Yourlawyer.com (Crestor News) http://www.yourlawyer.com/topics/overview/crestor Sat, 21 Nov 2009 00:58:27 -0800 pixel-app en Crestor Does Not Reduce Heart Failure Deaths, Study Says http://www.yourlawyer.com/articles/read/13409 Thu, 29 Nov 2007 00:00:00 -0800 http://www.yourlawyer.com/articles/read/13409 Crestor, a cholesterol lowering statin, does not appear to reduce deaths in heart failure patients, according to a new study published in the New England Journal of Medicine.   The results of the 5,000 person CORONA study are a big blow to AtraZeneca, which had hoped to market Crestor as the first statin to show clear benefits in treating chronic heart conditions in the elderly.

Crestor was approved by the Food & Drug Administration (FDA) in 2003.  It is a member of a drug class called statins, which lower so-called "bad" cholesterol, otherwise known as LDL cholesterol. Although Crestor's cholesterol lowering ability was already established, the CORONA study was the first to explore whether Crestor improved patient outcomes in heart failure patients. 

The CORONA study was conducted with 5,000 heart failure patients in Europe, Russia and South Africa.  All of the study participants where over 60-years-old, and all suffered from ischemic heart failure, a type of heart failure caused by coronary artery disease.  This type of heart failure weakens the heart's ability to pump blood efficiently.  During the study, all of the patients continued their usual heart medications, but half added Crestor to their regimens.  Most patients in the study participated for three years.

While the Crestor patients did have reduce levels of LDL -"bad"- cholesterol and an inflammatory marker called C-reactive protein, as well as reduced heart-related hospitalizations, these benefits did not translate to a lower death rate from heart failure in the Crestor patients.  After 33 months of treatment, 692 Crestor patients had heart attacks, strokes or died of heart complications.  Of those taking a placebo in place of Crestor, 732 suffered the same problems.  The small difference between the two groups is not considered to be statistically significant.

Crestor's August 2003 FDA approval came after a delay because of safety concerns. During Crestor's clinical trials, seven cases of the potentially fatal, muscle-destroying condition Rhabdomyolysis occurred. Rhabdomyolysis is a serious disorder that causes kidney damage resulting from toxic effects of the contents of muscle cells.  These studies also linked Crestor with cases of kidney abnormalities not seen with other statins. The FDA decided to approve Crestor but at lower dosages. However, records from the FDA and health agencies in Canada and Britain show life-threatening Crestor side effects occur even at those lower doses.  In 2005, the FDA issued a public health advisory to further explain the risks and benefits of Crestor. The drug now carries a new label that includes new recommended doses for patients at a higher risk of muscle damage, including Asian patients.

]]> Study, FDA Differ On Cholesterol Drug Crestor http://www.yourlawyer.com/articles/read/9783 Tue, 24 May 2005 00:00:00 -0700 http://www.yourlawyer.com/articles/read/9783
The conclusion is at odds with the most recent recommendation of the Food and Drug Administration, which in March rejected a petition to remove Crestor from the market. At the time, the FDA said Crestor appeared to be no more dangerous than other statins for most people.

Based on the number of side effects reported to the FDA, however, the researchers said yesterday that Crestor was two to six times as likely to cause complications over a 1-year period as three other statins on the market.

Although the number of serious side effects reported by Crestor users was small, the new findings suggest that the drug, whose generic name is rosuvastatin, probably should be reserved for patients who have a hard time lowering their overall cholesterol levels with other statins, said Dr. Richard Karas of the Tufts-New England Medical Center in Boston, who led the study.

Crestor's maker, AstraZeneca, defended its billion-dollar-a-year drug, saying, "We strongly disagree with the conclusions of this study." In a statement, the company said the FDA's voluntary system for soliciting reports of complications, called "adverse events," does not confirm the accuracy of the accounts it gets and so cannot be used to determine a drug's risks.

Sidney Wolfe of Public Citizen Health Research Group, who filed the petition rejected by the FDA, said the study confirmed his conclusions.

"This should be very embarrassing to the FDA," said Wolfe, whose group may try again to get the drug off the market.

But FDA spokeswoman Laura Alvey said that the new analysis yielded no new information. "We haven't found any convincing evidence that Crestor poses any more of a risk than the other statins," she said.

Doctors participating in a teleconference set up by the American Heart Association, which funded the study, said patients should not stop taking statins but should discuss any problems with their doctors.

"Statins in general are very safe drugs and they can be life-saving to high-risk patients," said Dr. Scott Grundy of the University of Texas Southwestern Medical Center in Dallas.

Both Karas and Grundy have received research contracts and speaking fees from statin makers, including AstraZeneca. The heart association also receives considerable financial support from drug companies.

Crestor is the most potent statin on the market. Its higher strength, however, does not make a dramatic difference in studies. While statins such as Lipitor, Zocor and Pravachol lower LDL or harmful cholesterol by 50 to 55 percent, Crestor decreases it by 55 to 60 percent, said Grundy and Karas.]]> Study Finds More Side Effects From Crestor Than Other Statins http://www.yourlawyer.com/articles/read/9784 Tue, 24 May 2005 00:00:00 -0700 http://www.yourlawyer.com/articles/read/9784
The findings suggest that Crestor, manufactured by AstraZeneca, should probably be reserved for patients who have had a hard time lowering their overall cholesterol levels with other statins, said Dr. Richard H. Karas of the Tufts-New England Medical Center in Boston, who led the study.

The study was based on adverse reactions to statins reported to the Food and Drug Administration by patients and physicians.

Most of those reports involved muscle damage, called rhabdomyolysis, and poor functioning of the kidneys.

Baycol, a statin manufactured by Bayer, was removed from the market in 2001 because it was found to have an unusually high incidence of rhabdomyolysis. The drug was linked to more than 100 deaths.

Comparing the number of reported events with the number of prescriptions written, the team concluded that Crestor, whose generic name is rosuvastatin, was responsible for 2.2 times as many reports as simvastatin, sold by Merck & Co. under the brand name Zocor, and 6.8 times as many as atorvastatin, sold by Pfizer Inc. under the name Lipitor.

The rate of reports for Crestor was about half that of Baycol, Karas said.

The absolute number of problems connected to any of the statins was very low, he emphasized.

In Crestor's first year on the market after being approved in 2003, there were 145 reported muscle or kidney complications out of 5.2 million prescriptions, an absolute risk of one in 35,862.

In virtually all cases, the side effects stopped when drug use was halted.

"The absolute risk [of Crestor] is very low, even though the relative risk is increased," said Dr. Alice K. Jacobs of Boston Medical Center, president of the American Heart Assn. "The overwhelming majority of people who are taking it will have no problem at all."

The study was reported in the online version of the heart association's journal, Circulation.

The American Heart Assn. held a news conference to announce the findings in an effort to reassure people that statins are safe and that patients should not stop using the drugs.

"These are lifesaving drugs and we would not like to see" people stop taking them, said Dr. Elliott Antman of Harvard Medical School, an associate editor of the journal.

An estimated 20 million Americans take statins, one of the latest wonder drugs in physicians' arsenal.

By lowering cholesterol levels, the drugs can significantly reduce the risk of heart attack and stroke.

Recent studies have shown that they also can help prevent certain types of cancer.

The latest study contradicts an FDA study, announced this year, that concluded that Crestor was no more dangerous than other statins.

Experts said the design of the new study made it difficult to draw firm conclusions.

Adverse event reports "are not adequate to make a comparison of different statins," said Dr. Scott Grundy of the University of Texas Southwestern Medical Center at Dallas, who wrote an editorial accompanying the paper.

Events in such reports are random and incompletely reported, he said. There is no indication of how many individuals are taking the drugs, no indication of the type of patient in which the adverse events were observed and no proof that the drugs caused the events.

Critics of Crestor said the findings reaffirmed their belief that the drug was unsafe.

Dr. Sidney Wolfe of the advocacy group Public Citizen said the findings were further evidence that the drug should be removed from the market. The earlier study by the FDA was an outgrowth of a petition filed by Public Citizen calling for the drug's removal.

In light of the new data, the group will resubmit the petition, Wolfe said.]]> New Fears Over Cholesterol Drug http://www.yourlawyer.com/articles/read/9785 Tue, 24 May 2005 00:00:00 -0700 http://www.yourlawyer.com/articles/read/9785
The report's authors said the analysis raises concerns about the drug's safety, and suggest that alternatives should be used before Crestor is prescribed in order to cut the risk.

The pharmaceuticals firm has fought calls for the drug to be banned from US consumer group Public Citizen, and yesterday said it "strongly disagreed" with the new research. A recent ruling by US regulator the food and drug administration backed the company's view that it is as safe as rival drugs.

Circulation, the journal of the American Heart Association, last night published a study into side effects seen in Crestor (also known as rosuvastatin), and other common anti-cholesterol drugs Lipitor, Zocor and Pravachol. All the drugs are in a class known as statins. It concluded that the rate of side effects including rhabdomyolysis, a potentially fatal muscle wasting disease, and kidney failure is higher when taking Crestor than the other drugs. The rate of ad verse events was 28 per million prescriptions for Crestor, more than twice that of its rivals.

The article said that the Crestor rate was less than half that of Baycol, a drug that was withdrawn in 2001 due to severe side effects and deaths.

The authors warned of limitations to their study, but concluded that steps should be taken to minimise the risk while further study takes place. "This analysis raises concerns about the safety of this drug at the range of doses used in common clinical practice," said the study, which was written by AHA investigator Dr Richard Karas and others.

However experts stressed that the side effects are still rare, even from Crestor. "Importantly, most side effects, including [muscle wasting], disappear upon withdrawal of medication," said Dr Scott Grundy, director of the centre for human nutrition in the US. "It would be unfortunate for patients to quit taking statins for fear of side effects because that would increase their risk of heart attack."

Last night AstraZeneca said: "The study implies that because post-marketing rates of spontaneous adverse event reports were higher, the risk is also higher. This is factually incorrect."]]> Study On Crestor Contradicts FDA http://www.yourlawyer.com/articles/read/9786 Tue, 24 May 2005 00:00:00 -0700 http://www.yourlawyer.com/articles/read/9786
The Tufts University study contradicted findings by the U.S. Food and Drug Administration and will not help Crestor's maker, AstraZeneca P.L.C. with U.S. operations in Wilmington build Crestor into the blockbuster product it has intended.

Crestor was the first cholesterol-lowering drug in a class known as statins to be introduced since Baycol was withdrawn in 2001 because of muscle problems called rhabdomyolysis.

While controlled studies have found no increased risk from Crestor, the FDA has received a relatively high number of anecdotal reports of side effects through its Adverse Event Reporting system, known as AER.

The FDA and AstraZeneca have played down the AER rates as deceptively high because of negative publicity around Baycol. On March 14, the FDA rejected calls by a consumer group, Public Citizen, to ban Crestor.

"We believe that all available evidence to date regarding Crestor does not indicate that it poses a greater risk of adverse events than other statins," said FDA spokeswoman Laura Alvey by e-mail yesterday. "We will continue to monitor this drug as we do with all FDA-regulated drugs."

In a statement, London-based AstraZeneca rejected the new study's implication as "factually incorrect" that Crestor was riskier than other statins, such as Pfizer Inc.'s Lipitor and Merck & Co. Inc.'s Zocor.

"AstraZeneca again reaffirms that the safety profile of Crestor is in line with other marketed statins," the company said.

The Tufts study was released after the stock market closed. AstraZeneca shares closed unchanged at $42.77 yesterday on the New York Stock Exchange.

The study leader, Richard Karas, director of the Molecular Cardiology Research Center at Tufts-New England Medical Center in Boston, emphasized in a separate statement that statins overall "are very safe drugs."

He said while Crestor was found "to be less safe than others, it does not mean patients should immediately stop taking this medication. In fact, the overall risks of [Crestor] remain low, and people taking this drug should talk to their doctor before deciding whether to continue on it or stop it."]]> Researchers Deal Crestor Another Blow http://www.yourlawyer.com/articles/read/9787 Tue, 24 May 2005 00:00:00 -0700 http://www.yourlawyer.com/articles/read/9787
The study is the latest stumbling block for Crestor, launched by AstraZeneca (AZN) in 2003, which had hoped it would compete with market leader Lipitor, made by Pfizer. Last year, it was one of several drugs FDA scientist David Graham said deserved further scrutiny, and it recently survived a challenge from an advocacy group seeking to have it removed from the market.

Researchers writing in the journal Circulation found that Crestor caused significantly more cases of a serious muscle disorder called rhabdomyolysis and kidney problems than competitors Zocor, Pravachol or Lipitor, with sixfold more of these side effects in Crestor patients than in those taking Lipitor.

But all of those side effects taken together were relatively rare, with Crestor causing 28 for every million prescriptions, Zocor 13 per million, Lipitor 4.3 per million and Pravachol 3.5 per million, says lead researcher Richard Karas of Tufts-New England Medical Center.

AstraZeneca sold $908 million of Crestor worldwide last year, but it remains fifth in market share in the USA. The study was released after the market closed. AstraZeneca stock fell 3.6% in after-hours trading to $41.23.

In a statement, AstraZeneca said it disagrees with the study. Crestor's safety profile is "in line with other marketed statins and is a highly effective cholesterol-lowering therapy," the company said.

The study draws upon a Food and Drug Administration database that consumer advocates have used to challenge the safety of other drugs. But the FDA and the author of the new study say the database is difficult to interpret and that Crestor's risks do not appear to outweigh its benefits.

"I would choose to use Crestor in patients who need very aggressive (cholesterol) lowering," says Karas, who has gotten funding from the drug's maker, AstraZeneca. "We're not raising concerns over the safety of statins, and we don't want to exaggerate concerns over Crestor."

Using those same FDA reports, the advocacy group Public Citizen called in 2004 for Crestor to be taken off the market, saying it was linked to rhabdomyolysis at a rate 6.2 times that of other drugs in its class combined, and was linked to a higher rate of kidney damage.

But in March, the FDA analyzed the same data and said it could not find convincing evidence that Crestor posed a greater risk of either condition.]]> Risks Posed By Crestor May Be Worse Than Previously Believed http://www.yourlawyer.com/articles/read/9793 Tue, 24 May 2005 00:00:00 -0700 http://www.yourlawyer.com/articles/read/9793
Although there is a risk of rhabdomyolysis (severe muscle damage) with all statin drugs, critics maintain that Crestor is, by far, the most likely to cause this condition. Public Citizen maintains that its analysis of adverse events reported to the FDA between September 2003 and September 2004 linked Crestor to incidents of rhabdomyolysis at a rate 6.2 times higher than all other statin drugs combined. The FDA has acknowledged that Crestor does pose a greater risk to Asian patients as well as patients with severe kidney disease and those taking cyclosporine. As a result, a warning to that effect was added to the Crestor label in March of this year.

Now, however, a study published in the American Heart Association journal Circulation (online 5/23/05) claims that, as among the statins, even though the incidence of rhabdomyolysis is relatively low, "Crestor has a poorer safety profile." Whether this will change the FDAs opinion as to the safety of the drug or cause it to require a more serious warning to be placed on the label remains to be seen.]]> Study: Crestor Side Effects Deemed Worse http://www.yourlawyer.com/articles/read/9777 Mon, 23 May 2005 00:00:00 -0700 http://www.yourlawyer.com/articles/read/9777
The review of leading cholesterol drugs taken by millions of Americans showed that most are very safe and that the risk of serious problems, even with Crestor, are very low. But the latest research seemed to challenge a Food and Drug Administration decision not to pull the drug off the market.

In March, the FDA had contended Crestor's risks were no greater than its competitors, and it rejected consumer efforts to remove the drug, made by AstraZeneca PLC, from store shelves. Instead, the FDA ordered a warning on the label, saying Crestor could cause serious muscle problems and kidney damage, especially among Asians.

The new study, based on side effects reported to the FDA, said that kidney problems and severe muscle weakness were two to eight times more frequent among Crestor users than those taking other statins.

"This will be further reason to take the drug off the market," said Dr. Sidney Wolfe of the consumer group Public Citizen. He said his group would try again to get the drug off the market.

FDA spokeswoman Laura Alvey said that the new analysis yielded no new information. "We haven't found any convincing evidence that Crestor poses any more of a risk than the other statins," she said.

The drug's maker, AstraZeneca, said the higher reports of side effects may have been the result of heightened awareness of the problems with another cholesterol drug, Baycol, which was pulled from the market in 2001. Crestor went on the market two years later.

"We strongly disagree with the conclusions of this study," the company said in a statement.

Shares of AstraZeneca fell 36 cents, or 0.8 percent, to $42.41 in after-hours trading Monday after the study was released.

An estimated 20 million Americans are believed to be taking drugs called statins, which researchers say are still the best drugs for lowering high cholesterol and reducing the risk of heart disease and stroke.

