Medication Guide App

Gattex

Generic Name: Teduglutide
Class: GI Drugs, Miscellaneous
Chemical Name: 2-Glycine-1-33-glucagon-like peptide II (human)
Molecular Formula: C164H252N44O55S
CAS Number: 197922-42-2

Warning(s)

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: communication plan and elements to assure safe use. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Biosynthetic (recombinant DNA origin) analog of human glucagon-like peptide-2 (GLP-2).1 4 5 6 7 8 9 10

Uses for Gattex

Short Bowel Syndrome

Treatment of short bowel syndrome in patients dependent on parenteral support (designated an orphan drug by FDA for use in this condition).1 2 4 5

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Gattex Dosage and Administration

General

Restricted Distribution Program

  • Teduglutide can be obtained only through a network of designated specialty home infusion providers.19 20

  • Clinician and patient must complete a referral form (available at ) that serves as the teduglutide prescription and also registers patient and clinician's office with NPS Advantage, a manufacturer-sponsored program that provides reimbursement assistance and clinical support services for patients and clinicians.19 20 21

  • Additional information available at or at 855-832-6677.20 21

Patient Monitoring

  • Determine urine output (ideally 1–2 L per day) prior to initiation of therapy.3

  • Reassess urine output 2–4 weeks following initiation of therapy; reduce parenteral support volume by 10–30% if urine output has increased from pretreatment levels by ≥10%.3 (See Fluid Overload under Cautions.) Assess patient's tolerance of parenteral volume adjustments 1–2 weeks after implementation.3

  • Monitor urine output regularly and adjust parenteral support volume accordingly, with the goal of reducing or eliminating need for parenteral support while maintaining patient's nutritional status.3

  • Carefully monitor fluid and electrolyte status if drug is discontinued, since fluid and electrolyte imbalance may occur.1

Administration

Administer by sub-Q injection; do not administer IV or IM.1

Patient may self-administer drug after receiving training from healthcare provider.1

Sub-Q Administration

Administer once daily.1

Inject sub-Q into abdomen, thighs, or upper arms; rotate sites.1

If dose is missed, administer missed dose as soon as possible; do not administer 2 doses on same day.1

Reconstitution

Use strict aseptic technique since drug product contains no preservative.1 Vials are for single use only.1

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.1 Reconstituted vial can deliver maximum volume of 0.38 mL (3.8 mg).1

Allow vial to stand for 30 seconds, then roll gently between palms for 15 seconds to dissolve.1 Do not shake vial.1

Allow vial to stand again for about 2 minutes.1 If powder not fully dissolved, attempt to dissolve by rolling between the palms once again.1 Thereafter, discard the vial if any undissolved material remains.1

Use manufacturer-supplied dosing syringe and needle to withdraw desired dose.1

Dosage

Adults

Short Bowel Syndrome
Sub-Q

0.05 mg/kg once daily.1

Special Populations

Hepatic Impairment

No dosage adjustment necessary in patients with mild or moderate hepatic impairment.1 (See Hepatic Impairment under Cautions.)

Not studied in patients with severe hepatic impairment.1

Renal Impairment

In patients with Clcr <50 mL/minute, reduce dosage by 50% (i.e., to 0.025 mg/kg once daily).1 14 (See Special Populations under Pharmacokinetics.)

Geriatric Patients

No dosage adjustment necessary in geriatric patients >65 years of age.1

Cautions for Gattex

Contraindications

  • Manufacturer states none.1

Warnings/Precautions

Acceleration of Neoplastic Growth

Because of its mechanism of action (see Actions), teduglutide has the potential to cause hyperplastic changes, including neoplasia.1 Benign adenomas of the bile duct and jejunem reported in carcinogenicity studies in rats.1 GI tract polyps reported in clinical studies.1

Discontinue teduglutide in patients with an active malignancy involving the digestive tract (i.e., GI tract, liver, biliary tract, pancreas).1 In patients with an active malignancy that does not involve the digestive tract, base decision regarding treatment continuation on evaluation of risks and benefits.1

In patients at increased risk for malignancy, consider use of teduglutide only if benefits outweigh risks.1

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

Monitor patients clinically for small bowel neoplasia.1 Remove any benign neoplasms.1 Discontinue teduglutide if small bowel cancer is diagnosed.1

Intestinal Obstruction

Intestinal obstruction or stenosis reported; onset 1 day to 7 months.1

Interrupt teduglutide therapy in patients with intestinal or stomal obstruction, and institute appropriate treatment.1

May resume teduglutide therapy after resolution of obstruction if clinically indicated.1

Biliary Tract Disease

Cholecystitis, cholangitis, and cholelithiasis reported.1

Determine bilirubin and alkaline phosphatase concentrations within 6 months prior to initiation of therapy.1 Repeat testing at least every 6 months, or more often as indicated, to identify new or worsening disease.1

