FDA Patient Safety News: Show #19, September 2003

First Biologic for Allergy-Related Asthma

FDA recently approved the first biotechnology product to treat patients with asthma caused by inhaled allergens. It's called Xolair, and it's manufactured by Genentech. Xolair's established name is omalizumab.

Xolair has been approved to treat patients 12 years and older with moderate to severe allergy-related asthma that's not adequately controlled with inhaled steroids. The drug is a monoclonal antibody that blocks the body's immune response to inhaled allergens like dust mites or animal dander. It's given as a subcutaneous injection once or twice a month.

Only a small percentage of asthma patients will be candidates for Xolair, for several reasons. First, Xolair is a second-line treatment. That is, it's intended for patients whose asthma has not been successfully treated with inhaled steroids. Second, it's not approved for children under 12, which eliminates a substantial proportion of asthma patients. And third, it's been shown to work only for patients with moderate to severe allergy-related asthma.

The effectiveness of Xolair was mainly assessed in two placebo-controlled studies that included over 1,000 patients. During the six-month studies, 80-85% of Xolair patients had no asthma exacerbations, compared to 70-75% of the patients treated with placebo.

During the clinical trials, more patients treated with Xolair developed a new or recurrent cancer compared to control patients. The numbers aren't large-0.5 percent among the Xolair patients vs. 0.2 percent among the controls-but the firm is planning long-term studies to determine whether there's a relationship between Xolair treatment and cancer.

Additional Information:

CBER: Product Approval Information - Licensing Action.
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm093373.htm


New Once-a-Day Protease Inhibitor for HIV

The FDA has approved a new protease inhibitor, called Reyataz, to treat HIV/AIDS that requires only two pills once a day. Other protease inhibitors can require patients to take up to sixteen pills a day, in addition to their other HIV medications. That can be difficult for some people. Reyataz is manufactured by Bristol-Meyers Squibb and its generic name is atazanavir sulfate.

Clinical trials showed that patients receiving Reyataz in combination with other anti-retroviral agents experienced a decrease in viral load and an increase in CD4 cell counts. These benefits occurred in patients who had not been previously treated, and also in those who had previously received other anti-retroviral therapy.

A major safety concern with protease inhibitors in general is that they tend to be associated with hyperlipidemia. Reyataz appears to have minimal impact on cholesterol and triglyceride levels.

The most common laboratory abnormality with Reyataz is hyperbilirubinemia, with 15 to 24 percent of patients showing jaundice or scleral icterus. In clinical trials, this was reversible upon discontinuation of the drug, and the jaundice did not appear to be associated with an increased risk of liver damage.

Additional Information:

FDA Talk Paper: FDA Approves a Once Daily Protease Inhibitor for HIV Infection.
http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm125077.htm


New Advice on Cypher Drug Eluting Stent

In an earlier show we talked about the new Cypher coronary stent that gradually releases a drug intended to help prevent restenosis. Since the approval by FDA, about 100,000 patients have received this stent. During that time, we've received a number of reports of stent thrombosis and hypersensitivity reactions occurring within 30 days of stenting.

The connection between the stent and the thrombotic events is not clear right now. At this point it's uncertain what effect the Cypher stent has on thrombosis risk, and what factors may contribute to the risk. FDA is evaluating the reports and working with the stent manufacturer, Cordis Corporation, to analyze the problem.

In the meantime, Cordis issued a letter to health care professionals on July 7 with some advice. The letter encouraged them to follow labeled indications and instructions for use. Since the exact cause of thromboses and hypersensitivity reactions has not yet been determined, methods to prevent them cannot be clearly defined at this point.

However, the letter reminds physicians that the Cypher stent is indicated for vessels that have not been previously treated, and not for the treatment of restenosis. It also stresses the importance of matching the stent size to the vessel size, deploying the stent fully so it's in contact with the vessel wall, and using an adequate antiplatelet regimen. The letter also highlights the importance of reporting adverse events to Cordis, and to the FDA.

