REMS: FDA approved a REMS for teduglutide to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of teduglutide and consists of the following: elements to assure safe use. See the FDA REMS page ([Web]). |
Teduglutide is a biosynthetic (recombinant DNA origin) analog of human glucagon-like peptide-2 (GLP-2), a pleiotropic hormone that enhances intestinal mucosal growth and affects intestinal function.1, 4, 5, 8, 9, 10, 16, 17
Teduglutide is used for the treatment of short bowel syndrome in adults and pediatric patients ≥1 year of age who are dependent on parenteral support.1 Teduglutide has been designated an orphan drug by FDA for use in this condition.2
In a double-blind, placebo-controlled study, 84 adults with short bowel syndrome who were dependent on parenteral support were randomized in a 2:2:1 ratio to receive teduglutide 0.05 mg/kg, teduglutide 0.1 mg/kg, or placebo subcutaneously daily for 24 weeks.1, 4 In this study, 29% of patients had a stoma (i.e., ileostomy or jejunostomy), and 67% had colon in continuity with small bowel; the mean length of remnant small bowel was 66 cm (range: 6-200 cm).4 Patients who were receiving antidiarrheal and/or antisecretory agents continued to receive stable dosages of these drugs during the study.4 Parenteral support was optimized to achieve urine output of 1-2 L daily and then stabilized prior to randomization.4 The mean baseline parenteral support volume was approximately 1.5 L daily.4 The algorithm employed to adjust parenteral support volume during the study period was based on urinary volume and allowed reduction of parenteral volume by up to 10% of the baseline stabilized parenteral volume every 4 weeks beginning at week 4 after randomization;4 the decision whether to decrease daily parenteral volume or eliminate one of more days of parenteral support per week was left to the discretion of the clinician.4 The primary efficacy end point, a graded categorical score that accounted for intensity and duration of response (as assessed by percent reduction in parenteral support volume at weeks 16, 20, and 24), indicated a difference in response for low-dose teduglutide (0.05 mg/kg) versus placebo but not for high-dose teduglutide (0.1 mg/kg) versus placebo.1, 4 At both 20 and 24 weeks of treatment, weekly parenteral support volume was reduced by at least 20% from baseline in 46, 25, or 6% of patients receiving teduglutide 0.05 mg/kg daily, teduglutide 0.1 mg/kg daily, or placebo, respectively.1, 4 At week 24, the mean reduction in parenteral volume was 2.5 L per week in patients receiving teduglutide 0.05 or 0.1 mg/kg daily and 0.9 L per week in those receiving placebo.1, 4 Parenteral support was discontinued in 2 patients receiving teduglutide 0.05 mg/kg daily and 1 patient receiving teduglutide 0.1 mg/kg daily.1, 4 Neither dosage level of teduglutide was associated with a reduction in the number of days of parenteral support per week.4
Response was maintained after one year of continuous therapy in 75% of patients who responded to teduglutide in this 24-week controlled study and then continued to receive the drug in a blinded, uncontrolled, 28-week extension study.1 After one year of continuous therapy, weekly parenteral support volume was reduced by at least 20% from baseline in 68 or 52% of patients receiving teduglutide 0.05 or 0.1 mg/kg daily, respectively; the mean reduction was 4.9 or 3.3 L per week (corresponding to reductions of 52 or 27%), respectively.1, 12, 18 The decreases in parenteral support volume translated into reductions of one or more days per week of parental support for 68 or 37% of patients receiving teduglutide 0.05 or 0.1 mg/kg daily, respectively.12 The 3 patients who discontinued parenteral support during the controlled trial remained free of parenteral support during the extension study, and one additional patient discontinued parenteral support.1, 12
