This information is not for clinical use. These highlights do not include all the information needed to use Crestor safely and effectively. Before taking Crestor please consult with your doctor. See full prescribing information for Crestor.

Indications And Usage

CRESTOR is an HMG Co-A reductase inhibitor indicated for: •adult patients with primary hyperlipidemia and mixed dyslipidemia as an adjunct to diet to reduce elevated total-C, LDL-C, ApoB, nonHDL-C, and TG levels and to increase HDL-C (1.1) •pediatric patients 8 to 17 years of age with heterozygous familial hypercholesterolemia (HeFH) to reduce elevated total-C, LDL-C and ApoB after failing an adequate trial of diet therapy (1.2) •pediatric patients 7 to 17 years of age with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C, total-C, nonHDL-C and ApoB as an adjunct to diet, either alone or with other lipid-lowering treatments (1.2) •adult patients with hypertriglyceridemia as an adjunct to diet (1.3) •adult patients with primary dysbetalipoproteinemia (Type III hyperlipoproteinemia) as an adjunct to diet (1.4) •adult patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C, total-C, and ApoB (1.5) •slowing the progression of atherosclerosis as part of a treatment strategy to lower total-C and LDL-C as an adjunct to diet (1.6) •risk reduction of MI, stroke, and arterial revascularization procedures in patients without clinically evident CHD, but with multiple risk factors (1.7) Limitations of use (1.8): CRESTOR has not been studied in Fredrickson Type I and V dyslipidemias. 1.1 Hyperlipidemia and Mixed Dyslipidemia CRESTOR is indicated as adjunctive therapy to diet to reduce elevated Total-C, LDL-C, ApoB, nonHDL‑C, and triglycerides and to increase HDL‑C in adult patients with primary hyperlipidemia or mixed dyslipidemia. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and nonpharmacological interventions alone has been inadequate. 1.2 Pediatric Patients with Familial Hypercholesterolemia CRESTOR is indicated as an adjunct to diet to: • reduce Total-C, LDL-C and ApoB levels in children and adolescents 8 to 17 years of age with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: LDL-C >190 mg/dL, or >160 mg/dL along with a positive family history of premature cardiovascular disease (CVD) or two or more other CVD risk factors. • reduce LDL-C, Total-C, nonHDL-C and ApoB in children and adolescents 7 to 17 years of age with homozygous familial hypercholesterolemia, either alone or with other lipid-lowering treatments (e.g., LDL apheresis). 1.3 Hypertriglyceridemia CRESTOR is indicated as adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia. 1.4 Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia) CRESTOR is indicated as an adjunct to diet for the treatment of adult patients with primary dysbetalipoproteinemia (Type III Hyperlipoproteinemia). 1.5 Adult Patients with Homozygous Familial Hypercholesterolemia CRESTOR is indicated as adjunctive therapy to other lipid-lowering treatments (e.g., LDL apheresis) or alone if such treatments are unavailable to reduce LDL‑C, Total‑C, and ApoB in adult patients with homozygous familial hypercholesterolemia. 1.6 Slowing of the Progression of Atherosclerosis CRESTOR is indicated as adjunctive therapy to diet to slow the progression of atherosclerosis in adult patients as part of a treatment strategy to lower Total‑C and LDL‑C to target levels. 1.7 Primary Prevention of Cardiovascular Disease In individuals without clinically evident coronary heart disease but with an increased risk of cardiovascular disease based on age ≥ 50 years old in men and ≥ 60 years old in women, hsCRP ≥ 2 mg/L, and the presence of at least one additional cardiovascular disease risk factor such as hypertension, low HDL‑C, smoking, or a family history of premature coronary heart disease, CRESTOR is indicated to: •reduce the risk of stroke •reduce the risk of myocardial infarction •reduce the risk of arterial revascularization procedures 1.8 Limitations of Use CRESTOR has not been studied in Fredrickson Type I and V dyslipidemias.

