Gattex
(teduglutide)Dosage & 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.
Evaluation Testing within 6 Months Prior to Starting GATTEX
Dosage and Administration
Dosage Adjustment for Renal Impairment
Discontinuation
Preparation
By using PrescriberAI, you agree to the AI Terms of Use.
Gattex Prescribing Information
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.
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)].
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.
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)].
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)].
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)].
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.
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.
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).
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.
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.
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)].
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)].
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)].
None.
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.
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.
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.
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)].
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)].