FDA Patient Safety News: Show #81, November 2008

Serious Fungal Infections with Humira, Cimzia, Enbrel and Remicade

The manufacturers of Humira (adalimumab), Cimzia (certolizumab pegol), Enbrel (etanercept), and Remicade (infliximab) must strengthen warnings about the risk of developing opportunistic fungal infections from these drugs. These infections have been fatal in some patients.

Humira, Cimzia, Enbrel, and Remicade are tumor necrosis factor alpha blockers (TNF blocker) which suppress the immune system. These drugs are approved to treat one or more of several diseases, including juvenile idiopathic arthritis, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, Crohn's disease, and ankylosing spondylitis.

The labeling for these drugs already includes warnings about the risk of serious infections, including fungal infections. But based on reports reviewed by FDA, cases of histoplasmosis and other invasive fungal infections have not been recognized consistently, and that has delayed antifungal treatment and led to death in some patients.

Healthcare providers should be alert to the risk of invasive fungal infections in patients being treated with TNF blockers, especially those who live or have traveled in areas where mycoses are endemic (e.g., the Ohio River and Mississippi River Valleys).

Patients who develop a fungal infection should stop TNF blocker therapy. They may be able to restart treatment after recovering from the infection, and after the benefits and risks of further treatment are evaluated. This evaluation is especially important for patients who live in areas where mycoses are commonly found.

Additional Information:

FDA MedWatch Safety Alert. Tumor necrosis factor-alpha blockers (TNF blockers), Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab), and Remicade (infliximab). September 4, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm163195.htm


Serious Injection Site Reactions with Vivitrol

FDA is alerting healthcare professionals about the risk of serious reactions at the injection site among patients treated with Vivitrol (naltrexone). Vivitrol is administered intramuscularly to treat alcohol dependence.

FDA has received nearly 200 reports of injection site reactions, including cellulitis, induration, hematoma, abscess, sterile abscess and necrosis. Some patients needed surgical intervention. The risk may be increased if the drug is injected subcutaneously or accidentally into fatty tissue.

Practitioners using Vivitrol should use only the specially designed needle that comes with the drug, and take care not to inject the material intravenously, subcutaneously, or into fatty tissue. The special needle may not be long enough to reach muscle tissue in patients with significant gluteal fat. Healthcare providers should consider alternative treatment in these cases.

Patients who develop pain, swelling, bruising, itching or redness that does not improve within two weeks should be instructed to report this, and should be referred to a surgeon.

Additional Information:

FDA MedWatch Safety Alert. Vivitrol (naltrexone). August 12, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm106211.htm


Updated Warning on Byetta

In October 2007, FDA warned healthcare professionals about reports of acute pancreatitis in patients taking the antidiabetic drug Byetta (exenatide). Since then, FDA has received reports of six cases of hemorrhagic or necrotizing pancreatitis in patients taking Byetta. Two were fatal.

Byetta and other suspect drugs should be promptly discontinued if pancreatitis is suspected. There are no known patient characteristics that can determine whether a case of pancreatitis associated with Byetta will develop into the hemorrhagic or necrotizing forms. If pancreatitis is confirmed, it should be treated without delay and the patient should be carefully monitored until recovery. Byetta should not be restarted. Physicians should consider antidiabetic therapies other than Byetta in patients who have a history of pancreatitis.

Additional Information:

FDA MedWatch Safety Alert. Byetta (exenatide). August 18, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm150839.htm


Importance of Influenza Vaccination for Health Care Personnel

As the flu season approaches, FDA is urging healthcare facilities to ensure that influenza vaccination programs are available for their personnel. Vaccinating healthcare workers will decrease the likelihood that they will contract influenza, and also decrease the chance that they will infect others. This is especially important because these personnel often provide care to patients at high risk of serious and even fatal complications if they contract influenza. Of course another benefit of vaccinating staff is that it also protects their families from getting the disease.

Persons who should be immunized include physicians, nursing staff, pharmacists, technicians, emergency personnel, dental personnel, and students. The list also includes those who are not directly involved in patient care, such as clerical, dietary, housekeeping, and security staff.

CDC estimates that only 40% of health care workers get the flu vaccine each year. Yet studies have shown that low vaccination rates among health care personnel contribute to influenza outbreaks in healthcare facilities, and this needlessly puts patients at risk. It has also been shown that there is a lower incidence of nosocomial influenza cases in those facilities where staff vaccination rates are higher.