Many of the drugs cause muscle problems among some people, but experts advise patients to talk to their doctors about lowering their dosage, which can solve the problem. Doctors said patients should not stop taking statins but should discuss any problems with their doctors.

In a teleconference, doctors reiterated that the drugs are safe overall.

"Statins in general are very safe drugs and they can be life-saving to high-risk patients," said Dr. Scott Grundy, of the University of Texas Southwestern Medical Center in Dallas.

For the new study, funded by the
American Heart Association and published online Monday by the association's journal Circulation, researchers analyzed reports of side effects sent to the FDA for Crestor and compared them to the rates during the same time period for three other statins: Lipitor, Zocor and Pravachol.

"What we've shown is that amongst this family of drugs, Crestor has a poorer safety profile, but that the overall rate of adverse effects is still quite low," said study leader Dr. Richard Karas, director of the preventive cardiology at Tufts-New England Medical Center in Boston.

Karas, who has received research grants and speaker fees from several drug companies including the maker of Crestor said that generally, the people who should consider taking Crestor are those who are unable to lower their cholesterol enough with other drugs or those who may be allergic to other drugs.

The year after Crestor came on the market in October 2003, more than 5 million prescriptions were filled for the drug.

The researchers also compared the rate of adverse event reports during the first year of marketing for the current statins and the earlier withdrawn drug, Baycol.

Complications were more common with Crestor than the other three statins available, but less than half the rate of those reported during the first year of Baycol's use. But even for Crestor, the absolute risk of a serious problem was very low; 1 in 35,862.

When side effects did occur, it tended to be within the first three months' of use. Only a few deaths occurred among the millions of users, and death rates were lower among those taking Crestor or Zocor. Karas said that scientists don't know whether the deaths were caused by the statins.

An expert and the study's authors agree that there were limitations to the study, including the possible underreporting of side effects. Also the removal of Baycol from the market likely heightened public awareness of drug safety concerns.

Dr. Benjamin Ansell, co-director of the cholesterol treatment program at UCLA medical center in Los Angeles, suggested there is also a tendency to overreport side effects, especially when a drug, like Crestor, has gotten a lot of media attention.

"I would say the study has to be interpreted with skepticism and recognizing its imitations," Ansell said.

Also, he said, those who were put on Crestor when it came out were likely those who had had problems with other statins.

"The people who are 'problem patients' are more likely to get Crestor," he said.

The bottom line, he said, is that the statins have an excellent safety record.]]> Crestor Has 'Poorest Safety Profile' Among Rival Heart Drugs: Study http://www.yourlawyer.com/articles/read/9779 Mon, 23 May 2005 00:00:00 -0700 http://www.yourlawyer.com/articles/read/9779
The study appearing in Circulation: Journal of the
American Heart Association, linked Crestor to possible kidney and muscle ailments that required hospitalization.

The drug, which generated some 908 million dollars in 2004 sales, is one of the major "statins" used to lower cholesterol and reduce the risk of heart attacks. Others include Pfizer's Lipitor, Merck's Zocor and Bristol-Myers Squibb's Pravachol.

The study concluded that Crestor had the largest number of adverse effects compared with the other medications.

"After reviewing a national database for adverse event reports, the study found rosuvastatin (Crestor) to have the poorest safety profile," said a summary of the study released by Tufts-New England Medical Center.

"The most serious reactions resulted in damage to the kidney (proteinuria/nephropathy), and muscle (rhabdomyolysis), which frequently resulted in patients requiring hospitalization."

"It is very important to note that as a family, statins are very safe drugs that have clearly been shown to reduce the risk of heart disease," said Richard Karas, Tufts University researcher and lead author of the report.

"Although rosuvastatin (Crestor) was found to be less safe than others, it does not mean patients should immediately stop taking this medication. In fact, the overall risks of rosuvastatin remain low, and people taking this drug should talk to their doctor before deciding whether to continue on it or stop it."

Earlier this year, the US Food and Drug Administration (FDA) backed the Anglo-Swedish pharmaceuticals giant's anti-cholesterol drug, saying there was no higher chance of developing muscle destruction with Crestor than for any other similar medicine.

But the latest study renewed concerns about the safety of the blockbuster drug, said the researchers.

"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," said Karas.

"I would advise healthcare 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."

There was no immediate comment from the company.]]> FDA Warns AstraZeneca On Crestor Again http://www.yourlawyer.com/articles/read/9448 Fri, 11 Mar 2005 00:00:00 -0800 http://www.yourlawyer.com/articles/read/9448
The latest letter, which was received in the last few days, said claims that Crestor lowers cholesterol better than Pfizer Inc.'s market leading medicine Lipitor are misleading because it cherry picks results from a study comparing the two medicines.

The information was reported on Forbes.com Friday.

The ads, which feature Dr.-Suess-like rhymes, were taken off the market in December. A company spokeswoman said Friday AstraZeneca believed the statements were presented appropriately, but takes the letter very seriously.

Another spokeswoman Kelly Caldwell declined to comment if the company would resume the campaign.

The company received a letter from the FDA last December over print ads it ran which said the agency confirmed the safety and efficacy of Crestor. Those ads were a response to statements made by FDA official Dr. David Graham, who said that Crestor was one of five drugs that should either be taken off the market or have its sales severely restricted. It was a one-time ad campaign.

Consumer advocacy group Public Citizen has asked the FDA to take the drug off the market because it says it causes serious health problems, including rhabdomyolysis, a severe muscle weakness condition.

Earlier this month, Crestor labels added a warning that starter doses should be reduced in Asian-Americans and some other patients.

A clinical trial found that levels of Crestor in patients with Asian heritage were double those of Caucasians taking the same dose, increasing the chance of muscle damage.]]> Crestor Warnings Too Weak, Group Says http://www.yourlawyer.com/articles/read/9452 Thu, 10 Mar 2005 00:00:00 -0800 http://www.yourlawyer.com/articles/read/9452
Debate over Crestor is set against a backdrop of growing concern over drug safety and comes four years after another cholesterol drug, Baycol, was pulled from the market after being linked to at least 31 deaths from a condition that causes muscle tissue to die.

Public Citizen says its analysis of adverse events reported to the Food and Drug Administration during a yearlong period ended in September linked Crestor to that muscle condition, called rhabdomyolysis, at a rate 6.2 times that of all currently marketed statin drugs combined.

But AstraZeneca (AZN), which makes the drug, said Public Citizen's report is based on "unscientific information and incomplete analysis."

Just last week, the FDA approved a new label for Crestor that, while warning of a higher risk in Asian patients, said the drug's rate of muscle problems among people using the recommended dosages is similar to that of other statins. On Thursday, the FDA said it stood by those comments.

In November, an FDA scientist revived debate over the drug when he told Congress that it was linked to kidney failure and rhabdomyolysis, a statement the agency later distanced itself from.

Sales of Crestor, launched in 2003, have been dampened by Public Citizen's petition in March 2004 for the FDA to withdraw the drug, and media attention around the congressional hearings into drug safety.

Still, the drug brought in $908 million in sales worldwide last year, according to AstraZeneca's annual report. U.S. sales were $608 million, and it ranked fifth in total prescriptions in the statin drug category, well behind top players Lipitor and Zocor, according to IMS Health, which tracks the industry.

Physician Sidney Wolfe of Public Citizen says his analysis of adverse-event information given to the FDA by drugmakers, doctors and patients shows 13.1 reports of the muscle damage per million prescriptions of Crestor. All other statins combined had a rate of 2.1 million reports during that same time period.

"Six times higher is not my definition of similar," says Wolfe, a longtime critic of the FDA.

Still, researchers caution that the data gathered from adverse-event reports are not definitive because the reports are voluntary, may be duplicative and are not independently verified. The reports can be useful, particularly when they spot rare side effects, as warning flags showing a drug may warrant additional study.]]> Health Canada Advises Patients Ab Risks of CRESTOout TheR (rosuvastatin) http://www.yourlawyer.com/articles/read/9438 Thu, 03 Mar 2005 00:00:00 -0800 http://www.yourlawyer.com/articles/read/9438
In Canada, and internationally, CRESTOR has been associated with reports of a serious condition called rhabdomyolysis. Rhabdomyolysis results in muscle breakdown and the release of muscle cell contents into the bloodstream.

Symptoms of rhabdomyolysis include muscle pain, weakness, tenderness, fever, dark urine, nausea, and vomiting. In severe cases, rhabdomyolysis can lead to kidney failure and be life-threatening.

For some patients, there may be pre-existing conditions or other personal factors that could cause a greater risk of developing muscle-related problems, including rhabdomyolysis, if they are using "statin" medications.

The risk of rhabdomyolysis is increased at the highest recommended daily dose of CRESTOR, which is 40 mg daily. For this reason, Health Canada has advised that the 40 mg dose must not be used in patients who have pre-existing medical conditions or other factors which put them at increased risk for rhabdomyolysis. These factors include:

Personal or family history of muscle problems
Past history of significant muscle pain or muscle weakness while using a "statin" drug
Taking any other cholesterol-lowering medications
Serious liver problems
An underactive thyroid gland
Alcohol abuse
Asian ethnicity

Asian patients (having either Filipino, Chinese, Japanese, Korean, Vietnamese or South Asian origin) may be at greater risk of developing muscle-related adverse events, including rhabdomyolysis, with CRESTOR(rosuvastatin). In a recent U.S. study, levels of rosuvastatin were found to be approximately two times greater in Asian-Americans when compared to a Caucasian control group.

Health Canada recommends that all patients taking CRESTOR should be using the lowest dose that will meet their treatment goal. A 5 mg starting dose is recommended for:

Asian patients
Patients with serious kidney problems
Patients who might have other risk factors for muscle problems

Health Canada continues to monitor the use of CRESTOR(rosuvastatin) for a possible association with kidney failure, and will update Canadians as further information becomes available.

In addition, Health Canada has asked all manufacturers of "statin" drugs to update the information in the Canadian Product Monographs to enhance the safe and effective use of this group of cholesterol-lowering medications. The new information will include the medical conditions and other factors that might cause a patient to have an increased risk of muscle-related adverse reactions to "statin" medications. The new information will also provide patients with more information about the safe use of "statin" drugs. The medical conditions and other factors which might cause a patient to be at greater risk of muscle related adverse reactions to "statin" medications include:

Personal or family history of muscular problems

Previous history of muscle problems with another "statin"

Use of other cholesterol medications
Underactive thyroid gland
Alcohol abuse
Excessive physical exercise
Aged 70 years or over
Kidney problems
Liver problems
Diabetes with fat deposits in the liver
Surgeries or injuries
Frail physical condition]]> Warning Issued On Use of Crestor by Asians http://www.yourlawyer.com/articles/read/9414 Wed, 02 Mar 2005 00:00:00 -0800 http://www.yourlawyer.com/articles/read/9414
The Food and Drug Administration said Wednesday that Crestor, like other drugs in the category known as statins, can have a rare side effect of serious muscle damage.

A clinical trial found that levels of Crestor in Asian patients were double those of Caucasians taking the same dose, increasing the chance of muscle damage.

The new label urges physicians to start Asian patients, those with severe kidney disease and patients taking cyclosporine at the lowest dose level.

The lowest available dose would be 5 milligrams, compared with a maximum dose of 40 milligrams.

The cholesterol-lowering drug has been prescribed to more than 4.3 million patients, according to manufacturer AstraZeneca.

"We continue to believe Crestor is safe and effective when used according to the prescribing information," said David Brennan, AstraZeneca president.

Dr. Steven Galson, acting director of the FDA's Center for Drug Evaluation and Research, said the "advisory on Crestor is part of an ongoing effort to notify the public of potentially significant emerging safety data so that they can make more informed choices about their medical care."

Crestor has drawn some criticism for the reported muscle damage, but the FDA statement said a review of available data indicates the risk from Crestor is no higher than that from other statin drugs.

The FDA noted that kidney failure has also been reported in patients treated with Crestor and other statins. However, the agency said, since many patients who take these drugs have diabetes, high blood pressure or heart disease, they may already be at higher risk for kidney failure.

Overall, the FDA said it believes the benefits of statin drugs, when used as recommended, outweigh their potential risks.

Crestor has drawn criticism from consumer advocate Dr. Sidney Wolfe of Public Citizen as well as FDA whistleblower David Graham.

Wolfe issued a statement calling the FDA's announcement "yet another example of the agency's dangerous cowardice in failing to adequately protect people in this country from uniquely dangerous prescription drugs."

He has petitioned to have Crestor pulled from the market, citing reports of muscle damage and kidney failure.

In December the manufacturer said it had halted ads that the FDA had criticized as misleading because they suggested Crestor was safer than had been proven.]]> FDA Public Health Advisory on Crestor (rosuvastatin) http://www.yourlawyer.com/articles/read/9415 Wed, 02 Mar 2005 00:00:00 -0800 http://www.yourlawyer.com/articles/read/9415
Background

Crestor, a member of a class of cholesterol-lowering drugs commonly referred to as "statins", was approved in the U.S. in August 2003, based on review of an extensive clinical database involving approximately 12,000 patients. These data supported the safety and efficacy of Crestor for use in lowering serum cholesterol, but also showed that Crestor, like all statins, rarely could cause serious muscle damage (myopathy and rhabdomyolysis). In the approved labeling, the FDA identified in the WARNINGS section of the product label those patients in whom more careful monitoring was warranted when prescribed Crestor. In a section titled: "Myopathy/Rhabdomyolysis", the label states that patients who are of advanced age (> 65 years), have hypothyroidism, and/or renal insufficiency should be considered to have a greater risk for developing myopathy while receiving a statin. Physicians are warned to prescribe Crestor with caution in these patients, particularly at higher doses, as the risk of myopathy increases with higher drug levels.

Based on these concerns, from the time of original approval, the FDA required Astra-Zeneca to make available in the U.S. a 5-mg dose that could be used in patients requiring less aggressive cholesterol-lowering or who were taking concurrent cyclosporine. The maximum recommended dose in the FDA-approved label is limited to 10 mg daily in patients with severe renal impairment or who are also taking gemfibrozil.

Description of current changes to the Crestor label

In a pharmacokinetic study involving a diverse population of Asians residing in the United States, rosuvastatin drug levels were found to be elevated approximately 2-fold compared with a Caucasian control group. As a result of these findings, the "Dosage and Administration" section of the label now states that the 5 mg dose of Crestor should be considered as the start dose for Asian patients and any increase in dose should take into consideration the increased drug exposure in this patient population. Results of this pharmacokinetic study are further discussed under the "Clinical Pharmacology" and "Precautions" section of labeling.

The "Warnings" and "Dosage and Administration" sections of the label have been revised to more strongly emphasize the risks of myopathy, particularly at the highest approved dose of 40 mg. In order to minimize risks of myopathy and rhabdomyolysis (the most severe form of statin muscle injury), the revised label now explicitly states that the 5 mg dose is available as a start dose for those individuals who do not require aggressive cholesterol reductions or who have predisposing factors for myopathy. This includes patients taking cyclosporine, Asian patients, and patients with severe renal insufficiency. It also emphasizes that the 40 mg dose is not an appropriate start dose and should be reserved only for those patients who have not achieved their cholesterol goals with the 20 mg dose. This information is included in a bolded paragraph under the "Dosage and Administration" section that also reminds prescribers who switch patients from other statins to initiate therapy only with approved doses of Crestor and titrate according to the patient's individualized goal of therapy.

Healthcare professionals are reminded of the following key safety messages from the Crestor label:

Start doses and maintenance doses of drug should be based on individual cholesterol goals and apparent risks for side-effects

All patients should be informed that statins can cause muscle injury, which in rare, severe cases, can cause kidney damage and organ failure that are potentially life-threatening

Patients should be told to promptly report to their healthcare provider signs or symptoms of muscle pain and weakness, malaise, fever, dark urine, nausea or vomiting

Review of Crestor muscle and kidney safety

Concerns have been raised about the possible increased muscle toxicity of Crestor compared to other statins on the market and about possible adverse effects on the kidney. The FDA has conducted an extensive review of Crestor data from pre-marketing and post-marketing clinical trials as well as adverse event reports submitted to the agency.

Muscle
Crestor, like all statins, has been associated with a low incidence of rhabdomyolysis (severe muscle damage). Data available to date from controlled trials, as well as post-marketing safety information, indicate that the risk of serious muscle damage is similar with Crestor compared to other marketed statins. As with all statins, some individuals taking Crestor will experience muscle side effects, most commonly mild aches and very rarely severe muscle damage. Like all drugs in this class, risks of muscle injury can be minimized by adhering to labeled warnings and precautions, carefully following dosing instructions, and instructing patients to be aware of and to report possible side effects to the physician. Finally, like all statins, Crestor should be prescribed at the lowest dose that achieves the goals of therapy (e.g., target LDL-C level).

