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FDA: New Warning Labels for Statins - Comments on FDA Warning. FDA said patients should not be scared off statins. "The value of statins in preventing heart disease has been clearly established"
  "If you have heart disease, you probably should be on a statin. If you're at high risk, a statin may be warranted. But we don't think these drugs should be put in the water supply," Nissen said. Feb 29, 2012

By Alice Park

The Food and Drug Administration (FDA) added new safety warnings to cholesterol-reducing statin drugs on Wednesday, noting increased risks of Type 2 diabetes and memory loss for patients who take the medications.

The changes to the prescribing information apply to the class of statins, including many popularly prescribed drugs such as Lipitor (atorvastatin), Crestor (rosuvastatin), Zocor (simvastatin) and Vytorin (simvastatin/ezetimibe). The new warnings are based on results from the latest clinical trials and reports of adverse events from patients, physicians and drugmakers.

The FDA said that statins may increase users' risk of brain-related effects like memory loss and confusion. The reports have generally not been serious, however, and the symptoms go away once the drug is stopped, the agency said.

Statins' labels will now also warn patients and doctors that the drugs may cause a small increase in blood sugar levels and Type 2 diabetes - an effect that has been shown previously in studies. Type 2 diabetes can further increase the risk of heart disease.

In addition, the FDA made a label change specific to Mevacor (lovastatin). Mevacor can interact with other drugs, increasing the risk for muscle pain and weakness, another side effect that has previously been associated with high-dose statin use. Other drugs may raise such risks by increasing the amount of statins in the blood, and the FDA warned that Mevacor should not be taken with protease inhibitors, which are used to treat HIV, certain antibiotics and some anti-fungal medications.

At the same time, the statins' labeling will no longer require the routine monitoring of patients' liver enzymes, which was originally intended to alert doctors if the medications were becoming toxic and starting to damage the liver. The FDA concluded that such serious damage is rare, and regular testing for all users isn't necessary. The agency now recommends that liver enzyme tests be performed before starting statin therapy, and as clinically indicated thereafter.

MORE: Who Should Take Statins? The Debate Continues

Despite the new safety warnings, the agency said patients should not be scared off statins. "The value of statins in preventing heart disease has been clearly established," said Dr. Amy G. Egan, deputy director for safety in the FDA's division of metabolism and endocrinology products, in an agency statement. "Their benefit is indisputable, but they need to be taken with care and knowledge of their side effects."

But some experts worried that the labeling changes would result in unnecessarily alarming patients and causing some who may benefit to shy away. "I do not believe there is enough hard evidence to justify information and warnings about memory loss and confusion or increase in blood sugar," Dr. Scott Grundy of the University of Texas Southwestern Medical Center told MedPage Today. "I also think that these warnings will cause some people who need statins to stop taking them. That would be unfortunate."

In general, however, experts tended to support the FDA's action, noting that while the potential diabetes and cognitive side effects were rare, they should still be highlighted to doctors and patients. "These are reasonable and prudent recommendations," Dr. Steven Nissen of the Cleveland Clinic also told MedPage Today. "I am pleased that FDA did not overstate the diabetes and cognitive function risks. Both problems are uncommon and don't diminish the importance of statins in cardiovascular protection. For the vast majority of patients, the benefits far outweigh the risks."

Dr. Gordon Tomaselli, president of the American Heart Association noted people concerned about their cholesterol levels should always focus on prevention through lifestyle changes first, trying drug treatment only if their physicians recommend it. "As with all therapies, the decision to use statins for primary or secondary prevention must include careful consideration of the risks and benefits, side effects and cost," Tomaselli said in a statement. "The FDA's announcement on the label changes does not question the benefit of statins to lowering cholesterol, but it does provide patients and healthcare providers the most current information about the safe use of statins."


FDA adds diabetes, memory loss warnings to statins

By Bill Berkrot and Ransdell Pierson

Tue Feb 28, 2012

(Reuters) - Health regulators are adding warnings to the labels of widely used cholesterol lowering drugs, such as Lipitor, to say they may raise levels of blood sugar and could cause memory loss.