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Dosage Forms And Strengths

5 mg: Yellow, round, biconvex, coated tablets. Debossed “CRESTOR” and “5” on one side of the tablet. 10 mg: Pink, round, biconvex, coated tablets. Debossed “CRESTOR” and “10” on one side of the tablet. 20 mg: Pink, round, biconvex, coated tablets. Debossed “CRESTOR” and “20” on one side of the tablet. 40 mg: Pink, oval, biconvex, coated tablets. Debossed “CRESTOR” on one side and “40” on the other side of the tablet. Tablets: 5 mg, 10 mg, 20 mg, and 40 mg (3)

Contraindications

CRESTOR is contraindicated in the following conditions: •Patients with a known hypersensitivity to any component of this product. Hypersensitivity reactions including rash, pruritus, urticaria, and angioedema have been reported with CRESTOR [see Adverse Reactions (6.1) ]. •Patients with active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels [see Warnings and Precautions (5.2) ]. • Pregnancy [see Use in Specific Populations (8.1 , 8.3) ]. • Lactation. Limited data indicate that CRESTOR is present in human milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require CRESTOR treatment should not breastfeed their infants [see Use in Specific Populations (8.2) ]. •Known hypersensitivity to product components (4) •Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels (4) •Pregnancy (4, 8.1, 8.3) •Lactation (4, 8.2)

Warning and Cautions

• Skeletal muscle effects (e.g., myopathy and rhabdomyolysis): Risks increase with use of 40 mg dose, advanced age (≥65), hypothyroidism, renal impairment, and combination use with cyclosporine, atazanavir/ritonavir, lopinavir/ritonavir, or simeprevir. Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported. Advise patients to promptly report to their physician unexplained and/or persistent muscle pain, tenderness, or weakness and discontinue CRESTOR if signs or symptoms appear. (5.1, 7.5, 7.6) • Liver enzyme abnormalities: Persistent elevations in hepatic transaminases can occur. Perform liver enzyme tests before initiating therapy and as clinically indicated thereafter. (5.2) 5.1 Skeletal Muscle Effects Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including CRESTOR. These risks can occur at any dose level, but are increased at the highest dose (40 mg). CRESTOR should be prescribed with caution in patients with predisposing factors for myopathy (e.g., age ≥ 65 years, inadequately treated hypothyroidism, renal impairment). The risk of myopathy during treatment with CRESTOR may be increased with concurrent administration of some other lipid-lowering therapies (fibrates or niacin), gemfibrozil, cyclosporine, atazanavir/ritonavir, lopinavir/ritonavir, or simeprevir [see Dosage and Administration (2) and Drug Interactions (7 )]. Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors, including rosuvastatin, coadministered with colchicine, and caution should be exercised when prescribing CRESTOR with colchicine [see Drug Interactions (7.7) ]. CRESTOR therapy should be discontinued if markedly elevated creatine kinase levels occur or myopathy is diagnosed or suspected. CRESTOR therapy should also be temporarily withheld in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis, hypotension, dehydration, major surgery, trauma, severe metabolic, endocrine, and electrolyte disorders, or uncontrolled seizures). There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents. All patients should be advised to promptly report to their physician unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing CRESTOR. 5.2 Liver Enzyme Abnormalities It is recommended that liver enzyme tests be performed before the initiation of CRESTOR, and if signs or symptoms of liver injury occur. Increases in serum transaminases [AST (SGOT) or ALT (SGPT)] have been reported with HMG‑CoA reductase inhibitors, including CRESTOR. In most cases, the elevations were transient and resolved or improved on continued therapy or after a brief interruption in therapy. There were two cases of jaundice, for which a relationship to CRESTOR therapy could not be determined, which resolved after discontinuation of therapy. There were no cases of liver failure or irreversible liver disease in these trials. In a pooled analysis of placebo-controlled trials, increases in serum transaminases to >3 times the upper limit of normal occurred in 1.1% of patients taking CRESTOR versus 0.5% of patients treated with placebo. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including rosuvastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with CRESTOR, promptly interrupt therapy. If an alternate etiology is not found, do not restart CRESTOR. CRESTOR should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of chronic liver disease [see Clinical Pharmacology (12.3) ]. Active liver disease, which may include unexplained persistent transaminase elevations, is a contraindication to the use of CRESTOR [see Contraindications (4) ]. 5.3 Concomitant Coumarin Anticoagulants Caution should be exercised when anticoagulants are given in conjunction with CRESTOR because of its potentiation of the effect of coumarin-type anticoagulants in prolonging the prothrombin time/INR. In patients taking coumarin anticoagulants and CRESTOR concomitantly, INR should be determined before starting CRESTOR and frequently enough during early therapy to ensure that no significant alteration of INR occurs [see Drug Interactions (7.4) ]. 5.4 Proteinuria and Hematuria In the CRESTOR clinical trial program, dipstick-positive proteinuria and microscopic hematuria were observed among CRESTOR treated patients. These findings were more frequent in patients taking CRESTOR 40 mg, when compared to lower doses of CRESTOR or comparator HMG‑CoA reductase inhibitors, though it was generally transient and was not associated with worsening renal function. Although the clinical significance of this finding is unknown, a dose reduction should be considered for patients on CRESTOR therapy with unexplained persistent proteinuria and/or hematuria during routine urinalysis testing. 5.5 Endocrine Effects Increases in HbA1c and fasting serum glucose levels have been reported with HMG‑CoA reductase inhibitors, including CRESTOR. Based on clinical trial data with CRESTOR, in some instances these increases may exceed the threshold for the diagnosis of diabetes mellitus [see Adverse Reactions (6.1) ]. Although clinical studies have shown that CRESTOR alone does not reduce basal plasma cortisol concentration or impair adrenal reserve, caution should be exercised if CRESTOR is administered concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones such as ketoconazole, spironolactone, and cimetidine.

