FDA issues public health advisory on rosuvastatin (Crestor)
The FDA has announced that Astra-Zeneca Pharmaceuticals has revised the package insert for the cholesterol-lowering drug rosuvastatin (Crestor). The label changes include results from a Phase IV pharmacokinetic study in Asian Ameri-cans and highlight important information on the safe use of rosuvastatin to reduce the risk for serious muscle toxicity (myopathy/rhabdomyolysis), especially at the highest approved dose of 40 mg.
In the previously approved labeling, the warnings section states that patients older than age 65 who have hypothyroidism and/or renal insufficiency should be considered to have a greater risk for developing myopathy while receiving a statin. Physicians were warned to prescribe rosuvastatin with caution in these patients, particularly at higher doses, as the risk of myopathy increases with higher drug levels.
At that time, the FDA required Astra-Zeneca to make available in the United States a 5 mg dose that could be used in patients requiring less aggressive cholesterol-lowering or who were taking concurrent cyclosporine. The maximum recommended dose in the FDA-approved label is limited to 10 mg daily in patients with severe renal impairment or who also are taking gemfibrozil.
In a recent pharmacokinetic study involving a diverse population of Asians residing in the United States, however, rosuvastatin drug levels were found to be elevated approximately two-fold compared with a Caucasian control group. As a result of these findings, the "Dosage and Administration" section of the new label now states that the 5 mg dose of rosuvastatin should be considered as the start dose for Asian patients and any increase in dose should take into consideration the increased drug exposure in this patient population.
The "Warnings" and "Dosage and Administra-tion" sections of the label have been revised to more strongly emphasize the risks of myopathy, particularly at the highest approved dose of 40 mg. To minimize risks of myopathy and rhabdomyolysis, the revised label now states that the 5 mg dose is available as a start dose for those individuals who do not require aggressive cholesterol reductions or who have predisposing factors for myopathy. This includes patients taking cyclosporine, Asian patients, and patients with severe renal insufficiency. It also emphasizes that the 40 mg dose is not an appropriate start dose and should be reserved only for those patients who have not achieved their cholesterol goals with the 20 mg dose.
This information is included in a bolded paragraph under the "Dosage and Administration" section that also reminds prescribers who switch patients from other statins to initiate therapy only with approved doses of rosuvastatin and titrate according to the patient’s individualized goal of therapy.
For more information, see www.fda.gov/medwatch/SAFETY/2005/safety05.htm# crestor.
The FDA has announced that Astra-Zeneca Pharmaceuticals has revised the package insert for the cholesterol-lowering drug rosuvastatin (Crestor). The label changes include results from a Phase IV pharmacokinetic study in Asian Ameri-cans and highlight important information on the safe use of rosuvastatin to reduce the risk for serious muscle toxicity (myopathy/rhabdomyolysis), especially at the highest approved dose of 40 mg.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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