FDA Patient Safety News: Show #62, April 2007

New Breast Cancer Prognostic Test

FDA recently cleared for marketing a new test called the MammaPrint that can predict the odds that an early stage breast cancer will metastasize in five to ten years. Using a biopsy sample taken from the tumor, the test analyzes the activity of 70 genes which affect whether or not an early stage breast cancer will spread. Based on this, it rates the patient as "high risk" or "low risk" for metastases. MammaPrint is intended for women who are under 61 years old with Stage I or II disease who are lymph node-negative and whose tumors are no larger than 5 cm.

MammaPrint's reliability differs a great deal depending on which risk category it places the woman in. When the test designates the woman as "low risk," there is 90% probability that she will not get metastatic disease at 5 years. But when the test designates the woman as "high risk," there is only a 25% chance that she will actually develop distant metastases at 5 years. It is important for women and their physicians to understand this difference, and to keep the test's limitations in mind.

It is also important to keep in mind that the MammaPrint test is not intended to diagnose breast cancer, or to select the type of therapy, or to predict the woman's response to it. It is a prognostic marker only, to be used along with other clinico-pathological factors.

MammaPrint is currently available overseas. The test's developer, the Dutch company Agendia, is exploring ways to make the test available in the U.S.

Additional Information:

FDA Press Release. FDA Clears Breast Cancer Specific Molecular Prognostic Test. February 6, 2007.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108836.htm


Narrower Indications and New Warnings for Ketek

FDA has removed two of the three previously approved indications for the antibiotic Ketek (telithromycin). This drug is no longer indicated for acute bacterial sinusitis and acute bacterial exacerbations of chronic bronchitis. FDA deleted the two indications because the benefits of using the drug in these cases do not outweigh its risks. The one remaining FDA-approved indication is for the treatment of mild to moderate community-acquired pneumonia due to certain specific organisms in patients 18 years and older.

Ketek's new labeling will also contain a boxed warning stating that the drug is contraindicated in patients with myasthenia gravis. Some patients who took Ketek have experienced serious respiratory effects, and some of them have died. Warnings about hepatotoxicity in patients taking Ketek were added in June 2006.

Stronger warnings are also included about the possibility of visual disturbances and loss of consciousness. Because of this, patients on Ketek should avoid potentially hazardous activities such as driving or operating heavy machinery. A new Patient Medication Guide with information about the risks of Ketek and how to take it safely will be provided to patients with each prescription.

Additional Information:

FDA MedWatch Safety Alert. Ketek (telithromycin). February 12, 2007.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm152681.htm


Higher Mortality when Treating Certain Anemias with Erythropoietic Agents

Amgen has notified healthcare professionals that the erythropoietic agent Aranesp (darbepoetin alfa) is not effective in treating cancer patients whose anemia is not associated with the use of chemotherapy. This treatment can also increase mortality in these patients. FDA is cautioning healthcare professionals that these findings also apply to similar products such as Procrit (epoetin alfa)and Epogen (epoetin alfa).

Amgen was studying how well the drug could treat anemia in patients with active malignant disease who were not receiving chemotherapy or radiation therapy as compared with similar patients given a placebo. The study showed that the drug did not reduce RBC transfusions in the patients treated with Aranesp. It also showed a higher mortality rate in patients treated with the drug.

Procrit, Aranesp and Epogen are all approved for treating anemia associated with cancer chemotherapy. They are not approved to treat anemia in patients who are not receiving chemotherapy. FDA warns that using these drugs to treat anemic cancer patients who are not currently on chemotherapy may offer no benefit and could cause serious harm.

Additional Information:

FDA MedWatch Safety Alert. Erythropoiesis Stimulating Agents: Aranesp (darbepoetin alfa), Epogen (epoetin alfa), Procrit (epoetin alfa). March 9, 2007.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm152281.htm


Higher Mortality when Treating Certain Anemias with Erythropoietic Agents

Amgen has notified healthcare professionals that the erythropoietic agent Aranesp (darbepoetin alfa) is not effective in treating cancer patients whose anemia is not associated with the use of chemotherapy. This treatment can also increase mortality in these patients. FDA is cautioning healthcare professionals that these findings also apply to similar products such as Procrit (epoetin alfa)and Epogen (epoetin alfa).