In another double-blind, placebo-controlled study (STEPS), 86 adults with short bowel syndrome who were dependent on parenteral support were randomized in a 1:1 ratio to receive teduglutide 0.05 mg/kg daily or placebo for 24 weeks.1, 5, 9 In this study, 44% of patients had a stoma, and 57% had colon in continuity with small bowel; the mean length of remnant small bowel was 77 cm (range: 5-343 cm).1, 5 Patients who were receiving antidiarrheal and/or antisecretory agents continued to receive stable dosages of these drugs during the study.5 Parenteral support was optimized to achieve urine output of 1-2 L daily and then stabilized prior to randomization.1, 5 The mean baseline parenteral support volume was nearly 1.9 L daily.5 The algorithm employed to adjust parenteral support volume during the study period was based on urinary volume and allowed reduction of parenteral volume by up to 30% of the baseline stabilized parenteral volume at 2, 4, 8, 12, 16, and 20 weeks;1, 5 the decision whether to decrease daily parenteral volume or eliminate one or more days of parenteral support per week was deferred to clinician judgment and patient preference.5 At both 20 and 24 weeks of treatment, weekly parenteral support volume was reduced by at least 20% from baseline in 63% of patients receiving teduglutide compared with 30% of those receiving placebo; the mean reduction at 24 weeks was 4.4 L per week (32% decrease from baseline) in patients receiving teduglutide compared with 2.3 L per week (21% reduction from baseline) in those receiving placebo.1, 5 No patient in either group discontinued parenteral support; however, the number of days of parenteral support per week was reduced by at least one day in 54% of patients receiving teduglutide compared with 23% of those receiving placebo.1, 5
Response was maintained after 2 years of continuous therapy in 16 of 29 (55%) patients who responded to teduglutide in the 24-week STEPS trial and then continued to receive the drug in an ongoing, open-label, 2-year extension study (STEPS-2).1 After 30 months of continuous therapy, weekly parenteral support volume was reduced by at least 20% from baseline in 93% of patients; the mean reduction was 7.55 L per week (a 66% reduction from baseline).1 In addition, 10 patients discontinued parenteral support while continuing to receive the drug; these patients had required 3.5-13.4 L per week of parenteral support prior to initiation of teduglutide therapy and had received parenteral support for periods of 1.2-15.5 years.1 Additional long-term data with teduglutide administration for up to 42 months in 14 patients revealed that the drug was well tolerated and associated with a sustained response (STEPS-3) with continued reduction in parenteral support; 2 patients achieved parenteral support independence, and an additional 2 patients who achieved parenteral support independence in STEPS-2 maintained enteral autonomy throughout the STEPS-3 trial.23
Safety and efficacy of teduglutide in pediatric patients were established in a 24-week, multicenter study in 59 pediatric patients ≥1 year of age who had short bowel syndrome and were dependent on parenteral support.1, 22 Caregivers of patients could choose their treatment group, either teduglutide or nonblinded standard of care.1, 22 Those who chose to receive teduglutide were stratified by age and randomized 1:1 to either a dosage of 0.025 mg/kg daily or 0.05 mg/kg daily.1, 22 In this study, 19% of patients had a stoma, and 85% had colon in continuity with the small bowel; the mean length of remnant small bowel was 47 cm (range: 9 to 120 cm).1, 22 At 24 weeks of treatment, weekly parenteral support volume was reduced by at least 20% from baseline in 54% of patients receiving teduglutide 0.025 mg/kg daily and in 69% of patients receiving teduglutide 0.05 mg/kg daily compared to 11% of patients receiving standard of care.22 The difference in response rates between the 2 teduglutide groups was not significant.22 The mean decrease from baseline in parenteral support volume at 24 weeks was 36% in patients receiving teduglutide 0.025 mg/kg daily, 42% in patients receiving teduglutide 0.05 mg/kg daily, and 10% in patients receiving standard of care.22 For the patients treated with teduglutide 0.05 mg/kg daily, parenteral support infusions were reduced by an average of 1.3 days weekly.22 Two patients who received the 0.025 mg/kg dose and 3 patients who received the 0.05 mg/kg dose were able to discontinue