Kidney
Various forms of kidney failure have been reported in patients taking Crestor, as well as with other statins. Renal failure due to other factors is known to occur at a higher rate in patients who are candidates for statin therapy (e.g., patients with diabetes, hypertension, atherosclerosis, heart failure). No consistent pattern of clinical presentation or of renal injury (i.e., pathology) is evident among the cases of renal failure reported to date that clearly indicate causation by Crestor or other statins.

Mild, transient proteinuria (or protein in the urine, usually from the tubules), with and without microscopic hematuria (minute amounts of blood in the urine), occurred with Crestor, as it has with other statins, in Crestors pre-approval trials. The frequency of occurrence of proteinuria appeared dose-related. In clinical trials with doses from 5 to 40 mg daily, this effect was not associated with renal impairment or renal failure (i.e., damage to the kidneys). It is recommended, nevertheless, that a dose reduction and an investigation into other potential causes be considered if a patient on Crestor develops unexplained, persistent proteinuria.]]> No Black Box for Crestor http://www.yourlawyer.com/articles/read/9428 Wed, 02 Mar 2005 00:00:00 -0800 http://www.yourlawyer.com/articles/read/9428
The agency's advisory included some revisions in the drug's label, telling doctors to start some patients at lower doses and to check for certain medical conditions before prescribing the drug.

Some critics wanted more. The consumer group Public Citizen urged that Crestor be banned. Crestor's foes alleged the drug causes more dangerous side effects, such as a rare muscle-damaging disease called rhabdomyolysis, than similar cholesterol-lowering drugs.

But the FDA said that "Crestor, like all statins, has been associated with a low incidence" of this muscle damage. Statins are the class of drugs that include Lipitor from Pfizer, Zocor from Merck and Pravachol from Bristol-Myers Squibb.

Data from clinical trials and postmarketing safety reports "indicate that the risk of serious muscle damage is similar with Crestor compared to other marketed statins," the FDA said.

The agency also said it "could not confirm that recommended doses of statins, including Crestor, can cause or worsen kidney failure."

The FDA concluded that the potential benefits of all statin drugs, when used properly, "outweigh the potential risks."

The news apparently softened the blow of the stronger label warnings. AstraZeneca's stock slipped 11 cents to $39.91 on trading volume that was about twice the daily average for the past three months.

"Post-marketing data for Crestor has been thoroughly reviewed over the past year and this labeling revision is the result of that analysis," said David Brennan, president and CEO of AstraZeneca's U.S. operations. "The revisions that the FDA has approved provide physicians with further clarification on how best to use Crestor with their patients. We continue to believe that Crestor is safe and effective when used according to the prescribing information."

Dr. Sidney Wolfe, director of Public Citizen's Health Research Group, called the FDA's decision "another example of the agency's dangerous cowardice in failing to adequately protect people in this country from uniquely dangerous prescription drugs."

Approved by the FDA in August 2003, Crestor hasn't achieved the sales growth that the company or financial analysts had expected thanks in part to critics such as Public Citizen, the British medical journal The Lancet and the veteran FDA researcher Dr. David Graham. During a Senate hearing in November about Merck's arthritis drug Vioxx, Graham told legislators that several other drugs on the market, including Crestor, should be reviewed, restricted or removed.

AstraZeneca has vigorously defended the safety of the drug sometimes too vigorously. In December, the FDA told it to stop running a Crestor advertisement, even thought AstraZeneca already had halted the ad.

New Cautions

The FDA's public health advisory says the new label contains a bolstering of the warning that people who take the highest daily dose 40 milligrams have the highest risk of the muscle disease. The agency said doctors should never prescribe 40 milligrams as a starting dose; it should be prescribed only if a patient hadn't achieved success with 20 milligrams.

The revised label tells doctors to start patients on the lowest daily dose 5 milligrams if they don't need aggressive lowering of their serum cholesterol. The lowest dose also should be prescribed for patients most at risk for the muscle disease Asians; people with kidney problems; or people taking the drug cyclosporine, a treatment for patients with transplated organs and with some autoimmune diseases.

The FDA also said doctors should monitor patients for protein in the urine, a potential indicator for kidney problems. The frequency of this condition -- called proteinuria -- appears to be related to the dose, said the FDA. It said clinical tests for Crestor at daily doses below 40 milligrams didn't show a link between this condition and kidney disease.

"If a patient on Crestor develops unexplained, persistent proteinuria," doctors should cut the dose and look for other possible causes, the FDA said.]]> Rosuvastatin Calcium (marketed as Crestor) Information http://www.yourlawyer.com/articles/read/9427 Tue, 01 Mar 2005 00:00:00 -0800 http://www.yourlawyer.com/articles/read/9427 Crestor Should Only Be Used As Last Resort, Says FDA Chief http://www.yourlawyer.com/articles/read/9316 Sat, 12 Feb 2005 00:00:00 -0800 http://www.yourlawyer.com/articles/read/9316
Dr Graham's views will be seen as a blow to AstraZeneca, which has been trying to reverse a sales slide of its anti-cholesterol drug which began when its safety was first publicly questioned by the scientist in November.

Dr Graham said during an interview that Crestor had a "unique toxicity", caused by the fact that, in a small number of patients, it has two adverse side-effects: muscle wasting and kidney failure. For this reason, Crestor should only be used "as a second-line drug when people have failed to respond to other statins", he said.

"Why would you push a drug that you know has potentially a high risk of muscle disease and renal failure when there are other drugs that you know work well?" Dr Graham added.

AstraZeneca strongly rejects Dr Graham's views. Gunnar Olsson, the head of cardiovascular therapies at the company, said Crestor had a "very good efficacy in lowering bad cholesterol and increasing good cholesterol and, at the same time, has a safety profile that is very much in line with all other marketed statins". He added that other statins a class of drug used to prevent ailments including chest pain and strokes also had side-effects which could include muscle wasting and kidney failure.

Crestor has been on the market in the US and UK since 2003. After Dr Graham first told a Senate hearing last year that Crestor was one of five drugs that required further testing, AstraZeneca's share of the anti-cholesterol drug market in the US fell from 8 per cent to 6 per cent. AstraZeneca's target for Crestor is nearer 20 per cent.

The scientist, who works in the FDA's office of drug safety, emphasised his opinion was a personal one and not the official view of the agency, which is still evaluating data being collected now Crestor is on the market.

Dr Graham's relationship with his employer has become fraught after a series of damning remarks he has made about the FDA's handling of issues surrounding Vioxx, the arthritis drug made by Merck.

The US pharmaceutical company withdrew Vioxx in September after scientific studies showed the drug increased the risk of heart attack.

Yesterday Merck defended itself against new claims that it tried to persuade doctors sceptical about Vioxx to offer the drug by offering them consultants' jobs and other perks.]]> New Guidance For Asians on Crestor http://www.yourlawyer.com/articles/read/9191 Thu, 13 Jan 2005 00:00:00 -0800 http://www.yourlawyer.com/articles/read/9191
The recommendation already exists for patients of Japanese and Chinese origin, and is being expanded, said AstraZeneca spokesman Steve Brown in London.

Studies show Crestor enters the bloodstream in higher concentrations in Asians than Caucasians.

U.S. prescribing guidelines mention the findings but do not explicitly recommend the lower dose. When the drug was approved by the FDA, AstraZeneca agreed to study the drug's effects on Asians in the United States, said company spokeswoman Emily Denney in Fairfax. That study is ongoing, she said.

The drug is now available in up to a 40-mg dose in the United States.

Crestor is nearing approval in Japan at doses ranging from 2.5 mg to 20 mg. About 150,000 of the globe's 15 million deaths from heart disease each year are in Japan, the company said.

Buoyed by tougher cholesterol-reduction guidelines and findings that it is the most potent anti-cholesterol drug at a given dose, AstraZeneca hopes to capture 20 percent of the statin market. But sales have been slower than expected because of competition and safety concerns.

In a report Wednesday, London equity firm Druganalyst suggested that AstraZeneca chief executive Tom McKillop had not been forthright with investors about prospects for its new drugs, including Crestor.]]> Crestor Gives AstraZeneca A Big Headache http://www.yourlawyer.com/articles/read/9192 Wed, 12 Jan 2005 00:00:00 -0800 http://www.yourlawyer.com/articles/read/9192
The latest negative sign came in a report this week by Deutsche Bank, Astra Zeneca's broker, highlighting that the company had informed regulators in December of a case of a patient taking Crestor who died in late 2004. While there is considerable debate about the significance of the case, it follows a string of bad news over the drug.

Last autumn David Graham, a scientist at the US Food and Drug Administration, darkened the mood when he told a congressional hearing that Crestor also known as rosuvastatin was one of five medicines that should be withdrawn from the market on health grounds.

The FDA, which played down Mr Graham's general criticisms, refuses to comment on the specific case, but it may not yet have had its last word. Sidney Wolfe from Public Citizen, a consumer watchdog that has waged a war against the drug, says: "The FDA is intensively looking at Crestor."

Public Citizen, which lobbied the FDA to make AstraZeneca remove a statement on its website claiming that the regulators had no safety concerns with Crestor, argues that it should be withdrawn.

Dr Wolfe says: "It is a doomed drug. It is not going to survive." He suggests it has caused more than 100 life threatening incidents.

AstraZeneca rejects such claims. Gunnar Olsson, vice-president of the company's cardiovascular division, stresses that Crestor was authorised during a climate of heightened sensitivity, just as the FDA was withdrawing Baycol, a rival drug in the same class of 'statins', from the market.

Mr Olsson says the company used a far larger group of patients in clinical trials some 12,500 than is normal to test its efficacy and safety, and has ongoing trials with 45,000. There are 15m prescriptions of Crestor to 4m patients in 50 countries.

By this summer, he says AstraZeneca should have detailed safety results, but autopsies showed that so far the only two previous suspicious deaths of patients taking Crestor were the result of other factors. He points out that many other explanations may have been behind the latest case.

The principal concern with the statins is that in rare cases they can cause a potentially life-threatening muscle condition known as rhabdomyolysis, triggering kidney failure.

Mr Olsson says that the results for Crestor suggest a lower risk than other statins. Baycol, which had 10m prescriptions, was linked to 31 deaths, for example.

"The key is to look at the data," he says. "I'm scared that if we have a lot of negative publicity about statin risks that forces people to stop therapy, the net effect will be very bad for society. Their beneficial effects are so well documented."

Aside from public health, it is precisely this kind of press that could damage AstraZeneca's financial position. Sales of Crestor this year are projected to reach about $900m (480m), and to peak at up to $3.4bn by 2008, making it one of the company's top three drugs.

"The question is whether the publicity which has helped cut Crestor's US market share from 8.5 per cent to 5.6 per cent will be sustained," says one analyst. "If it becomes a $1.5bn drug, that could cut AstraZeneca's earnings per share from 12 per cent to 10 per cent."

In the months ahead, medical researchers will be scrutinising the safety data closely and investors will in turn be studying their analyses more closely than ever.]]> Mixed Signals On Medical Warnings http://www.yourlawyer.com/articles/read/9147 Sun, 02 Jan 2005 00:00:00 -0800 http://www.yourlawyer.com/articles/read/9147
The back and forth on Crestor is dizzying. The newest and most-powerful cholesterol drug on the market is safe, insists its maker. No, it's not, some consumer advocates argue.

Crestor maker AstraZeneca says reports of adverse reactions to the drug are comparable to other cholesterol drugs. Advocacy group Public Citizen says those same reports show the drug has a higher-than-average rate of problems.

The debate isn't just between the company and Public Citizen. A Food and Drug Administration scientist last month told Congress that the drug is linked to kidney failure and a rare, but serious muscle disorder called rhabdomyolysis. He said Crestor is one of five drugs that needs more scrutiny. But, shortly afterward, the FDA issued a statement saying scientist David Graham's testimony does not reflect the agency's views.

All the while, a multimillion-dollar advertising blitz for Crestor continues. On television, viewers repeatedly see a Crestor commercial featuring a jogging woman fretting about her cholesterol. Readers of newspapers and magazines see full-page ads with coupons offering 15 days of free pills.

Caught between ubiquitous marketing and conflicting science, many consumers can't tell what to believe.

''Isn't it a shame we have a drug that's been on the market and reasonable people can disagree over whether it's too toxic to use?'' says Jerry Avorn, a professor at Harvard Medical School and author of ''Powerful Medicines, The Benefits, Risks and Costs of Prescription Drugs.'' ''No drug should be on the market this long and still have these questions unresolved.''

While all the talk may scare some patients, Avorn does not think that's bad. ''Americans, both patients and doctors, are more comfortable than they should be,'' he says. ''They think that somehow the safety of drugs is assured when they are marketed.''

The Crestor debate is set against a backdrop of growing concern over drug safety and comes just three years after another cholesterol drug, Baycol, was pulled from the market. It was linked with at least 31 deaths from rhabdomyolysis, which occurs when muscle tissues die and release toxins that can cause organ damage or kidney failure.

Ultimately, more attention to drug safety may result in changes at the FDA, longer approval times for drugs or increased oversight of drugs once they hit the market.

But the first effect may be to cool Americans' belief that newer is better and to steer them toward a wait-and-see approach that some doctors and consumer advocates have long urged.

''The real key is for people to go with newest drugs last,'' after trying older drugs with longer track records, ''not first,'' says Jay Cohen, an associate professor of Family and Preventive Medicine at the University of California-San Diego and author of ''Over Dose: The Case Against the Drug Companies.''

Insurers' warnings

Some large insurers already do that, placing most new drugs in a category that either requires prior approval before a prescription is written or requires that the patient make a larger co-payment toward the drug.

That gives the insurer time to consider the evidence in favor of the drug and weigh any safety concerns. Cost is also an issue with many new drugs, as they are often more expensive than the older products they aim to replace.

Insurers WellPoint, Premera Blue Cross, Anthem and Kaiser Permanente are among those with cautious policies on Crestor, which is in a class of drugs called statins. Those insurers encourage doctors and patients to try the older drugs first by offering them at a lower cost than Crestor.

David Campen of Kaiser Permanente, the nation's largest nonprofit HMO, says the generic statin drugs, along with name brands Zocor and Lipitor, work for most patients. Long-term studies of patients using those two drugs have shown that they not only bring down cholesterol levels, but also help prevent heart disease. Crestor is too new for such studies.

''If you have something that (you already know) is safe and effective for the vast majority of patients who have high cholesterol, why not use that first?'' says Campen, medical director for pharmacy services.

Kaiser Permanente patients filled 709,020 prescriptions for statin drugs in the first nine months of the year; only 293 were for Crestor.

Less drug testing

A concern about new drugs is that the tests leading to FDA approval often involve only a few thousand people not enough to reveal rare but significant side effects that may occur once in 10,000 patients. Those who don't try drugs when they are first marketed benefit from what doctors, drug companies and the FDA learn after tens of thousands of consumers do use them.

Some doctors say waiting a year or two before trying a new drug is long enough.

Sidney Wolfe, a doctor who heads Public Citizen's health research group, urges consumers not to use new drugs for the first seven years on the market, unless the drug is truly a breakthrough and there are no other options. Seven years are enough for regulators to uncover serious side effects and take action, he says.

Crestor's supporters say the drug offers advantages over the other statins. AstraZeneca says some patients on other drugs do not reduce their cholesterol enough.

AstraZeneca ads say Crestor lowers the so-called bad cholesterol an average of 46 percent at Crestor's typical starting dose of 10 milligrams. The ads say that's better than the performance of other brand-name statin drugs.

But the ad does leave out the generic competitor, lovastatin, which Consumer Reports magazine just named as the ''best buy'' in the statin category for many patients who need only a moderate reduction in cholesterol.

Crestor's ads imply that Crestor patients may be able to take a lower dosage of that drug than of another statin.

That's important, supporters say, because the possibility of side effects increases with a drug's dosage and strength. Warnings on statins include the possibility of rhabdomyolysis and of liver damage. Also, some patients do better on one drug than another, for reasons not always understood.

''It's important to have a variety of statins for patients to go with,'' says Michael Davidson, director of preventive cardiology at Rush University Medical Center in Chicago, who has done consulting for AstraZeneca. ''All the data we've seen says that Crestor is a safe statin.''

But Cohen says many patients with elevated cholesterol don't need a drug with Crestor's strength. A less-powerful statin might lower their cholesterol 25 percent to 35 percent.

''Most people with high cholesterol don't have major cardiovascular disease and don't need superstrong dosing,'' says Cohen, a doctor whose opinion is shared by some other doctors.

Cohen suggests patients ask doctors: ''Which is the mildest treatment that will do the job?''

An advertising blitz

''Mild'' is not an adjective associated with AstraZeneca's marketing, which touts Crestor's strength. AstraZeneca spent $122 million on TV and print advertising for Crestor from January through September - $28 million more than Pfizer spent on Lipitor, the top-selling cholesterol drug, says TNS Media Intelligence/CMR.