Amgen was studying how well the drug could treat anemia in patients with active malignant disease who were not receiving chemotherapy or radiation therapy as compared with similar patients given a placebo. The study showed that the drug did not reduce RBC transfusions in the patients treated with Aranesp. It also showed a higher mortality rate in patients treated with the drug.

Procrit, Aranesp and Epogen are all approved for treating anemia associated with cancer chemotherapy. They are not approved to treat anemia in patients who are not receiving chemotherapy. FDA warns that using these drugs to treat anemic cancer patients who are not currently on chemotherapy may offer no benefit and could cause serious harm.

Additional Information:

FDA MedWatch Safety Alert. Aranesp (darbepoetin alfa). January 27, 2007.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm150816.htm


Update on Avoiding Gadolinium-Containing Contrast Agents in Patients with Renal Failure

FDA has received reports of 65 more cases of a rare, possibly fatal disease in patients with renal failure who receive a contrast agent containing gadolinium while undergoing certain imaging procedures. The disease, called Nephrogenic Systemic Fibrosis/Nephrogenic Fibrosing Dermopathy (NSF/NFD), is characterized by fibrosis of the skin and internal organs.

These new reports are in addition to cases that were reported on in mid-2006. In the new reports, the affected patients had end-stage kidney failure, and had either Magnetic Resonance Angiography (MRA) or Magnetic Resonance Imaging (MRI) with a gadolinium-based contrast agent. Their NSF/NFD began from 2 days to 18 months after exposure to the contrast agent. Although many of these patients received large amounts of the contrast agent, some received only one dose. In addition, researchers have found gadolinium deposits in the skin of patients who developed NSF/NFD.

There are currently five FDA-approved gadolinium-based contrast agents. Magnevist, MultiHance, Omniscan, OptiMARK, and ProHance. These agents are approved for use during an MRI scan, but not for MRA.

Although NSF/NFD has been reported for only 3 of these 5 agents, FDA believes that there is a potential for NSF/NFD to occur with the use of any of the approved gadolinium-based agents.

Because of this, FDA is recommending that whenever possible, health care professionals choose imaging methods other than MRI or MRA with gadolinium for patients with moderate to end-stage kidney disease. If these patients must receive a gadolinium-based agent, consider prompt dialysis following the MRI or MRA.

Patients should be aware of the signs and symptoms of NSF/NFD and report these to their doctor. They include swelling and tightening of the skin, red or dark skin patches and difficulty flexing or extending the joints.

Finally, FDA is asking health care professionals and patients to report possible cases of NSF/NFD through FDA's MedWatch program.

Additional Information:

FDA Medwatch Safety Alert. Gadolinium-containing Contrast Agents for Magnetic Resonance Imaging (MRI): Omniscan, OptiMARK, Magnevist, ProHance, and MultiHance. December 22, 2006.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm150564.htm


Update on Avoiding Gadolinium-Containing Contrast Agents in Patients with Renal Failure

FDA has received reports of 65 more cases of a rare, possibly fatal disease in patients with renal failure who receive a contrast agent containing gadolinium while undergoing certain imaging procedures. The disease, called Nephrogenic Systemic Fibrosis/Nephrogenic Fibrosing Dermopathy (NSF/NFD), is characterized by fibrosis of the skin and internal organs.

These new reports are in addition to cases that were reported on in mid-2006. In the new reports, the affected patients had end-stage kidney failure, and had either Magnetic Resonance Angiography (MRA) or Magnetic Resonance Imaging (MRI) with a gadolinium-based contrast agent. Their NSF/NFD began from 2 days to 18 months after exposure to the contrast agent. Although many of these patients received large amounts of the contrast agent, some received only one dose. In addition, researchers have found gadolinium deposits in the skin of patients who developed NSF/NFD.

There are currently five FDA-approved gadolinium-based contrast agents. Magnevist, MultiHance, Omniscan, OptiMARK, and ProHance. These agents are approved for use during an MRI scan, but not for MRA.

Although NSF/NFD has been reported for only 3 of these 5 agents, FDA believes that there is a potential for NSF/NFD to occur with the use of any of the approved gadolinium-based agents.

Because of this, FDA is recommending that whenever possible, health care professionals choose imaging methods other than MRI or MRA with gadolinium for patients with moderate to end-stage kidney disease. If these patients must receive a gadolinium-based agent, consider prompt dialysis following the MRI or MRA.

Patients should be aware of the signs and symptoms of NSF/NFD and report these to their doctor. They include swelling and tightening of the skin, red or dark skin patches and difficulty flexing or extending the joints.

