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Teduglutide

Class: GI Drugs, Miscellaneous
Chemical Name: 2-Glycine-1-33-glucagon-like peptide II (human)
Molecular Formula: C164H252N44O55S
CAS Number: 197922-42-2
Brands: Gattex[Web]

Medically reviewed by Drugs.com on Mar 29, 2022. Written by ASHP.

Warning

Risk Evaluation and Mitigation Strategy (REMS):

FDA approved a REMS for teduglutide to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of teduglutide and consists of the following: elements to assure safe use. See https://www.accessdata.fda.gov/scripts/cder/rems/.

Introduction

Biosynthetic (recombinant DNA origin) analog of human glucagon-like peptide-2 (GLP-2).

Uses for Teduglutide

Short Bowel Syndrome

Treatment of short bowel syndrome in adults and pediatric patients ≥1 year of age who are dependent on parenteral support (designated an orphan drug by FDA for use in this condition).

Teduglutide Dosage and Administration

General

Pretreatment Screening

  • In adults, perform a colonoscopy of the entire colon with removal of polyps within 6 months prior to initiation of therapy.

  • In pediatric patients, perform fecal occult blood testing and additional colonoscopy or sigmoidoscopy if unexplained blood in the stool is observed.

  • Obtain baseline laboratory assessments including bilirubin, alkaline phosphatase, lipase, and amylase concentrations in all patients.

  • If possible, determine urine output (ideally 1–2 L per day) prior to initiating therapy.

Patient Monitoring

  • In adults, perform a follow-up colonoscopy (or alternate imaging) at the end of 1 year of therapy and at least every 5 years thereafter, or more frequently if indicated.

  • In pediatric patients, perform annual fecal occult blood testing throughout therapy. Perform a colonoscopy or sigmoidoscopy after 1 year of treatment and every 5 years thereafter, or more often if new unexplained GI bleeding is identified.

  • Obtain laboratory assessments (bilirubin, alkaline phosphatase, lipase, and amylase) in all patients every 6 months during treatment.

  • Monitor fluid and electrolyte status in patients who discontinue treatment.

Administration

Administer by sub-Q injection only; do not administer IV or IM.

Adult patients may self-administer drug after receiving training from healthcare provider. Self-administration in pediatric patients is not recommended.

Sub-Q Administration

Administer once daily.

Inject sub-Q into abdomen, thighs, or upper arms; rotate sites.

If dose is missed, administer missed dose as soon as possible; do not administer 2 doses on same day.

Reconstitution

Use strict aseptic technique since drug product contains no preservative. Vials are for single use only.

Slowly inject contents of manufacturer-supplied prefilled diluent syringe (0.5 mL of sterile water for injection) into vial containing 5 mg of teduglutide to provide a solution containing 10 mg/mL. Reconstituted vial can deliver maximum volume of 0.38 mL (3.8 mg).

Allow vial to stand for 30 seconds, then roll gently between palms for 15 seconds to dissolve. Do not shake vial.

Allow vial to stand again for about 2 minutes. If powder not fully dissolved, attempt to dissolve by rolling between the palms once again. Thereafter, discard the vial if any undissolved material remains.

Use manufacturer-supplied dosing syringe and needle to withdraw desired dose.

Dosage

Pediatric Patients

Short Bowel Syndrome
Sub-Q

Pediatric patients ≥1 year of age: 0.05 mg/kg once daily. Not recommended in pediatric patients weighing <10 kg.

Adults

Short Bowel Syndrome
Sub-Q

0.05 mg/kg once daily.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

In patients with Clcr <60 mL/minute, reduce dosage by 50% (i.e., to 0.025 mg/kg once daily).

Geriatric Patients

No specific dosage recommendations in geriatric patients >65 years of age.

Cautions for Teduglutide

Contraindications

  • Manufacturer states none.

Warnings/Precautions

Acceleration of Neoplastic Growth

Because of its mechanism of action, teduglutide has the potential to cause hyperplastic changes, including neoplasia. Benign adenomas of the bile duct and jejunum reported in carcinogenicity studies in rats. GI tract polyps reported in clinical studies.

Discontinue teduglutide in patients with an active malignancy involving the digestive tract (i.e., GI tract, liver, biliary tract, pancreas). In patients with an active malignancy that does not involve the digestive tract, evaluate risks and benefits of continued treatment.

In patients at increased risk for malignancy, consider use of teduglutide only if benefits outweigh risks.

In adults, obtain baseline colonoscopy of entire colon, with polypectomy as needed, within 6 months prior to initiation of teduglutide. Repeat colonoscopy (or perform alternate imaging study) after 1 year of therapy. Thereafter, perform colonoscopy every 5 years or more often as indicated. If a polyp is detected, manufacturer recommends following current standards of care for postpolypectomy surveillance. Discontinue teduglutide if colorectal cancer is diagnosed.

