Crestor (rosuvastatin calcium 10 mg) Dailymed

Indications & Usage Section

1 INDICATIONS AND USAGE1.1 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.

Pediatric Patients 10 to 17 years of age with Heterozygous Familial Hypercholesterolemia (HeFH)

Adjunct to diet to reduce Total-C, LDL-C and ApoB levels in adolescent boys and girls, who are at least one year post-menarche, 10-17 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 and there is a positive family history of premature cardiovascular disease (CVD) or two or more other CVD risk factors.1.2 Hypertriglyceridemia

CRESTOR is indicated as adjunctive therapy to diet for the treatment of adult patients with hypertriglyceridemia.

1.3 Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia)

CRESTOR is indicated as an adjunct to diet for the treatment of patients with primary dysbetalipoproteinemia (Type III Hyperlipoproteinemia).

1.4 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.

1.5 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.

1.6 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
  

1.7 Limitations of Use

CRESTOR has not been studied in Fredrickson Type I and V dyslipidemias.

Contraindications Section

4 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)].
  
• 
  Women who are pregnant or may become pregnant. 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. Additionally, there is no apparent benefit to therapy during pregnancy, and safety in pregnant women has not been established. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus and the lack of known clinical benefit with continued use during pregnancy [see Use in Specific Populations (8.1) and Nonclinical Toxicology (13.2)].
  
• 
  Nursing mothers. Because another drug in this class passes into breast milk, and because HMG-CoA reductase inhibitors have the potential to cause serious adverse reactions in nursing infants, women who require CRESTOR treatment should be advised not to nurse their infants [see Use in Specific Populations (8.3)].
  

Adverse Reactions Section

6 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)]
  

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
  

6.1 Clinical Studies ExperienceBecause 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. 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. 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 (14.7)].

Adverse reactions reported in ≥ 2% of patients and at a rate greater than placebo are shown in Table 2.

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 (14.8)].

Adverse reactions reported in ≥ 2% of patients and at a rate greater than placebo are shown in Table 3.

6.2 Pediatric patients 10 to 17 years of age:

In a 12-week controlled study in boys and postmenarchal girls, the safety and tolerability profile of CRESTOR 5 to 20 mg daily was generally similar to that of placebo [see Clinical Studies (14.6) and Use in Special Populations, Pediatric Use (8.4)].

However, 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.

6.3 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of CRESTOR: arthralgia, hepatic failure, hepatitis, jaundice and memory loss. 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.

Overdosage Section

10 OVERDOSAGE

There is no specific treatment in the event of overdose. In the event of overdose, the patient should be treated symptomatically and supportive measures instituted as required. Hemodialysis does not significantly enhance clearance of rosuvastatin.

Dosage & Administration Section

Enter section text here

How Supplied Section

16 HOW SUPPLIED/STORAGE AND HANDLING

CRESTOR^® (rosuvastatin calcium) Tablets are supplied as:

• 
  NDC 0310-0755-90: 5 mg. Yellow, round, biconvex, coated tablets. Debossed “CRESTOR” and “5” on one side; bottle of 90 tablets
  
• 
  NDC 0310-0751-90: 10 mg. Pink, round, biconvex, coated tablets. Debossed “CRESTOR” and “10” on one side; bottle of 90 tablets
  
• 
  NDC 0310-0751-39: 10 mg. Pink, round, biconvex, coated tablets. Debossed “CRESTOR” and “10” on one side; unit dose packages of 100
  
• 
  NDC 0310-0752-90: 20 mg. Pink, round, biconvex, coated tablets. Debossed “CRESTOR” and “20” on one side; bottles of 90
  
• 
  NDC 0310-0752-39: 20 mg. Pink, round, biconvex, coated tablets. Debossed “CRESTOR” and “20”on one side; unit dose packages of 100
  
• 
  NDC 0310-0754-30: 40 mg. Pink, oval, biconvex, coated tablets. Debossed “CRESTOR” on one side and “40” on the other side; bottles of 30
  

Information For Patients Section

17 PATIENT COUNSELING INFORMATION17.1 Skeletal Muscle Effects

Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.

17.2 Concomitant Use of Antacids

When taking CRESTOR with an aluminum and magnesium hydroxide combination antacid, the antacid should be taken at least 2 hours after CRESTOR administration.

17.3 Pregnancy

If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus and the lack of known clinical benefit with continued use during pregnancy.

17.4 Liver Enzymes

It is recommended that liver enzymes be checked before and at 12 weeks following both the initiation of therapy and any elevation of dose, and periodically (e.g., semiannually) thereafter.

Package Label.principal Display Panel