But its share of statin prescriptions remains well below AstraZeneca's goal of 20 percent. Crestor is the fifth-most-commonly prescribed statin in the United States, behind Lipitor, Zocor, Pravachol and generic lovastatin, according to IMS Health, a pharmaceutical information firm.

Even as it tries to whittle into competitors' leads, AstraZeneca also has had to counter concerns about Crestor's risks. The company's pre-market medical studies showed that Crestor at high doses was linked with rhabdomyolysis, the same disorder that led to Baycol's withdrawal. Seven patients taking a high dose of Crestor, 80 milligrams, developed the condition during pre-market tests. None died.

Those studies led AstraZeneca to withdraw its FDA application to market an 80-mg pill. In August 2003, the company was given approval to sell Crestor in doses ranging from 5 mg to 40 mg. AstraZeneca recommends a starting dose of 10 mg for most patients, although British health regulators suggest 5 mg may be more appropriate.

In its first week on the market, Crestor took off, garnering more than 18,000 prescriptions. Two months after it received FDA approval, company leaders were already calling it a ''megabrand.''

But a month later, the respected British medical journal The Lancet blasted AstraZeneca in a sharply worded editorial.

AstraZeneca ''pushed its marketing machine too hard and too fast'' with Crestor, the journal said. Physicians ''must tell their patients the truth'' that, compared with rival drugs, Crestor ''has an inferior evidence base supporting its safe use.''

Disputing the critics

AstraZeneca fired back in a Nov. 1, 2003, letter to The Lancet, saying 10,000 people had taken part in the drug's pre-market tests - more than for any other statin. The company had seen nothing unexpected in adverse-event reports since Crestor's launch.

''Post-marketing surveillance confirms its safety profile to be similar to that of other marketed products in the statin class,'' wrote Tom McKillop, chief executive of AstraZeneca.

But Crestor took another public relations blow in March when Public Citizen's Wolfe petitioned the FDA to remove the drug from the market. Public Citizen has a strong record as a drug-safety watchdog: Of 25 drugs that it has petitioned the FDA to remove over the years, 16 were withdrawn and five received new restrictions, Wolfe says. The FDA has not responded to the Public Citizen's petition.

The group said Crestor is more likely than other statins to lead to rhabdomyolysis.

AstraZeneca disputes that, saying Public Citizen relied on reports of muscle problems among patients in the pre-market trials who were taking 80-mg doses - dosages not approved by the FDA and not sold. Patients taking lower doses in the pre-clinical trials did not experience an unusual rate of muscle problems, the company says.

In October, Public Citizen criticized Crestor again, saying the FDA had received 29 reports of patients experiencing serious kidney problems, including kidney failure, since the drug's launch. That equals a rate per million prescriptions about 75 times higher than other statin drugs, Wolfe says.

He also says that by August, 65 reports of the muscle disease had been reported among patients taking the drug in the United States, many of them on a 10-mg dose. The rate of the muscle disorder, Wolfe says, is only slightly lower than that of the recalled Baycol.

'Uniquely dangerous'

''We think it's uniquely dangerous,'' Wolfe says.

AstraZeneca spokeswoman Emily Denney counters Wolfe, saying the company had investigated all 29 reports of kidney problems and found ''no causal relationship'' between them and the drug. Denney says the rate of the muscle disorder among Crestor patients worldwide is ''in line'' with other statins. All statins carry warnings that use could lead to muscle or liver problems.

''We have the utmost confidence in the safety and efficacy profile of Crestor,'' says Jim Blasetto, director of clinical development for Crestor.

A study published in February in the journal Cardiology, which reviewed AstraZeneca's pre-market clinical trials, concluded that statin drugs, including Crestor, may have a protective effect on the kidneys.

''My experience with Crestor suggests it is a safe statin,'' says Donald Vidt, one of the study's co-authors, who has been a paid consultant for AstraZeneca. He is also a consultant in the Department of Nephrology and Hypertension at the Cleveland Clinic.

Crestor's maker directs consumers to a company Web site, www.rosuvastatininformation.com, for more information about the drug. One chart on that site shows the rate of muscle-disorder reports per million Crestor prescriptions is comparable with other statins on the market, but it does not give the exact numbers of reports for any of the drugs, so it is hard to assess exactly where Crestor falls.

Other bar charts compare kidney failure reports for people taking Crestor and the other statins, showing kidney failures as a percentage of all adverse events reported to the FDA for each of the drugs. Again, consumers are not told the underlying number of cases from which the ratios are derived. Denney said the company would not release the totals.

But comparisons would be touchy even with precise numbers of adverse-event reports. Those reports, which are voluntary submissions to the drug company or the FDA by doctors and patients, are considered imperfect because not all adverse events get reported, nor are all reported problems caused by the drug in question.

Still, adverse-event reports are one of the ways the U.S. monitors drugs after they hit the market.

''The claims for its (Crestor's) danger as well as its safety are based primarily on these spontaneous reports, which everyone in the field recognizes are very unreliable,'' says Harvard doctor Avorn.

''Until this is clarified why not use the drugs that have been out there for years, where we know we have very solid safety track records and demonstrated outcomes?'' ]]> Crestor Debate Intensifies http://www.yourlawyer.com/articles/read/9121 Tue, 28 Dec 2004 00:00:00 -0800 http://www.yourlawyer.com/articles/read/9121
The consumer group Public Citizen has long been calling for Crestor's recall, citing a higher risk for a serious muscle disorder called rhaddomyolysis.

The Early Show medical correspondent Dr. Emily Senay notes that Crestor's statin cousins include Lipitor and Zocor.

Crestor lowers a person's bad cholesterol, the "LDL," and raises good cholesterol, the "HDL."

The difference between Crestor and the other statins, Senay points out, is that this one has been touted as being able to lower cholesterol more aggressively.

According to the FDA, Crestor is the only statin that causes acute kidney failure and carries a higher risk of rhabdomyolysis, a potentially life-threatening muscle disorder.

Crestor is available in doses of 5mg to 40mg. The higher the dose you're on, the higher the potential for problems, Senay explains. The company originally wanted to market an 80mg pill, but changed its mind when it discovered a much higher risk for this muscle disorder among people taking that high a dose in clinical trials. And actually, frequency of this muscle disorder was a problem for a statin that was pulled from the market in 2001, Baycol.

The maker of Crestor, AstraZeneca, swears up and down that the drug is safe. The company says reports of adverse reactions to the drug are in line with those for other cholesterol drugs. But Public Citizen is petitioning the FDA to pull the drug from the market, and has been since Crestor was unveiled in August 2003. What's changed now is that the FDA has begun to comment. In fact, just last week, the agency demanded that a print ad for Crestor be pulled due to what the FDA said were misleading safety claims.

Senay speculates that the reason the FDA is getting more into the Crestor mix now is that we've had so many issues with other drugs, such as Vioxx and Aleve. The FDA may just be airing the dirty laundry now because it doesn't want to be caught looking the other direction in this climate.

Crestor, Senay continues, is a much newer drug than Lipitor and Zocor, having only been on the market a little over a year. The first statin hit the market in 1987, and Lipitor, the most popular statin, was introduced in 1997. We have a lot more data on the other statins, and they've proven to have very low risk of dangerous side effects. All statins have risks of side effects. Some of the common ones are muscle tenderness, abdominal pain, dizziness, and liver problems -- but the issues with crestor reportedly can be much more serious.

What should people who use Crestor? Should they keep taking it, or perhaps switch to another statin?

If you need to lower your cholesterol, and diet and exercise aren't lowering it enough, statins are an excellent way to do it, Senay points out. Your first choice should be one of the statins that's been on the market longer, such as Lipitor, Zocor, Prevachol or the generic Lovastatin. These drugs have a very good track record, and have been widely prescribed for years. We have very good data on these drugs. If these don't lower your cholesterol enough or you have an allergic reaction, then you might want to try Crestor and see if it works for you. It's supposed to be more aggressive and in some cases, you might need it to really attack that cholesterol level. ]]> Crestor Ads Draw Fire; FDA Could Act http://www.yourlawyer.com/articles/read/8988 Wed, 08 Dec 2004 00:00:00 -0800 http://www.yourlawyer.com/articles/read/8988
Crestor is one of five drugs named as potentially hazardous by FDA drug safety officer David Graham in testimony to Congress. AstraZeneca, which manufactures and markets Crestor, responded with full-page advertisements in national and regional publications, including The Wall Street Journal, The Washington Post,The New York Times, and USA TODAY that said, "The FDA has confidence in the safety and efficacy of CRESTOR."

Rep. Henry Waxman, D-Calif., the ranking Democrat on the House Committee on Government Reform, said in a letter to the FDA on Friday that AstraZeneca's advertising conflicts with the FDA's public statements about the drug. He asked the FDA to review the company's statements and order them to post a correction if the statements are incorrect.

"Either AstraZeneca is misleading the public about Crestor's safety, or FDA officials are giving the company private assurances that conflict with the agency's public position," Waxman wrote. He said the company's statement on its Web site that it had been assured that senior-level FDA officials have "no concern in relation to Crestor's safety" appears to conflict with FDA statements.

Waxman pointed to one newspaper interview in which Steven Galson, acting director of the FDA's Center for Drug Evaluation and Research, said the agency "had been very concerned about Crestor since the day it was approved, and we've been watching it very carefully."

But Galson also said in a written statement following the congressional hearing that Graham's testimony didn't reflect the FDA's views and that all five of the drugs Graham mentioned are currently approved as "safe and effective" for use in the USA.

Waxman's letter echoes a similar letter sent in November by consumer activist group Public Citizen, which claims the drug is unsafe and should be banned from the market.

FDA spokeswoman Kathleen Quinn acknowledged the agency has received Waxman's letter. The FDA "takes his concerns seriously and will respond promptly," she said.

AstraZeneca stands by its advertising, spokeswoman Emily Denney said. "It is consistent with what has been communicated to us by the FDA," she said. She said the ad, which ran for two or three days, was essential to correct misinformation that emerged during the congressional testimony. She said the company was deluged with calls from doctors and patients.

Crestor, approved in August 2003, is a "statin" drug prescribed to lower cholesterol levels. The FDA issued a health advisory this year after AstraZeneca changed the label on Crestor for the European Union to include a warning about the risk of developing a muscle problem called rhabdomyolysis. Although the U.S. label already noted the risk, the FDA said it would alert physicians to be especially careful when prescribing the drug. ]]> Five Brands of Risk http://www.yourlawyer.com/articles/read/8974 Tue, 07 Dec 2004 00:00:00 -0800 http://www.yourlawyer.com/articles/read/8974
That hearing was held to explore the FDA's record on warning people about drug risks. During his testimony, David J. Graham, associate director of the FDA's office of drug safety, said underpublicized safety risks of five drugs weight loss medication Meridia; acne drug Accutane; asthma medication Serevent; cholesterol drug Crestor; and painkiller Bextra could lead to restrictions or withdrawal of the drugs from the market.

More than 15 million prescriptions were filled for the five drugs during the first nine months of this year, according to IMS Health, a pharmaceutical information and health care consulting company. While the makers rigorously defend the drugs' safety when taken as directed, some people who take them are scared.

Michael Miller, director of the Center for Preventive Cardiology at the University of Maryland Medical Center in Baltimore, said at least 10 patients have called asking what to do. While some research suggests that Crestor carries greater risk of serious side effects than other statins, Miller said current knowledge does not warrant taking most patients off the drug. He will continue to monitor patients carefully and won't prescribe Crestor to those at high risk for the most serious side effects.

If you are taking one of these drugs and want to consider another treatment, experts recommend consulting with your doctor before stopping or changing any regimen. Some drugs interact with others, so you should tell your doctor about any drugs -- prescription or over-the-counter -- you're taking on a regular basis.

For those taking any of the five drugs, risks and options are discussed below.


Meridia Used for weight loss, works by "acting on the appetite control centers in the brain," according to its maker, Abbott Laboratories. The drug works best when combined with a low-calorie diet, the company says.

Risks Elevated risk of cardiovascular side effects, including heart attack and stroke.

Drugmaker Response Illinois-based Abbott says it stands behind the safety of the drug.

Alternatives The best way to drop pounds: Eat less, move more, doctors said. "I very much believe in behavior modification and lifestyle changes," said Tania Heller, medical director of Suburban Hospital's Center for Eating Disorders and Adolescent Obesity. For patients at high risk for complications of obesity -- such as those with type 2 diabetes -- drugs may help speed weight loss, Heller said. "But the key point to get across is not to rely only on medication" to lose weight, she said.

For patients who need medication, obesity drug Xenical, made by Roche Pharmaceuticals, is another option. The drug works by preventing about a third of the fat in the food you eat from being digested. Studies show that patients taking the drug lost twice as much weight as those on the same diet without medication. Side effects -- increased frequency and urgent need to empty the bowels, and gas with an oily discharge do not enhance its popularity.

Accutane A synthetic form of Vitamin A, used to treat severe acne.

Risks Can cause severe birth defects when taken by pregnant women.

Drugmaker Response The risk for birth defects when the drug is taken by pregnant women has been known since its 1982 approval, said Carolyn Glynn, spokeswoman for Roche Pharmaceuticals. Roche and the companies that distribute the three generic forms of Accutane require doctors to test women for pregnancy before prescribing the drug, and to sign forms stating they've educated patients about known risks.

Alternatives Oral antibiotics and topical medications should be tried before taking Accutane. But neither type of drug is considered as effective as Accutane in treating the most severe cases of acne, said Paula Bourelly, assistant professor of dermatology at Georgetown University Hospital. Since Accutane is the only medication considered effective for the most severe forms of acne, patients with the very worst cases have limited options. Bourelly said she has had new patients report taking antibiotics for months in an effort to clear up their acne.

Serevent A long-acting inhaled bronchodilator (a drug that widens the airways in the lungs) used for long-term management of asthma and chronic obstructive pulmonary disease.

Risks "Rare but serious asthma episodes and asthma-related fatalities occurred in a study with Serevent," GlaxoSmithKline reports on its Web site. "These risks may be greater in African Americans." Researchers think risks are higher for people with certain types of beta receptors (which exist on cells that line the surface of organs, including the lungs); this type of receptor seems more common in black patients. Some people of other races may have this type of beta receptor, too, doctors said.

Drugmaker Response GlaxoSmithKline says it addressed this concern by adding a "black box" to Serevent's label in August 2003, warning patients and doctors of this risk, according to a written statement the company issued on the day of Graham's testimony. Patients should not stop taking Serevent without their doctor's approval, the statement says.

Alternatives For those who don't want to take Serevent, there are several options, depending on the severity of the patient's asthma. Those with mild asthma may use a rescue medication like albuterol, which is taken only when the patient feels short of breath or has other asthmatic symptoms, said Martha White, an allergist at the Institute for Asthma and Allergy in Wheaton and Chevy Chase.

People with asthma who have symptoms at least twice a week need more treatment, White said. Options include another long-acting bronchodilator called Foradil, inhaled corticosteroids and Singulair, a leukotriene inhibitor (which is thought to work by blocking a substance that is released by cells in the lungs during asthma attacks).

Inhaled corticosteroids are considered the most effective at managing asthma symptoms, but they carry a heightened risk particularly at higher dosages of oral thrush (mouth infection), skin thinning and bruising with long-term use. The side effects for Foradil, usually used in combination with inhaled corticosteroids, include tremors, fast or irregular heartbeat, headache, muscle cramps or pain and, in rare cases, bronchospasms (narrowing of the airways). The side effects for Singulair which is not as effective as inhaled corticosteroids at controlling asthma symptoms include fatigue, fever, stomach pain and upset stomach.

Bextra A COX-2 painkiller often used to treat osteoarthritis.

Risks Bextra may have the same cardiovascular risks as those that caused Merck & Co. to pull Vioxx from the market in September. Some experts say that COX-2 drugs in general may be unsafe for long-term use. Existing research both confirms and refutes this risk, so more studies are needed.

Drugmaker Response Pfizer considers the drug to be "safe and effective," said spokeswoman Mariann Caprino. The drug company looks forward to the FDA's February 2005 meeting on the safety of Bextra and Celebrex, the only other COX-2 drug left on the market, Caprino said.

Alternatives Other choices include NSAIDs (nonsteroidal anti-inflammatory drugs), available by prescription (including Mobic and Daypro) and over-the-counter (including Motrin, Aleve and Advil).

Weight loss, if needed, and regular exercise may also ease pain. To relieve pain temporarily, heat and ice may help. Topical medications such as corticosteroids, Bengay and capsaicin may also ease soreness. Some patients may find relief through corticosteroid or hyaluronic acid injections into sore joints. Injection complications include infection, and repeated corticosteroid shots can increase risks of cataracts and bone weakening. In rare cases, skin whitens and thins at the injection site.


