Xigduo XR Use In Pregnancy & Lactation

Pregnancy: There are no adequate and well-controlled studies of XIGDUO XR in pregnant women. When pregnancy is detected, XIGDUO XR should be discontinued and appropriate alternative therapies should be considered.
In the time period corresponding to second and third trimester of pregnancy with respect to human renal maturation, maternal exposure to dapagliflozin in rat studies was associated with increased incidence and/or severity of renal pelvic and tubular dilatations in progeny.
In conventional studies of embryo-fetal development in rats and rabbits, dapagliflozin was administered for intervals coinciding with the first trimester period of non-renal organogenesis in humans. No developmental toxicities were observed in rabbits at any dose tested (1191× the maximum recommended human dose [MRHD]). In rats, dapagliflozin was neither embryolethal nor teratogenic (1441× the MRHD) in the absence of maternal toxicity.
Determination of fetal concentrations demonstrated a partial placental barrier to metformin.
Lactation: XIGDUO XR must not be used by a nursing woman.
No studies in lactating animals have been conducted with the combined components of XIGDUO XR. In studies performed with the individual components, both dapagliflozin and metformin are excreted in the milk of lactating rats.
Direct and indirect exposure of dapagliflozin to weanling juvenile rats and during late pregnancy are each associated with increased incidence and/or severity of renal pelvic and tubular dilatations in progeny, although the long-term functional consequences of these effects are unknown. These periods of exposure coincide with a critical window of renal maturation in rats. As functional maturation of the kidneys in humans continues in the first 2 years of life, dapagliflozin-associated dilated renal pelvis and tubules noted in juvenile rats could constitute potential risk for human renal maturation during the first 2 years of life. Additionally, the negative effects on body-weight gain associated with lactational exposure in weanling juvenile rats suggest that dapagliflozin must be avoided during the first 2 years of life.
Metformin is excreted into human breast milk but this is not known for dapagliflozin.