A second cholesterol drug poses hazards, may spawn suits.A widely used cholesterol-lowering drug cholesterol-lowering drug Therapeutics Any of a family of agents that ↓ serum cholesterol; the most cost-effective agents for lowering LDL-C are nicotinic acid and lovastatin; the most efficient for ↑ HDL-C are nicotinic acid and gemfibrozil that is alleged to cause kidney failure kidney failure
or renal failure
Partial or complete loss of kidney function. Acute failure causes reduced urine output and blood chemical imbalance, including uremia. Most patients recover within six weeks. or insufficiency may soon be the subject of lawsuits around the country, echoing litigation An action brought in court to enforce a particular right. The act or process of bringing a lawsuit in and of itself; a judicial contest; any dispute.
When a person begins a civil lawsuit, the person enters into a process called litigation. over the health hazards of Baycol, a similar drug withdrawn from the market five years ago. Manufactured by London-based AstraZeneca, Crestor (rosuvastatin calcium ro·su·va·stat·in calcium
A statin drug used to treat hyperlipidemia.
Pharmacologic class: HMG-CoA reductase inhibitor
Therapeutic class: ) is still on the market and has been used by more than 4.3 million patients in more than 70 countries.
Like Baycol (cerivastatin cerivastatin Baycol® Cardiology Cholesterol-lowering, HMG-CoA reductase inhibitor/statin for managing hypercholesterolemia and mixed dyslipidemia; it ↑ HDL-C and ↓ LDL-C; withdrawn from the market as it was linked to rhabdomyolysis. See Statin. ), Crestor is one of a class of drugs called statins Statins
A class of drugs commonly used to lower LDL cholesterol levels.
Mentioned in: C-Reactive Protein , used in patients who have high cholesterol levels and are at risk for atherosclerosis--a hardening or thickening of the arteries. Statins block the production of enzymes the body uses to make cholesterol in the liver. By reducing the production of low-density lipoprotein (LDL LDL - ["LDL: A Logic-Based Data-Language", S. Tsur et al, Proc VLDB 1986, Kyoto Japan, Aug 1986, pp.33-41]. )--the so-called bad cholesterol that causes plaque to build up in arteries--statins decrease the patient's risk of a stroke or heart attack. Five other statins are currently on the U.S. market: Lipitor (atorvastatin atorvastatin /ator·va·stat·in/ (ah-tor?vah-stat´in) an antihyperlipidemic agent that acts by inhibiting cholesterol synthesis, used as the calcium salt in the treatment of hypercholesterolemia and other forms of dyslipidemia. ), Lescol (fluvastatin fluvastatin /flu·va·stat·in/ (floo´vah-stat?in) an inhibitor of cholesterol biosynthesis used as the sodium salt in the treatment of hyperlipidemia and to slow the progression of atherosclerosis associated with coronary heart disease. ), Mevacor (lovastatin lovastatin /lo·va·stat·in/ (lo´vah-stat?in) an antihyperlipidemic agent that acts by inhibiting cholesterol synthesis, used in the treatment of hypercholesterolemia and other forms of dyslipidemia and to lower the risks associated with ), Pravachol (pravastatin pravastatin /prav·a·stat·in/ (prav´ah-stat?in) an antihyperlipidemic agent that acts by inhibiting cholesterol synthesis, used as the sodium salt in the treatment of hypercholesterolemia and other forms of dyslipidemia and to lower the ), and Zocor (simvastatin simvastatin /sim·va·stat·in/ (sim´vah-stat?in) an antihyperlipidemic agent that acts by inhibiting cholesterol synthesis, used in the treatment of hypercholesterolemia and other forms of dyslipidemia and to lower the risks associated ).
But some consumer advocates say Crestor is dangerous, and the Web site WorstPills.org, maintained by the Washington, D.C.-based Public Citizen Health Research Group (HRG HRG Health Research Group
HRG Hogg Robinson Group
HRG Herausgeber (German: Editor)
HRG Hurghada, Egypt (Airport Code)
HRG Horn Rimmed Glasses (TV Show character, Heroes) ), has designated Crestor a "Do Not Use" drug.
"This drug has unique dangers compared with all the other statins currently on the market," said Sidney Wolfe, a physician who heads HRG. "There is an increased risk of rhabdomyolysis rhabdomyolysis /rhab·do·my·ol·y·sis/ (-mi-ol´i-sis) disintegration of striated muscle fibers with excretion of myoglobin in the urine.
n. , which is an often-fatal destruction of the muscle, and an increased risk of renal disease. Rhabdomyolysis can cause renal disease, but [Crestor can cause] renal disease in people who did not have rhabdomyolysis. Those are the two unique risks, and the drug offers no unique benefits."
Mark Robinson Jr., a Newport Beach, California Newport Harbor redirects here. For the MTV reality series, see .
Newport Beach, incorporated in 1906, is a city in Orange County, California, 10 miles south of downtown Santa Ana. , lawyer who represents plaintiffs in pharmaceutical cases, said AstraZeneca has misrepresented or omitted facts about adverse health effects in its advertising and marketing materials.
"It seems like every time you turn on the TV you see an ad for Crestor. Patients are given a nice picture of the drug, but the side-effect profile is not clear," he said.
