Teduglutide

FDA Drug Information • Also known as: Gattex

Brand Names: Gattex
Dosage Form: INJECTION
Product Type: DRUG FOR FURTHER PROCESSING

Description

11 DESCRIPTION The active ingredient in GATTEX (teduglutide) for injection is teduglutide, which is a 33 amino acid glucagon-like peptide-2 (GLP-2) analog manufactured using a strain of Escherichia coli modified by recombinant DNA technology. The chemical composition of teduglutide is L-histidyl-L-glycyl-L-aspartyl-L-glycyl-L-seryl-L-phenylalanyl-L-seryl-L-aspartyl-L-glutamyl-L-methionyl-L-asparaginyl-L-threonyl-L-isoleucyl-L-leucyl-L-aspartyl-L-asparaginyl-L-leucyl-L-alanyl-L-alanyl-L-arginyl-L-aspartyl-L-phenylalanyl-L-isoleucyl-L-asparaginyl-L-tryptophanyl-L-leucyl-L-isoleucyl-L-glutaminyl-L-threonyl-L-lysyl-L-isoleucyl-L-threonyl-L-aspartic acid. The structural formula is: Figure 1: Structural formula of teduglutide Teduglutide has a molecular weight of 3752 Daltons. Teduglutide drug substance is a clear, colorless to light-straw–colored liquid. Each single-dose vial of GATTEX contains 5 mg of teduglutide as a white lyophilized powder for reconstitution and administration by subcutaneous injection. In addition to the active pharmaceutical ingredient (teduglutide), each vial of GATTEX contains 3.434 mg dibasic sodium phosphate heptahydrate, 3.88 mg L-histidine, 15 mg mannitol, and 0.644 mg monobasic sodium phosphate monohydrate as excipients. No preservatives are present. At the time of administration, the lyophilized powder is reconstituted with 0.5 mL of Sterile Water for Injection, which is provided in a single-dose prefilled syringe. A 10 mg/mL sterile solution is obtained after reconstitution. Up to 0.38 mL of the reconstituted solution which contains 3.8 mg of teduglutide can be withdrawn for subcutaneous injection upon reconstitution. Chemical Structure

What Is Teduglutide Used For?

