duglutide antibodies appear to have no impact on short term (up to 2.5 years) efficacy and safety although the long-term impact is unknown.
In the same two trials, a total of 36 subjects were tested for neutralizing antibodies: 9 of these subjects had no neutralizing antibodies, and the remaining 27 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.
6.3 Postmarketing ExperienceThe following adverse reactions have been identified during post-approval use of GATTEX. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to GATTEX exposure.
Cardiac disorders: Cardiac Arrest, Cardiac Failure
Nervous system disorders: Cerebral Hemorrhage
7 DRUG INTERACTIONS
7.1 Potential for Increased Absorption of Oral MedicationsBased 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)]
7.2 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.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Category B
Risk Summary
Adequate and well controlled studies with GATTEX have not been conducted in pregnant women. In animal reproduction studies, no effects on embryo-fetal development were observed with the administration of subcutaneous teduglutide at doses up to 1000 times the recommended human dose in both rats and rabbits. Because animal reproductive studies are not always predictive of human response, GATTEX should be used during pregnancy only if clearly needed.
Data
Animal data
In animal studies, no effects on embryo-fetal development were observed in pregnant rats given subcutaneous teduglutide at doses up to 50 mg/kg/day (about 1000 times the recommended daily human dose of 0.05 mg/kg) or pregnant rabbits given subcutaneous doses up to 50 mg/kg/day (about 1000 times the recommended daily human dose of 0.05 mg/kg). 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).
8.3 Nursing MothersIt is not known whether GATTEX is present in human milk. Teduglutide is excreted in the milk of lactating rats, and the highest concentration measured in 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 GATTEX and because of the potential for t |
