FDA Patient Safety News: Show #33, November 2004

New Carotid Stent Approved

The FDA recently approved the first stent system that’s designed to treat stenosis in the carotid artery. It's called the Acculink Carotid Stent System, and it's manufactured by Guidant Corporation.

The stent, which is inserted during angioplasty, holds the carotid artery open. It's used with an umbrella-like filter called the Accunet that's designed to open up inside the vessel and catch emboli and other debris that might otherwise travel to the brain and trigger a stroke.

In a clinical study, the stent system successfully opened blockages in 92 percent of 581 patients who received the device. The risk of death, stroke and heart attack at 30 days, or stroke in the area of the blockage at one year, was about 10 percent in stent patients compared to 15 percent in patients who had surgery.

In practice, the Accunet filter is inserted into a vessel in the groin and advanced to the site of the carotid blockage. The filter then opens to catch any debris. An angioplasty balloon is dilated to open the blockage. The stent is then threaded up to the blockage and when it's in place, the stent emerges from the catheter and opens automatically. Another balloon catheter is positioned inside the stent, and debris is captured by the filter. The catheter is withdrawn, and another one is inserted to close the filter and remove it, along with any collected debris.

The new stent system is designed for patients who need carotid revascularization but are at high risk from surgical endarterectomy. Candidates for the stenting procedure must have at least a 50 percent stenosis along with neurological symptoms, or, if they have no neurological symptoms, they must have at least an 80 percent stenosis.

Patients who should not receive this device include those who can't tolerate anticoagulant or antiplatelet therapy, those with vascular anatomy that would preclude the safe introduction of a stent, and those with uncorrected bleeding disorders.

Additional Information:

FDA Approval Information - ACCULINK™ Carotid Stent System and RX ACCULINK™ Carotid Stent System - P040012.
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm080874.htm


New Carotid Stent Approved

The FDA recently approved the first stent system that’s designed to treat stenosis in the carotid artery. It's called the Acculink Carotid Stent System, and it's manufactured by Guidant Corporation.

The stent, which is inserted during angioplasty, holds the carotid artery open. It's used with an umbrella-like filter called the Accunet that's designed to open up inside the vessel and catch emboli and other debris that might otherwise travel to the brain and trigger a stroke.

In a clinical study, the stent system successfully opened blockages in 92 percent of 581 patients who received the device. The risk of death, stroke and heart attack at 30 days, or stroke in the area of the blockage at one year, was about 10 percent in stent patients compared to 15 percent in patients who had surgery.

In practice, the Accunet filter is inserted into a vessel in the groin and advanced to the site of the carotid blockage. The filter then opens to catch any debris. An angioplasty balloon is dilated to open the blockage. The stent is then threaded up to the blockage and when it's in place, the stent emerges from the catheter and opens automatically. Another balloon catheter is positioned inside the stent, and debris is captured by the filter. The catheter is withdrawn, and another one is inserted to close the filter and remove it, along with any collected debris.

The new stent system is designed for patients who need carotid revascularization but are at high risk from surgical endarterectomy. Candidates for the stenting procedure must have at least a 50 percent stenosis along with neurological symptoms, or, if they have no neurological symptoms, they must have at least an 80 percent stenosis.

Patients who should not receive this device include those who can't tolerate anticoagulant or antiplatelet therapy, those with vascular anatomy that would preclude the safe introduction of a stent, and those with uncorrected bleeding disorders.

Additional Information:

Consumer Information - ACCULINK™ Carotid Stent System and RX ACCULINK™ Carotid Stent System - P040012.
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm080874.htm


New Drug for Diabetic Peripheral Neuropathy

FDA recently approved the first drug indicated for the management of neuropathic pain associated with diabetic peripheral neuropathy. The drug is called Cymbalta (duloxetine hydrochloride) and it's made by Eli Lilly and Co. Cymbalta, an SSNRI, was also recently approved to treat major depressive disorder in adults.

Peripheral neuropathy is the most common complication of diabetes mellitus, affecting up to 62% of American diabetics. It's usually associated with long standing diabetes or poor glucose control, and it's usually characterized by burning, tingling, and numbing sensations that begin in the feet, and later affect the legs or hands.

Although the mechanism of action is unknown, in clinical trials, patients treated with Cymbalta reported a greater decrease in pain than those treated with placebo. In these trials, 51 percent of patients treated with Cymbalta reported at least a 30 percent sustained reduction in pain, as compared to 31 percent of placebo patients.

