Yourlawyer.com (Rhabdomyolysis News)

Simvastatin and Amiodarone Linked to Possibly Fatal Muscle Disease

Fri, 08 Aug 2008 00:00:00 -0700

The combination of simvastatin and amiodarone, an anti-arrhythmia medication, has been linked to a rare muscle condition that can cause kidney damage and death. The Food & Drug Administration (FDA) first warned against combining the drugs in 2002 because of their association with the condition - called rhabdomyolysis - but has continued to received reports of its occurrence.

Amiodarone is an ingredient in Wyeth's Cordarone and is also sold generically. Simvastatin is an ingredient in Merck & Co's Zocor and Abbott Laboratories Inc's Simcor, and is sold generically. It also a component of Merck and Schering-Plough Corp's Vytorin.

Simvastatin is a statin, a class of drugs which already carries a risk of rhabdomyolysis. However, the FDA said today that the risk of developing rhabdomyolysis is more pronounced when simvastatin is combined with amiodarone than it is with other statin medications.

Rhabdomyolysis is a muscle injury that causes the rapid breakdown of skeletal muscle tissue. The destruction of the muscle leads to the release of the breakdown products of damaged muscle cells into the bloodstream; some of these, such as myoglobin, are harmful to the kidney and may lead to acute kidney failure.

According to today's FDA warning, the risk of developing rhabdomyolysis is dose-related and increases when a dose of simvastatin greater than 20 mg per day is given with amiodarone. The agency said that healthcare professionals, who prescribe simvastatin or simvastatin-containing medications (Simcor, Zocor, Vytorin), should be aware that patients taking amiodarone should not take more than 20 mg per day of simvastatin.

Patients starting therapy with simvastatin, or who have had their dose of simvastatin increased, should contact their doctor immediately if they experience symptoms of unexplained muscle injury, such as muscle cramps, pain, tenderness, stiffness or spasm.

The FDA said it is working with the manufacturer of Cordarone (amiodarone) to modify prescribing information to warn of an increased risk of rhabdomyolysis when amiodarone is taken with simvastatin doses exceeding 20 mg daily. In 2002, the labeling of simvastatin was changed to include similar information.

Report: Bayer Held Back on Drug Dangers

Tue, 23 Nov 2004 00:00:00 -0800

Another pharmaceutical company may have concealed safety information about a dangerous drug this time Bayer and its once-popular cholesterol medication Baycol according to a report in a prominent medical journal.

Baycol was pulled from the market in 2001, but an analysis released Monday by the Journal of the American Medical Assn. argued there were strong indications of its dangers three months after its introduction in 1998.

The report adds to concerns that the Food and Drug Administration's drug monitoring system is too lax. The FDA is being criticized for its handling of Vioxx, the arthritis drug that remained on the market after concerns were raised that it increased the risk of heart attacks and strokes. Its manufacturer, Merck & Co., pulled Vioxx off the market in September.

Baycol belongs to a class of cholesterol-lowering drugs known as statins, which have been shown to reduce the risk of heart attacks, but have also been linked to a toxic muscle degeneration known as rhabdomyolysis, which can cause kidney problems and death.

Baycol had by far the highest rate of rhabdomyolysis of any statin, said Dr. Bruce Psaty, a professor of medicine and epidemiology at the University of Washington and the report's coauthor.

In a response to be published in the Dec. 1 issue of JAMA but released early with the other reports, a lawyer for Bayer, Joseph Piorkowski, questioned the objectivity of the authors, who had served as expert witnesses in lawsuits against the company.

Piorkowski argued that muscle degeneration was a known risk of all statins, that FDA surveillance had worked effectively, and that the company's conduct "was responsible, appropriate and consistently motivated by concern about the safety and welfare of patients."

The dangers of Baycol, known generically as cerivastatin, cast suspicion over all statins. But a separate study in the same issue of JAMA analyzed data from 250,000 patients who took statins between 1998 and 2001 and showed that three of the most common Lipitor, Pravachol and Zocor proved to be relatively safe.

