 This is FDA Patient Safety News. In this edition, a warning on bone loss in patients on depoprovera, preventing serious infections when cleaning wounds with pulsatile lavage and suction, dangerous mix-ups between the drug's reminil and amaryl, and choosing the right form of bycylin to treat syphilis. 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 Rayner. Let's start with some medical products FDA recently approved. FDA recently approved the first monoclonal antibody treatment for patients with relapsing forms of multiple sclerosis. The product, called Tysabri or Natalizumab, is intended to reduce the frequency of clinical exacerbations of the disease. Tysabri is marketed by Biogen Idec and Elan Pharmaceuticals. The product is given intravenously every four weeks in a physician's office. Tysabri appears to work by targeting part of the underlying inflammatory process in MS by inhibiting adhesion molecules on the surface of leukocytes. It's believed that this interaction prevents immune cells from migrating into the brain where they can cause damage. The drug's approval was based on positive results after the first year of treatment in two randomized double-blind clinical trials. In one of the trials in which Tysabri was compared to a placebo, it reduced the frequency of relapses by 66%. The manufacturer will continue these trials for another year. Serious but uncommon side effects included infections, severe or life-threatening allergic reactions, depression, and gallbladder problems. Common adverse reactions were generally mild and included non-serious infections, headache, and fatigue. FDA recently announced that a new black box warning is being added to the labeling for depoprovera contraceptive injection. The warning alerts prescribers that prolonged use may result in loss of bone density. Pfizer, the drug's manufacturer, has also issued a Dear Doctor letter with the same information, and the new information also appears in the patient information sheet. Now I'm assuming that the longer a woman is on the depoprovera, the greater the bone losses. That's right, and so the new warning says that depoprovera shouldn't be used as a long-term contraceptive unless other methods aren't adequate. Now, what does long term mean in this context? Well, the labeling says, for example, not longer than two years. Now, once the woman stops taking depoprovera, is the bone loss reversible? Well, it is partially reversible, but it may not be completely reversible. Some women are at increased risk for osteoporosis anyway. Now, are those the women that are most likely to develop bone loss with depoprovera? Well, they may, and so these women should consider other birth control methods. This high-risk group includes those with metabolic bone disease, chronic alcohol or tobacco use, anorexia nervosa, a strong family history of osteoporosis, or chronic use of drugs that can reduce bone mass such as anticonvulsives or corticosteroids. Another high-risk group is adolescent women. The label warns that it's not known whether depoprovera might reduce their peak bone mass and increase the risk of osteoporotic fractures later in life. The FDA recently announced that it would strengthen requirements to help prevent fetal exposure to the drug accutane or isotretinoin and its generic equivalents. Accutane, which is used to treat severe refractory acne, can cause serious birth defects if it's taken by pregnant women. Under the new system, which will take effect later this year, all prescribers, patients, and dispensing pharmacies will be registered in a single clearing house. Patient counseling, education, and informed consent will be required, and women will need to have a negative pregnancy test each month before the pharmacist can dispense the medication. For a complete discussion of the new risk management program, go to our website. The manufacturers of the drugs Humira, Remicade, and Enbrel have added new safety information to the labels for these products about malignancies. These three drugs are tumor necrosis factor blocking agents, and they're used to treat rheumatoid arthritis and other autoimmune diseases. In controlled studies of TNF blockers, more cases of lymphoma occurred among patients receiving the agents than among control patients. And in open-label uncontrolled clinical studies, the rate of malignancies in patients treated with TNF blockers was several times higher than would be expected in the general population. These uncontrolled studies can't establish a causal relationship between the TNF blockers and the excess malignancies because patients with highly active autoimmune disease may be at increased risk for lymphoma independent of the drugs they're taking. A recent FDA article in the journal Nursing 2005 reported an incident in which several patients developed serious infections after their wounds were debrided using pulsatile lavage with suction. These infections were highly drug resistant and some of the patients died. Pulsatile lavage with suction systems used pressure-pulsed irrigation and suction to clean wounds. According to one study, these devices can scatter infectious agents up to 8 feet. The article lists a number of precautions that can help minimize the likelihood of infections from pulsatile lavage procedures. Here are just a few of them. Use continuous suction and keep this flash shield in contact with the wound or the area around the wound at all times. Empty the suction waste canister after each patient use or as directed by the manufacturer. Always perform the procedure in a private room enclosed with walls and doors and properly ventilated. No large open areas, no privacy curtains, and no open shelves or cabinets. Consider covering those surfaces that are most likely to be contaminated with aerosol from the treatment. Wear a fluid-proof gown, gloves, mask, face shield, eye cover, and hair cover. Use a drape to cover all catheters, tubes, ports, and other devices and also cover any patient wounds that are not being treated. After each treatment, thoroughly clean and disinfect all environmental surfaces that were touched during the treatment. In an earlier program, we talked about serious skin and hypersensitivity reactions associated with the drug Bextra or Valdecoxib. Bextra is a cox-2 selective inhibitor used to treat osteoarthritis, rheumatoid arthritis, and dysmenorrhea. Now we want to tell you about strengthened warnings about these skin reactions and also about cardiovascular risks associated with Bextra. Despite earlier warnings, FDA is still receiving reports of rare but serious skin reactions with Bextra, including Steven Johnson