Crestor A statin drug used to treat high cholesterol.

Risks Kidney failure and rhabdomyolysis, a rare but potentially fatal muscle disease. Complications are more likely at higher doses (the highest approved dose in the United States is 20 milligrams; highest dosages elsewhere extend to 40 milligrams).

Drugmaker Response In a written statement issued Nov. 19, AstraZeneca said senior FDA officials reassured the firm that "there is no concern in relation to Crestor's safety and that they [the FDA] have issued a statement explaining that Dr. Graham's testimony does not reflect the views of the agency." The company has also run newspaper advertisements to reassure patients taking Crestor of the drug's safety.

Alternative treatments Other statin drugs include Lipitor, Zocor, Pravachol and Lescol. The decision on which to take should be made in consultation with your doctor, since dose and duration of treatment may vary depending on how high your cholesterol is, how low the target is and other factors. All statin drugs carry some risk for rhabdomyolysis, as well as risk of increasing liver enzymes. Liver function should be monitored regularly.

Diet and exercise are also powerful tools to help keep cholesterol and blood pressure in check, though doctors caution patients not to forego medication for levels deemed dangerously high by their doctors.

But don't stop taking your medication even if your cholesterol levels dip into safer territory. Former president Bill Clinton, who underwent emergency heart bypass surgery in September, had stopped taking his statin medication after losing weight and becoming more fit. His LDL or "bad" cholesterol level had decreased since his last presidential physical, from 177 to 114 when measured the week before his heart surgery. The recommended LDL level is less than 70.]]> Updated Safety Information Regarding Crestor http://www.yourlawyer.com/articles/read/8917 Wed, 24 Nov 2004 00:00:00 -0800 http://www.yourlawyer.com/articles/read/8917
Health Canada is actively reviewing the safety profile associated with rosuvastatin (Crestor), particularly the 40 mg dose, and is in receipt of additional safety information provided by its manufacturer, AstraZeneca Canada Inc.

In June 2004, Health Canada posted a Public Advisory about an association between Crestor and rhabdomyolysis, a rare but serious muscle disorder. The same month, AstraZeneca Canada Inc. issued a Dear Healthcare Professional Letter to advise Canadian healthcare professionals of this information.

Rhabdomyolysis is a condition that results in muscle breakdown and the release of muscle cell contents into the bloodstream. Symptoms of rhabdomyolysis include muscle pain, weakness, muscle tenderness, fever, dark urine, nausea, and vomiting. In severe cases, rhabdomyolysis can result in kidney failure and can be life-threatening.

Since June 2004, Health Canada has received a further 6 reports of rhabdomyolysis in patients using Crestor which are under assessment.

All patients taking Crestor, or any cholesterol lowering drug, are advised to report any unexplained muscle pain, muscle weakness or cramps, or any brown or discoloured urine, to their physician immediately. ]]> Danger Link Gets Stronger For Heart Drug http://www.yourlawyer.com/articles/read/8895 Mon, 22 Nov 2004 00:00:00 -0800 http://www.yourlawyer.com/articles/read/8895
As of August 31, five more cases of rhabdomyolysis a breakdown in muscle tissue that can lead to kidney damage had been reported in Crestor users since Health Canada advised Canadians in June of a possible link between Crestor and the muscle-wasting condition.

At that time, eight cases of rhabdomyolysis had been reported in patients taking Crestor since the drug was approved in February 2003.

There is no proof the latest cases of muscle damage were caused by exposure to Crestor. Health Canada says "causality assessments" have not been completed and that adverse drug reaction reports are based on suspicion only.

As well, of the eight cases of rhabdomyolysis reported as of June, all patients had at least one underlying risk factor, such as kidney problems or an under-active thyroid gland.

AstraZeneca, maker of Crestor, says it is fully confident in the drug's safety and efficacy and that the risk of muscle breakdown is in line with that for other statins less than 0.01 per cent.

Dr. Carley Vint-Reed, scientific director of cardiovascular research for AstraZeneca Canada, also said Health Canada has not alerted the company of any concerns about Crestor's safety.

The department says it is reviewing kidney-, liver- and muscle-related adverse events for Crestor and is comparing the risk of rhabdomyolysis for all cholesterol drugs in the "statin" family.

The analysis comes amid concerns about aggressive use of statins in people with no evidence of heart disease, and treatment guidelines that keep lowering the threshold for what doctors consider "safe" cholesterol.

Statins have become the fastest growing drug class in Canada. More than 17 million prescriptions - totalling more than $1.5 billion - were dispensed by Canadian drug stores in the 12-month period ending in September, according to IMS Health Canada, which tracks prescription drug sales.

Nearly 1.6 million prescriptions were filled for Crestor.

Health Canada says patients taking Crestor or any cholesterol-lowering drug should immediately report any unexplained muscle pain, muscle weakness or cramps, or any brown or discolored urine to their doctor.]]> Concern About Drug Safety Doesn't Stop With Vioxx http://www.yourlawyer.com/articles/read/8896 Mon, 22 Nov 2004 00:00:00 -0800 http://www.yourlawyer.com/articles/read/8896
That David Graham of the Food and Drug Administration's Office of Drug Safety named names was surprising. But to anyone who has kept up with the scientific literature and the drugs' evolving labels, the names themselves were not.

Steven Galson, an FDA administrator, attempted to temper Graham's testimony by saying the agency must consider benefits as well as risks, "so that safe and effective drugs remain available to patients who need them."

Some of what is known about the five drugs so far:

Accutane. Accutane can cause major fetal defects, and Roche, its maker, has warned against use during pregnancy since it came on the market in 1982. Yet, according to the March of Dimes, thousands of pregnant women have taken it.

In 2001, the FDA approved a voluntary system developed by Roche to prevent pregnant women from taking Accutane. But an FDA review found the proportion of Accutane users who were pregnant might actually have gone up in the year since the system went into effect.

In February, an FDA advisory panel recommended a more-restrictive program that would set up a registry of all Accutane prescribers, all pharmacists who dispense it and all users. It has not yet been implemented.

Bextra. As with Accutane, Graham did not call for Bextra in the same class of drugs as Vioxx to come off the market. But, he said, too little is known about Bextra's effect on heart attack or stroke risk. Last month, Pfizer sent a letter to health-care professionals mentioning results of two Bextra trials in heart-bypass-surgery patients. In both, the Bextra groups had more heart attacks and strokes than the placebo groups.

Crestor. This cholesterol drug has drawn regulators' attention in Europe and Canada.

At the Senate hearing, Graham said Crestor is the only statin drug that causes kidney failure. And, he said, it carries a higher risk of rhabdomyolysis than any other statin. Rhabdomyolysis is a potentially fatal muscle complication that benched another statin, Baycol, in 2001.

In June, Crestor maker AstraZeneca released a revised package insert for use in the European Union. It highlighted the rhabdomyolysis issue. Later that month, the Canadian government issued an advisory warning of a possible link between Crestor and rhabdomyolysis, especially at higher doses

Two months after the FDA approved Crestor in August 2003, consumer watchdog Public Citizen warned consumers not to use it because of kidney toxicity. The group has asked the FDA to ban Crestor.

Meridia. Graham said that few patients stay on the weight-loss drug very long because extended use can lead to increased blood pressure and stroke. Before Meridia was approved in 1997, an FDA advisory panel voted 5-4 that the drug's benefits did not outweigh its risks. Public Citizen has twice petitioned the FDA to pull it off the market.

Serevent. The Glaxo asthma drug, approved in 1994, dilates breathing passages. In 2003, its label began carrying a "black box" warning, the strongest type of warning, about the results of a large U.S. study that showed a small but significant increase in asthma-related deaths in patients who took Serevent. Advair, another Glaxo asthma treatment, which contains Serevent and a steroid, carries the same warning.

Richard Honsinger, a Los Alamos, N.M., asthma and allergy specialist, says he fielded some calls from worried patients after Graham's pronouncement. He says Serevent only relieves symptoms and should be taken along with a steroid to prevent permanent scarring in the lungs from inflammation.]]> Medical Experts Weigh Safety In Using Five Drugs http://www.yourlawyer.com/articles/read/8890 Fri, 19 Nov 2004 00:00:00 -0800 http://www.yourlawyer.com/articles/read/8890
David Graham, the Food and Drug Administration's associate director of drug safety, testified before a Senate committee Thursday that not only had his agency not given enough weight to safety concerns about the recalled painkiller Vioxx, but he also said regulators should be looking closely at five other drugs.

They are: Pfizer Inc.'s Bextra, a pain reliever in the same class as Vioxx; Crestor, a cholesterol-lowering drug manufactured by AstraZeneca PLC; Meridia, a weight-loss drug made by Abbott Laboratories; the acne drug Accutane made by Roche Holding AG; and Serevent, an asthma medicine from GlaxoSmithKline PLC.

Manufacturers of these drugs on Thursday defended their products, most of which already have the U.S. regulatory agency's "black box" warnings the strongest alert on their labels regarding safety issues. The five drugs Graham said warrant closer scrutiny have been approved as safe and effective by the FDA and "continue to be closely monitored with regard to safety and the balance of benefit to risk," FDA spokeswoman Kathleen Quinn said Friday.

Medical experts say patients taking those medications should not stop doing so without consulting with their physicians. Still, each of the medicines Graham criticized has been controversial. Here is why:

Bextra, in the same chemical class as Vioxx, was shown in a recent preliminary study to double the risk of heart attack and stroke among patients with heart disease, researchers reported at the annual meeting of the American Heart Association. Pfizer had already told regulators it intends to add to Bextra's packaging a black box warning that Bextra can cause potentially fatal skin reactions.

Crestor, a cholesterol medicine, has been linked to kidney failure and potentially life-threatening muscle damage. The consumer advocacy group Public Citizen asked the FDA in August to investigate AstraZeneca, alleging the drugmaker delayed reporting 23 cases of serious side effects. They included 19 cases of muscle weakening or rhabdomyolysis and four incidents of kidney damage.

Serevent, an asthma treatment, carries a boxed warning of a "small but significant increased risk" in asthma-related deaths in patients receiving the drug. The FDA said there were 13 deaths out of 13,174 patients treated for 28 weeks, versus four on placebo. The analysis also suggested the risk may be greater in black patients than Caucasians.

Meridia, an anti-obesity drug, increases blood pressure and heart rates and has been associated with a number of deaths and adverse reactions since it was introduced.

Accutane, an acne drug, can cause brain and heart defects, mental retardation and other abnormalities in babies of pregnant women taking the drug. Roche Holding and generic makers in February started a national registry mandating women cannot get their monthly supply of Accutane without a negative pregnancy test. They are told to use two forms of contraception while taking the drug.

Spokespersons for the five drugs' makers have said they are safe and effective when used as directed.

Public Citizen, founded by Ralph Nader, has asked the FDA to remove Crestor and Meridia from the market. Sidney M. Wolfe, the director of Public Citizen's Health Research Group, said Friday he also thinks Bextra should be pulled from the market.

"All these drugs are very problematic," Wolfe said. He added when people in the FDA like Graham raise questions, "their views are usually squelched. The FDA is too beholden to the manufacturers."

The problems "are generally known within the FDA, but the agency silences people who criticize the drugs or the policies," he said.

Daniel A. Hussar, a professor of pharmacy at University of the Sciences in Philadelphia, said Bextra was the only drug of the five Graham mentioned he thinks should be removed from the market. He said studies have indicated an increased risk of heart attacks and an association with a rare, but potentially fatal, skin reaction.

However, consumers should not be "unnecessarily alarmed" about health risks, he said. "Physician offices have to be overwhelmed with calls, but I think the alarm is excessive. When the drugs are appropriately used, and in appropriate doses, they can be safe."

Pfizer spokeswoman Mariann Caprino said her company is "committed to conducting long-term studies of Bextra" to detect possible problems.

AstraZeneca, maker of Crestor, said it remains "fully confident" the drug is safe. "We have been assured by the highest levels at the FDA that there are no new concerns about Crestor's safety and that Dr. Graham's testimony does not reflect the views of the FDA," said spokesman Steve Lampert.

Laureen Cassidy, a spokeswoman for Abbott Laboratories, said: "Science continues to support the safe use of Meridia to treat obesity, the leading health epidemic in the U.S. Meridia has been extensively studied in more than 100 clinical trials involving more than 12,000 patients throughout the world."

GlaxoSmithKline said Serevent "is safe and effective when used appropriately" and according to labeling guidelines, and it has a "black box" warning on its label.

LaRoche Holdings spokeswoman Carolyn Glynn said Accutane is reserved for "the most serious forms of acne unresponsive to other therapies."

The company and other generic manufacturers have a new national registry to monitor Accutane prescriptions. "This is something we have been very focused on for 23-plus years. It was a surprise to us that we ended up as one of the five drugs," she said. ]]> Advocate Suggests Crestor May Harm Kidneys http://www.yourlawyer.com/articles/read/8759 Fri, 29 Oct 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8759
Wolfe sent a letter to the Food and Drug Administration citing 29 cases of kidney problems 18 of kidney failure and 11 of kidney insufficiency out of some 4.5 million prescriptions for the drug between Jan. 1, 2001 and Sept. 30, 2003.

That is more kidney problems than reported by all other statin-type anti-cholesterol drugs, Wolfe said.

Emily Denney, a spokesperson for drugmaker AstraZeneca, responded that the company keeps close watch of safety reports for the drug and "we feel ever more confident with Crestor."

She said a company analysis of FDA data indicated that, compared to other statins, Crestor was about average for kidney failure as a percentage of side effects.

Data provided by AstraZeneca indicated that kidney failure made up 3.5 percent of adverse events for Crestor known by the generic name rosuvastatin compared to 5.7 percent for lovastatin, 4.0 percent for simvastatin and fluvastatin, 3.0 percent for pravastatin and 2.2 percent for atorvastatin.

There was no immediate response to Wolfe's letter from the FDA.]]> Group Renews Call for Withdrawal of Cholesterol Drug http://www.yourlawyer.com/articles/read/8760 Fri, 29 Oct 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8760
Public Citizen has been urging the U.S. Food and Drug Administration to pull Crestor off the shelves, and contended that the drug was dangerous even before it won FDA approval last year.

Its latest analysis found that the rate of reports to the FDA of acute renal failure or renal insufficiency in patients using Crestor is approximately 75 times higher than the rate for all other statin drugs put together.

"It becomes clearer by the day that this drug is uniquely toxic but offers no unique benefit, and must be removed from the market," Dr. Sidney Wolfe, director of Public Citizen's Health Research Group, wrote in a letter to the FDA. The FDA and Crestor's maker, AstraZeneca, contend that the drug is safe.]]> Rate of Kidney Damage in Crestor Patients Is 75 Times Higher Than in Patients Taking Other Cholesterol Drugs http://www.yourlawyer.com/articles/read/8761 Fri, 29 Oct 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8761
It becomes clearer by the day that this drug is uniquely toxic but offers no unique benefit, and must be removed from the market, wrote Dr. Sidney Wolfe, director of Public Citizens Health Research Group, to FDA Acting Commissioner Lester Crawford.

According to the analysis, the rate of reports to the FDA of acute renal failure or renal insufficiency per million prescriptions in patients using rosuvastatin (Crestor) 29 U.S. reports in less than one year since the drug was first marketed in this country is approximately 75 times higher than the rate for all other statin drugs combined.

The FDA had evidence before approving the cholesterol drug Crestor that it caused an increased incidence of rhabdomyolysis (severe muscle deterioration), yet the agency approved it anyway, erroneously believing that this toxicity was limited to an 80 milligram dose that was not ultimately approved. The drug went on the market in September 2003. In March 2004, Public Citizen petitioned the FDA to remove the drug from the market because it had been linked to muscle damage and kidney failure.

There have been 29 reported U.S. cases of acute renal failure or renal insufficiency out of 4.5 million Crestor prescriptions filled between September 2003 and the end of August 2004. For all other statins (including Lipitor, Zocor, Lescol, Pravachol and Mevacor), there have been 27 cases of acute renal failure or renal insufficiency reported from Jan. 1, 2001, through Sept. 30, 2003, out of 316 million prescriptions filled. This is a rate of .085 cases reported per million prescriptions filled.

Thus, the rate of reports of acute renal failure or renal insufficiency for Crestor is 6.4/.085, or 75 times higher than that of all of the other statins. In addition, as of August 26, 2004, there had been 65 reports of rhabdomyolysis among U.S. patients taking Crestor, a rate of reports approaching that of Baycol, a cholesterol drug that was taken off the market because of rhabdomyolysis.]]> Dear Dr. Crawford http://www.yourlawyer.com/articles/read/8762 Fri, 29 Oct 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8762 Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20854

Dear Dr. Crawford,

We have just completed an analysis of the FDAs adverse drug reaction database (AERS) and have found that the rate of reports to the FDA of acute renal failure or renal insufficiency per million prescriptions in patients using rosuvastatin (Crestor)29 U.S. reports in less than one year since the drug was first marketed in this country is approximately 75 times higher than the rate for all other statin drugs combined. This letter is a supplement to our petition of March 4, 2004, to ban this drug in the United States.

