Teduglutide

Teduglutide is a Glucagon-Like Peptide-2 (GLP-2) Analog belonging to Drug for short bowel syndrome.

Teduglutide is a glucagon-like peptide-2 (GLP-2) analog used to treat patients with Short Bowel Syndrome (SBS) who require parenteral nutritional support.

Teduglutide administered subcutaneously had an absolute bioavailability of 88% and reached maximum plasma teduglutide concentrations at 3 to 5 hours after administration. Teduglutide has a volume of distribution (103 mL/kg) similar to blood volume. In healthy subjects, teduglutide plasma clearance was approximately 123 mL/hr/kg which is similar to the GFR suggesting that teduglutide is primarily cleared by the kidney.

Teduglutide shows side effects like skin problems at the site of injection, hives, rash, itching, red spots on the skin, headache, gas, changes in appetite, difficulty falling asleep or staying asleep, runny nose, sneezing, cough, flu-like symptoms.

Teduglutide is available in the form of injectable solution.

Teduglutide is available in India, US, France, Italy, Russia, Spain, Canada, China, and Australia.

Teduglutide belongs to the Drug for short bowel syndrome acts as a Glucagon-Like Peptide-2 (GLP-2) Analog.

Teduglutide is an analog of naturally occurring human glucagon-like peptide-2 (GLP-2), a peptide secreted by L-cells of the distal intestine. GLP-2 is known to increase intestinal and portal blood flow and inhibit gastric acid secretion. Teduglutide binds to the glucagon-like peptide-2 receptors located in intestinal subpopulations of enteroendocrine cells, subepithelial myofibroblasts and enteric neurons of the submucosal and myenteric plexus. Activation of these receptors results in the local release of multiple mediators including insulin-like growth factor (IGF)-1, nitric oxide and keratinocyte growth factor (KGF).

The Data of Onset and duration of action of Teduglutideis not clinically established.

The Tmax of Teduglutide found to be within 3-5 hours.

Teduglutide is available in the form of injectable solution.

Teduglutide injectable solution given via subcutaneous route.

Teduglutide is a glucagon-like peptide-2 (GLP-2) analog used to treat patients with Short Bowel Syndrome (SBS) who require parenteral nutritional support.

Teduglutide is a Glucagon-Like Peptide-2 (GLP-2) Analog belonging to Drug for short bowel syndrome.

Teduglutide is an analog of naturally occurring human glucagon-like peptide-2 (GLP-2), a peptide secreted by L-cells of the distal intestine. GLP-2 is known to increase intestinal and portal blood flow and inhibit gastric acid secretion. Teduglutide binds to the glucagon-like peptide-2 receptors located in intestinal subpopulations of enteroendocrine cells, subepithelial myofibroblasts and enteric neurons of the submucosal and myenteric plexus. Activation of these receptors results in the local release of multiple mediators including insulin-like growth factor (IGF)-1, nitric oxide and keratinocyte growth factor (KGF).

Teduglutide is approved for use in the following clinical indications

• Short bowel syndrome, parenteral support dependent

Teduglutide is a glucagon-like peptide-2 (GLP-2) analog used to treat patients with Short Bowel Syndrome (SBS) who require parenteral nutritional support.

• Short bowel syndrome, parenteral support dependent

Adult Subcutaneous Dose: 0.05 mg/kg once daily.

Children and Adolescents weighing ≥10 kg:Subcutaneous: 0.05 mg/kg/dose once daily; reductions in parenteral nutrition requirements (including calorie and volume) and advancement of enteral nutrition were observed as early as week 4 of teduglutide therapy in an open-label trial.

Teduglutide is available in various strength as 5mg.

Teduglutide is available in the form of injectable solution.

• Dosage Adjustment in Hepatic impairment Patient

Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): There are no dosage adjustments provided.

