FDA Patient Safety News: Show #32, October 2004

New Injectable Facial Filler for HIV Patients

FDA recently approved the first injectable filler used to correct facial wasting in people with HIV/AIDS. The condition, called lipoatrophy, is caused by subcutaneous fat loss, resulting in a sinking of the cheeks, eyes and temples. The new product, called Sculptra, contains poly-L-lactic acid, a synthetic polymer from the alpha-hydroxy-acid family. It's manufactured by Dermik Laboratories.

Sculptra is injected into the deep dermis or the subcutaneous layer around the area of fat loss in the face. The effect can take several weeks to become evident, and three to six treatment sessions may be needed to achieve the desired result. The treatment can last up to two years. Touch-up treatments may be needed from time to time to maintain the effect.

Sculptra should be injected by health professionals who are expert in correcting volume deficiencies in HIV/AIDS patients. They should avoid injecting the product into the superficial layers of skin, and take special care when injecting into areas of thin skin. The most common adverse events have been hematoma, bruising, discomfort, inflammation and edema.

The long-term safety and effectiveness of Sculptra haven't yet been investigated, and so FDA is requiring the manufacturer to conduct a study to evaluate safety and effectiveness beyond two years.

Additional Information:

New Device Approval - Sculptra - P030050
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm080931.htm


Software for Certain Medtronic Implanted Infusion Pumps Recalled

Medtronic is recalling certain software application cards. They're used in the company's Model 8840 N'Vision Clinician Programmers. These hand-held devices are used to program a number of implantable devices, including the SynchroMed and SychroMed EL implantable infusion pumps.

The recall is prompted by reports of data entry errors that have led to serious drug overdoses, including two patient deaths. The overdoses occurred when clinicians who were programming the pump entered the wrong time duration or the wrong interval --- for example, mistakenly putting the time interval between periodic drug boluses in the "minutes" field, instead of the "hours" field.

The recalled software may have contributed to these errors because one part of the screen did not have labels on the fields for hours, minutes, and seconds. Medtronic is now distributing replacement software that adds time labels to the screen to help reduce the risk of these kinds of programming errors.

If you use the Model 8840 N'Vision Programmer with SynchroMed or SynchroMed EL infusion pumps, the company says you should pay particular attention to selecting the appropriate time field when entering time duration or time intervals. You should also be sure to check your software application card for your N'Vision Programmer. If you have the older software version (AAA 02), Medtronic says you should order the new version (AAD 02).

Additional Information:

FDA MedWatch Safety Alert - Medtronic 8870 Software Application Card Version AAA 02
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm155668.htm


Avoiding Deaths from Blood Transfusions

In 2003, transfusion-related acute lung injury, or TRALI, was the most frequent cause of transfusion-related deaths. So it's important to recognize and treat TRALI promptly.

TRALI is caused by an antigen-antibody reaction, but it’s not like an ordinary allergic reaction. In an allergy, the patient's own antibodies are reacting to a foreign antigen. In TRALI, the antibodies come from the blood donor. In other words, they're in the transfused blood that the patient receives. These are antibodies to human leukocytes, and once they're received by the patient through the transfusion, they attach to the patient's white blood cells and form microaggregates that end up in the lungs, where they can cause life-threatening vascular permeability and pulmonary edema.

Some blood donors are more likely to carry these antibodies than others.
Women who've had multiple births, and people who've received previous transfusions, are thought to be more likely to have these antibodies.

It’s important to recognize TRALI in patients who recently received a transfusion. This means being alert to the kinds of symptoms you might expect after an antigen-antibody reaction in the lungs. So you'd watch for shortness of breath, hypoxemia, hypotension, fever, and severe bilateral pulmonary edema. They usually begin within one to two hours after the transfusion and they're fully present within six hours. Depending on the severity of the symptoms, patients may require respiratory support. Diuretics are not effective in treating TRALI, since the underlying pathology involves microvascular injury, not fluid overload.

Dealing successfully with TRALI requires vigilance, prompt treatment, and reporting.

First, be alert that any respiratory distress experienced by a patient during or following a transfusion could potentially be TRALI. If you observe respiratory distress, discontinue the transfusion immediately and begin oxygen and supportive therapy.

Second, notify your transfusion service. They'll arrange for any remaining product to be returned to the blood collecting facility, and for the donor to be tested for the antibodies.

And finally, report any cases of TRALI to the FDA.

Report any transfusion deaths from TRALI to:
FDA’s Center for Biologics Evaluation and Research (CBER) by calling 301-827-6220, faxing to 301-827-6748, or e-mail to fatalities2@cber.fda.gov

Additional Information:

Report non-fatal TRALI-associated transfusion reactions to: FDA’s MedWatch program by calling 800-FDA-1088, faxing to 800-FDA-0178, or on-line at:
http://www.fda.gov/medwatch/report/hcp.htm


Avoiding Deaths from Blood Transfusions

In 2003, transfusion-related acute lung injury, or TRALI, was the most frequent cause of transfusion-related deaths. So it's important to recognize and treat TRALI promptly.

