teduglutide

Action and Spectrum

Actions and spectrum: 

teduglutide is a synthetic form of a naturally occurring human glucagon-like peptide-2 (GLP-2). It works as a long-acting GLP-2 analog that selectively targets the intestine to promote mucosal growth, increase intestinal blood flow, and improve nutrient absorption. teduglutide has been developed for the treatment of short bowel syndrome (SBS), a condition characterized by malabsorption and malnutrition due to the surgical removal of a significant portion of the small intestine. 

teduglutide is believed to work by stimulating intestinal epithelial cells to increase their surface area, leading to improved nutrient and fluid absorption. It also enhances the secretion of digestive enzymes and inhibits the secretion of gastric acid, which can further improve digestion and absorption in patients with SBS. Additionally, teduglutide can help reduce the need for parenteral nutrition, a form of nutrition that bypasses the digestive system and is given intravenously in patients with SBS. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Vomiting (11.7%) 

Fluid overload (11.7%) 

URTI (11.8%) 

Abdominal distension (13.8%) 

Headaches (15.9%) 

Nausea (18.2%) 

Abdominal distension (19.5%) 

Injection site reactions (22.4%) 

Abdominal pain (30%) 

GI stoma complication (41.9%) 

1-10% 

Sleep disturbances (5.2%) 

Skin hemorrhage (5.2%) 

Cough (5.2%) 

Appetite disorders (6.5%) 

Hypersensitivity (7.8%) 

Flatulence (9.1%)  

Post marketing Reports 

Nervous system: Cerebral hemorrhage 

Biliary and pancreatic disease 

Fluid imbalance and overload 

Cardiac disorders: cardiac failure, Cardiac arrest 

Neoplastic growth acceleration 

Intestinal obstruction 

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

teduglutide is contraindicated in individuals with a history of a known or suspected gastrointestinal or abdominal obstruction, as it may exacerbate the condition. It is also contraindicated in individuals who have a known hypersensitivity to teduglutide or to any of its components.  

Caution: 

teduglutide is contraindicated in patients with a history of multiple endocrine neoplasia syndrome type 2 (MEN 2) or medullary thyroid carcinoma (MTC), as it can cause thyroid tumors. teduglutide should also be used with caution in patients with inflammatory bowel disease (IBD), gastrointestinal cancer or precancerous conditions, and bowel obstruction or adhesions.

Additionally, teduglutide may increase the risk of fluid overload in patients with heart failure or renal impairment. Therefore, caution should be exercised when using teduglutide in these patient populations.  

Comorbidities: 

• Liver disease: teduglutide may increase the risk of liver problems in patients with liver disease, and caution should be exercised when administering the medication in such patients. 
• Kidney disease: The safety and efficacy have not been studied in patients with kidney disease, and caution should be exercised when administering the medication to such patients. 
• Gastrointestinal disorders: Patients with gastrointestinal disorders such as inflammatory bowel disease, diverticulitis, or cancer may be at increased risk of complications with teduglutide therapy, and the medication should be used with caution in such patients. 
• Pancreatitis: teduglutide may increase the risk of pancreatitis and should be used with caution when administering the medication in patients with a history of pancreatitis. 
• Cardiovascular disease: Patients with cardiovascular disease may be at increased risk of adverse effects with teduglutide therapy, and caution should be exercised when administering the medication to such patients. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned 

Lactation: It is unknown whether teduglutide is excreted in human milk  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

teduglutide is a recombinant analog of glucagon-like peptide-2 (GLP-2), a naturally occurring peptide hormone that is involved in the regulation of intestinal growth and function. 

teduglutide binds to and activates the GLP-2 receptor on the intestinal epithelial cells leading to an increase in the growth and proliferation of the epithelial cells, which enhances the absorptive capacity of the intestine.

It also promotes fluid and electrolyte absorption in the intestinal lumen, stimulates intestinal blood flow, and reduces gastrointestinal motility. teduglutide is not significantly absorbed systemically and acts locally in the gastrointestinal tract.  

Pharmacodynamics: 

teduglutide is a glucagon-like peptide-2 (GLP-2) analog that binds to GLP-2 receptors in the intestinal tract. GLP-2 is a naturally occurring hormone that is released after food intake, and it acts on the intestinal epithelium to increase the growth, proliferation, and differentiation of cells that make up the intestinal lining. This results in an increase in the absorptive surface area of the intestine, which leads to improved nutrient absorption and fluid balance. 

teduglutide mimics the action of GLP-2, and it has been shown to increase the size and number of intestinal villi, which are finger-like projections that increase the surface area of the intestinal lining. This promotes the absorption of water and nutrients, and it can help to improve intestinal function in patients with short bowel syndrome (SBS). Additionally, teduglutide has been shown to reduce gastric emptying, which can help to slow down the passage of food through the intestine and improve nutrient absorption.  

Pharmacokinetics: 

Absorption 

Following subcutaneous administration, teduglutide is absorbed slowly with a median Tmax of approximately 2 hours. The absolute bioavailability of teduglutide after subcutaneous administration is approximately 82%. 

Distribution 

The steady-state volume of the distribution of teduglutide is approximately 9.5 L, indicating that it is primarily distributed in the extracellular fluid compartment. 

Metabolism 

teduglutide is expected to undergo proteolytic degradation like endogenous GLP-2. 

Elimination and excretion 

The elimination half-life of teduglutide is approximately 2.5 hours. teduglutide is primarily eliminated via proteolytic degradation and renal clearance. 

Overall, the pharmacokinetic profile of teduglutide supports once-daily dosing. 

Adminstartion

Administration: 

teduglutide is administered as a subcutaneous injection. The injection should be given once daily and can be given at any time of the day, with or without food. The recommended starting dose is 0.05 mg/kg of body weight once daily, which can be increased gradually based on clinical response and tolerability.

The maximum dose should not exceed 0.25 mg/kg once daily. teduglutide should be injected into the thigh or abdomen, and the injection site should be rotated daily to avoid irritation.

Patient Information Leaflet

Patient information leaflet 

Generic Name: teduglutide 

Pronounced: [ TE-due-GLOO-tide]  

Why do we use teduglutide? 

teduglutide is a medication used for the treatment of short bowel syndrome (SBS) in adult patients who are dependent on parenteral support. It is administered subcutaneously once daily and works by stimulating the growth and repair of the intestinal lining, which can increase the absorption of fluids and nutrients from food. teduglutide can also help reduce the frequency and volume of parenteral support required by SBS patients.