Half-life of GATTEX in patients with SBS1,2
~42 Minutes
(AGE: 1-11 YEARS)
~60 MInutes
(AGE: 12-17 YEARS)
GATTEX Mechanism of Action
How GATTEX works
Half-life of naturally occurring GLP-2 is ~7 minutes1,2
The amino acid sequence of naturally occurring GLP-2 and GATTEX are nearly identical, except for a single amino acid substitution—alanine replaced with glycine.1-4
GLP-2=glucagon-like peptide-2
GATTEX (teduglutide) enhanced intestinal absorption in adult patients with short bowel syndrome (SBS)1,3
Increased
Villus Height
Increased
Crypt Depth
Not an actual biopsy. Image is for illustrative purposes only and does not represent results from the study.
GATTEX enhanced gastrointestinal fluid (wet weight) absorption in adults by approximately 750–1000 mL/day1
The ability of GATTEX to improve intestinal absorption in children has not been investigated.
The ability of GATTEX (teduglutide) to improve intestinal absorption was studied in 17 adult subjects with SBS (n=2-3 per dose group) using daily doses of 0.03, 0.1, or 0.15 mg/kg (doses ranging from 0.6 to 3 times the recommended dose) in a 21-day, open-label, multicenter, dose-ranging study. Fourteen of 17 patients were dependent on PS. All subcutaneous (abdomen) doses studied, except 0.03 mg/kg once daily, resulted in enhanced gastrointestinal fluid (wet weight) absorption of approximately 750 to 1000 mL/day, and increased villus height and crypt depth of the intestinal mucosa.1
The recommended dosage of GATTEX for both adult and pediatric patients is 0.05 mg/kg once daily by subcutaneous injection. The recommended dosage in adult and pediatric patients with moderate and severe renal impairment and end-stage renal disease (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2) is 0.025 mg/kg once daily.1
Understanding the GATTEX
Mechanism of Action
Share the video below with your patients to see how GATTEX works.
Pivotal study of GATTEX (teduglutide) in pediatric patients
In the pivotal Phase 3, 6-month, multicenter, clinical study of GATTEX in pediatric patients aged 1 through 17 years with short bowel syndrome (SBS) who were dependent on parenteral support (PS) (N=59)1,5,6:
-
Caregivers chose for patients to receive either GATTEX (n=50) or standard of care (SOC) (n=9)
- — Patients in the GATTEX arm were randomized to 0.025 mg/kg/day (n=24) or 0.05 mg/kg/day (n=26)
- Patients had SBS resulting from major intestinal resection and were dependent on PS that provided ≥30% of caloric and/or fluid/electrolyte needs for ≥3 months prior to screening
-
PS requirements at baseline in the 6-month study:
- — Stable PS support (defined as the inability to significantly reduce PS support [ie, 10% or less change in PS or advance in feeds]) for ≥3 months prior to and during screening as assessed by the investigator
- — PS and specialized enteral nutrition were recorded in intake diaries by the child’s parent or guardian
- The primary endpoint was a reduction in PS volume of ≥20% from baseline to the end of treatment. Additional endpoints included reduction in PS volume from baseline and infusion hours/day, mean change in baseline PS infusion days/week at Week 24, and enteral autonomy
6-month study1,5,6
Study design
Screening period
Caregivers chose for patients to receive either GATTEX (n=50) or SOC (n=9)
- Patients in the GATTEX arm were randomized to 0.025 mg/kg/day (n=24) or 0.05 mg/kg/day (n=26)
Enrolled and completed
study: 6 months
GATTEX + SOC
n=240.025 mg/kg/day
GATTEX + SOC
n=260.05 mg/kg/day
SOC only
n=9Follow-up period:
4 weeks
SOC only
Patient Baseline Characteristics
| INTENT-TO-TREAT POPULATION1,5 | GATTEX 0.05 mg/kg/day (n=26) |
|---|---|
| DEMOGRAPHICS | |
| Mean age, years (standard deviation [SD]) | 6 (4) |
| 1-11 years (%) | 24 (92) |
| 12-16 years (%) | 2 (8) |
| 17-<18 years (%) | 0 |
| Male, n (%) | 19 (73) |
| PRIMARY CAUSES OF SBS, n (%) | |
| Gastroschisis | 14 (84) |
| Midgut volvulus | 6 (23) |
| Necrotizing enterocolitis | 3 (12) |
| Intestinal atresia | 1 (4) |
| Hirschsprung’s disease | 1 (4) |
| Other | 1 (4) |
| BASELINE CHARACTERISTICS | |
| Mean remaining small intestine length, cm (SD) | 47 (28) |
| Stoma, n (%) Jejunostomy | 5 (18) 4 (80) |
| Patients with remaining colon, n (%) Colon-In-continuity | 25 (96) 22 (88) |
| Mean actual PS volume, mL/kg/day (SD) | 60 (29) |
| Mean PS infusion time, days/week (SD) | 7 (1) |
| Mean PS infusion time, hours/day (SD) | 11 (3) |
See how to get your appropriate patients started, or keep reading to explore results with GATTEX, safety profile, and dosing.
“As Penelope's mother, watching us reduce days of PS to get us where we are now has been the most rewarding experience in our SBS journey to date. She now sleeps line-free, and we have a lot more time together as a family.”
GATTEX reduced weekly parenteral support (PS) volume for the majority of pediatric patients1,5†
Reduction in PS volume requirements1,5
Percentage of patients who achieved ≥20% reduction in weekly parenteral support (PS) volume from baseline
At 6 months:
69%
(18/26)
of patients treated with GATTEX achieved ≥20% reduction in weekly PS volume1,5‡§¶
GATTEX reduced mean weekly parenteral support (PS) volume over time1,5‖
PS volume requirements were reduced by 23 mL/kg/day (±18), which was a 42% (±29) reduction from baseline§
GATTEX reduced the amount of time pediatric patients spent on parenteral support (PS)1,5
Time off of PS1,5
Patients who achieved time off of PS
At 6 months¶‖:
Patients treated with GATTEX achieved a mean reduction in time of
3
HOURS/DAY off of PS5#
(±3.8 Hours/Day)
38%
(10/26)
patients treated with GATTEX spent
≥1 fewer days per week on PS1,5**
≥1 fewer days per week on PS1,5**
†Primary efficacy endpoint.
†Results based on patient diary data from the intent-to-treat population.
§Weight-normalized reduction.
¶GATTEX 0.05 mg/kg/day dosage group.
‖Key secondary efficacy endpoint.
#11 hours/day mean baseline PS infusion time.
**7 days/week mean PS infusion time.
GATTEX helped some pediatric patients achieve complete freedom from parenteral support (PS)1,5
Complete freedom from PS
Number of patients who achieved complete freedom from PS††‡‡
At 6 months:
3
Patients
(3/26, 12%)
patients treated with GATTEX were able to wean off PS completely1,5
††GATTEX 0.05 mg/kg/day dosage group.
‡‡Key secondary efficacy endpoint.
GATTEX has a demonstrated safety profile1
In 2 clinical studies, 41 pediatric patients were treated with GATTEX 0.05 mg/kg/day1
- Overall, the safety profile of GATTEX for pediatric patients aged 1 to <17 years was similar to that for adults1
- The 41 patients included 1 infant (1 to <2 years), 37 children (2 to <12 years), and 3 adolescents (12 to <17 years)1
- In the long-term extension studies with a mean exposure of 41 weeks, no new safety signals were identified1
|
MOST COMMON ADVERSE REACTIONS IN ADULTS1 (≥5% in the GATTEX group and greater than in the placebo group) |
Placebo (n=59) (%) |
GATTEX 0.05 mg/kg/day (n=77) (%) |
|---|---|---|
| Abdominal pain§§ | 22 | 30 |
| Nausea | 20 | 23 |
| Upper respiratory tract infection¶¶ | 12 | 21 |
| Abdominal distension | 2 | 20 |
| Injection site reaction|| || | 12 | 13 |
| Vomiting | 10 | 12 |
| Fluid overload## | 7 | 12 |
| Hypersensitivity*** | 7 | 10 |
| Flatulence | 7 | 9 |
| Decreased appetite | 3 | 7 |
| Influenza†† | 2 | 7 |
| Skin hemorrhage‡‡‡ | 2 | 5 |
| Cough | 0 | 5 |
| Sleep disturbances§§§ | 0 | 5 |
- If pediatric patients have a stoma, advise patients and caregivers that, while they may experience abdominal pain and swelling of their stoma, especially when starting treatment with GATTEX, if they experience symptoms of intestinal obstruction, they should contact their physician1
Among the 53 patients with a stoma in the placebo-controlled studies, the percentage of patients with gastrointestinal stoma complication was 42% (13/31) for patients who were treated with GATTEX 0.05 mg/kg/day and 14% (3/22) for patients who received placebo.1
§§ Includes: Abdominal pain, upper abdominal pain, lower abdominal pain.
