The effect of miglitol (100 mg 3 times daily × 7 days) on the pharmacokinetics of a single 1000-mg dose of metformin was investigated in healthy volunteers. Mean AUC and Cmax values for metformin were 12% to 13% lower when the volunteers were given miglitol as compared with placebo, but this difference was not statistically significant.

In a healthy volunteer study, co-administration of either 50 mg or 100 mg miglitol 3 times daily together with digoxin reduced the average plasma concentrations of digoxin by 19% and 28%, respectively. However, in diabetic patients under treatment with digoxin, plasma digoxin concentrations were not altered by co-administration of miglitol 100 mg 3 times daily × 14 days.

Other healthy volunteer studies have demonstrated that miglitol may significantly reduce the bioavailability of ranitidine and propranolol by 60% and 40%, respectively. No effect of miglitol was observed on the pharmacokinetics or pharmacodynamics of either warfarin or nifedipine.

Intestinal adsorbents (e.g., charcoal) and digestive enzyme preparations containing carbohydrate-splitting enzymes (e.g., amylase, pancreatin) may reduce the effect of GLYSET and should not be taken concomitantly.

In 12 healthy males, concomitantly administered antacid did not influence the pharmacokinetics of miglitol.

Carcinogenesis, Mutagenesis, and Impairment of Fertility
Miglitol was administered to mice by the dietary route at doses as high as approximately 500 mg/kg body weight (corresponding to greater than 5 times the exposure in humans based on AUC) for 21 months. In a two-year rat study, miglitol was administered in the diet at exposures comparable to the maximum human exposures based on AUC. There was no evidence of carcinogenicity resulting from dietary treatment with miglitol.

In vitro, miglitol was found to be nonmutagenic in the bacterial mutagenesis (Ames) assay and the eukaryotic forward mutation assay (CHO/HGPRT). Miglitol did not have any clastogenic effects in vivo in the mouse micronucleus test. There were no heritable mutations detected in dominant lethal assay.

A combined male and female fertility study conducted in Wistar rats treated orally with miglitol at dose levels of 300 mg/kg body weight (approximately 8 times the maximum human exposure based on body surface area) produced no untoward effect on reproductive performance or capability to reproduce. In addition, survival, growth, development, and fertility of the offspring were not compromised.

Pregnancy
Teratogenic Effects
Pregnancy Category B
The safety of GLYSET in pregnant women has not been established. Developmental toxicology studies have been performed in rats at doses of 50, 150 and 450 mg/kg, corresponding to levels of approximately 1.5, 4, and 12 times the maximum recommended human exposure based on body surface area. In rabbits, doses of 10, 45, and 200 mg/kg corresponding to levels of approximately 0.5, 3, and 10 times the human exposure were examined. These studies revealed no evidence of fetal malformations attributable to miglitol. Doses of miglitol up to 4 and 3 times the human dose (based on body surface area), for rats and rabbits, respectively, did not reveal evidence of impaired fertility or harm to the fetus. The highest doses tested in these studies, 450 mg/kg in the rat and 200 mg/