 This is FDA Patient Safety News. In this edition, a new lab test to help identify anthrax, a warning about using the drug Tamiflu in infants, potentially dangerous sleep attacks with the drug Permax, and what to tell patients about silicone gel-filled breast implants. 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. And I'm Anita Rainer. Let's start with some medical products FDA recently approved. FDA recently cleared for marketing a new test kit that will make it easier for laboratories to distinguish basillus anthracis, the organism that causes anthrax disease from other basillus types. The test kit manufactured by Tetrachor Incorporated is called Redline Alert. It's an immunoassay that contains a monoclonal antibody which binds to a surface protein that's found on the anthrax basillus. If you use this test, how certain can you be that a patient has an anthrax infection? You can't be certain. A positive result with Redline Alert is presumptive evidence of infection with the anthrax basillus, but you'll need confirmatory tests to make a definitive identification of the organism. And of course that means that laboratories have to use a combination of methods and testing to definitively identify or rule out an anthrax infection. Well, given the concern about bioterrorism, could you use this test on suspicious materials like a package or a sample of powder? No, it's intended to be used on bacterial colonies that are grown from clinical specimens. And those colonies have to be grown on sheep blood agor plates. Now, once the cells are growing in the lab cultures, the test can be performed in about 15 minutes. Also, this test should only be used by labs whose staffs are trained and proficient with microbiological culture procedures and who use biological safety level 2 practices. Keep in mind too that CDC recommends consulting with your state public health laboratory director whenever infection with basillus anthraxus is suspected. You can find out how to report possible cases on our website and also how to transfer isolates to a higher level lab. FDA recently approved the first DNA-based laboratory tests for a heritable disorder. The two tests made by Roche Laboratories are called the Factor 5 Leiden Kit and the Factor 2 Prothrombin G20210A Kit. The tests allow the detection and genotyping of inherited mutations in the genes that encode two proteins that regulate blood clotting. Now, patients with these mutations may have thrombophilia which predisposes the individual to thrombotic events such as venous thrombosis. It's estimated that 5 to 10% of the U.S. population has at least one of these mutations and some people have both. The American College of Medical Genetics recommends that the tests be used selectively for people at risk for clotting-related health problems. They include those under age 50 with venous thrombosis or their relatives, those with recurrent venous thrombosis, those with venous thrombosis in unusual sites and women with venous thrombosis who are either pregnant or on oral contraceptives. Random screening of the population is not recommended. It's important for patients with positive test results to understand the genetic implications and the risk implications of these results so they should be counseled by the physician or a genetic counselor. Orthomacneal Pharmaceuticals has revised the prescribing information for the anti-epileptic drug Topomax to pyromate to include a warning that the drug causes hyperchloremic metabolic acidosis. In many patients, the only sign of this is decreased serum bicarbonate. But in some patients, metabolic acidosis can result in hyperventilation, nonspecific symptoms such as fatigue and anorexia, or more severe sequelae such as cardiac arrhythmias or stupor. If it's left untreated, chronic metabolic acidosis can lead to kidney stones, skeletal problems with an increased risk of fractures, and decreased growth in children. In clinical trials where Topomax was used as an adjunct treatment for epilepsy in adults and children, significantly more patients on the drug had persistently decreased serum bicarbonate levels than those treated with placebo. Decreases in serum bicarbonate generally occur soon after treatment is started, but they can occur at any time during treatment. Also, the decrease in bicarbonate can occur at doses as low as 50 milligrams per day. The bicarbonate lowering effect of Topomax can be made worse by certain drugs or by conditions that predispose patients to acidosis. These include renal disease, severe respiratory disorders, ketogenic diet, and diarrhea. The new labeling recommends measuring serum bicarbonate levels at baseline and then periodically during a patient's Topomax treatment. If metabolic acidosis develops and it persists, consider reducing the dose or gradually discontinuing the drug. If a patient with persistent acidosis continues on Topomax, then consider alkali treatment. Roche Laboratories has cautioned health care professionals about using the flu drug Tamiflu in infants under one year of age. Tamiflu, or Osseltamivir phosphate, is approved to treat influenza in patients one year and older. It's also indicated for flu prophylaxis in adults and adolescents 13 and older. However, it's not indicated for either flu treatment or prophylaxis in infants under one. New pre-clinical safety data from animal studies have shown high drug exposure in the brains of very young animals. The company says that these high exposures may be related to an immature blood-brain barrier. Although the clinical significance of these findings is uncertain, Roche recommends that Tamiflu not be given to children younger than one year, that is, before the blood-brain barrier is thought to be fully developed. The company also emphasizes the importance of using Tamiflu only for the labeled indications. You can find details about the new findings on our website. Here's a new warning about the dopamine agonist Permax, or pergolid mesolate. Eli Lilly, the manufacturer, says that patients treated with Permax have reported falling asleep while performing daily activities, including driving, and some of these events have led to accidents. Now, I'm assuming that when these sleep attacks occur, they're in patients who've already experienced some drowsiness while they were on the drug. Well, not necessarily, although many of these patients did report somnolence while on Permax. Some of these patients said they got no warning signs, such as excessive drowsiness, and in fact, they recall being alert immediately before the event. Now, if you've got a patient who's been on Permax for a while and they haven't had a sleep