In August 2003, the Food and Drug Administration (FDA) approved Crestor (rosuvastatin) for the purpose of lowering cholesterol. Astra / Zeneca, the parent company of this delayed newcomer to the already burgeoning stable of powerful statin drugs was happy to point out that Crestor could result in as much as a 52% lowering of cholesterol.
True to expectations of those monitoring the side effects of statin drugs this new kid on the block soon began to develop a reputation for myopathy and rhabdomyolysis.
In March of 2004, only eight months after release of Crestor, the consumer advocacy group Public Citizen called for the FDA to ban Crestor.
Three cases of kidney failure associated with severe rhabdomyolysis already had occurred in the United States resulting in one death but more ominously seven additional cases of rhabdomyolysis and nine additional cases of kidney failure also had occurred in Canada and the United Kingdom.
Recommendations that patients should be monitored for liver function abnormalities before treatment, at 12 weeks following initial therapy, after any dose elevation and periodically thereafter already were in place.
In June 2004, the FDA issued a Public Health Advisory notifying healthcare professionals of a revised package insert for use in the 22 member states of the European Union (EU). The changes to the European labeling were in response to adverse event reports in patients receiving Crestor and highlighted 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.
FDA then alerted physicians in the United States 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. Clearly this newer and more powerful statin drug was off to a very bad start in terms of the public good.
In May of 2005, a study published in the American Heart Association's journal, Circulation, revealed that kidney problems and muscle weakness were two to eight times more frequent among Crestor users than those taking other cholesterol-lowering drugs such as Lipitor and Zocor. The study analyzed reports of Crestor side effects sent to the FDA and compared them to similar reports sent for other Statins.
Ubiquinone, known also as Co-enzyme Q10, is collaterally damaged during the statin drug effect on the so- called mevalonate pathway of cholesterol biosynthesis. Ubiquinone metabolism is a branch on the mevalonate "tree" inevitably damaged by these statin drug "reductase inhibitor" action and the stronger the statin, the more severe this effect.
This problem has long been known and over a decade ago provoked serious consideration by Merck to market a combination pill of both Q10 and statin. However this very rational solution to a very serious problem was dismissed, presumably because of marketing concerns. Sadly for the users of Statins, most of the serious side effects of this class of drugs are due to ubiquinone interference.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor