 This is FDA Patient Safety News. In this edition, a new device to treat descending thoracic aneurysms, recent FDA actions on NSAIDs, a warning about liver injury with Avonex, and an alert about increased mortality when certain antipsychotics are used off-label. These stories and more on this edition of FDA Patient Safety News. Welcome to the program. For the U.S. Food and Drug Administration, I'm Mark Barnett. Our co-host Anita Reiner is out of town, but she's going to be back for the next broadcast. Well, let's start out with a couple of medical products FDA recently approved. FDA recently approved the first device to prevent ruptures of descending thoracic aneurysms. It's an endovascular graft called the Gore-Tag endoprosthesis system, and it's made by W.L. Gore and associates. Descending thoracic aneurysms have traditionally been managed either with antihypertensive drugs or by open surgical repair. This Gore-Tag graft can provide an alternative to these treatments. Now, using the device is less invasive than conventional surgery, but it still requires regular follow-up and testing to monitor the success of the treatment over time. The Gore-Tag system consists of an endovascular graft of expanded polytetrafluoroethylene and an outer metal stent. The endovascular graft is delivered by a catheter that's inserted into the femoral artery in the groin. At the site of the aneurysm, the graft is deployed, and then it self-expands to the diameter of the aorta and that excludes the aneurysm and relines the artery wall. This can prevent further growth and possible rupture of the aneurysm. FDA approved the device based on review of two clinical studies of approximately 200 people. Study results show that aneurysm-related deaths were lower in patients who had received the endoprosthesis than in this original control group. FDA is requiring the company to conduct additional studies, to evaluate its long-term clinical performance, and to assure that when the device is used in the large general population, its safety and effectiveness are going to be comparable to the clinical trials. FDA recently approved a new cranial sealing system for duramatter surgery to prevent CSF leakage from the incision site. The product, which is used as an adjunct to suturing, is called the duraceal sealant system, and it's manufactured by Confluence Surgical Incorporated. This is the first device that's specifically approved for this purpose. Until now, surgeons have used a variety of approaches to prevent spinal fluid leakage, such as over-sewing the area or packing the area with other tissue. The duraceal system consists of two solutions and an applicator. The solutions mix in the tip of the applicator as the product is being applied, forming a hydrogel that seals the duramatter. The gel biodegrades in four to eight weeks, which is enough time for healing to take place. Duraceal should not be used in confined bony structures where nerves are present because the swelling of the hydrogel can result in neural compression. The manufacturer will continue to study the duraceal system to further investigate infection rates and to compare the device to existing methods of preventing CSF leakage. On April 7th, FDA announced several important changes that pertain to the marketing of NSAIDs. FDA has asked that one product be withdrawn from the market and is requiring stronger warnings in the labeling for the other products. In a sense, this is a continuation of the process that began several months ago with Vioxx. You'll recall that Merck withdrew that product from the market because of concerns about adverse cardiovascular events. These later actions are being taken because of concerns about other NSAIDs. Now, it's important to understand that the new actions don't just apply to COX-2 selective inhibitors. They apply to both the COX-2 inhibitors and to other non-selective NSAIDs, and they apply to both prescription and non-prescription products. FDA has to manufacture one of the COX-2 inhibitors, Bextra, to withdraw it from the market, and people may be wondering why that particular drug. Well, the answer is that the decision was based on concerns about cardiovascular events and also about serious skin reactions. In deciding about Bextra, FDA noted the lack of adequate data on the cardiovascular safety of this drug when it's used chronically and also reports of serious skin reactions, including deaths. Another factor in deciding to ask that Bextra be withdrawn was the lack of demonstrated advantages of Bextra over other NSAIDs. That leaves just one COX-2 inhibitor, Celebrex, still on the market. Why is that? FDA decided that the benefits of Celebrex outweigh the risks provided that patients are properly selected and informed. But FDA is requiring that certain actions be taken to minimize the risk with Celebrex, and let me mention just two of them. First of all, there will be a boxed warning in the labeling about CV and GI risks, and the labeling will encourage physicians to discuss benefits and risks with the patient. And a medication guide will be given to the patient each time the drug is dispensed and forming them of the risks and the importance of using the lowest effective dose for the shortest possible time. Now, what about nonselective NSAIDs like ibuprofen and naproxen? Some of them are prescription-only, and some of them are over-the-counter. For the prescription-only products, the requirements are similar to those for Celebrex, including the boxed warning in the labeling and the medication guide for patients. For the over-the-counter products, FDA is asking manufacturers of ibuprofen, naproxen, ketoprofen, to change their labeling to give more information on CV and GI risks and provide other warnings. Biogen IDEC has notified healthcare professionals about safety changes in the labeling for Avonex, or interferon beta 1A, which is used to treat relapsing forms of MS. The labeling now warns that severe hepatic injury, including hepatic failure, hepatitis, and elevated serum hepatic enzyme levels, has been reported in patients on Avonex. Patients have also experienced asymptomatic elevation of hepatic transaminases, and this recurred in some patients when they were re-challenged with Avonex. In some cases, these events occurred when the patient was taking other drugs that are associated with hepatic injury. So the company says, consider the potential for injury when Avonex is used in combination with other hepatotoxic products, such as alcohol, or when new agents are added to the regimen of patients already on Avonex. The company also says that patients on Avonex should be monitored for signs of hepatic injury. FCA has issued an alert about increased mortality when using atypical antipsychotic drugs to treat behavioral disorders in elderly patients with