CRESTOR- rosuvastatin calcium tablet, coated 
Lake Erie Medical DBA Quality Care Products LLC

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Crestor 10 MG

11 DESCRIPTION
CRESTOR (rosuvastatin calcium) is a synthetic lipid-lowering agent for oral administration.

The chemical name for rosuvastatin calcium is bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino] pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt with the following structural formula

The empirical formula for rosuvastatin calcium is (C22H27FN3O6S)2Ca and the molecular weight is 1001.14. Rosuvastatin calcium is a white amorphous powder that is sparingly soluble in water and methanol, and slightly soluble in ethanol. Rosuvastatin calcium is a hydrophilic compound with a partition coefficient (octanol/water) of 0.13 at pH of 7.0.

Inactive Ingredients: Each tablet contains: microcrystalline cellulose NF, lactose monohydrate NF, tribasic calcium phosphate NF, crospovidone NF, magnesium stearate NF, hypromellose NF, triacetin NF, titanium dioxide USP, yellow ferric oxide, and red ferric oxide NF.



12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action

CRESTOR is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol. In vivo studies in animals, and in vitro studies in cultured animal and human cells have shown rosuvastatin to have a high uptake into, and selectivity for, action in the liver, the target organ for cholesterol lowering. In in vivo and in vitro studies, rosuvastatin produces its lipid-modifying effects in two ways. First, it increases the number of hepatic LDL receptors on the cell-surface to enhance uptake and catabolism of LDL. Second, rosuvastatin inhibits hepatic synthesis of VLDL, which reduces the total number of VLDL and LDL particles.

12.3 Pharmacokinetics

1 INDICATIONS AND USAGE
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.

 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:


1.7 Limitations of Use

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


 


4 CONTRAINDICATIONS

CRESTOR is contraindicated in the following conditions:

6 ADVERSE REACTIONS

The following serious adverse reactions are discussed in greater detail in other sections of the label:


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:


The most commonly reported adverse reactions (incidence ≥ 2%) in the CRESTOR controlled clinical trial database of 5394 patients were:


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.


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.

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16 HOW SUPPLIED/STORAGE AND HANDLING

CRESTOR® (rosuvastatin calcium) Tablets are supplied as:

17 PATIENT COUNSELING INFORMATION
17.1 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.

Image of label

CRESTOR 
rosuvastatin calcium tablet, coated
Product Information
Product TypeHUMAN PRESCRIPTION DRUG LABELItem Code (Source)NDC:49999-873(NDC:0310-0751)
Route of AdministrationORALDEA Schedule    
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
ROSUVASTATIN CALCIUM (ROSUVASTATIN) ROSUVASTATIN CALCIUM10 mg
Inactive Ingredients
Ingredient NameStrength
CELLULOSE, MICROCRYSTALLINE 
LACTOSE MONOHYDRATE 
TRIBASIC CALCIUM PHOSPHATE 
CROSPOVIDONE 
MAGNESIUM STEARATE 
HYPROMELLOSES 
TRIACETIN 
TITANIUM DIOXIDE 
FERRIC OXIDE YELLOW 
FERRIC OXIDE RED 
Product Characteristics
ColorpinkScoreno score
ShapeROUND (biconvex) Size7mm
FlavorImprint Code CRESTOR;10
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:49999-873-9090 in 1 BOTTLE, PLASTIC
2NDC:49999-873-3030 in 1 BOTTLE, PLASTIC
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NDANDA02136611/09/2010
Labeler - Lake Erie Medical DBA Quality Care Products LLC (831276758)
Establishment
NameAddressID/FEIBusiness Operations
Lake Erie Medical DBA Quality Care Products LLC831276758repack(49999-873)

Revised: 12/2012
Document Id: 53a2af25-fd90-46f0-b0c1-60399e543ff2
Set id: e498b80d-7177-4f9d-8471-2e8f913196af
Version: 454
Effective Time: 20121204
 
Lake Erie Medical DBA Quality Care Products LLC