parenteral support.22 In an open-label, prospective long-term extension study, pediatric patients who completed the original clinical trial could receive additional treatment with teduglutide 0.05 mg/kg daily if they deteriorated or stopped improving after discontinuation of previous teduglutide treatment.1 Thirteen of the 15 (87%) patients who initially responded in the randomized double blind study required additional teduglutide treatment.1 Efficacy results at a mean total treatment duration of 40 weeks were similar to those achieved at the end of the first 24 weeks of treatment in the original study; one additional patient was able to discontinue parenteral support during follow-up.1
A clinical practice update on the management of short bowel syndrome was published by the American Gastroenterological Association (AGA) in 2022.24 According to the AGA, appropriate management of patients with short bowel syndrome requires a comprehensive approach involving specific dietary interventions, medical management, and, occasionally, surgical strategies.24 Pharmacologic therapy in short bowel syndrome frequently involves the administration of antimotility (e.g., loperamide, diphenoxylate with atropine, codeine, tincture of opium, clonidine) and antisecretory (e.g., H2-receptor antagonists, proton pump inhibitors, octreotide) agents.24 Teduglutide is recommended to be administered only in carefully selected patients after optimizing diet and conventional treatments for short bowel syndrome due to its significant adverse effects and cost.24
Administer teduglutide by subcutaneous injection only; do not administer IV or IM.1 Adult patients may self-administer teduglutide if the clinician determines that the patient and/or their caregiver is competent to prepare and safely administer the drug after appropriate training.1 Self-administration in pediatric patients is not recommended.1 Parents or an adult caregiver may administer the drug to pediatric patients if trained by a healthcare provider.1
Administer subcutaneous injections into the abdomen, thighs, and upper arms; rotate injection sites.1
If a dose is missed, administer the missed dose as soon as possible on the same day; do not administer 2 doses to make up for a missed dose.1
Teduglutide is supplied in single-use vials in a kit containing components for reconstitution (i.e., alcohol swabs, prefilled diluent syringes, needles) and administration (i.e., alcohol swabs, dosing syringes with needles).1 Strict aseptic technique must be observed since the drug contains no preservative.1
Reconstitute teduglutide lyophilized powder by slowly injecting the contents of the prefilled diluent syringe (0.5 mL of sterile water for injection) provided by the manufacturer into a vial labeled as containing 5 mg of the drug to yield a solution with a final concentration of 10 mg/mL.1 Allow the vial to stand for approximately 30 seconds, then roll gently between the palms for about 15 seconds.1 Do not shake the vial.1 Thereafter, allow the vial to stand again for approximately 2 minutes.1 If any undissolved material remains, gently roll the vial between the palms once again.1 Do not use solutions containing any undissolved material after this second dissolution attempt.1
Withdraw the desired dose of the reconstituted solution from the vial using the dosing syringe with needle provided by the manufacturer.1 Each reconstituted vial can deliver a maximum volume of 0.38 mL (3.8 mg).1 After reconstitution, administer teduglutide within 3 hours and discard any unused portion.1
Prior to dispensing, refrigerate intact and unopened teduglutide one-vial kits at 2-8°C (do not freeze).1 Once dispensed, store the kits at room temperature up to 25°C.1 Kits can be used up to 90 days after removal from refrigeration.1 Consult the manufacturer's labeling for additional details on preparation and administration of the drug.1
The recommended dosage of teduglutide for the management of short bowel syndrome in adults and pediatric patients ≥1 year of age who are dependent on parenteral support is 0.05 mg/kg once daily.1
Use of the teduglutide 5 mg kit is not recommended in pediatric patients who weigh <10 kg.