The Food and Drug Administration announced on Tuesday the changes to the safety information on the labels of statins such as Pfizer Inc's Lipitor, AstraZeneca's Crestor and Merck & Co's Zocor that are taken by tens of millions of people.

Statins have been shown to significantly reduce the risk of heart attack and heart disease, and the FDA said the new information should not scare people into stopping taking the drugs.

"The value of statins in preventing heart disease has been clearly established," Amy Egan, deputy director for safety in FDA's Division of Metabolism and Endocrinology Products, said in a statement. "Their benefit is indisputable, but they need to be taken with care and knowledge of their side effects."

Lipitor, which became available late last year in generic form as atorvastatin, is the world's all-time biggest selling prescription medicine with cumulative sales in excess of $130 billion. As a class, statins have helped enrich the world's largest drugmakers, but most of the major brands are now prescribed as far cheaper generic medicines.

Last year, more than 20 million Americans were taking some form of statin, according to IMS Health.

"These are nuances, tiny little tweaks to the label, and the bigger picture doesn't change," said Steven Nissen, chief of cardiology at Cleveland Clinic. "There are few drugs that have saved as many lives as statins and we don't want to throw the baby out with the bathwater here.

"If you have heart disease, you probably should be on a statin. If you're at high risk, a statin may be warranted. But we don't think these drugs should be put in the water supply," Nissen said.

Asked what prompted the label changes, FDA spokeswoman Erica Jefferson said they were based on the agency's review of medical literature, clinical trial data and reports of adverse events.

"I wouldn't point to any one thing," she said. "We've been looking at all the information for some time. It's part of our ongoing surveillance."


The FDA said it was aware of studies in which some patients taking statins may have a small increased risk of higher blood sugar levels and of being diagnosed with type 2 diabetes.

The statin labels will also now reflect reports of certain cognitive effects such as memory loss and confusion experienced by some patients taking the drugs, the agency said. It said those reports generally have not been serious and the symptoms were reversed by stopping use of the statin.

"We have known for three or four years that statins slightly increase blood sugar," Nissen said. "The fact that the blood sugar went up a little bit did not diminish the effectiveness of the statins in reducing (heart) risk for patients."

The elevated diabetes risk cropped up in a 2008 Crestor study of nearly 18,000 patients. A separate study published in the Lancet medical journal in 2010 found that statins can raise the risk of diabetes by 9 percent.

The memory loss issue was more anecdotal from adverse event reporting and not from formal studies, the FDA said, adding that there was no proof that the problem was caused by statins but that it wanted people to be aware of the possibility.

One safety warning long associated with the class of medicines will be reversed, the FDA said. Patients taking statins will no longer need periodic monitoring of liver enzymes, since cases of serious liver injury are rare and unpredictable in individual patients.

Other statins, most of which are available as generics, include Livalo, Mevacor, Pravachol, Altoprev and Lescol. There are also combination medicines that include statins, such as Merck's Vytorin and Abbott Laboratories' Simcor.

Jon LeCroy, an analyst who follows the pharmaceutical industry for MKM Partners, said he did not believe the label changes would have a lasting impact on statin use.

"The overwhelming evidence on statins is they save lives, so I can't imagine this would reduce anyone prescribing them," LeCroy said.

"There are some buzzwords that tend to scare the lay public. This is not a cancer warning," he said.

The FDA also specifically said that Merck's Mevacor, the world's first approved statin, known generically as lovastatin, should never be taken with certain drugs used to treat HIV and certain bacterial and fungal infections due to increased risk of a serious muscle disease.

"I don't think we should change our practice based on this report," said Dr. Kenneth Ong, acting chief of cardiology at the Brooklyn Hospital Center in New York.

"But the report is a sobering reminder there's no such thing as a free lunch," Ong said. "Every drug has its problems and its side effects, despite the benefits."


