Introduction
Gattex (teduglutide [rDNA origin]) is a glucagon-like peptide-2 (GLP-2) analog approved for the treatment of Short Bowel Syndrome (SBS) in adults and pediatric patients 1 year of age and older who are dependent on parenteral support. It represents a significant advancement in the management of this chronic condition by promoting intestinal adaptation and potentially reducing the need for parenteral nutrition.
Mechanism of Action
Teduglutide is an analog of naturally occurring human glucagon-like peptide-2 (GLP-2). GLP-2 is a gastrointestinal peptide hormone that regulates digestion and absorption processes in the gut. Gattex works by binding to GLP-2 receptors located on enteroendocrine cells, subepithelial myofibroblasts, and enteric neurons throughout the gastrointestinal tract.
The drug exerts its effects through several mechanisms:
- Stimulation of intestinal epithelial cell proliferation
- Inhibition of gastric acid secretion and gastric emptying
- Enhancement of intestinal blood flow
- Reduction of intestinal permeability
- Promotion of nutrient absorption
These actions collectively contribute to intestinal adaptation, potentially increasing the functional capacity of the remaining intestine in SBS patients.
Indications
Gattex is indicated for:
- Treatment of Short Bowel Syndrome (SBS) in adults dependent on parenteral support
- Treatment of Short Bowel Syndrome (SBS) in pediatric patients 1 year of age and older who are dependent on parenteral support
Dosage and Administration
Adult Patients:- Recommended dose: 0.05 mg/kg once daily
- Administered by subcutaneous injection
- Rotate injection sites between thighs, abdomen, or upper arms
- Recommended dose: 0.05 mg/kg once daily
- Administered by subcutaneous injection
- Renal impairment: No dosage adjustment needed for mild to moderate impairment; use with caution in severe renal impairment
- Hepatic impairment: No specific recommendations; use with caution
- Geriatric patients: No dosage adjustment required
- Reconstitute with provided diluent
- Allow solution to reach room temperature before administration
- Administer at approximately the same time each day
Pharmacokinetics
Absorption:- Bioavailability: Approximately 88% following subcutaneous administration
- Tmax: 3-5 hours after subcutaneous injection
- Volume of distribution: Approximately 103 L
- Protein binding: Not extensively bound to plasma proteins
- Undergoes catabolism by proteolytic enzymes throughout the body
- No significant hepatic metabolism via cytochrome P450 enzymes
- Half-life: Approximately 2 hours in healthy subjects; prolonged in SBS patients
- Clearance: Primarily renal (approximately 40% of administered dose recovered in urine)
- Elimination: Mainly via proteolytic degradation
Contraindications
- History of hypersensitivity to teduglutide or any component of the formulation
- Active gastrointestinal malignancy (current or history within past 5 years)
- History of recurrent gastrointestinal obstruction
Warnings and Precautions
Accelerated Neoplastic Growth:- May stimulate neoplasia in patients with active or recurrent gastrointestinal cancer
- Discontinue if gastrointestinal malignancy is detected
- May cause fluid overload and heart failure due to increased intestinal absorption
- Monitor fluid status, particularly in patients with cardiovascular disease
- Increased incidence of cholecystitis, cholangitis, cholelithiasis, and biliary duct disease
- Monitor with ultrasound at baseline and periodically during treatment
- Increased incidence of pancreatitis
- Monitor pancreatic enzymes at baseline and periodically
- May cause intestinal obstruction; evaluate patients with persistent abdominal symptoms
- May increase absorption of concomitant oral medications
- Monitor for potential increased effects or toxicity
- May cause adenomatous polyps; perform colonoscopy at baseline and periodically
- Patients may develop antibodies to teduglutide
- Clinical significance of antibody development is unknown
Drug Interactions
Oral Medications:- May enhance absorption of concomitant oral medications
- Monitor for increased effects of drugs with narrow therapeutic indices (warfarin, cyclosporine, digoxin)
- Theoretical potential for additive effects; use with caution
- Potential interaction with drugs that alter gastrointestinal transit time
Adverse Effects
Most Common Adverse Reactions (≥10%):- Abdominal pain (30%)
- Injection site reactions (27%)
- Nausea (24%)
- Upper respiratory tract infection (19%)
- Abdominal distension (17%)
- Vomiting (13%)
- Fluid overload (12%)
- Headache (12%)
- Flatulence (10%)
- Intestinal obstruction (2%)
- Pancreatitis (1%)
- Gallbladder and biliary tract disease
- Neoplasms and polyps
- Fluid overload and congestive heart failure
Monitoring Parameters
Baseline Assessment:- Complete medical history and physical examination
- Nutritional status and parenteral support requirements
- Colonoscopy (within 6 months prior to initiation)
- Abdominal ultrasound (gallbladder, biliary tree, pancreas)
- Electrolytes, renal function, liver function tests
- Pancreatic enzymes (amylase, lipase)
- Cardiac function assessment in patients with cardiovascular risk
- Weekly monitoring of fluid status and body weight (first month)
- Monthly assessment of parenteral support requirements
- Quarterly laboratory monitoring (electrolytes, renal function, liver function)
- Semi-annual pancreatic enzyme monitoring
- Annual colonoscopy surveillance
- Annual abdominal ultrasound
- Regular assessment of injection sites
- Growth and development parameters
- Nutritional status assessment
- Age-appropriate fluid status monitoring
Patient Education
Administration Instructions:- Proper technique for subcutaneous injection
- Rotation of injection sites
- Storage and handling requirements
- Recognition and management of injection site reactions
- Report any new or worsening abdominal pain, nausea, or vomiting
- Monitor for signs of fluid overload (weight gain, swelling, shortness of breath)
- Report symptoms of gallbladder disease (right upper quadrant pain, fever, jaundice)
- Recognize signs of pancreatitis (severe abdominal pain radiating to back, nausea, vomiting)
- Importance of maintaining adequate oral hydration
- Dietary recommendations as advised by healthcare provider
- Regular follow-up appointments and monitoring
- Importance of regular cancer screening
- Need for immediate reporting of unusual symptoms
- Understanding potential risks and benefits of therapy
References
1. FDA Prescribing Information: Gattex (teduglutide) [Revised: 2023] 2. 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(6):1473-1481. 3. Carter EP, Youssef NN, Brandt LJ. Long-term efficacy of teduglutide in the treatment of short bowel syndrome. Therap Adv Gastroenterol. 2020;13:1756284820966928. 4. Schwartz LK, O'Keefe SJ, Fujioka K, et al. Long-term safety and efficacy of teduglutide in patients with short bowel syndrome: results from the STEPS-2 study. JPEN J Parenter Enteral Nutr. 2018;42(5):927-934. 5. 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(4):621-631. 6. NICE Technology Appraisal Guidance [TA694]: Teduglutide for treating short bowel syndrome. 2021. 7. American Gastroenterological Association technical review on short bowel syndrome and intestinal transplantation. Gastroenterology. 2003;124(4):1111-1134.
Note: This monograph provides general information and should not replace professional medical advice. Healthcare providers should consult current prescribing information and clinical guidelines for specific patient care decisions.