FDA Patient Safety News: Show #61, March 2007

New Cooling Device to Treat Infants with HIE

FDA recently approved the Olympic Cool-Cap, a new device to treat infants with hypoxic-ischemic encephalopathy(HIE), which can cause brain injury and severe neurological deficits. Up to 20 percent of infants with this condition die, and another 25 percent suffer permanent disability. Until the introduction of the new device, the only treatment has been supportive care.

The Cool-Cap is designed to reduce brain damage by selectively cooling the infant's head during the first few days of life. This is achieved by delivering a steady flow of water through a cap placed over the infant's head.

The Cool-Cap was found safe and effective in a study of 234 infants with moderate to severe HIE. At 18 months of age, there were fewer deaths and severe neurological deficits in the cooled group compared with the control group. The device should not be used in infants with major intracranial hemorrhage, an imperforate anus, or a birth weight of less than 1,800 g.

Additional Information:

FDA Press Release. FDA Approves Novel Device That Prevents or Reduces Brain Damage in Infants. December 20, 2006.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108813.htm


Thrombosis Associated with Coronary Drug-Eluting Stents

In December 2006, FDA convened an advisory panel to evaluate what is known about the risk of thrombosis in patients with drug-eluting stents. These stents, the Cypher and Taxus, were approved by FDA because they can reduce the incidence of vessel restenosis when compared with bare metal stents. But information collected after they were marketed showed that both of them are associated with an increased risk of thrombosis after one year compared with bare metal stents.

This presents a benefit vs. risk situation for the healthcare provider and the patient. The device can reduce restenosis rates and thereby avoid subsequent surgery, but it can also increase the risk of serious clotting. The risk is small (from less than 1 percent to about 5 percent) but when a thrombus occurs it can lead to sudden death or acute MI.

When the panel looked at the risk of thrombosis in patients with these stents, they found that this risk varies depending on how the device is used. When the stents were used in clinically stable patients with lesions less than 28-30 mm (i.e., the criteria specified in the product labeling), the benefits of the device in reducing restenosis could outweigh the thrombosis risk. But when the stents were used "off label" (i.e., in patients with more complex lesions or various co-existing conditions) the risk of thrombosis was higher.

The panel emphasized the importance of giving these patients antiplatelet medication after the surgery to reduce the risk of clotting. The panel also noted that current guidelines suggest giving these patients the antiplatelet therapy for 12 months after surgery, provided the patient is not at high risk of bleeding.

In addition, the panel recommended that larger, longer studies be done to determine how long the risk of thrombosis persists after surgery and how long antiplatelet therapy needs to be continued. Until these studies are completed, there are a few patient management issues that clinicians might want to consider.

First, there is the finding that the risk of thrombosis is higher when the device is used "off-label”. Second, clinicians should understand importance of keeping patients on antiplatelet therapy for a long enough time, and educating them not to discontinue this therapy without medical consultation. Patients who cannot comply with long-term antiplatelet therapy may not be good candidates for a drug eluting stent. The same holds true for patients who have planned surgical procedures that would require discontinuing this therapy.

Additional Information:

Update to FDA Statement on Coronary Drug-Eluting Stents. January 4, 2007.
http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/UCM062120


Serious Infection in Lupus Patients Treated with Rituxan

FDA is alerting health care professionals and patients about new reports of a serious viral infection in patients with systemic lupus erythematosus who were treated with Rituxan (rituximab). Rituxan is an immunosuppressant drug that is approved to treat certain patients with rheumatoid arthritis and non-Hodgkin's lymphoma. It is not approved to treat lupus.

The FDA advisory says that two patients with lupus died after being treated with Rituxan. These patients developed a life-threatening viral infection of the brain called progressive multifocal leuko-encephalopathy (PML). PML is caused by reactivation of the JC virus. There are no known treatments for PML and it is usually fatal. PML has also occurred in patients with lymphoid malignancies who have been treated with Rituxan.

FDA is working with Genentech, the manufacturer of Rituxan, to get more information about the occurrence of PML in patients treated with the drug and to strengthen the warnings for this product. Here is what FDA's advisory recommends:

• Physicians who are thinking about treating a patient with Rituxan for any condition should tell their patients about the chance of PML because there is no effective treatment for the disease.

• Healthcare professionals should be on the alert for the development of PML in patients being treated with the drug.

• Patients on Rituxan should contact their physicians if they experience any new neurological signs or symptoms such as confusion, dizziness, loss of balance, difficulty talking or walking and vision problems. These could be warning signs of PML, but they could also be associated with the underlying disease for which the drug was prescribed.