For example, in one study, influenza cases and immunization records at a single hospital were followed for 12 years. Over that time, staff vaccination coverage increased from 4 percent to 67 percent, while influenza cases among the staff decreased from 42 percent to 9 percent. At the same time, nosocomial influenza cases among hospitalized patients decreased from 32 percent to zero.

So educate staff about the importance of getting a flu shot, and try to ensure that vaccination programs are available for them. Fall is the best time to be immunized, but getting the vaccine in the winter months is also recommended.

Additional Information:

CDC. Health Care Personnel Initiative to Improve Influenza Vaccination Toolkit. September 2008.
http://www.cdc.gov/h1n1flu/nivw/toolkit.htm


Importance of Influenza Vaccination for Health Care Personnel

As the flu season approaches, FDA is urging healthcare facilities to ensure that influenza vaccination programs are available for their personnel. Vaccinating healthcare workers will decrease the likelihood that they will contract influenza, and also decrease the chance that they will infect others. This is especially important because these personnel often provide care to patients at high risk of serious and even fatal complications if they contract influenza. Of course another benefit of vaccinating staff is that it also protects their families from getting the disease.

Persons who should be immunized include physicians, nursing staff, pharmacists, technicians, emergency personnel, dental personnel, and students. The list also includes those who are not directly involved in patient care, such as clerical, dietary, housekeeping, and security staff.

CDC estimates that only 40% of health care workers get the flu vaccine each year. Yet studies have shown that low vaccination rates among health care personnel contribute to influenza outbreaks in healthcare facilities, and this needlessly puts patients at risk. It has also been shown that there is a lower incidence of nosocomial influenza cases in those facilities where staff vaccination rates are higher.

For example, in one study, influenza cases and immunization records at a single hospital were followed for 12 years. Over that time, staff vaccination coverage increased from 4 percent to 67 percent, while influenza cases among the staff decreased from 42 percent to 9 percent. At the same time, nosocomial influenza cases among hospitalized patients decreased from 32 percent to zero.

So educate staff about the importance of getting a flu shot, and try to ensure that vaccination programs are available for them. Fall is the best time to be immunized, but getting the vaccine in the winter months is also recommended.

Additional Information:

FDA/CBER Influenza Virus Vaccine 2008-2009. October 29, 2008.
http://www.fda.gov/cber/flu/flu2008.htm


Increased Risk of Death in Elderly Patients Taking Conventional Antipsychotics for Dementia

FDA is requiring that "conventional" antipsychotic drugs carry a boxed warning stating that these drugs increase the risk of death when they are used to treat dementia-related psychosis in elderly patients. This category includes such drugs as Haldol (haloperidol) and Prolixin (fluphenazine). A similar warning was added to "atypical" antipsychotic drugs in 2005. Atypicals include such drugs as Zyprexa (olanzapine), Seroquel (quetiapine) and Risperdal (risperidone).

Both conventional and atypical antipsychotics are approved to treat schizophrenia, but neither type is approved for dementia-related psychosis. FDA is reminding physicians that antipsychotic drugs are not indicated for this condition, and that elderly patients treated with antipsychotics are at increased risk of death.

At this time there is no approved drug to treat dementia-related psychosis, and FDA advises healthcare professionals to consider other options to manage these patients. Physicians who prescribe antipsychotics for elderly patients with dementia-related psychosis should discuss the increased risk of death with the patient, the patient's family, and caregivers.

Additional Information:

FDA MedWatch Safety Alert. Antipsychotics, Conventional and Atypical. June 16, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm110212.htm


Serious Hypersensitivity Reactions with Abacavir (Ziagen)

FDA is alerting healthcare professionals that certain patients are more likely to experience serious and potentially fatal hypersensitivity reactions when treated with the antiretroviral drug abacavir. Abacavir is sold under the trade name Ziagen and is part of the combination products Epzicom and Trizivir.

Evidence from two studies indicates that patients with a particular HLA allele, HLA-B*5701, are at increased risk for developing a hypersensitivity reaction if treated with abacavir. Because of this, all patients should be screened for this allele before starting or restarting abacavir therapy, including patients who have taken abacavir without a reaction in the past.

Abacavir is not recommended for patients who carry the HLA-B*5701 allele and should be considered only under exceptional circumstances when the potential benefit outweighs the risk. If a patient develops a hypersensitivity reaction, the drug should be stopped immediately and permanently, whether or not the patient carries the HLA-B*5701 allele.

