Europe, USA, Canada.

AstraZeneca has revised the package insert for rosuvastatin (Crestor) for use in the 25 Member States of the European Union. The revised insert includes new prescribing information regarding the maximum dose of rosuvastatin (Crestor). These changes were advised by the UK Medicines and Healthcare products Regulatory Agency and Committee on Safety of Medicines, following a Europewide review of safety information regarding the association between rosuvastatin use and rhabdomyolysis. The new information advises the following:

• all patients to start on 10mg once daily, only increased to 20mg if necessary after 4 weeks
• 40mg dose contraindicated in patients with predisposing risk factors for muscle toxicity
• specialist supervision recommended when 40mg given, with this dose only necessary for a minority of patients.

Patients currently receiving the 40mg dose, who have not already been seen by a specialist, are advised to have their treatment reviewed at their next routine appointment.

Following these measures in Europe, the US FDA has issued a public advisory for rosuvastatin, advising that many of these recommendations are "already captured in the FDA approved labelling for rosuvastatin (Crestor)", with this labelling including a specific section titled Myopathy/Rhabdomyolysis. The FDA is not proposing to change the rosuvastatin (Crestor) labelling following the recent review, but wishes to "reemphasize to physicians the importance of carefully following the recommendations in the current product label".

In the Canadian Adverse Drug Reactions Monitoring Programme (CADRMP) database, there are eight Canadian post-market cases of rhabdomyolysis associated with rosuvastatin.

Five cases occurred with rosuvastatin 40mg daily, two cases have occurred at the 10mg usual recommended daily dose and for the remaining case the dose was not specified. The involved patients all had one or more pre-existing risk factors for statin induced myotoxicity.

AstraZeneca, under advice from Health Canada has warned health-care professionals to be cautious when prescribing rosuvastatin in patients with preexisting risk factors or concomitant medications which pose an increased risk for statin induced myopathy or rhabdomyolysis.

Reference:

1. Medicines and Healthcare products Regulatory Agency News, 9 June 2004. Available on the Internet at www.mhra.gov.uk/news

2. US FDA Public Health Advisory, 9 June 2004. Available on the Internet at www.fda.gov

3. "Dear Healthcare Professional" letter from AstraZeneca, 15 June 2004. Available on the Internet at www.hc-sc.gc.ca