¶¶ Includes: Upper respiratory tract infection, nasopharyngitis, pharyngitis, sinusitis, laryngitis, rhinitis, viral upper respiratory tract infection.
|| || Includes: Injection site hematoma, injection site erythema, injection site pain, injection site swelling, injection site hemorrhage, injection site discoloration, injection site reaction, injection site rash.
## Includes: Fluid overload, peripheral edema, edema, generalized edema, fluid retention, and jugular vein distension.
*** Includes: Erythema, rash, dermatitis allergic, pruritus, rash macular, drug eruption, eyelid edema, flushing.
†† Includes: Influenza, influenza-like illness.
‡‡‡ Includes: Hematoma, abdominal wall hematoma, post-procedural hematoma, umbilical hematoma, blood blister.
§§§ Includes: Insomnia (3 patients) and hypersomnia (1 patient).
Monitoring timeline for pediatric patients receiving GATTEX
Within 6 months prior to starting GATTEX treatment1:
- Perform fecal occult blood testing; if there is unexplained blood in the stool, perform colonoscopy/sigmoidoscopy1
- Obtain baseline laboratory assessments (bilirubin, alkaline phosphatase, lipase, and amylase)1
| Ongoing | Every 6 months |
After 1 year of GATTEX¶¶¶ |
Every year |
At least every 5 years |
||
|---|---|---|---|---|---|---|
| Fecal occult blood test1 |
Examine for unexplained blood in stool |
|
||||
|
Colonoscopy/ Sigmoidoscopy1¶¶¶ |
Assess for colorectal polyps |
|
|
|||
| Laboratory assessments1 | Bilirubin |
|
||||
| Alkaline phosphatase |
|
|||||
| Lipase |
|
|||||
| Amylase |
|
|||||
|
Clinical evaluations1 |
Signs and symptoms of intestinal obstruction |
|
||||
| Signs and symptoms of fluid imbalance and fluid overload |
|
|||||
| Increased absorption of concomitant oral medication(s) |
|
|||||
| Observation of other adverse events |
|
| Fecal occult blood test every year1 |
|---|
| Examine for unexplained blood in stool |
| Colonoscopy/Sigmoidoscopy after 1 year of GATTEX and every 5 years thereafter 1¶¶¶ |
| Assess for colorectal polyps |
| Laboratory assessments every 6 months1 |
| Bilirubin |
| Alkaline phosphatase |
| Lipase |
| Amylase |
| Ongoing Clinical Evaluations1 |
| Signs and symptoms of intestinal obstruction |
| Signs and symptoms of fluid imbalance and fluid overload |
| Increased absorption of concomitant oral medication(s) |
| Observation of other adverse events |
Discontinuation of treatment with GATTEX may result in fluid and electrolyte imbalance. Fluid and electrolyte status should be monitored in patients who discontinue treatment with GATTEX.1
¶¶¶Colonoscopy/sigmoidoscopy is recommended for all children and adolescents after 1 year of treatment, every 5 years thereafter while on continuous treatment with GATTEX, and if they have new or unexplained gastrointestinal bleeding.1
See how to get your appropriate patients started, or keep reading for information on dosing.
GATTEX Pediatric
Dosing & Administration1
The recommended dosage in pediatric patients 1 year of age and older is 0.05 mg/kg once daily by subcutaneous injection
- The recommended dosage in pediatric patients with moderate and severe renal impairment and end-stage renal disease (estimated glomerular filtration rate less than 60 mL/min/1.73 m2) is 0.025 mg/kg once daily
- GATTEX is available in a 5 mg vial
- Use of the GATTEX 5 mg kit is not recommended in pediatric patients weighing less than 10 kg
Calculation of weight-based dosing
patient weight (kg)
patient weight (kg)
Multiply by 0.05 OR
0.025 per above
Divide by 200 (0.05 dose)
OR 400 (0.025 dose)
patient dose (mg/day)
volume (mL/day)
GATTEX should always be administered by a caregiver
- Full preparation and injection instructions can be found in the GATTEX Instructions for Use
- Self-administration in pediatric patients has not been tested
- Caregivers should inject GATTEX into 1 of the 4 quadrants of the abdomen, either thigh, or either arm. They should use a different injection site each time
-
GATTEX should be administered by subcutaneous injection once daily
— Not for intravenous (IV) or intramuscular (IM) injection - GATTEX should be administered within 3 hours after reconstitution
Hypothetical Patient Profile
Meet Kevin, a hypothetical SBS patient. His symptoms, history, and exam demonstrate how SBS may present in children.
Kevin | 7 years
- Diagnosed with SBS in infancy
- Started GATTEX at 5
- Underlying cause of SBS: surgical resection due to Hirschsprung's disease (diagnosed shortly after birth)
History of illness
- Pediatric gastroenterologist diagnosed Hirschsprung’s disease in 2015, shortly after birth
- Surgery as a newborn resected entire colon and majority of small intestine (30 cm remaining)
- Permanent stoma
- G-tube to enhance nutrition and growth
- Parenteral support (PS) since infancy (age 1 mo.)
Kevin’s experience starting GATTEX
- At 1-month visit, patient experienced injection site bruising; persistent abdominal distension and flatulence
- At 2-month visit, increased weight (7 kg) largely from oral nutrition
Kevin’s experience weaning with GATTEX
- At 1-month visit, PS was reduced by 10% based on 48-hour urine output*
- At 2-month visit, decision was made to maintain current PS and re-evaluate weaning at next visit
- At 4-month visit, PS was reduced by 15% as 48-hour urine output had improved*
- At the 6-month mark, patient was able to reduce PS by another 20%*
*Reductions followed by safety evaluation after 1 week, including 48-hour urine collection and clinical evaluation: signs and symptoms of dehydration, weight changes, review of recorded oral fluid intake, blood samples (hematocrit, creatinine, blood urea nitrogen), and urine sodium.
Want to learn more about Kevin and other hypothetical patient profiles, or how GATTEX may help your patients?
- GATTEX (teduglutide) for injection [package insert]. Cambridge, MA: Takeda Pharmaceuticals U.S.A., Inc.
- Tappenden KA et al. J Clin Gastroenterol. 2013;47(7):602-607.
- Jeppesen PB et al. Gut. 2005;54(9):1224-1231 .
- Tavares W et al. Am J Physiol Endocrinol Metab. 2000;278(1):E134-E139.
- Kocoshis SA et al. JPEN J Parenter Enteral Nutr. 2019. doi:10.1002/jpen.1690.
- A 24-week, double-blind, safety, efficacy, and pharmacodynamic study investigating two doses of teduglutide in pediatric subjects through 17 years of age with short bowel syndrome who are dependent on parenteral support. ClinicalTrials.gov identifier: NCT02682381. Accessed May 8, 2020. https://clinicaltrials.gov/ct2/show/study/NCT02682381.
INDICATION
GATTEX® (teduglutide) for injection 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.
IMPORTANT SAFETY INFORMATION
Warnings and Precautions
GATTEX has been associated with acceleration of neoplastic growth, intestinal obstruction, biliary and pancreatic disease, fluid imbalance and fluid overload, and increased absorption of concomitant oral medication. Click here for additional Safety Information.
INDICATION
GATTEX® (teduglutide) for injection 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.
IMPORTANT SAFETY INFORMATION
Warnings and Precautions
Acceleration of Neoplastic growth
Intestinal polyps were identified during clinical trials. Postmarketing cases of colorectal, gastric, and small intestinal (duodenum, ileum, and jejunum) polyps have been reported. There is a risk for acceleration of neoplastic growth. In adults, within 6 months prior to starting treatment with GATTEX, perform colonoscopy and an upper gastrointestinal (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. Subsequent colonoscopies and upper GI endoscopies (or alternate imaging) should be performed every 5 years or more often as needed. If a polyp is found, adherence to current polyp follow-up guidelines is recommended.
In pediatric patients, perform fecal occult blood testing within 6 months prior to initiating treatment with GATTEX. 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, followed by colonoscopy/sigmoidoscopy and an upper GI endoscopy if there is new or unexplained blood in the stool. Colonoscopy/sigmoidoscopy is recommended for all pediatric patients after 1 year of treatment and at least every 5 years thereafter while on continuous treatment with GATTEX. Consider upper GI endoscopy (or alternate imaging) during treatment with GATTEX.
In adult and pediatric patients who develop active gastrointestinal malignancy (GI tract, hepatobiliary, pancreatic), discontinue GATTEX. The clinical decision to continue GATTEX in patients with non-gastrointestinal malignancy should be made based on benefit-risk considerations.
Intestinal obstruction
Intestinal obstruction has been reported in clinical trials
and postmarketing. In patients who develop intestinal or stomal obstruction, GATTEX should be temporarily
discontinued pending further clinical evaluation and management.
