CAVSTAT

What it is

CAVSTAT is rosuvastatin calcium, available in 5 mg, 10 mg, 20 mg or 40 mg tablets. Rosuvastatin 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. — Prevention of major cardiovascular events in men aged 50 years and older and women aged 60 years and older 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, nonfatal stroke, and coronary artery revascularisation procedures.

Dosing overview

Prior to initiating rosuvastatin, the patient should be placed on a standard cholesterol-lowering diet. Rosuvastatin may be given at any time of the day, with or without food. For Asian patients, initiation of rosuvastatin therapy with 5 mg once daily should be considered. In patients taking ciclosporin, rosuvastatin dosage should be limited to 5 mg once daily. If rosuvastatin is used in combination with gemfibrozil, the dose of rosuvastatin should be limited to 10 mg once daily. For patients with severe renal impairment (CLcr <30 mL/min/1.73m²) not on dialysis, the dose of rosuvastatin should be started at 5 mg once daily and not exceed 10 mg once daily. Patients with severe hepatic impairment should start therapy with rosuvastatin 5 mg.

Key safety warnings

Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with rosuvastatin and with other drugs in this class. 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. 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 the upper limit of normal persist, reduction of dose or withdrawal of rosuvastatin is recommended. Rosuvastatin should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease. Increases in HbA1c and serum glucose levels have been observed in patients treated with rosuvastatin, including increases that exceeded the threshold for the diagnosis of diabetes mellitus in some cases. 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, rosuvastatin 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 (ULN). <cite index index="1-51">During pregnancy, in nursing mothers and in women of childbearing potential, unless they are taking adequate contraceptive precautions.</cite> Concomitant use of fusidic acid. Rosuvastatin 40 mg 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, situations where an increase in rosuvastatin plasma levels may occur, severe renal impairment (CrCl <30 mL/min), Asian patients, and concomitant use of fibrates.

Regulatory history

CAVSTAT was first registered on the Australian Register of Therapeutic Goods on 4 February 2016, with eight product registrations covering 5 mg, 10 mg, 20 mg and 40 mg strengths in both bottle and blister pack presentations.