1 INDICATIONS AND USAGE GATTEX ® 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 . GATTEX ® is a glucagon-like peptide-2 (GLP-2) analog 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. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Important Administration Information GATTEX is for adult self-administration or caregiver administration. Self-administration in pediatric patients has not been tested. Use of the GATTEX 5 mg kit is not recommended in pediatric patients weighing less than 10 kg. ( 2.1 ) Evaluation Testing within 6 Months Prior to Starting GATTEX Adult Patients : Perform a colonoscopy and upper GI endoscopy with removal of polyps. ( 2.1 , 5.1 ) Pediatric Patients : Perform fecal occult blood testing. If new or unexplained blood in the stool, perform colonoscopy/sigmoidoscopy and upper GI endoscopy. ( 2.1 , 5.1 ) Adult and Pediatric Patients : Obtain baseline laboratory assessments (bilirubin, alkaline phosphatase, lipase and amylase). ( 2.1 , 5.3 ) Dosage and Administration For subcutaneous use only. ( 2.2 ) The recommended dosage of GATTEX for both adults and pediatric patients is 0.05 mg/kg once daily by subcutaneous injection. ( 2.2 ) Alternate sites between 1 of the 4 quadrants of the abdomen, or into alternating thighs or alternating arms. ( 2.2 ) Dosage Adjustment for Renal Impairment For adult and pediatric patients with moderate and severe renal impairment and end-stage renal disease (estimated glomerular filtration rate less than 60 mL/min/1.73 m 2 ) the recommended dosage is 0.025 mg/kg once daily. ( 2.3 ) Discontinuation When treatment is discontinued, monitor for fluid and electrolyte imbalances. ( 2.5 , 5.4 ) Preparation See full prescribing information for instructions on reconstitution. ( 2.6 ) 2.1 Important Administration Information GATTEX is for adult self-administration or caregiver administration. Self-administration in pediatric patients has not been tested. Use of the GATTEX 5 mg kit is not recommended in pediatric patients weighing less than 10 kg. Evaluation and testing prior to starting treatment with GATTEX: Within 6 months prior to treatment: Adult patients Perform a colonoscopy and an upper gastrointestinal (GI) endoscopy with removal of polyps [see Warnings and Precautions ( 5.1 )] . Obtain baseline laboratory assessments (bilirubin, alkaline phosphatase, lipase and amylase) [see Warnings and Precautions ( 5.3 )] . Pediatric patients Perform fecal occult blood testing; if there is new or unexplained blood in the stool, perform colonoscopy/sigmoidoscopy and an upper GI endoscopy [see Warnings and Precautions ( 5.1 )] . Obtain baseline laboratory assessments (bilirubin, alkaline phosphatase, lipase and amylase) [see Warnings and Precautions ( 5.3 )] . 2.2 Recommended Dosage and Administration for Adults and Pediatric Patients 1 Year of Age and Older GATTEX is for subcutaneous injection only. Not for intravenous or intramuscular administration. The recommended dosage of GATTEX is 0.05 mg/kg once daily administered by subcutaneous injection. If a dose is missed, that dose should be taken as soon as possible on that day. Do not take 2 doses on the same day. Alternation of sites for subcutaneous injection is...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Acceleration of Neoplastic Growth [see Warnings and Precautions ( 5.1 )] Intestinal Obstruction [see Warnings and Precautions ( 5.2 )] Biliary and Pancreatic Disease [see Warnings and Precautions ( 5.3 )] Fluid Imbalance and Fluid Overload [see Warnings and Precautions ( 5.4 )] Most common adverse reactions (≥10%) are: abdominal pain, nausea, upper respiratory tract infection, abdominal distension, injection site reaction, vomiting, fluid overload, and hypersensitivity. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals U.S.A., Inc. at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Adults Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice. The rates of adverse reactions in 136 adult patients with SBS participating in two randomized, placebo-controlled, 24-week, double-blind clinical studies (Study 1 and Study 3) are summarized in Table 1 . Only those reactions with a rate of at least 5% in the GATTEX group, and greater than placebo group, are summarized in Table 1 . Table 1: Common Adverse Reactions Reported at a rate of at least 5% in the GATTEX group, and greater than the placebo group. in Adult Patients with SBS in Placebo-Controlled Studies: Studies 1 and 3 Adverse Reaction Placebo (N=59) (%) GATTEX 0.05 mg/kg Once Daily (N=77) (%) Abdominal pain Includes: Abdominal pain, upper abdominal pain, lower abdominal pain 22 30 Nausea 20 23 Upper respiratory tract infection Includes: Upper respiratory tract infection, nasopharyngitis, pharyngitis, sinusitis, laryngitis, rhinitis, viral upper respiratory tract infection 12 21 Abdominal distension 2 20 Injection site reaction Includes: Injection site hematoma, injection site erythema, injection site pain, injection site swelling, injection site hemorrhage, injection site discoloration, injection site reaction, injection site rash 12 13 Vomiting 10 12 Fluid Overload Includes: Fluid overload, peripheral edema, edema, generalized edema, fluid retention and jugular vein distension 7 12 Hypersensitivity Includes: Erythema, rash, dermatitis allergic, pruritus, rash macular, drug eruption, eyelid edema, flushing 7 10 Flatulence 7 9 Decreased appetite 3 7 Influenza Includes: Influenza, influenza-like illness 2 7 Skin hemorrhage Includes: Hematoma, abdominal wall hematoma, post procedural hematoma, umbilical hematoma, blood blister 2 5 Cough 0 5 Sleep disturbances Includes: Insomnia (3 patients) and hypersomnia (1 patient) 0 5 Adverse Reactions in the Subset of Patients with a Stoma Among the 53 patients with a stoma in the placebo-controlled studies (Study 1 and Study 3), the percentage of patients with gastrointestinal stoma complication was 42% (13/31) for patients receiving GATTEX 0.05 mg/kg/day and 14% (3/22) for patients receiving placebo. Pediatric Patients 1 Year to Less Than 17 Years of Age In two clinical studies of 24-week and 12-week duration, 41 pediatric patients aged 1 year to less than 17 years were treated with GATTEX 0.05 mg/kg/day [see Use in Specific Populations ( 8.4 ), Clinical Studies ( 14.2 )] . Overall, the safety profile of GATTEX was similar to that in adults. In the long-term extension studies with mean exposure of 41 weeks, no new safety signals were identified. Less Common Adverse Reactions Adverse Reactions of Special Interest Malignancy Three patients were diagnosed with malignancy in the SBS clinical studies in adults, all of whom were male and had received GATTEX 0.05 mg/kg/day in Study 2. One patient had a history of abdominal radiation for Hodgkin's disease two decades prior to receiving GATTEX and prior liver lesion on CT scan, and was diagnosed with metastatic adenocarcinoma of...

