kg in the rabbit promoted maternal and/or fetal toxicity. Fetotoxicity was indicated by a slight but significant reduction in fetal weight in the rat study and slight reduction in fetal weight, delayed ossification of the fetal skeleton and increase in the percentage of non-viable fetuses in the rabbit study. In the peri-postnatal study in rats, the NOAEL (No Observed Adverse Effect Level) was 100 mg/kg (corresponding to approximately four times the exposure to humans, based on body surface area). An increase in stillborn progeny was noted at the high dose (300 mg/kg) in the rat peri-postnatal study, but not at the high dose (450 mg/kg) in the delivery segment of the rat developmental toxicity study. Otherwise, there was no adverse effect on survival, growth, development, behavior, or fertility in either the rat developmental toxicity or peri-postnatal studies. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nursing Mothers
Miglitol has been shown to be excreted in human milk to a very small degree. Total excretion into milk accounted for 0.02% of a 100-mg maternal dose. The estimated exposure to a nursing infant is approximately 0.4% of the maternal dose. Although the levels of miglitol reached in human milk are exceedingly low, it is recommended that GLYSET not be administered to a nursing woman.
Pediatric Use
Safety and effectiveness of GLYSET in pediatric patients have not been established.
Geriatric Use
Of the total number of subjects in clinical studies of GLYSET in the United States, patients valid for safety analyses included 24% over 65, and 3% over 75. No overall differences in safety and effectiveness were observed between these subjects and younger subjects. The pharmacokinetics of miglitol were studied in elderly and young males (n=8 per group). At the dosage of 100 mg 3 times daily for 3 days, no differences between the two groups were found.
ADVERSE REACTIONS
Gastrointestinal
Gastrointestinal symptoms are the most common reactions to GLYSET Tablets. In U.S. placebo-controlled trials, the incidences of abdominal pain, diarrhea, and flatulence were 11.7%, 28.7%, and 41.5% respectively in 962 patients treated with GLYSET 25–100 mg 3 times daily, whereas the corresponding incidences were 4.7%, 10.0%, and 12.0% in 603 placebo-treated patients. The incidence of diarrhea and abdominal pain tended to diminish considerably with continued treatment.
Dermatologic
Skin rash was reported in 4.3% of patients treated with GLYSET compared to 2.4% of placebo-treated patients. Rashes were generally transient and most were assessed as unrelated to GLYSET by physician-investigators.
Abnormal Laboratory Findings
Low serum iron occurred more often in patients treated with GLYSET (9.2%) than in placebo-treated patients (4.2%) but did not persist in the majority of cases and was not associated with reductions in hemoglobin or changes in other hematologic indices.
OVERDOSAGE
Unlike sulfonylureas or insulin, an overdose of GLYSET Tablets will not result in hypoglycemia. An overdose may result in transient increases in flatulence, diarrhea, and abdominal discomfort. Because of the lack of extra-intestinal effects seen with GLYSET, no serious systemic reactions are expected in the event of an overdose.
DOSAGE AND ADMINISTRATION
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