We’re still in the fact-gathering stage on this issue. As new information becomes available, we'll keep health care professionals posted. We'll also cover it on future editions of FDA Patient Safety News, and also on our web site, so stay tuned.

Additional Information:

FDA Press Release July 8, 2003.
http://www.fda.gov/CombinationProducts/MeetingsConferencesWorkshops/ucm118247.htm


New Advice on Cypher Drug Eluting Stent

In an earlier show we talked about the new Cypher coronary stent that gradually releases a drug intended to help prevent restenosis. Since the approval by FDA, about 100,000 patients have received this stent. During that time, we've received a number of reports of stent thrombosis and hypersensitivity reactions occurring within 30 days of stenting.

The connection between the stent and the thrombotic events is not clear right now. At this point it's uncertain what effect the Cypher stent has on thrombosis risk, and what factors may contribute to the risk. FDA is evaluating the reports and working with the stent manufacturer, Cordis Corporation, to analyze the problem.

In the meantime, Cordis issued a letter to health care professionals on July 7 with some advice. The letter encouraged them to follow labeled indications and instructions for use. Since the exact cause of thromboses and hypersensitivity reactions has not yet been determined, methods to prevent them cannot be clearly defined at this point.

However, the letter reminds physicians that the Cypher stent is indicated for vessels that have not been previously treated, and not for the treatment of restenosis. It also stresses the importance of matching the stent size to the vessel size, deploying the stent fully so it's in contact with the vessel wall, and using an adequate antiplatelet regimen. The letter also highlights the importance of reporting adverse events to Cordis, and to the FDA.

We’re still in the fact-gathering stage on this issue. As new information becomes available, we'll keep health care professionals posted. We'll also cover it on future editions of FDA Patient Safety News, and also on our web site, so stay tuned.

Additional Information:

Cordis Dear Colleague Letter.

http://www.fda.gov/bbs/topics/news/cordis_ltr.pdf


Caution on Glucose Testing in Neonates

Here's a caution about measuring blood glucose levels in neonates and premature infants. Glucose testing is commonly done in infants to rapidly identify both high and low blood sugar.

Some “bedside” glucose monitors will give falsely low results with neonates. That's because infants may have higher hematocrit levels than older children and adults, and that can interfere with the function of some glucose meters, which can lead to false readings. Why this happens isn't fully understood, but there are several ways to help address this problem. First, check the labeling and instructions for glucose meters used on neonates and premature infants to be sure they're cleared by FDA for this use.

Second, validate glucose meters by comparing them against a central laboratory's current reference method. It's also a good idea to periodically reevaluate these meters against the reference standard and to develop quality assurance and quality control programs.

And finally, if a glucose result in a neonate doesn't make sense, reassess the patient. If clinically appropriate, get a new sample and verify the result using an accepted reference method.

Additional Information:

OIVD – Laboratory Information. Lab Safety Tip #5: Make sure glucose meters used in testing neonates are FDA cleared for testing in neonates – Update June 19, 2003.
http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/TipsandArticlesonDeviceSafety/ucm109513.htm


New Medication Guide for Patients on Lariam

There's a new medication guide for patients taking the drug Lariam, used to prevent malaria. These written instructions were developed by FDA in cooperation with the drug's manufacturer, Roche Pharmaceuticals.

In addition to explaining how to take the drug, the guide alerts patients about the possibility of rare but potentially serious psychiatric side effects from Lariam, and cautions them to contact a health care professional if they experience such symptoms as anxiety, depression, hallucinations, restlessness or confusion. It also explains that Lariam should not be used in people with a history of depression, mental illness or seizures.

Roche Pharmaceuticals is also issuing a letter to physicians alerting them to the new medication guide, and a letter to pharmacists reminding them that they're required to provide the patient with a copy of the guide each time a Lariam prescription is filled.

Additional Information:

MedWatch - 2003 Safety Information Alerts.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm153319.htm


FDA Approves Prilosec OTC to Treat Frequent Heartburn

Now for the part of the program that helps you answer questions about medical products and procedures that are on patients' minds. FDA recently approved the proton-pump inhibitor Prilosec for over-the-counter sale, and patients may be asking about taking it for their heartburn.

