FDA Patient Safety News: Show #77, July 2008

New Skin Graft Adhesive Approved

FDA recently approved a new medical adhesive called Artiss to attach skin grafts onto burn patients. Artiss is made by Baxter Healthcare.

Artiss has a lower thrombin concentration than other fibrin sealants, which gives surgeons more time to position the skin graft over a burn before the graft starts to adhere to the skin.

In a multicenter clinical trial, Artiss was compared to surgical staples using two different wound sites on the same patient. The results showed that Artiss was comparable to staples in achieving complete wound closure. The most frequent adverse events, which were seen in both treatment groups, included bleeding and fluid collection in the tissues. Both of these events are common during skin grafting.

Additional Information:

FDA Press Release. FDA Approves New Medical Adhesive to Treat Burn Patients. March 29, 2008.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116868.htm


New Non-Refrigerated Coagulation Product

FDA has approved a new formulation of the genetically engineered version of Factor VIIa that does not need to be refrigerated. Factor VIIa is a plasma protein essential for blood clotting that can be used to treat and prevent bleeding in people with certain bleeding disorders, including hemophilia. The new product, called NovoSeven RT, can be stored at room temperature for up to two years.

NovoSeven RT is a re-formulated version of NovoSeven Coagulation Factor VIIa Recombinant. The original formula could be stored for up to three years, but required refrigeration. The new formulation contains sucrose and L-methionine, which allows the product to be stored at room temperature.

The re-formulation could be helpful to facilities with limited refrigeration space, and it could give health care providers and patients greater flexibility in the management of certain blood disorders.

Additional Information:

FDA Press Release. FDA Approves New Formulation of Coagulation Therapy. May 9, 2008.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116894.htm


Update on Potentially Contaminated Heparin

Over the past several months, FDA has been alerting healthcare professionals and the public about medical products that may contain contaminated heparin, which has been associated with a number of serious adverse events. Here is an update and recommendations on this continuing issue.

Heparin is an anticoagulant commonly used subcutaneously and intravenously in patients undergoing kidney dialysis, certain types of cardiac surgery and other procedures. It is also used in lock flush solutions to maintain the patency of IV catheters, and as a coating or ingredient in certain medical devices and diagnostic products.

Towards the end of 2007, FDA started receiving an increasing number of reports of adverse events associated with injectable heparin products, especially when the heparin was administered as a bolus dose. Many of these events were consistent with either an anaphylactic-type reaction or acute hypotension. A small number of similar events have also been reported for heparin flush solutions. FDA has identified a contaminant in the heparin, an oversulfated chondroitin sulfate, that may have led to the adverse events.

This contaminant mimics heparin activity so closely that routine testing did not uncover it. Special test methods are needed to detect this contaminant, and the major U.S. heparin manufacturers and suppliers have agreed to perform these tests to screen all heparin active ingredient that they receive.

FDA has also asked medical device companies to identify any product they market that contains heparin or uses heparin in processing. A number of companies have recalled heparin or products containing heparin. They did this based either on reports of adverse events or as a precaution after the special testing revealed that the company had been supplied with contaminated lots of heparin.

FDA is asking healthcare professionals and facilities to take the following steps:

• Report adverse reactions associated with any drug or device that contains heparin. FDA is continuing to actively monitor this situation and it is essential that new events are reported as soon as possible. FDA is focusing on events involving injectable heparin, heparin lock flush solutions or medical devices that contain heparin. That could include certain blood collection tubes, intravascular catheters, vascular stents and grafts, and other devices used during cardiac procedures, such as oxygenators, pumps, filters and blood reservoirs.

• Pay attention to recalls of heparin or heparin-containing products, including those by Baxter Healthcare, American Health Packaging, B. Braun, Covidien, Medtronic and Atrium Medical.

• Check all drug and device storage areas, including emergency kits, crash carts, dialysis units and automated drug storage cabinets, to make sure that all recalled heparin products have been removed and are no longer available for use.

The investigation of contaminated heparin is still underway. The links (see "Additional Information" below) will be updated with the latest information as it becomes available.

Additional Information:

FDA. Update to healthcare facilities and healthcare professionals about Heparin and Heparin-containing medical products.
http://www.fda.gov/cder/drug/infopage/heparin/default.htm#healthcare


Update on Potentially Contaminated Heparin

Over the past several months, FDA has been alerting healthcare professionals and the public about medical products that may contain contaminated heparin, which has been associated with a number of serious adverse events. Here is an update and recommendations on this continuing issue.

Heparin is an anticoagulant commonly used subcutaneously and intravenously in patients undergoing kidney dialysis, certain types of cardiac surgery and other procedures. It is also used in lock flush solutions to maintain the patency of IV catheters, and as a coating or ingredient in certain medical devices and diagnostic products.

Towards the end of 2007, FDA started receiving an increasing number of reports of adverse events associated with injectable heparin products, especially when the heparin was administered as a bolus dose. Many of these events were consistent with either an anaphylactic-type reaction or acute hypotension. A small number of similar events have also been reported for heparin flush solutions. FDA has identified a contaminant in the heparin, an oversulfated chondroitin sulfate, that may have led to the adverse events.