Safety Alerts Cite Cholesterol Drugs' Side Effects


nytime blog Published: February 28, 2012

Federal health officials on Tuesday added new safety alerts to the prescribing information for statins, the cholesterol-reducing medications that are among the most widely prescribed drugs in the world, citing rare risks of memory loss, diabetes and muscle pain

. It is the first time that the Food and Drug Administration has officially linked statin use with cognitive problems like forgetfulness and confusion, although some patients have reported such problems for years. Among the drugs affected are huge sellers like Lipitor, Zocor, Crestor and Vytorin.

But federal officials and some medical experts said the new alerts should not scare people away from statins. "The value of statins in preventing heart disease has been clearly established," said Dr. Amy G. Egan, deputy director for safety in the F.D.A.'s division of metabolism and endocrinology products. "Their benefit is indisputable, but they need to be taken with care and knowledge of their side effects."

Diabetes patients and even those who develop diabetes while taking statins should continue taking the medicines, said Dr. Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic, who has studied the medicines extensively.

"These are not major issues, and they really do not alter the decision-making process with regard to statins," Dr. Nissen said.

Last year, nearly 21 million patients in the United States were prescribed statins. Whether that number of users is too high or too low has been debated for years. While advice on whether to take statins involves a complex mix of factors like age, family history and blood pressure, some experts have suggested that those with total cholesterol levels around 200 would benefit from treatment. Others have argued that treatment should not start until a cholesterol level of 240 or higher, all other factors being equal.

Dr. Sidney M. Wolfe, director of Public Citizen's health research group, is among those who contend statins are overused. He said the new alerts about risks provided more reasons that otherwise healthy people with cholesterol levels less than 240 "should not be taking these drugs."

The F.D.A. said that routine monitoring of liver enzymes in the blood, once considered standard procedure for statin users, was no longer needed because the liver injury associated with statin therapy was so rare.

Reports about memory loss, forgetfulness and confusion span all statin drugs and all age groups of patients, the F.D.A. said. Dozens of well-controlled trials of statins have offered few hints that the drugs cause any kind of cognitive impairment, Dr. Egan said. Still, the F.D.A. has received many reports over the years that some patients felt unfocused or "fuzzy" in their thinking after taking the medicines.

Officials in the F.D.A. debated whether such reports were truly worrisome, Dr. Egan said. But in recent years, the F.D.A. - criticized for waiting too long to issue some safety alerts - has become more willing to be public about possible drug risks, even when the evidence is uncertain

"We are trying to be as transparent as possible with our alerts and labeling," Dr. Egan said, even though the alert on the possibility of fuzzy thinking "is not overly helpful."

Statins seem to increase blood sugar levels in some patients by small amounts, and when millions are treated, that change leads to a diagnosis of diabetes for more people.

The F.D.A. had already placed an alert about diabetes risks on the label of Crestor, a big-selling statin made by AstraZeneca, because a Crestor trial showed an increased risk. The agency decided to extend that alert to all drugs in the class with the exception of Pravachol, an older medicine manufactured by Bristol-Myers Squibb.

A well-controlled trial of Pravachol previously showed that it reduced the risks of developing diabetes by 30 percent, but other trials have found Pravachol less effective in reducing cardiac risks.

Dr. Egan suggested that doctors check the blood sugar levels of patients after starting them on statin therapy.

That statins can cause muscle pain, particularly at high doses, has long been known, but in its new alert the F.D.A. reminded doctors that some other medications increase the likelihood that statins linger in the body longer than normal and increase the risk of muscle pain. Among the drugs that conflict with statins are hepatitis C protease inhibitors like telaprevir and boceprevir and the antibiotics erythromycin and clarithromycin.


How Rare Are Statin-Related Memory Issues? Very

How Rare Are Statin-Related Memory Issues? Forbes

Do statins like Lipitor, Zocor, and Crestor make people confused? And, if so, how often do they do it?