The manufacturer makes no special dosage recommendations for patients with mild or moderate hepatic impairment.1 Use of teduglutide in patients with severe hepatic impairment has not been studied.1
In patients with moderate to severe renal impairment (creatinine clearance <60 mL/minute) or end-stage renal disease, reduce dosage of teduglutide by 50% to 0.025 mg/kg once daily.1, 14
No dosage adjustment is necessary in geriatric patients >65 years of age.1
Acceleration of Neoplastic Growth
Because of its mechanism of action and tumor findings in animal carcinogenicity studies, teduglutide has the potential to cause hyperplastic changes, including neoplasia.1 In a 2-year carcinogenicity study in rats receiving teduglutide at dosages approximately 60-700 times the recommended daily human dosage, an increased incidence of benign adenomas of the bile duct and jejunum was observed.1 In clinical studies in adults, GI tract polyps (e.g., colorectal, duodenal, and peristomal polyps, including hyperplastic polyps and villous adenomas) have been detected in patients receiving the drug.1 In pediatric clinical studies, 1 case of cecal polyp was observed and was not seen again on repeat colonoscopy.1 Malignancies have been reported in several adult patients receiving teduglutide, including metastatic adenocarcinoma of unconfirmed origin in a patient who had received prior abdominal irradiation for Hodgkin lymphoma and lung cancer (squamous and non-small cell carcinoma) in 2 patients with a history of smoking.1
Discontinue teduglutide therapy in patients with an active malignancy involving the digestive system (i.e., GI tract, liver, biliary tract, pancreas).1 In patients with a malignancy that is active but does not involve the digestive system, the decision to continue treatment with teduglutide should be made based on evaluation of the risks and benefits.1 In patients at increased risk for malignancy, consider use of teduglutide only if the benefits outweigh the risks.1
During clinical studies, intestinal polyps were reported.1 Cases of colorectal, gastric, and small intestinal polyps have also occurred in the postmarketing setting.1
In adults, perform a colonoscopy and upper GI endoscopy with removal of polyps within 6 months prior to initiating teduglutide therapy.1, 3 A follow-up colonoscopy and upper GI endoscopy (or alternate imaging) is recommended after 1 year of teduglutide therapy; subsequent colonoscopies and upper GI endoscopies (or alternate imaging) should be performed every 5 years thereafter, or more often as indicated.1 The manufacturer states that if a polyp is detected, postpolypectomy surveillance should be performed in accordance with current standards of care.1 Discontinue teduglutide therapy if GI cancer is diagnosed.1
In pediatric patients, perform fecal occult blood testing within 6 months prior to initiating teduglutide therapy.1 If new or unexplained blood is identified in the stool, performance of a colonoscopy/sigmoidoscopy and an upper GI endoscopy is required.1 Annual fecal occult blood testing should be performed throughout the duration of treatment.1 If there is new or unexplained blood in the stool, perform colonoscopy/sigmoidoscopy and an upper GI endoscopy.1 A colonoscopy/sigmoidoscopy is recommended after 1 year of treatment and every 5 years thereafter while on continuous therapy.1 Upper GI endoscopy (or alternate imaging) should be considered during treatment with teduglutide.1 Discontinue teduglutide therapy if GI cancer is diagnosed.1
Cases of intestinal obstruction or stenosis have been reported in patients receiving teduglutide.1 In adult placebo-controlled trials, intestinal obstruction was reported in 3 of 77 patients (4%) receiving teduglutide 0.05 mg/kg daily and 3 of 32 patients (9%) receiving teduglutide 0.1 mg/kg daily; no cases were reported in patients receiving placebo.1 In adult extension studies, 6 additional patients receiving teduglutide 0.05 mg/kg daily were diagnosed with intestinal obstruction or stenosis and 2 of the 6 patients from placebo-controlled studies experienced recurrence of obstruction.1 The onset of intestinal obstruction or stenosis observed in adults has ranged from 1 day to 19 months.1 In pediatric clinical studies, 1 patient had a serious adverse reaction of obstruction; therapy with teduglutide was held until the obstruction resolved and no recurrence was observed after the drug was re-initiated.1
