FDA Patient Safety News: Show #75, May 2008

FDA Licenses New Hemophilia Treatment

FDA recently licensed a new treatment for hemophilia A called Xyntha. Xyntha, which is made by Wyeth Pharmaceuticals, is a genetically engineered version of factor VIII, a protein essential for blood clotting that is decreased or absent in patients with hemophilia A.

Xyntha is produced without additives from human or animal material. This provides hemophilia A patients with an additional treatment option that can further minimize the risk of infection from the product.

Additional Information:

FDA Press Release. FDA Licenses New Hemophilia Treatment. February 21, 2008.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116860.htm


Unsafe Use of Extended-Release Tussionex Suspension

FDA is cautioning healthcare professionals, patients and caregivers about the unsafe use of Tussionex Pennkinetic Extended-Release Suspension. This product is a long-acting cough suppressant containing hydrocodone, a narcotic antitussive, and chlorpheniramine, an antihistamine. Overdoses of hydrocodone can result in respiratory depression and death. FDA has reviewed over a hundred adverse event reports associated with this product. Twenty four reports were in children under the age of six, nine of whom died.

Tussionex is not approved for children under six because of the risk of respiratory depression and death. Even though it is specifically contraindicated in this age group some physicians are prescribing this product for them. Also, family members may take a prescription for an older family member and give it to younger children.

Irrespective of the child's age, parents are also running into trouble when they try to measure the dose. For example, they may be using ordinary teaspoons, which can vary in size. Pharmacists can contribute to the problem if they mis-state the dose on the prescription label. In one case, the physician's order of 2 mL was written as two teaspoons on the label.

Another problem with any long-acting or extended-release medication is that patients or caregivers may be tempted to use it more often than it is prescribed. Some of the reports also indicated that physicians were prescribing it to be taken more often than every 12 hours.

To help avoid these overdoses, FDA is working with the manufacturer to strengthen the prescribing information and the instructions for use. But preventing these kinds of tragedies requires understanding and vigilance from everyone involved.

• Prescribers should not prescribe the product for children under six. They should specify that it not be taken more often than every 12 hours and also specify the dose on the prescription in milliliters.

• Pharmacists should clearly state the dose in milliliters on the prescription label, give the patient or parent a measuring device that can deliver this dose in milliliters, and counsel them on how to use it.

• Patients or parents should understand that they should not use more of the drug than prescribed, or use it more often than prescribed or give it to anyone under the age of six. The proper device should be used to measure the dose. In addition, this medicine should not be mixed with any other fluids before taking it or giving it to someone else, because this could increase the release rate of the drug and that could result in an overdose. Patients and parents should also be alert to the symptoms of hydrocodone overdose, including, respiratory depression, extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold, clammy skin and sometimes bradycardia or hypotension.

Additional Information:

FDA MedWatch Safety Alert. Long-Acting Hydrocodone-Containing Cough Product (marketed as Tussionex Pennkinetic Extended-Release Suspension). March 11, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm091793.htm


Unsafe Use of Extended-Release Tussionex Suspension

FDA is cautioning healthcare professionals, patients and caregivers about the unsafe use of Tussionex Pennkinetic Extended-Release Suspension. This product is a long-acting cough suppressant containing hydrocodone, a narcotic antitussive, and chlorpheniramine, an antihistamine. Overdoses of hydrocodone can result in respiratory depression and death. FDA has reviewed over a hundred adverse event reports associated with this product. Twenty four reports were in children under the age of six, nine of whom died.

Tussionex is not approved for children under six because of the risk of respiratory depression and death. Even though it is specifically contraindicated in this age group some physicians are prescribing this product for them. Also, family members may take a prescription for an older family member and give it to younger children.

Irrespective of the child's age, parents are also running into trouble when they try to measure the dose. For example, they may be using ordinary teaspoons, which can vary in size. Pharmacists can contribute to the problem if they mis-state the dose on the prescription label. In one case, the physician's order of 2 mL was written as two teaspoons on the label.

