8.1 Pregnancy

Pregnancy Category X 

Atorvastatin calcium is contraindicated in women who are or may become pregnant. Serum cholesterol and triglycerides increase during normal pregnancy. Lipid lowering drugs offer no benefit during pregnancy because cholesterol and cholesterol derivatives are needed for normal fetal development. Atherosclerosis is a chronic process, and discontinuation of lipid-lowering drugs during pregnancy should have little impact on long-term outcomes of primary hypercholesterolemia therapy. 

There are no adequate and well-controlled studies of atorvastatin use during pregnancy. There have been rare reports of congenital anomalies following intrauterine exposure to statins. In a review of about 100 prospectively followed pregnancies in women exposed to other statins, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed the rate expected in the general population. However, this study was only able to exclude a three-to-four-fold increased risk of congenital anomalies over background incidence. In 89% of these cases, drug treatment started before pregnancy and stopped during the first trimester when pregnancy was identified. 

Atorvastatin crosses the rat placenta and reaches a level in fetal liver equivalent to that of maternal plasma. Atorvastatin was not teratogenic in rats at doses up to 300 mg/kg/day or in rabbits at doses up to 100 mg/kg/day. These doses resulted in multiples of about 30 times (rat) or 20 times (rabbit) the human exposure based on surface area (mg/m2) [see Contraindications, Pregnancy (4.3)]. 

In a study in rats given 20, 100, or 225 mg/kg/day, from gestation day 7 through to lactation day 21 (weaning), there was decreased pup survival at birth, neonate, weaning, and maturity in pups of mothers dosed with 225 mg/kg/day. Body weight was decreased on days 4 and 21 in pups of mothers dosed at 100 mg/kg/day; pup body weight was decreased at birth and at days 4, 21, and 91 at 225 mg/kg/day. Pup development was delayed (rotorod performance at 100 mg/kg/day and acoustic startle at 225 mg/kg/day; pinnae detachment and eye-opening at 225 mg/kg/day). These doses correspond to 6 times (100 mg/kg) and 22 times (225 mg/kg) the human AUC at 80 mg/day. 

Statins may cause fetal harm when administered to a pregnant woman. Atorvastatin calcium should be administered to women of childbearing potential only when such patients are highly unlikely to conceive and have been informed of the potential hazards. If the woman becomes pregnant while taking atorvastatin calcium, it should be discontinued immediately and the patient advised again as to the potential hazards to the fetus and the lack of known clinical benefit with continued use during pregnancy. 

8.3 Nursing Mothers

It is not known whether atorvastatin is excreted in human milk, but a small amount of another drug in this class does pass into breast milk. Nursing rat pups had plasma and liver drug levels of 50% and 40%, respectively, of that in their mother’s milk. Animal breast milk drug levels may not accurately reflect human breast milk levels. Because another drug in this class passes into human milk and because statins have a potential to cause serious adverse reactions in nursing infants, women requiring atorvastatin calcium treatment should be advised not to nurse their infants [see Contraindications (4)]. 

8.4 Pediatric Use 

Safety and effectiveness in patients 10 to 17 years of age with heterozygous familial hypercholesterolemia have been evaluated in a controlled clinical trial of 6 months’ duration in adolescent boys and postmenarchal girls. Patients treated with atorvastatin calcium had an adverse experience profile generally similar to that of patients treated with placebo. The most common adverse experiences observed in both groups, regardless of causality assessment, were infections. Doses greater than 20 mg have not been studied in this patient population. In this limited controlled study, there was no significant effect on growth or sexual maturation in boys or on menstrual cycle length in girls [see Clinical Studies (14.6); Adverse Reactions, Pediatric Patients (ages 10 to 17 years) (6.3); and Dosage and Administration, Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10 to 17 years of age) (2.2)]. Adolescent females should be counseled on appropriate contraceptive methods while on atorvastatin calcium therapy [see Contraindications, Pregnancy (4.3) and Use in Specific Populations, Pregnancy (8.1)]. Atorvastatin calcium has not been studied in controlled clinical trials involving pre-pubertal patients or patients younger than 10 years of age. 

Clinical efficacy with doses up to 80 mg/day for 1 year have been evaluated in an uncontrolled study of patients with homozygous FH including 8 pediatric patients [see Clinical Studies, Homozygous Familial Hypercholesterolemia (14.5)]. 

8.5 Geriatric Use

Of the 39,828 patients who received atorvastatin calcium in clinical studies, 15,813 (40%) were ≥65 years old and 2,800 (7%) were ≥75 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older adults cannot be ruled out. Since advanced age (≥65 years) is a predisposing factor for myopathy, atorvastatin calcium should be prescribed with caution in the elderly. 

8.6 Hepatic Impairment 

Atorvastatin calcium is contraindicated in patients with active liver disease which may include unexplained persistent elevations in hepatic transaminase levels [see Contraindications (4)and Pharmacokinetics (12.3)].