Interrupt teduglutide therapy in patients who develop intestinal or stomal obstruction, and institute appropriate treatment.1 Treatment with the drug may be resumed if clinically indicated when manifestations of obstruction have resolved.1
Gallbladder and Biliary Tract Disease
Cholecystitis, cholangitis, and cholelithiasis have been reported in patients receiving teduglutide.1 Serum concentrations of bilirubin and alkaline phosphatase should be determined within 6 months prior to initiation of teduglutide therapy and at least every 6 months during treatment, or more often as clinically indicated, to identify the onset or worsening of biliary tract disease.1 If clinically important changes in bilirubin or alkaline phosphatase concentrations are observed, further evaluation (e.g., imaging study of the biliary tract) is recommended, and the need for continued therapy with teduglutide should be reassessed.1
Pancreatic disease, including acute and chronic pancreatitis and pancreatic pseudocyst, have been reported in patients receiving teduglutide.1 Serum concentrations of lipase and amylase should be determined within 6 months prior to initiation of teduglutide therapy and at least every 6 months during treatment, or more often as clinically indicated, to identify the onset or worsening of pancreatic disease.1 If clinically important changes in lipase or amylase concentrations are observed, further evaluation (e.g., imaging study of the pancreas) is recommended, and the need for continued therapy with teduglutide should be reassessed.1
Fluid Imbalance and Fluid Overload
Teduglutide increases fluid absorption, which can precipitate or exacerbate congestive heart failure.1, 5 Both fluid overload and congestive heart failure have been reported in clinical trials in patients receiving teduglutide.1 In adult placebo-controlled trials, fluid overload or peripheral edema was reported in 9 of 77 patients (11%) receiving teduglutide 0.05 mg/kg daily and 2 of 59 patients (3%) receiving placebo.1 Congestive heart failure was reported in 2 adult patients (3%) who received teduglutide in placebo-controlled trials; one case was serious.1
Monitor fluid status routinely and adjust parenteral support volume accordingly.1, 3 Patients with cardiovascular disease (e.g., cardiac insufficiency, hypertension) should be monitored for fluid overload, especially during initiation of teduglutide therapy.3 If fluid overload occurs, reduce parenteral support volume and reassess teduglutide therapy, especially in patients with cardiovascular disease.1 If clinically important cardiac deterioration occurs, reassess the need for continued therapy with teduglutide.1 Monitor fluid and electrolyte status in patients who discontinue treatment with teduglutide, as imbalances may occur upon discontinuation.1
Increased GI Absorption of Drugs
Teduglutide may increase intestinal absorption of drugs and should be used with caution in patients receiving concomitant oral therapy with CNS agents (e.g., benzodiazepines, antipsychotic agents), drugs that require dosage titration, or drugs that have a narrow therapeutic index.1, 15
As with all therapeutic proteins, there is a potential for immunogenicity with teduglutide therapy.1 In a 6-month randomized placebo-controlled study followed by a 24-month open-label study in adults with short bowel syndrome, anti-teduglutide antibodies were detected in 2 of 60 (3%), 13 of 77 (17%), 16 of 67 (24%), 11 of 33 (33%), and 14 of 29 (48%) patients receiving the drug at 3, 6, 12, 24, and 30 months, respectively.1 In 5 of 6 patients tested for cross-reactivity, anti-teduglutide antibodies demonstrated cross-reactivity with native glucagon-like peptide-2 (GLP-2).1
In a series of 36 adult patients tested for neutralizing antibodies to teduglutide, 1 patient developed borderline positive neutralizing antibodies at month 24 of the extension study.1 The antibody formation was not associated with any adverse safety findings, reduced efficacy, or altered pharmacokinetics of teduglutide.1
