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Gattex

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Gattex

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Acceleration Of Neoplastic Growth

Based on the pharmacologic activity and findings in animals, GATTEX has the potential to cause hyperplastic changes including neoplasia. In patients at increased risk for malignancy, the clinical decision to use GATTEX should be considered only if the benefits outweigh the risks. In patients with active gastrointestinal malignancy (GI tract, hepatobiliary, pancreatic), GATTEX therapy should be discontinued. In patients with active non-gastrointestinal malignancy, the clinical decision to continue GATTEX should be made based on risk-benefit considerations. [see CLINICAL PHARMACOLOGY and Nonclinical Toxicology]

Colorectal Polyps

Colorectal polyps were identified during the clinical trials. Colonoscopy of the entire colon with removal of polyps should be done within 6 months prior to starting treatment with GATTEX. A follow-up colonoscopy (or alternate imaging) is recommended at the end of 1 year of GATTEX. Subsequent colonoscopies should be done every 5 years or more often as needed. If a polyp is found, adherence to current polyp follow-up guidelines is recommended. In case of diagnosis of colorectal cancer, GATTEX therapy should be discontinued. [see ADVERSE REACTIONS]

Small Bowel Neoplasia

Based on tumor findings in the rat and mouse carcinogenicity studies, patients should be monitored clinically for small bowel neoplasia. If a benign neoplasm is found, it should be removed. In case of small bowel cancer, GATTEX therapy should be discontinued. [see Nonclinical Toxicology]

Intestinal Obstruction

Intestinal obstruction has been reported in clinical trials. In patients who develop intestinal or stomal obstruction, GATTEX should be temporarily discontinued while the patient is clinically managed. GATTEX may be restarted when the obstructive presentation resolves, if clinically indicated. [see ADVERSE REACTIONS]

Biliary And Pancreatic Disease

Gallbladder and Biliary Tract Disease

Cholecystitis, cholangitis, and cholelithiasis, have been reported in clinical studies. For identification of the onset or worsening of gallbladder/biliary disease, patients should undergo laboratory assessment of bilirubin and alkaline phosphatase within 6 months prior to starting GATTEX, and at least every 6 months while on GATTEX; or more frequently if needed. If clinically meaningful changes are seen, further evaluation including imaging of the gallbladder and/or biliary tract is recommended; and the need for continued GATTEX treatment should be reassessed. [see ADVERSE REACTIONS]

Pancreatic Disease

Pancreatitis has been reported in clinical studies. For identification of onset or worsening of pancreatic disease, patients should undergo laboratory assessment of lipase and amylase within 6 months prior to starting GATTEX, and at least every 6 months while on GATTEX; or more frequently if needed. If clinically meaningful changes are seen, further evaluation such as imaging of the pancreas is recommended; and the need for continued GATTEX treatment should be reassessed. [see ADVERSE REACTIONS and Nonclinical Toxicology]

Fluid Overload

Fluid overload and congestive heart failure have been observed in clinical trials, which were felt to be related to enhanced fluid absorption associated with GATTEX. If fluid overload occurs, parenteral support should be adjusted and GATTEX treatment should be reassessed, especially in patients with underlying cardiovascular disease. If significant cardiac deterioration develops while on GATTEX, the need for continued GATTEX treatment should be reassessed. [see ADVERSE REACTIONS]

Increased Absorption Of Concomitant Oral Medication

Altered mental status in association with GATTEX has been observed in patients on benzodiazepines in clinical trials. Patients on concomitant oral drugs (e.g., benzodiazepines, phenothiazines) requiring titration or with a narrow therapeutic index may require dose adjustment while on GATTEX. [see ADVERSE REACTIONS]

Patient Counseling Information

See FDA-approved patient labeling (Medication Guide and Instructions for Use).

General Counseling Information – Prior to treatment, patients should fully understand the risks and benefits of GATTEX. Ensure that all patients receive the Medication Guide prior to initiating GATTEX therapy.

Acceleration Of Neoplastic Growth

Advise patients with active gastrointestinal malignancy (GI tract, hepatobiliary, pancreatic), that GATTEX therapy should be discontinued. In patients with active non-gastrointestinal malignancy, the clinical decision to continue GATTEX should be discussed with patients and be made based on risk-benefit considerations. [see CLINICAL PHARMACOLOGY and Nonclinical Toxicology]

Colorectal polyps

Advise patients that colonoscopy of the entire colon with removal of polyps should be done within 6 months prior to starting treatment with GATTEX. A follow-up colonoscopy (or alternate imaging) is recommended at the end of 1 year of GATTEX. Subsequent colonoscopies should be done every 5 years or more often as needed. If a polyp is found, adherence to current polyp follow-up guidelines is recommended. In case of diagnosis of colorectal cancer, GATTEX therapy should be discontinued. [see ADVERSE REACTIONS]

