Antidiabetic Agent
PREGNANCY RECOMMENDATION: Human Data Suggest Risk in 3rd Trimester
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
Although the use of tolazamide during human gestation does not appear to be related to structural anomalies, insulin is still the treatment of choice for this disease. Oral hypoglycemics might not be indicated for the pregnant diabetic. Moreover, insulin, unlike tolazamide, does not cross the placenta and, thus, eliminates the additional concern that the drug therapy is adversely affecting the fetus. 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 adverse effects, including structural anomalies if the hyperglycemia occurs early in gestation. To prevent this toxicity, the American College of Obstetricians and Gynecologists recommends that insulin be used for types 1 and 2 diabetes occurring during pregnancy and, if diet therapy alone is not successful, for gestational diabetes (1,2). If tolazamide is used during pregnancy, therapy should be changed to insulin and tolazamide discontinued before delivery (the exact time before delivery is unknown) to lessen the possibility of prolonged hypoglycemia in the newborn.
FETAL RISK SUMMARY
Tolazamide is a sulfonylurea used for the treatment of adult-onset diabetes mellitus. It is not indicated for the pregnant diabetic.
No reports describing the placental transfer of tolazamide have been located. The molecular weight (about 311) suggests that transfer to the fetus probably occurs (see Chlorpropamide).
A 1991 report described the outcomes of pregnancies in 21 noninsulin-dependent diabetic women who were treated with oral hypoglycemic agents (17 sulfonylureas, 3 biguanides, and 1 unknown type) during the 1st trimester (3). The duration of exposure ranged from 3 to 28 weeks, but all patients were changed to insulin therapy at the first prenatal visit. Forty noninsulin-dependent diabetic women matched for age, race, parity, and glycemic control served as a control group. Eleven (52%) of the exposed infants had major or minor congenital malformations compared with six (15%) of the controls. Moreover, ear defects, a malformation that is observed, but uncommonly, in diabetic embryopathy, occurred in six of the exposed infants and in none of the controls (1). One of the infants with an ear defect (thickened curved pinnae and malformed superior helices) was exposed in utero to tolazamide during the first 12 weeks of gestation. Sixteen live births occurred in the exposed group compared with 36 in controls. The groups did not differ in the incidence of hypoglycemia at birth (53% vs. 53%), but three of the exposed newborns had severe hypoglycemia lasting 2, 4, and 7 days even though the mothers had not used oral hypoglycemics (none of the three was exposed to tolazamide) close to delivery. The authors attributed this to irreversible β-cell hyperplasia that may have been increased by exposure to oral hypoglycemics. Hyperbilirubinemia was noted in 10 (67%) of 15 exposed newborns compared with 13 (36%) controls (p <0.04), and polycythemia and hyperviscosity requiring partial exchange transfusions were observed in 4 (27%) of 15 exposed vs. 1 (3.0%) control (p <0.03) (1 exposed infant was not included in these data because the infant was delivered after completion of the study) (3).
BREASTFEEDING SUMMARY
No reports describing the use of tolazamide during human lactation have been located. The molecular weight (about 311) is low enough that excretion in milk should be expected (see Chlorpropamide). The effect of exposure to the drug in milk on the nursing infant is unknown, but hypoglycemia is a potential toxicity.
References
1.American College of Obstetricians and Gynecologists. Pregestational diabetes mellitus. ACOG Practice Bulletin. No. 60. March 2005. Obstet Gynecol 2005;105:675–85.
2.American College of Obstetricians and Gynecologists. Gestational diabetes. ACOG Practice Bulletin. No. 30. September 2001. Obstet Gynecol 2001;98:525–38.
3.Piacquadio K, Hollingsworth DR, Murphy H. Effects of in-utero exposure to oral hypoglycaemic drugs. Lancet 1991;338:866–9.