Finally, FDA is asking health care professionals and patients to report possible cases of NSF/NFD through FDA's MedWatch program.

Additional Information:

CDC MMWR. Nephrogenic Fibrosing Dermopathy Exposure to Gadolinium Contrasting Agents – St. Louis, Missouri 2002-2006. Vol. 56, No. 7. February 23, 2007.
http://www.cdc.gov/mmwr/PDF/wk/mm5607.pdf


Alert on Custom Ultrasonics Endoscope Washers and Disinfectors

FDA is notifying healthcare professionals that Custom Ultrasonics has agreed to stop making and distributing all of its endoscopic washer/disinfectors because of the company's failure to comply with FDA manufacturing regulations.

When a company does not comply with these regulations, the safety and effectiveness of the product cannot be assured. In this case, the result could be an increase in the risk of transmitting pathogenic agents from patient to patient.

The affected products are the System 83 Plus and the System 83 Plus Mini-flex, and all accessories. Products already in use are not being recalled. There have been no reports to date of patient infections attributed directly to these devices. But because follow-up of hospital-acquired infections is difficult, and because the company has failed to report problems to FDA, infections may have occurred and been unreported.

FDA is recommending that facilities stop using Custom Ultrasonics endoscope washer/disinfectors if alternative automated endoscope reprocessors are immediately available, and if it is feasible to make the switch. Before doing so, be sure that your endoscopes are compatible with the alternative reprocessors, and that the staff is trained in using the alternative device. Verify that the alternative devices are properly maintained and operating correctly according to the labeling.

If, after looking at the feasibility of switching to an alternative reprocesser, you decide to continue using Custom Ultrasonics washer/disinfectors, be sure that these devices have been adequately maintained and that the most current instructions are being followed. Report any concerns or questions to Custom Ultrasonics immediately.

FDA does not recommend manual reprocessing as an alternative to using automated reprocessors, because the risks inherent in manual reprocessing outweigh the benefits.

Additional Information:

FDA MedWatch Safety Alert. Custom Ultrasonics System 83 Plus Washer/Disinfector System 83 Plus Mini-flex Washer/Disinfector. February 7, 2007.
http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/ucm062075.htm


Warning on Using Cough and Cold Medicines in Young Children

The CDC recently warned about the potential hazards of administering cough and cold medications to children and infants under two years old. The article cites over 1500 cases in which children under two were treated in emergency departments for adverse events associated with these drugs. It also described 3 cases where infants died as a result of these medicines.

The instructions on OTC cough and cold medications advise consumers to "consult a doctor" for children under the age of two. But clinical trials that would establish dosing guidelines for this age group do not exist. The article also cites clinical trials indicating that these medicines are no more effective than placebo in reducing coughs and other upper respiratory symptoms in this age group.

Because of the risks of toxicity, lack of scientifically established doses for young children, and limited evidence of effectiveness, the CDC says clinicians should use caution when prescribing cough and cold medications to children under two. In addition, clinicians should always ask caregivers about their use of OTC combination medications, in order to avoid overdose from multiple medications that contain the same ingredient.

Parents and other caregivers should only administer cough and cold medications to children in this age group when following the exact advice of their doctor. Clinicians should be certain that caregivers understand both the importance of administering these medications only as directed and the risk of overdose if they administer additional medications that might contain the same ingredient.

Additional Information:

FDA MedWatch Safety Alert. Cough and Cold Medications in Children Less Than Two Years of Age. January 12, 2007.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm152111.htm


Safe Use of Pneumatic Tourniquet Cuffs

Pneumatic tourniquet systems are used to compress the patient's blood vessels during a surgical procedure, which helps to ensure a bloodless operative field. But their effectiveness can be compromised if the tourniquet cuffs become crinkled, folded or bent. This can cause insufficient or inconsistent pressure, resulting in poor control of blood flow to the affected area.

Here are several precautions you can take to prevent this from happening:

• Be sure to select a cuff that will overlap between 3-6 inches when used on the patient. Too much overlap causes increased pressure and wrinkling of the underlying soft tissues.

• Before applying the cuff to the patient, inspect it for rips or holes, and be sure that the tubing connecting the cuff to the system is not kinked or occluded.

• When applying the cuff, be sure it is smooth because wrinkles or tunneling in the cuff could damage the underlying skin and soft tissue. If the manufacturer's instructions suggest it, use a soft, wrinkle-free padding between the cuff and the skin for added protection.

