FDA Patient Safety News: Show #83, February 2009

Serious Infections and Neurological Events with Raptiva

FDA is highlighting the risk of life-threatening infections in patients treated with Raptiva (efalizumab). Raptiva is an immunosuppressant approved as a once a week injection to treat certain adult patients with moderate to severe plaque psoriasis.

FDA has received reports of serious infections in patients treated with Raptiva, in some cases leading to hospitalization and even death. A new boxed warning will highlight the risk of bacterial sepsis, viral meningitis, invasive fungal disease, progressive multifocal leukoencephalopathy (PML) and other opportunistic infections.

Raptiva's label will also be updated to include data from studies of juvenile mice. These data suggest that repeated administration of Raptiva to pediatric patients may lead to permanent suppression of the immune system. Raptiva is not approved for children under 18 years of age.

Prescribers should carefully evaluate the risk/benefit profile of Raptiva for patients who may be more susceptible to these risks. Before starting Raptiva, make sure patients are up-to-date on their vaccinations. During therapy, do not vaccinate patients with live or live attenuated vaccines. Also, giving inactivated vaccines during Raptiva treatment may not produce an adequate immune response.

Patients should be taught to recognize the signs and symptoms of serious infections, as well as neurological disorders, anemia, thrombocytopenia, or the worsening of their psoriasis. If any of these signs appear, they should be told to seek immediate medical attention.

FDA is requiring Raptiva's manufacturer to submit a Risk Evaluation and Mitigation Strategy (REMS) which will include a medication guide for patients.

Additional Information:

FDA MedWatch Safety Alert. Raptiva (efalizumab). October 17, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm092089.htm


Recall of ReliOn Insulin Syringes

Covidien, formerly Tyco Health Care, has recalled one lot of ReliOn disposable insulin syringes because of mislabeling. Some of the U-40 syringes in this lot were mistakenly labeled as U-100 syringes. Patients using U-100 insulin could experience a serious overdose if they used one of these mislabeled U-40 syringes, and that could lead to severe hypoglycemia and possibly death.

The recalled lot is number 813900. These 1 cc, 31 gauge insulin syringes, which were mistakenly labeled U-100, were sold only by Wal-Mart and Sam's Club, under the ReliOn name, from August 1 to October 8, 2008.

FDA is urging healthcare professionals and patients to check their supplies of U-100 insulin syringes for the recalled products and not use them. The recalled syringes can be returned to Wal-Mart or Sam's Club for replacement.

Additional Information:

FDA MedWatch Safety Alert. ReliOn Insulin Syringes for use with U-100 Insulin (Tyco Healthcare - Covidien). November 6, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm079021.htm


Ethex Corp. Recalls Several Generic Drugs

UPDATE: Ethex Corporation is also recalling a single lot (Lot #90219, Exp: 03/2010; NDC #58177-0620-04) of hydromorphone HCl tablets because they may be oversized. In addition, as a precautionary measure, the parent company of Ethex, KV Pharmaceutical, has announced that it is voluntarily suspending shipments of all FDA-approved drug products in tablet form.

The generic drug company Ethex Corporation has recalled certain lots of several products because these lots may contain oversized tablets. Oversized tablets may have as much as about twice the labeled amount of active ingredient.

The recall affects specific lots of dextroamphetamine sulfate tablets, propafenone HCl tablets, isosorbide mononitrate extended release tablets, and morphine sulfate immediate and extended release tablets. Affected lot numbers can be found at the “Additional Information” links, below. Overdoses of these drugs could have serious or life-threatening consequences. For example, a dextroamphetamine sulfate overdose could result in tachycardia and hypertension. Overdoses of morphine sulfate can cause respiratory depression and hypotension.

Ethex Corporation has sent instructions to affected wholesalers and retailers for returning the recalled products and for contacting consumers who received them. Consumers and their caregivers should not use any tablets that appear to be larger than usual. If they experience any adverse reactions to these drugs, they should contact their healthcare provider immediately. For more information contact Ethex Customer Service at 1-800-748-1472.

Additional Information:

FDA MedWatch Safety Alert. Propafenone HCl Tablets, Isosorbide Mononitrate Extended Release, Morphine Sulfate Immediate Release, Dextroamphetamine Sulfate Tablets. November 10, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm090774.htm


Ethex Corp. Recalls Several Generic Drugs

UPDATE: Ethex Corporation is also recalling a single lot (Lot #90219, Exp: 03/2010; NDC #58177-0620-04) of hydromorphone HCl tablets because they may be oversized. In addition, as a precautionary measure, the parent company of Ethex, KV Pharmaceutical, has announced that it is voluntarily suspending shipments of all FDA-approved drug products in tablet form.