syndrome and toxic epidermal necrolysis, both of which can be fatal. So now the manufacturer, Pfizer, has added a boxed warning about this risk. Now we know that other cox-2 agents also increase the risk of these serious skin reactions, and in fact, so do traditional NSAIDs like naproxen and ibuprofen. The difference is that with Bextra, the rate of these occurrences seems to be greater. So what does the label tell practitioners to do? Well, the main thing is to be alert for these symptoms. Now they usually occur within two weeks of starting therapy, but they can occur any time during the treatment. The labeling says to discontinue Bextra at the first appearance of a skin rash, mucosal lesions, or any other sign of allergic reactions. And also remember that Bextra is contraindicated in patients who are allergic to sulfonamides. What about this new information on cardiovascular risks? Well, that comes from a study that included over 1,500 patients who received Bextra for postoperative pain after coronary artery bypass surgery. The study showed that they were more likely to have cardiovascular adverse events such as MI, stroke, deep vein thrombosis, and pulmonary embolism, than placebo-treated patients. But Bextra isn't approved to treat postoperative pain. Well, that's right. That's not one of the approved indications, but now it's specifically contraindicated for postoperative pain after cabbage. The Institute for Safe Medication Practices recently reported on three cases where the anti-diabetic agent, amaryl, had been dispensed to geriatric patients instead of the Alzheimer's medication, reminal. We've also received other reports of prescribing and dispensing errors caused by confusion between these two drugs. Mistakenly administering amaryl to non-diabetic Alzheimer's patients has caused serious adverse events, including severe hypoglycemia and two deaths. According to the ISMP, accidentally giving amaryl to an older patient can be especially dangerous because they may be more sensitive to its hypoglycemic effects. ISMP says that these mix-ups may have been linked to poor prescriber handwriting, along with the sound alike look alike names. Three other factors may contribute to possible confusion. Both drugs come in tablets, both are available in a four milligram dosage strength, and they have generic names galantamine and glymiporide that could lead them to being stored closely together. ISMP also notes that since amaryl may be prescribed more often than reminal, pharmacists and nurses may automatically assume that an illegible reminal prescription is for amaryl. The distributors of reminal and amaryl have recently sent letters to prescribers and pharmacists, warning them about the potential for these mix-ups. These letters also contain recommendations on how to prevent such errors. For example, they remind prescribers to spell out the drug name when prescribing over the phone and to clearly print written prescriptions. And they suggest that pharmacists should physically separate these two drugs on the shelf, confirm the brand name with prescribers, and counsel patients about the product. ISMP has additional recommendations, for example, reminding prescribers to indicate the medication's purpose on prescriptions. And they advise pharmacists and nurses to confirm that the patient is diabetic before dispensing or administering any anti-diabetic medication. In a previous program, we talked about the dangers of mistakenly injecting long-acting penicillin IV rather than IM. Now we want to update you on recent changes to the product labeling that emphasize this warning and also tell you about other labeling changes that weren't against using the wrong type of by-cellin product to treat sexually transmitted diseases. If long-acting penicillin products such as by-cellin CR or by-cellin LA are administered IV, the insoluble matter in the injection can cause cardiorespiratory arrest and death due to pulmonary embolism. So these products should only be administered by deep intramuscular injection. King Pharmaceuticals, the maker of by-cellin, has now added a black box warning to the labeling of both of these products to remind practitioners about this risk. A new warning not to use these products IV also appears on product cartons and syringe labels. To reduce the risk of injecting these products IV, practitioners should also pay attention to safety features on the pre-filled by-cellin syringes and tubex cartridges. These improvements can help visualize aspirated blood if a blood vessel is entered. With this design, blood that enters the needle can be quickly seen as a red or dark colored spot on the barrel of the glass cartridge immediately proximal to the blue syringe hub. To find where to look for a blood spot, first locate the yellow rectangle at the base of the blue hub and draw an imaginary straight line from that rectangle to the shoulder of the glass cartridge. When the needle cover is removed, look for a second yellow rectangle which is also aligned with the spot. The old metal tubex holder which is no longer distributed should not be used because the metal strut may obstruct the view of a blood spot if it's improperly aligned. King Pharmaceuticals also reminded practitioners that by-cellin LA is the only penicillin G benzithine product indicated for sexually transmitted infections, including syphilis. In a number of US STD clinics, patients with syphilis have been inappropriately treated with by-cellin CR, a combination of penicillin G benzithine and penicillin G pro cane. This product should not be used to treat syphilis because the patient may receive inadequate treatment. To help practitioners distinguish between the two types of by-cellin, the background colors on the by-cellin CR cartons have been changed, and a reminder statement that syphilis should not be treated with by-cellin CR now appears in several places on the carton and on syringe labels. Patients with cochlear implants and their caregivers need an up-to-date source of information on these devices. FDA is now providing that service in a new website. The site explains what cochlear implants are and how they work and what the surgery entails. It presents the benefits and risks involved. It provides news about cochlear implant recalls and safety issues and it tells how to report problems. And it also gives information that educators of implant patients need to know. Well, that's all for this edition of FDA Patient Safety News. Remember, you can get more information on all the stories in 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 Anita Reiner and I'm Mark Barnett. See you next time.