Biliary and pancreatic disease
Cholecystitis, cholangitis, cholelithiasis, and
pancreatitis have been reported in clinical trials and postmarketing. Laboratory assessment (bilirubin,
alkaline phosphatase, lipase, amylase) should be obtained within 6 months prior to starting GATTEX. Subsequent
laboratory tests should be done every 6 months or more often as needed. If clinically meaningful changes are
seen, further evaluation is recommended including imaging, and continued treatment with GATTEX should be
reassessed.
Fluid imbalance and fluid overload
Fluid overload and congestive heart failure
have been observed in clinical trials. If fluid overload occurs, especially in patients with underlying
cardiovascular disease, parenteral support should be adjusted and GATTEX treatment reassessed. If significant
cardiac deterioration develops while on GATTEX, continued GATTEX treatment should be reassessed.
Discontinuation of treatment with GATTEX may also result in fluid and electrolyte imbalance. Fluid and electrolyte status should be monitored in patients who discontinue treatment with GATTEX.
Increased absorption of concomitant oral medication
In clinical trials, one
patient receiving prazepam concomitantly with GATTEX experienced dramatic deterioration in mental status
progressing to coma during first week of GATTEX therapy. Patients receiving concomitant oral drugs requiring
titration or with a narrow therapeutic index should be monitored for adverse reactions due to potential
increased absorption of the concomitant drug. The concomitant drug may require a reduction in dosage.
Adverse Reactions
The most common adverse reactions (≥ 10%) with GATTEX are
abdominal pain, nausea, upper respiratory tract infection, abdominal distension, injection site reaction,
vomiting, fluid overload, and hypersensitivity.
Use in Specific Populations
Breastfeeding is not recommended during
treatment with GATTEX.
Please click here for full Prescribing Information or Información de prescripción en español.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use GATTEX safely and effectively. See full prescribing information for GATTEX.
GATTEX® (teduglutide) for injection, for subcutaneous use
Initial U.S. Approval: 2012
RECENT MAJOR CHANGES
Dosage and Administration
Important Administration Information (2.1) 09/2024 Monitoring to Assess Safety (2.4) 09/2024
Acceleration of Neoplastic Growth (5.1) 09/2024
INDICATIONS AND USAGE
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 m2) 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)
DOSAGE FORMS AND STRENGTHS
For injection: 5 mg teduglutide in a single-dose vial supplied with 0.5 mL Sterile Water for Injection in a single-dose prefilled syringe. (3)
CONTRAINDICATIONS
None. (4)
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)
ADVERSE REACTIONS
Most common adverse reactions (≥10%) are: abdominal pain, nausea, upper respiratory tract infection, abdominal distension, injection site reaction, vomiting, fluid overload, and hypersensitivity. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals U.S.A., Inc. at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
Lactation: Breastfeeding not recommended. (8.2)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 9/2024
FULL PRESCRIBING INFORMATION: CONTENTS*
- INDICATIONS AND USAGE
-
DOSAGE AND ADMINISTRATION
- Important Administration Information
- Recommended Dosage and Administration for Adults and
Pediatric Patients 1 Year of Age and Older - Dosage Adjustment for Renal Impairment
- Monitoring to Assess Safety
- Discontinuation of Treatment
- Preparation Instructions
- DOSAGE FORMS AND STRENGTHS
- CONTRAINDICATIONS
-
WARNINGS AND PRECAUTIONS
- Acceleration of Neoplastic Growth
- Intestinal Obstruction
- Biliary and Pancreatic Disease
- Fluid Imbalance and Fluid Overload
- Increased Absorption of Concomitant Oral Medication
-
ADVERSE REACTIONS
- Clinical Trials Experience
- Postmarketing Experience
-
DRUG INTERACTIONS
- Potential for Increased Absorption of Oral Medications
-
USE IN SPECIFIC POPULATIONS
- Pregnancy
- Lactation
- Pediatric Use
- Geriatric Use
- Renal Impairment
- Hepatic Impairment
- OVERDOSAGE
- DESCRIPTION
-
CLINICAL PHARMACOLOGY
- Mechanism of Action
- Pharmacodynamics
- Pharmacokinetics
- Immunogenicity
-
NONCLINICAL TOXICOLOGY
- Carcinogenesis, Mutagenesis, Impairment of Fertility
-
CLINICAL STUDIES
- Treatment of SBS in Adults
- Treatment of SBS in Pediatric Patients
- HOW SUPPLIED/STORAGE AND HANDLING
- PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information are not listed.
FULL PRESCRIBING INFORMATION
1 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.
2 DOSAGE AND ADMINISTRATION
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 m2) 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.
3 DOSAGE FORMS AND STRENGTHS
For Injection: 5 mg teduglutide as a white lyophilized powder for reconstitution in a single-dose vial supplied with 0.5 mL Sterile Water for Injection in a single-dose prefilled syringe.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
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)].
6 ADVERSE REACTIONS
The following serious adverse reactions are described elsewhere in the labeling:
- Acceleration of Neoplastic Growth [see Warnings and Precautions (5.1)]
- Intestinal Obstruction [see Warnings and Precautions (5.2)]
- Biliary and Pancreatic Disease [see Warnings and Precautions (5.3)]
- Fluid Imbalance and Fluid Overload [see Warnings and Precautions (5.4)]
6.1 Clinical Trials Experience
Adults
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice.
The rates of adverse reactions in 136 adult patients with SBS participating in two randomized, placebo-controlled, 24-week, double-blind clinical studies (Study 1 and Study 3) are summarized in Table 1. Only those reactions with a rate of at least 5% in the GATTEX group, and greater than placebo group, are summarized in Table 1.
Table 1: Common Adverse Reactions* in Adult Patients with SBS in Placebo-Controlled Studies: Studies 1 and 3
| Adverse Reaction | Placebo (N=59) (%) |
GATTEX 0.05 mg/kg Once Daily (N=77) (%) |
|---|---|---|
| Abdominal pain1 | 22 | 30 |
| Nausea | 20 | 23 |
| Upper respiratory tract infection2 | 12 | 21 |
| Abdominal distension | 2 | 20 |
| Injection site reaction3 | 12 | 13 |
| Vomiting | 10 | 12 |
| Fluid overload4 | 7 | 12 |
| Hypersensitivity5 | 7 | 10 |
| Flatulence | 7 | 9 |
| Decreased appetite | 3 | 7 |
| Influenza6 | 2 | 7 |
| Skin hemorrhage7 | 2 | 5 |
| Cough | 0 | 5 |
| Sleep disturbances8 | 0 | 5 |
Reported at a rate of at least 5% in the GATTEX group, and greater than the placebo group.
Includes: Abdominal pain, upper abdominal pain, lower abdominal pain
Includes: Upper respiratory tract infection, nasopharyngitis, pharyngitis, sinusitis, laryngitis, rhinitis, viral upper respiratory tract infection
Includes: Injection site hematoma, injection site erythema, injection site pain, injection site swelling, injection site hemorrhage, injection site discoloration, injection site reaction, injection site rash
Includes: Fluid overload, peripheral edema, edema, generalized edema, fluid retention and jugular vein distension
Includes: Erythema, rash, dermatitis allergic, pruritus, rash macular, drug eruption, eyelid edema, flushing
Includes: Influenza, influenza-like illness
Includes: Hematoma, abdominal wall hematoma, post procedural hematoma, umbilical hematoma, blood blister
Includes: Insomnia (3 patients) and hypersomnia (1 patient)
Adverse Reactions in the Subset of Patients with a Stoma
Among the 53 patients with a stoma in the placebo-controlled studies (Study 1 and Study 3), the percentage of patients with gastrointestinal stoma complication was 42% (13/31) for patients receiving GATTEX 0.05 mg/kg/day and 14% (3/22) for patients receiving placebo.
Pediatric Patients 1 Year to Less Than 17 Years of Age
In two clinical studies of 24-week and 12-week duration, 41 pediatric patients aged 1 year to less than 17 years were treated with GATTEX 0.05 mg/kg/day [see Use in Specific Populations (8.4), Clinical Studies (14.2)]. Overall, the safety profile of GATTEX was similar to that in adults. In the long-term extension studies with mean exposure of 41 weeks, no new safety signals were identified.
Less Common Adverse Reactions
Adverse Reactions of Special Interest
Malignancy
Three patients were diagnosed with malignancy in the SBS clinical studies in adults, all of whom were male and had received GATTEX 0.05 mg/kg/day in Study 2. One patient had a history of abdominal radiation for Hodgkin’s disease two decades prior to receiving GATTEX and prior liver lesion on CT scan, and was diagnosed with metastatic adenocarcinoma of unconfirmed origin after 11 months of exposure to GATTEX. Two patients had extensive smoking histories and were diagnosed with lung cancers (squamous and non-small cell) after 12 months and 3 months of GATTEX exposure, respectively [see Warnings and Precautions (5.1)].