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.1

Pancreatic Disease

Pancreatic disease (e.g., acute and chronic pancreatitis, pancreatic pseudocyst) reported.1

Determine lipase and amylase concentrations within 6 months prior to initiation of therapy.1 Repeat testing at least every 6 months, or more often as indicated, to identify new or worsening disease.1

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.1

Fluid Overload

Teduglutide increases fluid absorption, which can precipitate or exacerbate heart failure.1 Fluid overload and CHF reported.1

Routinely monitor fluid status and adjust parenteral support volume accordingly.1 3 (See Patient Monitoring under Dosage and Administration.)Monitor patients with cardiovascular disease (e.g., cardiac insufficiency, hypertension), especially during initiation of therapy.3

If fluid overload occurs, reduce parenteral support volume and reassess teduglutide therapy, especially in patients with cardiovascular disease.1

If clinically important cardiac deterioration occurs, reassess need for teduglutide therapy.1

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.1 15 (See Interactions.)

Immunogenicity

Nonneutralizing antiteduglutide antibodies detected.1 5 Do not appear to affect short-term efficacy and safety; however, long-term implications unknown.1

Specific Populations

Pregnancy

Category B.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established.1

Geriatric Use

No overall differences in safety or efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1

Hepatic Impairment

Not studied in patients with severe hepatic impairment.1 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.1 15 (See Special Populations under Pharmacokinetics.)

Renal Impairment

Exposure to teduglutide appears to increase with decreasing renal function.1 14 15 (See Special Populations under Pharmacokinetics and also see Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI stomal complications,1 abdominal pain,1 upper respiratory tract infection,1 nausea,1 abdominal distention,1 vomiting,1 fluid overload,1 flatulence,1 hypersensitivity,1 appetite disorder,1 sleep disturbance,1 cough,1 skin hemorrhage,1 injection site reaction,1 headache.1

Interactions for Gattex

Does not inhibit or induce CYP isoenzymes in vitro.1

No formal drug interaction studies to date.1

Effects on GI Absorption of Drugs

Possible increased absorption of orally administered drugs.1 15

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.1

Specific Drugs

Drug

Interaction

Comments

Antipsychotic agents (e.g., phenothiazines)

Possible increased CNS effects due to increased absorption1

Use with caution; may need to reduce antipsychotic dosage1

Benzodiazepines

Possible increased CNS effects due to increased absorption; altered mental status and coma observed 1

Use with caution; may need to reduce benzodiazepine dosage1

Gattex Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is approximately 88% after sub-Q injection;1 bioavailability is similar following injection into abdomen, thigh, or arm.6 7 15

Peak plasma concentrations attained approximately 3–5 hours following sub-Q administration in healthy individuals.1 6

Distribution

Extent

Distributed into milk in rats; not known whether distributed into human milk.1

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-2.1 Unlike GLP-2, teduglutide is resistant to degradation by dipeptidyl peptidase-4 (DPP-4).4 5 6 7 9 10

Elimination Route

Appears to be eliminated mainly by the kidneys.1 9

Half-life

Terminal half-life: 2 hours in healthy individuals; 1.3 hours in patients with short bowel syndrome.1

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.1 15

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.1 14 15

No age-related differences in pharmacokinetics identified in geriatric individuals compared with younger adults.1 15

Stability

Storage

Parenteral

Powder for Injection

2–8°C; do not freeze.1

After dispensing, vials may be stored at room temperature up to 25°C for up to 90 days.1

Use reconstituted solution within 3 hours.1

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.1 4 5 8 9 10 16 17

  • 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.4 5 6 7 9 10

  • 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).1 9 10 16 17

  • 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.1 4 5

Advice to Patients

  • Importance of providing medication guide to the patient each time the drug is dispensed.1 Importance of patient reading the medication guide before initiating therapy and each time the prescription is refilled.1 13

  • Risk of accelerated neoplastic growth, enhanced growth of colon polyps, intestinal obstruction, biliary and pancreatic disease, and fluid overload.1

  • Importance of undergoing colonoscopy before initiating therapy and at recommended intervals during treatment.1 Importance of clinical monitoring for small bowel neoplasia.1 Importance of discontinuing therapy if a malignancy involving the digestive system is diagnosed; if other malignancy is diagnosed, importance of discussing with clinician whether teduglutide should be discontinued.1

  • Potential for abdominal pain and swelling of stoma, especially upon initiation of therapy.1 Importance of informing clinician if manifestations of intestinal obstruction (e.g., abdominal pain or distention, nausea, vomiting, inability to have a bowel movement) or stomal obstruction occur.1 13

  • Importance of informing clinician if manifestations of cholecystitis, cholangitis, cholelithiasis, or pancreatic disease (e.g., abdominal pain or tenderness, chills, fever, nausea, vomiting, dark urine, jaundice) occur.1 13 Importance of routine laboratory monitoring.1 13