This contaminant mimics heparin activity so closely that routine testing did not uncover it. Special test methods are needed to detect this contaminant, and the major U.S. heparin manufacturers and suppliers have agreed to perform these tests to screen all heparin active ingredient that they receive.

FDA has also asked medical device companies to identify any product they market that contains heparin or uses heparin in processing. A number of companies have recalled heparin or products containing heparin. They did this based either on reports of adverse events or as a precaution after the special testing revealed that the company had been supplied with contaminated lots of heparin.

FDA is asking healthcare professionals and facilities to take the following steps:

• Report adverse reactions associated with any drug or device that contains heparin. FDA is continuing to actively monitor this situation and it is essential that new events are reported as soon as possible. FDA is focusing on events involving injectable heparin, heparin lock flush solutions or medical devices that contain heparin. That could include certain blood collection tubes, intravascular catheters, vascular stents and grafts, and other devices used during cardiac procedures, such as oxygenators, pumps, filters and blood reservoirs.

• Pay attention to recalls of heparin or heparin-containing products, including those by Baxter Healthcare, American Health Packaging, B. Braun, Covidien, Medtronic and Atrium Medical.

• Check all drug and device storage areas, including emergency kits, crash carts, dialysis units and automated drug storage cabinets, to make sure that all recalled heparin products have been removed and are no longer available for use.

The investigation of contaminated heparin is still underway. The links (see "Additional Information" below) will be updated with the latest information as it becomes available.

Additional Information:

FDA. Information on Heparin Sodium Injection. April 25, 2008.
http://www.fda.gov/cder/drug/infopage/heparin/default.htm


Update on Potentially Contaminated Heparin

Over the past several months, FDA has been alerting healthcare professionals and the public about medical products that may contain contaminated heparin, which has been associated with a number of serious adverse events. Here is an update and recommendations on this continuing issue.

Heparin is an anticoagulant commonly used subcutaneously and intravenously in patients undergoing kidney dialysis, certain types of cardiac surgery and other procedures. It is also used in lock flush solutions to maintain the patency of IV catheters, and as a coating or ingredient in certain medical devices and diagnostic products.

Towards the end of 2007, FDA started receiving an increasing number of reports of adverse events associated with injectable heparin products, especially when the heparin was administered as a bolus dose. Many of these events were consistent with either an anaphylactic-type reaction or acute hypotension. A small number of similar events have also been reported for heparin flush solutions. FDA has identified a contaminant in the heparin, an oversulfated chondroitin sulfate, that may have led to the adverse events.

This contaminant mimics heparin activity so closely that routine testing did not uncover it. Special test methods are needed to detect this contaminant, and the major U.S. heparin manufacturers and suppliers have agreed to perform these tests to screen all heparin active ingredient that they receive.

FDA has also asked medical device companies to identify any product they market that contains heparin or uses heparin in processing. A number of companies have recalled heparin or products containing heparin. They did this based either on reports of adverse events or as a precaution after the special testing revealed that the company had been supplied with contaminated lots of heparin.

FDA is asking healthcare professionals and facilities to take the following steps:

• Report adverse reactions associated with any drug or device that contains heparin. FDA is continuing to actively monitor this situation and it is essential that new events are reported as soon as possible. FDA is focusing on events involving injectable heparin, heparin lock flush solutions or medical devices that contain heparin. That could include certain blood collection tubes, intravascular catheters, vascular stents and grafts, and other devices used during cardiac procedures, such as oxygenators, pumps, filters and blood reservoirs.

• Pay attention to recalls of heparin or heparin-containing products, including those by Baxter Healthcare, American Health Packaging, B. Braun, Covidien, Medtronic and Atrium Medical.

• Check all drug and device storage areas, including emergency kits, crash carts, dialysis units and automated drug storage cabinets, to make sure that all recalled heparin products have been removed and are no longer available for use.

The investigation of contaminated heparin is still underway. The links (see "Additional Information" below) will be updated with the latest information as it becomes available.

Additional Information:

FDA MedWatch Safety Alert. Heparin Sodium Injection. May 15, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm103558.htm


FDA Takes Action on Injectable Colchicine

FDA is taking action against companies marketing injectable colchicine, which is an unapproved form of the drug. Colchicine is an anti-inflammatory used in the treatment of gout. Colchicine tablets, which are less hazardous, are not affected by FDA's action at this time.

The injectable form of colchicine is especially hazardous because the therapeutic index, which is the margin between an effective dose and a toxic dose, is very narrow. Also, certain side effects that might alert the clinician that the dose is too high do not appear until the patient has already reached toxic levels, which adds to the problem.

Because of its toxicity and the availability of safer therapies, injectable colchicine is rarely used to treat gout anymore. But some practitioners are using this product to treat back pain. FDA believes that the risks of this treatment outweigh the benefits.

FDA is also cautioning pharmacies against compounding injectable colchicine products. Because the drug is so toxic, and because the therapeutic index is so narrow, any errors that occur during compounding can have potentially fatal consequences.

