Vytorin combines simvastatin (sold as in individual ingredient under the brand name Zocor) and ezetimibe (also known as Zetia) to reduce the production of “bad” cholesterol. An FDA review of data from clinical studies, adverse event reports, and prescription use of simvastatin indicated patients who took doses of 80 mg or more of simvastatin were at greater risk for developing a muscle injury known as myopathy. Myopathy, which causes pain, tenderness or weakness, is a known side effect of all statin drugs. Myopathy can lead to rhabdomyolysis, a more serious condition that can lead to kidney failure, which can be fatal.

Much of the data reviewed by the FDA came from the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH), a clinical trial aimed to better understand the relationship between high-dose simvastatin use and muscle injury.

Vytorin also carries a risk of liver damage and liver problems such as hepatitis, cirrhosis and even liver failure. A February 2008 study also found that Vytorin was no more effective than simvastatin alone in lowering cholesterol, and that patients taking Vytorin actually had more plaque buildup than patients taking simvastatin alone.

SOURCE: Vytorin Recall › FDA warns of link between cholesterol drug, muscle injury

The SEAS study sought to test Vytorin’s effectiveness as an alternative to surgery in reducing arterial clogging caused by high cholesterol. The results, which were announced in a July 2008 press conference, did not favor the drug. Not only did researchers find that Vytorin worked no better than cheaper, generic statins, they also discovered that patients taking Vytorin experienced 50 percent more new cancer cases and cancer deaths than the subjects who took placebos.

Merck and some of the researchers connected to the SEAS study dismissed the results as a “fluke,” while many physicians and medical researchers not connected to the drug company remained skeptical and cautioned consumers to stick with traditional statins to control cholesterol levels. For instance, Merck’s Zocor, taken alone, was shown to be more effective than Vytorin and cost about one-third as much because it had become available as a generic drug.

That research promoted many municipalities that had included Vytorin in their health plans to file lawsuits against Merck, essentially asking for their money back. Vytorin and its sister drug Zetia, made by Schering-Plough, brought in sales of more than $5 billion at their peak. The sales have fallen but continue to earn $4 billion annually.

Vytorin is a hybrid drug which combines Merck’s Zocor with Schering-Plough’s Zetia to combat both dietary and hereditary cholesterol. The FDA said that ample evidence exists showing Zocor to be safe, but insufficient evidence exists on Zetia to “rule out a cancer risk at this time.”

Two additional Vytorin studies known by the acronyms SHARP and IMPROVE-IT are ongoing and scheduled to end in 2010 and 2012.

SOURCE: Vytorin Recall › FDA says it finds no Vytorin-cancer link, but unsure

Now Congress is investigating the promotion of Vytorin as lawsuits against its makers pile up in state and federal courts. But Vytorin isn’t the only heavily promoted new drug to cause problems, so some congressmen are planning to pull in the reins of direct-to-consumer (DTC) drug advertising.

Rep. Henry Waxman (D-Cal.) has renewed the call to give regulators the power to ban DTC advertising for new prescription drugs when their safety profiles aren’t fully known. The would-be legislation, which emerged in 2007 but ultimately failed to pass, is plowing ahead in the wake of some heavily promoted but beleaguered blockbuster drugs.

Like Vytorin, Chantix and Vioxx were more or less indicted after tests and reports brought unknown risks to light, and each made billions in profit before negative news rained on their parade.

Rep. Waxman, who becomes chairman of the House of Representatives Energy and Commerce Committee when the new Congress convenes in January, has expressed his interest in revisiting the drug ad issue.

“It is these first few years of a drug’s life that drug companies often aggressively market their products and engage in direct-to-consumer advertising. This increases the number of consumers exposed to safety risks of new products long before those risks are truly understood,” Waxman said at a Prescription Project Conference.

Merck’s blockbuster anti-inflammatory drug Vioxx was taken by approximately 20 million people before its risk of cardiac events became known. Chantix was taken by millions of people as well before researchers understood the risks the drug posed for depression, suicide, and other serious side effects. And, of course, Vytorin, which millions of people took before one test exposed it as a dud and another as a possible caner risk.

