Xiglip Use In Pregnancy & Lactation

Pregnancy: Category B.
The limited available data with sitagliptin in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations as follows). No adverse developmental effects were observed when sitagliptin was administered to pregnant rats and rabbits during organogenesis at oral doses up to 30-times and 20-times, respectively, the 100 mg clinical dose, based on AUG (see Data as follows).
The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a Hemoglobin A1c >7% and has been reported to be as high as 20-25% in women with a Hemoglobin A1c >10%. 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: Maternal and/or Fatal Risk: Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity.
Data: In embryo-fetal development studies, sitagliptin administered to pregnant rats and rabbits during organogenesis (gestation day 6 to 20) did not adversely affect developmental outcomes at oral doses up to 250 mg/kg (30-times the 100 mg clinical dose) and 125 mg/kg (20-times the 100 mg clinical dose), respectively, based on AUC. Higher doses in rats associated with maternal toxicity increased the incidence of rib malformations in offspring at 1000 mg/kg, or approximately 100-times the clinical dose, based on AUC. Placental transfer of sitagliptin was observed in pregnant.
Lactation: Sitagliptin is present in rat milk. It is secreted in the milk of lactating rats at a milk to plasma ratio of 4:1. Therefore, possibly present in human milk. It is unknown whether sitagliptin excreted in human breast milk and due to lack of human data, sitagliptin should not be used during breastfeeding.
Fertility: In rat fertility studies with oral gavage doses of 125, 250, and 1000 mg/kg, males were treated for 4 weeks prior to mating, during mating, up to scheduled termination (approximately 8 weeks total) and females were treated 2 weeks prior to mating through gestation day 7. No adverse effect on fertility was observed at 125 mg/kg (approximately 12 times human exposure at the MRHD of 100 mg/day based on AUC comparisons). At higher doses, non-dose related increased resorptions in females were observed (approximately 25 and 100 times human exposure at the MRHD based on AUC comparison).
No human fertility studies.