TRALI is caused by an antigen-antibody reaction, but it’s not like an ordinary allergic reaction. In an allergy, the patient's own antibodies are reacting to a foreign antigen. In TRALI, the antibodies come from the blood donor. In other words, they're in the transfused blood that the patient receives. These are antibodies to human leukocytes, and once they're received by the patient through the transfusion, they attach to the patient's white blood cells and form microaggregates that end up in the lungs, where they can cause life-threatening vascular permeability and pulmonary edema.

Some blood donors are more likely to carry these antibodies than others.
Women who've had multiple births, and people who've received previous transfusions, are thought to be more likely to have these antibodies.

It’s important to recognize TRALI in patients who recently received a transfusion. This means being alert to the kinds of symptoms you might expect after an antigen-antibody reaction in the lungs. So you'd watch for shortness of breath, hypoxemia, hypotension, fever, and severe bilateral pulmonary edema. They usually begin within one to two hours after the transfusion and they're fully present within six hours. Depending on the severity of the symptoms, patients may require respiratory support. Diuretics are not effective in treating TRALI, since the underlying pathology involves microvascular injury, not fluid overload.

Dealing successfully with TRALI requires vigilance, prompt treatment, and reporting.

First, be alert that any respiratory distress experienced by a patient during or following a transfusion could potentially be TRALI. If you observe respiratory distress, discontinue the transfusion immediately and begin oxygen and supportive therapy.

Second, notify your transfusion service. They'll arrange for any remaining product to be returned to the blood collecting facility, and for the donor to be tested for the antibodies.

And finally, report any cases of TRALI to the FDA.

Report any transfusion deaths from TRALI to:
FDA’s Center for Biologics Evaluation and Research (CBER) by calling 301-827-6220, faxing to 301-827-6748, or e-mail to fatalities2@cber.fda.gov

Additional Information:

FDA "Dear Colleague" Letter on TRALI (October 2001)
http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ucm105850.htm


Avoiding Confusion with Broselow Tapes

Determining the dose of medication to give a child in an emergency can be a challenge. In most cases the dose is based on the child's weight, and this can be very difficult to estimate. Even parents can be far off the mark when they're asked their child's weight. And even if the estimate is accurate, there's the added chore of looking up the dose for a child of that weight.

Some clinicians avoid these difficulties by using a Broselow Tape, which measures the child from head to toe and uses this measurement to estimate the child's weight, and thus the dose. The tape is divided into color-coded segments based on the child's length, and each of the colored segments shows the approximate weight for that length child, along with the dose for commonly used emergency drugs for children of that weight.

But errors are often made using Broselow tapes. In a recent Medication Safety Alert, the Institute for Safe Medication Practices notes that the tapes can be placed alongside the child upside down, which would give the wrong length for the child and thus the wrong dose. ISMP also says that the 1998 edition of the tape can be confusing in several respects, and that some of these problems were corrected in the newer 2002 version. They also point out that errors can occur if physicians wrongly assume that the listing of drugs on the tape means that they're to be given in sequence.

Here are some of the measures ISMP recommends to prevent errors when using Broselow tapes.

First, replace outdated Broselow tapes with the most recent edition, issued in 2002.

To prevent using the tapes upside down, hang them with the red arrow that says "Measure from this end" at the top. Teach staff to remember "RED TO HEAD" when placing the tape alongside the child's body.

And if the tape is laminated in plastic, be sure the plastic doesn't extend beyond the red arrow, which could change the measurement starting point.

For in-service training on how to properly use Broselow tapes, the Duke University Medical Center has a comprehensive programmed instruction course under its program for enhancing pediatric safety.

Additional Information:

ISMP Medication Safety Alert. Broselow Tape: Measuring the Changes from 1998 to Today - February 26, 2004
http://www.ismp.org/Newsletters/acutecare/articles/20040226.asp


Avoiding Confusion with Broselow Tapes

Determining the dose of medication to give a child in an emergency can be a challenge. In most cases the dose is based on the child's weight, and this can be very difficult to estimate. Even parents can be far off the mark when they're asked their child's weight. And even if the estimate is accurate, there's the added chore of looking up the dose for a child of that weight.

Some clinicians avoid these difficulties by using a Broselow Tape, which measures the child from head to toe and uses this measurement to estimate the child's weight, and thus the dose. The tape is divided into color-coded segments based on the child's length, and each of the colored segments shows the approximate weight for that length child, along with the dose for commonly used emergency drugs for children of that weight.