The most commonly reported side effects were nausea, somnolence, dizziness, decreased appetite and constipation. Cymbalta is contraindicated in patients with uncontrolled narrow-angle glaucoma and those taking MAO inhibitors.

Additional Information:

FDA Talk Paper - FDA Approves Drug for Neuropathic Pain Associated With Diabetes.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108349.htm


New Lab Test to Screen Infants for Inborn Metabolism Errors

The FDA recently cleared for marketing a new screening test for newborns that will help detect a variety of inborn errors of metabolism. The test is called the NeoGram Amino Acids and Acylcarnitines Tandem Mass Spectrometry Kit, manufactured by PerkinElmer Life and Analytical Sciences.

The test starts with a heel-stick blood sample from the infant - the same kind of heel-stick sample that's already being used for other newborn screening tests required by various states. It applies mass spectrometry to the sample in order to measure amino acids, free carnitine and acylcarnitines. Abnormal patterns of these substances may indicate a wide variety of disease states, including phenylketonuria, maple syrup urine disease, and homocystinuria.

While each of these conditions is relatively rare, taken together they're fairly common, and can cause developmental delay, seizures, mental retardation, and death. With early identification, many of the effects of these diseases can be mitigated, with improved long-term outcome and quality of life.

This product is not a stand-alone test for predicting inborn errors of metabolism. Rather, it's a screening tool that must be used along with clinical information and other tools to determine a newborn's risk.

Additional Information:

FDA Talk Paper - FDA Clears New Lab Test to Help Screen Newborn Infants for Congenital Disease.
http://www.fda.gov/bbs/topics/ANSWERS/2004/ANS01308.html


Adjusting Lovenox Dosage for Severe Renal Impairment

Aventis Pharmaceuticals has revised the labeling for the anticoagulant drug Lovenox (enoxaparin sodium injection) stressing the need to adjust the dose in patients with severe renal impairment-that is, those with a creatinine clearance of less than 30 mL per minute. These patients don't clear and eliminate the drug normally, and so they may require a lower dose to prevent bleeding.

The label notes that low-weight patients and those with mild or moderate renal impairment don't require a specific dosage adjustment, but that low-weight patients on the drug should be carefully monitored for bleeding.

The label also contains a "black box warning," cautioning that patients on anticoagulant drugs who receive epidural or spinal anesthesia, or who receive a spinal puncture, are at risk of developing an epidural or spinal hematoma, which can result in long-term or permanent paralysis. The black box warns that these patients should be frequently monitored for signs of neurological impairment, and if neurologic compromise is noted, urgent treatment is needed. It also recommends that physicians consider benefits versus risks before deciding on neuraxial intervention in patients who are receiving or will receive anticoagulant drugs.

Additional Information:

FDA MedWatch Safety Alert - Lovenox (enoxaparin sodium injection).
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm155077.htm


Warning on Thromboembolic Events with Avastin

Genentech, Inc. has alerted healthcare providers about an increased risk of serious arterial thromboembolic events with the use of Avastin (bevacizumab), a drug used to treat metastatic colorectal cancer. These adverse events include stroke, MI, TIA, and angina.

In randomized, active-controlled studies in patients with metastatic colorectal cancer, the risk of a serious arterial thrombotic event was about five percent in patients who received Avastin along with 5-FU based chemotherapy. That's twice as high as the rate in patients who received the 5-FU regimen alone. Patients who are 65 years or older or who have a history of arterial thromboembolism are at higher risk for these events. The company says that patients who experience an arterial thromboembolic event during treatment should permanently discontinue Avastin.

Additional Information:

FDA MedWatch Safety Alert – Avastin (bevacizumab).
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm075132.htm


Hematologic and Neurologic Warnings for Remicade

Centocor Inc. has notified healthcare professionals about new warnings for Remicade (infliximab), a drug used to treat rheumatoid arthritis and Crohn's disease. The new safety information describes both hematologic and neurologic events that have occurred in patients being treated with Remicade.

The hematologic events, some of them fatal, have included leukopenia, neutropenia, thrombocytopenia and pancytopenia. Although it's not clear that Remicade therapy causes these events and no high risk groups have been identified, Centocor advises practitioners to be cautious with patients who have significant hematologic abnormalities, or a history of these problems.

The company also says that all patients on Remicade should be told to seek immediate medical attention if they develop signs suggestive of blood dyscrasias or infection, such as persistent fever, bruising or bleeding. Practitioners should consider discontinuing Remicade therapy in patients who develop significant hematologic abnormalities.