In pediatric patients ≥1 year of age who received teduglutide for 24 weeks, the rate of anti-teduglutide antibody formation was similar to the rate of antibody formation in adult patients, with 5 of 26 (19%) patients who had detectable anti-teduglutide antibodies at 6 months.1 Of the 5 patients who developed antibodies, 2 patients developed neutralizing antibodies at 6 months.1 With longer duration of treatment, anti-teduglutide antibody formation at 12 months was higher in pediatric patients compared to adults, with 14 of 26 (54%) pediatric patients developing antibodies.1 One of these patients had neutralizing antibodies at 12 months.1 The antibody formation was not associated with any adverse safety findings or reduced efficacy in the pediatric population.1
Case reports describing use of teduglutide in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.1 Malnutrition, a risk in pregnant women with untreated short bowel syndrome, is associated with known adverse maternal and fetal outcomes, including preterm delivery, low birth weight, intrauterine growth restriction, congenital malformations, and perinatal mortality.1
Animal reproduction studies demonstrated no effects on embryo-fetal development after subcutaneous administration of teduglutide to pregnant rats and rabbits at exposures up to 686 and 657 times, respectively, the clinical exposure at the recommended human dose.1
It is not known whether teduglutide is distributed into human milk; however, the drug is distributed into milk in rats.1 Because of the potential for serious adverse reactions to teduglutide in nursing infants and because of the tumorigenic potential of the drug in animal studies, breast-feeding is not recommended during treatment with teduglutide.1
Safety and efficacy of teduglutide have not been established in pediatric patients <1 year of age.1
Use of teduglutide in pediatric patients ≥1 year of age is based on evidence from well-controlled studies in adults and additional efficacy, safety, pharmacokinetic, and pharmacodynamic data in pediatric patients in this age group.1 Across two studies of 24-week and 12-week duration, 41 pediatric patients ≥1 year of age were treated with teduglutide 0.05 mg/kg daily.1 In these studies and corresponding extension studies, 29 pediatric patients received teduglutide prospectively for up to 94 weeks; adverse reactions in pediatric patients were similar to those seen in adults.1 In pharmacokinetic studies, similar peak plasma concentrations of teduglutide were noted across all age groups, including pediatric and adult groups.1 However, pediatric patients had lower systemic exposure compared to adults.1
In clinical studies, 14% of patients who received teduglutide at the recommended dosage of 0.05 mg/kg daily were ≥65 years of age and 4% were ≥75 years of age.1 Although no overall differences in safety or efficacy were observed between geriatric patients and younger adults, the possibility of increased sensitivity to the drug in some geriatric patients cannot be ruled out.1 No age-related differences in the pharmacokinetics of teduglutide have been identified in geriatric individuals compared with younger adults.1, 15
Teduglutide has not been studied in patients with severe hepatic impairment (Child-Pugh class C).1 In patients with moderate hepatic impairment (Child-Pugh class B), peak plasma concentrations and systemic exposure to teduglutide following subcutaneous administration of a single 20-mg dose of the drug were about 10-15% lower than values achieved in healthy individuals; such reductions in exposure are unlikely to cause substantial loss of efficacy.1, 15 A population pharmacokinetic analysis of pooled demographic data from this study and other studies in healthy individuals and patients with short bowel syndrome or Crohn disease revealed no relationship between the pharmacokinetic parameters of teduglutide and biochemical markers of hepatic impairment.7
Exposure to teduglutide appears to increase with decreasing renal function.1, 14, 15 Following subcutaneous administration of a single 10-mg dose of teduglutide, peak plasma concentrations and systemic exposure to the drug were increased by 1.4- to 1.6-fold and by 1.5- to 1.7-fold, respectively, in patients with moderate to severe renal impairment and by 2.1- and 2.6-fold, respectively, in patients with end-stage renal disease.1, 14, 15
The most common adverse effects reported in ≥10% of patients receiving teduglutide in clinical trials include abdominal pain, nausea, upper respiratory tract infection, abdominal distension, injection site reaction, vomiting, fluid overload, and hypersensitivity.1
No formal drug interaction studies have been conducted with teduglutide to date.1
Effects on GI Absorption of Oral Drugs
