CRESTOR

What it is

CRESTOR contains rosuvastatin calcium in tablets of 5 mg, 10 mg, 20 mg and 40 mg. Rosuvastatin calcium is a HMG-CoA reductase inhibitor for the treatment of dyslipidaemia and is a fully synthetic competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol.

Approved indications —

Treatment of hypercholesterolaemia (including familial hypercholesterolaemia) when the response to diet and exercise is inadequate. — Prevention of major cardiovascular events in men ≥ 50 years old and women ≥ 60 years old with no clinically evident cardiovascular disease but with at least two conventional risk factors for cardiovascular disease (hypertension, low HDL-C, smoking, or a family history of premature coronary heart disease). — Reduction of the risk of nonfatal myocardial infarction. — Reduction of the risk of nonfatal stroke. — Reduction of the risk of coronary artery revascularisation procedures.

Dosing overview

Prior to initiating CRESTOR, the patient should be placed on a standard cholesterol-lowering diet. The dose should be individualised according to the goal of therapy and patient response and should take into account the potential risk for adverse reactions. CRESTOR may be given at any time of the day, with or without food. For Asian patients, initiation of CRESTOR therapy with 5 mg once daily should be considered. In patients taking ciclosporin, CRESTOR dosage should be limited to 5 mg once daily. If CRESTOR is used in combination with gemfibrozil, the dose should be limited to 10 mg once daily.

Key safety warnings

Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with rosuvastatin. Patients should be advised to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Rosuvastatin therapy should be discontinued if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Fusidic acid must not be co-administered with statins. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving this combination. Liver function tests should be performed before initiation of treatment and periodically thereafter. Patients who develop increased transaminase levels should be monitored until the abnormalities have resolved. Should an increase in ALT or AST of >3 times ULN persist, reduction of dose or withdrawal of rosuvastatin is recommended. Increases in HbA1c and serum glucose levels have been observed in patients treated with rosuvastatin. An increased frequency of diabetes mellitus has been reported with rosuvastatin in patients with risk factors for diabetes mellitus. Exceptional cases of interstitial lung disease have been reported with some statins, especially with long term therapy. Presenting features can include dyspnoea, non-productive cough and deterioration in general health (fatigue, weight loss and fever). If it is suspected a patient has developed interstitial lung disease, statin therapy should be discontinued.

Contraindications

Known hypersensitivity to any of the ingredients. Patients with active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 x the upper limit of normal (ULN). During pregnancy, in nursing mothers and in women of childbearing potential, unless they are taking adequate contraceptive precautions. Concomitant use of fusidic acid. The 40 mg dose is contraindicated in patients with pre-disposing factors for myopathy/rhabdomyolysis such as hypothyroidism, personal or family history of hereditary muscular disorders, previous history of muscular toxicity with another HMG-CoA reductase inhibitor or fibrate, alcohol abuse, severe renal impairment (CrCl <30 mL/min), Asian patients, and concomitant use of fibrates.

Regulatory history

CRESTOR was first listed on the ARTG on 26 April 2006 as rosuvastatin calcium tablets in strengths of 5 mg, 10 mg, 20 mg and 40 mg. An AusPAR was approved on 22 February 2011, extending the indications for CRESTOR to include the prevention of major cardiovascular events in at-risk individuals and refining the existing indication for the treatment of hypercholesterolaemia. The TGA's evaluation focused on data, primarily from the pivotal JUPITER study, which demonstrated the efficacy of rosuvastatin 20 mg for the primary prevention of major cardiovascular events in men ≥ 50 years old or women ≥ 60 years old with specific risk factors but no clinically evident cardiovascular disease.