Identification

Summary

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

Brand Names
Gattex, Revestive
Generic Name
Teduglutide
DrugBank Accession Number
DB08900
Background

Teduglutide is a glucagon-like peptide-2 (GLP-2) analogue. It is made up of 33 amino acids and is manufactured using a strain of Escherichia coli modified by recombinant DNA technology. Teduglutide differs from GLP-2 by one amino acid (alanine is substituted by glycine). The significance of this substitution is that teduglutide is longer acting than endogenous GLP-2 as it is more resistant to proteolysis from dipeptidyl peptidase-4. FDA approved on December 21, 2012.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Other protein based therapies
Protein Chemical Formula
C164H252N44O55S
Protein Average Weight
3752.0 Da
Sequences
>Protein sequence for teduglutide
HGDGSFSDEMNTILDNLAARDFINWLIQTKITD
Download FASTA Format
Synonyms
  • (Gly2)GLP-2
  • Glucagon-like peptide II (2-glycine) (human)
  • Gly(2)-GLP-2
  • Teduglutida
  • Teduglutide
  • Teduglutide [rDNA origin]
  • Teduglutide Recombinant
External IDs
  • ALX 0600
  • ALX-0600

Pharmacology

Indication

Teduglutide is indicated for the treatment of adults and pediatric patients 1 year of age and older with Short Bowel Syndrome (SBS) who are dependent on parenteral support.4

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

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.

Mechanism of action

Teduglutide is an analog of naturally occurring human glucagon-like peptide-2 (GLP-2), a peptide secreted by L-cells of the distal intestine in response to meals. GLP-2 increases intestinal and portal blood flow and inhibit gastric acid secretion. Teduglutide binds to the glucagon-like peptide-2 receptors located in enteroendocrine cells, subepithelial myofibroblasts and enteric neurons of the submucosal and myenteric plexus. This causes the release of insulin-like growth factor (IGF)-1, nitric oxide and keratinocyte growth factor (KGF). These growth factors may contribute to the increase in crypt cell growth and surface area of the gastric mucosa. Ultimately, absorption through the intestine is enhanced.

TargetActionsOrganism
AGlucagon-like peptide 2 receptor
agonist
Humans
Absorption

The pharmacokinetic profile of teduglutide (when administered subcutaneously) is described by a one-compartment model with first order absorption in the abdomen, arm, and thigh. With escalating doses, teduglutide demonstrates linear pharmacokinetics. Absolute bioavailability, SubQ = 88%; Tmax, SubQ = 3-5 hours;
Cmax, 0.05 mg/kg SubQ, SBS patients = 36 ng/mL; AUC, 0.05 mg/kg SubQ, SBS patients = 0.15 µg•hr/mL; Teduglutide does not accumulate following multiple subcutaneous administrations.

Volume of distribution

Vd, healthy subjects = 103 mL/kg

Protein binding

Not Available

Metabolism

Although a formal investigation has not been conducted, it is expected because teduglutide is a peptide-based drug, it will be degraded into smaller peptides and amino acids via catabolic pathways. The cytochrome P450 enzyme system is not involved in the metabolism of this drug.

Route of elimination

Urine

Half-life

Terminal half-life, healthy subjects = 2 hours; Terminal half-life, SBS patients = 1.3 hours

Clearance

Plasma clearance, healthy subjects = 123 mL/hr/kg; This value indicates that teduglutide is primarily cleared by the kidney.

Adverse Effects
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Toxicity

The most common adverse reactions (≥ 10%) across all studies with GATTEX are abdominal pain, injection site reactions, nausea, headaches, abdominal distension, upper respiratory tract infection. In addition, vomiting and fluid overload were reported in the SBS studies (1 and 3) at rates ≥ 10%.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe serum concentration of 1,2-Benzodiazepine can be increased when it is combined with Teduglutide.
AbacavirAbacavir may decrease the excretion rate of Teduglutide which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Teduglutide which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Teduglutide which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Teduglutide which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Teduglutide which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Teduglutide which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Teduglutide which could result in a higher serum level.
AcrivastineTeduglutide may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Teduglutide which could result in a higher serum level.
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Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
GattexInjection, powder, lyophilized, for solution5 mg/0.5mLSubcutaneousShire-NPS Pharmaceuticals, Inc.2012-12-21Not applicableUS flag
RevestiveKit; Powder, for solution5 mg / vialSubcutaneousTakeda2015-10-28Not applicableCanada flag
RevestiveInjection, powder, for solution5 mgSubcutaneousTakeda Pharmaceuticals International Ag Ireland Branch2020-12-22Not applicableEU flag
RevestiveInjection, powder, for solution1.25 mgSubcutaneousTakeda Pharmaceuticals International Ag Ireland Branch2020-12-22Not applicableEU flag
RevestiveInjection, powder, for solution5 mgSubcutaneousTakeda Pharmaceuticals International Ag Ireland Branch2016-09-08Not applicableEU flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
GattexTeduglutide (5 mg/0.5mL) + Ethanol (0.7 mL/1mL)Injection, powder, lyophilized, for solution; KitSubcutaneous; TopicalShire-NPS Pharmaceuticals, Inc.2012-12-21Not applicableUS flag
GattexTeduglutide (5 mg/0.5mL) + Ethanol (0.7 mL/1mL)Injection, powder, lyophilized, for solution; KitSubcutaneous; TopicalShire-NPS Pharmaceuticals, Inc.2012-12-21Not applicableUS flag