Adverse Reactions

The following serious adverse reactions are discussed in greater detail in other sections of the label: •Rhabdomyolysis with myoglobinuria and acute renal failure and myopathy (including myositis) [see Warnings and Precautions (5.1) ] •Liver enzyme abnormalities [see Warnings and Precautions (5.2) ] Most frequent adverse reactions (rate >2%) are headache, myalgia, abdominal pain, asthenia, and nausea. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. In the CRESTOR controlled clinical trials database (placebo or active-controlled) of 5394 patients with a mean treatment duration of 15 weeks, 1.4% of patients discontinued due to adverse reactions. The most common adverse reactions that led to treatment discontinuation were: •myalgia •abdominal pain •nausea The most commonly reported adverse reactions (incidence ≥2%) in the CRESTOR controlled clinical trial database of 5394 patients were: •headache •myalgia •abdominal pain •asthenia •nausea Adverse reactions reported in ≥2% of patients in placebo-controlled clinical studies and at a rate greater than placebo are shown in Table 1. These studies had a treatment duration of up to 12 weeks. Table 1. Adverse ReactionsAdverse reactions by COSTART preferred term. Reported in ≥2% of Patients Treated with CRESTOR and > Placebo in Placebo-Controlled Trials (% of Patients) Adverse Reactions CRESTOR 5 mg N=291 CRESTOR 10 mg N=283 CRESTOR 20 mg N=64 CRESTOR 40 mg N=106 Total CRESTOR 5 mg‑40 mg N=744 Placebo N=382 Headache 5.5 4.9 3.1 8.5 5.5 5.0 Nausea 3.8 3.5 6.3 0 3.4 3.1 Myalgia 3.1 2.1 6.3 1.9 2.8 1.3 Asthenia 2.4 3.2 4.7 0.9 2.7 2.6 Constipation 2.1 2.1 4.7 2.8 2.4 2.4 Other adverse reactions reported in clinical studies were abdominal pain, dizziness, hypersensitivity (including rash, pruritus, urticaria, and angioedema) and pancreatitis. The following laboratory abnormalities have also been reported: dipstick-positive proteinuria and microscopic hematuria [see Warnings and Precautions (5.4) ]; elevated creatine phosphokinase, transaminases, glucose, glutamyl transpeptidase, alkaline phosphatase, and bilirubin; and thyroid function abnormalities. In the METEOR study, involving 981 participants treated with rosuvastatin 40 mg (n=700) or placebo (n=281) with a mean treatment duration of 1.7 years, 5.6% of subjects treated with CRESTOR versus 2.8% of placebo-treated subjects discontinued due to adverse reactions. The most common adverse reactions that led to treatment discontinuation were: myalgia, hepatic enzyme increased, headache, and nausea [ see Clinical Studies (14.8) ]. Adverse reactions reported in ≥ 2% of patients and at a rate greater than placebo are shown in Table 2. Table 2. Adverse ReactionsAdverse reactions by MedDRA preferred term. Reported in ≥2% of Patients Treated with CRESTOR and > Placebo in the METEOR Trial (% of Patients) Adverse Reactions CRESTOR 40 mg N=700 Placebo N=281 Myalgia 12.7 12.1 Arthralgia 10.1 7.1 Headache 6.4 5.3 Dizziness 4.0 2.8 Increased CPK 2.6 0.7 Abdominal pain 2.4 1.8 ALT >3x ULNFrequency recorded as abnormal laboratory value. 2.2 0.7 In the JUPITER study, 17,802 participants were treated with rosuvastatin 20 mg (n=8901) or placebo (n=8901) for a mean duration of 2 years. A higher percentage of rosuvastatin-treated patients versus placebo-treated patients, 6.6% and 6.2%, respectively, discontinued study medication due to an adverse event, irrespective of treatment causality. Myalgia was the most common adverse reaction that led to treatment discontinuation. In JUPITER, there was a significantly higher frequency of diabetes mellitus reported in patients taking rosuvastatin (2.8%) versus patients taking placebo (2.3%). Mean HbA1c was significantly increased by 0.1% in rosuvastatin-treated patients compared to placebo-treated patients. The number of patients with a HbA1c > 6.5% at the end of the trial was significantly higher in rosuvastatin-treated versus placebo-treated patients [see Warnings and Precautions (5.5 ) and Clinical Studies (14.9) ]. Adverse reactions reported in ≥ 2% of patients and at a rate greater than placebo are shown in Table 3. Table 3. Adverse ReactionsTreatment-emergent adverse reactions by MedDRA preferred term. Reported in ≥ 2% of Patients Treated with CRESTOR and > Placebo in the JUPITER Trial (% of Patients) Adverse Reactions CRESTOR 20 mg N=8901 Placebo N=8901 Myalgia 7.6 6.6 Arthralgia 3.8 3.2 Constipation 3.3 3.0 Diabetes mellitus 2.8 2.3 Nausea 2.4 2.3 Pediatric Patients with Heterozygous Familial Hypercholesterolemia In a 12-week controlled study in boys and postmenarcheal girls 10 to 17 years of age with heterozygous familial hypercholesterolemia with CRESTOR 5 to 20 mg daily [see Use in Specific Populations (8.4) and Clinical Studies (14.7) ], elevations in serum creatine phosphokinase (CK) >10 x ULN were observed more frequently in rosuvastatin compared with placebo-treated children. Four of 130 (3%) children treated with rosuvastatin (2 treated with 10 mg and 2 treated with 20 mg) had increased CK >10 x ULN, compared to 0 of 46 children on placebo. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of CRESTOR: arthralgia, fatal and non-fatal hepatic failure, hepatitis, jaundice, thrombocytopenia, depression, sleep disorders (including insomnia and nightmares), peripheral neuropathy and gynecomastia. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. There have been rare reports of immune-mediated necrotizing myopathy associated with statin use [see Warnings and Precautions (5.1) ]. There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).