The concern about acute renal failure was expressed by an FDA medical officer in the July 2003 FDA hearing preceding the approval of the drug. FDA documents discussed during the hearing stated, in the context of dozens of patients with blood and/or protein in their urine after using Crestor and several cases of acute renal failure or renal insufficiency, that:

"These three cases of renal insufficiency of unknown etiology are of concern because they present with a clinical pattern, which is similar to the renal disease seen with rosuvastatin in these clinical trials. Proteinuria and hematuria could be potentially managed with regular urinalysis screening. However, if they are the signals for the potential progression to renal failure in a small number of patients, this may represent an unacceptable risk since currently approved statins do not have similar renal effects. [1]

The results contained in our analysis are based on the most recent adverse reaction data available from the FDA for statins other than Crestor (reactions filed between January 1, 2001, and September 30, 2003), and all data on adverse reactions to Crestor from the time of its approval through August 26, 2004, combined with data on prescriptions filled in the United States for these same intervals. We did not include cases of acute renal failure or renal insufficiency in which rhabdomyolysis had been diagnosed since this statin-induced adverse reaction can frequently cause renal failure and we only counted cases reported from the U.S. and only those cases in which the adverse drug reaction report stated that Crestor was the primary suspect drug related to the adverse reaction.

Crestor: There have been 29 reported cases of acute renal failure or renal insufficiency (18 cases of failure and 11 cases of renal insufficiency) out of 4.5 million prescriptions filled between the first time the drug was marketed in the U.S. September 2003 and the end of August 2004. This is a rate of 6.4 reports of acute renal failure or renal insufficiency per million prescriptions filled.

All other statins (Lipitor, Zocor, Lescol, Pravachol and Mevacor, including other versions of lovastatin): There have been 27 cases of acute renal failure or renal insufficiency reported from January 1, 2001, through September 30, 2003, out of 316 million prescriptions filled for these drugs during this interval. This is a rate of 0.085 cases reported per million prescriptions filled. The highest rate for any of these other statins was for Zocor, which had a rate of 0.26 cases per million prescriptions filled.

Thus, the rate of reports of acute renal failure or renal insufficiency for Crestor is 6.4/.085, or 75 times higher than that of all of the other statins combined. In comparison to Zocor, the rate of reports of acute renal failure or renal insufficiency for Crestor is 6.4/.26, or 25 times higher than that of Zocor.

Based on less than one full year of adverse reaction reports of acute renal failure or renal insufficiency, it appears that the concerns of the FDA medical officer cited in the above briefing document were extraordinarily prescient: However, if they [blood and protein in the urine] are the signals for the potential progression to renal failure in a small number of patients, this may represent an unacceptable risk since currently approved statins do not have similar renal effects.

We based our opposition to the approval of this drug on its unique renal toxicity and on the higher rate of life-threatening rhabdomyolysis (destruction of muscle) than had been seen with other statins in pre-approval clinical trials. Seven cases of rhabdomyolysis had shown up in clinical trials prior to the approval of Crestor, compared to no cases for any of the other statins, including the ultimately doomed Baycol.

As of August 26, 2004, there had been 65 U.S. reports of rhabdomyolysis among patients taking Crestor in less than the first full year of its availability in this country, for a rate of 65 reports per 4.5 million prescriptions, or 14.4 reports per million prescriptions. In the first two years of marketing of Baycol, which eventually was taken off the market because of an unusually high rate of reports of rhabdomyolysis, there were 42 reports out of 2.8 million prescriptions filled in this country, for a rate of 15 reports per million prescriptions filled. Thus, it appears that Crestor is in the range much closer to the rate of rhabdomyolysis reports for Baycol than that of any other statin.

It becomes clearer by the day that this drug is uniquely toxic without offering any unique benefit, and that it must be removed from the market.

Sincerely,

Sidney M. Wolfe, MD
Director, Public Citizen's Health Research Group ]]> When Statins Cause Problems http://www.yourlawyer.com/articles/read/8338 Mon, 09 Aug 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8338
"My legs were throbbing and I would have to stop midway, and I'd have to sit down," said Mulvey, of Oakdale, who stopped taking the medication even before her doctor ran a blood test showing she had suffered muscle damage from the statin. "This wasn't normal for me. I wasn't short of breath - my muscles were screaming.

"And I'm a very vigorous person," Mulvey added. "For me to be complaining about something is unusual."

Harvey Gardner, a 73-year- old from Huntington, started taking a different statin, Zocor, March 10. After just a few doses, he said, he started feeling "lousy."

"The symptoms were dramatic," Gardner said. "I had pain in my arms and my legs. I felt like I had arthritis all over my body."

The pain subsided when he quit taking the drug, but now he wonders whether the numbness he's had in his toes for several years might be a side effect of another statin, Mevacor, that he took several years ago. Doctors have diagnosed the numbness as peripheral neuropathy, which is listed as one of the potential side effects of statins.

Millions of Americans now take statins, a class of medications whose remarkable ability to lower blood cholesterol levels has endowed them with virtual miracle drug status. But many who take the drugs worry about the effects they may have on their kidneys, liver and muscles, and a consumer advocacy group's call in June to ban Crestor, the newest statin, has reawakened concerns about the potential side effects. Officials for AstraZeneca, which makes Crestor, have dismissed the consumer group's allegations as inaccurate and misleading. "Statins overall are remarkably safe," said Gary Bruell, a spokesman for AstraZeneca. "Every drug ever invented has adverse effects."

A rare side effect

Rhabdomyolysis, a breakdown of muscle fibers that can cause kidney damage and may be fatal, is an extremely rare side effect, occurring in one in 10,000 patients, drug manufacturers say. But up to 5 percent of statin patients suffer non-life-threatening muscle pain disorders that can nevertheless be debilitating, according to doctors who have studied statin-related muscle syndromes. And, they say, certain patients smaller people, women, the elderly, and athletes and people who exercise a lot may be more vulnerable. People of Japanese descent also are at higher risk, as are patients with some other medical complications.

"I think the muscle part of the statins is underappreciated," said Dr. Paul Thompson, director of preventive cardiology at Hartford Hospital and author of a paper on statin-associated muscle disease published in the Journal of the American Medical Association in April 2003. "Some people not everybody, but a fair number of people get a mild myalgia [muscle pain] on the drug. With some of these patients, it can be extreme."

Public Citizen Health Research Group, a consumer organization, called on the Food and Drug Administration in 2001 to add a new warning, known as a black box warning, to the labels on statins, emphasizing that patients must notify their doctors if they experience muscle pain, tenderness and weakness, the symptoms that may precede rhabdomyolysis. The FDA has not taken any action, and an FDA official, Dr. Mary Parks, would not comment on the issue last week. At the time Public Citizen made its request, 72 deaths during a three-year period had been linked to statin use; 20 of those were linked to Baycol, which the FDA withdrew from the market the same year.

Dr. Robert Rosenson, director of preventative cardiology at Northwestern's Feinberg School of Medicine in Chicago, whose review of statin-induced myopathy was published in the American Journal of Medicine in March, said 3 percent to 5 percent of statin patients experience muscle problems. He often tries switching drugs or lowering the dose, he said, but "some people can't tolerate any dose of a statin."

Still, not all physicians recognize the link between the drugs and the muscle syndromes, Thompson said, and some of his colleagues dismiss it as insignificant. "A lot of lipid experts say: 'The myalgia stuff you talk about doesn't exist,'" he said. "I say, 'You're not taking care of enough patients.'"

Jeanne Bruderman is one patient whose physicians did not recognize a link: After going through surgery to treat back problems, she experienced pain, weakness and cramps in her arms and legs and tingling in her fingers. She sought help from a rheumatologist, a neurosurgeon and a pain-management doctor. Finally, a physician's assistant mentioned the symptoms could be related to statins and ordered a blood test to measure levels of the enzyme creatine kinase, an indication of muscle damage. "I nearly fell off my chair," said Bruderman, who lives in Bellport, is only 39 and had been put on Lipitor 19 months earlier. She quit the drugs and says the tingling in her fingers has subsided.

Wonder drugs?

Many cardiologists consider statins to be wonder drugs - especially for people who are at high risk for cardiovascular disease. "You can't go to a cardiology meeting and ask who's on the drug without everyone's hand going up," Thompson said. He takes a statin himself, and acknowledged that he serves as a consultant to several pharmaceutical companies that make them. But, he said, "they do have nagging side effects in some people."

That description doesn't quite capture the experience of Rena Sweeney, a physical education teacher in upstate Kinderhook who was raised in Yonkers and now lives in what she calls "a whirlwind of pain." Sweeney, who is 53, started taking a low dose of Lipitor around the end of October, after blood tests showed her total cholesterol was 239. By the time her family came to visit around Thanksgiving, she said she couldn't even enjoy their company.

"I was feeling old and shriveled up, fatigued," she said. Until then, Sweeney said, she had been the kind of person who rarely even suffered a cold. "I'm a P.E. teacher, and I am in very, very good shape; I work out all the time."

Her leg muscles had started twitching, and her legs had started feeling weak, "like rubber." A blood test showed she had elevated creatine kinase levels, an indication of muscle damage, but the level was not high enough to convince her doctor that it was related to the medication. Her doctor thought she was having panic attacks.

Once an avid skier, Sweeney was barely able to complete two runs down the mountain last winter. The pain in her legs was so intense at times, she said, "I was crying, the fronts of my calves, my shins, were killing me. I felt poisoned." She feared she may have developed lupus or a neurological illness, and saw several specialists to rule out connective-tissue diseases.

An acquaintance who is an orthopedic surgeon was the first to ask whether she had started taking any new medications - and advised her to quit the drug immediately.

Sweeney stopped taking Lipitor on New Year's Eve and said her weakness and the "shriveled-up feeling" are gone, though she still has muscle pain after exertion, even gardening.

A spokeswoman for Pfizer, maker of Lipitor, declined to comment on the product's safety. In clinical trials, 5.6 percent of patients taking a 20-milligram dose of Lipitor reported myalgia or muscle pain, compared to 1.1 percent of subjects taking a placebo, according to the prescribing information. At a 40-milligram dose, 5.1 percent of patients taking Lipitor reported arthralgia or joint pain, compared to 1.5 percent on placebo.

Sweeney said doctors have been unable to give her a definitive answer about what triggered her symptoms. Such myalgia can occur without the elevated enzyme levels that mean muscle damage has resulted in protein leaking out of the muscle cells into the blood. Doctors who followed four patients at Scripps Mercy Hospital Clinical Research Center in San Diego found the patients were able to guess correctly whether they were given statins or placebos, based on their muscle pain and performance on strength tests, even though they had normal creatine kinase levels in their blood.

A number of other small studies have shown statins may exacerbate muscle injury during exercise. A study of 58 healthy men at the University of Pittsburgh in 1997, for example, found that those taking Mevacor (lovastatin) had much higher creatine kinase levels after 45 minutes of downhill walking on a treadmill than a group taking a placebo.

Jim Baggett, a housing inspector in Wilmington, N.C., said he started taking Zocor in July 2002 and became unable to do yardwork, couldn't get through his usual 2 1/2-hour weekend workouts and developed a cough, numbness in his feet, joint aches, weakness and tremors.

Baggett, who is 58, underwent thousands of dollars' worth of tests to rule out Lyme disease, chronic fatigue syndrome, tuberculosis and amyotrophic lateral sclerosis, among other diseases. All of the test results were negative. Since quitting the drug, Baggett said, his health has improved, but he is not yet symptom-free.

"I'm not one to say, 'Don't take it' I'm not a doctor," Baggett said. "But at least be aware of what the problems are."

Tony Plohoros, a spokesman for Merck, which makes Zocor and Mevacor, said side effects from both drugs are rare. "Both Mevacor and Zocor have excellent safety profiles," he said, adding that Merck is seeking FDA permission to sell Mevacor without a prescription. "The 20 milligram dose has shown in clinical trials to have roughly the same side effects as a placebo."

Risks and benefits

The risk-to-benefit ratio of taking a statin must be evaluated for each patient individually, said Dr. Sidney Wolfe, director of Public Citizen.

"There are millions of people getting statins who shouldn't be getting statins," Wolfe said. "These drugs have been especially useful for people when they are used for secondary prevention," in patients with established heart disease who are at risk for another heart attack, he said - and for them, "the benefits outweigh the risks."

For people who don't have heart disease and who have no other risk factors, he said, "the risks outweigh the benefits."

Dr. Mary Parks, deputy director of the FDA's division of metabolic and endocrine drug products, said she could not comment on the consumer group's 2001 petition to the agency to strengthen warnings on statins. She said the labels contain warnings already, and doctors need to convey the information to their patients.

"People need to be aware that with any drug, there are going to be side effects," Parks said. "If you're taking this product and having aches and pains and it is in some way affecting daily activity, you need to contact your physician and talk about it. You may need to do a trial and go off the medicine. It may go away. It may also not be the medication.

"Even in milder cases, it's worth people paying attention to it and not ignoring it," she said. In some cases of rhabdomyolysis, "if you can stop it early on, it may be of benefit to the patient."

1) This wasn't normal for me. My muscles were screaming.' - Eileen Mulvey, right, who was unable to climb stairs for two weeks after she started taking Crestor 2) 'The symptoms were dramatic. I had pain in my arms and my legs I felt like I had arthritis all over my body.' Harvey Gardner, who began having symptoms after taking a few does of Zocar 3) 'A lot of lipid experts say: "The myalgia (pain) stuff you talk about doesn't exist." I say: "You're not taking care of enough patients.'' Dr. Paul Thompson, director of preventive cardiology at Hartford Hospital 4) 'With any drug, there are going to be side effects. If you're taking this product and having aches and pains and it is in some way affecting daily activity, you need to contact your physician and talk about it It may also not be the medication.' Dr. Mary Parks of the FDA's division of metabolic and endocrine drug products. ]]> Group: Crestor Side Effect Report Delayed http://www.yourlawyer.com/articles/read/8293 Wed, 04 Aug 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8293
It's the latest attack on Crestor by the private group Public Citizen, which argues that Crestor is riskier than its competitors and should be banned.

FDA requires drug makers to reveal reports of serious and unexpected side effects within 15 days of learning about them. While those reports don't prove a drug was to blame, FDA evaluates them to determine whether a medicine is riskier than initially thought.

Public Citizen's Dr. Sidney Wolfe charged that AstraZeneca delayed its reports to the FDA by as long as 97 days. The company ultimately reported that 19 Crestor users suffered an often life threatening muscle-destroying condition and filed four reports of kidney failure.

The delays "have unquestionably impaired FDA's ability to promptly assess the safety of this uniquely dangerous drug," Wolfe wrote FDA Acting Commissioner Lester Crawford Tuesday.

AstraZeneca insists that Crestor is no more risky than other cholesterol-lowering "statin" drugs, and that it followed FDA rules. The company says it wasn't subject to the 15-day deadline because the side effects were mentioned on the drug's label.

Wolfe countered that Crestor's label implies the muscle-destroying side effect occurs only with an unapproved high dose. The company's own reports, however, implicate far lower doses. The drug's label only mentions kidney failure in passing, Wolfe said.

FDA hasn't formally determined whether AstraZeneca should meet the 15-day deadline, said Dr. Mary Parks, medical officer.

So far, the agency says it sees no signal that Crestor is riskier than other statins, which all can cause rare cases of the muscle side effect.]]> Crestor Comes Under Fire http://www.yourlawyer.com/articles/read/8174 Fri, 25 Jun 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8174
In a letter published in this week's edition of Lancet, a British medical journal, Dr. Sidney Wolfe, director of Public Citizen's Health Research Group, alleged that the drug causes more cases of muscle deterioration than other so-called statin drugs like Pfizer Inc.'s (PFE) Lipitor, and is also associated with cases of acute kidney failure.

"There's nothing new in the Public Citizen letter," AstraZeneca spokesman Gary Bruell said. "Much of what Dr. Wolfe is saying is an inappropriate and misleading interpretation of the data. In fact both the FDA and the regulatory authorities in 60 countries continue to say that Crestor is safe when used according to its label."

Bruell said two million people have taken Crestor and five million prescriptions have been written.

"The safety profile continues to be similar to all the other marketed statins," Bruell said.

A Public Citizen spokeswoman wasn't immediately available to comment.

Wolfe is saying that none of the approved doses of Crestor are safe. In a press release on the Public Citizen Web site, Wolfe says that from the time of its approval in August 2003 to mid-April, 18 patients, including 11 in the U.S., 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 by Public Citizen from the FDA.