Another problem with any long-acting or extended-release medication is that patients or caregivers may be tempted to use it more often than it is prescribed. Some of the reports also indicated that physicians were prescribing it to be taken more often than every 12 hours.

To help avoid these overdoses, FDA is working with the manufacturer to strengthen the prescribing information and the instructions for use. But preventing these kinds of tragedies requires understanding and vigilance from everyone involved.

• Prescribers should not prescribe the product for children under six. They should specify that it not be taken more often than every 12 hours and also specify the dose on the prescription in milliliters.

• Pharmacists should clearly state the dose in milliliters on the prescription label, give the patient or parent a measuring device that can deliver this dose in milliliters, and counsel them on how to use it.

• Patients or parents should understand that they should not use more of the drug than prescribed, or use it more often than prescribed or give it to anyone under the age of six. The proper device should be used to measure the dose. In addition, this medicine should not be mixed with any other fluids before taking it or giving it to someone else, because this could increase the release rate of the drug and that could result in an overdose. Patients and parents should also be alert to the symptoms of hydrocodone overdose, including, respiratory depression, extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold, clammy skin and sometimes bradycardia or hypotension.

Additional Information:

FDA Press Release. FDA Issues Alert on Tussionex, a Long-Acting Prescription Cough Medicine Containing Hydrocodone. March 11, 2008.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116866.htm


Liver Injury with Tysabri

Biogen Idec and Elan Pharmaceuticals are warning healthcare professionals about reports of clinically significant liver injury in patients taking Tysabri (natalizumab). Tysabri is a monoclonal antibody used to treat certain patients with relapsing forms of multiple sclerosis.

Signs of liver injury, such as elevated total bilirubin and significantly elevated serum hepatic enzymes, have occurred as early as six days after the first dose of Tysabri. These signs can also occur for the first time even in patients who have taken multiple doses of Tysabri. Some patients had liver injury that recurred after rechallenge with the drug, which provides evidence that Tysabri caused the injury.

The combination of elevated bilirubin and transaminase levels without evidence of obstruction is an important indicator that a medication may be causing severe liver injury. This could lead to death or the need for a liver transplant in some patients. Therefore Tysabri should be discontinued in patients with jaundice or other evidence of significant liver injury. Patients should also be told that Tysabri may cause liver injury and advised to contact their doctors if they develop symptoms of hepatotoxicity such as jaundice, fatigue, nausea, vomiting and dark urine.

Additional Information:

FDA MedWatch Safety Alert. Tysabri (natalizumab). February 27, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm110608.htm


Updated Labeling Changes for Tamiflu and Relenza

Roche Laboratories has updated information on neuropsychiatric events for Tamiflu (oseltamivir phosphate), a drug that's used to treat or prevent influenza in patients 1 year and older.

The revised labeling reminds practitioners that some patients taking Tamiflu for influenza have experienced delirium and abnormal behavior, leading to accidental injury and a small number of deaths. Most of these events occurred in Japan, and the majority were in children, often with abrupt onset and rapid resolution. Similar events have also been reported with Relenza (zanamivir), an inhaled drug used to prevent and treat influenza, and similar labeling changes have been adopted for that drug.

The role of the drugs in contributing to these events is not established. In fact, the labeling points out that influenza itself can be associated with a variety of neurologic and behavioral symptoms, including hallucinations, delirium, and abnormal behavior.

Patients with influenza should be closely monitored for signs of abnormal behavior, and if a patient does experience neuropsychiatric symptoms, the practitioner should evaluate the risks and benefits of continuing Tamiflu treatment.

Additional Information:

FDA MedWatch Safety Alert. Tamiflu (oseltamivir phosphate). March 4, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm095044.htm


Updated Labeling Changes for Tamiflu and Relenza

Roche Laboratories has updated information on neuropsychiatric events for Tamiflu (oseltamivir phosphate), a drug that's used to treat or prevent influenza in patients 1 year and older.