The neurologic events have included rare cases of a central nervous system manifestation of systemic vasculitis. Again, practitioners should consider discontinuing Remicade in patients who develop significant CNS reactions.

Additional Information:

FDA MedWatch Safety Alert - Remicade (infliximab).
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm166900.htm


Caution on Ethyl Chloride Flammability

The Institute for Safe Medication Practices recently highlighted the dangers of using flammable medical products around heat sources. ISMP has cited cases where fires occurred because practitioners didn't realize that ethyl chloride spray, a topical skin anesthetic, is highly flammable.

Ethyl chloride has been used for many years, and in a wide variety of settings. Physical therapists use it to treat myofascial problems, podiatrists use it before they do minor foot surgery, dentists use it to test the vitality of tooth pulp, athletic coaches and trainers use it for sports injuries. So people may not realize - or may not remember - that it's flammable.

Also, they may not realize that it doesn’t take a flame to ignite ethyl chloride. An electrical spark or static electricity can do it. So can electro-cautery, and in fact that’s what was used in one of the cases that ISMP cites. In this case, a nurse practitioner was preparing to treat a 6-year-old child's infected toe. She sprayed his foot with ethyl chloride to numb the area, and then lanced the area with surgical cautery. As soon as she triggered the cautery device, the entire surgical field went up in flames and the pad underneath the child's foot ignited. The child's mother, who was holding her son, quickly pulled the child away from the fire, and luckily he wasn't burned.

Later, the nurse practitioner admitted that she was unaware that ethyl chloride was a very dangerous fire hazard and should never be used in the presence of electrical cautery equipment. She also mentioned that she had observed a physician doing the same procedure previously on another child, without any problems.

Another thing to remember is that the spray doesn’t have to be close to the source of ignition, like a spark or a cautery device, in order for it to ignite. ISMP points out that the vapors from ethyl chloride are heavier than air, so they can sink to the floor and then move. That means ignition can take place at some distant source and then a sudden flashback can occur, in which the flame comes back to the person using the ethyl chloride spray.

ISMP has two basic recommendations, one of them focused on the people who use the spray, and the other on the spray itself. First of all, they say, make sure that all healthcare workers know about the dangers of flammable products such as ethyl chloride, and that they understand the potential for burns when these products are used with a heat source. And second, they suggest that you reevaluate whether you really need each of the flammable products in your facility. ISMP says that there are often safer alternatives, especially for topical anesthetics.

Additional Information:

ISMP Medication Safety Alert: Extreme caution needed with flammable products. March 11, 2004.
http://www.ismp.org/Newsletters/acutecare/articles/20040311.asp?ptr=y


Caution on Ethyl Chloride Flammability

The Institute for Safe Medication Practices recently highlighted the dangers of using flammable medical products around heat sources. ISMP has cited cases where fires occurred because practitioners didn't realize that ethyl chloride spray, a topical skin anesthetic, is highly flammable.

Ethyl chloride has been used for many years, and in a wide variety of settings. Physical therapists use it to treat myofascial problems, podiatrists use it before they do minor foot surgery, dentists use it to test the vitality of tooth pulp, athletic coaches and trainers use it for sports injuries. So people may not realize - or may not remember - that it's flammable.

Also, they may not realize that it doesn’t take a flame to ignite ethyl chloride. An electrical spark or static electricity can do it. So can electro-cautery, and in fact that’s what was used in one of the cases that ISMP cites. In this case, a nurse practitioner was preparing to treat a 6-year-old child's infected toe. She sprayed his foot with ethyl chloride to numb the area, and then lanced the area with surgical cautery. As soon as she triggered the cautery device, the entire surgical field went up in flames and the pad underneath the child's foot ignited. The child's mother, who was holding her son, quickly pulled the child away from the fire, and luckily he wasn't burned.

Later, the nurse practitioner admitted that she was unaware that ethyl chloride was a very dangerous fire hazard and should never be used in the presence of electrical cautery equipment. She also mentioned that she had observed a physician doing the same procedure previously on another child, without any problems.

Another thing to remember is that the spray doesn’t have to be close to the source of ignition, like a spark or a cautery device, in order for it to ignite. ISMP points out that the vapors from ethyl chloride are heavier than air, so they can sink to the floor and then move. That means ignition can take place at some distant source and then a sudden flashback can occur, in which the flame comes back to the person using the ethyl chloride spray.