A troubled history
Crestor's problems began before the FDA FDA
Food and Drug Administration
n.pr See Food and Drug Administration.
n.pr the abbreviation for the Food and Drug Administration. approved it in August 2003. When AstraZeneca submitted its New Drug Application to the agency in June 2001, two safety issues came up in the first review cycle: six cases of rhabdomyolysis among 1,365 patients exposed to the 80-mg dose, and urine abnormalities--specifically, protein and blood in the urine in some patients.
The rhabdomyolysis finding was notable because in 2001, Bayer Pharmaceuticals voluntarily (with the FDA's support) withdrew Baycol from the market after the FDA received 31 reports of fatal rhabdomyolysis linked to the drug. (See Rebecca Porter, Attorneys Press Discovery Effort in Litigation over Cholesterol Drug, TRIAL, June 2003, at 12.)
The FDA approved Crestor in doses of 5, 10, 20, and 40 mg, but not the 80-mg dose. It also required AstraZeneca to provide more extensive data to address concerns about muscle and renal toxicity.
HRG opposed the drug's approval, and after losing that battle, it petitioned the FDA to require that the drug be withdrawn from the market. The agency declined last March.
"Our review of all the available evidence (including preclinical data, premarketing clinical studies, Phase 4 clinical studies, and post-marketing adverse event reports) indicates that Crestor does not pose a risk of muscle toxicity greater than that of other approved statins. With respect to renal toxicity, there is no convincing evidence that Crestor poses a risk of serious renal injury," the FDA said. "However, to help ensure the safe and effective use of Crestor, AstraZeneca has revised the labeling to address certain concerns regarding dose-related risks, proper doses, and other matters related to information from adverse event reports and Phase 4 studies."
AstraZeneca reiterated its claim that its product is safe. "Patient safety is our top priority, and the FDA's rejection of Public Citizen's petition should reassure the millions of people who have been unnecessarily alarmed by HRG's allegations," AstraZeneca U.S. President and CEO (1) (Chief Executive Officer) The highest individual in command of an organization. Typically the president of the company, the CEO reports to the Chairman of the Board. David Brennan said in a statement.
Wolfe called the changes in Crestor's labeling "cosmetic" and said they will have no significant impact. When doctors start prescribing a drug, they consult the labeling, he said, but after that, they rarely notice even major labeling changes.
At least one study supports HRG's concerns about the drug. In an article published last May in Circulation, the journal of the American Heart Association American Heart Association (AHA),
n.pr a national voluntary health agency that has the goal of increasing public and medical awareness of cardiovascular diseases and stroke, and thereby reducing the number of associated deaths and disabilities. , researchers from Tufts-New England Medical Center's Molecular Cardiology Research Center reported their finding that Crestor isn't as safe as three other statins--Lipitor, Pravachol, and Zocor.
Lead author Richard Karas and three colleagues analyzed 145 rosuvastatin-associated adverse events during Crestor's first year of marketing and found that the drug was significantly more likely to be associated with rhabdomyolysis, proteinuria proteinuria /pro·tein·uria/ (-ur´e-ah) an excess of serum proteins in the urine, as in renal disease or after strenuous exercise.proteinu´ric
1. (protein in the urine), or kidney failure than the other statins. (Alawi A. Alsheikh-Ali et al., The Safety of Rosuvastatin as Used in Common Clinical Practice: A Postmarketing Analysis, 111 Circulation 3051-57 (2005).)
"This study raises concern about the safety of this drug at the range of doses currently used in common clinical practice in the general population," Karas said in a press release issued by Tufts. "I would advise health care providers to consider other statins as first-line therapy, to initiate therapy in appropriate patients at lower doses, to consider combination [cholesterol]lowering therapy, and to closely monitor patients for adverse events if rosuvastatin (Crestor) is used."
AstraZeneca spokeswoman Emily Denney cited shortcomings in the study. "Only the number of spontaneous event reports for Crestor through 2004 were considered, whereas important issues concerning causality or confounding factors were not," Denney said.
Robinson, whose firm represents more than a dozen clients alleging they were injured by Crestor, said the cases involve classic failure-to-warn claims. The plaintiffs allege that the manufacturer failed to warn patients about the increased risk of kidney problems (as compared with other statins) when the drug went on the market and overpromoted it without disclosing those risks.
Steven Skikos, a San Francisco lawyer, said his firm is currently evaluating cases. "The direct-to-consumer ads are leading us to believe that we have potential failure-to-warn and negligence claims, and possibly fraud," he said. "In most cases, pharmaceutical companies market their products appropriately, but in this case they did not."
In some states, a manufacturer may be held liable if aggressive marketing leads health care providers to overlook a drug's dangers despite warnings. (See Gerald D. Jowers Jr., Drug Advertising &Accountability, TRIAL, July 2003, at 68.) Robinson cited the California Supreme Court's decision in Stevens v. Park, Davis & Co., holding that a manufacturer's overpromotion of a drug undermines its warning labels. (107 Cal. Rptr. 45, 54 (1973).)
"In California, evidence of a subsequent change in your warning is admissible in evidence to prove there was an initial failure to warn," Robinson said.
Wolfe said his organization plans to continue warning patients against using Crestor. "More and more of these cases are occurring. People are being severely injured and in some cases killed by this drug," he said.