To help ease the dangers posed by new medicines, Congress sought last year to give the FDA the authority to ban the television advertising of new prescription drugs for as long as three years if it was deemed necessary to protect the public. The ban would not be a blanket ban on all new prescription drugs, but would be enacted on a case by case basis.

Exaggerated benefits and minimized perception of side effects are two pitfalls of DTC advertising for the general public. Excessive prescribing is another, but that seems to be the whole point, at least from the drug manufacturers’ point of view. Television ads for new prescriptions aren’t made with the public’s good in mind. They’re made to maximize profit. Advertising for profit is the American way, but when it amounts to messing with the health of millions, clearly some restraint is needed.

According to a report by Reuters, drug makers claim that their ads are informative to the general public and that they have adopted voluntary guidelines that have them refrain from advertising for “an appropriate amount of time” so doctors can be informed of the new drugs first.

In the case of Merck’s diabetes drug Januvia, however, little time was wasted between the drug’s approval and Merck’s massive marketing efforts.

Another report by Reuters says that the “the product Web site was functional within 90 minutes of approval, and within eight days, Merck had reached 70 percent of target doctors and made first deliveries of [Januvia] to pharmacies. Within 14 days, discussions were completed with managed care organizations covering around 188 million patients or 73 percent of the insured U.S. population.”

The 2007 attempt failed after some lawmakers objected it would violate constitutional protections of free speech. Instead, Congress gave the FDA authority to fine companies for running false or misleading promotions.

Whatever restraint is exercised, no time is wasted in infiltrating the market.

The 2007 attempt to reign in advertising for new drugs failed after some lawmakers objected it would violate constitutionally protected free speech. Congress instead granted the FDA authority to fine drug companies for false or misleading advertising.

SOURCE: Vytorin Recall › Vytorin illustrates the problems of direct-to-consumer advertising

The answer is a surprising, and disconcerting, NO.

Trials for new prescription drugs that are vying for a place in the market focus on efficacy rather than safety. If pre-market clinical tests find a drug to be effective and that drug does not appear to be unsafe, then the FDA typically approves the drug and that drug enters the market. Many pre-market studies, however, simply are not large enough to allow researchers to gauge the safety of a new drug. A determination of safety is made usually after thousands of people have taken the drug. That is to say, the safety of a new drug is only fully known once it has been widely available to consumers.

Taking new prescription medicines makes the consumer an unwitting guinea pig of sorts. The hybrid anti-cholesterol drug Vytorin, for instance, was prescribed to millions of people before the ENHANCE trial found it to be effective in lowering LDL cholesterol levels but ineffective in preventing cardiac events, which is its ultimate purpose. Another trial named SEAS later suggested that Vtytorin increased the odds of developing and dying from cancer. Vytorin continues to be sold while researchers continue probing its effectiveness and safety. The results from larger tests aren’t expected until 2012.

Currently, the rights of consumers who have been harmed by toxic prescription drugs and faulty medical devices are standing on unsteady ground. The issue of pre-emption, the legal notion that FDA approval of a drug trumps state laws concerning safety, efficacy, and proper labeling, is now before the United States Supreme Court. Diane Levine, a musician from Vermont, sued Wyeth earlier this month over inadequate labeling of the drug Phenergan, which caused her to lose part of her right arm. Wyeth’s defense argues that the company shouldn’t be held responsible by state laws because the drug met federal standards by gaining FDA approval.

If the Supreme Court rules that federal standards do supersede state laws, or if it throws the case out altogether, then many people may have no legal recourse should they ever fall victim to risky drugs and medical devices.

Keeping the issue of pre-emption in the public eye as the Supreme Court mulls the Levine case, a non-profit group called Alliance for Justice has created a documentary about pre-emption. A trailer for “Access Denied: The Fight for Corporate Accountability” can be viewed here. The video can also be viewed in its entirety by going here.

SOURCE: Vytorin Recall › Will FDA regulations and pre-emption silence Vytorin victims?

MK-0524A, as the new drug is called, is the subject of a study based in Oxford University in England. Merck submitted the drug to the FDA for approval, but it was rejected last April. The FDA wanted results from the study known as THRIVE (Treatment of HDL to Reduce the Incidence of Vascular Events) before it made another ruling.