The most important thing for patients to understand is that Prilosec OTC is for frequent heartburn, the kind that occurs two or more days per week. So patients who have infrequent heartburn --- once a week or less --- should be told that Prilosec OTC is not for them. It's also not for people who want immediate relief from heartburn. For acute heartburn symptoms, they should be advised to use OTC antacids or acid reducers.

Patients who do have frequent heartburn should be told that Prilosec OTC must be taken before eating once a day, every day for 14 days. They should understand that the drug may take one to four days for full effect, although some patients may get complete relief of symptoms within 24 hours. And they should be cautioned to wait at least four months before taking another 14-day course of treatment, unless instructed by a doctor. If the frequent heartburn returns soon after the 14 days of treatment, patients should contact their physicians.

Certain patients should be warned not to take Prilosec OTC. They include anyone who has had an allergic reaction to Prilosec in the past and anyone who has dysphagia, bloody vomitus or bloody or black stools.

Additional Information:

Drug Information - Prilosec OTC (Omeprazole).
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm152692.htm


New Trans Fatty Acid Information on Food Labels

FDA has issued a new regulation that will require manufacturers of foods and some dietary supplements to list the amount of trans fatty acids on the Nutrition Facts panel of the product label. Trans fatty acids are formed in the manufacture of food products when liquid vegetable oils are hydrogenated to make them more solid. They’re found mainly in processed foods such as vegetable shortening, crackers, cookies and, some margarines.

The reason for the new regulation is that trans fatty acids have emerged as an important public health issue. Like saturated fatty acids and dietary cholesterol, they raise low density lipoprotein, or LDL levels and thus increase the risk of heart disease. So it's important that people know how much trans fatty acid they're getting when they purchase a food product. Some manufacturers have already begun to list trans fatty acids on their nutrition labeling. Under the new regulation, all of them will be required to do so by January, 2006.

The label is just one part of a larger effort by the FDA. We also plan to develop educational materials for consumers on the importance of lowering their intake of saturated and trans fat and cholesterol. That should help motivate them to read the nutritional labels on the foods they buy, and avoid the ones with high levels of trans fat and saturated fat. You might be interested in using these educational materials to help teach your patients about healthy eating. We'll let you know as soon as they're available.

Additional Information:

FDA Acts to Provide Better Information to Consumers on Trans Fats.
http://www.fda.gov/Food/LabelingNutrition/LabelClaims/NutrientContentClaims/ucm110179.htm


Two-channel Pump Mix-up

The Institute for Safe Medication Practices recently reported on a medication mix-up with the use of a two-channel infusion pump. These pumps are used to infuse two drugs through one pump.

In the case cited by ISMP, heparin was being infused through one channel, and the anti-platelet drug Aggrastat through the other channel. When hanging a new bag for each solution, the nurse inadvertently threaded the tubing for Aggrastat through the channel already programmed for heparin and vice versa. Luckily, the error was noticed before the patient was harmed. The same type of error could happen with triple channel pumps or even with two single channel pumps being used on the same pole.

ISMP suggests the following practices to help avoid these kinds of errors. First of all, hang one solution at a time. Physically trace each line from the solution, through the pump, and then to the insertion site to make sure it's in the correct channel.

If a high alert medication will be infused, have one clinician hang the solution and ready it for infusion, and another clinician independently validate the correct patient, the dose and concentration, the insertion site and the pump or channel settings. Consider labeling each channel with the product being infused, but don't rely only on the label to avoid mistakes. And finally, never use a dual-channel pump to infuse solutions into two different patients.

Additional Information:

ISMP: Confusion reported between AGGRASTAT (tirofiban) and heparin while using a two-channel pump.
http://www.ismp.org/Newsletters/acutecare/articles/20030417.asp



FDA Patient Safety News is available at www.fda.gov/psn