FDA Patient Safety News: Show #89, August 2009

Liver Failure with Propylthiouracil

FDA is notifying healthcare professionals about the risk of serious and possibly fatal liver injury associated with propylthiouracil, an anti-thyroid drug used to treat Graves' disease. Propylthiouracil is generally considered second-line therapy in Graves' disease. The drug of choice in most cases is methimazole, because it has been associated with fewer cases of serious liver damage than propylthiouracil.

Children are especially vulnerable to liver damage with propylthiouracil. FDA has identified 10 pediatric cases of serious liver injury from propylthiouracil, and none from methimazole. The risk profile is different for patients in the first trimester of pregnancy, however, since methimazole has been associated with embryopathy and propylthiouracil has not.

FDA is working to change the propylthiouracil prescribing information to reflect the risk of hepatotoxicity, and the American Thyroid Association plans to update its treatment guidelines for Graves' disease.

In the meantime, FDA is recommending that clinicians reserve the use of propylthiouracil for patients who cannot take methimazole because of allergy or intolerance, or for patients in the first trimester of pregnancy.

Propylthiouracil should not be used in children unless they cannot take methimazole and there are no other treatment options available.

If propylthiouracil is prescribed, patients should be closely monitored for liver injury, especially during the first six months of treatment. Advise patients to promptly report symptoms such as fatigue, weakness, vague abdominal pain, loss of appetite, itching, easy bruising, or yellowing of the eyes or skin. If liver injury is suspected, the drug should be discontinued and the patient evaluated.

Additional Information:

FDA MedWatch Safety Alert. Propylthiouracil. June 3, 2009.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm164162.htm


Liver Failure with Propylthiouracil

FDA is notifying healthcare professionals about the risk of serious and possibly fatal liver injury associated with propylthiouracil, an anti-thyroid drug used to treat Graves' disease. Propylthiouracil is generally considered second-line therapy in Graves' disease. The drug of choice in most cases is methimazole, because it has been associated with fewer cases of serious liver damage than propylthiouracil.

Children are especially vulnerable to liver damage with propylthiouracil. FDA has identified 10 pediatric cases of serious liver injury from propylthiouracil, and none from methimazole. The risk profile is different for patients in the first trimester of pregnancy, however, since methimazole has been associated with embryopathy and propylthiouracil has not.

FDA is working to change the propylthiouracil prescribing information to reflect the risk of hepatotoxicity, and the American Thyroid Association plans to update its treatment guidelines for Graves' disease.

In the meantime, FDA is recommending that clinicians reserve the use of propylthiouracil for patients who cannot take methimazole because of allergy or intolerance, or for patients in the first trimester of pregnancy.

Propylthiouracil should not be used in children unless they cannot take methimazole and there are no other treatment options available.

If propylthiouracil is prescribed, patients should be closely monitored for liver injury, especially during the first six months of treatment. Advise patients to promptly report symptoms such as fatigue, weakness, vague abdominal pain, loss of appetite, itching, easy bruising, or yellowing of the eyes or skin. If liver injury is suspected, the drug should be discontinued and the patient evaluated.

Additional Information:

FDA Press Release. FDA Warns About Serious Liver Injury Associated With Anti-Thyroid Drug. June 3, 2009.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm164207.htm


Neuropsychiatric Events with Certain Asthma Drugs

FDA has asked the manufacturers of leukotriene-modifying drugs to include a precaution in their labeling about the potential for neuropsychiatric events with these medications. The drugs include Accolate (zafirlukast), Zyflo (zileuton) and Zyflo CR (zileuton), which are used to treat asthma, and Singulair (montelukast), which is used to treat asthma and allergic rhinitis, and to prevent exercise-induced asthma.

Reported neuropsychiatric events with these drugs have included agitation, aggression, anxiousness, irritability, restlessness and insomnia. Patients have also experienced tremors, dream abnormalities, hallucinations, depression and suicidality, including suicide.

Healthcare professionals should be alert to the possibility of neuropsychiatric events in patients taking leukotriene modifiers, and should advise patients to report neuropsychiatric symptoms if they occur. If these symptoms develop, clinicians should consider discontinuing the medication.

Additional Information:

FDA MedWatch Safety Alert. Leukotriene Inhibitors: Montelukast (marketed as Singulair), Zafirlukast (marketed as Accolate), and Zileuton (marketed as Zyflo and Zyflo CR). June 12, 2009.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm166246.htm


Recall of Certain Infant Apnea Monitors

Philips/Respironics is recalling some of the company's SmartMonitor 2 Infant Apnea Monitors. These devices are used to monitor infants' heart rate and respiration in the hospital or at home. The monitors are being recalled because they may fail to alarm if the infant experiences breathing problems or an abnormal heart rate.

