FDA Patient Safety News: Show #84, March 2009

Serious Skin Reactions in Asian Patients on Phenytoin and Fosphenytoin

FDA is investigating new preliminary data suggesting an increased risk of serious skin reactions from the anti-epileptic drugs phenytoin and fosphenytoin if they are taken by Asian patients who are positive for the human leukocyte antigen allele HLA-B*1502. These reactions include Stevens Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN). Phenytoin is marketed as Dilantin, Phenytek and generics. Fosphenytoin sodium is marketed as Cerebyx and generics.

It is estimated that in parts of China, Taiwan, Thailand, Malaysia, Indonesia and the Philippines, 15 percent or more of the population may carry the HLA-B*-1502 allele. The frequency in South Asia, including India, is somewhat lower, and in Japan and Korea it is under one percent.

It was previously established that another anti-epileptic drug, carbamazepine, increases the risk of these skin reactions in Asian patients with the HLA-B*1502 allele. FDA has recommended screening patients of Asian ancestry for this allele before prescribing carbamazepine and not starting the drug unless the expected benefit clearly outweighs the risk.

In the case of phenytoin and fosphenytoin, the possible risk is still being studied, and there is not enough information at this point to recommend testing for the allele before starting therapy. However, FDA is recommending that physicians avoid using phenytoin as a substitute for carbamazepine in patients who test positive for the HLA-B*1502 allele.

With carbamazepine, over 90 percent of serious skin reactions occur during the first few months of treatment. Patients who have taken the drug for longer than this without having a skin reaction are at low risk for developing one. Likewise, the risk for serious skin reactions with phenytoin seems to be greatest during the first few months of treatment.

Patients on phenytoin, fosphenytoin or carbamazepine should be instructed to contact their physicians immediately if they develop a skin rash and ask whether they should take another dose. At the same time, they should understand the risk of discontinuing their medication without medical consultation.

Additional Information:

FDA MedWatch Safety Alert. Phenytoin (marketed as Dilantin, Phenytek and generics) and Fosphenytoin Sodium (marketed as Cerebyx and generics). November 24, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094919.htm


Higher Mortality for Certain Elderly Patients with Innohep

Celgene is alerting healthcare professionals of an increased mortality risk among certain elderly patients treated with Innohep (tinzaparin sodium injection). Innohep is a low-molecular weight heparin that is used along with warfarin to treat acute symptomatic deep vein thrombosis with or without pulmonary embolism.

Results of a controlled clinical study conducted in Europe suggest that elderly patients with kidney dysfunction may have a greater risk of death when treated with Innohep than comparable patients treated with unfractionated heparin. In a July 2008 letter, Celgene had highlighted this risk for patients who are 90 years and older, but the company has now changed the labeling to indicate that these risks apply to patients with kidney dysfunction who are 70 and older. The company says to consider alternatives to Innohep when treating these patients.

Additional Information:

FDA MedWatch Safety Alert. Innohep (tinzaparin sodium injection). December 31, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm090743.htm


Limitations of Skin Patch Testing for Diagnosing Hypersensitivity Reactions with Abacavir

FDA is cautioning healthcare professionals against using skin patch testing to immunologically confirm suspected cases of hypersensitivity reaction in patients treated with the antiretroviral drug abacavir. Abacavir is sold under the trade name Ziagen and is part of the combination products Epzicom and Trizivir.

Abacavir is associated with serious and potentially fatal hypersensitivity reactions. Patients with a particular HLA allele, HLA-B*5701, have a higher risk of developing these reactions if they are treated with abacavir, and so abacavir is not recommended for these patients. Because of this, a boxed warning recommends that all patients be screened for the HLA-B*5701 allele before starting or restarting abacavir therapy. If a hypersensitivity reaction is suspected in any patient, even those without the allele, the drug should be stopped immediately and permanently, because rechallenging the patient with abacavir could be fatal.

Abacavir hypersensitivity reactions can be difficult to diagnose because they can be confused with adverse events from the patient's other HIV medications, or they may mimic the infections that frequently occur in HIV patients.

Several research reports have described using skin patch testing to confirm suspected cases of abacavir hypersensitivity immunologically. However, data suggest that skin patch testing may miss cases of true hypersensitivity reaction or provide false positive results. FDA points out that the accuracy of skin patch testing is unknown, and that using skin patch testing to confirm cases of abacavir hypersensitivity has not been validated clinically. Given that rechallenging a patient with a suspected hypersensitivity reaction could be fatal, these reactions must continue to be diagnosed clinically.