Intestinal Polyps
In the adult clinical studies, 14 patients with SBS were diagnosed with polyps of the GI tract after initiation of study treatment. In the SBS placebo-controlled studies, 1/59 (2%) of patients on placebo and 1/109 (1%) of patients on GATTEX 0.05 mg/kg/day were diagnosed with intestinal polyps (inflammatory stomal and hyperplastic sigmoidal after 3 and 5 months, respectively). The remaining 12 polyp cases occurred in the extension studies — 2 colorectal villous adenomas (onset at 6 and 7 months in GATTEX 0.1 mg/kg/day (twice the recommended dose) and 0.05 mg/kg/day dose groups, respectively), 2 hyperplastic polyps (onset 6 months in GATTEX 0.1 mg/kg/day dose group and 24 months in GATTEX 0.05 mg/kg/day dose group), 4 colorectal tubular adenomas (onset between 24 and 29 months in GATTEX 0.05 mg/kg/day dose group), 1 serrated adenoma (onset at 24 months in GATTEX 0.05 mg/kg/day dose group), 1 colorectal polyp biopsy not done (onset at 24 months in GATTEX 0.05 mg/kg/day dose group), 1 rectal inflammatory polyp (onset at 10 months in the GATTEX 0.05 mg/kg/day dose group, and 1 small duodenal polyp (onset at 3 months in GATTEX 0.05 mg/kg/day dose group) [see Warnings and Precautions (5.1)].
In the pediatric clinical studies (up to 69 weeks of exposure), there was one case of cecal polyp that was not biopsied and was not seen on repeat colonoscopy.
Gastrointestinal Obstruction
Overall, in the adult clinical studies, 12 patients with SBS experienced one or more episodes of intestinal obstruction/stenosis: 6 in SBS placebo-controlled studies and 6 in the extension studies. The 6 patients in the placebo-controlled studies were all on GATTEX: 3/77 (4%) on GATTEX 0.05 mg/kg/day and 3/32 (9%) on GATTEX 0.1 mg/kg/day (twice the recommended dose). No cases of intestinal obstruction occurred in the placebo group. Onset ranged from 1 day to 6 months. In the adult extension studies, 6 additional patients (all on GATTEX 0.05 mg/kg/day) were diagnosed with intestinal obstruction/stenosis with onsets ranging from 6 days to 19 months. Two of the 6 patients from the placebo-controlled studies experienced recurrence of obstruction in the extension studies. Of all 8 patients with an episode of intestinal obstruction/stenosis in these extension studies, 2 patients required endoscopic dilation and 1 required surgical intervention) [see Warnings and Precautions (5.2)].
In the pediatric clinical studies (up to 69 weeks of exposure), there was 1 serious adverse reaction of obstruction. Teduglutide was temporarily withheld, obstruction resolved without additional intervention, and there was no recurrence once teduglutide was restarted.
Gallbladder, Biliary and Pancreatic Disease
For gallbladder and biliary disease in the adult placebo-controlled studies, 3 patients with SBS were diagnosed with cholecystitis, all of whom had a prior history of gallbladder disease and were in the GATTEX 0.05 mg/kg/day dose group. No cases were reported in the placebo group. One of these 3 cases had gallbladder perforation and underwent cholecystectomy the next day. The remaining 2 cases underwent elective cholecystectomy at a later date. In the adult extension studies, 4 patients had an episode of acute cholecystitis; 3 patients had new-onset cholelithiasis; and 1 patient experienced cholestasis secondary to an obstructed biliary stent. For pancreatic disease in the adult placebo-controlled studies, 1 patient (GATTEX 0.05 mg/kg/day dose group) had a pancreatic pseudocyst diagnosed after 4 months of GATTEX. In the adult extension studies, 1 patient was diagnosed with chronic pancreatitis; and 1 patient was diagnosed with acute pancreatitis) [see Warnings and Precautions (5.3)].
Fluid Overload
In the adult placebo-controlled studies, peripheral edema was reported in 2/59 (3%) of patients on placebo and 8/77 (10%) patients on GATTEX; fluid overload was reported in 1/77 (1%) patient in the GATTEX group; no cases of fluid overload were seen in the placebo arm. There were 2 cases of congestive heart failure (CHF, 3%) in the GATTEX arm, 1 of which was reported as a serious adverse event and the other as non-serious. The serious case had onset at 6 months and was possibly associated with previously undiagnosed hypothyroidism and/or cardiac dysfunction [see Warnings and Precautions (5.4)].
Other Less Common Adverse Reactions
Reported in less than 5% of patients treated with GATTEX:
Gastrointestinal disorders: Colonic stenosis, Pancreatic duct stenosis, Small intestinal stenosis
Respiratory, thoracic and mediastinal disorders: Dyspnea
6.2 Postmarketing Experience
The following adverse reactions have been identified during post approval use of teduglutide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Gastrointestinal Neoplasia: colorectal polyps, gastric polyps, small intestinal polyps (duodenum, ileum, and jejunum)
7 DRUG INTERACTIONS
7.1 Potential for Increased Absorption of Oral Medications
Based upon the pharmacodynamic effect of GATTEX, there is a potential for increased absorption of concomitant oral medications. Altered mental status has been observed in patients taking GATTEX and benzodiazepines in the adult clinical studies [see Warnings and Precautions (5.5)].
Monitor patients on concomitant oral drugs requiring titration or with a narrow therapeutic index for adverse reactions related to the concomitant drug while on GATTEX. The concomitant drug may require a reduction in dosage.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Available data from case reports with GATTEX use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Pregnant women with short bowel syndrome are at risk for malnutrition, which is associated with adverse maternal and fetal outcomes (see Clinical Considerations). In animal reproduction studies, no effects on embryo-fetal development were observed with the subcutaneous administration of teduglutide to pregnant rats and rabbits during organogenesis at exposures up to 686 and 657 times, respectively, the clinical exposure at the recommended human dose (based on AUC) (see Data).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations
Disease-associated maternal and/or embryo/fetal risk
Pregnant women with short bowel syndrome are at risk for malnutrition. Severe malnutrition in pregnant women is associated with preterm delivery, low birth weight, intrauterine growth restriction, congenital malformations and perinatal mortality.
Data
Animal Data
Reproduction studies have been performed in pregnant rats at subcutaneous doses of teduglutide up to 25 mg/kg twice daily (50 mg/kg/day) (about 686 times the clinical exposure (AUC) at the recommended daily human dose of 0.05 mg/kg) and in pregnant rabbits at subcutaneous doses up to 25 mg/kg twice daily (50 mg/kg/day) (about 657 times the clinical exposure (AUC) at the recommended daily human dose of 0.05 mg/kg) during the period of organogenesis. These studies did not reveal any evidence of impaired fertility or harm to the fetus due to teduglutide. In a pre- and postnatal development study in rats (gestation day 7 to lactation day 20), teduglutide did not show any significant adverse effects on pre- and postnatal development at doses up to 25 mg/kg twice daily (50 mg/kg/day) (about 343 times the clinical exposure (AUC) at the recommended daily human dose of 0.05 mg/kg).
8.2 Lactation
Risk Summary
There is no information regarding the presence of GATTEX in human milk, the effects of GATTEX on the breastfed infant, or the effects of GATTEX on milk production. Teduglutide is present in the milk of lactating rats (see Data). Systemic exposure of teduglutide to a breastfed infant is expected to be low. However, because of the potential for serious adverse reactions in a breastfed infant, including tumorigenicity [see Nonclinical Toxicology (13.1)], advise patients that breastfeeding is not recommended during treatment with GATTEX.
Data
In a milk excretion study in the rat, a single subcutaneous dose of 25 mg/kg of teduglutide (81 times the recommended daily human dose of 0.05 mg/kg based on body surface area) was administered to lactating female rats at Day 12 postpartum. The maximum concentration of teduglutide in the milk corresponded to 0.9% and 2.9% of the plasma concentration at 1.5 and 4 hours after dosing, respectively.
8.4 Pediatric Use
The safety and effectiveness in pediatric patients less than 1 year of age have not been established.
The safety and effectiveness of GATTEX have been established in pediatric patients 1 year to less than 17 years of age who are dependent on parenteral support for the treatment of SBS. Use of GATTEX in this population is supported by evidence from adequate and well-controlled studies in adults, with additional efficacy, safety, pharmacokinetic and pharmacodynamic data in pediatric patients 1 year to less than 17 years of age [see Dosage and Administration (2), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.2)]. These data were derived from two studies of 24-week (Study 5) and 12-week (NCT01952080) duration in which 41 pediatric patients were treated with GATTEX in the following groups: 1 infant (1 year to less than 2 years), 37 children (2 years to less than 12 years) and 3 adolescents (12 years to less than 17 years).
In these 2 studies and the corresponding extension studies (Study 6 and NCT02949362), 29 pediatric patients were administered GATTEX prospectively for up to 94 weeks [see Clinical Studies (14.2)]. Adverse reactions in pediatric patients were similar to those seen in adults [see Adverse Reactions (6.1)].
