Drugs in Pregnancy and Lactation: Tenth Edition

TEDUGLUTIDE

Gastrointestinal Agent (Glucagon-Like Peptide-2 Analog)

PREGNANCY RECOMMENDATION: No Human Data—Probably Compatible

BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity

PREGNANCY SUMMARY

No reports describing the use of teduglutide in human pregnancy have been located. In the animal data, comparisons to the human dose were based on body weight. Even though such comparisons usually cannot be interpreted, the doses were up to 1000 times the human dose and might suggest low risk. Moreover, the drug is an analog of a naturally occurring peptide secreted by L-cells of the distal intestine (1). Consequently, if indicated the drug should not be withheld because of pregnancy.

FETAL RISK SUMMARY

Teduglutide, given as a daily SC injection, is a 33 amino acid analog of naturally occurring human glucagon-like peptide-2 that is known to increase intestinal and portal blood flow and inhibit gastric acid secretion. It is indicated for the treatment of adult patients with short bowel syndrome (SBS) who are dependent on parenteral support. It is metabolized to inactive components. The mean terminal half-life is about 2 hours in healthy subjects and 1.3 hours in SBS patients (1). However, information regarding plasma protein binding is apparently unknown.

Reproduction studies have been conducted in rats and rabbits. In these species, SC doses up to 1000 times the recommended human daily dose based on body weight (RHDD) did not reveal any evidence of fetal harm or impaired fertility. In addition, no evidence of adverse effects were observed in predevelopment and postdevelopment studies in rats with SC doses up to 1000 times the RHDD (1).

In a 2-year carcinogenicity rat study, teduglutide caused significant increases in the incidence of adenomas in the bile duct and jejunum of male rats. Studies for mutagenicity were negative, as were studies of impaired fertility and reproductive performance in male and female rats (1).

It is not known if teduglutide crosses the human placenta. The molecular weight (about 3752) and the relatively short mean terminal half-life suggest that clinically significant amounts of the drug probably will not reach the embryo or fetus, at least early in gestation.

BREASTFEEDING SUMMARY

No reports describing the use of teduglutide during human lactation have been located. The molecular weight (about 3752) and the relatively short (1.3 hours) mean terminal half-life in SBS patients suggest that the drug will probably not be excreted into breast milk, at least in clinically significant amounts. Even if some excretion did occur, the peptide would probably be digested in the infant’s gut. However, teduglutide is given as a daily SC injection and the manufacturer states that women receiving teduglutide should not breastfeed because of the tumorigenicity shown in rats (1).

Reference

1.Product information. Gattex. NPS Pharmaceuticals, 2013.