Risk Factor: BM
Class: Gastrointestinal agents/ Lipase inhibitor
Fetal Risk Summary
Orlistat is a lipase inhibitor used in the management of obesity. The agent inhibits the absorption of dietary fats. The mechanism of action of orlistat involves bonding to gastric and pancreatic lipases, thereby inactivating these enzymes. The inactive enzymes are unable to hydrolyze dietary fat to absorbable free fatty acids and monoglycerides (1). The systemic bioavailability of orlistat is minimal (1).
Reproduction studies in rats and rabbits at doses up to 23 and 47 times the recommended human daily dose on a body surface area basis (RHD) revealed no evidence of embryotoxicity or teratogenicity (1). In two rat studies, but not in two others, doses of 6 and 23 times the RHD were associated with an increased incidence of dilated cerebral ventricles. At 12 times the RHD in rats, no evidence of impaired fertility was observed (1).
It is not known if orlistat crosses the placenta. Although the molecular weight (about 496) is low enough for passage to the fetus, the minimal systemic bioavailability of the agent following oral administration suggests that little, if any, of the agent would be available for transfer from the maternal circulation.
No reports describing the use of orlistat during human pregnancy have been located. Because of its minimal systemic bioavailability, orlistat appears to present a very low risk, if any, to the embryo or fetus. Orlistat may cause a deficiency of fat-soluble vitamins (vitamins A [both retinol and beta-carotene], D, and E) if a daily multiple vitamin supplement is not taken. The vitamin should be taken either 2 hours before or after an orlistat dose (1). Maternal deficiency of these vitamins may result in fetal adverse effects (see also Vitamin A, Vitamin D, and Vitamin E).
Breast Feeding Summary
No reports describing the use of orlistat during human lactation have been located. The minimal systemic bioavailability suggests that the drug would not be found in breast milk, but maternal hypovitaminosis A, D, and E may occur (see above).
- Product information. Xenical. Roche Laboratories, 2000.