FDA Cautions On Memory, Diabetes Side Effects In Cholesterol-Lowering Drugs

Short answer: they seem to, but not nearly as often as neurological or psychiatric side effects occur through no fault of the drug. The Food and Drug Administration just decided to add cautionary language to the labeling of these popular statin lowering drugs, which are taken by 20 million Americans, according to IMS Health.

Given the new FDA notice, it seems worth going back to the most recent data to show that a statin had mental side effects: the 17,802-patient study of Crestor called JUPITER. This study showed that Crestor, made by AstraZeneca, reduced the risk of a major cardiovascular event (that includes heart attack, stroke, hospitalization, and surgery to open clogged arteries) by 44%. In these people, the risk of a heart problem during the course of the study was low: 142 of 8,901 patients on Crestor had a major cardiovascular event during the course of the study, compared to 252 of the 8,901 patients taking placebo.

The issues of cognitive side effects were made public in briefing documents provided by the FDA to a panel of experts who voted on whether Crestor should be approved for preventing heart attacks, strokes, and heart procedures in patients who had never had one. You can read them here. Overall, 69 of the 8,901 patients taking Crestor reported "nervous system disorder" compared to 76 on placebo; 515 Crestor patients reported psychiatric issues, including insomnia and depression, compared to 533 on placebo.

The evidence for confused state comes up here:

The Applicant reported that 18 rosuvastatin-treated subjects versus 4 placebo-treated subjects experienced the AE of "confusional state". Six of the 18 confusional states in rosuvastatin-treated subjects were considered as a SAE. Two subjects were not on study medication at the time and others had concurrent medical conditions and/or medications ongoing at the time of the event

So 18 patients out of a total of 8,901 reported having a confused state quadruple the number on placebo. (Two of the patients were not taking drug when the confusional state happened, but normally they'd be included in a safety analysis anyway to be conservative.) So although we're talking about quadrupling of risk of becoming extremely confused, Crestor would have only caused this side effect in 0.16% of patients.

But about 600, or 7%, of patients reported neurologic and psychiatric side effects while on Crestor in this same clinical trial. That means that for ever person in this trial whose confusional state was caused by Crestor, another 43 had neurological or psychiatric side effects that were probably not due to the drug.

I think all of these side effects are probably under-reported, and I think that doctors are probably too fast to shrug off cases of muscle pain or memory issues that might be the result of statin therapy. It's also important to note that the FDA's decision was probably based on a lot more than this analysis. But this shows pretty clearly why this poses a difficult situation for doctors and patients: a particular case of fogginess or forgetfulness is probably not caused by the drug - except in the rare cases where it is.



"statins re useful in preventing heart disease"

Federal regulators announced today they would add additional safety warnings to the labels on statins, a class of drugs that lower cholesterol.

Statins -- more commonly known by the brand names Lipitor, Crestor and Zocor -- inhibit the enzyme that plays a big part in the liver's production of cholesterol.

The U.S. Food and Drug Administration now requires that statin labels include warnings about the rare but serious risk of liver damage, memory loss and confusion, and type 2 diabetes. Certain statins, known by the generic name lovastatin, can raise the risk of muscle weakness.

The decision came following an internal meeting between the FDA's Office of Surveillance and Epidemiology and Office of New Drugs, according to Dr. Amy Egan, the FDA's deputy director of safety in the division of metabolism drug products.

Egan said most of the information reviewed, especially the effect of statins on memory loss, came from a small number anecdotal reports compiled over one year. She added that the warning for memory loss was more for serious cognitive problems than simple forgetfulness.

"We can't establish causality with statin therapy," said Egan, regarding the new warnings.

Also, most of the studies the division evaluated were short-term studies, suggesting that the long-term effects of statin therapy were unclear. Egan also said it had yet to be determined which statins and at what dose could increase the risk of the listed side effects.

However, many experts said they'd seen these effects in some of their patients. Although the need for liver-monitoring tests have also been removed from statin labels -- and instead replaced with recommendations to perform liver enzyme tests before starting statin therapy -- many experts said they still prescribed these tests for their patients.

