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FDA Public Health Advisory for
Crestor (rosuvastatin)
Astra-Zeneca Pharmaceuticals today released a revised package
insert for Crestor (rosuvastatin) for use in the 22 member states of
the European Union (EU). The changes to the European labeling are in
response to postmarketing spontaneous adverse event reports in
patients receiving Crestor and highlight certain patient populations
who may be at an increased risk for serious muscle toxicity (myopathy)
associated with Crestor use, especially at the highest approved dose
of 40 mg. These risk factors and many of the recommendations for how
to minimize the risk of myopathy are already captured in the
FDA approved
labeling for Crestor
in the U.S. FDA is
alerting physicians to the need to carefully read the Crestor
product label and follow the recommendations for starting doses,
dose adjustments, and maximum daily doses to minimize the risk of
myopathy in individual patients.
Crestor, a member of a class of cholesterol-lowering drugs commonly
referred to as “statins”, was approved in the U.S. in August 2003,
based on review of an extensive clinical database involving
approximately 12,000 patients. At that time, the FDA identified in
the WARNINGS section of the product label those patients whose
increased baseline risk for myopathy warranted more careful
monitoring when prescribed Crestor. The U.S. approved labeling
included a specific section titled, “Myopathy/Rhabdomyolysis”, which
states that patients who are of advanced age (³ 65 years), have
hypothyroidism, and/or renal insufficiency should be considered to
have a greater risk for developing myopathy while receiving a statin.
Physicians are warned to prescribe Crestor with caution in these
patients, particularly at higher doses, as the risk of myopathy
increases with higher drug levels.
In addition, the U.S. approved labeling for Crestor states that
increased rosuvastatin drug levels were observed in certain
sub-populations of patients (e.g., subgroups of Asians, patients
concomitantly using cyclosporine and gemfibrozil), conferring
increased risk of myopathy. Because of these findings, the FDA
required Astra-Zeneca to make available in the U.S. 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 are also
taking gemfibrozil.
FDA has received reports of rhabdomyolysis in association with
Crestor, as it has with other drugs in the statin class. In ongoing
fashion, we are evaluating these reports of adverse muscle effects
with regard to clinical severity and apparent relationship to the
drug. FDA is comparing the frequency of reporting of muscle injury
with Crestor to that with other statins, given differences in
prescribing rates for the different drugs. Pending the evaluation of
the recent Crestor safety experience, FDA is not proposing to change
the US labeling for Crestor, but does want to re-emphasize to
physicians to the importance of carefully following the
recommendations in the current product label. Analysis of
accumulating safety data in the U.S. and worldwide will be
considered in any future labeling changes for Crestor, and to make
recommendations on risk management plans for Crestor.
Healthcare professionals prescribing Crestor are reminded of the
following key safety messages from the Crestor label: start doses
and maintenance doses of drug should be based on individual
cholesterol goals and apparent risks for side-effects; all patients
should be informed that statins can cause muscle injury, which in
rare, severe cases, can cause kidney damage and other organ failure
that are potentially life-threatening; and patients should be told
to promptly report to their physician signs or symptoms of muscle
pain and weakness, malaise, fever, dark urine, nausea, or vomiting.
The current FDA-approved label can be obtained at
http://www.fda.gov/cder/foi/label/2003/21366_crestor_lbl.pdf
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Date created: June 9, 2004 |
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