The generic drug company Ethex Corporation has recalled certain lots of several products because these lots may contain oversized tablets. Oversized tablets may have as much as about twice the labeled amount of active ingredient.

The recall affects specific lots of dextroamphetamine sulfate tablets, propafenone HCl tablets, isosorbide mononitrate extended release tablets, and morphine sulfate immediate and extended release tablets. Affected lot numbers can be found at the “Additional Information” links, below. Overdoses of these drugs could have serious or life-threatening consequences. For example, a dextroamphetamine sulfate overdose could result in tachycardia and hypertension. Overdoses of morphine sulfate can cause respiratory depression and hypotension.

Ethex Corporation has sent instructions to affected wholesalers and retailers for returning the recalled products and for contacting consumers who received them. Consumers and their caregivers should not use any tablets that appear to be larger than usual. If they experience any adverse reactions to these drugs, they should contact their healthcare provider immediately. For more information contact Ethex Customer Service at 1-800-748-1472.

Additional Information:

FDA MedWatch Safety Alert. Hydromorphone HCl 2 mg Tablets. December 24, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm090576.htm


Serious Complications with Surgical Mesh for Gynecologic Surgery

The FDA is alerting healthcare professionals about rare but serious complications associated with the surgical mesh used to treat pelvic organ prolapse and stress urinary incontinence. The mesh is usually placed transvaginally using minimally invasive techniques.

Over the past three years, FDA has received over a thousand reports of complications. The most frequent included erosion of the mesh through the vaginal epithelium, infection, pain, urinary problems, and recurrence of the prolapse or the incontinence. There were also reports of bowel, bladder, and blood vessel perforation during insertion. In some cases, vaginal scarring and mesh erosion led to a significant decrease in quality of life due to discomfort and pain, including dyspareunia.

Treatment of the complications included IV therapy, blood transfusions, drainage of hematomas or abscesses, and additional surgical procedures, in some cases to remove the mesh.

Clinicians using mesh for treatment of pelvic organ prolapse and stress urinary incontinence should:

• Obtain specialized training for each mesh placement technique, and be aware of its risks.

• Be vigilant for potential adverse events from the mesh, especially erosion and infection, and also from the tools used in transvaginal placement, especially bowel, bladder and blood vessel perforations.

• Inform patients about the potential for serious complications and their effect on quality of life, including scarring and pain during sexual intercourse. Patients should also be informed that implantation of surgical mesh is permanent, and that some complications associated with the mesh may require additional surgery that may or may not correct the problem.

• Provide patients with a written copy of the patient labeling from the surgical mesh manufacturer, if it is available.

Additional Information:

FDA MedWatch Safety Alert. Transvaginal Placement of Surgical Mesh. October 21, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm079028.htm


More Mix-ups between Propylthiouracil and Purinethol

The Institute for Safe Medication Practices (ISMP) is warning about mix-ups between the trade name of one drug and the generic name of another. Purinethol® (mercaptopurine), is the trade name of a potent antimetabolite used in oncology. Propylthiouracil is an anti-thyroid agent that only comes in generic form.

The ISMP points out that although these drug names may appear to be quite distinct, there are several common characteristics that may cause confusion. Both names start with "P" and end with "L", both come in 50 mg. tablets, and the "your" sound in "purine" and "uracil" can increase the risk of error. Also, propylthiouracil is sometimes abbreviated "PTU," which can be mistaken to mean Purinethol®.

ISMP describes several examples of mix-ups between Purinethol® and propylthiouracil. In one case, a child with acute lymphoblastic leukemia mistakenly received propylthiouracil instead of Purinethol® for 6 months, even after his parents asked why the tablet looked different. As a result, the patient missed 6 months of chemotherapy.

The reverse type of error, when Purinethol® is given instead of propylthiouracil, can be even more serious. The dose of propylthiouracil is often several hundred milligrams a day, which could be many times more than the maximum dose for Purinethol®. If Purinethol® is given at these high doses, this can lead to significant harm, including bone marrow suppression, hepatotoxicity, immunosuppression, and teratogenicity.