In pediatric patients, obtain baseline fecal occult blood testing prior to initiation of therapy; perform a colonoscopy or sigmoidoscopy if unexplained blood is identified in the stool. Perform annual fecal occult blood testing throughout duration of therapy. Perform a colonoscopy or sigmoidoscopy after 1 year of treatment and every 5 years thereafter, or if there is new unexplained GI bleeding.

Monitor patients clinically for small bowel neoplasia. Remove any benign neoplasms. Discontinue teduglutide if small bowel cancer is diagnosed.

Intestinal Obstruction

Intestinal obstruction or stenosis reported; onset 1 day to 19 months.

Interrupt teduglutide therapy in patients with intestinal or stomal obstruction, and institute appropriate treatment.

May resume teduglutide therapy after resolution of obstruction if clinically indicated.

Gallbladder and Biliary Tract Disease

Cholecystitis, cholangitis, and cholelithiasis reported.

Determine bilirubin and alkaline phosphatase concentrations within 6 months prior to initiation of therapy. Repeat testing at least every 6 months, or more often as indicated, to identify new or worsening disease.

If clinically important changes in laboratory assessments occur, conduct further diagnostic evaluation (e.g., imaging study of biliary tract) and reassess need for continued therapy.

Pancreatic Disease

Pancreatic disease (e.g., acute and chronic pancreatitis, pancreatic pseudocyst) reported.

Determine lipase and amylase concentrations within 6 months prior to initiation of therapy. Repeat testing at least every 6 months, or more often as indicated, to identify new or worsening disease.

If clinically important changes in laboratory assessments occur, conduct further diagnostic evaluation (e.g., imaging study of the pancreas) and reassess need for continued therapy.

Fluid Imbalance and Fluid Overload

Teduglutide increases fluid absorption, which can precipitate or exacerbate heart failure. Fluid overload and CHF reported.

Routinely monitor fluid status and adjust parenteral support volume accordingly. Monitor patients with cardiovascular disease (e.g., cardiac insufficiency, hypertension), especially during initiation of therapy.

If fluid overload occurs, reduce parenteral support volume and reassess teduglutide therapy, especially in patients with cardiovascular disease.

If clinically important cardiac deterioration occurs, reassess need for teduglutide therapy.

Increased GI Absorption of Drugs

Teduglutide may increase intestinal absorption of drugs; use with caution in patients receiving oral drugs that act on the CNS, require dosage titration, or have a narrow therapeutic index. (See Interactions.)

Immunogenicity

Neutralizing anti-teduglutide antibodies detected. Do not appear to affect short-term efficacy and safety; however, long-term implications unknown.

Specific Populations

Pregnancy

No risk of birth defects, miscarriage, or adverse maternal or fetal outcomes identified. Malnutrition in pregnant women with untreated short bowel syndrome may result in adverse maternal and fetal outcomes, including preterm delivery, low birth weight, intrauterine growth restriction, congenital malformations, and perinatal mortality.

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Also not known if the drug has any effects on the nursing infant or on milk production. Breast-feeding is not recommended.

Pediatric Use

Safety and efficacy not established in children <1 year of age.

Geriatric Use

No overall differences in safety or efficacy relative to younger adults, but increased sensitivity cannot be ruled out.

Hepatic Impairment

Not studied in patients with severe hepatic impairment. Reduced exposure to the drug reported in patients with mild or moderate hepatic impairment, but not of sufficient magnitude to be expected to substantially affect efficacy.

Renal Impairment

Exposure to teduglutide appears to increase with decreasing renal function.

Common Adverse Effects

Most common adverse effects (≥10%): Abdominal pain, nausea, upper respiratory tract infection, abdominal distension, injection site reaction, vomiting, fluid overload, hypersensitivity.

Interactions for Teduglutide

Does not inhibit or induce CYP isoenzymes in vitro.

No formal drug interaction studies to date.

Effects on GI Absorption of Drugs

Possible increased absorption of orally administered drugs.

Use teduglutide with caution in patients receiving oral drugs that act on the CNS, require dosage titration, or have a narrow therapeutic index; may need to adjust dosages of these drugs.

Specific Drugs

Drug

Interaction

Comments

Antipsychotic agents (e.g., phenothiazines)

Possible increased CNS effects due to increased absorption

Use with caution; may need to reduce antipsychotic dosage

Benzodiazepines

Possible increased CNS effects due to increased absorption; altered mental status and coma observed

Use with caution; may need to reduce benzodiazepine dosage

Teduglutide Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is approximately 88% after sub-Q injection; bioavailability is similar following injection into abdomen, thigh, or arm.

