es. In a randomized, double-blind, placebo-controlled, parallel-group, multi-national, multi-center, clinical trial (Study 1) in adults with SBS, the incidence of anti-GATTEX antibody was 0% (0/16) at Week 12 and 18% (6/34) at Week 24 in subjects who received subcutaneous administration of 0.05 mg/kg GATTEX once daily. The anti-GATTEX antibodies were cross-reactive to native glucagon-like peptide (GLP-2) in five of the six subjects (83%) who had anti-GATTEX antibodies. In the extension study (Study 2), the immunogenicity incidence rate increased over time to 27% (14/51) at 12 months and 38% (13/34) at 18 months. Anti-GATTEX antibodies appear to have no impact on short term (up to 1.5 years) efficacy and safety although the long-term impact is unknown.
A total of 40 subjects were tested for neutralizing antibodies – 20 of these subjects had no neutralizing antibodies, and the remaining 20 subjects had no detectable neutralizing antibodies although, the presence of teduglutide at low levels in these study samples could have resulted in false negatives (no neutralizing antibody detected although present).
Immunogenicity assay results are highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying diseases. For these reasons, comparison of the incidence of antibodies to GATTEX with the incidence of antibodies to other products may be misleading.
Drug Interactions
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, which should be considered if these drugs require titration or have a narrow therapeutic index. [see Warnings and Precautions (5.5)]
Concomitant Drug Therapy
Clinical interaction studies were not performed. No inhibition or induction of the cytochrome P450 enzyme system has been observed based on in vitro studies although the relevance of in vitro studies to an in vivo setting is unknown.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category B
Reproduction studies with teduglutide have been performed in pregnant rats at subcutaneous doses up to 50 mg/kg/day (about 1000 times the recommended daily human dose of 0.05 mg/kg) and in rabbits at subcutaneous doses up to 50 mg/kg/day (about 1000 times the recommended daily human dose of 0.05 mg/kg). These studies did not reveal any evidence of impaired fertility or harm to the fetus due to teduglutide. A pre- and postnatal development study in rats showed no evidence of any adverse effect on pre- and postnatal development at subcutaneous doses up to 50 mg/kg/day (about 1000 times the recommended daily human dose of 0.05 mg/kg). There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, teduglutide should be used during pregnancy only if clearly needed.
Nursing Mothers
It is unknown whether teduglutide is excreted in human milk. Teduglutide is excreted in the milk of lactating rats, and the highest concentration in the milk was 2.9% of the plasma concentration following a single subcutaneous injection of 25 mg/kg. Because many drugs are excreted in human milk; because of the potential for serious adverse reactions to nursing infants from teduglutide and because of the potential for tumorigenici |
