RECENT MAJOR CHANGES

Indications and Usage,

Pediatric Patients 10 to 17 years of age with Heterozygous Familial Hypercholesterolemia (HeFH) (1.1) 10/2009

Dosage and Administration, HeFH in Pediatric Patients (10 to 17 years of age) (2.2) 10/2009

Dosage and Administration, Use with Cyclosporine, Lopinavir/Ritonavir or Atazanavir/Ritonavir (2.5) 01/2010

Warnings and Precautions, Skeletal muscle effects (e.g., myopathy and rhabdomyolysis) (5.1) 01/2010

Indications and Usage, Primary Prevention of Cardiovascular Disease (1.6) 02/2010

INDICATIONS AND USAGE

CRESTOR is an HMG Co-A reductase inhibitor indicated for:

• 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)

• patients with hypertriglyceridemia as an adjunct to diet (1.2)

• patients with primary dysbetalipoproteinemia (Type III hyperlipoproteinemia) as an adjunct to diet (1.3)

• patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C, total-C, and ApoB (1.4)

• slowing the progression of atherosclerosis as part of a treatment strategy to lower total-C and LDL-C as an adjunct to diet (1.5)

• pediatric patients 10 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 (1.1)

• risk reduction of MI, stroke, and arterial revascularization procedures in patients without clinically evident CHD, but with multiple risk factors (1.6)

Limitations of use (1.7):

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

DOSAGE AND ADMINISTRATION

• CRESTOR can be taken with or without food, at any time of day. (2.1)

• Dose range: 5-40 mg once daily. Use 40 mg dose only for patients not reaching LDL-C goal with 20 mg. (2.1)

• HoFH: Starting dose 20 mg. (2.3)

• In pediatric patients 10 to 17 years of age with HeFH, the usual dose range is 5-20 mg/day; doses greater than 20 mg have not been studied in this patient population. (2.2)

DOSAGE FORMS AND STRENGTHS

Tablets: 5 mg, 10 mg, 20 mg, and 40 mg (3)

CONTRAINDICATIONS

• Known hypersensitivity to product components (4)

• Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels (4)

• Women who are pregnant or may become pregnant (4, 8.1)

• Nursing mothers (4, 8.3)

WARNINGS AND PRECAUTIONS

• 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, lopinavir/ritonavir, atazanavir/ritonavir, or certain other lipid-lowering drugs. Advise patients to promptly report unexplained muscle pain, tenderness, or weakness and discontinue CRESTOR if signs or symptoms appear (5.1)

• Liver enzyme abnormalities and monitoring: Persistent elevations in hepatic transaminases can occur. Monitor liver enzymes before and during treatment. (5.2)

ADVERSE REACTIONS

Most frequent adverse reactions (rate > 2%) are headache, myalgia, abdominal pain, asthenia, and nausea. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Med Health Pharma, LLC. at 1-877-896-6654 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

DRUG INTERACTIONS

• Cyclosporine: Combination increases rosuvastatin exposure. Limit CRESTOR dose to 5 mg once daily. (2.5, 7.1)

• Gemfibrozil: Combination should be avoided. If used together, limit CRESTOR dose to 10 mg once daily. (2.6, 5.1, 7.2)

• Lopinavir/Ritonavir or atazanavir/ritonavir: Combination increases rosuvastatin exposure. Limit CRESTOR dose to 10 mg once daily. (2.5, 5.1, 7.3)

• 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 and niacin products may increase the risk of skeletal muscle effects. (2.6, 5.1, 7.5, 7.6)

USE IN SPECIFIC POPULATIONS

• Severe renal impairment (not on hemodialysis): Starting dose is 5 mg, not to exceed 10 mg. (2.7, 5.1, 8.6)

• Asian population: Consider 5 mg starting dose. (2.4, 8.8)