But errors are often made using Broselow tapes. In a recent Medication Safety Alert, the Institute for Safe Medication Practices notes that the tapes can be placed alongside the child upside down, which would give the wrong length for the child and thus the wrong dose. ISMP also says that the 1998 edition of the tape can be confusing in several respects, and that some of these problems were corrected in the newer 2002 version. They also point out that errors can occur if physicians wrongly assume that the listing of drugs on the tape means that they're to be given in sequence.

Here are some of the measures ISMP recommends to prevent errors when using Broselow tapes.

First, replace outdated Broselow tapes with the most recent edition, issued in 2002.

To prevent using the tapes upside down, hang them with the red arrow that says "Measure from this end" at the top. Teach staff to remember "RED TO HEAD" when placing the tape alongside the child's body.

And if the tape is laminated in plastic, be sure the plastic doesn't extend beyond the red arrow, which could change the measurement starting point.

For in-service training on how to properly use Broselow tapes, the Duke University Medical Center has a comprehensive programmed instruction course under its program for enhancing pediatric safety.

Additional Information:

USP – Patient Safety. Practitioners' Reporting News: Cases Submitted to MER (January 30, 2004) (See Case 4)
http://www.usp.org/patientSafety/briefsArticlesReports/practitionerReportingNews/prn1112004-01-30.html


Caution on Use of Enteryx

Boston Scientific has sent a safety alert to health professionals about the use of Enteryx, a permanently implanted product used to treat patients with GERD symptoms. It's a liquid copolymer that's injected endoscopically into the muscle layer of the lower esophageal sphincter to help prevent acid reflux.

The alert describes the death of a patient who had been treated with Enteryx three weeks earlier. During the procedure, the needle may have penetrated the patient's esophageal wall. The cause of death is believed to be hemorrhage. Autopsy results indicated a fistula from the aorta to the esophagus, inflammation, and evidence of Enteryx material in the superficial layer of the aorta.

The letter reinforces the importance of closely following the product directions for use, and reiterates the following points on proper injection technique:

First, the Enteryx solution should only be injected at or just below the squamo-columnar junction. The needle should be inserted into the muscle of the esophagus with the needle angled towards the stomach. And fluoroscopy should always be used during injection to help identify a possible transmural injection.

The firm will also be updating the product labeling with a warning statement and additional recommendations for close patient follow-up in cases of transmural injection or suspected transmural injection.

Additional Information:

New Device Approval – Enteryx Procedure Kit (P020006)
http://www.accessdata.fda.gov/cdrh_docs/pdf2/P020006a.pdf


Kaopectate Reformulation Causes Confusion

Recent articles by FDA staff and the USP point out how reformulations of Kaopectate, the commonly-used OTC antidiarrheal, may be confusing for patients. Many years ago, Kaopectate was made with kaolin and pectin. Since then, two changes in the formulation of Kaopectate have been necessary because of changes in FDA regulations. About 15 years ago the product was reformulated to contain attapulgite, and then in 2003 it was modified again to contain bismuth subsalicylate as the active ingredient.

One source of confusion is that the supplies of Kaopectate containing attapulgite will stay in the stores until they're sold. But much of the concern comes from the fact that the latest formulation, labeled as "New and Improved," contains bismuth subsalicylate. Like aspirin, bismuth subsalicylate products have the potential for many drug-to-drug and drug-to-disease interactions. And in particular, salicylates are generally not recommended for children because of the risk of Reye's syndrome, salicylate allergies and salicylate overdosage.

The labeling for the Kaopectate that contains bismuth subsalicylate can add to the confusion. When the product was reformulated in 2003 with bismuth subsalicylate, the dosing instructions on the label included children. But just this year, FDA said that antidiarrheals containing bismuth subsalicylate can only be labeled for use by adults and children 12 years and older. So the most recent version of the Kaopectate label has doesn't have the pediatric dosing information at all.

The result is that there could be three versions of Kaopectate on store shelves at one time: the older formulation with attapulgite, and two versions of bismuth subsalicylate formulation - one with a dose given for children under 12 and one without the pediatric dose. Although the new formulation has a salicylate warning statement on the label, it could be easily overlooked. So a consumer who doesn't know about the reformulation could unknowingly ingest a salicylate-containing product, or give it to a child, particularly because some of the "New and Improved" Kaopectate bottles on the shelf may have pediatric dosing information on the label.

Other than making patients aware of these multiple formulations and labeling, FDA's article also suggests that pharmacists physically separate the different formulations to minimize the potential for confusing consumers.

The FDA article also suggests using "shelf talkers" or some other visual aid to alert consumers about the change in ingredients, and advising patients not to remove the peel-up label from the back panel, which contains all the Drug Facts. Without this label, important information such as drug warnings, dosing directions, and detailed salicylate warnings could be lost.

Additional Information:

USP Practitioner Reporting News. Kaopectate Reformulated. June 3, 2003
http://www.usp.org/hqi/practitionerPrograms/newsletters/practitionerReportingNews/prn1032003-06-03.html



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