Vioxx "scandal risks, side effects

VIOXX 2 © AP
Of the drug now suggests itself from the manufacturer
Market players were told how it always earlier than doctors and patients. "Sell" recommendation of analysts for the shares of Merck, Sharp & Dohme, MSD was short, as on 30th September at noon, the largest voluntary recall in the history of medicine began.
Patients, doctors and authorities, however, it had to learn harder, why the popular pain medication Vioxx from the market suddenly disappeared. The Federal Institute for Drugs in Bonn had arrived in the morning from share legal reasons only an indication that there was to be expected around noon an important warning to the company. After the investor conference then rang all the phones in the German medical practices.More articles

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Suddenly, it was necessary to inform the world more insecure two million patients and advise them which of the alternative drugs they should now take place against Vioxx their often unbearable pain.
Touted as "super aspirin"
Because Vioxx was touted as "super aspirin" against joint rheumatism, because it performs differently than the traditional pain relievers, aspirin, ibuprofen or diclofenac, rarely cause serious stomach bleeding. In the United States, the Group MSD ever $ 100 million per year for TV advertising in order to differentiate themselves from competitors.
Vioxx tablets were prescribed as a painkiller and in Germany by some doctors "like lollipops," says an outraged Bruno Müller-Oerlinghausen of the Drug Commission of the German Medical Association: "This is what has always been wrong and dangerous." The Drug Commission of the German Medical Journal has regularly published warnings, but the doctors in the "fog marketing were often ignored." An increased risk of heart attacks among experts will discuss intensively for years.
Worldwide Recall
The potential damage to the cardiovascular system was then at the end of the reason for the worldwide recall of Vioxx. In a clinical study involving 2600 patients, the manufacturer "APPROVe" baptized, Vioxx was tested as a means of long-term prevention of colon polyps. The aim was thus to open up a new field of application of the remedy. After three years of daily intake of 25 milligrams of Vioxx, the routine monitoring of the data showed, however, that 45 of the patients had suffered "serious thrombotic events" - in the control group, there were only 25
For the first time is a tangible indication of an increased prior to the double risk of heart attack and stroke. When 400 patients taking Vioxx for a year, would be expected according to the British Medicines Authority six instead of three with severe thrombosis. However, this effect in the study was only after more than eighteen months of treatment have been detectable.
Flood of class actions
The MSD decided after receipt of such data for the immediate withdrawal - possibly because of the stringent U.S. liability law. In fact, off victims' lawyers in the United States immediately release sites to the Merck with a flood of unprecedented class actions cover.
Fire pours into oil heated debate now, the renowned U.S. cardiologist Eric Topol in the New England Journal of Medicine. The MSD and the U.S. Food and Drug Administration had "paid more attention to warning signs along the way" the many, the physician writes the Cleveland Clinic, a "debacle can be avoided such" would. Topol will have calculated using data from the APPROVe study, even the potential total loss of the use of Vioxx since 1999. According to his figures could in ten million with Vioxx treated patients, "tens of thousands" have suffered a heart attack or stroke. This assumption is supported by Merck vehemently rejected such an extrapolation based on a single trial is inadmissible.
From the results, "not surprised"
First indications for blood clotting disorders recognized scientists actually shortly after the launch of the first two super-aspirin. "The experimental pharmacology, the cardiovascular risk is postulated many years ago," says Kay Brune of the University of Erlangen. He was of the results, "not really surprised."
Not only for the clinical pharmacologist is now more the question of whether it is at increased risk for a problem by acting alone or whether Vioxx behind it previously underestimated risks lurking around the pipeline. That is the billion-dollar question. Because in addition to Vioxx, there are a number of so-called coxibs, which all have a similar mechanism.
"The theory and the results of experimental pharmacology, there should be true for all coxibs" suspects Brune, where he emphasized that the risk of cardiovascular events would "of course not necessarily meet all drugs equally." The traditional pain relievers ibuprofen and diclofenac have a one as good for pain like Vioxx & Co, but have the distinct disadvantage that they attack the stomach lining and in patients at risk for stomach ulcers and bleeding can cause sometimes fatal. The reason is that they inhibit an enzyme called Cox-1 in the stomach wall. It normally protects them from the corrosive stomach acids.