• Colorectal polyps

Short bowel syndrome: Development of colorectal polyps has occurred. In adults, perform a baseline colonoscopy of the entire colon with polyp removal ≤6 months prior to initiation of therapy. Follow-up colonoscopy (or alternative imaging) should be performed at 1 year and at least every 5 years thereafter, or more frequent if clinically indicated. In children and adolescents, perform fecal occult blood testing at baseline (prior to therapy) and annually; if unexplained blood detected, perform colonoscopy/sigmoidoscopy. Additionally, perform colonoscopy/sigmoidoscopy after 1 year, every 5 years thereafter during therapy, or for new or unexplained GI bleeding. Discontinue teduglutide in patients who develop colorectal cancer.

• Fluid overload

Increased fluid absorption and subsequent fluid overload/congestive heart failure has been reported; consider modification of parenteral support in patients who develop fluid overload, especially in patients with underlying cardiovascular disease. If significant cardiac deterioration develops, reassess the need for continued teduglutide treatment.

• Gallbladder/biliary tract disease

Cholecystitis, cholangitis, and cholelithiasis have been reported; monitor serum bilirubin and alkaline phosphatase ≤6 month prior to initiation of therapy and at least every 6 months for duration of therapy. If clinically meaningful changes are detected, perform further evaluation including gallbladder/biliary tract imaging and reassess the need for continued teduglutide treatment.

• Intestinal obstruction

Temporarily discontinue treatment in patients that develop intestinal or stomal obstruction; teduglutide may be resumed (if clinically indicated) once the obstruction is resolved.

• Malignancy

Teduglutide may increase the risk of hyperplastic changes, including neoplasia. In patients at increased risk for malignancy, consider treatment only if benefits outweigh the risks. Discontinue treatment in patients with active gastrointestinal malignancy (GI tract, hepatobiliary, pancreatic); evaluate risk versus benefit in patients with active non-GI malignancy. Monitor for small bowel neoplasia; remove any benign neoplasm. Discontinue in patients who develop small bowel cancer.

• Pancreatitis

Pancreatitis has been reported; monitor serum lipase and amylase ≤6 months prior to initiation of therapy and at least every 6 months for duration of therapy. If clinically meaningful changes are detected, evaluate for pancreatitis, and reassess the need for continued teduglutide treatment.

There is no information regarding the presence of teduglutide in human milk, the effects of teduglutide on the breastfed infant, or the effects of teduglutide on milk production. Teduglutide is present in the milk of lactating rats. Systemic exposure of teduglutide to a breastfed infant is expected to be low. However, because of the potential for serious adverse reactions in a breastfed infant, including tumorigenicity, advise patients that breastfeeding is not recommended during treatment with teduglutide.

Available data from case reports with teduglutide use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Pregnant women with short bowel syndrome are at risk for malnutrition, which is associated with adverse maternal and fetal outcomes. In animal reproduction studies, no effects on embryo-fetal development were observed with the subcutaneous administration of teduglutide to pregnant rats and rabbits during organogenesis at exposures up to 686 times the clinical exposure at the recommended human dose. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Common

• Fluid retention, Abdominal pain, nausea, abdominal distension, vomiting, Antibody development, Injection site reaction, Upper respiratory tract infection, Intestinal stoma complication, Peripheral edema, cardiac failure, Sleep disturbance, Dermal hemorrhage, Flatulence, decreased appetite, intestinal stenosis, pancreatic disease, cholecystitis, intestinal obstruction, gallbladder perforation, Hypersensitivity reaction Influenza, Cough, dyspnea.

Rare

• Edema, flushing, jugular vein distention, Erythema of skin, pruritus, skin rash, Cholelithiasis, cholestasis, colonic polyp, pancreatic pseudocyst, pancreatitis, Hematoma, Eyelid edema, Cholangitis, malignant neoplasm.

Potential for Increased Absorption of Oral Medications Based upon the pharmacodynamic effect of teduglutide, there is a potential for increased absorption of concomitant oral medications. Altered mental status has been observed in patients taking teduglutide and benzodiazepines in the adult clinical studies. Monitor patients on concomitant oral drugs requiring titration or with a narrow therapeutic index for adverse reactions related to the concomitant drug while on teduglutide. The concomitant drug may require a reduction in dosage.