Categories

ATC Codes
A16AX08 — Teduglutide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
7M19191IKG
CAS number
197922-42-2

References

General References
  1. Burness CB, McCormack PL: Teduglutide: a review of its use in the treatment of patients with short bowel syndrome. Drugs. 2013 Jun;73(9):935-47. doi: 10.1007/s40265-013-0070-y. [Article]
  2. Semrad CE: The long road to a new short-bowel therapy: teduglutide for clinical use. Clin Gastroenterol Hepatol. 2013 Jul;11(7):824-5. doi: 10.1016/j.cgh.2013.03.030. Epub 2013 Apr 13. [Article]
  3. Jeppesen PB: Teduglutide, a novel glucagon-like peptide 2 analog, in the treatment of patients with short bowel syndrome. Therap Adv Gastroenterol. 2012 May;5(3):159-71. doi: 10.1177/1756283X11436318. [Article]
  4. FDA Approved Drug Products: Gattex (teduglutide) for subcutaneous injection [Link]
KEGG Drug
D06053
KEGG Compound
C16049
PubChem Substance
347910383
RxNav
1364468
ChEBI
72305
ChEMBL
CHEMBL2104987
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Teduglutide
FDA label
Download (410 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentShort Bowel Syndrome (SBS)2
3CompletedTreatmentShort Bowel Syndrome (SBS)15
3Not Yet RecruitingTreatmentStoma Ileostomy1
3RecruitingTreatmentShort Bowel Syndrome (SBS)1
2CompletedTreatmentAcute Malnutrition, Severe Acute Malnutrition1
2CompletedTreatmentCrohn's Disease (CD)2
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentPostoperative Fistula1
2, 3CompletedBasic ScienceHyperlipidemias3
2, 3RecruitingBasic ScienceHyperlipidemias1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionSubcutaneous5 mg/0.5mL
Injection, powder, lyophilized, for solution; kitSubcutaneous; Topical
Injection, powder, for solutionParenteral; Subcutaneous1.25 MG
Injection, powder, for solutionParenteral; Subcutaneous5 MG
Injection, powder, for solutionSubcutaneous1.25 mg
Kit; powder, for solutionSubcutaneous5 mg / vial
Injection, powder, for solutionSubcutaneous5 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5789379Yes1998-08-042020-10-14US flag
US7056886Yes2006-06-062023-03-18US flag
US7847061Yes2010-12-072026-05-01US flag
US9060992Yes2015-06-232026-05-01US flag
US9555079Yes2017-01-312026-05-01US flag
US9545434Yes2017-01-172026-05-01US flag
US9539310Yes2017-01-102026-05-01US flag
US9545435Yes2017-01-172026-05-01US flag
US9592273Yes2017-03-142026-05-01US flag
US9592274Yes2017-03-142026-05-01US flag
US9572867Yes2017-02-212026-05-01US flag
US9987334Yes2018-06-052026-05-01US flag
US9968658Yes2018-05-152026-05-01US flag
US9981016Yes2018-05-292026-05-01US flag
US9974837Yes2018-05-222026-05-01US flag
US9974835Yes2018-05-222026-05-01US flag
US9981014Yes2018-05-292026-05-01US flag
US9968656Yes2018-05-152026-05-01US flag
US9968655Yes2018-05-152026-05-01US flag
US9987335Yes2018-06-052026-05-01US flag
US9993528Yes2018-06-122026-05-01US flag

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Glucagon receptor activity
Specific Function
This is a receptor for glucagon-like peptide 2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name
GLP2R
Uniprot ID
O95838
Uniprot Name
Glucagon-like peptide 2 receptor
Molecular Weight
63000.84 Da
References
  1. Burness CB, McCormack PL: Teduglutide: a review of its use in the treatment of patients with short bowel syndrome. Drugs. 2013 Jun;73(9):935-47. doi: 10.1007/s40265-013-0070-y. [Article]

Drug created at June 06, 2013 05:11 / Updated at June 03, 2022 07:24