teduglutide (Rx)

>10%

GI stoma complication (41.9%)

Abdominal pain (30%)

Injection site reactions (22.4%)

Abdominal distension (19.5%)

Nausea (18.2%)

Headaches (15.9%)

Abdominal distension (13.8%)

Upper respiratory tract infection (11.8%)

Fluid overload (11.7%)

Vomiting (11.7%)

1-10%

Flatulence (9.1%)

Hypersensitivity (7.8%)

Appetite disorders (6.5%)

Sleep disturbances (5.2%)

Cough (5.2%)

Skin hemorrhage (5.2%)

Postmarketing Reports

Cardiac disorders: Cardiac arrest, cardiac failure

Nervous system disorders: Cerebral hemorrhage

Acceleration of neoplastic growth

Biliary and pancreatic disease

Intestinal obstruction

Fluid imbalance and overload

Contraindications

None

Cautions

Cholecystitis, cholangitis, cholelithiasis, and pancreatitis reported; assess bilirubin, alkaline phosphatase, and lipase and amylase within 6 months prior to starting treatment, and then every 6 months

Intestinal obstruction reported; discontinue temporarily and restart when obstruction resolves

Discontinuation of treatment may also result in fluid and electrolyte imbalance; monitor fluid and electrolyte status in patients who discontinue treatment

Fluid overload and congestive heart failure observed in clinical trials

Neoplastic growth

• Based on pharmacologic activity and animal findings, has potential to cause hyperplastic changes, including neoplasia
• Discontinue with active GI malignancy
• Small bowel neoplasia observed in rats

• Colorectal polyps

  • Colorectal polyps identified during clinical trials
  • For adults, perform colonoscopy within 6 months before initiating treatment and after 1 year of treatment
  • Colonoscopy/sigmoidoscopy is recommended for all children and adolescents after 1 year of treatment, every 5 years thereafter while on continuous treatment, and if they have new or unexplained gastrointestinal bleeding
  • For children and adolescents, perform fecal occult blood testing before initiating treatment and after 1 year of treatment; colonoscopy/sigmoidoscopy required if there is unexplained blood in the stool
  • See Dosing Considerations for recommendations

Drug interaction overview

• Based on the pharmacodynamic effect of teduglutide, absorption of concomitantly administered oral medications may be increased
• Monitor patients receiving concomitant oral drugs requiring titration or with a narrow therapeutic index for adverse reactions due to potential increased absorption of concomitant drug
• Concomitant drug may require dosage reduction

Pregnancy

Available data from case reports 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; severe malnutrition in pregnant women is associated with preterm delivery, low birth weight, intrauterine growth restriction, congenital malformations and perinatal mortality

Animal data

• In animal reproduction studies, no effects on embryo-fetal development were observed with subcutaneous administration to pregnant rats and rabbits during organogenesis at exposures up to 686 times the clinical exposure at recommended human dose

Lactation

There is no information regarding presence in human milk, effects on the breastfed infant, or on milk production; drug is present in milk of lactating rats; systemic exposure to a breastfed infant is expected to be low; however, because of the potential for serious adverse reactions in a breastfed infant, including tumorigenicity, advise patients that breastfeeding is not recommended during treatment

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Analog of naturally occurring glucagonlike peptide-2 (GLP-2); binds to the GLP-2R receptors located in intestinal subpopulations of enteroendocrine cells, subepithelial myofibroblasts, and enteric neurons of the submucosal and myenteric plexus

Activation of these receptors results in local release of intestinal mediators that increase intestinal absorptive capacity, resulting in increased fluid and nutrient absorption

Absorption

Bioavailability: 88%

Peak plasma time: 3-5 hr

Peak plasma concentration

• 36 ng/mL (adults)
• 29.7 ng/mL (adolescents aged 12-17 yr)
• 33.5 ng/mL (children aged 1-11 yr)

AUC

• 0.15 mcg•hr/mL (adults)
• 154 mcg•hr/mL (adolescents aged 12-17 yr)
• 128 mcg•hr/mL (children aged 1-11 yr)

Distribution

Vd: 103 mL/kg

Metabolism

Expected to be metabolized by hydrolytic degradation (like native BLP-2)

Elimination

Renal clearance: 123 mL/hr/kg (adults)

Excretion: Primarily in urine

Half-life

• 1.3 hr (SBS)
• ~2 hr (healthy volunteers)
• 1 hr (adolescents aged 12-17 yr)
• 0.7 hr (children aged 1-11 yr)

SC Preparation

Reconstitute each vial by slowly injecting 0.5 mL of preservative-free sterile water for injection provided; allow vial to stand for ~30 seconds and then gently roll the vial between your palms for about 15 seconds; DO NOT SHAKE

Allow mixed contents to stand for ~2 minutes, then inspect for any undissolved powder

If undissolved powder observed, gently roll vial again until all material is dissolved; if the product remains undissolved after the second attempt, do not use

Sterile solution should appear, clear, colorless to light straw-colored

Following reconstitution, each vial contains a maximum of 0.38 mL of the reconstituted solution, which contains 3.8 mg of teduglutide for dosing

For single use only; does not contain preservatives; discard unused portion

Use within 3 hr after reconstitution

SC Administration

For adult self-administration or by caregiver administration

For SC injection only; do not administer IV or IM

Alternate injection sites between thighs, arms, and quadrants of the abdomen

Missed dose: Take as soon as possible on that day; do not take 2 doses on the same day

Discontinuation

• Fluid and electrolyte imbalance may occur if discontinued; monitor

Storage

Unopened vial

• Before dispensing

  • Refrigerate vial at 2-8°C (35-45°F)
  • Do not freeze
  • Ancillary supplies from kit may be stored at room temperature up to 25°C (77°F)

• After dispensing by pharmacist

  • Stored at room temperature up to 25°C (77°F); use within 90 days
  • Do not freeze

Reconstituted vial

• Administer within 3 hr after reconstitution; discard any unused portion
• Do not shake or freeze the reconstituted solution
• For single use only