Juvenile Animal Toxicity Data
In a juvenile toxicity study, teduglutide was administered to juvenile minipigs at subcutaneous doses of 0.5, 2.5 and 12.5 mg/kg twice daily (1, 5, and 25 mg/kg/day) from post-natal day 7 and continuing for 90 days). Exposures (AUC) at these doses were at least 12-, 25-, and 170-fold the pediatric clinical exposure for ages 1 year to 11 years at 0.05 mg/kg, respectively, and 10-, 21-, and 141-fold the pediatric clinical exposure for ages 12 years to 17 years at 0.05 mg/kg, respectively.
In juvenile minipigs, subcutaneous teduglutide caused intestinotrophic effects, gall bladder mucosal hyperplasia, bile duct mucosal hyperplasia, and injection site reactions, similar to those observed in adult animals.
8.5 Geriatric Use
Of the 134 patients with SBS that were treated with GATTEX at the recommended dosage of 0.05 mg/kg/day in the clinical studies, 19 patients were 65 years or older while 5 patients were 75 years of age or older. No overall differences in safety or efficacy were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3)].
8.6 Renal Impairment
In adult subjects with moderate to severe renal impairment or end-stage renal disease (ESRD) (creatinine clearance <60 mL/min), the exposure to teduglutide increased with the degree of renal impairment [see Clinical Pharmacology (12.3)]. Reduce the dosage of GATTEX by half in both pediatric and adult patients with eGFR less than 60 mL/min/1.73 m2 [see Dosage and Administration (2.3)].
8.7 Hepatic Impairment
GATTEX has not been studied in patients with severe hepatic impairment (Child-Pugh grade C). No dosage adjustment is recommended for patients with mild and moderate hepatic impairment (Child-Pugh grade A and B) [see Clinical Pharmacology (12.3)].
10 OVERDOSAGE
The maximum dose of GATTEX studied during clinical development was 80 mg/day for 8 days. No unexpected systemic adverse reactions were seen. In the event of overdose, the patient should be carefully monitored by the medical professional.
11 DESCRIPTION
The active ingredient in GATTEX (teduglutide) for injection is teduglutide, which is a 33 amino acid glucagon-like peptide-2 (GLP-2) analog manufactured using a strain of Escherichia coli modified by recombinant DNA technology. The chemical composition of teduglutide is L-histidyl-L-glycyl-L-aspartyl-L-glycyl-L-seryl-L-phenylalanyl-L-seryl-L-aspartyl-L-glutamyl-L-methionyl-L-asparaginyl-L-threonyl-L-isoleucyl-L-leucyl-L-aspartyl-L-asparaginyl-L-leucyl-L-alanyl-L-alanyl-L-arginyl-L-aspartyl-L-phenylalanyl-L-isoleucyl-L-asparaginyl-L-tryptophanyl-L-leucyl-L-isoleucyl-L-glutaminyl-L-threonyl-L-lysyl-L-isoleucyl-L-threonyl-L-aspartic acid. The structural formula is:
Figure 1: Structural formula of teduglutide
Teduglutide has a molecular weight of 3752 Daltons. Teduglutide drug substance is a clear, colorless to light-straw–colored liquid.
Each single-dose vial of GATTEX contains 5 mg of teduglutide as a white lyophilized powder for reconstitution and administration by subcutaneous injection. In addition to the active pharmaceutical ingredient (teduglutide), each vial of GATTEX contains 3.434 mg dibasic sodium phosphate heptahydrate, 3.88 mg L-histidine, 15 mg mannitol, and 0.644 mg monobasic sodium phosphate monohydrate as excipients. No preservatives are present.
At the time of administration, the lyophilized powder is reconstituted with 0.5 mL of Sterile Water for Injection, which is provided in a single-dose prefilled syringe. A 10 mg/mL sterile solution is obtained after reconstitution. Up to 0.38 mL of the reconstituted solution which contains 3.8 mg of teduglutide can be withdrawn for subcutaneous injection upon reconstitution.
12 CLINICAL PHARMACOLOGY
12.1 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).
12.2 Pharmacodynamics
Intestinal Fluid Absorption
The ability of GATTEX to improve intestinal absorption was studied in 17 adult subjects with Short Bowel Syndrome (N=2-3 per dose group) using daily doses of 0.03, 0.1, 0.15 mg/kg (doses ranging from 0.6 to 3 times the recommended dose) in a 21-day, open-label, multicenter, dose-ranging study. All subcutaneous (abdomen) doses studied, except 0.03 mg/kg once daily, resulted in enhanced gastrointestinal fluid (wet weight) absorption of approximately 750 to 1000 mL/day, and increased villus height and crypt depth of the intestinal mucosa.
Cardiac Electrophysiology
At a dose 5 times the recommended dose, GATTEX did not prolong the QT interval to any clinically relevant extent.
12.3 Pharmacokinetics
Absorption
In healthy subjects, GATTEX administered subcutaneously had an absolute bioavailability of 88% and reached maximum plasma teduglutide concentrations at 3 to 5 hours after administration. Following a 0.05 mg/kg subcutaneous dose in SBS subjects, the median peak teduglutide concentration (Cmax) was 36 ng/mL and the median area under the curve at steady state (AUCtau) was 0.15 μg•hr/mL. No accumulation of teduglutide was observed following repeated subcutaneous administrations.
The Cmax and AUC of teduglutide was dose proportional over the dose range of 0.05 to 0.4 mg/kg (up to 8 times the recommended dose of GATTEX).
Distribution
In healthy subjects, teduglutide has a volume of distribution (103 mL/kg) similar to blood volume.
Elimination
Metabolism
The metabolic pathway of teduglutide was not investigated in humans. However, teduglutide is expected to be degraded into small peptides and amino acids via catabolic pathways, similar to the catabolism of endogenous GLP-2.
Excretion
In healthy subjects, teduglutide plasma clearance was approximately 123 mL/hr/kg which is similar to the GFR suggesting that teduglutide is primarily cleared by the kidney. Teduglutide has a mean terminal half-life (t1/2) of approximately 2 hours in healthy subjects and 1.3 hours in SBS subjects.
Use in Specific Populations
Geriatric Patients
No differences were observed between healthy subjects younger than 65 years and those older than 65 years. Experience in subjects 75 years and above is limited.
Pediatric Patients
Following subcutaneous administration, similar steady state Cmax of teduglutide across age groups was demonstrated by population pharmacokinetics modeling (see Table 2). However, lower AUC was seen in pediatric patients 1 to 17 years of age as compared with adults and increases with increasing age.
Table 2: Teduglutide Pharmacokinetic Parameters Following Subcutaneous Dosing of GATTEX 0.05 mg/kg by Age Groups
| Parameters (Mean ± SD) | ||||
|---|---|---|---|---|
| Age | Cmax, ss (ng/mL) | AUCss (ng•h/mL) | CL/F (L/h) | t1/2 (h) |
| 12 to 17 years (n=3) | 29.7 ± 8.4 | 154 ± 17.6 | 13.0 ± 2.3 | 1.0 ± 0.01 |
| 1 to 11 years (n=37) | 33.5 ± 11.5 | 128 ± 56.7 | 7.45 ± 2.1 | 0.7 ± 0.2 |
Male and Female Patients
No clinically relevant gender differences were observed.
Patients with Renal Impairment
In adult subjects with moderate to severe renal impairment or end stage renal disease (ESRD) (creatinine clearance <60 mL/min), the Cmax and AUC0-inf of teduglutide increased with the degree of renal impairment following a single subcutaneous dose of 10 mg GATTEX. Teduglutide exposure increased by a factor of 1.6, 1.4, and 2.1 (Cmax) and 1.5, 1.7, and 2.6 (AUC0-inf) in subjects with moderate, severe renal impairment and ESRD, respectively, compared to healthy subjects [see Dosage and Administration (2.3), Use in Specific Populations (8.6)].
Patients with Hepatic Impairment
Subjects with moderate hepatic impairment (Child-Pugh Class B) had an approximately 10 to 15% lower teduglutide Cmax and AUC compared to healthy matched control subjects after a single subcutaneous dose of 20 mg GATTEX. This reduction in teduglutide exposure is not thought to be clinically meaningful. GATTEX was not studied in subjects with severe hepatic impairment (Child-Pugh Class C).
Drug Interaction Studies
Clinical interaction studies were not performed. No inhibition or induction of the cytochrome P450 enzyme system has been observed based on in vitro studies although the relevance of in vitro studies to an in vivo setting is unknown.
12.6 Immunogenicity
The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of GATTEX or of other teduglutide products.