• If the patient experiences uncontrolled bleeding at the site, increasing the pressure may not be effective if the cuff is not allowing the pressure to be applied properly. Before increasing the pressure, check the cuff to be sure that it is inflated properly, is not damaged, and does not have wrinkles or crinkling.

• If the location or position of the cuff needs to be adjusted, remove the cuff and reapply it. Never pull the cuff up or down while it is on the limb.

Additional Information:

MedSun Newsletter. Safety Tip - Pneumatic Tourniquet Cuffs, with the Tourniquet Systems. Volume 7, Issue 1. January 2007.
http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/TipsandArticlesonDeviceSafety/ucm070189.htm


Dangers of Patient-Applied Local Anesthetic Skin Products

Creams, gels and ointments containing topical anesthetics such as lidocaine, tetracaine, benzocaine and prilocaine can be valuable in relieving or preventing pain. But they can be dangerous when used by patients without medical supervision.

FDA is aware of two instances in which young women applied these preparations before laser hair removal. They wrapped the affected areas in plastic wrap to increase the numbing effect. Both women experienced seizures, became comatose and died. FDA has other reports of serious side effects from these anesthetic skin preparations, including cardiac arrhythmias, coma, and respiratory failure.

If patients are considering medical or cosmetic skin procedures, advise them to consult a healthcare professional about whether a topical anesthetic is needed and, if so, how it can be safely used.

Here are some recommendations for patients to consider:

• First, patients should be advised to use a topical anesthetic approved by FDA. These can be found by searching for its name or active ingredient in FDA's Electronic Orange Book of Approved Drug Products. If it is not there, it may not be approved.

• Patients should use a topical product that contains the lowest concentration of anesthetic drug that will satisfactorily relieve pain. They should apply as little of the product as possible, for the shortest possible time.

• Patients should get instructions from a healthcare professional on how to safely use the product, particularly if there will not be medical supervision during the procedure. They should understand that wrapping the skin or increasing its temperature will increase absorption of the drug into the body and thus increase the likelihood of adverse events. Absorption is also increased if the product is applied to broken or abraded skin.

• Certain patients, including those with respiratory problems, cardiac conditions, or susceptibility to seizures, may be at increased risk of life threatening adverse events if these topical anesthetic agents are used. For these individuals, the safest use is under the direct supervision of health care personnel.

Additional Information:

FDA MedWatch Safety Alert. Topical Anesthetic Drugs for Cosmetic Procedures. February 6, 2007.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm170312.htm


Dangers of Patient-Applied Local Anesthetic Skin Products

Creams, gels and ointments containing topical anesthetics such as lidocaine, tetracaine, benzocaine and prilocaine can be valuable in relieving or preventing pain. But they can be dangerous when used by patients without medical supervision.

FDA is aware of two instances in which young women applied these preparations before laser hair removal. They wrapped the affected areas in plastic wrap to increase the numbing effect. Both women experienced seizures, became comatose and died. FDA has other reports of serious side effects from these anesthetic skin preparations, including cardiac arrhythmias, coma, and respiratory failure.

If patients are considering medical or cosmetic skin procedures, advise them to consult a healthcare professional about whether a topical anesthetic is needed and, if so, how it can be safely used.

Here are some recommendations for patients to consider:

• First, patients should be advised to use a topical anesthetic approved by FDA. These can be found by searching for its name or active ingredient in FDA's Electronic Orange Book of Approved Drug Products. If it is not there, it may not be approved.

• Patients should use a topical product that contains the lowest concentration of anesthetic drug that will satisfactorily relieve pain. They should apply as little of the product as possible, for the shortest possible time.

• Patients should get instructions from a healthcare professional on how to safely use the product, particularly if there will not be medical supervision during the procedure. They should understand that wrapping the skin or increasing its temperature will increase absorption of the drug into the body and thus increase the likelihood of adverse events. Absorption is also increased if the product is applied to broken or abraded skin.

• Certain patients, including those with respiratory problems, cardiac conditions, or susceptibility to seizures, may be at increased risk of life threatening adverse events if these topical anesthetic agents are used. For these individuals, the safest use is under the direct supervision of health care personnel.

Additional Information:

FDA Electronic Orange Book of Approved Drug Products.
http://www.fda.gov/cder/ob/default.htm



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