Gastrointestinal Agent (Lipase Inhibitor)
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
One report describing the use of orlistat during human pregnancy has 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 β-carotene], D, and E) if a daily multiple vitamin supplement is not taken. The vitamin should be taken 2 hours either 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). If orlistat is used in pregnancy, health care professionals are encouraged to call the toll-free number 800-670-6126 for information about patient enrollment in the Motherisk study.
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 based on BSA (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.
A 2005 case report described the pregnancy outcome of a 33-year-old woman treated with orlistat in the first 8 weeks of an unplanned pregnancy (2). Diseases in the patient included morbid obesity, type 2 diabetes mellitus, hypertension, and hypercholesterolemia. Other drugs used by the woman were glimepiride, ramipril, thiocolchicoside (a muscle relaxant), simvastatin, metformin, ciprofloxacin, and aspirin. When pregnancy was diagnosed at 8 weeks all medications were stopped, and she was started on methyldopa and insulin. She gave birth at 38 weeks to a 3.470-kg female infant with Apgar scores of 5 and 7 at 1 and 5 minutes, respectively. No minor or major malformations were observed in the infant (2).
BREASTFEEDING 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).
References
1.Product information. Xenical. Roche Laboratories, 2000.
2.Kalyoncu NI, Yaris F, Kadioglu M, Kesim M, Ulku C, Yaris E, Unsal M, Dikici M. Pregnancy outcome following exposure to orlistat, ramipril, glimepiride in a woman with metabolic syndrome. Saudi Med J 2005;26:497–9.