  • Importance of informing clinician if any manifestations of fluid overload or cardiac decompensation (e.g., weight gain, difficulty breathing, swelling of ankles or feet) occur.1 13

  • Importance of instructing patients and/or caregivers regarding proper dosage, preparation, and administration, including use of aseptic technique and safe disposal of needles and syringes.1 Importance of providing patient with a copy of the manufacturer's instructions for use.1

  • If a dose is missed, importance of administering the dose as soon as possible on the same day.1 Importance of not administering >1 dose on the same day.1

  • Risk of fluid and electrolyte imbalance following drug discontinuance.1 Importance of careful monitoring following discontinuance.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1 13 Potential for teduglutide therapy to increase absorption of orally administered drugs.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

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

Distribution of teduglutide is restricted.19 20 (See Restricted Distribution Program under Dosage and Administration.)

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, 2004-2014, Selected Revisions January 22, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. NPS Pharmaceuticals. Gattex (teduglutide) for injection for subcutaneous use prescribing information. Bedminster, NJ; 2012 Dec.

2. Food and Drug Administration. FDA Application: Search Orphan Drug Designations and Approvals. Rockville, MD. From FDA website (http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm). Accessed [2013 02 26]

3. Gattex (teduglutide) risk evaluation and mitigation strategy (REMS). From FDA website. Accessed 2013 Jun 3.

4. Jeppesen PB, Gilroy R, Pertkiewicz M et al. Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut. 2011; 60:902-14. [PubMed 21317170]

5. Jeppesen PB, Pertkiewicz M, Messing B et al. Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology. 2012; 143:1473-1481.e3. [PubMed 22982184]

6. Marier JF, Beliveau M, Mouksassi MS et al. Pharmacokinetics, safety, and tolerability of teduglutide, a glucagon-like peptide-2 (GLP-2) analog, following multiple ascending subcutaneous administrations in healthy subjects. J Clin Pharmacol. 2008; 48:1289-99. [PubMed 18974283]

7. Marier JF, Mouksassi MS, Gosselin NH et al. Population pharmacokinetics of teduglutide following repeated subcutaneous administrations in healthy participants and in patients with short bowel syndrome and Crohn's disease. J Clin Pharmacol. 2010; 50:36-49. [PubMed 19773525]

8. Thompson JS, Weseman R, Rochling FA et al. Current management of the short bowel syndrome. Surg Clin North Am. 2011; 91:493-510. [PubMed 21621693]

9. Vipperla K, O'Keefe SJ. Teduglutide for the treatment of short bowel syndrome. Expert Rev Gastroenterol Hepatol. 2011; 5:665-78. [PubMed 22017694]

10. Nørholk LM, Holst JJ, Jeppesen PB. Treatment of adult short bowel syndrome patients with teduglutide. Expert Opin Pharmacother. 2012; 13:235-43. [PubMed 22224470]

11. Compher C, Gilroy R, Pertkiewicz M et al. Maintenance of parenteral nutrition volume reduction, without weight loss, after stopping teduglutide in a subset of patients with short bowel syndrome. JPEN J Parenter Enteral Nutr. 2011; 35:603-9. [PubMed 21825090]

12. O'Keefe SJ, Jeppesen PB, Gilroy R et al. Safety and Efficacy of Teduglutide After 52 Weeks of Treatment in Patients With Short Bowel Intestinal Failure. Clin Gastroenterol Hepatol. 2013; :. [PubMed 23333663]

13. NPS Pharmaceuticals. Gattex (teduglutide) for injection medication guide. Bedminster, NJ; 2012 Dec.

14. Nave R, Halabi A, Herzog R et al. Pharmacokinetics of teduglutide in subjects with renal impairment. Eur J Clin Pharmacol. 2013; 69:1149-55. [PubMed 23187965]

15. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 203441Orig1s000: Clinical pharmacology and biopharmaceutics review(s). From FDA website.

16. Dubé PE, Brubaker PL. Frontiers in glucagon-like peptide-2: multiple actions, multiple mediators. Am J Physiol Endocrinol Metab. 2007; 293:E460-5. [PubMed 17652153]

17. Rowland KJ, Brubaker PL. The “cryptic” mechanism of action of glucagon-like peptide-2. Am J Physiol Gastrointest Liver Physiol. 2011; 301:G1-8. [PubMed 21527727]

18. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 203441Orig1s000: Medical review(s). From FDA website.

19. NPS Pharmaceuticals. NPS Pharmaceuticals signs agreements with leading specialty home infusion providers to support distribution and home-based clinical care services for Gattex. Bedminster, NJ; 2012 Dec 27. Press release.

20. NPS Pharmaceuticals. Starting patients on Gattex. From Gattex website. Accessed 2013 Jul 25.

21. NPS Pharmaceuticals. Information for healthcare providers. From NPS Advantage website. Accessed 2013 Jul 25.

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