The revised labeling reminds practitioners that some patients taking Tamiflu for influenza have experienced delirium and abnormal behavior, leading to accidental injury and a small number of deaths. Most of these events occurred in Japan, and the majority were in children, often with abrupt onset and rapid resolution. Similar events have also been reported with Relenza (zanamivir), an inhaled drug used to prevent and treat influenza, and similar labeling changes have been adopted for that drug.

The role of the drugs in contributing to these events is not established. In fact, the labeling points out that influenza itself can be associated with a variety of neurologic and behavioral symptoms, including hallucinations, delirium, and abnormal behavior.

Patients with influenza should be closely monitored for signs of abnormal behavior, and if a patient does experience neuropsychiatric symptoms, the practitioner should evaluate the risks and benefits of continuing Tamiflu treatment.

Additional Information:

FDA MedWatch Safety Alert. Relenza (zanamivir). April 1, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094982.htm


New Instructions for Using Talecris IG Syringes

Talecris Biotherapeutics has revised the directions for administering some of the company's immune globulin products -- ones that come in uncalibrated prefilled 2 mL syringes with fixed needles. The products are HyperRAB™ S/D , which is an anti-rabies product, and GamaSTAN™ S/D, which is indicated for the prophylaxis of hepatitis A, measles and other infectious diseases.

In certain situations, the fixed needle and lack of graduation marks on the affected 2 mL syringes may make it difficult to administer the recommended dose. That can happen when a pediatric dose of less than 2mL is required, or when the dose is administered at more than one site or when using a needle size other than the one that's provided.

The company has sent out revised instructions on how to use the product properly under these circumstances or call the Talecris Biotherapeutics help line at 919-412-1030.

Additional Information:

FDA Center for Biologics Evaluation and Research. Dosing and Administration of Immune Globulin (Human), GamaSTAN™ S/D Packaged in 2-ml Syringes. March 5, 2008.
http://www.fda.gov/cber/safety/gamastan030508.htm


New Instructions for Using Talecris IG Syringes

Talecris Biotherapeutics has revised the directions for administering some of the company's immune globulin products -- ones that come in uncalibrated prefilled 2 mL syringes with fixed needles. The products are HyperRAB™ S/D , which is an anti-rabies product, and GamaSTAN™ S/D, which is indicated for the prophylaxis of hepatitis A, measles and other infectious diseases.

In certain situations, the fixed needle and lack of graduation marks on the affected 2 mL syringes may make it difficult to administer the recommended dose. That can happen when a pediatric dose of less than 2mL is required, or when the dose is administered at more than one site or when using a needle size other than the one that's provided.

The company has sent out revised instructions on how to use the product properly under these circumstances or call the Talecris Biotherapeutics help line at 919-412-1030.

Additional Information:

FDA Center for Biologics Evaluation and Research. Dosing and Administration of Rabies Immune Globulin (Human), HyperRAB™ S/D Packaged in 2-ml Syringes. February 22, 2009.
http://www.fda.gov/cber/safety/hyperrab022208.htm


Hepatotoxicity with Prezista

FDA and Tibotec Therapeutics are alerting healthcare professionals about the risk of hepatotoxicity associated with the antiretroviral drug Prezista (darunavir). Prezista, co-administered with ritonavir and other antiretroviral agents, is used to treat certain patients with HIV-1.

Some patients receiving the Prezista/ritonavir combination have experienced drug-induced hepatitis and liver injuries, a small number of them fatal. Most of these patients were taking multiple medications that can affect the liver or had other co-morbid conditions. Patients with underlying liver disease, such as chronic hepatitis B or C may be at increased risk for developing liver function abnormalities.

It is not clear that the Prezista/ritonavir combination caused the adverse reactions. Still, clinicians should be alert to the signs and symptoms of liver toxicity in patients taking this drug combination.

Appropriate hepatic lab tests should be done before starting the drug, and patients should be monitored during treatment according to HIV treatment guidelines. Elevated levels of ALT, AST and GGT may indicate liver injury. Patients with underlying chronic hepatitis or cirrhosis, or patients who have elevated transaminase levels before treatment, should be monitored more frequently.

