Pregnancy is recognized as a contraindication for the use of calcium atorvastatin, as it may cause harm to the fetus. Atorvastatin is derived from biologically active substances that are involved in the synthesis of cholesterol and other substances. During pregnancy, the use of calcium atorvastatin is contraindicated due to the lack of apparent benefits and established safety for pregnant women. It is recommended to discontinue the use of calcium atorvastatin as soon as pregnancy is recognized. Limited data published on the use of atorvastatin during pregnancy is insufficient to determine the risk of major congenital malformations or miscarriage. The recommended maximum human dose and exposure for atorvastatin are 20 and 30 times higher, respectively, than the doses that have been associated with major congenital malformations.

The estimated background risk of major birth defects and miscarriage for the indicated population is currently unknown. In the general population of the United States, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is approximately 2 to 4% and 15 to 20%, respectively.

Data.

HumanData.

In the study conducted on pregnancies that were prospectively followed, it was found that the drug treatment initiated prior to pregnancy was discontinued at some point in the first trimester. This led to a 4-fold increase in the incidence of congenital anomalies, excluding cases where there were at least 3 anomalies. However, the incidences of stillbirths/fetal deaths and spontaneous abortions did not exceed what would be expected in the general population. A review of approximately 100 pregnancies followed prospectively in women exposed to lovastatin or simvastatin revealed rare reports of congenital anomalies following intrauterine exposure to other HMG-CoA reductase inhibitors. Limited published data on atorvastatin’s effect on calcium have not shown an increased risk of miscarriage or major congenital malformations, based on case reports, meta-analyses, and observational studies.

AnimalData.

Atorvastatin, similar to maternal plasma, crosses the placenta in rats and reaches a level in the liver of the fetus. In pregnant rats and rabbits, Atorvastatin was respectively administered during organogenesis at oral doses up to 300 mg/kg/day and 100 mg/kg/day. At doses up to 300 mg/kg/day in rats or 100 mg/kg/day in rabbits, Atorvastatin did not cause birth defects. When considering surface area (mg/m2), these doses were about 30 times (rat) or 20 times (rabbit) higher than the human exposure at the MRHD. In rats, a toxic dose of 300 mg/kg resulted in increased loss after implantation and decreased fetal body weight. At a dose of 100 mg/kg/day, fetal body weights were decreased, and there was increased loss after implantation at toxic doses of 50 and 100 mg/kg/day in rabbits.

Based on the area under the curve (AUC), these dosages are equivalent to 6 times (100 mg/kg) and 22 times (225 mg/kg) the level of exposure experienced by humans at the maximum recommended human dose (MRHD). The development of the pups was delayed, as indicated by their performance on the rotarod test at a dosage of 100 mg/kg/day and their response to acoustic startle at a dosage of 225 mg/kg/day. Additionally, the detachment of the pinnae and the opening of the eyes were also delayed at a dosage of 225 mg/kg/day. The body weight of the pups was decreased until postnatal day 21 at a dosage of 100 mg/kg/day and until postnatal day 91 at a dosage of 225 mg/kg/day. Furthermore, there was a decrease in survival rates at birth, postnatal day 4, during the weaning period, and after weaning in the offspring of mothers who were administered a dosage of 225 mg/kg/day, which is a dosage that caused toxicity in the mothers. A study conducted on pregnant rats revealed that when they were given dosages of 20, 100, or 225 mg/kg/day from gestation day 7 until lactation day 20 (weaning), similar effects were observed.