The risk of the rhabdomyolysis rose slightly when combined with medications known as fibrates, which lower triglyceride fats and are often prescribed in conjunction with statins.

Baycol, taken alone, posed 10 times the risk of other statins, the study said. When taken with fibrates, the danger was enormous: 10% of patients got the muscle disorder.

The study was led by Dr. David J. Graham, the FDA scientist who told a Senate panel last week that his agency was failing to monitor the safety of drugs it had approved.

His analysis did not look at the most powerful statin, Crestor, which was introduced last year. Graham has said that Crestor should be studied further. Its manufacturer, AstraZeneca, has stated that the drug is safe.

Dr. Benjamin Ansell, a cholesterol expert at UCLA, said that the risk posed by statins was far outweighed by their benefits. "More people die every month from aspirin, which is considered to be relatively safe, than have ever died from the statins," he said.

During clinical trials to win FDA approval for Baycol, there were no signs of serious side effects. When the drug was released in February 1998, it carried a standard warning that statins had been linked to muscle degeneration.

But in the first three months of sales, seven cases of rhabdomyolysis were collected through the FDA's adverse-event reporting system. Six of the patients had also been taking a fibrate, according to Psaty.

Psaty, whose analysis was partially based on internal Bayer documents made public during a lawsuit, said the six cases should have been a serious warning.

"There were opportunities to advance science and protect patients that were missed," he said.

In December 1999, Bayer changed the label to warn against an interaction with the fibrate gemfibrozil.

By the time Bayer removed the drug in 2001, the number of rhabdomyolysis cases was estimated to have reached the tens of thousands. By this fall, the company had settled 2,861 lawsuits over Baycol.

A JAMA editorial questioned the FDA's system of monitoring drug safety. The editors said the FDA relied too much on the drug companies to collect information about dangerous side effects of their products. They supported calls for an independent body to monitor drugs on the market.

Advocate Suggests Crestor May Harm Kidneys

Fri, 29 Oct 2004 00:00:00 -0700

Consumer advocate Dr. Sidney Wolfe renewed his effort Friday to get the anti-cholesterol drug Crestor removed from sale.

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.

Rate of Kidney Damage in Crestor Patients Is 75 Times Higher Than in Patients Taking Other Cholesterol Drugs

Fri, 29 Oct 2004 00:00:00 -0700

The rate of reports of kidney failure or damage among patients taking the cholesterol drug Crestor is 75 times higher than in all patients taking all other statins, according to a Public Citizen analysis of government data. Public Citizen sent the information today to the U.S. Food and Drug Administration and renewed its call for the drug to be taken off the market.

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

Fri, 29 Oct 2004 00:00:00 -0700

Lester Crawford, DVM, Acting Commissioner
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

Rhabdomyolysis Baycol Crestor Statin Drugs Side Effects Lawyer

Fri, 29 Oct 2004 00:00:00 -0700

Rhabdomyolysis

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.

Myoglobin breaks down into potentially toxic compounds, which will also cause kidney failure. It is important to treat Rhabdomyolysis quickly. Early and aggressive hydration may prevent complications by rapidly eliminating the myoglobin out of the kidneys. The hydration needs with muscle necrosis may approximate the massive fluid volume needs of a severely burned patient. This may involve intravenous administration of several liters of fluid until the condition stabilizes.

Diuretic medications such as mannitol or furosemide may aid in flushing the pigment out of the kidneys. If the urine output is sufficient, bicarbonate may be given to maintain an alkaline urine state. This helps to prevent the dissociation of myoglobin into toxic compounds.

Rhabdomyolysis results from any condition that causes significant muscle damage. These include:

Certain muscle diseases
Severe muscle injuries (e.g., crush injury)
Overuse of alcohol or illicit drugs
Use of some prescription drugs
Severe seizures or convulsions

If you or a loved one has taken the Statin drugs, Baycol or Crestor and have been diagnosed with Rhabdomyolysis, please fill out the form at the right for a free case evaluation by a qualified defective drug attorney.