have been
` 
` 
` 
` 
` 
` 
`reported in clinical studies .
` 
` 
` 
` 
`– Patients must undergo initial (within 6 months prior)
` 
` 
` 
` 
` 
` 
` 
` 
`laboratory assessment of bilirubin and alkaline
` 
` 
` 
` 
` 
` 
`phosphatase.
`  
`– Subsequent laboratory assessments are recommended
` 
` 
` 
` 
` 
`every 6 months; if a clinically meaningful elevation is
` 
` 
` 
`  
` 
` 
` 
` 
` 
`seen imaging of the biliary tract is recommended to
` 
` 
` 
` 
` 
` 
` 
` 
` 
`identify possible obstruction.
` 
` 
`
`Reference ID: 3235717
`
`12
`
`

`

`
`
` Pancreatic Disease
`
`
`  3/173 (1.7%) of GATTEX‐treated patients developed          
`
`
`
`
`
`
`
`  pancreatitis in pooled Phase III SBS studies*          
`
`
`
`
`
`  – All 3 patients had a history of pancreatitis          
`
`
`
`
`
`
`
`  – None of these events resulted in study withdrawal
`          
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`  * As of October 30th, 2011      
`
`
`
`
`
`Reference ID: 3235717
`
`13
`
`

`

`Pancreatic Disease
` 
` 
`GATTEX Label – Warnings and Precautions
` 
` 
` 
` 
`
`Pancreatic Disease
` 
` 
`– Pancreatitis has been reported in clinical studies.
`
` 
` 
` 
` 
` 
` 
`  
`– Patients must undergo initial (within 6 months prior)
` 
` 
` 
` 
` 
` 
` 
` 
`laboratory assessment of lipase and amylase.
` 
` 
`  
` 
`  
` 
`– Subsequent laboratory assessments are recommended
` 
` 
` 
` 
` 
`every 6 months; if a clinically meaningful elevation is
` 
` 
` 
` 
` 
` 
` 
` 
` 
`seen imaging of the pancreas is recommended to
` 
` 
` 
` 
` 
` 
` 
` 
`identify possible obstruction.
` 
` 
`
`Reference ID: 3235717
`
`14
`
`

`

`
`
` Fluid Overload
`
`
`
`
`  23/173 (13.3%) of patients treated with GATTEX reported              
`
`
`
`
`
`
` fluid overload in pooled Phase III SBS studies*              
`
`
`
`
`
`
`
`
`  Fluid overload should be considered when administering            
`
`
`
`
`
`
` GATTEX in patients with underlying heart disease          
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`  * As of October 30th, 2011      
`
`
`
`
`
`Reference ID: 3235717
`
`15
`
`

`

`Fluid Overload
`
` 
`GATTEX Label – Warnings and Precautions
`
` 
` 
` 
` 
`
`Cardiovascular Disease
` 
`– Due to increased intestinal fluid absorption, patients with
` 
` 
` 
` 
` 
` 
` 
` 
`cardiovascular disease, such as cardiac insufficiency and
` 
` 
` 
` 
` 
` 
` 
`hypertension, should be monitored with regard to fluid
` 
` 
` 
` 
` 
` 
` 
` 
`overload, especially during initiation of therapy.
` 
` 
` 
` 
` 
`  
`– Parenteral nutrition/intravenous (PN/IV) fluid volume
` 
` 
` 
` 
` 
`should be reassessed relative to signs of fluid overload.
` 
` 
` 
` 
` 
` 
` 
` 
`  
`In case of a significant deterioration of the cardiovascular
` 
` 
` 
` 
` 
` 
` 
` 
` 
`disease, the need for continued GATTEX treatment should
` 
` 
` 
` 
` 
` 
` 
` 
`be reassessed.
` 
`
`–
`
`Reference ID: 3235717
`
`16
`
`

`

`
`
` PN/IV Volume Adjustment
`    
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`  In order to reduce risk for fluid overload the following PN/IV volume                      
`
`
`
`
`
`
` adjustment algorithm is suggested    
`
`
`
` – Determine pre‐treatment urine output (ideally 1 to 2 L/day)              
`
`
`
`
`
`
`
`
`
` – Determine urine output 2 to 4 weeks after starting treatment                 
`
`
`
`
`
`
`
`
` – Reduce weekly PN/IV volume by 10% to 30% if urine output increased at                        
`
`
`
`
`
`
`
`
`
`
`
` least 10% compared with pre‐treatment volume        
`
`
`
`
`
` – Evaluate if the patient tolerated the PN/IV reduction 1 to 2 weeks later                      
`
`
`
`
`
`
`
`
`
`
`
`
`
` – Continue monitoring urine output on a regular basis and adjust PN/IV                    
`
`
`
`
`
`
`
`
`
`
` volume accordingly with the goal of reducing or achieving complete                  
`
`
`
`
`
`
`
`
`
`
` independence from PN/IV support and maintaining clinical nutrition              
`
`
`
`
`
`
`
`
`status
`
`
`
`
`
`
`
`Reference ID: 3235717
`
`17
`
`