• Finally, healthcare providers and patients should report suspected PML or other serious adverse events following Rituxan therapy through FDA's MedWatch program.

Additional Information:

FDA Medwatch Safety Alert. Rituxan (rituximab). December 18, 2006.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm150747.htm


Serious Infection in Lupus Patients Treated with Rituxan

FDA is alerting health care professionals and patients about new reports of a serious viral infection in patients with systemic lupus erythematosus who were treated with Rituxan (rituximab). Rituxan is an immunosuppressant drug that is approved to treat certain patients with rheumatoid arthritis and non-Hodgkin's lymphoma. It is not approved to treat lupus.

The FDA advisory says that two patients with lupus died after being treated with Rituxan. These patients developed a life-threatening viral infection of the brain called progressive multifocal leuko-encephalopathy (PML). PML is caused by reactivation of the JC virus. There are no known treatments for PML and it is usually fatal. PML has also occurred in patients with lymphoid malignancies who have been treated with Rituxan.

FDA is working with Genentech, the manufacturer of Rituxan, to get more information about the occurrence of PML in patients treated with the drug and to strengthen the warnings for this product. Here is what FDA's advisory recommends:

• Physicians who are thinking about treating a patient with Rituxan for any condition should tell their patients about the chance of PML because there is no effective treatment for the disease.

• Healthcare professionals should be on the alert for the development of PML in patients being treated with the drug.

• Patients on Rituxan should contact their physicians if they experience any new neurological signs or symptoms such as confusion, dizziness, loss of balance, difficulty talking or walking and vision problems. These could be warning signs of PML, but they could also be associated with the underlying disease for which the drug was prescribed.

• Finally, healthcare providers and patients should report suspected PML or other serious adverse events following Rituxan therapy through FDA's MedWatch program.

Additional Information:

Medwatch: The FDA Safety Information and Adverse Event Reporting Program. Reporting Adverse Experiences to FDA.
http://www.fda.gov/medwatch/how.htm


Expanded Recall/Market Withdrawal of Hernia Repair Patch

Davol, Inc. is expanding its earlier recall of the Composix Kugel Patch, which is used to repair ventral hernias that can appear at the site of a prior surgical incision.

The recalled patches have a "memory recoil ring" that allows the patch to be folded for insertion and then once in place, to spring open and lay flat. The problem is that this ring can break, and if that happens, it can cause a bowel perforation or chronic intestinal fistula.

Davol is now notifying health care professionals about an expanded recall and market withdrawal of additional patches that have a similar design. These actions affect Large Oval and Large Circle patches that have this design. Health care providers who have patches from the recalled lots should stop using them immediately.

Here's what the company recommends for managing patients who have already received one of the recalled devices:

• First, identify these patients. Advise them about the recall and tell them to seek attention immediately if they experience symptoms that could be associated with ring breakage such as unexplained or persistent abdominal pain, fever, tenderness at the implant site or other unusual symptoms.

• Examine symptomatic patients for conditions that could be associated with ring breakage. These include bowel obstruction, perforation or fistula, abdominal wall pain or infection, palpable abdominal wall mass, or migration or movement of the ring.

• Evaluate the patient's condition based on clinical signs and symptoms and clinical judgment.

• And finally, report any problems to the company.

Note that Davol has redesigned this product to correct the problem. These newer patches are not being recalled. They are identifiable by a label that says "redesigned for improved ring integrity."

Additional Information:

FDA MedWatch Safety Alert. Davol/Bard Composix Kugel Large Sized Patch, Recall and Market Withdrawal. January 12, 2007.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm152454.htm


Precautions in Using Vapotherm Humidifier

The Vapotherm 2000i Respiratory Gas Humidifier, which had previously been recalled because of potential bacterial contamination, has now been re-introduced to the market. The company has taken steps to correct the problem, but FDA is cautioning healthcare facilities to take certain precautions before using the re-introduced device.

The Vapotherm device uses a nasal cannula to deliver moisture and warm breathing gases to the patient. When the device was recalled, FDA noted that certain patients, including premature neonates and the immuno-compromised, would be at particularly high risk for infection if they were exposed to breathing gases from a contaminated device.

If using the re-introduced Vapotherm 2000i, here are the precautionary steps to take:

• Be sure that the base unit has been disinfected by Vapotherm under the recall's corrective plan. Do not use the unit if this has not been done. Send it back to the company for disinfection.

• Discard all used Vapor Transfer Cartridges, all used disinfection kit components, and any disinfection kit that has been opened.

• If you have unopened Vapor Transfer Cartridges with product codes VT01-A and VT01-B, contact the distributor and exchange them for new ones with product codes VT01-AS and VT01-BS.