ISMP has two basic recommendations, one of them focused on the people who use the spray, and the other on the spray itself. First of all, they say, make sure that all healthcare workers know about the dangers of flammable products such as ethyl chloride, and that they understand the potential for burns when these products are used with a heat source. And second, they suggest that you reevaluate whether you really need each of the flammable products in your facility. ISMP says that there are often safer alternatives, especially for topical anesthetics.

Additional Information:

ISMP Medication Safety Alert: Ethyl chloride ignites. August 26, 2004.
http://www.ismp.org/Newsletters/acutecare/articles/20040826.asp


More Mix-Ups between TD and PPD

An earlier FDA Patient Safety News program described several cases where a mix-up between tetanus diphtheria toxoid vaccine and tuberculin PPD led to unnecessary treatment. In that situation, both products were manufactured by the same company, Aventis Pasteur. Since then, several more of these mixups have occurred, and some of them have involved products manufactured by other companies. Overall, FDA has received reports of over 80 cases of these kinds of mix-ups since 1990.

The mistakes are being made in both directions. That is, patients who are supposed to get PPD are getting the tetanus diphtheria toxoid instead, and vice versa. Also, sometimes PPD is being mixed up with vaccines other than the Td vaccine.

Most of the mix-ups occurred with patients who were supposed to get PPD skin tests but were inadvertently given intradermal injections of the Td vaccine. In some cases, the reactions from the Td injections were read as positive PPDs, and patients were started on isoniazid. And there are reports of the opposite mix-up occurring --- where patients received intramuscular injection of PPD, instead of receiving the Td vaccine. We've also gotten reports of similar mix-up errors between PPD skin tests and other vaccines, such as pneumococcal vaccine, flu vaccine, and hepatitis B vaccine.

One of the main reasons for the mixups seems to be the way the products are stored. Both Td vaccine and the PPD require refrigeration and are often stored side by side. Another factor may be similar product packaging - both Aventis Pasteur products come in stylized, colorful cartons of the same size.

To deal with this problem, FDA is recommending several things. The most obvious is to carefully read the label before you administer the product, particularly where packaging may look similar. But there are other things you can do, too. For example, consider storing these products separately. It's also a good idea to prepare only enough product for that particular patient at that particular time. And be sure to keep good records of lot numbers for vaccines and other injectable products. If your facility has barcode scanning technology, scanning the package could help to catch errors when dispensing or administering the product.

You can report vaccine-PPD mix-ups or send in suggestions on how to prevent such errors by going to our web site.

Additional Information:

To report inadvertent vaccine administration, call 1-800-822-7967, or email VAERS at
http://vaers.hhs.gov/index


More Mix-Ups between TD and PPD

An earlier FDA Patient Safety News program described several cases where a mix-up between tetanus diphtheria toxoid vaccine and tuberculin PPD led to unnecessary treatment. In that situation, both products were manufactured by the same company, Aventis Pasteur. Since then, several more of these mixups have occurred, and some of them have involved products manufactured by other companies. Overall, FDA has received reports of over 80 cases of these kinds of mix-ups since 1990.

The mistakes are being made in both directions. That is, patients who are supposed to get PPD are getting the tetanus diphtheria toxoid instead, and vice versa. Also, sometimes PPD is being mixed up with vaccines other than the Td vaccine.

Most of the mix-ups occurred with patients who were supposed to get PPD skin tests but were inadvertently given intradermal injections of the Td vaccine. In some cases, the reactions from the Td injections were read as positive PPDs, and patients were started on isoniazid. And there are reports of the opposite mix-up occurring --- where patients received intramuscular injection of PPD, instead of receiving the Td vaccine. We've also gotten reports of similar mix-up errors between PPD skin tests and other vaccines, such as pneumococcal vaccine, flu vaccine, and hepatitis B vaccine.

One of the main reasons for the mixups seems to be the way the products are stored. Both Td vaccine and the PPD require refrigeration and are often stored side by side. Another factor may be similar product packaging - both Aventis Pasteur products come in stylized, colorful cartons of the same size.

To deal with this problem, FDA is recommending several things. The most obvious is to carefully read the label before you administer the product, particularly where packaging may look similar. But there are other things you can do, too. For example, consider storing these products separately. It's also a good idea to prepare only enough product for that particular patient at that particular time. And be sure to keep good records of lot numbers for vaccines and other injectable products. If your facility has barcode scanning technology, scanning the package could help to catch errors when dispensing or administering the product.

You can report vaccine-PPD mix-ups or send in suggestions on how to prevent such errors by going to our web site.

