Teduglutide Disease Interactions

Cholecystitis, cholangitis, cholelithiasis, and pancreatitis have been reported in clinical studies with teduglutide. For identification of the onset or worsening of gallbladder/biliary/pancreatic disease, patients should undergo laboratory assessment of bilirubin, alkaline phosphatase, lipase and amylase within 6 months prior to starting teduglutide, and at least every 6 months while on treatment; or more frequently if needed. If clinically meaningful changes are seen, further evaluation including imaging of the gallbladder, biliary tract and/or pancreas is recommended; and the need for continued teduglutide treatment should be reassessed.

Fluid overload and congestive heart failure have been observed in clinical trials with teduglutide. This was probably related to enhanced fluid absorption associated with the medication. If fluid overload occurs, parenteral support should be adjusted and treatment should be reassessed, especially in patients with underlying cardiovascular disease. If significant cardiac deterioration develops while on teduglutide, the need to continue treatment should be reassessed.

Intestinal obstruction has been reported in clinical trials with teduglutide. In patients who develop intestinal or stomal obstruction, treatment with teduglutide should be temporarily discontinued while the patient is clinically managed. Treatment may be restarted when the obstructive episode resolves, if clinically indicated. Caution is advised in patients with risk factors for intestinal obstruction.

Teduglutide pharmacokinetics has not been assessed in patients with severe hepatic impairment. Caution and monitoring is advised. Patients with moderate hepatic impairment showed lower Cmax and AUC when compared to healthy matched control subjects after a single subcutaneous dose of teduglutide. However, no dose adjustment is necessary for patients with mild and moderate liver impairment.

Based on the pharmacologic activity and findings in animals, teduglutide has the potential to cause hyperplastic changes including neoplasia. In patients at increased risk for malignancy, the clinical decision to use teduglutide should be considered only if the benefits outweigh the risks. In patients with active gastrointestinal malignancy (GI tract, hepatobiliary, pancreatic), therapy should be discontinued. Patients with colorectal polyps, should have these removed within 6 months prior to starting treatment with teduglutide. In patients with active non- gastrointestinal malignancy, the clinical decision to continue therapy should be made based on risk- benefit considerations.

Teduglutide is primarily cleared by the kidney and caution is advised when using in patients with moderate to severe renal impairment. The manufacturers recommend to reduced the dose by 50% in patients with moderate and severe renal impairment (creatinine clearance less than 50 mL/min), and end-stage renal disease.