Peak plasma concentrations attained approximately 3–5 hours following sub-Q administration in healthy individuals.

Distribution

Extent

Not known whether distributed into human milk.

Elimination

Metabolism

Not investigated in humans; expected to be degraded to small peptides and amino acids via catabolic pathways similar to those of endogenous GLP-2. Unlike GLP-2, teduglutide is resistant to degradation by dipeptidyl peptidase-4 (DPP-4).

Elimination Route

Appears to be eliminated mainly by the kidneys.

Half-life

Terminal half-life: 2 hours in healthy individuals; 1.3 hours in patients with short bowel syndrome.

Special Populations

In patients with moderate hepatic impairment, peak concentrations and AUC after single 20-mg dose are about 10–15% lower than values in healthy individuals.

Peak concentrations and AUC after single 10-mg dose are increased by 1.4- to 1.6-fold and 1.5- to 1.7-fold, respectively, in patients with moderate to severe renal impairment and by 2.1- and 2.6-fold, respectively, in patients with end-stage renal disease.

No age-related differences in pharmacokinetics identified in geriatric individuals compared with younger adults.

Stability

Storage

Parenteral

Powder for Injection

2–8°C; do not freeze.

After dispensing, vials may be stored at room temperature up to 25°C for up to 90 days.

Use reconstituted solution within 3 hours.

Actions

  • GLP-2, a hormone secreted from enteroendocrine L-cells located mainly in the terminal ileum and colon, promotes intestinal mucosal growth by stimulating cell proliferation and inhibiting apoptosis; has been shown to increase intestinal transit time, inhibit motility and gastric emptying, increase intestinal and portal blood flow, inhibit gastric acid secretion, increase or maintain intestinal barrier function, and enhance fluid and nutrient absorption.

  • Teduglutide differs from human GLP-2 by 1 amino acid substitution, which enhances receptor binding and confers resistance to degradation by DPP-4, thereby prolonging the half-life.

  • Teduglutide binds to and activates GLP-2 receptors located in small and large intestines, resulting in local release of mediators, including insulin-like growth factor I (IGF-I), nitric oxide, and keratinocyte growth factor (KGF).

  • Changes in intestinal morphology (increases in villus height and crypt depth) and increased plasma concentrations of citrulline, biomarker of mucosal mass, reported in teduglutide-treated patients with short bowel syndrome.

Advice to Patients

  • Instruct patients to read the medication guide before initiating therapy and each time the prescription is refilled.

  • Advise patients of the risks of accelerated neoplastic growth, enhanced growth of colon polyps, intestinal obstruction, biliary and pancreatic disease, and fluid overload.

  • Instruct patients of the importance of undergoing colonoscopy before initiating therapy and at recommended intervals during treatment, clinical monitoring for small bowel neoplasia, and discontinuing therapy if a malignancy involving the digestive system is diagnosed. If other malignancy is diagnosed, advise patients to discuss with their clinician whether teduglutide should be discontinued.

  • Potential for abdominal pain and swelling of stoma, especially upon initiation of therapy. Advise patients to inform their clinician if manifestations of intestinal obstruction (e.g., abdominal pain or distention, nausea, vomiting, inability to have a bowel movement) or stomal obstruction occur.

  • Advise patients to inform their clinician if manifestations of cholecystitis, cholangitis, cholelithiasis, or pancreatic disease (e.g., abdominal pain or tenderness, chills, fever, nausea, vomiting, dark urine, jaundice) occur and the importance of routine laboratory monitoring.

  • Advise patients to inform their clinician if any manifestations of fluid overload or cardiac decompensation (e.g., weight gain, difficulty breathing, swelling of ankles or feet) occur.

  • Instruct patients and/or caregivers regarding proper dosage, preparation, and administration, including use of aseptic technique and safe disposal of needles and syringes.

  • If a dose is missed, counsel patients to administer the missed dose as soon as possible on the same day. Do no administer more than one dose on the same day.

  • Inform patients of the risk of fluid and electrolyte imbalance following drug discontinuance and the importance of careful monitoring following discontinuance.

  • Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed. Advise women that breast-feeding is not recommended during treatment with teduglutide.

  • Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses. Advise patients regarding the potential for teduglutide therapy to increase absorption of orally administered drugs.

  • Advise patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Teduglutide can be obtained only through a network of designated specialty pharmacies.

Additional information available at [Web] or at 866-888-0660.

Teduglutide (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for subcutaneous use

5 mg (delivers 3.8 mg/0.38 mL)

Gattex (available as a kit with sterile water for injection diluent, needles, syringes, and alcohol swabs)

NPS Pharmaceuticals

AHFS DI Essentials™. © Copyright 2022, Selected Revisions March 29, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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