attack, can you more or less rest assured that they're not going to have one? Well, not necessarily. Some of these events occurred as late as one year after starting treatment. And so the drugs labeling now says that prescribers should continually reassess their patients for drowsiness or sleepiness while they're being treated with Permax, especially since some of these events can occur well after the start of treatment. And it points out that patients may not mention drowsiness or sleepiness until their question directly about whether they experienced somnolence during specific activities. Well, that's what clinicians should know, but shouldn't patients be warned about the possibility that they're going to have a sleep attack? They certainly should. Before starting treatment with Permax, Lilly says that patients should be told about the potential for drowsiness during daily activities and specifically asked about factors that may increase this risk, such as whether they're using other sedating medications or whether they have a sleep disorder. Patients should also be cautioned about operating hazardous machinery, including automobiles, until they're reasonably sure that Permax doesn't cause them to be drowsy. And they should be told that if drowsiness or episodes of falling asleep increase at any time during treatment, they shouldn't drive or participate in other potentially dangerous activities until they've contacted their physician. If a patient does develop significant daytime sleepiness or if they fall asleep during activities that generally require some kind of participation, the company says that Permax should ordinarily be discontinued. But if the medication is continued, patients should be advised not to drive and to avoid other potentially dangerous activities. In previous broadcasts, we've talked about the ways that abbreviations can cause medication errors. Although abbreviations and other symbols can save time, they aren't always read correctly and they can be interpreted differently by different practitioners. The Institute for Safe Medication Practices recently published an updated list of some of the most error-prone abbreviations and dose designations. ISMP identifies dozens of dangerous abbreviations, including the prohibited abbreviations that are a part of JCO's National Patient Safety Goals for 2004. Let's take a look at the items on JCO's Do Not Use list. First, the abbreviations U and IU. The U can easily be mistaken as a number zero, particularly when the U is written too closely after the number. This can lead to 10-fold overdoses. And IU can be mistaken for IV or for the number 10. So, instead of using U and IU, use the terms unit and international unit. Next, there's QD meaning every day and QOD every other day. QD can be mistaken as QID, especially if the period after the Q or the tail of the Q is misunderstood as an I. And QOD can be mistaken for QD or QID if the O is poorly written. Instead, write out daily or every other day. Then there's the possible confusion with dose designations that include decimal points. A trailing zero after a decimal point can make a 1.0 milligram dose look like a 10 milligram dose if the decimal point isn't seen. Similarly, 0.5 milligrams can look like 5 milligrams. So, don't use trailing zeros for doses expressed in whole numbers and be sure to use a leading zero when the dose is less than a whole unit. Finally, the confusion between the abbreviations for magnesium sulfate and morphine sulfate, which can look similar or be misinterpreted. Here, write out magnesium sulfate or morphine sulfate. The ISMP list has many more examples of potentially dangerous abbreviations. You can find the complete list on our website. Your patients may be asking about FDA's recent decision to turn down a manufacturer's application to market silicone gel-filled breast implants. Women may want to know why the FDA did this, what the decision means in terms of safety, what kinds of implants remain available and under what circumstances and what the future holds. So why did FDA decide to turn this application down? Well, after reviewing the manufacturer's application for marketing, FDA decided that it didn't contain sufficient data to establish a safety profile for this device. FDA was particularly concerned that there wasn't enough information about the long-term performance of these implants in actual use. For example, at what rate do they rupture? What causes rupture and how long do the implants remain intact before rupture takes place? Also, more information is needed about the silicone that leaches out of the implant over time. Without this information, FDA can't decide whether there's a reasonable assurance that the implants are safe and effective. So is the FDA saying that these implants are not safe? No, we're not saying they're unsafe, and that's an important point to keep in mind for women who have these implants. What we're saying is simply that there isn't enough information right now to give women and their physicians an accurate picture of how these devices will perform and what the various risks might be. So what's FDA doing to try to get the information? Well, of course, it's not FDA's responsibility to generate the scientific information to demonstrate that a new medical product is safe and effective enough for marketing. That's the manufacturer's responsibility if he wants to market the product. But FDA is helping the process by updating its guidance for breast implant manufacturers. This guidance spells out in detail the kinds of data FDA will need to make a determination on the safety and effectiveness. It's now up to manufacturers to use the guidance to develop this information and then submit it to the FDA. That's the future. What about now? What do we tell women who want the implants now? Well, there are several options for those women. First of all, saline-filled implants continue to be available without restriction. And there are two circumstances where the silicone gel-filled implants are available. First, a woman who wants the implants for breast reconstruction, for example, after mastectomy or to replace an existing implant, can still get them by having her surgeon enroll her in a clinical study. Also, a limited number of women who want the silicone gel-filled implants for breast augmentation may be able to get them by enrolling in studies that may be conducted by the implant manufacturer based on FDA's updated guidelines. 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 so we can alert others. We'll 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. And I'm Anita Rayner. See you next time. Thank you.