FDA knew of drug’s dangers, but approved it anyway says Public Citizen

The U.S. Food and Drug Administration (FDA) had evidence that the cholesterol drug Crestor caused an increased incidence of rhabdomyolysis (severe muscle deterioration) – but the agency approved it anyway, according to Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group, in the June 26, 2004 issue of The Lancet. The FDA erroneously believed the toxicity was limited to an 80 milligram dose that was not ultimately approved, he noted.

The approval came despite the fact agency officials had said that any new cholesterol drug should be approved only if it has a comparable or lower risk of rhabdomyolysis than drugs already on the market. Records show that patients taking Crestor experience severe muscle deterioration at much higher rates than patients taking other cholesterol-lowering drugs. The rate of post-marketing reports of rhabdomyolysis for Crestor appears to exceed that of all other currently marketed statins (cholesterol-lowering drugs). Also, the drug is associated with primary kidney failure.

“To allow AstraZeneca to continue desperately seeking a piece of the estimated $20 billion-a-year statin market hardly justifies governments allowing this ultimately doomed drug to stay on the market,” Wolfe wrote.

From the time of its approval in August 2003 to mid-April, 18 patients, including 11 in the United States, suffered severe muscle deterioration. In addition, there have been eight reported cases of acute kidney failure and four of kidney insufficiency, according to data obtained from the FDA. Most of these patients were using the low 10 milligram dose. More than 20 additional cases of rhabdomyolysis have been reported to the FDA since mid-April, agency sources say.

In March, Public Citizen filed a petition with the FDA to have the drug taken off the market. The petition is still pending. Meanwhile, AstraZeneca has launched a major direct-to-consumer advertising campaign to promote the drug.

The group put most of the blame on the drug maker and, in August, called on the FDA to investigate AstraZeneca for illegally delaying the submission of reports of serious adverse reactions to the drug.

In a letter to FDA’s Acting Commissioner Lester Crawford, Wolf noted that the company delayed the submission to the FDA of 23 such reports, with some delays being as long as 97 days beyond the 15-day reporting limit.

“For months the FDA did not have an accurate count of reported cases,” Wolfe wrote. “Such apparently criminal behavior by a major drug company severely impairs the FDA’s ability to promptly and accurately evaluate the safety of marketed drugs.”

SOURCES: “Dangers of rosuvastatin identified before and after FDA approval,” The Lancet, Volume 363, Number 9427, June 26, 2004.

Letter to FDA calling for criminal investigation of AstraZeneca (HRG Publication #1703), August 3, 2003.