Additional Information:

FDA MedWatch Safety Alert. Abacavir (marketed as Ziagen) and Abacavir-containing Medications. July 24, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm075124.htm


Preventing Dosing Errors with Alteplase

In a recent report, the Institute for Safe Medication Practices warned about the possibility of prescribing and administering the wrong dose of alteplase when the indication for the drug is not specified.

ISMP described a case of a patient in an interventional radiology department who suffered respiratory arrest from a pulmonary embolism. The physician in charge of the radiology procedure called a code and requested Activase 100 mg IV. The pharmacist who responded to the code called the IV admixture staff and asked for tPA, or tissue plasminogen activator, a synonym for alteplase.

Because the call came from the radiology department, and because the prescribed dose and the intended use were not communicated, the pharmacy staff did not realize that the drug was intended to treat a pulmonary embolus. Instead, they assumed that the alteplase was intended to restore catheter function, so instead of the 100 mg dose that had been prescribed, they dispensed 2 mg of alteplase.

The physician running the code assumed the syringe he received contained the correct dose and administered it, which gave the patient a 50-fold underdose. The patient died, although it's not clear what impact, if any, the medication error had on his death.

In analyzing the problem, ISMP points out that alteplase is used for a number of indications at a number of different dosages This makes it all the more important for persons who prescribe, dispense and administer alteplase to understand why it is being used in each case and to match the indication with the dose.

In non-urgent cases, ISMP recommends considering using disease-specific protocols and order forms. In an emergency, if you cannot use a disease specific order set, specify the purpose of the drug with the order, as well as the dose, the route of administration, and directions. ISMP says that pharmacists should not dispense the medication without this information.

Additional Information:

ISMP Medication Safety Alert! Communicate alteplase dose and indication. Volume 13, Issue 17. August 28, 2008.
http://www.ismp.org/newsletters/acutecare/articles/20080828-1.asp


Potentially Fatal Salmonella Infections from Pet Turtles

Turtles may look like cute pets, but it is estimated that they are responsible for over 70,000 cases of Salmonella infections every year in this country.

Some of these infections can be serious or even fatal. In one case, a four week-old infant died of a Salmonella infection that was traced to a pet turtle in the home. In another case, two teenage girls became very ill after they swam in an unchlorinated family pool where pet turtles had been allowed to swim.

Children, people with compromised immune systems, the elderly and pregnant women are especially susceptible to Salmonella infections. In addition to their susceptibility from an immune standpoint, young children are at high risk because they are likely to handle the turtles, and then without washing their hands, handle food or touch their mouths, which increases the possibility of ingesting the bacteria.

It does not require touching the turtle to be exposed to the Salmonella, because the turtle sporadically sheds the bacteria into its water and housing. So people cleaning the turtle’s bowl can become infected, too. Salmonella is also carried by other reptiles and amphibians.

FDA’s primary recommendation is to not buy small turtles as pets or gifts. For those who already own a turtle, reptile, or amphibian, here are some basic rules to help prevent illness:

• If your family is expecting a child, remove the animal from the home before the baby arrives.

• Keep turtles out of homes with children under five, the elderly, or those with weakened immune systems.

• Always wash hands thoroughly with soap and water after touching the turtle or any object it has come in contact with.

• Do not clean turtle tanks or other supplies in the kitchen sink, and use bleach to disinfect the area where the turtle tank is cleaned.

• Be aware that children can contract Salmonella infections from turtles in petting zoos, parks, classrooms and daycare facilities.

• If you do have a turtle, watch for symptoms of Salmonella infection, such as diarrhea, abdominal pain, nausea, vomiting, fever and headache, and call a doctor if these occur.

Additional Information:

FDA Press Release. FDA Re-Emphasizes Warnings to Consumers on Risks of Pet Turtles. April 6, 2007.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108885.htm


Potentially Fatal Salmonella Infections from Pet Turtles

Turtles may look like cute pets, but it is estimated that they are responsible for over 70,000 cases of Salmonella infections every year in this country.

Some of these infections can be serious or even fatal. In one case, a four week-old infant died of a Salmonella infection that was traced to a pet turtle in the home. In another case, two teenage girls became very ill after they swam in an unchlorinated family pool where pet turtles had been allowed to swim.

Children, people with compromised immune systems, the elderly and pregnant women are especially susceptible to Salmonella infections. In addition to their susceptibility from an immune standpoint, young children are at high risk because they are likely to handle the turtles, and then without washing their hands, handle food or touch their mouths, which increases the possibility of ingesting the bacteria.

