Rosuvastatin calcium reaches one-year mark

Physician: Changed perception of statins’ potential 

Rosuvastatin calcium (Crestor) just passed its one-year anniversary since being approved by the U.S. Food and Drug Administration (FDA). Although by reports it has generated almost $4 billion in annual sales for AstraZeneca, the approval initially brought mixed feelings for many physicians, says Peter H. Jones, MD, associate professor of medicine and co-director of the Lipid Metabolism and Atherosclerosis Clinic at Baylor College of Medicine in Houston.

"The efficacy was tantalizing that you could get 50% LDL lowering at a reasonable dose," he says. "But there were obviously some issues or reports of whether there was a greater incidence of adverse events compared to the other statins, specifically relating to muscle. Physicians have had to finally get comfortable with whether it was safe."

Consumer safety concerns

Although AstraZeneca says rosuvastatin is safe and effective, one consumer group says it’s not. Public Citizen in Washington, DC, is fighting to have the cholesterol drug banned and to have a criminal investigation of AstraZeneca opened for allegedly delaying the submission to the FDA of reports of serious adverse reactions involving rosuvastatin.

Public Citizen says rosuvastatin has a significant potential to cause kidney damage and failure, as well as muscle destruction (rhabdomyolysis). In the correspondence section of the June 26 Lancet, Sidney M. Wolfe, MD, director of Public Citizen’s Health Research Group, charged that the FDA had evidence before approving rosuvastatin that it caused an increased incidence of rhabdomyolysis, yet the agency approved it anyway. In the letter, Wolfe says that there have been 18 cases of rhabdomyolysis — including 11 in the United States, eight reported cases of acute renal failure, and four of renal insufficiency in patients since marketing of the drug began.

In March, Public Citizen filed a petition with the FDA to have the drug taken off the market. The petition is still pending. In August, Wolfe sent a letter to Lester Crawford, DVM, FDA’s acting commissioner, requesting a criminal investigation of AstraZeneca for illegally delaying the submission to the FDA of 23 reports of serious adverse reactions to rosuvastatin in the United States for as long as 97 days beyond the allowable 15-day legal limit for reporting such reactions.

In July, AstraZeneca gave the FDA a 30-page response. The company says the allegation was "one more false, misleading, and inaccurate report from Dr. Wolfe and his organization." None of the 23 events cited required 15-day reporting, the company says. AstraZeneca says the consumer group chose to misrepresent the FDA-approved label for rosuvastatin as well as the agency’s guidance to pharmaceutical companies on the requirements for 15-day expedited reporting of serious unlabeled, adverse events. "This latest allegation is once again causing undue concern among patients about the safety profile of Crestor, which remains similar to that of other marketed statins."

Jones appears to agree with the manufacturer. "Being out a year and being out in many countries around the world and the accumulated data, I think that [the greater incidence of adverse effects] is not the case. I don’t think there are any greater issues of safety compared to other statins."

Overall, rosuvastatin has changed physicians’ perceptions that greater efficacy is important, Jones says. "I need whatever I have in my armamentarium to lower LDL; rouvastatin gives that option. It has helped in changing the perception of what is possible to achieve in patients."