Most of these patients were using the low 10 milligram dose, the consumer group said. More than 20 additional cases of rhabdomyolysis, the name for this kind of muscle deterioration, have been reported to the FDA since mid-April, agency sources have said, according to Public Citizen.

"Without further details on the cases described by Wolfe, it is difficult to predict what might constitute the tipping point for the FDA to change its position on Crestor," Bear Stearns analyst Alexandra Hauber wrote in a Friday research note. "However, we would expect the new attack to have some impact on prescription data in the coming weeks."

Hauber doesn't own shares of the company. Bear Stearns has been compensated by AstraZeneca for non-investment banking related services in the last year.

An FDA spokeswoman wasn't immediately available to comment.

"The key to this debate in our view, is reported vs. confirmed cases of side effects," Merrill Lynch analyst James Culverwell wrote in a Friday research note. "Before Baycol (the last new statin to be launched before Crestor), awareness of (muscle deterioration) was low. With heightened sensitivity since Baycol's withdrawal, doctors are inclined to report the slightest abnormality." That has led to a major distortion to current and historic reporting, he said. "The reported cases are not translating into confirmed cases."

Bruell echoed that sentiment. "Reports don't mean a confirmed case," he said. So far, this muscle deterioration has been confirmed in 0.01% of the patients on the drug, he said.

Culverwell said the kidney-related issues are already in the drug's label and that long-term studies have shown it isn't a problem.

While Public Citizen said Crestor and Lipitor work equally well, Culverwell said it takes four times as much Lipitor to equal the efficacy of Crestor. Crestor also raises so-called good-cholesterol and is cheaper at the 10 mg dose than either 20 mg or 40 mg of Lipitor, he said.

Culverwell thinks the Public Citizen letter might have an influence on Crestor's market share trends, but said it shouldn't affect its long-term potential.

In March, Public Citizen filed a petition with the FDA to have the drug taken off the market. The petition is still pending. ]]> FDA Pressed To Ban Crestor http://www.yourlawyer.com/articles/read/8175 Fri, 25 Jun 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8175
The drug's maker, AstraZeneca, insists the medication is safe.

Crestor is the newest member of the class of drugs known as statins, medications that some doctors have dubbed vitamins for the heart because of their effectiveness in controlling the bad form of cholesterol in the blood.

But Dr. Sidney Wolfe, director of Public Citizen's Health Research Group in Washington, D.C., has petitioned the Food and Drug Administration to ban Crestor, saying it can cause serious harm.

Writing in today's issue of the British medical journal The Lancet, Wolfe says Crestor the generic name is rosuvastatin can cause muscle deterioration, a condition known as rhabdomyolysis, as well as kidney failure.

The drug's potential for rhabdomyolysis "is probably higher than the highest of any other currently marketed statin," he wrote.

Primary kidney failure, Wolfe said, occurs when the medication directly damages the organs. Secondary damage occurs, he said, when proteins released during muscle breakdown infiltrate the kidneys.

Other statins include Lipitor, Zocor and Pravachol. Muscle deterioration is a known side effect of any statin, but has been particularly severe with Crestor, Wolfe said yesterday.

"This drug [Crestor] is inherently dangerous and it should not be used," Wolfe said in an interview. "Crestor has unique risks because of its effects on the muscles and the kidneys."

Symptoms of rhabdomyolysis include muscle pain, weakness, tenderness, fever, dark urine, nausea and vomiting. In severe cases, rhabdomyolysis can result in kidney failure.

Gary Bruell, spokesman for AstraZeneca, said Wolfe is being alarmist. "Sidney Wolfe continues to make misleading claims based on inappropriate interpretation of the data," Bruell said.

He added that Wolfe's "views are well known and have not changed since the [drug's] approval," Bruell said. "Crestor has a safety profile comparable to that of other marketed statins." The drug was approved in August 2003.

Wolfe's claims and data involving patients' adverse reactions are being reviewed by the FDA.

Last August, Wolfe argued before an FDA panel that the drug should not be approved because muscle deterioration had occurred among people during clinical testing.

Wolfe compared Crestor's performance with that of Baycol, a statin developed by the Bayer Group that was banned in 2001 by the FDA after 31 people died.

Dr. David Orloff, director of the metabolic and endocrine drug products division at the FDA, said in a telephone interview, "There is no evidence that Crestor's label needs to be changed or that there are any safety signals that make Crestor like Baycol."

Bruell added that Crestor "is a totally different molecule."

Although Wolfe's charges come days after Canadian health authorities advised patients to take only the lowest possible Crestor doses, following eight cases of muscle deterioration, Orloff said the Canadians are now making their rules as tight as those in the U.S. Crestor dosages can range as low as five milligrams.

"Crestor is a potent statin. All statins cause muscle injury," Orloff said. "We feel comfortable that [information regarding use on] our label is for safe and effective use." ]]> Crestor's Withdrawal Urged http://www.yourlawyer.com/articles/read/8176 Fri, 25 Jun 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8176
The letter, written by Sidney Wolfe of Public Citizen's Health Research Group, said that in its first seven months on the market, Crestor was linked to 18 cases of rhabdomyolysis -- a breakdown of muscle fibers that releases proteins that can severely harm the kidney.

The letter said that the drug has greater risk than other statins without providing greater benefit.

"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."

The conclusion was vigorously disputed by the drugmaker, AstraZeneca, and the Food and Drug Administration. Both said the risk-to-benefit equation was similar in all statins, including Crestor.

David Orloff, director of the FDA division of endocrinologic and metabolic drugs, said Wolfe's information about Crestor's record is similar to the agency's. But he said that the FDA has come to a very different conclusion about the meaning of the data.

"At this time, we have not concluded that this drug is different with regard to risk-versus-benefit, and see it as no different than other statin drugs on the market," Orloff said. "We are watching, but now we see no unusual signal."

Crestor is a particularly potent statin and has been shown to be effective in lowering LDL cholesterol, the kind associated with heart disease. It was approved by the FDA last August and went on the market soon after, with an aggressive advertising campaign.

Another powerful statin, Baycol, was taken off the market in 2001 after it was linked to the deaths of 31 patients from kidney disease. The drug's manufacturer, Bayer AG, removed the drug after consultations with the FDA.

Orloff said Crestor is not similar to Baycol in the severity of the muscle and kidney problems it appeared to be causing.

Gary Bruell, spokesman for AstraZeneca, said Wolfe's Public Citizen group has "launched a highly public crusade against our drug."

He said both the FDA advisory panel that reviewed the drug and the FDA staff unanimously approved Crestor. "Since that time, Public Citizen has continued to make misleading comments using selective information to attack the product," Bruell said.

European and Canadian regulators have recently issued warnings about Crestor, saying that people using it at higher dosages should be especially careful. ]]> Consumer Group Urges Ban of Cholesterol Drug http://www.yourlawyer.com/articles/read/8170 Thu, 24 Jun 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8170
(I) just couldnt stand it anymore, the pain was too severe, says Elliott. But by then it was nearly too late; Elliott went into kidney failure, which doctors say almost killed him.

In a letter published Thursday in the medical journal The Lancet, a consumer advocacy group warns that the danger of such life-threatening side effects is unacceptably high with Crestor, a statin that was approved by the Food and Drug Administration last August.

So everywhere you turn there are ads for Crestor and there is no question that those ads help to sell drugs, but what patients have not known and what I think a lot of doctors have not known is that the drug has unique risks," says Dr. Sidney Wolfe of the nonprofit group Public Citizen. All statins carry a slight risk of muscle damage, but the consumer group says the danger is higher with Crestor, and only Crestor threatens the kidneys.

Ever since Crestor was approved by the FDA, the manufacturer, AstraZeneca, has been heavily advertising the drug.

AstraZeneca says the concern about side effects is just flat-out wrong. We believe the safety profile for Crestor has been very, very extensively studied and were confident that it is comparable to the other statins," says David Brennan, the company's CEO.

What is at stake is a potential portion of an enormous market and human lives. Sales of statin drugs in the United States now total $14 billion a year, with 13 million people taking them. And experts say the number of people who should be taking the drugs is triple the number who are currently taking them.

FDA officials say they agree with the manufacturer that Crestor is safe and effective, but add that they will continue to study reports of harmful side effects, such as Elliotts case, to see if they reveal an unusual pattern.]]> Group Ties More Illnesses to Cholesterol Drug http://www.yourlawyer.com/articles/read/8171 Thu, 24 Jun 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8171
"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," Dr. Sidney Wolfe, director of Public Citizen's Health Research Group, writes in the June 26 issue of The Lancet.

An AstraZeneca representative, noting that Wolfe has opposed the drug since before it was approved, called his claims unfounded.

At the heart of Wolfe's argument are concerns that Crestor (generic name rosuvastatin) causes primary kidney failure and rhabdomyolysis, a breakdown of muscle fiber that also can cause kidney failure.

Between the drug's approval in August 2003 and mid-April, Wolfe stated, 18 users around the world, including 11 in the US, have suffered from rhabdomyolysis. Wolfe said all this data came from the FDA.

In the intervening two months, Wolfe said, there have been 20 more reports to the FDA, and there may be more from Canada. "Canada has eight cases of rhabdomyolysis, and it is my understanding that those cases are not yet reflected in FDA data," Wolfe said.

On June 21, Health Canada issued an advisory detailing a possible association between Crestor and rhabdomyolysis, recommending that all patients take the lowest possible dose and urging them to check with their doctor to see if they had one of the risk factors for developing the problem.

AstraZeneca denies that the drug's safety profile is any different from other statins and discounts the severity of the reports. "A report is not a confirmed case. Typically, if you were on a drug and got a headache and called your doctor, the doctor would file a report," said Gary Bruell, a spokesman for AstraZeneca.

"We believe Dr. Wolfe has made misleading claims based on inappropriate interpretation of data," Bruell said. "His views are well-known and have not changed since before the approval of Crestor, despite a continuous evolution of a large volume of data in support of the fact that Crestor's safety profile remains similar to that of other marketed statins."

Public Citizen filed a petition with the FDA in March to have the drug removed from the market. That petition is pending. Last month, the group renewed its call, but Jason Brodsky, an FDA spokesman, told HealthDay that the agency wasn't too concerned about the drug.

In 2001, Baycol, another statin, was voluntarily removed from the market by its maker, Bayer Corp., because of reports of sometimes fatal rhabdomyolysis.

According to Public Citizen, many of the reports of problems with Crestor occurred in people taking lower doses (10 and 20 milligrams), while pre-approval data had indicated toxicity in people taking the 80-mg dose, which was not approved. In The Lancet piece, Wolfe cited pre-approval documents from the FDA: "The data show, for the first time, the development of severe myopathy and rhabdomyolysis in clinical trials submitted for the original approval of a new statin. This risk is clearly increased at the highest dose studied (80 mg), which has subsequently been discontinued from development. "

In June, AstraZeneca released a revised package insert for Crestor for use in the European Union. An FDA announcement stated that "these risk factors and many of the recommendations for how to minimize the risk of myopathy [diseases of the muscles] are already captured in the FDA approved labeling for Crestor in the U.S."

Wolfe said he had received a report of a patient with no contraindications for Crestor who had nevertheless developed rhabdomyolysis and had to go on dialysis temporarily. "Even if people don't die, having to go into renal failure, which is life-threatening, and being in kidney dialysis for a week or two or three is a pretty awful adverse reaction when they are other drugs that aren't as dangerous," Wolfe said. "The drug really does have unique dangers, and it shows no difference in terms of LDL ["bad" cholesterol]."

AstraZeneca, on the other hand, has a different point of view. "We have more than 2 million patients on Crestor, more than 5 million prescriptions dispensed, and we've not seen anything that was not seen in the clinical trials," Bruell said. "I don't want to give much credence to what Public Citizen is doing."]]> Consumer Advocacy Group Attacks AstraZeneca http://www.yourlawyer.com/articles/read/8172 Thu, 24 Jun 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8172
Public Citizen, which lobbied against the approval of Crestor, claims it has new evidence about the risks of taking the drug.

The claims, to be published in a letter in Friday's edition of The Lancet, the medical journal, come two weeks after European regulators tightened the rules on prescribing Crestor.

Crestor, part of a group of drugs known as statins, is tipped by analysts to achieve peak sales of around $4bn (2.2bn) a year and is central to the Anglo-Swedish group's plans to overcome generic competition on other drugs.

In the letter, Sidney Wolfe, director of Public Citizen, said the reports of adverse events to regulators showed that the level of rhabdomyolosis [a breakdown of muscle tissue that can lead to kidney damage] caused by Crestor "is probably higher than the highest of any other currently marketed statin".

AstraZeneca responded that the letter made "misleading claims based on inappropriate interpretation of data". It added that there was "a large volume of data supporting our view, that of the European regulatory authorities and the FDA, that Crestor has a favourable benefit risk profile".

Analysts believe there is little chance of the drug being withdrawn, but said sales growth could be slowed by safety concerns.

Timothy Anderson, at Prudential Financial, said the argument adds to growing noise about Crestor's safety and could help its competitors, particularly Merck and Schering-Plough.

The letter in The Lancet is not the first time the magazine has clashed with AstraZeneca over Crestor. An editorial published last October accused AstraZeneca of using "blatant marketing dressed up as research" and said the evidence to support Crestor's safety was "inferior" to that of rivals.

Sir Tom McKilop, chief executive of the drugs group, replied that the article was "flawed and incorrect".

"I deplore the fact that a respected scientific journal like The Lancet should make such an outrageous critique of a serious, well-studied and important medicine," he wrote in a letter.]]> Health Canada Is Advising Canadians About A Possible Association Between Crestor And Rhabdomyolysis http://www.yourlawyer.com/articles/read/8918 Mon, 21 Jun 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8918
Rhabdomyolysis is a condition that results in muscle breakdown and the release of muscle cell contents into the bloodstream. Symptoms of rhabdomyolysis include muscle pain, weakness, tenderness, fever, dark urine, nausea, and vomiting. In severe cases, rhabdomyolysis can result in kidney failure and can be life-threatening.

Rhabdomyolysis has also been reported with other cholesterol lowering drugs in the "statin" family. "Statins" are a specific type of cholesterol lowering medication. Between February 2003 and June 2004 there have been eight cases of rhabdomyolysis reported in Canadian patients taking Crestor. In five of those cases the patients were taking the maximum recommended dose (40 mg) of the drug, in two cases the patients were taking the lowest recommended starting dosage (10 mg) and in the remaining case, the dosage was not stated. All of the Canadian reported cases were associated with predisposing risk factors, and no deaths have been reported.

There are certain factors that might cause an individual to have a greater risk of developing muscle related problems, including rhabdomyolysis, if they are taking a statin. These factors include: kidney problems, an underactive thyroid gland, alcohol abuse, a past history of significant muscle pain or significant muscle weakness while on statin therapy, a personal or family history of inherited muscle problems, and Japanese or Chinese ethnicity. The risk is also increased for patients who may be taking other medications which might interact with statins. Health Canada recommends that all patients taking Crestor consult with their doctors to determine if any of these factors apply to them.

Because the risk of rhabdomyolysis is increased at higher doses, Health Canada recommends that all patients taking Crestor, or any cholesterol lowering drug, should be on the lowest dose that will meet their treatment goal.

All patients taking Crestor, or any cholesterol lowering drug, are advised to report any unexplained muscle pain, muscle weakness or cramps, or any brown or discoloured urine, to their physician immediately.

This advisory is in addition to a letter issued by the manufacturers of Crestor, following consultation with Health Canada, to health care professionals reminding them of the above mentioned safety concerns. ]]> Serious Side-Effects of Statins http://www.yourlawyer.com/articles/read/8157 Mon, 14 Jun 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8157
The manufacturer of Crestor says its drug is as safe as any other statin. But you need to know more than that they all have side effects.

Statins these little pills are touted by many as the next wonder drug. They're considered safe and effective, but they don't work for everyone.

Kraus: A small but significant percent of the population will not show a cholesterol reduction even if they are taking a good dose of statins. They appear to have some resistance to the cholesterol lowering effects.

And, like all medications there are risks to taking statins, including a rare but potentially life-threatening condition called rhabdomyolysis. That's where skeletal muscle fibers are damaged, releasing proteins into the bloodstream. Some of these are toxic to the kidney and may lead to kidney failure or even death.

Rhabdomyolysis can be triggered by trauma, extreme exertion like running a marathon, heatstroke, or drug use especially cocaine, amphetamines, heroin or PCP.

And statistics show it can be caused by statins. Over a twenty-nine month period 601 cases of rhabdomyolysis were reported to the FDA, including 38 deaths.

Three years ago, Baycol was taken off the market after a significantly higher number of deaths were linked to the drug compared to other statins.

