In late December, FDA approved teduglutide (Gattex—NPS) to treat short bowel syndrome in adult patients who need additional nutrition from I.V. parenteral nutrition. The drug is a glucagon-like peptide-2 (GLP-2) analog that improves intestinal absorption of fluids and nutrients, thereby reducing the frequency and volume of parenteral nutrition. Teduglutide is only the third drug approved to treat adults with short bowel syndrome receiving nutritional support.
Short bowel syndrome is a serious, complex disorder in which the body is unable to absorb enough nutrients and fluids through the gastrointestinal tract to sustain life. The condition typically occurs when a large portion of the intestine has been removed by surgery caused by disease or injury. Patients with short bowel syndrome are commonly infused with parenteral nutrition and I.V. fluids five to seven nights per week for up to 10 to 12 hours at a time. In extreme cases, some patients may receive parenteral support 24 hours a day. Life-threatening complications such as liver damage, serious bloodstream infections, and blood clots can occur with long-term use of parenteral nutrition support.
The overall treatment goal for patients with short bowel syndrome is intestinal rehabilitation, a process of maximizing the digestive and absorptive capacity of the remnant gastrointestinal tract to improve uptake of fluid, electrolytes, and nutrients. In its March 2013 issue, the Journal of Enteral and Parenteral Nutrition published an article by Douglas Seidner, MD, AGAF, FACG, CNSC, and colleagues detailing the clinical considerations and best practice recommendations for intestinal rehabilitation. The authors focused on optimization of fluids, electrolytes, and nutrients; integration of teduglutide therapy; and approaches to parenteral nutrition and fluid weaning.
FDA based its approval of teduglutide on data from two clinical trials and two extension studies. Patients in these trials were randomized to teduglutide or placebo. Results from the two clinical trials showed that 46% and 63% of patients treated with teduglutide achieved a clinical response, defined as achieving at least a 20% reduction in the volume of weekly parenteral nutrition, compared with 6% and 30% of patients in the placebo group. In addition, there was a mean reduction in parenteral nutrition of 2.5 L/wk and 4.4 L/wk in teduglutide-treated patients, compared with 0.9 L/wk and 2.3 L/wk reductions in placebo-treated patients. Data from the two extension studies showed that patients treated with teduglutide experienced a 4.9 L/wk and 5.2 L/wk mean reduction in parenteral nutrition after 1 year of continuous treatment, and six patients in the extension studies were weaned off parenteral nutrition while on teduglutide.
Abdominal pain, injection-site reactions, nausea, headaches, abdominal distension, and upper respiratory tract infection were the most common adverse events in the trials. Teduglutide may also be associated with more serious events such as neoplastic growth and intestinal obstruction (see sidebar). The drug was approved with a Risk Evaluation and Mitigation Strategy to ensure that the benefits of therapy outweigh the risks.
Drug class: Glucagon-like peptide-2 analog
Indication: Treatment of adult patients with short bowel syndrome who are dependent on parenteral support
Dosage: 0.05 mg/kg administered once daily via subcutaneous injection. Alternate injection sites between one of the four quadrants of the abdomen or alternating thighs or arms.
Of note: Teduglutide is associated with a risk of accelerating neoplastic growth; a colonoscopy of the entire colon with removal of polys is recommended before initiating treatment. Teduglutide should be discontinued in those with intestinal malignancy, and the risks and benefits of therapy should be considered in those with nongastrointestinal malignancy.
Give patients the FDA-approved Medication Guide and review the information with them. Explain to patients how to prepare the injection properly and administer teduglutide subcutaneously. Discuss possible injection sites on the abdomen, thighs, and arms, and explain that injection sites should be rotated daily. Review proper disposal of syringes and needles as well as common (e.g., nausea, headaches) and more serious adverse events (e.g., bowel obstruction).