Risk Summary
Available data from a small number of published studies and postmarketing experience with GLUCOTROL XL use in pregnancy over decades have not identified any drug associated risks for major birth defects, miscarriage, or adverse maternal outcomes. However, sulfonylureas (including glipizide) cross the placenta and have been associated with neonatal adverse reactions such as hypoglycemia. Therefore, GLUCOTROL XL should be discontinued at least two weeks before expected delivery (see Clinical Considerations). Poorly controlled diabetes in pregnancy is also associated with risks to the mother and fetus (see Clinical Considerations). In animal studies, there were no effects on embryofetal development following administration of glipizide to pregnant rats and rabbits during organogenesis at doses 833 times and 8 times the human dose based on body surface area, respectively. However, increased pup mortality was observed in rats administered glipizide from gestation day 15 throughout lactation at doses 2 times the maximum human dose based on body surface area (see Data).
The estimated background risk of major birth defects is 6–10% in women with pre-gestational diabetes with a HbA1c >7 and has been reported to be as high as 20–25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
Clinical Considerations
Disease-Associated Maternal and/or Embryo/Fetal Risk
Poorly-controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, miscarriage, preterm delivery, stillbirth, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.
Fetal/Neonatal Adverse Reactions
Neonates of women with gestational diabetes who are treated with sulfonylureas during pregnancy may be at increased risk for neonatal intensive care admission and may develop respiratory distress, hypoglycemia, birth injury, and be large for gestational age. Prolonged severe hypoglycemia, lasting 4–10 days, has been reported in neonates born to mothers receiving a sulfonylurea at the time of delivery and has been reported with the use of agents with a prolonged half-life. Observe newborns for symptoms of hypoglycemia and respiratory distress and manage accordingly.
Dose adjustments during pregnancy and the postpartum period
Due to reports of prolonged severe hypoglycemia in neonates born to mothers receiving a sulfonylurea at the time of delivery, GLUCOTROL XL should be discontinued at least two weeks before expected delivery (see Fetal/Neonatal Adverse Reactions).