Rosuvastatin (Crestor®, AstraZeneca), a third generation statin, is indicated for dyslipidaemia. It was registered in Singapore in December 2002.

Across the statin class, muscle toxicity is a recognised, dose-related, adverse reaction leading in rare cases to rhabdomyolysis, which can be potentially fatal.

Suspected reports of rhabdomyolysis (very rare, <0.01%, according to CIOMS definition¹) have been received with rosuvastatin worldwide.

Several regulatory authorities including UK, US, Canada and the European Union have recently issued advisories to remind their doctors who are using rosuvastatin in their patients to initiate patients on the lowest recommended start dose of rosuvastatin. These recommendations were in response to the post-marketing spontaneous adverse event reports of muscle toxicity associated with rosuvastatin.

In the UK, the Committee on Safety of Medicines (CSM) received 6 suspected reports of rhabdomyolysis of which 5 of these patients were on 40 mg rosuvastatin and 1 was on 80 mg rosuvastatin. There were 8 reported cases of rhabdomyolysis in Canada: 2 at 10 mg, 5 at 40 mg and 1 at an unspecified dose of rosuvastatin. The majority of the cases were seen in patients who had predisposing factors for myopathy/rhabdomyolysis.

To-date, HSA has not received any local reports of rhabdomyolysis except for 2 reports of muscle ache and severe myalgia suspected with the 10 mg dose of rosuvastatin.

HSA is closely monitoring the safety profile of this product and will be reviewing the significance of these findings in the light of international and postmarket experience.

Physicians are reminded to start all patients, including those who are switching from another statin, on rosuvastatin 10 mg, the recommended start dose. If necessary, dose increases should be performed after a 4-6 week trial of the lower dose. The 40 mg dose of rosuvastatin should only be reserved for patients who do not achieve their treatment goal on lower doses and do not have predisposing factors for adverse muscle effects. Patients who are appropriately titrated to 40 mg rosuvastatin daily based on their cardiovascular risk profile and response to lower doses should be closely monitored. The following recommendations are to be considered when prescribing rosuvastatin:

• Use with caution in patients with predisposing risk factors for myopathy, such as renal impairment, advanced age, and hypothyroidism, previous history of hereditary muscular disorders or muscular toxicity with another statin/fibrate, alcohol abuse, and situations where an increase in plasma level may occur or concomitant use of fibrates.
• Patients with renal or liver dysfunction should be closely monitored.
• Patients should be advised to promptly report to their physicians signs or symptoms of muscle pain and weakness, malaise, fever, dark urine, nausea or vomiting.

1. CIOMS definition for frequency of ADR: very common (= 10%); common (= 1% and < 10%); uncommon (= 0.1% and < 1%); rare (= 0.01% and < 0.1%) and very rare (< 0.01%)