Adults
Based on integrated data from two studies in adults with SBS (a 6‑month randomized placebo‑controlled study, followed by a 24‑month open‑label study), the development of anti‑teduglutide antibodies in patients who received subcutaneous administration of 0.05 mg/kg GATTEX once daily was 3% (2/60) at Month 3, 17% (13/77) at Month 6, 24% (16/67) at Month 12, 33% (11/33) at Month 24, and 48% (14/29) at Month 30. Anti-teduglutide antibodies were cross-reactive to native glucagon-like peptide (GLP‑2) in 5 of the 6 patients (83%) who had anti-teduglutide antibodies and were tested for cross‑reactivity. In the same two studies, a total of 36 patients were tested for neutralizing antibodies: one patient developed borderline positive neutralizing antibody responses at month 24 of the extension study. The antibody formation has not been associated with clinically relevant safety findings, reduced efficacy or changed pharmacokinetics of GATTEX.
Pediatric Patients 1 Year to Less than 17 Years of Age
In pediatric patients who received subcutaneous administration of 0.05 mg/kg GATTEX once daily for 24 weeks, the rate of anti‑teduglutide antibody formation at Month 6 was 19% (5/26) and was similar to the rate of antibody formation in adult patients (17%). Of the 5 pediatric patients who had developed antibodies to teduglutide at Month 6, 2 patients had neutralizing antibodies. However, with the longer duration of treatment, the rate of anti‑teduglutide formation at Month 12 was higher in pediatric patients with 54% (14/26), compared to that of adults (24%). Of the 14 pediatric patients who had developed antibodies to teduglutide at Month 12, 1 patient had neutralizing antibodies.
Among the small number of pediatric patients who developed anti‑teduglutide antibodies, no association with adverse events or lack of efficacy was observed.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenic potential of GATTEX was assessed in 2-year subcutaneous carcinogenicity studies in rats and mice. In a 2-year carcinogenicity study in Wistar Han rats at subcutaneous doses of 3, 10, and 35 mg/kg/day (about 15, 41, and 199 times the exposures [AUC] achieved at the recommended daily human dose of 0.05 mg/kg, respectively), teduglutide caused statistically significant increases in the incidences of adenomas in the bile duct and jejunum of male rats. In a 2-year carcinogenicity study in Crl:CD1(ICR) mice at subcutaneous doses of 1, 3.5, and 12.5 mg/kg/day (about 32, 66, and 244 times the exposures [AUC] achieved at the recommended daily human dose of 0.05 mg/kg, respectively), teduglutide caused a significant increase in papillary adenomas in the gall bladder; it also caused adenocarcinomas in the jejunum in male mice at the high dose of 12.5 mg/kg/day.
Teduglutide was negative in the Ames test, chromosomal aberration test in Chinese hamster ovary cells, and in vivo mouse micronucleus assay.
Teduglutide at subcutaneous doses up to 25 mg/kg twice daily (50 mg/kg/day or at least 202 times the clinical exposure (AUC) at the recommended daily human dose of 0.05 mg/kg) was found to have no adverse effect on fertility and reproductive performance of male and female rats.
14 CLINICAL STUDIES
14.1 Treatment of SBS in Adults
Study 1 (Placebo-controlled) and Study 2 (Open-label Extension of Study 1)
Study 1 (CL0600-020, NCT00798967)
The efficacy, safety, and tolerability of GATTEX was evaluated in a randomized, double-blind, placebo-controlled, parallel-group, multi-national, multicenter clinical study (Study 1) in adults with SBS who were dependent on parenteral nutrition/intravenous (PN/I.V.) support for at least 12 months and required PN at least 3 times per week. For 8 weeks (or less) prior to randomization, investigators optimized the PN/I.V. volume of all patients. Optimization was followed by a 4-week to 8-week period of fluid stabilization. Patients then were randomized (1:1) to placebo (n=43) or GATTEX 0.05 mg/kg/day (n=43). Study treatment was administered subcutaneously once daily for 24 weeks. PN/I.V. volume adjustments (up to 30% decrease) and clinical assessments were made at 2, 4, 8, 12, 20, and 24 weeks.
The primary efficacy endpoint was based on a clinical response, defined as a patient achieving at least 20% reduction in weekly PN/I.V. volume from Baseline (immediately before randomization) to both Weeks 20 and 24.
The mean age of patients was 50 years. Mean duration of PN/I.V. dependency prior to enrollment was 6 years (range 1 to 26 years). The most common reasons for intestinal resection leading to SBS were vascular disease (34%, 29/85), Crohn’s Disease (21%, 18/85), and “other” (21%, 18/85). Stoma was present in 45% (38/85) of patients, and the most common type was jejunostomy/ileostomy (82%, 31/38). The mean length of remaining small intestine was 77.3±64.4 cm (range: 5 to 343 cm). The colon was not in continuity in 44% (37/85) patients. At baseline, the mean (± SD) prescribed days per week for PN/I.V. infusion was 5.73 (±1.59) days.
The percentages of treatment group responders were compared in the intent-to-treat population of this study which was defined as all randomized patients. Sixty-three percent (27/43) of GATTEX-treated patients versus 30% (13/43) of placebo-treated patients were considered responders (p=0.002).
At Week 24, the mean reduction in weekly PN/I.V. volume was 4.4 Liters for GATTEX-treated patients (from pre-treatment baseline of 12.9 Liters) versus 2.3 Liters for placebo-treated patients (from pre-treatment baseline of 13.2 Liters/week) (p<0.001).
Twenty-one patients on GATTEX (54%) versus 9 on placebo (23%) achieved at least a one-day reduction in PN/I.V. support.
The mean changes from Baseline in PN/I.V. volume by visit are shown in Figure 2.
Figure 2: Change (±95% CI) in PN/I.V. volume (L/week)
Study 2 (CL0600-021, NCT00930644)
Study 2 was a 2-year open-label extension of Study 1 in which 88 patients received GATTEX 0.05 mg/kg/day. Ninety-seven percent (76/78) of patients who completed Study 1 elected to enroll in Study 2 (37 received GATTEX; 39 received Placebo). An additional 12 patients entered Study 2, who had been optimized and stabilized but not randomized in Study 1 because of closed enrollment.
30 months exposure
Thirty GATTEX patients completed a total duration of 30 months (Study 1 followed by Study 2 treatment). Of these, 28 patients (93%) achieved a 20% or greater reduction of parenteral support (PS). Of responders in Study 1 who had completed 2 additional years of continuous treatment with GATTEX, 96% (21/22) sustained their response to GATTEX. The mean reduction in PN/I.V. (n=30) was 7.55 L/week (a 66% reduction from baseline). Ten patients were weaned off their PN/I.V. support while on GATTEX treatment for 30 months. Patients were maintained on GATTEX even if no longer requiring PN/I.V. support. These 10 patients had required PN/I.V. support for 1.2 to 15.5 years, and prior to GATTEX had required between 3.5 L/week and 13.4 L/week of PN/I.V. support. At the end of study, 21 (70%), 18 (60%) and 18 (60%) of the 30 completers achieved a reduction of 1, 2, or 3 days per week in PN/I.V. support, respectively.
24 months exposure
Of the 39 placebo-treated patients from Study 1 entering Study 2, 29 completed 24 months of treatment with GATTEX. The mean reduction in PN/I.V. was 3.11 L/week (an additional 28.3% reduction) from the start of Study 2. Sixteen (55%) of the 29 completers achieved a 20% or greater reduction of PS. At the end of the study, 14 (48%), 7 (24%) and 5 (17%) achieved a reduction of 1, 2, or 3 days per week in PN/I.V. support, respectively. Two patients were weaned off their PN/I.V. support while on GATTEX. Of the 12 patients entering Study 2 directly, 6 completed 24 months of treatment with GATTEX. Similar effects were seen. One of the six patients was weaned off their PN/I.V. support while on GATTEX.
Study 3 (Placebo-controlled) and Study 4 (Blinded Uncontrolled Extension of Study 3)
Study 3 (CL0600-004, NCT00081458)
Study 3 was a randomized, double-blind, placebo-controlled, three parallel-group, multinational study in adults with SBS who were dependent on parenteral nutrition/intravenous (PN/I.V.) support for at least 12 months and required PN at least 3 times per week. After a period of optimization and stabilization similar to Study 1, patients were randomized to receive 24 weeks of one of the following treatment regimens: GATTEX 0.05 mg/kg/day (n=35), GATTEX 0.1 mg/kg/day (twice the recommended dose) (n=33), or placebo (n=16). GATTEX 0.1 mg/kg/day is not a recommended dosage [see Dosage and Administration (2.2)]. The treatment groups were compared using the intent-to-treat population of this study which was defined as all randomized patients who were administered at least one dose of study drug. This population contained one less patient in the 0.1 mg/kg/day dose group hence n=32 in this group for all analyses. The primary efficacy endpoint was a graded categorical score that did not achieve statistical significance for the high dose. Further evaluation of PN/I.V. volume reduction using the endpoint of response (defined as at least 20% reduction in PN/I.V. fluid from Baseline to Weeks 20 and 24) showed that 46% of patients on GATTEX 0.05 mg/kg/day responded versus 6% on placebo. Patients on GATTEX in both dose groups experienced a 2.5 L/week reduction in PS requirements versus 0.9 L/week for placebo at 24 weeks. Two patients in the GATTEX 0.05 mg/kg/day dose group were weaned off PS by Week 24.
