inistered regularhuman insulin [see Data].
The estimated background risk of major birth defects is 6-10% inwomen with pre-gestational diabetes with a HbA1c >7% and hasbeen reported to be as high as 20-25% in women with a HbA1c >10%.
The estimated background risk of miscarriage for the indicatedpopulation is unknown. In the U.S. general population, the estimatedbackground risk of major birth defects and miscarriage in clinicallyrecognized pregnancies is 2-4% and 15-20%, respectively.
Clinical Considerations
Disease-Associated Maternal and/or Embryo-Fetal RiskPoorly controlled diabetes in pregnancy increases the maternal riskfor diabetic ketoacidosis, preeclampsia, spontaneous abortions,preterm delivery, stillbirth and delivery complications. Poorlycontrolled diabetes increases the fetal risk for major birth defects,still birth, and macrosomia related morbidity.
Data
Human Data
Published data from 5 randomized controlled trials of 441 pregnantwomen with diabetes mellitus treated with insulin aspart startingduring the late 2nd trimester of pregnancy did not identify anassociation of insulin aspart with major birth defects or adversematernal or fetal outcomes. However, these studies cannot definitely
establish the absence of any risk because of methodologicallimitations, including a variable duration of treatment and small sizeof the majority of the trials.
Animal Data
Fertility, embryo-fetal and pre-and postnatal development studieshave been performed with insulin aspart and regular humaninsulin in rats and rabbits. In a combined fertility and embryo-fetaldevelopment study in rats, insulin aspart was administered beforemating, during mating, and throughout pregnancy. Further, in apre- and postnatal development study insulin aspart was giventhroughout pregnancy and during lactation to rats. In an embryofetaldevelopment study insulin aspart was given to female rabbitsduring organogenesis. The effects of insulin aspart did not differfrom those observed with subcutaneous regular human insulin.
Insulin aspart, like human insulin, caused pre- and post-implantationlosses and visceral/skeletal abnormalities in rats at a dose of200 units/kg/day (approximately 32 times the human subcutaneousdose of 1.0 unit/kg/day, based on human exposure equivalents) andin rabbits at a dose of 10 units/kg/day (approximately three times
the human subcutaneous dose of 1.0 unit/kg/day, based on humanexposure equivalents). No significant effects were observed in ratsat a dose of 50 units/kg/day and in rabbits at a dose of 3 units/kg/day. These doses are approximately 8 times the human subcutaneousdose of 1.0 unit/kg/day for rats and equal to the human
subcutaneous dose of 1.0 unit/kg/day for rabbits, based on humanexposure equivalents. The effects are considered secondary tomaternal hypoglycemia.
8.2 Lactation
Risk Summary
There are no data on the presence of FIASP® in human milk, theeffects on the breastfed infant, or the effect on milk production. Onesmall published study reported that exogenous insulin, includinginsulin aspart, was present in human milk. However, there is insufficientinformation to determine the effects of insulin aspart on the
breastfed infant and no available information on the effects of insulinaspart on milk production. The developmental and health benefits ofbreastfeeding should be considered along with the mother’s clinicalneed for insulin, any potential adver |