Additional Information:

To report inadvertent PPD administration, call 1-800-FDA-1088, or email MedWatch at
http://vaers.hhs.gov/index


More Mix-Ups between TD and PPD

An earlier FDA Patient Safety News program described several cases where a mix-up between tetanus diphtheria toxoid vaccine and tuberculin PPD led to unnecessary treatment. In that situation, both products were manufactured by the same company, Aventis Pasteur. Since then, several more of these mixups have occurred, and some of them have involved products manufactured by other companies. Overall, FDA has received reports of over 80 cases of these kinds of mix-ups since 1990.

The mistakes are being made in both directions. That is, patients who are supposed to get PPD are getting the tetanus diphtheria toxoid instead, and vice versa. Also, sometimes PPD is being mixed up with vaccines other than the Td vaccine.

Most of the mix-ups occurred with patients who were supposed to get PPD skin tests but were inadvertently given intradermal injections of the Td vaccine. In some cases, the reactions from the Td injections were read as positive PPDs, and patients were started on isoniazid. And there are reports of the opposite mix-up occurring --- where patients received intramuscular injection of PPD, instead of receiving the Td vaccine. We've also gotten reports of similar mix-up errors between PPD skin tests and other vaccines, such as pneumococcal vaccine, flu vaccine, and hepatitis B vaccine.

One of the main reasons for the mixups seems to be the way the products are stored. Both Td vaccine and the PPD require refrigeration and are often stored side by side. Another factor may be similar product packaging - both Aventis Pasteur products come in stylized, colorful cartons of the same size.

To deal with this problem, FDA is recommending several things. The most obvious is to carefully read the label before you administer the product, particularly where packaging may look similar. But there are other things you can do, too. For example, consider storing these products separately. It's also a good idea to prepare only enough product for that particular patient at that particular time. And be sure to keep good records of lot numbers for vaccines and other injectable products. If your facility has barcode scanning technology, scanning the package could help to catch errors when dispensing or administering the product.

You can report vaccine-PPD mix-ups or send in suggestions on how to prevent such errors by going to our web site.

Additional Information:

MMWR. Notice to Readers. Inadvertent Intradermal Administration of Tetanus Toxoid-Containing Vaccines Instead of Tuberculosis Skin Tests. July 30, 2004. 53(29); 662-664.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5329a5.htm


Caution on Ethyl Chloride Flammability

The Institute for Safe Medication Practices recently highlighted the dangers of using flammable medical products around heat sources. ISMP has cited cases where fires occurred because practitioners didn't realize that ethyl chloride spray, a topical skin anesthetic, is highly flammable.

Ethyl chloride has been used for many years, and in a wide variety of settings. Physical therapists use it to treat myofascial problems, podiatrists use it before they do minor foot surgery, dentists use it to test the vitality of tooth pulp, athletic coaches and trainers use it for sports injuries. So people may not realize - or may not remember - that it's flammable.

Also, they may not realize that it doesn’t take a flame to ignite ethyl chloride. An electrical spark or static electricity can do it. So can electro-cautery, and in fact that’s what was used in one of the cases that ISMP cites. In this case, a nurse practitioner was preparing to treat a 6-year-old child's infected toe. She sprayed his foot with ethyl chloride to numb the area, and then lanced the area with surgical cautery. As soon as she triggered the cautery device, the entire surgical field went up in flames and the pad underneath the child's foot ignited. The child's mother, who was holding her son, quickly pulled the child away from the fire, and luckily he wasn't burned.

Later, the nurse practitioner admitted that she was unaware that ethyl chloride was a very dangerous fire hazard and should never be used in the presence of electrical cautery equipment. She also mentioned that she had observed a physician doing the same procedure previously on another child, without any problems.

Another thing to remember is that the spray doesn’t have to be close to the source of ignition, like a spark or a cautery device, in order for it to ignite. ISMP points out that the vapors from ethyl chloride are heavier than air, so they can sink to the floor and then move. That means ignition can take place at some distant source and then a sudden flashback can occur, in which the flame comes back to the person using the ethyl chloride spray.

ISMP has two basic recommendations, one of them focused on the people who use the spray, and the other on the spray itself. First of all, they say, make sure that all healthcare workers know about the dangers of flammable products such as ethyl chloride, and that they understand the potential for burns when these products are used with a heat source. And second, they suggest that you reevaluate whether you really need each of the flammable products in your facility. ISMP says that there are often safer alternatives, especially for topical anesthetics.

Additional Information:

JCAHO Sentinel Event Alert.
http://www.jcaho.org/about+us/news+letters/sentinel+event+alert/sea_29.htm



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