Study 4 (CL0600-005, NCT00172185)
Study 4 was a blinded, uncontrolled extension of Study 3, in which 65 patients from Study 3 received GATTEX for up to an additional 28 weeks of treatment. Of responders in Study 3 who entered Study 4, 75% sustained response on GATTEX after one year of treatment. In the GATTEX 0.05 mg/kg/day dose group, a 20% or greater reduction of PS was achieved in 68% (17/25) of patients. The mean reduction of weekly PN/I.V. volume was 4.9 L/week (52% reduction from baseline) after one year of continuous GATTEX treatment. The patients who had been completely weaned off PN/I.V. support in Study 3 remained off PS through Study 4. During Study 4, an additional patient from Study 3 was weaned off PS.
14.2 Treatment of SBS in Pediatric Patients
Study 5 (TED-C14-006, NCT02682381)
Study 5 was a 24-week, multicenter study conducted in 59 pediatric patients aged 1 year through 17 years with SBS who were dependent on PS. Patients chose whether to receive GATTEX or standard of care (SOC). Patients who chose to receive GATTEX treatment were subsequently randomized in a double-blind manner to 0.025 mg/kg/day (n=24) or 0.05 mg/kg/day (n=26), while 9 patients enrolled in the SOC arm. Randomization to the GATTEX dose groups was stratified by age.
Patients treated with 0.05 mg/kg had a mean age of 6 years at baseline. The most common reasons for intestinal resection leading to SBS were gastroschisis (54%, 14/26), midgut volvulus (23%, 6/26), and necrotizing enterocolitis (12%, 3/26). Stoma was present in 19% (5/26) of patients, and the most common type was jejunostomy (80%, 4/5). The mean length of remaining small intestine was 47 (±28) cm (range: 9 to 120 cm). In the 25 patients who had remaining colon, the colon was in continuity in 22 patients. At baseline, the mean PS volume was 60 (±29) mL/kg/day (range: 24 to 133 mL/kg/day) [8 (±4) L/week (range: 3 to 19 L/week)] and mean PS infusion time was 7 (±1) days/week (range: 5 to 7 days/week) and 11 (±3) hours/day (range: 7 to 20 hours/day).
Results described in Table 3 correspond to the recommended GATTEX dosage of 0.05 mg/kg subcutaneously once daily.
Table 3: Summary of Efficacy Endpoints at Week 24* for Study 5 – Patients treated with GATTEX 0.05 mg/kg/day (N = 26)
| Efficacy Endpoints | Results |
|---|---|
| Reduction in PS volume of at least 20%, n/N (%) | 18/26 (69%) |
| Achieved enteral autonomy, n/N (%) | 3/26 (12%) |
| Reduction in PS infusion of ≥1 day/week, n/N (%) | 10/26 (38%) |
| Change in PS volume from baseline (mL/kg/day), mean (SD) and [mean% (SD)] | -23 (18) mL/kg/day [-42% (29%)] |
Results based on patient diary data, ITT population
Study 6 (SHP633-304, NCT02954458)
Study 6 was a prospective, open-label, long-term extension study of pediatric patients who completed Study 5. In the extension study, patients received additional treatment with GATTEX 0.05 mg/kg subcutaneously once daily if they deteriorated or stopped improving after discontinuation of prior GATTEX treatment. Of the 15 patients who initially responded in Study 5 and enrolled in Study 6, 13 patients (87%) required additional treatment with GATTEX. Efficacy results at the end of the first 24-week treatment period in Study 6 (total treatment for a mean of 40 weeks) were similar to those achieved at the end of 24 weeks treatment in Study 5. One additional patient treated with 0.05 mg/kg in Study 5 eventually achieved enteral autonomy during follow-up in Study 6.
16 HOW SUPPLIED/STORAGE AND HANDLING
GATTEX (teduglutide) for injection is supplied as 5 mg of teduglutide as a white, lyophilized powder for reconstitution in a sterile, single-dose glass vial with 0.5 mL Sterile Water for Injection in a single-dose prefilled syringe. The product to be dispensed is either a one-vial kit or a 30-vial kit.
One-vial kits are pre-assembled and ready to be used:
GATTEX 5 mg One-vial Kit (NDC 68875-0103-1):
- One single-dose vial of 5 mg teduglutide (NDC 68875-0101-1)
- One disposable prefilled syringe containing 0.5 mL Sterile Water for Injection USP for reconstitution, with a separate needle (23G x 1½ in) to attach to the syringe
- One sterile disposable 1-mL syringe with needle (27G x 1/2 in) for dosing
- Four alcohol swabs
Storage and Handling of One-Vial Kit
Prior to Dispensing:
- Store GATTEX 5 mg Strength one-vial kits refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze. Do not use beyond the expiration date on the label.
After Dispensing by the Pharmacist:
- Store GATTEX 5 mg Strength one-vial kits at room temperature up to 25°C (77°F). Do not freeze. Dispense with a 90-day “use by” dating.
GATTEX is also supplied in 30-vial cartons to be assembled by the dispensing pharmacist into a 30-vial kit by transferring the trays containing 30 vials from a Carton of Drug Vials into a Carton of Ancillary Supplies:
GATTEX 5 mg Carton of Drug Vials (NDC 68875-0101-2):
- Thirty single-dose vials of GATTEX 5 mg (NDC 68875-0101-1)
-
Carton of Ancillary Supplies:
- Thirty disposable prefilled syringes containing diluent (0.5 mL Sterile Water for Injection USP) for reconstitution
- Thirty separate needles (23G x 1½ in) to attach to the syringes for reconstitution
- Thirty sterile disposable 1-mL syringes with needle (27G x 1/2 in)
- Sixty alcohol swabs
The final assembled 30-Vial Kit should contain the items:
GATTEX 5 mg Strength 30-Vial Kit (NDC 68875-0102-1):
- Thirty single-dose vials of 5 mg teduglutide (NDC 68875-0101-1)
- Thirty disposable prefilled syringes containing 0.5 mL Sterile Water for Injection USP for reconstitution, with 30 separate needles (23G x 1½ in) to attach to the syringes
- Thirty sterile disposable 1-mL syringes with needle (27G x 1/2 in) for dosing
- Sixty alcohol swabs
Storage and Handling of 30-Vial Cartons and 30-Vial Kits
Prior to Dispensing:
- Store GATTEX 5 mg vials refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze. Do not use beyond the expiration date on the label.
- Store the Carton of Ancillary Supplies at room temperature up to 25°C (77°F).
After Dispensing by the Pharmacist:
- Store GATTEX 5 mg Strength 30-vial kits at room temperature up to 25°C (77°F). Do not freeze. Dispense with a 90-day “use by” dating.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).
Acceleration of Neoplastic Growth
Advise adult patients and their caregivers that the patient will need to undergo clinical examinations, repeated colonoscopies and upper GI endoscopies (or alternate imaging) before and during treatment with GATTEX to monitor for the development of polyps and/or neoplasia of the GI tract. Advise pediatric patients and their caregivers that the patient will need to undergo clinical examinations, fecal occult blood testing before and during treatment and colonoscopies after 1 year of treatment, every 5 years thereafter while on continuous treatment with GATTEX or if they have new or unexplained gastrointestinal bleeding. Advise pediatric patients and their caregivers that an upper GI endoscopy will be performed if there is any new or unexplained blood in the stool [see Warnings and Precautions (5.1)].
Intestinal Obstruction
Advise patients and their caregivers to immediately contact their healthcare provider if they experience any symptoms suggestive of intestinal or stomal obstruction [see Warnings and Precautions (5.2)].
Biliary and Pancreatic Disease
Advise patients and their caregivers that laboratory assessments will be done periodically while on GATTEX to monitor for the onset or worsening of gallbladder, biliary and pancreatic disease, and to report immediately to their healthcare provider if they develop symptoms suggestive of cholecystitis, cholangitis, cholelithiasis or pancreatic disease [see Warnings and Precautions (5.3)].
Fluid Overload
Advise patients and their caregivers to immediately contact their healthcare provider if they develop fluid overload or symptoms of congestive heart failure while on GATTEX [see Warnings and Precautions (5.4)].
Fluid Imbalance
Advise patients and their caregivers of the risk of fluid and electrolyte imbalance with discontinuation of GATTEX, and to contact their healthcare provider if they develop symptoms suggestive of electrolyte imbalances [see Warnings and Precautions (5.4)].
Increased Absorption of Concomitant Oral Medication
Instruct patients and their caregivers to report to their healthcare provider any concomitant oral medications that they are taking in order to assess any potential for increased absorption during GATTEX treatment of those oral medications requiring titration or with a narrow therapeutic index [see Warnings and Precautions (5.5)].
Lactation
Advise women that breastfeeding is not recommended during treatment with GATTEX [see Use in Specific Populations (8.2)].