Drug Interactions

7 DRUG INTERACTIONS 7.1 Potential for Increased Absorption of Oral Medications Based upon the pharmacodynamic effect of GATTEX, there is a potential for increased absorption of concomitant oral medications. Altered mental status has been observed in patients taking GATTEX and benzodiazepines in the adult clinical studies [see Warnings and Precautions ( 5.5 )] . Monitor patients on concomitant oral drugs requiring titration or with a narrow therapeutic index for adverse reactions related to the concomitant drug while on GATTEX. The concomitant drug may require a reduction in dosage.

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Available data from case reports with GATTEX 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 (see Clinical Considerations ) . 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 and 657 times, respectively, the clinical exposure at the recommended human dose (based on AUC) ( see Data ). 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. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Pregnant women with short bowel syndrome are at risk for malnutrition. Severe malnutrition in pregnant women is associated with preterm delivery, low birth weight, intrauterine growth restriction, congenital malformations and perinatal mortality. Data Animal Data Reproduction studies have been performed in pregnant rats at subcutaneous doses of teduglutide up to 25 mg/kg twice daily (50 mg/kg/day) (about 686 times the clinical exposure (AUC) at the recommended daily human dose of 0.05 mg/kg) and in pregnant rabbits at subcutaneous doses up to 25 mg/kg twice daily (50 mg/kg/day) (about 657 times the clinical exposure (AUC) at the recommended daily human dose of 0.05 mg/kg) during the period of organogenesis. These studies did not reveal any evidence of impaired fertility or harm to the fetus due to teduglutide. In a pre- and postnatal...

Overdosage

10 OVERDOSAGE The maximum dose of GATTEX studied during clinical development was 80 mg/day for 8 days. No unexpected systemic adverse reactions were seen. In the event of overdose, the patient should be carefully monitored by the medical professional.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING GATTEX (teduglutide) for injection is supplied as 5 mg of teduglutide as a white, lyophilized powder for reconstitution in a sterile, single-dose glass vial with 0.5 mL Sterile Water for Injection in a single-dose prefilled syringe. The product to be dispensed is either a one-vial kit or a 30-vial kit. One-vial kits are pre-assembled and ready to be used: GATTEX 5 mg One-vial Kit (NDC 68875-0103-1): One single-dose vial of 5 mg teduglutide (NDC 68875-0101-1) One disposable prefilled syringe containing 0.5 mL Sterile Water for Injection USP for reconstitution, with a separate needle (23G × 1½ in) to attach to the syringe One sterile disposable 1 mL syringe with needle (27G × 1/2 in) for dosing Four alcohol swabs Storage and Handling of One-Vial Kit Prior to Dispensing: Store GATTEX 5 mg Strength one-vial kits refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze. Do not use beyond the expiration date on the label. After Dispensing by the Pharmacist: Store GATTEX 5 mg Strength one-vial kits at room temperature up to 25°C (77°F). Do not freeze. Dispense with a 90-day "use by" dating. GATTEX is also supplied in 30-vial cartons to be assembled by the dispensing pharmacist into a 30-vial kit by transferring the trays containing 30 vials from a Carton of Drug Vials into a Carton of Ancillary Supplies : GATTEX 5 mg Carton of Drug Vials (NDC 68875-0101-2): Thirty single-dose vials of GATTEX 5 mg (NDC 68875-0101-1) Carton of Ancillary Supplies : Thirty disposable prefilled syringes containing diluent (0.5 mL Sterile Water for Injection USP) for reconstitution Thirty separate needles (23G × 1½ in) to attach to the syringes for reconstitution Thirty sterile disposable 1 mL syringes with needle (27G × 1/2 in) Sixty alcohol swabs The final assembled 30-Vial Kit should contain the items: GATTEX 5 mg Strength 30-Vial Kit (NDC 68875-0102-1): Thirty single-dose vials of 5 mg teduglutide (NDC 68875-0101-1) Thirty disposable prefilled syringes...

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.