It does not require touching the turtle to be exposed to the Salmonella, because the turtle sporadically sheds the bacteria into its water and housing. So people cleaning the turtle’s bowl can become infected, too. Salmonella is also carried by other reptiles and amphibians.

FDA’s primary recommendation is to not buy small turtles as pets or gifts. For those who already own a turtle, reptile, or amphibian, here are some basic rules to help prevent illness:

• If your family is expecting a child, remove the animal from the home before the baby arrives.

• Keep turtles out of homes with children under five, the elderly, or those with weakened immune systems.

• Always wash hands thoroughly with soap and water after touching the turtle or any object it has come in contact with.

• Do not clean turtle tanks or other supplies in the kitchen sink, and use bleach to disinfect the area where the turtle tank is cleaned.

• Be aware that children can contract Salmonella infections from turtles in petting zoos, parks, classrooms and daycare facilities.

• If you do have a turtle, watch for symptoms of Salmonella infection, such as diarrhea, abdominal pain, nausea, vomiting, fever and headache, and call a doctor if these occur.

Additional Information:

FDA Center for Veterinary Medicine. Pet Turtles: A Common Source of Salmonella (brochure). October 2008.
http://www.fda.gov/downloads/AnimalVeterinary/ResourcesforYou/AnimalHealthLiteracy/UCM117790.pdf


Potentially Fatal Salmonella Infections from Pet Turtles

Turtles may look like cute pets, but it is estimated that they are responsible for over 70,000 cases of Salmonella infections every year in this country.

Some of these infections can be serious or even fatal. In one case, a four week-old infant died of a Salmonella infection that was traced to a pet turtle in the home. In another case, two teenage girls became very ill after they swam in an unchlorinated family pool where pet turtles had been allowed to swim.

Children, people with compromised immune systems, the elderly and pregnant women are especially susceptible to Salmonella infections. In addition to their susceptibility from an immune standpoint, young children are at high risk because they are likely to handle the turtles, and then without washing their hands, handle food or touch their mouths, which increases the possibility of ingesting the bacteria.

It does not require touching the turtle to be exposed to the Salmonella, because the turtle sporadically sheds the bacteria into its water and housing. So people cleaning the turtle’s bowl can become infected, too. Salmonella is also carried by other reptiles and amphibians.

FDA’s primary recommendation is to not buy small turtles as pets or gifts. For those who already own a turtle, reptile, or amphibian, here are some basic rules to help prevent illness:

• If your family is expecting a child, remove the animal from the home before the baby arrives.

• Keep turtles out of homes with children under five, the elderly, or those with weakened immune systems.

• Always wash hands thoroughly with soap and water after touching the turtle or any object it has come in contact with.

• Do not clean turtle tanks or other supplies in the kitchen sink, and use bleach to disinfect the area where the turtle tank is cleaned.

• Be aware that children can contract Salmonella infections from turtles in petting zoos, parks, classrooms and daycare facilities.

• If you do have a turtle, watch for symptoms of Salmonella infection, such as diarrhea, abdominal pain, nausea, vomiting, fever and headache, and call a doctor if these occur.

Additional Information:

FDA Center for Veterinary Medicine. Pet Turtles: A Common Source of Salmonella (poster). October 2008.
http://www.fda.gov/downloads/AnimalVeterinary/ResourcesforYou/AnimalHealthLiteracy/UCM117797.pdf


Potentially Fatal Salmonella Infections from Pet Turtles

Turtles may look like cute pets, but it is estimated that they are responsible for over 70,000 cases of Salmonella infections every year in this country.

Some of these infections can be serious or even fatal. In one case, a four week-old infant died of a Salmonella infection that was traced to a pet turtle in the home. In another case, two teenage girls became very ill after they swam in an unchlorinated family pool where pet turtles had been allowed to swim.

Children, people with compromised immune systems, the elderly and pregnant women are especially susceptible to Salmonella infections. In addition to their susceptibility from an immune standpoint, young children are at high risk because they are likely to handle the turtles, and then without washing their hands, handle food or touch their mouths, which increases the possibility of ingesting the bacteria.

It does not require touching the turtle to be exposed to the Salmonella, because the turtle sporadically sheds the bacteria into its water and housing. So people cleaning the turtle’s bowl can become infected, too. Salmonella is also carried by other reptiles and amphibians.

