JEDDAH, 10 October 2004 — Astra-Zeneca Pharmaceuticals, manufacturers of the cholesterol-lowering drug, Crestor (rosuvastatin), are in the process of trying to get approval for distributing the drug in the Saudi market. Although clinical studies which are being carried out in Saudi Arabia have shown the drug is linked to rhabdomyolysis — a breakdown of muscle fibers which releases proteins that can severely harm the kidney — there is still a good chance that the drug will be approved. There are fears that Crestor will be allowed into the Saudi market before it is proven to be safe or, at worst, that it produces only minor side effects.
Crestor has more potentially harmful side effects than similar drugs and should be taken off the market, according to a lengthy correspondence published in a recent issue of the respected British medical journal, The Lancet. The letter, written by Sidney Wolfe of Public Citizen’s Health Research Group, said that in its first seven months on the market, Crestor had been linked to 18 cases of rhabdomyolysis. “I can’t think of another instance where there’s better documentation of elevated risk during clinical trials, and it is now being seen post-market,” said Wolfe, who heads the health care advocacy organization. “There are many other statins so I see no reason for this one to be on the market.”
Referring to his presentation to the US Food and Drug Administration (FDA) in July 2003, Wolfe said that his research group was also seriously concerned because of seven cases of rhabdomyolysis which appeared during the field trials — with that number being large enough to raise concerns. In the trials, a dosage of 80 milligrams was used. The Endocrinologic and Metabolic Drugs Advisory Committee recommended that kidney monitoring be required for patients taking 40 milligrams of rosuvastatin per day.
The FDA failed to take this advice but did point out on the packaging insert that “dose reduction should be considered for patients on rosuvastatin 40 mg therapy with unexplained persistent proteinuria during routine urinalysis testing.” This suggests that 40 mg/day would be a maximum dose but some medical authorities suggest that the dosages be as low as 20mg/day. “Not one case of rhabdomyolysis appeared in any of the pre-approval studies of the previously approved statins, including cerivastatin, which was removed from the market because of rhabdomyolysis.”
David Orloff, director of the FDA division of endocrinologic and metabolic drugs, said Wolfe’s information about Crestor’s record is similar to his. It was approved by the FDA last August and went on the market soon after with an aggressive advertising campaign.
Astra-Zeneca Pharmaceuticals, the drug’s manufacturer, recently 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 adverse event reports in patients receiving Crestor and highlight certain patient populations who may be at increased risk for serious muscle toxicity (myopathy) associated with Crestor use, especially at the highest approved dose of 40 mg/day.
Rosuvastatin became the sixth cholesterol lowering “statin” drug on the US market when it was approved by the Food and Drug Administration (FDA) on Aug. 13, 2003. The other members of the statin family are atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), pravastatin (Pravachol), and simvastatin (Zocor). These drugs are only approved to be used along with a low-cholesterol diet and an exercise program to lower cholesterol.
On Aug. 9, 2001, Bayer, the manufacturer of Baycol, another member of the statin family, Cerrivastatin, voluntarily stopped the distribution of Baycol in all countries because of reports of deaths from rhabdomyolysis, an adverse reaction involving the destruction of muscle tissue that can lead to kidney failure
Orloff said Crestor is not similar to Baycol in the severity of the muscle and kidney problems it appeared to be causing.