Consider interrupting or stopping the treatment if there is evidence of new or worsening liver dysfunction, including clinically significant elevation of liver enzymes, or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, or hepatomegaly. Patients should be told to promptly seek medical attention if they experience these symptoms.

Additional Information:

FDA MedWatch Safety Alert. Prezista (darunavir). March 12, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094964.htm


Information on Mortality Rates with the AneuRx® Stent Graft System

In a recent Public Health Notification, FDA informed healthcare professionals about new data on mortality rates associated with the AneuRx® Stent Graft System. This endovascular graft, made by Medtronic, is used as an alternative to open surgery in preventing the rupture of abdominal aortic aneurysms (AAA). The new information suggests that the average aneurysm-related death rate several years after treatment is higher in patients with the AneuRx® device than in patients who receive open surgery. FDA's Notification focused on the AneuRx® product because it's the only device of its kind with significant long-term mortality data.

Based on these new findings, FDA recommends that the AneuRx® graft only be used in patients who meet the appropriate risk-benefit profile. In deciding on whether to use open surgery or the graft, physicians should take into account that the average risk of late mortality related to the aneurysm may be greater for AneuRx® than for open surgery.

However, they should also consider other factors that can modify these risk comparisons. For example, the mortality rates with both open surgery and the graft may be considerably higher than average if performed in institutions or by physicians who have little experience with these procedures. The risk is also higher with open surgery if the patient has cardiac, renal or pulmonary co-morbidities. For a 70-year old patient, the risk could range from 2 percent with no risk factors to over 40 percent with multiple co-morbidities.

Another factor that could influence this risk comparison is the willingness of the patient to comply with the follow-up schedule required with the endovascular graft. If a patient were non-compliant, this could increase the risk associated with the graft.

Finally, FDA recommends that clinicians stay abreast of the information in the product labels and in the yearly clinical updates from Medtronic and other graft manufacturers.

Additional Information:

FDA Public Health Notification. Updated Data on Mortality Associated with the Medtronic AneuRx® Stent Graft System. March 17, 2008.
http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/ucm062008.htm


Mistakenly Swallowing Inhaler Capsules

FDA has issued an advisory about the danger of mistakenly swallowing Spiriva (tiotropium bromide inhalation powder) and Foradil (formoterol fumarate inhalation powder) inhalation capsules. These capsules are intended to be used with inhalation devices to treat patients with asthma and chronic obstructive pulmonary disease.

FDA and the American Association of Poison Control Centers have received many reports of patients swallowing these capsules. This may occur because the capsules resemble those taken by mouth. Not many patients have suffered side effects from swallowing the capsules, but their respiratory problems will not be treated if the drugs are taken orally rather than inhaled.

Warn patients not to swallow Spiriva or Foradil capsules. Remind them that the capsules should be removed from the blister pack and placed in the inhalation device - for Spiriva, it's the HandiHaler, and for Foradil, the Aerolizer. Advise them to follow the instructions that come with the prescription. And if the breathing condition of patients using Spiriva or Foradil does not improve, ask whether they are swallowing the medicine rather than inhaling it.

Additional Information:

FDA MedWatch Safety Alert. Spiriva (tiotropium bromide inhalation powder) Capsules Foradil (formoterol fumarate inhalation powder) Capsules. February 29, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm080885.htm


Choosing the Correct Test Strip for a Blood Glucose Meter

FDA is aware of cases where patients have used LifeScan OneTouch Ultra test strips with their Abbott Precision Xtra blood glucose meters.

As a result, the meters recorded lower-than-expected blood glucose levels, which can have serious clinical consequences. This problem is not limited to just these two products. Using the wrong strip in any brand of blood glucose meter could result in erroneous readings, or no readings at all.

Instruct diabetic patients who use blood glucose meters to use only the strips recommended for that particular meter. The owner's manual for each meter specifies which strips are suitable. As an additional check, the instructions with the test strips identify the meters that are compatible with those strips.

Additional Information:

FDA MedWatch Safety Alert. Blood Glucose Meters and Test Strips. March 11, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm078672.htm



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