Teduglutide

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Kit, Subcutaneous [preservative free]:

Gattex: 5 mg

Pharmacology

Mechanism of Action

Teduglutide is an analog of glucagon-like peptide-2 (GLP-2), which is secreted in the distal intestine. Endogenous GLP-2 increases intestinal and portal blood flow while inhibiting gastric acid secretion, thereby reducing intestinal losses and improving intestinal absorption. Teduglutide binds and activates GLP-2 receptors, resulting in release of mediators including insulin-like growth factor (IGF)-1, nitric oxide and keratinocyte growth factor (KGF).

Pharmacokinetics/Pharmacodynamics

Distribution

0.1 L/kg

Metabolism

Similar to endogenous catabolism of GLP-2 but slower due to a single amino acid substitution (Ferrone 2006)

Excretion

Urine

Time to Peak

Plasma: SubQ: 3 to 5 hours

Half-Life Elimination

Children 1 to 11 years: 0.7 ± 0.2 hours

Children 12 to 17 years: 1 ± 0.01 hours

Adults: 1.3 hours

Use in Specific Populations

Special Populations: Renal Function Impairment

Teduglutide exposure is increased in patients with moderate or severe renal impairment or ESRD.

Special Populations: Hepatic Function Impairment

Teduglutide exposure is decreased in patients with moderate hepatic impairment.

Use: Labeled Indications

Short bowel syndrome: Treatment of short bowel syndrome in adults and pediatric patients ≥1 year of age who are dependent on parenteral support.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to teduglutide or any component of the formulation; active gastrointestinal (GI) malignancy (GI tract, hepatobiliary, pancreatic); history of GI tract malignancies (including the hepatobiliary system and pancreas) within the last 5 years.

Dosage and Administration

Dosing: Adult

Short bowel syndrome: SubQ: 0.05 mg/kg once daily

Missed doses: If a dose is missed, take as soon as possible on that day; do NOT take 2 doses on the same day.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Short bowel syndrome (requiring parenteral support): Children and Adolescents weighing ≥10 kg: SubQ: 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 (Carter 2017).

Reconstitution

Reconstitute each vial with 0.5 mL of preservative-free SWFI (provided in syringe); let stand for 30 seconds and then roll vial between palms for 15 seconds. Do not shake. Allow vial to stand for an additional ~2 minutes; if undissolved material remains, roll between palms again. If particles are not dissolved after second attempt, discard vial. Once reconstituted, each vial provides 3.8 mg/0.38 mL (concentration is 10 mg/mL).

Administration

SubQ: Rotate injection site between thighs, upper arms, and quadrants of the abdomen. Do not administer IM or IV. Following patient training and instructions on self-administration, adult patients may self-administer treatment.

Storage

Prior to dispensing, store intact vials refrigerated at 2°C to 8°C (36°F to 46°F); do not freeze. The carton of ancillary supplies should be stored at 25°C (77°F). After dispensing, store vials at 25°C (77°F); once dispensed, vials must be used within 90 days. Once reconstituted, store at <25°C (77°F); do not shake or freeze; use within 3 hours. Discard any unused portion.

Drug Interactions

Benzodiazepines: Teduglutide may increase the serum concentration of Benzodiazepines. Monitor therapy

Adverse Reactions

>10%:

Endocrine & metabolic: Fluid retention (1% to 12%)

Gastrointestinal: Abdominal pain (30%), nausea (23%), abdominal distension (20%), vomiting (12%)

Immunologic: Antibody development (3% to 54%; incidence increased with prolonged use)

Local: Injection site reaction (13%)

Respiratory: Upper respiratory tract infection (21%)

Miscellaneous: Intestinal stoma complication (42%)

1% to 10%:

Cardiovascular: Peripheral edema (10%), cardiac failure (3%)

Central nervous system: Sleep disturbance (5%)

Dermatologic: Dermal hemorrhage (5%)

Gastrointestinal: Flatulence (9%), decreased appetite (7%), intestinal stenosis (<5%; including colonic), pancreatic disease (<5%; duct stenosis), cholecystitis (4%), intestinal obstruction (≤4%), gallbladder perforation (1%)

Hypersensitivity: Hypersensitivity reaction (10%)

Infection: Influenza (7%)

Respiratory: Cough (5%), dyspnea (<5%)

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

<1%, postmarketing, and/or case reports: Cholangitis, malignant neoplasm

Warnings/Precautions

Concerns related to adverse effects:

• 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. In children and adolescents, perform fecal occult blood testing at baseline 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 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.

Concurrent drug therapy issues:

• Oral medications: Teduglutide may increase absorption of oral medications; monitor for adverse effects of concomitant oral medications, particularly those with a narrow therapeutic index.

Special populations:

• Renal function impairment: Use with caution; reduced doses required in moderate to severe renal impairment and end-stage renal disease (ESRD).

Other warnings/precautions:

• Discontinuation: Treatment discontinuation may result in fluid and electrolyte imbalance. Carefully monitor fluid/electrolyte status.

Monitoring Parameters

In all patients, serum bilirubin, alkaline phosphatase, lipase, and amylase (baseline [within 6 months prior to initiation] and every 6 months thereafter); monitor fluid status in patients with cardiovascular disease; signs/symptoms of intestinal obstruction; signs/symptoms suggestive of gallbladder disease or pancreatitis; monitor fluid and electrolyte balance following therapy discontinuation. In adults, perform colonoscopy of entire colon with removal of polyps at baseline (within 6 months prior to initiation), 1 year, and ≤5 years thereafter if no polyps found; follow current guidelines if polyps are found. In children/adolescents, test fecal occult blood at baseline (within 6 months prior to initiation) and yearly during treatment; perform colonoscopy/sigmoidoscopy if unexplained blood in stool at baseline and after 1 year of treatment, every 5 years thereafter during treatment, or if new or unexplained GI bleeding occurs.

Pregnancy

Pregnancy Considerations

Information related to use of teduglutide in pregnancy is limited.

Short bowel syndrome may cause maternal malnutrition, which is associated with adverse fetal effects, including congenital malformations, intrauterine growth restriction, low birth weight, perinatal mortality and preterm birth.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience nausea, vomiting, passing gas, common cold symptoms, flu-like signs, lack of appetite, or injection site irritation. Have patient report immediately to prescriber signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of gallstones (pain in the upper right abdominal area, right shoulder area, or between the shoulder blades; yellow skin; or fever with chills),, severe abdominal pain, shortness of breath, excessive weight gain, swelling of arms or legs, severe constipation, abdominal edema, or edema of stoma (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.