Rosuvastatin

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Crestor (AstraZeneca)
5 mg, 10 mg, 20 mg and 40 mg tablets
Approved indication: hypercholesterolaemia
Australian Medicines Handbook section 6.6.1

When patients have hypercholesterolaemia that fails to respond to diet and exercise they may require treatment with an HMG-Co A reductase inhibitor. These drugs are widely prescribed and the approval of rosuvastatin adds to the choice of 'statins'.

Rosuvastatin is taken once a day. Although the tablet's bioavailability is only 20% it does not have to be taken on an empty stomach or at a particular time of day. While most of the dose is excreted unchanged in the faeces approximately 10% is metabolised in the liver by cytochrome P450 2C9. Rosuvastatin is contraindicated in people with liver disease. Other patients should have liver function tests before and during treatment.

Rosuvastatin has been compared with atorvastatin, pravastatin and simvastatin in an open-label randomised trial involving 2431 patients. After six weeks rosuvastatin had reduced total cholesterol concentrations significantly more than the other drugs had. It also produced larger increases in concentrations of high density lipoprotein (HDL) cholesterol. A 10 mg dose of rosuvastatin will reduce low density lipoprotein (LDL) cholesterol by 46% compared to 37% with 10 mg atorvastatin, 35% with 20 mg simvastatin and 30% with 40 mg pravastatin^.1 (The approximate equivalent doses are rosuvastatin 5 mg = atorvastatin 10 mg, simvastatin 20 mg, pravastatin 40 mg and fluvastatin 80 mg.²)

The effect on LDL cholesterol may assist patients who are having trouble meeting their targets for risk reduction. In a retrospective study of 8251 patients starting statins, patients taking rosuvastatin were more likely to attain the target concentration of LDL cholesterol. However, the differences in HDL concentrations between statins were not significant.³

High doses can reduce the volume of atheroma in coronary vessels, but it is not known if this will improve the clinical outcomes. The doses used in this trial were above the usual maximum daily dose of 20 mg.⁴ Higher doses are likely to cause a higher frequency of adverse reactions.

Adverse effects resulted in 3.7% of patients in trials discontinuing treatment. These adverse effects include nausea, asthenia, diarrhoea and myalgia. There is a risk of rhabdomyolysis which may be increased if the patient is also taking drugs such as gemfibrozil. There are also clinically significant interactions with warfarin and cyclosporin. A few patients develop proteinuria or haematuria while taking rosuvastatin. Asian patients could be at greater risk of adverse effects because they tend to have higher plasma concentrations of rosuvastatin than Caucasians.

Dose for dose, rosuvastatin has a greater effect than other statins on cholesterol concentrations, but it should not become the first choice until data about its longer-term safety and effect on cardiovascular outcomes are available. An American drug bulletin has advised its readers not to use rosuvastatin at all.^5,6 Although there has been criticism that the data supporting rosuvastatin is weak, the company is alleged to have spent an estimated US$1 billion to persuade doctors to prescribe.^6,7

manufacturer provided the clinical evaluation

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

Note on references

At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).