The new coxib inhibitors emerged as researchers realized that there is a second body, the so-called Cox-2 enzyme. It is increasingly formed by inflammatory reactions in the body. Pharmaceutical companies then developed selective inhibitors, which only slow down the activity of Cox-2 enzymes, but not Cox-1. Because old painkillers like ibuprofen blocked both enzymes, although they relieve the pain, let your stomach bleed but sometimes literally. The stomach was to preserve that property, which established the special reputation of new painkillers.
Antagonist of blood coagulation
Unfortunately, it's a catch. For long pharmacologists know that Cox-1 also plays an important role outside of the stomach. Thus, both enzymes act in the blood vessels as antagonists in blood clotting. Device their interaction out of balance may increase the propensity for thrombus formation. The more selective the new "super aspirin" Cox-2 block in the blood vessels, the more there could shift the microenvironment in favor of Cox-1-effects. In animal experiments it was found that under administration of coxibs - can lead to vasoconstriction and Blutplättchenverklumpungen - but not in the old painkillers. The more risk factors a patient in the cardiovascular system, show the more likely it is that when the coxibs, this mechanism increases the blood pressure, increase the risk of atherosclerosis and in the end may bring about the risk of life-threatening blood clots.
Garret FitzGerald, the least of the University of Pennsylvania in Philadelphia believes the last few years. In a recent article for the New England Journal of Medicine, he calls after the end of Vioxx now, "reverse burden of proof for all coxibs the". It would now have long-term and meaningful safety studies are required. They alone could rebut the presumption established by cardiovascular risk. Eric Topol had just called for such studies in patients at risk in 2001 in vain.
Questionable advertising
Whether representing the remaining substances on the market at risk for blood clotting system or not, remains unclear for now. The world's largest pharmaceutical company Pfizer, who brought with Celebrex the pioneer of coxibs on the market advertised, just hours after the recall of Vioxx to that for Celebrex until now all studies of pain patients with rheumatoid not indicate an increased risk for severe heart cardiovascular disease have shown. However, older patients were present with risk factors for heart attack or stroke in the previous studies, no. In currently ongoing long-term studies on prevention of intestinal polyps in patients with Alzheimer's and it says at Pfizer, was also also "no evidence of an increased risk of" recognizable. And, although some patients would have been treated for longer than three years with Celebrex. Verified, such statements are naturally only in the moment when the first results of these studies appear in journals would.
Novartis also recently presented data from their new drug that will inhibit Cox-2 is extremely selective. The tablet with the name Prexige is currently in the United States and Europe in the approval process. In the so-called target-study of 18 325 patients have not only a clear reduction in the incidence of serious gastrointestinal bleeding showed, the company issued a press release dated August, but "no significant increase in cardiovascular events." Garret FitzGerald has pointed out, however, that in the group treated with Prexige patients taking aspirin to thin the blood, after all, 14 patients suffering from heart and vascular diseases. In the placebo group there were only nine.
Start again at MSD
Of the German public so far unnoticed, and MSD is already back on track. While the U.S. Food and Drug Administration is still hesitating with the authorization, a press release praising the just recently approved anti-inflammatory drug Arcoxia in Germany with the words, the new Cox-2 inhibitors could "relieve joint pain quickly and effectively sustained 'the. In "terms of security," there is scarce, fill etoricoxib, the active ingredient of the agent that "expectations of a modern day anti-inflammatory drug" would be made.
However, what concerns the risk of heart attacks and strokes, even when there Arcoxia certainly still "not enough experience to give the all clear." Stichtenoth Dirk believes that the pharmacist at the Medical University of Hanover, who has published several review articles on the latest generation of coxibs. Main characteristic of these novel agents, except that it is the Cox-2 enzyme far more selective inhibited as Vioxx & Co. "caution" was therefore also for new active substances, the need of the hour, in any case in rheumatic patients with cardiovascular risk factors - or if the pain killer must be taken for more.