• Get the latest users manual from the company, and closely follow the revised instructions, particularly three important precautions:

- Each new Vapor Transfer Cartridge should be used only on a single patient and must be discarded after 30 days of use.

- Each disinfection kit is for a single use, and must be discarded after it is used.

- Only sterile water should be used in operating the device.

Additional Information:

FDA Public Health Notification. Precautions In Using the Reintroduced Vapotherm 2000i [Respiratory Gas Humidifier] System. February 1, 2007.
http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/UCM062083


New Safety Information on Trasylol

Based on additional data on adverse events, Bayer Pharmaceuticals has now revised the prescribing information for Trasylol (aprotinin). Trasylol is used to prevent perioperative blood loss in patients undergoing CABG surgery.

The labeling now warns that Trasylol increases the risk of renal dysfunction and may increase the need for perioperative dialysis. It also warns about the possibility of anaphylactic reactions.

Trasylol is now contraindicated in patients with known or suspected exposure to the drug during the past 12 months, since this increases the probability of an anaphylactic reaction. The new labeling states that Trasylol is only indicated for patients who are at increased risk for blood loss and blood transfusion during the surgical procedure, and it should be administered only in the operative setting.

Additional Information:

FDA MedWatch Safety Alert. Trasylol (aprotinin). December 15, 2006.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm150765.htm


New Safety Information on Trasylol

Based on additional data on adverse events, Bayer Pharmaceuticals has now revised the prescribing information for Trasylol (aprotinin). Trasylol is used to prevent perioperative blood loss in patients undergoing CABG surgery.

The labeling now warns that Trasylol increases the risk of renal dysfunction and may increase the need for perioperative dialysis. It also warns about the possibility of anaphylactic reactions.

Trasylol is now contraindicated in patients with known or suspected exposure to the drug during the past 12 months, since this increases the probability of an anaphylactic reaction. The new labeling states that Trasylol is only indicated for patients who are at increased risk for blood loss and blood transfusion during the surgical procedure, and it should be administered only in the operative setting.

Additional Information:

Renal and Cardiovascular Toxicities with Trasylol. FDA Patient Safety News Show 51. May 2006.
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/psn/transcript.cfm?show=51#7


Possible Dose-Counter Errors with the Asmanex Twisthaler

The Institute for Safe Medication Practices has alerted health care professionals about a potential problem with Asmanex Twisthalers. Each Twisthaler contains multiple metered doses of mometasone furoate, a corticosteroid inhalation powder used to treat asthma. ISMP notes that under certain circumstances, the dose counter of an empty Asmanex Twisthaler could indicate that the product still contained medication. This might cause patients to try to administer the drug from an empty container, and thus not receive a needed dose of medication.

To prepare a dose, the patient twists the white cap counter-clockwise and removes it while holding the inhaler upright. This loads a single dose, ready for inhalation, and it also decreases the dosage counter by one. After the dose is inhaled, the patient replaces the cap and turns it clockwise until it clicks, indicating that the device is ready for the next dose to be loaded. When the dose counter reaches "00," the Twisthaler locks shut to prevent the patient from using an empty device.

The problem can occur if the patient twists the cap forcefully after the dosage counter reaches "00." This could reset the counter to show some remaining doses, even though the device could not deliver them.

Before prescribing, dispensing or administering this product, show the patient the dosage counter window, found under the indented arrow on the white part of the cylinder. Remind patients to refill the prescription when the dosage counter reaches "10" and to discard the Twisthaler when the dosage counter reaches "00”. Also, instruct patients not to keep the product more than 45 days after the pouch has been opened, regardless of the remaining doses.

Additional Information:

ISMP Medication Safety Alert! Safety Briefs – Dose Counter May Not Work. November 16, 2006.
http://www.ismp.org/Newsletters/acutecare/articles/20061116_3.asp


Possible Dose-Counter Errors with the Asmanex Twisthaler

The Institute for Safe Medication Practices has alerted health care professionals about a potential problem with Asmanex Twisthalers. Each Twisthaler contains multiple metered doses of mometasone furoate, a corticosteroid inhalation powder used to treat asthma. ISMP notes that under certain circumstances, the dose counter of an empty Asmanex Twisthaler could indicate that the product still contained medication. This might cause patients to try to administer the drug from an empty container, and thus not receive a needed dose of medication.

To prepare a dose, the patient twists the white cap counter-clockwise and removes it while holding the inhaler upright. This loads a single dose, ready for inhalation, and it also decreases the dosage counter by one. After the dose is inhaled, the patient replaces the cap and turns it clockwise until it clicks, indicating that the device is ready for the next dose to be loaded. When the dose counter reaches "00," the Twisthaler locks shut to prevent the patient from using an empty device.

