Teduglutide (Gattex) is an analog of GLP -2 (glucagon-like peptide-2) that is secreted in the distal intestine. Endogenous GLP-2 increases the portal and intestinal blood flow while inhibiting the secretion of gastric acid. This results in better absorption and reduces intestinal losses. Unlike the GLP-1 agonist (like dulaglutide and liraglutide), plasma glucose is little impacted by it.

• It is employed in the therapy of short bowel syndrome in adults and pediatric patients who are dependent on parenteral nutrition support.

Teduglutide dose in Adults

Dose in the treatment of Short bowel syndrome:

• 0.05 mg/kg subQ once a day
  • Missed doses:
    • Take as soon as possible if a dose is missed.
    • Two doses shouldn't be taken on the same day if one dosage is missed.

Teduglutide dose in Children

Dose in the treatment of Short bowel syndrome (requiring parenteral support):

• Children and teenagers weighing at least 10 kg or above:
  • 0.05 mg/kg/dose subQ once a day
  • With teduglutide therapy, reductions in parenteral nutrition requirements and advancement of enteral nutrition were observed within 4 weeks.

Pregnancy Risk Factor: B

• Limited data are available on the pregnancy effects of teduglutide.
• Maternal malnutrition may occur in short bowel syndrome. This might result in low birth weight, congenital defects, intrauterine growth restriction, and perinatal death.

Use of Teduglutide during breastfeeding  

• It is unknown if breastmilk contains any data regarding its excretion.
• Due to the possibility of major side effects, such as tumorigenicity, the manufacturer does not advise breastfeeding.

Teduglutide dose in kidney impairment:

• eGFR of 60 mL per minute per 1.73 m2 or more:
  • No dosage change is necessary.
• eGFR of less than 60 mL per minute per 1.73 m2:
  • Once day, lower the dosage to 0.025 mg/kg.
• ESRD:
  • Once day, lower the dosage to 0.025 mg/kg.

Teduglutide dose in liver disease:

• Mild-to-moderate impairment (Child-Pugh class B):
  • Adjustment in the dose is not necessary.
• Severe impairment:
  • Patients with severe hepatic impairment have not been examined with it.
  • No dosage modification has been advised by the manufacturer.

Common Side Effects of Teduglutide (Gattex) Include:

• Endocrine & Metabolic:
  • Fluid Retention
• Miscellaneous:
  • Intestinal Stoma Complication
• Local:
  • Injection Site Reaction
• Immunologic:
  • Antibody Development
• Gastrointestinal:
  • Abdominal Distension
  • Vomiting
  • Abdominal Pain
  • Nausea
• Respiratory:
  • Upper Respiratory Tract Infection

Less Common Side Effects of Teduglutide (Gattex) Include:

• Cardiovascular:
  • Peripheral Edema
  • Cardiac Failure
• Central Nervous System:
  • Sleep Disturbance
• Dermatologic:
  • Dermal Hemorrhage
• Gastrointestinal:
  • Flatulence
  • Decreased Appetite
  • Intestinal Stenosis
  • Pancreatic Disease
  • Cholecystitis
  • Intestinal Obstruction
  • Gallbladder Perforation
• Hypersensitivity:
  • Hypersensitivity Reaction
• Infection:
  • Influenza
• Respiratory:
  • Cough
  • Dyspnea

Frequency Not Defined:

• Cardiovascular:
  • Edema
  • Flushing
  • Jugular Vein Distention
• Dermatologic:
  • Erythema Of Skin
  • Pruritus
  • Skin Rash
• Gastrointestinal:
  • Cholelithiasis
  • Cholestasis
  • Colonic Polyp
  • Pancreatic Pseudocyst
  • Pancreatitis
  • Rectal Polyp
• Hematologic & Oncologic:
  • Hematoma
• Ophthalmic:
  • Eyelid Edema

Contraindication to Teduglutide (Gattex) Include:

• Manufacturers do not list contraindications.

Canadian labeling

• Allergy reactions to teduglutide and any component of the formulation
• Active gastrointestinal malignancy (GI tract or pancreatic),
• The history of GI tract malignancies, including the pancreas, in the past five years.