Instructions for Use
GATTEX® (Ga’-tex)
(teduglutide)
for injection, for subcutaneous use
5 mg per vial
This Instructions for Use contains information on how to inject GATTEX.
Read this Instructions for Use before you start using GATTEX and each time you get a refill. There may be new information. Your healthcare provider or nurse should show you how to prepare, measure your dose, and give your injection of GATTEX the right way.
If you cannot give yourself the injection:
- ask your healthcare provider or nurse to help you, or
- ask someone who has been trained by a healthcare provider or nurse to give your injections.
Self-administration is not recommended in pediatric patients. In pediatric patients, GATTEX should be injected by:
- a healthcare provider or nurse, or
- a parent or adult caregiver who has been trained by a healthcare provider or nurse to give injections of GATTEX to pediatric patients.
Important information:
- Use of the GATTEX 5 mg kit is not recommended in pediatric patients weighing less than 22 pounds (10 kg).
- Before you start, check the “Use By” date on your GATTEX kit. Make sure that the “Use By” date has not passed. Do not use anything in the GATTEX kit after the “Use By” date on the kit.
- Give GATTEX within 3 hours after you mix the powder with the Diluent (Sterile Water for Injection).
- Use the syringes and needles provided in the GATTEX kit.
- Do not use a GATTEX vial more than 1 time, even if there is medicine left in the vial.
- Throw away (dispose of) any unused GATTEX after you give your injection.
- Safely throw away GATTEX vials after use.
- Do not re-use syringes or needles. See “Step 7: Dispose of syringes and needles” for information about how to safely throw away needles and syringes.
- To help avoid needle-stick injuries, do not recap needles.
GATTEX kit
Gather the supplies you will need to prepare GATTEX and to give your injection (See Figure A).
Figure A
From your GATTEX kit you will need:
-
5-mg vial of GATTEX with green cap.
Your healthcare provider will tell you how many vials of GATTEX you will need for your injection. - 2 alcohol swab pads
- Diluent syringe with a white snap-off cap
- Needle for reconstitution (23G, 1½ inch)
- Plastic dosing syringe (1 mL) with needle attached (27G, 1/2 inch)
- A sharps disposal container (not included in the GATTEX kit). See “Step 7: Dispose of needles and syringes.”
You may also need an adhesive bandage (not included in your GATTEX kit).
Step 1: Prepare the injection.
- Choose a well-lit, clean, flat work surface.
- Wash your hands with soap and water.
Step 2: Preparing the Diluent syringe.
- Put the Diluent syringe (See Figure B1) and the 23G, 1½ inch needle in front of you on your work surface.
- Hold the Diluent syringe by the barrel. Snap off the white cap (bend the cap sideways until the cap comes off). Only the top portion of the white cap should be snapped off. The lower portion of the cap will remain in place (See Figure B2). Throw the cap away.
Figure B1
Figure B2
- Remove the 23G, 1½ inch needle from the package. Use the fold in the package to peel back the plastic cover (See Figure C). Leave the plastic cap on the needle.
- Push the open end of the needle onto the end of the Diluent syringe (See Figure D). Twist the needle clockwise (to the right) until it stops turning.
- When the needle is tightly in place, put the Diluent syringe and needle on your work surface.
Figure C
Figure D
Step 3: Mix GATTEX powder with Diluent.
- Remove the green cap from the GATTEX vial. Throw away the green cap.
- Find the gray rubber seal on top of the GATTEX vial (See Figure E).
- Use an alcohol swab pad to clean the gray rubber seal (See Figure F).
- Do not touch the gray rubber seal after you clean it.
Figure E
Figure F
- Pick up the Diluent syringe with the needle attached.
- Remove the plastic cap that covers the needle (See Figure G). Throw the cap away.
- Hold the GATTEX vial between your thumb and index (pointer) finger (See Figure H). Be careful not to touch the gray rubber seal.
Figure G
Figure H
- Push the needle down through the center of the gray rubber seal.
- Slowly push down on the plunger of the Diluent syringe. Empty all the Diluent into the GATTEX vial.
- Leave the needle and Diluent syringe in place.
- Gently tap the barrel of the Diluent syringe with a finger (See Figure I).
- Make sure all the Diluent has gone into the GATTEX vial.
- Remove the Diluent syringe and needle from the GATTEX vial. Let the vial sit for about 30 seconds.
- Do not put the needle cap back on the needle.
- Throw away (dispose of) the Diluent syringe and needle in your sharps disposal container.
- After 30 seconds, place the GATTEX vial between the palms of your hands. Gently roll the vial for about 15 seconds (See Figure J).
- Do not shake the GATTEX vial.
- Do not touch the gray rubber seal. If you do, clean it again with a new alcohol pad.
- Let the GATTEX vial stand on your work surface for about 2 minutes.
Figure I
Figure J
Step 4: Check the mixed GATTEX.
- After 2 minutes, look at the vial of GATTEX. The liquid in the vial should be clear and colorless to pale yellow, and should not have any particles in it.
- If there is any powder in the GATTEX vial that did not dissolve, gently roll the vial between your hands for 15 seconds more.
- Do not shake the GATTEX vial.
- Check the GATTEX vial again for anything that did not dissolve.
- Do not use the GATTEX vial if there is anything in it that did not dissolve. Start from the beginning of this Instructions for Use to prepare a new vial. Use a new GATTEX vial, new Diluent syringe, and a new needle.
Step 5: Draw up your dose of GATTEX.
- Remove the plastic dosing syringe from the package. Use the fold in the package to peel back the plastic cover (See Figure K).
- Remove the needle cap from the plastic dosing syringe (See Figure L).
- Throw the needle cap away. Do not touch the needle or allow it to touch anything.
- Carefully pull back on the plunger to the line that matches the dose prescribed by your healthcare provider.
Figure K
Figure L
- Use 1 hand to hold the GATTEX vial steady. Use your other hand to insert the needle straight down into the middle of the gray rubber seal on the GATTEX vial (See Figure M). You may feel some resistance as the needle passes through the rubber seal.
- Gently push down the plunger until all of the air has gone from the plastic dosing syringe into the GATTEX vial.
- Turn the GATTEX vial and plastic dosing syringe upside down (See Figure N).
- Hold the GATTEX vial with 1 hand.
- Slowly pull back the plunger of the plastic dosing syringe with your other hand.
Figure M
Figure N
- Fill the plastic dosing syringe until the black tip of the plunger lines up with the mark that matches your prescribed dose (See Figure O).
- Keep the plastic dosing syringe and needle in the GATTEX vial.
- You may see some bubbles inside the GATTEX vial when the plastic dosing syringe is filled. This is normal. With the needle still in the vial, gently tap the side of the plastic dosing syringe with a finger to make any air bubbles rise to the top (See Figure P).
Figure O
Figure P
- Slowly push the plunger up until all air bubbles are out of the plastic dosing syringe. Make sure the tip of the needle is in the fluid. Slowly pull back the plunger to draw up the right dose of GATTEX into the plastic dosing syringe.
- Remove the plastic dosing syringe and needle from the GATTEX vial (See Figure Q). Do not touch the needle or allow it to touch anything.
Figure Q
Step 6: Inject GATTEX.
- Choose an injection site on the stomach area (abdomen), thighs, or upper arms.
- Choose a different site to give the injection each day. Do not inject into areas where the skin is tender, bruised, red, or hard. (See Figure R and Figure S)
Figure R
Figure S
- Clean the skin where you plan to give the injection with a new alcohol swab pad. Do not touch this area again before giving the injection.
- Use 1 hand to gently pinch up a fold of skin around the injection site (See Figure T).
- Use your other hand to hold the plastic dosing syringe. Insert the full length of the needle into the skin at a 45-degree angle with a quick, “dart-like” motion (See Figure U).
- Let go of the skin. Hold the syringe barrel with 1 hand while you slowly push down the plunger until the plastic dosing syringe is empty (See Figure V).
Figure T
Figure U
- When the plastic dosing syringe is empty, quickly pull the needle out of your skin. There may be a little bleeding at the injection site. Apply an adhesive bandage to the injection site if needed.
Figure V
Step 7: Dispose of syringes and needles.
- Do not re-use a syringe or needle.
- To help avoid needle-stick injuries, do not recap a needle.
- Put your needles and syringes in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and syringes in your household trash.
- If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:
- made of heavy-duty plastic,
- can be closed with a tight-fitting, puncture-resistant lid, without sharp items being able to come out,
- upright and stable during use,
- leak-resistant, and
- properly labeled to warn of hazardous waste inside the container.
- When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container.
There may be local or state laws about how to throw away syringes and needles. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: http://www.fda.gov/safesharpsdisposal. - Do not dispose of your sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your sharps disposal container.
- Throw away the GATTEX vial into the container where you put the syringes and needles.
- If you have any questions, talk to your healthcare provider or pharmacist.