The problem can occur if the patient twists the cap forcefully after the dosage counter reaches "00." This could reset the counter to show some remaining doses, even though the device could not deliver them.

Before prescribing, dispensing or administering this product, show the patient the dosage counter window, found under the indented arrow on the white part of the cylinder. Remind patients to refill the prescription when the dosage counter reaches "10" and to discard the Twisthaler when the dosage counter reaches "00”. Also, instruct patients not to keep the product more than 45 days after the pouch has been opened, regardless of the remaining doses.

Additional Information:

Asmanex Website. How to Use Asmanex Tutorial.
http://www.asmanex.com/asmanex/application?namespace=main&origin=all_nav_left.jsp&event=content_display&event_input=how_to_use_asmanex_tutorial&catego


Danger in Products Containing Quinine

FDA has told manufacturers to stop marketing unapproved drug products containing quinine because of serious safety concerns. There are many of these products presently on the market. While quinine has traditionally been used as a treatment for malaria, many patients use these products to treat leg cramps and similar conditions, a use which is not approved by FDA.

FDA has received 665 reports of serious adverse events associated with quinine use since 1969, including 93 deaths. Among the side effects of quinine are cardiac arrhythmias, thrombocytopenia, and severe hypersensitivity reactions.

Because of these serious side effects, and because the toxic dose for quinine is only slightly higher than the therapeutic dose, patients should be warned against treating their leg cramps with quinine products.

At the present time, Qualaquin, manufactured by Mutual Pharmaceutical Company, is the only quinine product approved by the FDA. Qualaquin is indicated for the treatment of malaria, and its labeling specifically warns that the product is not indicated for treating leg cramps.

Additional Information:

FDA Medwatch Safety Alert. Quinine products. December 12, 2006.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm150746.htm


New Cooling Device to Treat Infants with HIE

FDA recently approved the Olympic Cool-Cap, a new device to treat infants with hypoxic-ischemic encephalopathy(HIE), which can cause brain injury and severe neurological deficits. Up to 20 percent of infants with this condition die, and another 25 percent suffer permanent disability. Until the introduction of the new device, the only treatment has been supportive care.

The Cool-Cap is designed to reduce brain damage by selectively cooling the infant's head during the first few days of life. This is achieved by delivering a steady flow of water through a cap placed over the infant's head.

The Cool-Cap was found safe and effective in a study of 234 infants with moderate to severe HIE. At 18 months of age, there were fewer deaths and severe neurological deficits in the cooled group compared with the control group. The device should not be used in infants with major intracranial hemorrhage, an imperforate anus, or a birth weight of less than 1,800 g.

Additional Information:

FDA Pre-Market Approval Information. Olympic Cool-Cap® -P040025. December 20, 2006.
http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2007/ucm076538.htm


Precautions in Using Vapotherm Humidifier

The Vapotherm 2000i Respiratory Gas Humidifier, which had previously been recalled because of potential bacterial contamination, has now been re-introduced to the market. The company has taken steps to correct the problem, but FDA is cautioning healthcare facilities to take certain precautions before using the re-introduced device.

The Vapotherm device uses a nasal cannula to deliver moisture and warm breathing gases to the patient. When the device was recalled, FDA noted that certain patients, including premature neonates and the immuno-compromised, would be at particularly high risk for infection if they were exposed to breathing gases from a contaminated device.

If using the re-introduced Vapotherm 2000i, here are the precautionary steps to take:

• Be sure that the base unit has been disinfected by Vapotherm under the recall's corrective plan. Do not use the unit if this has not been done. Send it back to the company for disinfection.

• Discard all used Vapor Transfer Cartridges, all used disinfection kit components, and any disinfection kit that has been opened.

• If you have unopened Vapor Transfer Cartridges with product codes VT01-A and VT01-B, contact the distributor and exchange them for new ones with product codes VT01-AS and VT01-BS.

• Get the latest users manual from the company, and closely follow the revised instructions, particularly three important precautions:

- Each new Vapor Transfer Cartridge should be used only on a single patient and must be discarded after 30 days of use.

- Each disinfection kit is for a single use, and must be discarded after it is used.

- Only sterile water should be used in operating the device.

Additional Information:

CDC MMWR Weekly. Update: Ralstonia Species Contamination Associated with Vapotherm® 2000i Respiratory Gas Humidifier Systems --- United States, 2005--2006. Volume 56, Number 8. March 2, 2007.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5608a6.htm?s_cid=mm5608a6_e



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