Warnings and precautions  

• Colorectal polyps
  • Treatment with teduglutide has been shown to cause colorectal polyps.
  • For adults:
    • Do a baseline full-length colonoscopy and remove any polyps at least 6 months before you start therapy.
    • A follow-up colonoscopy should take place every year, and every five years thereafter.
  • For children and adolescents:
    • Do fecal occult blood tests at baseline and every year.
    • If positive for fecal occult blood tests, you should have a colonoscopy or sigmoidoscopy performed.
    • After 1 year, every 5 years thereafter and whenever there is new or unexplained GI bleeding, perform sigmoidoscopy or colonoscopy.
  • Patients with colorectal cancer must stop receiving teduglutide treatments.
• Fluid overload
  • Fluid overload may be caused by increased fluid absorption.
  • Patients with cardiac disease may get congestive heart failure.
  • Patients with significant cardiac disease may require evaluation to continue teduglutide therapy.
• Gallbladder disease and biliary tract diseases:
  • Patients with gallbladder disease or biliary tract diseases should be evaluated. The need for continued teduglutide treatment must also be considered.
  • Cholecystitis and cholelithiasis were reported.
  • Serum bilirubin, alkaline phosphatase, and bilirubin levels should be monitored at the start of treatment and every six months after that.
• Obstructive intestinal disease:
  • Treatment should be stopped temporarily for patients with stomal or intestinal obstruction.
  • Once the obstruction has been removed, treatment can be resumed.
• Malignancy
  • Neoplasia and hyperplastic alterations may become more likely as a result of therapy.
  • Teglutide avoidance should be suggested to those who are more susceptible.
  • Patients with active gastrointestinal cancers (gut, pancreas and hepatobiliary) should stop taking the medication.
  • Patients with a non-GI malignancy must be informed about the drug and the benefits and risks.
  • Small bowel neoplasms should be checked in patients. If detected, the treatment should be stopped and the neoplasm should be removed.
• Pancreatitis
  • Patients who have received GLP agonists have reported pancreatitis.
  • Monitoring serum lipase or amylase at baseline and every 6 months should be done.
  • Patients with pancreatitis must stop taking the medication.

Teduglutide: Drug Interaction

Monitor:

• Monitor serum bilirubin and alkalinephosphatase as well as amylase and lipase at baseline and every 6 months thereafter.
• Patients with heart disease should monitor their fluid status
• Examine your intestinal for signs and symptoms of obstruction.
• Look out for signs that could indicate gallbladder or pancreatitis.
• After treatment is stopped, monitor the electrolyte and fluid balance.
  • Screening adults should take place at the baseline, one-year, and five years, if there is no evidence of a polyp.
  • Screening children and adolescents should begin at the beginning of treatment. This can be done within six months. Then, every year during the course of treatment.
  • A colonoscopy/sigmoidoscopy should always be done on children who have been tested positive for fecal blood.
  • This should be done at baseline and after one year. Then, every five years during treatment. If new or unexplained gastrointestinal bleeding occurs, it will need to be repeated.

How to administer Teduglutide?

• It is administered as a subQ injection.
• The injection site should be rotated between the upper arms, thighs, and quadrants of the abdomen.

IM or IV administration should be avoided.

Adult patients may self administer the injection after appropriate training and instrucitons.

Mechanism of action of Teduglutide:

• Teduglutide, an analog to GLP-2 (glucagonlike peptide-2), is secreted from the distal intestinal tract.Endogenous GLP-2 increases portal blood flow and intestinal blood flow, while inhibiting the production of gastric acid. This improves intestinal absorption and decreases intestinal losses.
• Teduglutide activates GLP-2 by binding to it. This results in the release mediators such as insulin-like growth factors (IGF-1), nitric oxygen and keratinocyte proliferation factor.

Metabolism is similar to endogenous catabolism of GLP-2 but slower because of alterations in a single amino acid substitution.

Bioavailability after SubQ administration is 88%.

Half-life elimination: Children 1 - 11 years: 0.7 ± 0.2 hours Children 12 - 17 years: 1 ± 0.01 hours Adults: 1.3 hours

The time to reach peak plasma concentration after SubQ administration is 3 - 5 hours

Excretion is via Urine

International Brands of Teduglutide:

• Gattex
• Revestive

Teduglutide Brands in Pakistan:

No brands available in Pakistan