(5–50 mg/kg). This fetotoxicity has been similarly noted with other sulfonylureas, such as tolbutamide and tolazamide. The effect is perinatal and believed to be directly related to the pharmacologic (hypoglycemic) action of glipizide. In studies in rats and rabbits no teratogenic effects were found. There are no adequate and well controlled studies in pregnant women. Glipizide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Because recent information suggests that abnormal blood-glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities, many experts recommend that insulin be used during pregnancy to maintain blood-glucose levels as close to normal as possible.
Nonteratogenic Effects
Prolonged severe hypoglycemia (4 to 10 days) has been reported in neonates born to mothers who were receiving a sulfonylurea drug at the time of delivery. This has been reported more frequently with the use of agents with prolonged half-lives. If glipizide is used during pregnancy, it should be discontinued at least one month before the expected delivery date.
Nursing Mothers
Although it is not known whether glipizide is excreted in human milk, some sulfonylurea drugs are known to be excreted in human milk. Because the potential for hypoglycemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. If the drug is discontinued and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.
Pediatric Use
Safety and effectiveness in children have not been established.
Geriatric Use
Of the total number of patients in clinical studies of Glipizide XL, 33 percent were 65 and over. Approximately 1–2 days longer were required to reach steady-state in the elderly. (See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION.) There were no overall differences in effectiveness or safety between younger and older patients, but greater sensitivity of some individuals cannot be ruled out. As such, it should be noted that elderly, debilitated or malnourished patients, and those with adrenal or pituitary insufficiency, are particularly susceptible to the hypoglycemic action of glucose-lowering drugs. Hypoglycemia may be difficult to recognize in the elderly. In addition, in elderly, debilitated or malnourished patients, and patients with impaired renal or hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycemic reactions.
ADVERSE REACTIONS
In U.S. controlled studies the frequency of serious adverse experiences reported was very low and causal relationship has not been established.
The 580 patients from 31 to 87 years of age who received Glipizide XL extended-release tablets in doses from 5 mg to 60 mg in both controlled and open trials were included in the eva luation of adverse experiences. All adverse experiences reported were tabulated independently of their possible causal relation to medication.
Hypoglycemia
See PRECAUTIONS and OVERDOSAGE sections.
Only 3.4% of patients receiving Glipizide XL extended-release tablets had hypoglycemia documented by a blood-glucose measurement <60 mg/dL and/or symptoms believed to be associated with hypoglycemia. In a comparative efficacy study of Glipizide XL and glipizide table