Drug Interactions

• Cyclosporine: Combination increases rosuvastatin exposure. Limit CRESTOR dose to 5 mg once daily. (2.4, 5.1, 7.1, 12.3) • Gemfibrozil: Combination should be avoided. If used together, limit CRESTOR dose to 10 mg once daily. (2.4, 5.1, 7.2) • Atazanavir/ritonavir, lopinavir/ritonavir, or simeprevir: Combination increases rosuvastatin exposure. Limit CRESTOR dose to 10 mg once daily. (2.4, 5.1, 7.3, 12.3) • Coumarin anticoagulants: Combination prolongs INR. Achieve stable INR prior to starting CRESTOR. Monitor INR frequently until stable upon initiation or alteration of CRESTOR therapy. (5.3, 7.4) • Concomitant lipid-lowering therapies: Use with fibrates or lipid-modifying doses (≥1 g/day) of niacin increases the risk of adverse skeletal muscle effects. Caution should be used when prescribing with CRESTOR. (5.1, 7.5, 7.6) 7.1 Cyclosporine Cyclosporine increased rosuvastatin exposure (AUC) 7‑fold. Therefore, in patients taking cyclosporine, the dose of CRESTOR should not exceed 5 mg once daily [see Dosage and Administration (2.4) , Warnings and Precautions (5.1) and Clinical Pharmacology (12.3) ]. 7.2 Gemfibrozil Gemfibrozil significantly increased rosuvastatin exposure. Due to an observed increased risk of myopathy/rhabdomyolysis, combination therapy with CRESTOR and gemfibrozil should be avoided. If used together, the dose of CRESTOR should not exceed 10 mg once daily [see Clinical Pharmacology (12.3) ]. 7.3 Protease Inhibitors Coadministration of rosuvastatin with certain protease inhibitors has differing effects on rosuvastatin exposure. Simeprevir, which is a hepatitis C virus (HCV) protease inhibitor, or combinations of atazanavir/ritonavir or lopinavir/ritonavir, which are HIV-1 protease inhibitors, increase rosuvastatin exposure (AUC) up to threefold [see Table 4 – Clinical Pharmacology (12.3) ]. For these protease inhibitors, the dose of CRESTOR should not exceed 10 mg once daily. The combinations of fosamprenavir/ritonavir or tipranavir/ritonavir, which are HIV-1 protease inhibitors, produce little or no change in rosuvastatin exposure. Caution should be exercised when rosuvastatin is coadministered with protease inhibitors [see Dosage and Administration (2.4) , Warnings and Precautions (5.1) and Clinical Pharmacology (12.3) ]. 7.4 Coumarin Anticoagulants CRESTOR significantly increased INR in patients receiving coumarin anticoagulants. Therefore, caution should be exercised when coumarin anticoagulants are given in conjunction with CRESTOR. In patients taking coumarin anticoagulants and CRESTOR concomitantly, INR should be determined before starting CRESTOR and frequently enough during early therapy to ensure that no significant alteration of INR occurs [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3) ]. 7.5 Niacin The risk of skeletal muscle effects may be enhanced when CRESTOR is used in combination with lipid-modifying doses (≥1 g/day) of niacin; caution should be used when prescribing with CRESTOR [see Warnings and Precautions (5.1) ]. 7.6 Fenofibrate When CRESTOR was coadministered with fenofibrate, no clinically significant increase in the AUC of rosuvastatin or fenofibrate was observed. Because it is known that the risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concomitant use of fenofibrates, caution should be used when prescribing fenofibrates with CRESTOR [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3) ]. 7.7 Colchicine Cases of myopathy, including rhabdomyolysis, have been reported with HMG‑CoA reductase inhibitors, including rosuvastatin, coadministered with colchicine, and caution should be exercised when prescribing CRESTOR with colchicine [see Warnings and Precautions (5.1) ].