The affected devices are the SmartMonitor 2, Models 4002 and 4003 with serial numbers 3000033364 through 3000038740.

In April, the company notified their distributors about the problem and asked them to return all recalled monitors in their inventory, and also to retrieve and return all of these monitors that have been shipped to patients. If hospitals or caregivers think they may have one of the affected monitors, they should contact their medical supply distributor, or call Respironics directly at 1-888-345-4630.

Additional Information:

FDA CDRH Medical Device Recalls. Respironics, Inc., SmartMonitor 2 Infant Apnea Monitor (Models 4002 and 4003). May 18, 2009.
http://www.fda.gov/MedicalDevices/Safety/RecallsCorrectionsRemovals/ListofRecalls/ucm152725.htm


Alert on Stolen Levemir Insulin

FDA is alerting the public that certain vials of the long-acting insulin Levemir were stolen and are being sold in the U.S. market. The stolen vials, which had come from three specific lots, may not have been stored or handled properly. Because of that, they may be dangerous to use. At least one patient has suffered an adverse event because of poor blood glucose control after using a vial from one of the stolen lots.

Novo Nordisk, the manufacturer of Levemir, says the following three lots were stolen: XZF0036, XZF0037, and XZF0038. These lots contain almost 130,000 vials of insulin.

Here's FDA's advice for patients who use Levemir:

• First, check your supply of insulin to see if you have Levemir from one of the affected lots. You can find the lot number on the side of the box and also on the side of the vial.

• Don't use your Levemir insulin if it comes from one of these lots. Use a vial of Levemir from another lot, and contact Novo Nordisk for instructions on what to do with vials from the stolen lots. Their number is 1-800-727-6500.

• If you have to switch to another brand of insulin for any reason, contact your healthcare provider before you do, because the dose may need to be changed.

• And as a reminder, always inspect your insulin before you use it. Levemir is a clear, colorless solution. If your Levemir looks different, check with your doctor or pharmacist.

Additional Information:

FDA MedWatch Safety Alert. Levemir Insulin (Novo Nordisk). June 13, 2009.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm166359.htm


Serious Fungal Infections with Simponi

FDA is reminding healthcare professionals about the risk of serious fungal infections with TNF blockers, including Simponi (golimumab), which was recently approved. TNF blockers are immunosuppressants used to treat chronic inflammatory diseases, including rheumatoid arthritis. FDA had previously warned about the risk of serious fungal infections associated with TNF blockers, including Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab) and Remicade (infliximab). FDA is concerned that invasive fungal infections, including histoplasmosis, have not been consistently recognized in patients taking these drugs, resulting in delayed treatment and, in some cases, death.

In a recent letter to clinicians, Centocor Ortho Biotech, the manufacturer of Simponi, recommended that patients be closely monitored for signs of invasive fungal infections during and after treatment with TNF blockers. The company's letter said that TNF blockers, including Simponi, should be discontinued if such infections occur, and suggested that clinicians consider empiric antifungal therapy until the specific pathogens can be identified.

Additional Information:

FDA MedWatch Safety Alert. Simponi (golimumab). May 27, 2009.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm162802.htm


Practicing Hospital Bed Safety

Here's a reminder about the importance of keeping patients safe in hospital beds. These beds are not only found in hospitals, but also in outpatient care centers, long-term care facilities and even at home.

FDA has received hundreds of reports of patients suffering serious injuries or dying of strangulation when they became entrapped in the spaces around the bed rail, the mattress or the bed frame. Entrapment occurs mainly in patients who are elderly, frail or confused.

Seven "zones of entrapment" have been identified, most of which involve bed rails. FDA urges users to carefully check hospital beds to be sure that there are no openings large enough to entrap the patient. Even if the bed rails fit properly, they may present other hazards, such as serious injuries when the patient tries to climb over the rail. Healthcare professionals and caregivers should consider whether bedrails are necessary in each situation.

In addition to entrapment, there is also a rare but potentially lethal risk of electrical fires in power-operated beds. These fires are mainly caused by poor maintenance. FDA recommends several steps to reduce this risk - for example, not using extension cords, keeping dust and lint from accumulating near the motor, and checking the bed control panel for signs of spilled liquids.

Additional Information:

FDA Consumer Update. Practice Hospital Bed Safety. June 9, 2009.
http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm164366.htm


Antiepileptic Drugs and Suicidality

FDA is alerting healthcare professionals that the labeling for antiepileptic drugs will now warn that patients taking these drugs have an increased risk of suicidal thoughts and actions.

The warnings are based on FDA's analysis of placebo-controlled clinical studies of eleven drugs used to treat epilepsy, psychiatric disorders and other conditions. In this analysis, the risk was approximately doubled in patients receiving the anti-epileptic drugs compared with those getting placebo -- 0.43% vs. 0.22%.

