Black Box for Crestor. The Food and Drug Administration on Wednesday told physicians to be more judicious in prescribing AstraZeneca’s cholesterol-fighting drug Crestor.
The agency’s advisory included some revisions in the drug’s label, telling doctors to start some patients at lower doses and to check for certain medical conditions before prescribing the drug.
Some critics wanted more. The consumer group Public Citizen urged that Crestor be banned. Crestor’s foes alleged the drug causes more dangerous side effects, such as a rare muscle-damaging disease called rhabdomyolysis, than similar cholesterol-lowering drugs.
But the FDA said that “Crestor, like all statins, has been associated with a low incidence” of this muscle damage. Statins are the class of drugs that include Lipitor from Pfizer, Zocor from Merck and Pravachol from Bristol-Myers Squibb.
Data from clinical trials and postmarketing safety reports “indicate that the risk of serious muscle damage is similar with Crestor compared to other marketed statins,” the FDA said.
The agency also said it “could not confirm that recommended doses of statins, including Crestor, can cause or worsen kidney failure.”
The FDA concluded that the potential benefits of all statin drugs, when used properly, “outweigh the potential risks.”
The news apparently softened the blow of the stronger label warnings. AstraZeneca’s stock slipped 11 cents to $39.91 on trading volume that was about twice the daily average for the past three months.
“Post-marketing data for Crestor has been thoroughly reviewed over the past year and this labeling revision is the result of that analysis,” said David Brennan, president and CEO of AstraZeneca’s U.S. operations.
The revisions that the FDA has approved provide physicians with further clarification
“The revisions that the FDA has approved provide physicians with further clarification on how best to use Crestor with their patients. We continue to believe that Crestor is safe and effective when used according to the prescribing information.”
Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group, called the FDA’s decision “another example of the agency’s dangerous cowardice in failing to adequately protect people in this country from uniquely dangerous prescription drugs.”
Approved by the FDA in August 2003, Crestor hasn’t achieved the sales growth that the company or financial analysts had expected thanks in part to critics such as Public Citizen, the British medical journal The Lancet and the veteran FDA researcher Dr. David Graham. During a Senate hearing in November about Merck’s arthritis drug Vioxx, Graham told legislators that several other drugs on the market, including Crestor, should be reviewed, restricted or removed.
AstraZeneca has vigorously defended the safety of the drug sometimes too vigorously. In December, the FDA told it to stop running a Crestor advertisement, even thought AstraZeneca already had halted the ad.
The FDA’s public health advisory says the new label contains a bolstering of the warning that people who take the highest daily dose 40 milligrams have the highest risk of the muscle disease. The agency said doctors should never prescribe 40 milligrams as a starting dose; it should be prescribed only if a patient hadn’t achieved success with 20 milligrams.
The revised label tells doctors to start patients on the lowest daily dose 5 milligrams if they don’t need aggressive lowering of their serum cholesterol. The lowest dose also should be prescribed for patients most at risk for the muscle disease Asians; people with kidney problems; or people taking the drug cyclosporine, a treatment for patients with transplated organs and with some autoimmune diseases.
The FDA also said doctors should monitor patients for protein in the urine, a potential indicator for kidney problems. The frequency of this condition — called proteinuria — appears to be related to the dose, said the FDA. It said clinical tests for Crestor at daily doses below 40 milligrams didn’t show a link between this condition and kidney disease.
“If a patient on Crestor develops unexplained, persistent proteinuria,” doctors should cut the dose and look for other possible causes, the FDA said.