Because teduglutide increases intestinal absorption of fluids and many nutrients, the drug also might increase intestinal absorption of oral medications.1, 15 Altered mental status has been observed in patients receiving benzodiazepines concomitantly with teduglutide during clinical trials.1 One patient receiving a benzodiazepine experienced mental status changes that progressed to coma during the first week of teduglutide therapy; coma resolved 5 days after both drugs were discontinued.1
Use teduglutide with caution in patients receiving concomitant oral therapy with CNS agents (e.g., benzodiazepines, antipsychotic agents), drugs that require dosage titration, or drugs that have a narrow therapeutic index, as dosages of these drugs may need to be adjusted during teduglutide therapy.1
Teduglutide is a biosynthetic analog of human glucagon-like peptide-2 (GLP-2), a pleiotropic hormone that enhances intestinal mucosal growth and affects intestinal function.1, 4, 5, 8, 9, 10, 16, 17 In response to food from enteroendocrine L-cells located predominantly in the terminal ileum and colon, GLP-2 is secreted.1, 4, 5, 8, 9, 10 GLP-2 has been shown to promote growth of intestinal epithelial cells by stimulating crypt cell proliferation and inhibiting apoptosis of crypt and villi cells, thereby increasing the functional mucosal surface area.9, 10, 16, 17 Additionally, GLP-2 has been shown to increase intestinal transit time, inhibit motility and gastric emptying, increase intestinal and portal blood flow, inhibit gastric acid secretion, increase or maintain intestinal barrier function, and enhance fluid and nutrient absorption.1, 4, 5, 8, 9, 10, 16, 17 Teduglutide is prepared from cultures of a modified strain of Escherichia coli using recombinant DNA technology.1 The drug is identical to human GLP-2 except for the substitution of glycine for alanine at position 2 of the 33-amino acid peptide;9, 10 this substitution enhances receptor binding and confers resistance to degradation by dipeptidyl peptidase-4 (DPP-4), which prolongs the half-life from about 7 minutes (for human GLP-2) to about 1-3 hours.4, 5, 6, 7, 9, 10 Binding of teduglutide to GLP-2 receptors located mainly in the small and large intestines in enteroendocrine cells, subepithelial myofibroblasts, and enteric neurons of the submucosal and myenteric plexus results in activation of the receptors and local release of multiple mediators, including insulin-like growth factor I (IGF-I), nitric oxide, and keratinocyte growth factor (KGF).1, 9, 10, 16, 17 Changes in intestinal morphology (increases in villus height and crypt depth) and increased plasma concentrations of citrulline, a biomarker of mucosal mass, have been reported in teduglutide-treated patients with short bowel syndrome.1, 4, 5
Teduglutide is readily absorbed from subcutaneous injection sites; the absolute bioavailability of the drug is approximately 88% and peak plasma concentrations are attained about 3-5 hours after subcutaneous administration in healthy individuals.1, 6 Although the single amino acid substitution at position 2 renders teduglutide resistant to degradation by DPP-4,4, 5, 6, 7, 9, 10 teduglutide is expected to be degraded to small peptides and amino acids via catabolic pathways similar to those of endogenous GLP-2.1 The metabolic pathway of teduglutide has not been investigated in humans, and no inhibition or induction of the cytochrome P-450 (CYP) enzyme system has been observed during in vitro studies.1 Like GLP-2, teduglutide appears to be eliminated mainly by the kidneys.1, 9 Teduglutide has a mean terminal half-life of approximately 2 hours in healthy individuals and 1.3 hours in patients with short bowel syndrome.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Teduglutide can be obtained only through a network of designated specialty pharmacies.20 Additional information available at [Web] or at866-888-0660.20
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for subcutaneous use | 5 mg (delivers 3.8 mg/0.38 mL) | Gattex® (available as a kit with sterile water for injection diluent, needles, syringes, and alcohol swabs) | Takeda Pharmaceuticals |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions March 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Takeda Pharmaceuticals. Gattex® (teduglutide) for injection for subcutaneous use prescribing information. Cambridge, MA; 2024 Sept.