The study already involves 20,000 people from the UK, Scandinavia, and China who are taking the experimental drug. The problem for Merck, however, is the timeline. The study began in 2006 and is set to end in January of 2013. Sufficient data wouldn’t be available until 2010.

To speed the study along, Merck will increase the number of participants in THRIVE to 25,000. Merck hopes that having more trial participants will amount to obtaining results several months earlier.

In a statement issued by Oxford University, Professor Jane Armitage, one of the principal investigators of MK-0524A sounded hopeful about the study’s expansion, saying that “In terms of numbers, bigger is very much better.”

“This enhancement will give us a more powerful tool with which to assess this intervention for the benefit of heart patients everywhere. The study is scheduled to end in 2013, but with these additional patients, we hope that it will be able to report sooner,” she said.

Merck expected the new drug to stimulate its share of the cholesterol market, which suffered a serious blow when Vytorin was revealed to be first a dud and then a danger. Researcher claim that by speeding up the THRIVE trial, they will be able to help people with vascular disease sooner. For Merck, it’s likely to be a matter of replacing lost profits and establishing a pipeline that’s more appetizing to investors.

SOURCE: Vytorin Recall › Merck speeds trial of new cholesterol drug

The University of Washington’s Thomas Fleming is one respected statistician and adviser to the FDA who cautions against dismissing Vytorin’s link to cancer as merely an anomaly. Leading researchers involved with the SEAS study, which uncovered a Vytorin-cancer link, maintain that the results were a fluke.

In an editorial published in The New England Journal of Medicine, Fleming says that at this point in time, it’s too early to dismiss the Vytorin-cancer link. He suggests that the drug may have more adverse side effects than actual benefits. “ … There are numerous recent cases in which it has been established or strongly suggested that [side] effects of such [drugs] have adversely altered their risk–benefit profile.”

Scientists quick to dismiss Vytorin’s apparent link to cancer support their case by pointing to two larger ongoing studies that appear to diminish the drug’s risks. According to Fleming, however, “There are clinically important increases in the risk of cancer-related death that are not ruled out by this data.” He also argues that prematurely releasing results from the other tests jeopardizes their conclusions.

Vytorin sales soared to the tune of $5 billion in 2007, but dropped by a third after reports of negative tests began to surface. Considering such profits, altering and masking potentially harmful clinical trial data might seem like a good profit-preserving strategy, but it makes you wonder what it’s like to work in the Public Relations department at Merck and Schering-Plough.

SOURCE: Vytorin Recall › scientist cautions against dismissing Vytorin-cancer link

The study, which monitored the progress of 1,873 subjects, found that 37 of the subjects taking Vytorin died of cancer, compared to 20 subjects who died of cancer while receiving a placebo. The data is rightfully alarming, but the study’s leaders maintain that it is a fluke. To support their claim, they point to two larger studies still in progress – SHARP and IMPROVE-IT. Numbers from those studies combined still show a higher rate of cancer among Zetia users, but only enough to be statistically irrelevant or at least inconclusive.

However, some professionals who are following the study, including a panel of doctors from The New England Journal of Medicine, argue that there is indeed a legitimate cause for concern, not the least of which that all three trials revealed more cancer in Zetia users. They also point out that Zetia “interferes with the gastrointestinal absorption not only of cholesterol but also of other molecular entities that could conceivably affect the growth of cancer cells.”

The other “molecular entities” include the tumor-fighting and cholesterol-busting superhero: plant-derived sterols. People ingest sterols every time they eat fruits and vegetables. Because Vytorin interferes with the body’s absorption of sterols, then it may, in theory, promote cancer.

The FDA expects to receive a final SEAS report in about 12 weeks. The agency anticipates it will take another 6 months to review and evaluate the study data, after which it will issue its conclusions and recommendations. In the meantime, the FDA has advised health care professionals to monitor their patients on Vytorin and to report side effects to the agency.

SOURCE: Vytorin Recall › SEAS study may link Vytorin, cancer