Additional Information:

FDA MedWatch Safety Alert. Injectable Colchicine (including drugs containing colchicine). February 6, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm110232.htm


FDA Studying Heart Attack Risk with Ziagen, Videx

FDA has informed the health care community about ongoing safety reviews of several drugs. FDA is doing this as part of its commitment to inform health care professionals and the public about its ongoing drug safety reviews. Because the information is preliminary and there is scientific uncertainty, FDA is not taking regulatory action at this point, and is not advising health care professionals to stop using the drugs. FDA is continuing to evaluate the safety of these products, and will provide updates as more information becomes available.

One communication concerns the possibility of an increased risk of heart attack among HIV patients taking the nucleoside reverse transcriptase inhibitors Ziagen (abacavir) and Videx (didanosine). This information comes from an ongoing international study of over 30,000 HIV patients. This study did not address the heart attack risk with tenofovir or emtricitabine, two other nucleoside reverse transcriptase inhibitors.

Results to date show that patients on Ziagen or Videx experience an increased risk of MI that ranges from roughly 50 to 90 percent. The excess risk appears to be greater among patients with other risk factors for heart disease, to remain stable over time, and to be reversible if the drugs are stopped. When the manufacturers of these two drugs, GlaxoSmithKline and Bristol Myers Squibb, searched their own databases, they did not find an increased risk of heart attack.

FDA is continuing to evaluate the risk of heart attack with Ziagen and Videx. This evaluation may result in the need to revise the labeling for these products. In the meantime, clinicians should consider the potential risks and benefits of each antiretroviral drug they prescribe.

Again, these communications are preliminary information, and they are in keeping with FDA's commitment to inform the public about its ongoing drug safety reviews. FDA urges healthcare professionals and patients to report drug adverse reactions through FDA's Medwatch program (see link below).

Additional Information:

FDA MedWatch Safety Alert. Ziagen (abacavir) and Videx (didanosine). March 27, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm110619.htm


FDA Studying Heart Attack Risk with Ziagen, Videx

FDA has informed the health care community about ongoing safety reviews of several drugs. FDA is doing this as part of its commitment to inform health care professionals and the public about its ongoing drug safety reviews. Because the information is preliminary and there is scientific uncertainty, FDA is not taking regulatory action at this point, and is not advising health care professionals to stop using the drugs. FDA is continuing to evaluate the safety of these products, and will provide updates as more information becomes available.

One communication concerns the possibility of an increased risk of heart attack among HIV patients taking the nucleoside reverse transcriptase inhibitors Ziagen (abacavir) and Videx (didanosine). This information comes from an ongoing international study of over 30,000 HIV patients. This study did not address the heart attack risk with tenofovir or emtricitabine, two other nucleoside reverse transcriptase inhibitors.

Results to date show that patients on Ziagen or Videx experience an increased risk of MI that ranges from roughly 50 to 90 percent. The excess risk appears to be greater among patients with other risk factors for heart disease, to remain stable over time, and to be reversible if the drugs are stopped. When the manufacturers of these two drugs, GlaxoSmithKline and Bristol Myers Squibb, searched their own databases, they did not find an increased risk of heart attack.

FDA is continuing to evaluate the risk of heart attack with Ziagen and Videx. This evaluation may result in the need to revise the labeling for these products. In the meantime, clinicians should consider the potential risks and benefits of each antiretroviral drug they prescribe.

Again, these communications are preliminary information, and they are in keeping with FDA's commitment to inform the public about its ongoing drug safety reviews. FDA urges healthcare professionals and patients to report drug adverse reactions through FDA's Medwatch program (see link below).

Additional Information:

FDA MedWatch - Reporting Adverse Experiences to FDA.
http://www.fda.gov/medwatch/how.htm


Preventing Fatal Overdoses with Cerebyx

The Institute for Safe Medication Practices (ISMP) and FDA are warning healthcare professionals that potentially fatal dosing errors continue to occur with the anti-epileptic drug Cerebyx (fosphenytoin), despite clarifications in the drug's labeling that date back to 1999. FDA's MedWatch program has reports of seven cases where young children received an overdose of Cerebyx and died.

Cerebyx doses are expressed as phenytoin equivalents (PE). The problem is that electronic and printed displays in many facilities list the drug as "50 mg PE/mL, 10 mL." That could cause users to believe that a 10 mL vial contains just 50 mg PE rather than 500 mg PE, which could lead to a significant overdose.

To help prevent these errors, the ISMP article recommends that medication screen displays, facility-generated auxiliary labeling, displays on automatic dispensing cabinets and printed requisitions read "100 mg PE per 2 mL" or "500 mg PE per 10 mL." Because the 10 mL vial appears to be most frequently involved in massive overdosing, ISMP recommends that pediatric facilities consider stocking only the 2 mL vials.

ISMP notes that it would take ten of these vials to prepare a potentially fatal 1,000 mg dose. Retrieving this many vials might alert the practitioner that a dosing error has been made.

Additional Information:

ISMP Medication Safety Alert! FDA Advise-ERR: Medication Errors Associated with Cerebyx. April 10, 2008. Volume 13, Issue 7, Page 1-2.
http://www.ismp.org/Newsletters/acutecare/articles/20080410.asp



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