2. Food and Drug Administration. FDA Application: Search Orphan Drug Designations and Approvals. Rockville, MD. From FDA website. [Web]
3. Gattex® (teduglutide) risk evaluation and mitigation strategy (REMS). From FDA website. [Web]
4. Jeppesen PB, Gilroy R, Pertkiewicz M et al. Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut . 2011; 60:902-14. [PubMed 21317170]
5. Jeppesen PB, Pertkiewicz M, Messing B et al. Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology . 2012; 143:1473-1481.e3. [PubMed 22982184]
6. Marier JF, Beliveau M, Mouksassi MS et al. Pharmacokinetics, safety, and tolerability of teduglutide, a glucagon-like peptide-2 (GLP-2) analog, following multiple ascending subcutaneous administrations in healthy subjects. J Clin Pharmacol . 2008; 48:1289-99. [PubMed 18974283]
7. Marier JF, Mouksassi MS, Gosselin NH et al. Population pharmacokinetics of teduglutide following repeated subcutaneous administrations in healthy participants and in patients with short bowel syndrome and Crohn's disease. J Clin Pharmacol . 2010; 50:36-49. [PubMed 19773525]
8. Thompson JS, Weseman R, Rochling FA et al. Current management of the short bowel syndrome. Surg Clin North Am . 2011; 91:493-510. [PubMed 21621693]
9. Vipperla K, O'Keefe SJ. Teduglutide for the treatment of short bowel syndrome. Expert Rev Gastroenterol Hepatol . 2011; 5:665-78. [PubMed 22017694]
10. NOrholk LM, Holst JJ, Jeppesen PB. Treatment of adult short bowel syndrome patients with teduglutide. Expert Opin Pharmacother . 2012; 13:235-43. [PubMed 22224470]
11. Compher C, Gilroy R, Pertkiewicz M et al. Maintenance of parenteral nutrition volume reduction, without weight loss, after stopping teduglutide in a subset of patients with short bowel syndrome. JPEN J Parenter Enteral Nutr . 2011; 35:603-9. [PubMed 21825090]
12. O'Keefe SJ, Jeppesen PB, Gilroy R et al. Safety and Efficacy of Teduglutide After 52 Weeks of Treatment in Patients With Short Bowel Intestinal Failure. Clin Gastroenterol Hepatol . 2013; :. [PubMed 23333663]
14. Nave R, Halabi A, Herzog R et al. Pharmacokinetics of teduglutide in subjects with renal impairment. Eur J Clin Pharmacol . 2013; 69:1149-55. [PubMed 23187965]
15. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 203441Orig1s000: Clinical pharmacology and biopharmaceutics review(s). From FDA website. [Web]
16. Dubé PE, Brubaker PL. Frontiers in glucagon-like peptide-2: multiple actions, multiple mediators. Am J Physiol Endocrinol Metab . 2007; 293:E460-5. [PubMed 17652153]
17. Rowland KJ, Brubaker PL. The “cryptic” mechanism of action of glucagon-like peptide-2. Am J Physiol Gastrointest Liver Physiol . 2011; 301:G1-8. [PubMed 21527727]
18. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 203441Orig1s000: Medical review(s). From FDA website. [Web]
20. Takeda. Starting patients on Gattex®. From Gattex website. Accessed 2025 Feb 10. [Web]
22. Kocoshis SA, Merritt RJ, Hill S et al. Safety and Efficacy of Teduglutide in Pediatric Patients With Intestinal Failure due to Short Bowel Syndrome: A 24-Week, Phase III Study. JPEN J Parenter Enteral Nutr . 2020; 44:621-631. [PubMed 31495952]
23. Seidner DL, Fujioka K, Boullata J, et al. Reduction of parenteral nutrition and hydration support and safety with long-term teduglutide treatment in patients with short bowel syndrome-associated intestinal failure: STEPS-3 study. Nutr Clin Pract . 2018;33:520-7.
24. Iyer K, DiBaise JK, Rubio-Tapia A. AGA clinical practice update on management of short bowel syndrome: expert review. Clin Gastroenterol Hepatol . 2022;20:2185-94.