Small Bowel Neoplasia

Advise patients that they should be monitored clinically for small bowel neoplasia. If a benign neoplasm is found, it should be removed. In case of small bowel cancer, GATTEX therapy should be discontinued. [see Nonclinical Toxicology]

Intestinal Obstruction

Advise patients to tell their physician if they experience any signs or symptoms suggestive of intestinal obstruction. If obstruction is present, the physician should temporarily discontinue GATTEX. [see WARNINGS AND PRECAUTIONS]

Gallbladder And Bile Duct Disease

Advise patients that laboratory assessments should be done before and then every 6 months while on GATTEX to monitor gallbladder and biliary function. If clinically significant change occurs, further evaluation (i.e., imaging studies or other) may be necessary. Advise patients to report to their physician all signs and symptoms suggestive of cholecystitis, cholangitis, or cholelithiasis while on GATTEX. [see WARNINGS AND PRECAUTIONS]

Pancreatic Disease

Advise patients that laboratory assessments should be done before and then every 6 months while on GATTEX. If clinically significant change occurs, further evaluation (i.e., imaging studies or other) may be necessary. Advise patients to report to their physician all signs and symptoms suggestive of pancreatic disease while on GATTEX. [see WARNINGS AND PRECAUTIONS]

Cardiovascular Disease

Advise patients with cardiovascular disease to report to their physician any signs of fluid overload or cardiac decompensation while on GATTEX. [see WARNINGS AND PRECAUTIONS]

Risks Resulting From Increased Absorption Of Concomitant Oral Medication

Instruct patients to report to all of their physicians 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]

Instructions

Inform patients that GATTEX should not be administered intravenously or intramuscularly. The drug should be used for subcutaneous injection within 3 hours after reconstitution. Advise patients that subcutaneous administration has been associated with injection site reactions, but if they experience a severe reaction including severe rash, they should contact their physician.

Advise patients that while they may experience abdominal pain and swelling of their stoma especially when starting therapy with GATTEX, if they experience symptoms of intestinal obstruction, they should contact their physician.

Instruct patients to read the Medication Guide as they are starting GATTEX therapy and to re-read it each time their prescription is renewed.

Nonclinical Toxicology

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 60, 200 and 700 times 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 20, 70 and 250 times 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 (about 250 times the recommended human dose).

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 50 mg/kg/day (about 1000 times 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.

Use In Specific Populations

Pregnancy

Category B

Risk Summary

Adequate and well controlled studies with GATTEX have not been conducted in pregnant women. In animal reproduction studies, no effects on embryo-fetal development were observed with the administration of subcutaneous teduglutide at doses up to 1000 times the recommended human dose in both rats and rabbits. Because animal reproductive studies are not always predictive of human response, GATTEX should be used during pregnancy only if clearly needed.

Data

Animal data

In animal studies, no effects on embryo-fetal development were observed in pregnant rats given subcutaneous teduglutide at doses up to 50 mg/kg/day (about 1000 times the recommended daily human dose of 0.05 mg/kg) or pregnant rabbits given subcutaneous doses up to 50 mg/kg/day (about 1000 times the recommended daily human dose of 0.05 mg/kg). A pre-and postnatal development study in rats showed no evidence of any adverse effect on pre-and postnatal development at subcutaneous doses up to 50 mg/kg/day (about 1000 times the recommended daily human dose of 0.05 mg/kg).

Nursing Mothers

It is not known whether GATTEX is present in human milk. Teduglutide is excreted in the milk of lactating rats, and the highest concentration measured in milk was 2.9% of the plasma concentration following a single subcutaneous injection of 25 mg/kg. Because many drugs are excreted in human milk, because of the potential for serious adverse reactions to nursing infants from GATTEX and because of the potential for tumorigenicity shown for teduglutide in mice and rats, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. [see Nonclinical Toxicology]

Pediatric Use

Safety and efficacy in pediatric patients have not been established.

Geriatric Use

No dose adjustment is necessary in patients above the age of 65 years. Of the 595 subjects treated with teduglutide, 43 subjects were 65 years or older, whereas 6 subjects were 75 years of age or older. In the SBS studies, no overall differences in safety or efficacy were observed between these subjects and younger subjects, 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]

Renal Impairment

Reduce the dose of GATTEX by 50% in patients with moderate and severe renal impairment (creatinine clearance less than 50 mL/min) and end-stage renal disease (ESRD). [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY]

Hepatic Impairment

GATTEX has not been formally studied in subjects with severe hepatic impairment. No dosage adjustment is necessary for patients with mild and moderate hepatic impairment based on a study conducted in Child-Pugh grade B subjects. [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY]

Last reviewed on RxList: 7/10/2014
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
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