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


Serious Muscle Injury with Simvastatin/Amiodarone Combination

FDA is reminding healthcare professionals that patients who take amiodarone along with drugs that contain simvastatin have an increased risk of rhabdomyolysis, a type of muscle injury that can lead to kidney failure and death. Amiodarone is an antiarrhythmic drug and simvastatin (found in Zocor, Vytorin and Simcor) is used to lower cholesterol.

This increased risk has been described in the labeling for both amiodarone and simvastatin since 2002, but FDA continues to receive reports of rhabdomyolysis in patients treated concurrently with these two drugs, especially when the simvastatin dose is greater than 20 mg per day. Prescribers should avoid doses of simvastatin greater than 20 mg per day in patients who are also taking amiodarone.

When patients start taking simvastatin or their dose is increased, they should be told about the risk of rhabdomyolysis and advised to promptly report any unexplained muscle pain, tenderness or weakness.

Additional Information:

FDA MedWatch Safety Alert. Simvastatin Used With Amiodarone. August 8, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm095009.htm


Tragic Events with Concentrated Opiate Oral Solutions

An alert from the Institute for Safe Medication Practices warns about potentially fatal errors that can occur with concentrated oral opiate solutions.

ISMP cites a recent case involving an 18 year old who was prescribed oxycodone oral solution to treat throat pain associated with strep throat. He mistakenly received a 100 mg dose of concentrated oxycodone solution instead of the prescribed 5 mg. He suffered organ failure, went into a coma, and required mechanical ventilation.

It is not certain how this event occurred, but ISMP points out several factors that have contributed to these kinds of errors in the past. In some cases, concentrated oral liquid opiates have been confused with conventional concentrations. This may be more likely to happen when concentrated products are stored near the conventional ones on pharmacy shelves. Also, some physicians prescribe oral liquid medications in milliliters instead of milligrams, which presents problems when a product is available in multiple concentrations.

ISMP recommends several ways to reduce the chance of these kinds of errors. Here are some of them:

• When appropriate, consider non-opiate medications and non-drug therapies for pain relief, especially for less severe pain.

• Reserve concentrated solutions for patients who either need higher than usual doses because of severe chronic pain, or who can't swallow larger volumes of liquid.

• Always prescribe and dispense liquid medications with the dose specified in milligrams.

• Build alerts into computer order entry systems to warn about potential mix-ups between various concentrations of oral opiate solutions.

• Consider adding the word "concentrated" immediately after the drug name on computer screens to better differentiate concentrated products from other concentrations.

• Use barcode scanning to verify that the right product was selected. When the concentrated formulation is scanned, a hard stop alert should require pharmacist documentation.

• Purchase and dispense concentrated solutions in dropper bottles. This can help prevent dose-measurement errors and to differentiate the concentrated solution from other non-concentrated strength solutions.

• And finally, counsel all patients or their caregivers about how to use oral opiate solutions safely. To check their understanding, have them repeat back this information and demonstrate how to measure the dose. Advise them to question any change in product appearance, because this could signal an error in prescribing or dispensing the drug.

Additional Information:

ISMP Medication Safety Alert! Community/Ambulatory Care Edition. Tragic Events with Concentrated Opiate Oral Solutions. Volume 7, Issue 7. July 2008.
http://www.ismp.org/Newsletters/ambulatory/archives/200807-1.asp


FDA’s Drug Safety Newsletter Now Available

Every year, FDA receives more than 400,000 reports of adverse events associated with the use of drugs marketed in the U.S. FDA continually reviews these reports to identify signals of potential drug risks.

The Drug Safety Newsletter is one way FDA keeps physicians, dentists, nurses and pharmacists up to date on important safety findings derived from these reports and other sources of information.

The latest issue of the Drug Safety Newsletter features an article on medication errors and the steps healthcare professionals can take to prevent them. Other articles explore associations between reported adverse events and several specific drugs.

FDA hopes the Drug Safety Newsletter helps in making decisions about the drugs you use in your practice, and that it encourages you to report adverse events to the FDA. Subscribe to the newsletter, free of charge, by clicking on the link below.

Additional Information:

FDA Drug Safety Newsletter Home Page.
http://www.fda.gov/Drugs/DrugSafety/DrugSafetyNewsletter/default.htm



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