The following drugs were included in the analyses:

Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
Felbamate (marketed as Felbatol)
Gabapentin (marketed as Neurontin)
Lamotrigine (marketed as Lamictal)
Levetiracetam (marketed as Keppra)
Oxcarbazepine (marketed as Trileptal)
Pregabalin (marketed as Lyrica)
Tiagabine (marketed as Gabitril)
Topiramate (marketed as Topamax)
Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)
Zonisamide (marketed as Zonegran)

The increased risk was seen as early as one week after starting therapy and continued through 24 weeks. And it was generally consistent for all eleven drugs in the analysis, and across a range of indications. This suggests that this risk applies to all antiepileptic drugs when they're used for any indication - even those that weren't part of the analysis.

Healthcare professionals should closely monitor all patients starting or taking antiepileptic drugs. They should be alert to changes in behavior that could signal an emerging or worsening of depression or suicidal thoughts or behavior. Patients will also be given Medication Guides explaining these risks each time their prescriptions are dispensed.

Additional Information:

FDA MedWatch Safety Alert. Antiepileptic Drugs. May 5, 2009.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm074939.htm


Increased Mortality in Liver Transplant Patients Treated with Rapamune

FDA is alerting healthcare professionals that stable liver transplant patients may have an increased risk of death if they are switched from an immunosuppressive regimen based on a calcineurin inhibitor (CNI) to sirolimus. Sirolimus, which is marketed as Rapamune, is approved to prevent organ rejection in patients 13 and older who receive kidney transplants. It is not approved to treat patients with liver or lung transplants.

The higher mortality risk was found in a clinical trial conducted by Wyeth, the manufacturer of Rapamune. The trial also suggested that patients converted to Rapamune were more likely to experience treatment failure at one year, and more likely to discontinue the drug because of adverse events, than patients who remained on CNI-based therapy.

FDA is reminding healthcare professionals that the boxed warning for Rapamune states that the safety and efficacy of the drug as an immunosuppressant have not been established in liver or lung transplant patients. FDA's alert also points out that therapeutic drug monitoring is recommended for all Rapamune patients, but it should not be used as the sole basis for adjusting Rapamune therapy.
The patient's signs and symptoms should also be considered, along with tissue biopsy and laboratory findings.

Additional Information:

FDA MedWatch Safety Alert. Sirolimus (marketed as Rapamune) June 11, 2009.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm165731.htm


Certain Skin Sanitizers/Protectants Contaminated

FDA is alerting the public that certain skin sanitizers and skin protectants made by Clarcon Biological Chemistry Laboratory are being recalled because they have been found to contain high levels of bacteria. Some of these bacteria could cause infections of the skin and underlying tissues, which may require medical attention and lead to permanent damage. The contamination of these products can be especially dangerous since they are promoted to treat open wounds and damaged skin, and to actually protect against infections.

The recalled products include Citrushield Lotion, Dermasentials DermaBarrier, Dermassentials by Clarcon Antimicrobial Hand Sanitizer, Iron Fist Barrier Hand Treatment, Skin Shield Restaurant, Skin Shield Industrial, Skin Shield Beauty Salon Lotion, Total Skin Care Beauty, and Total Skin Care Work. Consumers who have any of these products should not use them and throw them away.

Additional Information:

FDA MedWatch Safety Alert. Skin Products Made by Clarcon. June 9, 2009.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm165028.htm


Intranasal Zinc May Cause Loss of Smell

FDA has issued a warning that zinc-containing cold remedies administered directly into the nose have been associated with anosmia, which is a loss of the sense of smell. This warning is directed at several over-the-counter products marketed by Matrixx Initiatives: Zicam Cold Remedy Nasal Gel, Zicam Cold Remedy Nasal Swabs, and Zicam Cold Remedy Nasal Swabs Kids Size, which has been discontinued. FDA is advising people to stop using them. This warning does not apply to oral zinc tablets or lozenges taken by mouth.

FDA has received more than 130 reports of anosmia in people using intranasal products that contain zinc. In some cases, the problem occurred with the first dose of the product, and in other cases it began after later doses.
The anosmia may be long-lasting or even permanent, while the common cold usually goes away without treatment in seven to ten days.

People with anosmia may have serious safety and quality of life problems, including the inability to detect smoke, a gas leak, or spoiled food. Losing the ability to smell also compromises a person's sense of taste.

People who have lost their sense of smell or taste after using intranasal zinc-containing products should contact their healthcare provider. Patients and providers should report these events to FDA's MedWatch program.

Additional Information:

FDA MedWatch Safety Alert. Zicam Cold Remedy Nasal Products (Cold Remedy Nasal Gel, Cold Remedy Nasal Swabs, and Cold Remedy Swabs, Kids Size). June 16, 2009.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm166996.htm



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