The FDA ( Food and Drug Administration ) has approved Crestor ( Rosuvastatin calcium ) for use in pediatric patients ages 10-17 with heterozygous familial hypercholesterolemia ( HeFH ) when diet therapy fails to reduce elevated cholesterol.

Heterozygous familial hypercholesterolemia, a genetic disease, is characterized by high LDL cholesterol and increased risk of early cardiovascular disease.
HeFH affects 10 million people worldwide and is most commonly caused by a defect in the LDL-C receptor gene that leads to elevated LDL-C levels.
The American Academy of Pediatrics states that pharmacological intervention should be considered for children with LDL levels greater than 190 mg/dL.

The FDA decision was based on a supplemental New Drug Application submitted by AstraZeneca which included data from the PLUTO ( Pediatric Lipid-redUction Trial of rOsuvastatin ) study.

The PLUTO trial was a 12-week, double-blind, randomized multicenter, placebo-controlled study with a 40-week, open-label follow-up.
The PLUTO study was designed to evaluate the efficacy and safety of Rosuvastatin in children ages 10-17 with heterozygous familial hypercholesterolemia.

Studies have previously shown that Rosuvastatin, as an adjunct to diet in adult patients, significantly lowered LDL-C, had a significant effect on raising HDL-C and slowed the progression of atherosclerosis, an underlying cause of cardiovascular disease.

Crestor is also indicated as an adjunct to diet to reduce elevated total-C, LDL-C, ApoB, non-HDL-C, and TG levels and to increase HDL-C in patients with primary hyperlipidemia and mixed dyslipidemia.
Crestor is indicated as an adjunct 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.
Crestor is not approved to reduce cardiovascular morbidity and mortality.

Crestor is contraindicated in patients with a known hypersensitivity to any component of this product, in patients with active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels, in women who are pregnant or may become pregnant, and in nursing mothers.

Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors ( or statins ), including Crestor.
These risks can occur at any dose level, but are increased at the highest dose of Rosuvastatin ( 40 mg ).

Crestor should be prescribed with caution in patients with predisposing factors for myopathy ( eg, age greater than or equal to 65 years, inadequately treated hypothyroidism, renal impairment ). The risk of myopathy during treatment with Rosuvastatin may be increased with concurrent administration of some other lipid-lowering therapies ( fibrates or Niacin), Gemfibrozil, Cyclosporine, or Lopinavir / Ritonavir.

Therapy with Rosuvastatin should be discontinued if markedly elevated CK levels occur or myopathy is diagnosed or suspected.
All patients should be advised to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.
It is recommended that liver enzyme tests be performed before and at 12 weeks following both the initiation of therapy and any elevation of dose, and periodically ( e.g., semiannually ) thereafter. Should an increase in ALT or AST of 3 times higher than the ULN persist, reduction of dose or withdrawal of Crestor is recommended.
Rosuvastatin should be used with caution in patients who consume substantial quantities of alcohol.

In the controlled clinical trials database, the most common adverse reactions were headache ( 3.7% ), myalgia ( 3.1% ), abdominal pain ( 2.6% ), asthenia ( 2.5% ), and nausea ( 2.2% ).

Source: AstraZeneca, 2009

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