Evidence of a heightened risk of rhabdomyolysis in Asian Americans led the Food and Drug Administration to issue an alert and to require a label revision for the statin rosuvastatin last month.
According to the FDA Public Health Advisory, in a phase IV pharmacokinetic study “involving a diverse population of Asians residing in the United States, rosuvastatin [Crestor] drug levels were found to be elevated approximately twofold, compared with a Caucasian control group.”
Because the risks of statin side effects have been shown to be dose dependent, a change to the Dosage and Administration section of the label was made to state that the 5-mg dose should be considered the starting dose for Asian patients, and any increase in dose should take into consideration the increased drug exposure in this patient population. The new label also emphasizes that 40 mg should not be used as a starting dose and should only be used in patients “who have not achieved their cholesterol goals with the 20-mg dose.”
All statins are known to create a risk of myopathy/rhabdomyolysis, and the original Crestor product label included a warning that patients of advanced age (older than 65 years) or those who had hypothyroidism and/or renal insufficiency should be considered to be at greater risk of developing myopathy while receiving a statin and should be started at low doses and carefully monitored.
In 2004 the drug's maker, AstraZeneca Pharmaceuticals LP, found itself under attack by Public Citizen Health Research Group, which petitioned the FDA to have rosuvastatin removed from the market because of safety concerns regarding the risk of myopathy/rhabdomyolysis.
In June, the FDA issued a public health advisory alert to physicians emphasizing that physicians should pay close attention to the rosuvastatin label regarding dosage, “to cut the risk of myopathy.”
Just days after the current advisory was released, Public Citizen renewed its call for the drug's withdrawal, citing its own analysis of adverse event reports in which the rate of rhabdomyolysis per million prescriptions filled for rosuvastatin was 6.2 times higher than the rate for all of the other statins combined.
The FDA denied the request, stating, “We do not believe that the adverse event reports on Crestor indicate the drug poses and unacceptable risk of rhabdomyolysis” and that extensive preapproval and ongoing clinical trial-safety experience indicates that rosuvastatin's muscle safety is comparable to that of other statins.