dementia. The alert applies to drugs such as Abilify, Cyprexa, Cyroquel, Risperdol, Clozaryl, and Geodon. Symbax, an anti-depressant, is also covered by the advisory. Now we should note that these drugs are not approved for treating behavioral disorders in patients with dementia, and in fact, they're approved only for treating schizophrenia and mania. So this constitutes an unapproved, off-label use. The situation came to light when these drugs were being tested in clinical trials on elderly patients with dementia, and it turned out that those treated with the drugs had a higher mortality rate than those receiving placebo. The causes of death were varied, but most of them appeared to be either cardiovascular or due to infections, such as pneumonia. So here's a situation where the off-label use of certain drugs can cause an increase in mortality rate. It's important that physicians know about this, and so we've asked the manufacturers of these drugs to add a boxed warning to the labeling describing the increased mortality risk. The labeling will also state that these drugs are not approved for treating behavioral symptoms in elderly patients with dementia. FDA is also considering adding a warning to the labeling of older antipsychotic medications because limited data suggest that there may be a similar increase in mortality for these drugs. The review of the data on these older drugs is still ongoing, and we'll update you as we get more information. Dr. Gartis has notified healthcare professionals about new warnings and dosing recommendations for the company's Bysphosphonate Drug Zomata, or Zolodronic Acid. It's used to treat multiple myeloma and metastatic bone lesions from solid tumors and hypercalcemia of malignancy. The changes are intended to improve the renal safety of Zomata. The revised labeling includes an additional warning regarding patients with preexisting renal impairment who are undergoing multiple treatments with Zomata and other Bysphosphonates because those patients may be at increased risk of renal deterioration. The new dosing recommendations are intended for patients with advanced cancer who also have reduced renal function. That is those patients whose baseline creatinine clearance is 60 milliliters per minute or lower. The revised labeling stratifies the recommended Zomata doses for patients with mild and moderate renal impairment according to the baseline creatinine clearance rates. The company recommends that during Zomata treatment, serum creatinine be measured before each dose and that treatment should be withheld when there's evidence of renal deterioration. You can find more specific recommendations on adjusting dosing levels on our website. Here's news about a contraindication when prescribing combination antiretroviral therapy in treating HIV infection. It's been known that rifampin is contraindicated with sequinivir because the rifampin will reduce plasma levels of sequinivir. And so a study was recently performed to see whether boosting sequinivir with ratonivir would overcome this problem. But when healthy volunteers in the study were given rifampin along with a combination of sequinivir and ratonivir, 39% developed significant hepaticellular toxicity. As a result, Roche Pharmaceuticals is cautioning that rifampin should not be given to patients who are also receiving a combination of sequinivir and ratonivir. In a recent letter, Wyeth Pharmaceuticals alerted health professionals about changes in the tuberculosis drug tracotor, which may make it necessary to re-titrate patient dosages. The older sugar-coated version of the drug called tracotor SC has been replaced by a film-coated version called tracotor. The new formulation is more rapidly absorbed, leading to higher peak concentrations, and that could result in patient intolerance if it's given the same dose as the tracotor SC. So it's important that patients switching from tracotor SC to tracotor be monitored and have their dosages adjusted. You can see Wyeth's letter, which includes dosing information on our website. Pharm Medium Services of Houston, Texas is recalling some of its magnesium sulfate solution because of a possible sterility problem. All strengths of 50 milliliter admixtures of magnesium sulfate in 5% dextrose solution are affected by this recall. Two loss of this product have been associated with outbreaks of seraceum marcessin's infection. This can cause serious or life-threatening conditions, particularly among immunocompromised patients. The company has stopped producing and distributing this product until it can determine and correct the source of the problem. Hospitals with questions should contact the company at 1-847-457-2300. For more information, go to our website. FDA is notifying physicians and pharmacists that a medication guide for patients must be distributed with each prescription for cordarone tablets or generic amiodarone. This is an anti-arrhythmic drug that's used to treat severe ventricular arrhythmias. FDA requires these guides for drugs that pose a serious public health concern. The guide explains to patients that cordarone can cause lung damage and liver damage, and in some cases can worsen the heart rhythm problems that the drug is intended to treat. It describes the warning symptoms that should lead patients to seek medical attention, and it explains that the drug should only be used when other agents did not work. In a letter to healthcare professionals, cordarone's manufacturer, Wyeth Laboratories, cautions that the medication guide should not be used as a substitute for talking to patients about the risks and benefits of the drug. How many cents out of every consumer dollar spent in the U.S. goes to buy products that are regulated by FDA? Is it less than one cent of every dollar spent? One cent? Five cents? Ten cents? Twenty-five cents? Believe it or not, an estimated 25 cents out of every consumer dollar spent in the U.S. is for products that FDA regulates. In addition to overseeing the safety and efficacy of new drugs and safeguarding the food supply, FDA also is responsible for products that run the gamut of modern life, including the nation's blood supply, vaccines, feed and drugs for animals, cosmetics, medical devices of nearly every description, and consumer products that emit radiation like microwave ovens and TV sets. Well, that's all for this edition of FDA Patient Safety News. Remember, you can get more information on all the stories you've seen here today by visiting our website. We also urge you to use the website to report problems you've encountered with medical products. That's how we learn about problems and need a rainer and I will be back next month with another edition, so watch for us. Until then, for the U.S. Food and Drug Administration, I'm Mark Barnett. See you next time.