`

`Increased Absorption of Concomitant Oral Medication
`
` 
` 
` 
` 
` 
`
` Based on the pharmacodynamic effect of GATTEX, there is a
` 
` 
` 
` 
` 
` 
` 
` 
` 
` 
`potential for increased absorption of concomitant oral
` 
` 
` 
` 
` 
` 
` 
`medications
` 
`
` Considerations should be given for dosage adjustment of
` 
` 
` 
` 
` 
` 
` 
` 
`concomitant oral medication requiring titration or that have a
` 
` 
` 
` 
` 
` 
` 
` 
` 
`narrow therapeutic index
` 
` 
` 
`
`Reference ID: 3235717
`
`18
`
`

`

`Increased Absorption of Concomitant Oral Medication
` 
` 
` 
` 
` 
` 
`GATTEX Label – Warnings and Precautions
` 
` 
` 
` 
`
`Risks Resulting from Increased Absorption of Concomitant Oral
` 
` 
` 
` 
` 
` 
` 
` 
`Medication
` 
`– Altered mental status in association with GATTEX has been
`
` 
` 
` 
` 
` 
` 
` 
` 
` 
`observed in patients on benzodiazepines in clinical trials.
`
` 
` 
` 
` 
` 
` 
` 
`– Patients on concomitant oral drugs (e.g., benzodiazepines,
` 
` 
` 
` 
` 
` 
` 
`phenothiazines, etc.) requiring titration or with a narrow
` 
` 
` 
` 
` 
` 
` 
` 
`therapeutic index may require dose adjustment while on
` 
` 
` 
` 
` 
` 
` 
` 
`GATTEX.
`
`Reference ID: 3235717
`
`19
`
`

`

`
`
` GATTEX® Patient and Caregiver
`Counseling Guide
`
`GATTEX® (Teduglutide [rDNA origin]) for Injection is indicated for the treatment of adult
`patients with Short Bowel Syndrome (SBS) who are dependent on parenteral support.
`Healthcare providers: Please review this guide with your patient and/or your
`
`patient’s caregiver.
`Patients: Please read the enclosed Medication Guide in full and ask your doctor if you
`have any questions.
`
`Reference ID: 3235717
`
`

`

`Understanding the Risks With GATTEX®
`GATTEX may cause serious side effects, including:
`• Making abnormal cells grow faster. GATTEX can make abnormal cells that are already in your
`body grow faster. There is a higher chance the abnormal cells could become cancer. If you
`get cancer of the bowel (intestines), liver, gallbladder, or pancreas while using GATTEX, your
`healthcare provider should stop GATTEX.
`• If you get other types of cancers, you and your healthcare provider should discuss the risks and
`benefits of using GATTEX.
`
`
`
` Polyps in the colon (large intestine). Polyps are growths on the inside of the colon.
`Before you start using GATTEX, your healthcare provider will:
`• Have your colon checked for polyps within 6 months before starting GATTEX
`• Have any polyps removed
`
`
`
`To keep using GATTEX, your healthcare provider should:
` • Have your colon checked for new polyps at the end of 1 year of using GATTEX. If no polyp
`
` is found, your healthcare provider should check you for polyps as needed and at least every
`5 years.
`• Have any new polyps removed
`
`If cancer is found in a polyp, your healthcare provider should stop GATTEX.
`
`
` Monitor Your Treatment With GATTEX
`
`GATTEX may cause serious side effects, including:
`• Fluid overload. Your healthcare provider will check you for too much fluid in your body. Too
`much fluid in your body may lead to heart failure, especially if you have heart problems. Tell
`your healthcare provider if you get swelling in your feet and ankles, you gain weight very quickly
`(water weight), or you have trouble breathing.
`• See “Understanding the risks with GATTEX” on page 2 of this guide
`
`The most common side effects of GATTEX include:
`• Stomach area (abdomen) pain or swelling
`• Cold or flu-like symptoms
`• Nausea
`• Vomiting
`• Holding too much fluid in the body (swelling of face, ankles, hands or feet)
`
`Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
`
`Blockage of the bowel (intestines). A bowel blockage keeps food, fluids, and gas from
`moving through the bowels in the normal way. Tell your healthcare provider if you have any
`of these symptoms of a bowel blockage:
`
` • trouble having a bowel movement or
`passing gas
`• stomach area (abdomen) pain or swelling
`• nausea
`If blockage is found, your healthcare provider may temporarily stop GATTEX.
`
`• vomiting
` • swelling and blockage of your stoma
`opening, if you have a stoma
`
`
`
`Swelling (inflammation) or blockage of your gallbladder or pancreas.
`Your healthcare provider will do tests to check your gallbladder and pancreas within
`
`
`6 months before starting GATTEX and at least every 6