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]. Lexington, 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
Colorectal polyps were identified during
clinical trials. There is a risk for acceleration of neoplastic growth. In adults, within 6 months prior to
starting treatment with GATTEX, colonoscopy of the entire colon with removal of polyps should be performed and
follow-up colonoscopy (or alternate imaging) is recommended at the end of 1 year of GATTEX. Subsequent
colonoscopies should be performed every 5 years or more often as needed.
In children and adolescents, perform fecal occult blood testing prior to initiating treatment with GATTEX. Colonoscopy/sigmoidoscopy is required if there is unexplained blood in the stool. Perform subsequent fecal occult blood testing annually in children and adolescents while they are receiving GATTEX. 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.
In case of intestinal 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.