"I disagree with the notion that you can stop checking for liver function test abnormalities," said Dr. Andrew Carroll, a physician at the Renaissance Medical Group in Phoenix.

Carroll said he saw high liver enzymes in about 5 percent of the patients to whom he prescribed statins, prompting him to recommend they stop taking the medication.

Still, many experts said the added labels should not deter patients from statins. Instead, they should report any side effects they experience to their physician.

"This information highlights the importance of being alert to any new symptom that occurs around the time that you have started any new medication, and making sure that we only recommend drugs where there is a chance of a substantial benefit since all drugs have risks," said Dr. Harlan Krumholz, a cardiologist and associate professor of medicine at Yale University School of Medicine.

While the risk of the side effects remains low, Egan said larger and longer-term studies need to be completed to understand exactly what type of patients may be at higher risk.

"We really don't feel the changes in the drug labels we made today alter the risk status of statins," Egan told ABC News. "We still think the benefits of the drug outweigh the risks."

Consumers will be able to see the label changes on their medications within the next 30 days, Egan said.


By Robert Bazell Chief science and health correspondent NBC News

Not long ago, statins were jokingly promoted by some doctors with a "put them in the drinking water" argument. Physicians and drug company experts suggested that the ubiquitous cholesterol-lowering drugs -- including Lipitor, Mevacor, Crestor and Zocor -- should be sold over the counter like cold medications, or offered to everyone above a certain age. The medications appeared so beneficial to health and seemed so free of side effects.

But on Tuesday, the Food and Drug Administration issued a new health alert requiring the drugs carry labels warning about confusion and memory loss, elevated blood sugar leading to Type 2 diabetes, and muscle weakness.

"These warnings should put an end to the all the silliness about giving the drugs to everyone," says Dr. Garret FitzGerald, chairman of pharmacology at the University of Pennsylvania.

Warnings for diabetes, memory loss added to statins

There is no question that statins -- the most profitable and among the most prescribed drugs ever -- have saved or prolonged millions of lives and will continue to do so. Most people at elevated risk for heart disease should be taking statins. The big issue now will center on determining whose risk is low to moderate and may not need medication.

The FDA approved the first statin, Merck's lovastatin, in 1987. Other companies produced their own versions over the last two decades as evidence of the drugs' effectiveness continued to accumulate, adding to their popularity. But, early on, plenty of side effects warnings popped up.

Every time NBC News reported on statins I would receive many communications from viewers who had suffered the muscle-weakening condition, known as rhabdomyolysis, after taking the medication. When they stopped the drug, their muscles usually returned to normal. Doctors who frequently prescribe statins report that a certain percentage -- the best guess is about 1/2 to 1 percent -- suffer the muscle problems. That's a rare occurrence as side effects go, but when many millions are taking the drugs, the numbers add up.

As for elevated blood sugar and memory problems, both conditions have been reported for years, but it is harder to guess how widespread the complications are. In fact, last month, a survey of 150,000 participants in the Women's Health Initiative -- the government's gigantic study that ended most hormone replacement -- found that older women taking statins were 48 percent more likely to develop diabetes. (The researchers tried to control for obesity and other risk factors.)

Because most people who take statins tend to be older, they're already more likely to develop diabetes or memory problems. The only test to accurately measure the risk from statins would be a long, controlled trial of thousands of people at low risk for heart disease where half get the drug and half get a placebo. No drug company will pay for it.

Astra Zeneca's Crestor remains the only statin still under patent protection, and it would be foolish for that company to go looking for harmful side effects. The government's resources for big expensive studies grow ever more scarce. We may never know the true danger, but at least now the drugs have labels telling patients and doctors to be aware of them

Why did the FDA chose to label the drugs now when the danger signs have been around for years? There is no official answer, but the officials in charge of the FDA now have shown far more willingness to be honest about public health risks than many of their recent predecessors.

As for whether you or a loved one should be taking a statin drug: This is certainly not an automatic decision, but definitely a subject for a discussion with your physician. Because of the FDA's labeling actions that decision should now be far better informed.

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