Use In Specific Populations

• Females of reproductive potential: Advise females of reproductive potential to use effective contraception during treatment with CRESTOR. (8.3) • Severe renal impairment (not on hemodialysis): Starting dose is 5 mg, not to exceed 10 mg. (2.5, 5.1, 8.6) • Asian population: Consider 5 mg starting dose. (2.3, 8.8) 8.1 Pregnancy Risk Summary CRESTOR is contraindicated for use in pregnant women since safety in pregnant women has not been established and there is no apparent benefit to therapy with CRESTOR during pregnancy. Because HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, CRESTOR may cause fetal harm when administered to pregnant women. CRESTOR should be discontinued as soon as pregnancy is recognized [see Contraindications (4) ]. Limited published data on the use of rosuvastatin are insufficient to determine a drug-associated risk of major congenital malformations or miscarriage. In animal reproduction studies, there were no adverse developmental effects with oral administration of rosuvastatin during organogenesis at systemic exposures equivalent to a maximum recommended human dose (MRHD) of 40 mg/day in rats or rabbits (based on AUC and body surface area, respectively). In rats and rabbits, decreased pup/fetal survival occurred at 12 times and equivalent, respectively, to the MRHD of 40 mg/day [see Data]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Human Data Limited published data on rosuvastatin have not shown an increased risk of major congenital malformations or miscarriage. Rare reports of congenital anomalies have been received following intrauterine exposure to other statins. In a review of approximately 100 prospectively followed pregnancies in women exposed to simvastatin or lovastatin, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed what would be expected in the general population. The number of cases is adequate to exclude a ≥3 to 4-fold increase in congenital anomalies over the background incidence. In 89% of the prospectively followed pregnancies, drug treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. Animal Data Rosuvastatin crosses the placenta in rats and rabbits and is found in fetal tissue and amniotic fluid at 3% and 20%, respectively, of the maternal plasma concentration following a single 25 mg/kg oral gavage dose on gestation day 16 in rats. A higher fetal tissue distribution (25% maternal plasma concentration) was observed in rabbits after a single oral gavage dose of 1 mg/kg on gestation day 18. Rosuvastatin administration did not indicate a teratogenic effect in rats at ≤25 mg/kg/day or in rabbits ≤3 mg/kg/day (doses equivalent to the MRHD of 40 mg/day based on AUC and body surface area, respectively). In female rats given 5, 15 and 50 mg/kg/day before mating and continuing through to gestation day 7 resulted in decreased fetal body weight (female pups) and delayed ossification at 50 mg/kg/day (10 times the human exposure at the MRHD dose of 40 mg/day based on AUC). In pregnant rats given 2, 10 and 50 mg/kg/day of rosuvastatin from gestation day 7 through lactation day 21 (weaning), decreased pup survival occurred at 50 mg/kg/day (dose equivalent to 12 times the MRHD of 40 mg/day based body surface area). In pregnant rabbits given 0.3, 1, and 3 mg/kg/day of rosuvastatin from gestation day 6 to day 18, decreased fetal viability and maternal mortality was observed at 3 mg/kg/day (dose equivalent to the MRHD of 40 mg/day based on body surface area). 8.2 Lactation Risk Summary Rosuvastatin use is contraindicated during breastfeeding [see Contraindications (4) ]. Limited data indicate that CRESTOR is present in human milk. There is no available information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. Because of the potential for serious adverse reactions in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with CRESTOR. 8.3 Females and Males of Reproductive Potential Contraception CRESTOR may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ]. Advise females of reproductive potential to use effective contraception during treatment with CRESTOR. 