FDA’s primary recommendation is to not buy small turtles as pets or gifts. For those who already own a turtle, reptile, or amphibian, here are some basic rules to help prevent illness:

• If your family is expecting a child, remove the animal from the home before the baby arrives.

• Keep turtles out of homes with children under five, the elderly, or those with weakened immune systems.

• Always wash hands thoroughly with soap and water after touching the turtle or any object it has come in contact with.

• Do not clean turtle tanks or other supplies in the kitchen sink, and use bleach to disinfect the area where the turtle tank is cleaned.

• Be aware that children can contract Salmonella infections from turtles in petting zoos, parks, classrooms and daycare facilities.

• If you do have a turtle, watch for symptoms of Salmonella infection, such as diarrhea, abdominal pain, nausea, vomiting, fever and headache, and call a doctor if these occur.

Additional Information:

FDA Center for Veterinary Medicine. Pet Turtles: A Common Source of Salmonella (book cover art). October 2008.
http://www.fda.gov/downloads/AnimalVeterinary/ResourcesforYou/AnimalHealthLiteracy/UCM117802.pdf


Caution Using Topical Anesthetics Prior to Mammography

FDA is alerting patients and healthcare professionals about the potential danger of using topical anesthetics to relieve pain before having mammography or other medical procedures. The concern is that patients may apply these drugs improperly, which could cause excessive absorption of the drug. This could result in seizures, cardiac arrhythmias, respiratory failure, coma, and even death.

In a recent study (published in the journal “Radiology”) of the use of topical anesthetics to relieve pain during mammography, women spread lidocaine gel over a wide area of skin and covered it with plastic wrap before the getting the mammogram. No serious side effects from the drug were reported, but the study was too small to detect rare but serious events, like toxicity from systemic absorption.

FDA is concerned that as more women become aware of this study through the Internet or word-of-mouth, they may start using topical anesthetics without medical advice before getting a mammogram, and this could set the stage for at least a few tragic events.

FDA is aware of two cases in which the use of topical anesthetics led to fatal outcomes. In these cases, young women applied topical anesthetics before having laser hair removal. They experienced seizures, became comatose and died. They apparently applied a large amount of the drug to a large area of skin, then covered it with plastic wrap to increase the numbing effect.

Before using a topical anesthetic for a mammogram or other procedures, women should talk to their doctors about whether it is advisable to do this. If the doctor recommends using a topical anesthetic, use a product containing the lowest concentration of the drug, and apply it sparingly. To decrease the chance that the drug may be absorbed into the body, do not apply it to broken or irritated skin, do not wrap the skin, and do not apply heat to the area.

Additional Information:

FDA MedWatch Safety Alert. Topical Anesthetics. January 16, 2009.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm092082.htm


Caution Using Topical Anesthetics Prior to Mammography

FDA is alerting patients and healthcare professionals about the potential danger of using topical anesthetics to relieve pain before having mammography or other medical procedures. The concern is that patients may apply these drugs improperly, which could cause excessive absorption of the drug. This could result in seizures, cardiac arrhythmias, respiratory failure, coma, and even death.

In a recent study (published in the journal “Radiology”) of the use of topical anesthetics to relieve pain during mammography, women spread lidocaine gel over a wide area of skin and covered it with plastic wrap before the getting the mammogram. No serious side effects from the drug were reported, but the study was too small to detect rare but serious events, like toxicity from systemic absorption.

FDA is concerned that as more women become aware of this study through the Internet or word-of-mouth, they may start using topical anesthetics without medical advice before getting a mammogram, and this could set the stage for at least a few tragic events.

FDA is aware of two cases in which the use of topical anesthetics led to fatal outcomes. In these cases, young women applied topical anesthetics before having laser hair removal. They experienced seizures, became comatose and died. They apparently applied a large amount of the drug to a large area of skin, then covered it with plastic wrap to increase the numbing effect.

Before using a topical anesthetic for a mammogram or other procedures, women should talk to their doctors about whether it is advisable to do this. If the doctor recommends using a topical anesthetic, use a product containing the lowest concentration of the drug, and apply it sparingly. To decrease the chance that the drug may be absorbed into the body, do not apply it to broken or irritated skin, do not wrap the skin, and do not apply heat to the area.

Additional Information:

Lambertz CK, Johnson CJ, Montgomery PG, Maxwell, JR. Premedication to Reduce Discomfort during Screening Mammography. Radiology. Volume 248, Number 3. September 2008.
http://radiology.rsnajnls.org/cgi/content/abstract/2482071490v1



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