CROSUVA

What it is

CROSUVA 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

— Reduction of the risk of nonfatal myocardial infarction. — Reduction of the risk of nonfatal stroke. — Reduction of the risk of coronary artery revascularisation procedures. — 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. — Treatment of hypercholesterolaemia, including familial hypercholesterolaemia.

Dosing overview

For hypercholesterolaemia, the recommended starting dose is 5 mg or 10 mg once per day in both statin-naïve patients and those switched from another HMG-CoA reductase inhibitor, with the choice based on the individual patient's cholesterol level and cardiovascular risk. Dose adjustment can be made after 4 weeks of therapy where necessary. The usual maximum dose of rosuvastatin is 20 mg once per day. A dose of 40 mg once per day should only be considered in patients who remain at high cardiovascular risk after response to 20 mg is assessed, particularly those with familial hypercholesterolaemia, and is recommended only in patients in whom regular follow-up is planned. For prevention of cardiovascular events, a dose of 20 mg once daily has been found to reduce the risk of major cardiovascular events. For Asian patients, initiation of CROSUVA therapy with 5 mg once daily should be considered, as the potential for increased systemic exposures relative to Caucasians is relevant when considering dose escalation.

Key safety warnings

HMG-CoA reductase inhibitors have been associated with biochemical abnormalities of liver function. The incidence of persistent elevations exceeding 3 times the upper limit of normal in serum transaminases in fixed dose studies was 0.4%, 0%, 0% and 0.1% in patients receiving rosuvastatin 5, 10, 20 and 40 mg respectively. In most cases, the elevations were transient and resolved or improved on continued therapy or after brief interruption. Liver function tests should be performed before initiation of treatment and periodically thereafter. Patients who develop increased transaminase levels should be monitored until abnormalities resolve. Should an increase in ALT or AST exceeding 3 times the upper limit of normal persist, reduction of dose or withdrawal of rosuvastatin is recommended. Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with rosuvastatin and other drugs in this class. Uncomplicated myalgia has been reported in rosuvastatin-treated patients. Creatine kinase elevations exceeding 10 times the upper limit of normal occurred in 0.2% to 0.4% of patients taking rosuvastatin at doses up to 40 mg in clinical studies. Treatment-related myopathy, defined as muscle aches or muscle weakness in conjunction with CK increases exceeding 10 times the upper limit of normal, was reported in up to 0.1% of patients. Reports of rhabdomyolysis with rosuvastatin are rare, but higher at the highest marketed dose of 40 mg. Rosuvastatin should be prescribed with caution in patients with predisposing factors for myopathy such as renal impairment, advanced age and hypothyroidism. 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. Increases in HbA1c and fasting serum glucose levels have been reported with rosuvastatin. Increases in HbA1c and serum glucose levels have been observed in patients treated with rosuvastatin, and an increased frequency of diabetes mellitus has been reported 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. If it is suspected a patient has developed interstitial lung disease, statin therapy should be discontinued.

Contraindications

Known hypersensitivity to any of the ingredients. Active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 times the upper limit of normal. Use is contraindicated during pregnancy, in nursing mothers and in women of childbearing potential unless they are taking adequate contraceptive precautions. Concomitant use of fusidic acid. CROSUVA 40 is contraindicated in patients with pre-disposing factors for myopathy or rhabdomyolysis, including 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

CROSUVA 5 mg, 10 mg, 20 mg and 40 mg tablets were first listed on the Australian Register of Therapeutic Goods on 2 February 2012.