8.4 Pediatric Use In children and adolescents 8 to 17 years of age with heterozygous familial hypercholesterolemia, the safety and effectiveness of CRESTOR as an adjunct to diet to reduce total cholesterol, LDL-C, and ApoB levels when, after an adequate trial of diet therapy, LDL-C exceeds 190 mg/dL or when LDL-C exceeds 160 mg/dL and there is a positive family history of premature CVD or two or more other CVD risk factors, were established in one controlled trial and in one open-label, uncontrolled trial [see Clinical Studies (14.7) ]. The long-term efficacy of CRESTOR therapy initiated in childhood to reduce morbidity and mortality in adulthood has not been established. The safety and effectiveness of CRESTOR in children and adolescents 10 to 17 years of age with heterozygous familial hypercholesterolemia were evaluated in a controlled clinical trial of 12 weeks duration followed by 40 weeks of open-label exposure. Patients treated with 5 mg, 10 mg, and 20 mg daily CRESTOR had an adverse experience profile generally similar to that of patients treated with placebo. There was no detectable effect of CRESTOR on growth, weight, BMI (body mass index), or sexual maturation [see Clinical Studies (14.7) ] in children and adolescents (10 to 17 years of age). CRESTOR has not been studied in controlled clinical trials involving prepubertal patients or patients younger than 10 years of age with heterozygous familial hypercholesterolemia. However, the safety and effectiveness of CRESTOR were evaluated in a two year open-label uncontrolled trial that included children and adolescents 8 to 17 years of age with heterozygous familial hypercholesterolemia [see Clinical Studies (14.7) ]. The safety and efficacy of CRESTOR in lowering LDL-C appeared generally consistent with that observed for adult patients, despite limitations of the uncontrolled study design. Children and adolescents 7 to 15 years of age with homozygous familial hypercholesterolemia were studied in a 6-week randomized, placebo-controlled, cross-over study with CRESTOR 20 mg once daily followed by 12 weeks of open-label treatment [see Clinical Studies (14.6) ]. In general, the safety profile in this trial was consistent with that of the previously established safety profile in adults. Although not all adverse reactions identified in the adult population have been observed in clinical trials of children and adolescent patients, the same warnings and precautions for adults should be considered for children and adolescents. Adolescent females should be counseled on appropriate contraceptive methods while on CRESTOR therapy [see Use in Specific Populations (8.1)] . 8.5 Geriatric Use Of the 10,275 patients in clinical studies with CRESTOR, 3159 (31%) were 65 years and older, and 698 (6.8%) were 75 years and older. 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 individuals cannot be ruled out. Elderly patients are at higher risk of myopathy and CRESTOR should be prescribed with caution in the elderly [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3) ]. 8.6 Renal Impairment Rosuvastatin exposure is not influenced by mild to moderate renal impairment (CLcr ≥ 30 mL/min/1.73 m2). Exposure to rosuvastatin is increased to a clinically significant extent in patients with severe renal impairment (CLcr <30 mL/min/1.73 m2) who are not receiving hemodialysis and dose adjustment is required [see Dosage and Administration (2.5) , Warnings and Precautions (5.1) and Clinical Pharmacology (12.3) ]. 8.7 Hepatic Impairment CRESTOR is contraindicated in patients with active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels. Chronic alcohol liver disease is known to increase rosuvastatin exposure; CRESTOR should be used with caution in these patients [see Contraindications (4) , Warning and Precautions (5.2), and Clinical Pharmacology (12.3) ]. 8.8 Asian Patients Pharmacokinetic studies have demonstrated an approximate 2‑fold increase in median exposure to rosuvastatin in Asian subjects when compared with Caucasian controls. CRESTOR dosage should be adjusted in Asian patients [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3) ].