The common side effectsof Teduglutide include the following

Common side effects

• Skin problems at the site of injection, hives, rash, itching, red spots on the skin, headache, gas, changes in appetite, difficulty falling asleep or staying asleep, runny nose, sneezing, cough, flu-like symptoms.

Rare side effects

• Rash, pain, swelling, or tenderness in the abdomen (stomach area), swelling and blockage at the stoma opening, fever, chills, change in your stools, difficulty having a bowel movement or passing gas, nausea, vomiting, dark urine, yellowing of the skin or eyes, swelling of the feet or ankles, rapid weight gain, difficulty breathing.

• Pregnancy

Pregnancy Category B

Available data from case reports with teduglutide use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Pregnant women with short bowel syndrome are at risk for malnutrition, which is associated with adverse maternal and fetal outcomes. In animal reproduction studies, no effects on embryo-fetal development were observed with the subcutaneous administration of teduglutide to pregnant rats and rabbits during organogenesis at exposures up to 686 times the clinical exposure at the recommended human dose. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

• Nursing Mothers

There is no information regarding the presence of teduglutide in human milk, the effects of teduglutide on the breastfed infant, or the effects of teduglutide on milk production. Teduglutide is present in the milk of lactating rats. Systemic exposure of teduglutide to a breastfed infant is expected to be low. However, because of the potential for serious adverse reactions in a breastfed infant, including tumorigenicity, advise patients that breastfeeding is not recommended during treatment with teduglutide.

• Pediatric Use

The safety and effectiveness in pediatric patients less than 1 year of age have not been established. The safety and effectiveness of teduglutide have been established in pediatric patients 1 year to less than 17 years of age who are dependent on parenteral support for the treatment of SBS. Use of teduglutide in this population is supported by evidence from adequate and well-controlled studies in adults, with additional efficacy, safety, pharmacokinetic and pharmacodynamic data in pediatric patients 1 year to less than 17 years of age. These data were derived from two studies of 24-week (Study 5) and 12- week duration in which 41 pediatric patients were treated with teduglutide in the following groups: 1 infant (1 year to less than 2 years), 37 children (2 years to less than 12 years) and 3 adolescents (12 years to less than 17 years). In these 2 studies and the corresponding extension studies, 29 pediatric patients were administered teduglutide prospectively for up to 94 weeks. Adverse reactions in pediatric patients were similar to those seen in adults

• Geriatric Use

Of the 134 patients with SBS that were treated with teduglutide at the recommended dosage of 0.05 mg/kg/day in the clinical studies, 19 patients were 65 years or older while 5 patients were 75 years of age or older. No overall differences in safety or efficacy were observed between these patients and younger patients, 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.

Pharmacodynamic

An enhancement of gastrointestinal fluid absorption (750-1000 mL/day) was observed following daily administrations of teduglutide. An increase in villus height and crypt depth of the intestinal mucosa was also noted. A decrease in fecal weight has also been observed. Teduglutide does not prolong the QTc interval.

Pharmacokinetics

• Absorption

In healthy subjects, teduglutide administered subcutaneously had an absolute bioavailability of 88% and reached maximum plasma teduglutide concentrations at 3 to 5 hours after administration

• Distribution

In healthy subjects, teduglutide has a volume of distribution (103 mL/kg) similar to blood volume.

• Metabolism and Excretion

In healthy subjects, teduglutide plasma clearance was approximately 123 mL/hr/kg which is similar to the GFR suggesting that teduglutide is primarily cleared by the kidney.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/203441s013lbl.pdf
• https://www.uptodate.com/contents/teduglutide-drug-information?search=teduglutide&source=panel_search_result&selectedTitle=1~7&usage_type=panel&kp_tab=drug_general&display_rank=1
• https://go.drugbank.com/drugs/DB08900
• https://www.rxlist.com/gattex-drug.htm#clinpharm
• https://www.drugs.com/mtm/teduglutide.html