ACARBOSE

Fetal Risk Summary

Acarbose is an oral a-glucosidase inhibitor that delays the digestion of ingested carbohydrates within the gastrointestinal tract, thereby reducing the rise in blood glucose after meals (1). It is used in the management of non-insulin-dependent diabetes mellitus (type II). Less than 2% of a dose is absorbed as active drug in adults, but the systemic absorption of metabolites is much higher (about 34% of the dose) (1).

Reproductive studies in rats found no evidence of impaired fertility or reproductive performance (1). Doses of acarbose up to 9 and 32 times the human dose in pregnant rats and rabbits, respectively, were not teratogenic in either species nor, at 10 times the human dose, not embryotoxic in rabbits (1).

A 1998 non-interventional observational cohort study described the outcomes of pregnancies in women who had been prescribed one or more of 34 newly marketed drugs by general practitioners in England (2). Data were obtained by questionnaires sent to the prescribing physicians one month after the expected or possible date of delivery. In 831 (78%) of the pregnancies, a newly marketed drug was thought to have been taken during the 1st trimester with birth defects noted in 14 (2.5%) singleton births of the 557 newborns (10 sets of twins). In addition, two birth defects were observed in aborted fetuses. However, few of the aborted fetuses were examined. Acarbose was taken during the 1st trimester in five pregnancies. The outcomes of these pregnancies included two spontaneous abortions and three normal newborns (one premature) (2).

No other reports describing the use of acarbose during human pregnancy have been located. Less than 2% of a dose is absorbed systemically, but several metabolites are absorbed in much greater proportions, and the embryo or fetal risk from any of these is unknown. Acarbose is normally used in combination with oral hypoglycemic agents, and these hypoglycemic drugs are not indicated for the pregnant diabetic as they may not provide good control in patients who cannot be controlled by diet alone (3). Carefully prescribed insulin therapy will provide better control of the mother's blood glucose, thereby preventing the fetal and neonatal complications that occur with this disease. High maternal glucose levels, as may occur in diabetes mellitus, are closely associated with a number of maternal and fetal effects, including fetal structural anomalies, if the hyperglycemia occurs early in gestation. To prevent this toxicity, most experts, including the American College of Obstetricians and Gynecologists, recommend that insulin be used for types I and II diabetes occurring during pregnancy and, if diet therapy alone is not successful, for gestational diabetes (4,5).

Breast Feeding Summary

Small amounts of acarbose, or its metabolites, are excreted in the milk of lactating rats (1). No studies describing the use of acarbose during human lactation, or measuring the amount of the drug or its metabolites in milk, have been located. Because the drug acts within the gastrointestinal tract to slow the absorption of ingested carbohydrates, and less than 2% of a dose is absorbed systemically, the amount of unmetabolized drug in the mother's circulation available for transfer to the milk is probably clinically insignificant. As with all drugs, however, the safest course while taking acarbose is not to breast feed until data on its safety during lactation are available.

References

1. Product information. Precose. Bayer Corporation, 1997.
2. Wilton LV, Pearce GL, Martin RM, Mackay FJ, Mann RD. The outcomes of pregnancy in women exposed to newly marketed drugs in general practice in England. Br J Obstet Gynaecol 1998;105:882–9.
3. Friend JR. Diabetes. Clin Obstet Gynecol 1981;8:353–82.
4. American College of Obstetricians and Gynecologists. Diabetes and pregnancy. Technical Bulletin. No. 200. December 1994.
5. Coustan DR. Management of gestational diabetes. Clin Obstet Gynecol 1991;34:558–64.