Data
Animal Data
ENTRESTO treatment during organogenesis resulted in increased embryo-fetal lethality in rats at doses
≥ 49 mg sacubitril/51 mg valsartan/kg/day (≤ 0.14 [LBQ657, the active metabolite] and 1.5 [valsartan]fold the maximum recommended human dose [MRHD] of 97/103 mg twice-daily on the basis of the area
under the plasma drug concentration-time curve [AUC]) and rabbits at doses ≥ 5 mg sacubitril/5 mg
valsartan/kg/day (4-fold and 0.06-fold the MRHD on the basis of valsartan and LBQ657 AUC, respectively). ENTRESTO is teratogenic based on a low incidence of fetal hydrocephaly, associated with maternally toxic doses, which was observed in rabbits at an ENTRESTO dose of ≥ 5 mg sacubitril/5 mg
valsartan/kg/day. The adverse embryo-fetal effects of ENTRESTO are attributed to the angiotensin receptor antagonist activity.
Pre- and postnatal development studies in rats at sacubitril doses up to 750 mg/kg/day (4.5-fold the
MRHD on the basis of LBQ657 AUC) and valsartan at doses up to 600 mg/kg/day (0.86-fold the MRHD
on the basis of AUC) indicate that treatment with ENTRESTO during organogenesis, gestation and lactation may affect pup development and survival.
8.2 Lactation
Risk Su