Symptoms include unexplained muscle pain, tenderness or weakness, generalized weakness, and urine that's dark red or cola colored.

If you take statins and have any of these symptoms, contact your doctor. Also, this risk of developing this muscle condition is greatest when starting a statin, increasing the dose, or when it's combined with certain other medications including Erythromycin - a very common antibiotic. ]]> European Regulators Toughen Rules for Crestor http://www.yourlawyer.com/articles/read/8151 Wed, 09 Jun 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8151
Doctors have been told they should start with low doses of the drug and must seek specialist advice before prescribing the highest, 40mg, dose after a small number of patients suffered a potentially dangerous muscle wasting syndrome.

The move comes less than a month after AstraZeneca was forced to write to doctors in the UK and Netherlands following reports of kidney problems and will heighten fears over the safety of Crestor.

Crestor is the most potent member of a class of powerful cholesterol-lowering treatments called statins that have saved millions of lives. Bayer was forced to withdraw its statin Baycol two years ago, after it was linked with over 100 deaths.

AstraZeneca said more patients reached their target cholesterol level with Crestor than any other treatment, while side effects were extremely rare and nobody had died from taking it.

The side effects appear to have occurred after doctors transferred patients from other cholesterol lowering drugs, without taking account of the fact that Crestor is more effective at lower doses than its rivals. ""This should be viewed against a background of caution towards statins in general," the company said.

Crestor has been winning market share from Lipitor, the $9.3bn-a-year market leader made by Pfizer of the US. Any serious doubts about its safety would have devastating consequences for AstraZeneca, which analysts predict could achieve peak sales of more than $4bn (2.2bn) a year with the drug.

However, the shares fell only 15p to 25.94 as investors took the view that the warning would not seriously affect sales. James Culverwell, analyst at Merrill Lynch, said the new prescribing rules would have "minimal impact" on the sales prospects of Crestor.

However, rival companies in the $26bn-a-year statin market are likely to seize on the new prescribing rules, and dangers of doctors making mistakes, when promoting their statins to the medical community.

Public Citizen, a US consumer group, has advised patients to take other available statins because of Crestor's alleged "unique kidney toxicity".

An editorial last year in The Lancet, the UK medical journal, said the drug had less safety data than rivals and accused AstraZeneca of using "blatant marketing dressed up as research".

However, AstraZeneca said it was one of the most closely studied medicines on the market. "We've had no deaths. We've had 2m patients and 5m prescriptions. We've had some cases of myopathy and rhabdomyolysis but it's very rare. Less than 0.01 per cent," the company said.]]> FDA: Use Caution When Prescribing Crestor http://www.yourlawyer.com/articles/read/8153 Wed, 09 Jun 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8153
The FDA advisory follows a new warning label released in Europe by Crestor maker Astra-Zeneca Pharmaceuticals. The changes are a response to recent reports of serious toxicity in some patients taking the drug. The new European label stresses that patients over 65, patients with underactive thyroid, and patients with kidney problems may be at particular risk especially at the highest dose, 40 mg.

Crestor labels in the U.S. already carry this information, the FDA says.

Crestor is one of the statins, a popular class of cholesterol-lowering drugs. Statins save many lives by reducing the risk of heart disease and stroke. However, all statins have to one degree or another -a dangerous potential side effect. They can injure muscle tissue and can even cause a muscle-destroying disease called rhabdomyolysis. Muscle dissolved during rhabdomyolysis releases substances harmful to the kidney. This can be deadly.

Public Citizen, a U.S. consumer watchdog group, says Crestor is particularly likely to cause rhabdomyolysis and fatal kidney damage. The group opposed the drug's approval and has twice petitioned the FDA to ban Crestor.

The FDA and the drug's manufacturer say Crestor is safe when given to the right patients at the right dose. But Public Citizen maintains that many younger patients taking low doses of the drug have died.

"In an ongoing fashion, we are evaluating these reports of adverse muscle effects with regard to clinical severity and apparent relationship to the drug," the FDA advisory says. "Pending the evaluation of the recent Crestor safety experience, FDA is not proposing to change the U.S. labeling for Crestor, but does want to re-emphasize to physicians the importance of carefully following the recommendations in the current product label."

The FDA stresses several key safety messages regarding Crestor:

Starting doses as well as continuing doses should be based on each individual patient's cholesterol goals AND on each individual patient's risk of side effects.

Doctors should tell patients that statin drugs can cause muscle injury.

Doctors should tell patients that this muscle injury can be severe. In rare cases, it can lead to life-threatening failure of the kidneys and other organs.

Patients taking Crestor or any other statin, the FDA says, should "promptly" call their doctor if they have:

Muscle pain or weakness

Malaise (feeling weak or sick)

Fever

Dark urine

Nausea

Vomiting ]]> Consumer Group Urges Ban of Cholesterol Drug http://www.yourlawyer.com/articles/read/8050 Wed, 19 May 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8050
Public Citizen's renewed call comes days after Crestor's maker, AstraZeneca, wrote doctors in Britain urging them to start patients on a mere 10-milligram dose because of concern about that muscle-destroying condition, rhabdomyolysis.

Food and Drug Administration records show 11 cases of the muscle condition in Crestor patients reported to the agency since late February, on top of 14 previously known with the drug - and seven of those newest patients were taking the 10-mg dose, said Sidney Wolfe of Public Citizen.

Nine of the new cases required hospitalization; at least five were under age 50, he said.

Crestor "is a doomed drug," Wolfe wrote the FDA.

FDA spokesman Brad Stone said the agency is closely monitoring Crestor.]]> ASTRAZENECA ISSUES WARNING LETTER TO BRITISH PHYSICIANS REGARDING OFF-LABEL CRESTOR USE http://www.yourlawyer.com/articles/read/8043 Tue, 18 May 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8043
After discovering four cases of rhabdomyolysis a muscle toxicity condition that can lead to kidney damage among high-dose Crestor users, the company cautioned physicians to adhere to indications on the label and not begin patients on high doses of the drug.

AstraZeneca advised that patients be administered 10 mg doses of Crestor initially and be increased to 20 mg or 40 mg doses only as required.

The rate of adverse events from Crestor use was similar to the side effect profile observed in other competing statins. The four cases of rhabdomyolysis occurred after patients were initiated on a high Crestor dose, according to AstraZeneca spokeswoman Kirsty Walker.

]]> Public Citizen Seeks Cholesterol Drug Ban http://www.yourlawyer.com/articles/read/8040 Mon, 17 May 2004 00:00:00 -0700 http://www.yourlawyer.com/articles/read/8040
Public Citizen's renewed call comes days after Crestor's maker, AstraZeneca, wrote doctors in Britain urging them to start patients on a mere 10-milligram dose because of concern about that muscle-destroying condition, rhabdomyolysis.

Food and Drug Administration records show 11 cases of the muscle condition reported to the agency since late February, on top of 14 previously known - and seven of those newest patients were taking the 10-mg dose, said Sidney Wolfe of Public Citizen.

Nine of the new cases required hospitalization; at least five were under age 50, he said.

Crestor "is a doomed drug," Wolfe wrote the FDA. "We renew our effort to get the FDA to ban this uniquely dangerous drug before it does any further damage."

FDA spokesman Brad Stone said the agency is closely monitoring Crestor. He said, however, that many of the side-effect cases reported so far are among patients with other risks for the muscle problem.

"So far, what we've seen doesn't indicate a disturbing pattern, but we'll continue to look at the data" from Wolfe and other sources, Stone said Monday.

A spokesman for AstraZeneca said the drug's safety "is totally consistent" with competitors in the popular cholesterol-lowering statin family.

Crestor was approved last August, although seven cases of rhabdomyolysis had occurred in patients taking an 80-mg dose during studies.

Rhabdomyolysis is caused by a breakdown in muscle fibers that end up circulated in the body. Those fibers can be toxic for kidneys and can cause them to fail.

The condition, characterized by muscle pain and weakness, is very rare. It prompted another statin, Baycol, to be pulled off the market in 2001 after dozens of deaths worldwide.

But FDA ultimately declared Crestor an important option for some patients because it appeared slightly more potent than other statins. To lower the side-effect risk, the agency recommended starting doses of 5 mg to 10 mg, and warned never to exceed 40 mg.

Wolfe initially urged a Crestor ban in March, citing seven more rhabdomyolysis cases in the drug's first months of sales, including a 39-year-old American who died after taking a 20-mg dose.]]> Crestor Left Off Insurer Listing http://www.yourlawyer.com/articles/read/7759 Wed, 10 Mar 2004 00:00:00 -0800 http://www.yourlawyer.com/articles/read/7759
The decision by Medco Health Solutions Inc. is a blow to the new cholesterol drug AstraZeneca PLC calls vital to its future.

Medco's recommendation could mean that companies and insurers won't pay for Crestor, or that patients who take it will pay more out of pocket.

Medco made its decision in recent weeks after a "clinical and financial review" of Crestor, spokeswoman Jennifer Leone said. The company would not detail the reasons for its recommendation.

AstraZeneca has said it has confidence in Crestor, especially when compared to rival drugs.

"We will continue to seek opportunities to partner with Medco in the future," AstraZeneca spokeswoman Rachel Bloom- Baglin said in an e-mail message.

The Medco recommendation already has had an impact.

General Motors Corp., a Medco client with 1.2 million beneficiaries making it the nation's largest self-insured corporate health plan, will not reimburse for Crestor.

"We're going to follow the recommendation of Medco," said GM spokeswoman Doris Powers.

Another Medco client, United Health Care, the nation's largest private health insurer, said it had included Crestor on its list of drugs approved for reimbursement, but at the highest of three out-of-pocket payment categories. United has about 21 million members.

Crestor was approved by the federal Food and Drug Administration last August for treatment of high cholesterol.

The agency approved Crestor pills in doses between 5 milligrams and 40 milligrams after AstraZeneca withdrew an earlier application that also included 80 milligram doses. The withdrawal followed clinical trials linking Crestor use at that dosage to kidney diseases.

Last week, Public Citizen, the Washington-based public advocacy group founded by presidential candidate Ralph Nader, petitioned the federal agency to ban Crestor, claiming there were 11 reports of life-threatening kidney ailments in Crestor patients in the United States, United Kingdom, and Canada, where AstraZeneca began selling the drug last year. In one case, a 39-year-old U.S. woman died of kidney disease.

All but one of the 11 reported cases cited by Public Citizen occurred in patients taking 40 milligrams or less of Crestor a day. The woman who died was taking 20 milligrams a day, along with several other medications.

In a statement released Saturday, AstraZeneca called Public Citizen's claims "misleading, irresponsible and needlessly alarming to patients.

"Crestor is the most extensively studied statin ever approved by FDA." AstraZeneca said. "More than one million patients have taken the medication, with more than two million prescriptions dispensed."

David Moskowitz, a vice president of Friedman, Billings Ramsey & Co. Inc., an Arlington, Va.-based investment bank, said reservations about the drug are having an impact.

"The fact that there are now several major insurance companies refusing to put Crestor on preferred status on their formularies suggests fears not just in the physician community, but in the insurance community," Moskowitz said.

Last October, WellPoint Health Networks Inc. said it would not reimburse its 15 million patients for Crestor. Among other issues, WellPoint cited concerns about kidney problems in clinical trials of Crestor. WellPoint would replace United Health Care as the nation's largest private health insurer if a pending merger is approved.

Lisa Mee-Stephenson, spokeswoman for WellPoint, said doctors can get WellPoint to reimburse for Crestor in most cases if they specify in writing a medical necessity for the drug. The patient would then need to make the highest co-payment, in most cases.

Mee-Stephenson said the insurer will review Crestor's status later this month. WellPoint said it has eight cholesterol-lowering drugs on its recommended list and Medco has three.

AstraZeneca executives have described Crestor's acceptance as solid.

For example, Advance PCS, another health care consultant that influences prescriptions for about 75 million Americans, recommended Crestor last fall with a relatively low out-of-pocket payment. A spokesman said the Irving, Texas-based consultant did so after its own review of the drug's safety and the federal drug agency's approval.

AstraZeneca told Wall Street last fall that it hoped Crestor would capture up to one-fifth of the $20 billion annual worldwide market for statins, whose sales are led by Pfizer Inc.'s Lipitor, the world's best-selling prescription drug.

"Crestor is central to our ambitions, it is off to a very good start and we are confident we will make it a major megabrand," AstraZeneca's chief executive, Sir Tom McKillop, told analysts in January. ]]> Group Seeks Ban of Anti-Cholesterol Drug http://www.yourlawyer.com/articles/read/7725 Thu, 04 Mar 2004 00:00:00 -0800 http://www.yourlawyer.com/articles/read/7725
Crestor is in the popular family of cholesterol-lowering drugs called statins.

It won Food and Drug Administration approval in August, after a delay because of safety concerns: Seven cases of the potentially fatal, muscle-destroying condition called rhabdomyolysis occurred during studies involving patients on an 80-milligram dose. For that rare condition to pop up in clinical trials was unusual -- and particularly worrisome since another statin, Baycol, had been pulled off the market in 2001, linked to dozens of rhabdomyolysis-caused deaths worldwide.

In studies, Crestor also was linked to some cases of kidney abnormalities not seen with other statins.

Still, FDA ultimately decided to approve Crestor, saying it appeared to be slightly more potent than other statins and thus may be important for some patients. To lower the risk of side effects, FDA recommended starting doses of 5 mg. to 10 mg, and said patients should never exceed 40 mg.

But records from the FDA and health agencies in Canada and Britain show life-threatening side effects occur even at those lower doses, said Dr. Sidney Wolfe of the consumer advocacy group Public Citizen, in a petition filed with FDA Thursday seeking a ban.

Among the records:

Seven patients with rhabdomyolysis, including the 39-year-old American who died after using a 20-mg dose, and a second death from an unspecified country.

Four patients with acute kidney failure, including a 79-year-old U.S. man who died.

Five additional patients with less severe kidney damage.

Also, among six patients, Crestor interacted dangerously with the blood-thinner Coumadin, commonly used by heart-disease patients. One had a hemorrhage, Wolfe said.

Crestor maker AstraZeneca wouldn't comment on the deaths or other serious side effects except to say "the safety profile is totally comparable" to what pre-marketing studies had predicted, said spokesman Gary Bruell.

"We're very pleased with the performance of the drug thus far," he said, noting that 1 million patients worldwide have tried Crestor, including 600,000 in the United States. The company is about to begin major television advertising for the drug.

But Wolfe contended that Crestor "has no unique advantage, but some unique risks" over other statins. He told the FDA there is growing concern about the drug, citing two major U.S. insurers who refuse to pay for it because of the muscle risk and a recent recommendation against use by Sweden's drug advisers.

The FDA will evaluate the petition, said spokeswoman Laura Bradbard.]]> Crestor Side Effects Lawsuit Rhadomyolysis Lawyer http://www.yourlawyer.com/topics/overview/crestor Thu, 04 Mar 2004 00:00:00 -0800 http://www.yourlawyer.com/topics/overview/crestor DOWNLOAD OUR CRESTOR INFORMATION PACKAGE

Injured By Crestor?

Crestor has been linked to kidney damage and kidney failure. On October 22, 2004, the consumer group Public Citizen said twenty-nine patients who took AstraZeneca's cholesterol drug Crestor developed kidney damage. Crestor has also been linked to the potentially fatal disease Rhabdomyolysis.

Consumer group, Public Citizens states, the rate of reported kidney problems is approximately 75 times higher with Crestor than with all other drugs in the same class combined. According to its analysis, there have been 6.4 reports of acute kidney failure or kidney damage for every 1 million Crestor prescriptions filled.

Crestor has been linked to numerous cases of Rhabdomyolysis, a rare muscle destroying disease. Crestor is in the popular family of cholesterol-lowering drugs called Statins. Several years ago Baycol, another popular statin drug, was banned for its link to Rhabdomyolysis.

Crestor Side Effects were Evident Before it was Approved

Crestor was approved by the FDA in August 2003, after a delay because of safety concerns. During FDA studies seven cases of the potentially fatal, muscle-destroying condition Rhabdomyolysis occurred.

These studies also linked Crestor with cases of kidney abnormalities not seen with other Statins. The FDA decided to approve Crestor but at lower dosages. However, records from the FDA and health agencies in Canada and Britain show life-threatening side effects occur even at those lower doses.

Rhabdomyolysis is a serious disorder that causes kidney damage resulting from toxic effects of the contents of muscle cells. Myoglobin is an iron-containing pigment found in the skeletal muscle. When the skeletal muscle is damaged, the Myoglobin is released into the bloodstream. It is filtered out of the bloodstream by the kidneys. Myoglobin may obstruct the structures of the kidney, causing damage such as acute tubular necrosis or kidney failure.

If you or a loved one took Crestor and suffered side effects, please fill out the form at the right for a free case evaluation by a qualified drug side effects attorney.

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