ISMP cites a tragic case where a pregnant patient with a longstanding history of hyperthyroidism was given a prescription for "PTU". The prescription was mistakenly filled and refilled with Purinethol®. The patient became increasingly fatigued and over time developed a fever, a painful anal fissure and vaginal bleeding. She was sent to the emergency department where she was diagnosed with sepsis and spontaneously aborted the fetus at 16 weeks gestation. She was then taken to the OR to deliver the placenta, where she coded multiple times and died. The patient's death remained a mystery until her family gave prescription records from her community pharmacy to a pathologist, who was then able to see the link with Purinethol toxicity.

ISMP says that electronic prescribing and barcode-assisted dispensing can offer some protection, but they cannot entirely eliminate errors. Here are some of ISMP’s additional suggestions:

• First, install computer order entry system warnings for both drugs, with hard stops that require documentation before proceeding.

• Do not store Purinethol and propylthiouracil near each other, and consider use of warning labels on product containers.

• Encourage prescribers to avoid using abbreviations, list the brand and generic names on orders for Purinethol, and include the purpose when prescribing either drug.

• When dispensing in community pharmacies, match the drug's NDC number to the one listed in the computer unless barcode scanning is used.

• Finally, counsel patients before dispensing these two drugs, and fully investigate situations where patients report that their drugs look different than usual.

Additional Information:

ISMP Medication Safety Alert! Mix-ups with propylthiouracil and Purinethol
http://www.ismp.org/newsletters/acutecare/articles/20080522-2.asp


More Mix-ups between Propylthiouracil and Purinethol

The Institute for Safe Medication Practices (ISMP) is warning about mix-ups between the trade name of one drug and the generic name of another. Purinethol® (mercaptopurine), is the trade name of a potent antimetabolite used in oncology. Propylthiouracil is an anti-thyroid agent that only comes in generic form.

The ISMP points out that although these drug names may appear to be quite distinct, there are several common characteristics that may cause confusion. Both names start with "P" and end with "L", both come in 50 mg. tablets, and the "your" sound in "purine" and "uracil" can increase the risk of error. Also, propylthiouracil is sometimes abbreviated "PTU," which can be mistaken to mean Purinethol®.

ISMP describes several examples of mix-ups between Purinethol® and propylthiouracil. In one case, a child with acute lymphoblastic leukemia mistakenly received propylthiouracil instead of Purinethol® for 6 months, even after his parents asked why the tablet looked different. As a result, the patient missed 6 months of chemotherapy.

The reverse type of error, when Purinethol® is given instead of propylthiouracil, can be even more serious. The dose of propylthiouracil is often several hundred milligrams a day, which could be many times more than the maximum dose for Purinethol®. If Purinethol® is given at these high doses, this can lead to significant harm, including bone marrow suppression, hepatotoxicity, immunosuppression, and teratogenicity.

ISMP cites a tragic case where a pregnant patient with a longstanding history of hyperthyroidism was given a prescription for "PTU". The prescription was mistakenly filled and refilled with Purinethol®. The patient became increasingly fatigued and over time developed a fever, a painful anal fissure and vaginal bleeding. She was sent to the emergency department where she was diagnosed with sepsis and spontaneously aborted the fetus at 16 weeks gestation. She was then taken to the OR to deliver the placenta, where she coded multiple times and died. The patient's death remained a mystery until her family gave prescription records from her community pharmacy to a pathologist, who was then able to see the link with Purinethol toxicity.

ISMP says that electronic prescribing and barcode-assisted dispensing can offer some protection, but they cannot entirely eliminate errors. Here are some of ISMP’s additional suggestions:

• First, install computer order entry system warnings for both drugs, with hard stops that require documentation before proceeding.

• Do not store Purinethol and propylthiouracil near each other, and consider use of warning labels on product containers.

• Encourage prescribers to avoid using abbreviations, list the brand and generic names on orders for Purinethol, and include the purpose when prescribing either drug.

• When dispensing in community pharmacies, match the drug's NDC number to the one listed in the computer unless barcode scanning is used.

• Finally, counsel patients before dispensing these two drugs, and fully investigate situations where patients report that their drugs look different than usual.

Additional Information:

ISMP Medication Safety Alert! Is an Anti-thyroid or Anti-metabolite Needed? August 21, 2003.
http://www.ismp.org/newsletters/acutecare/articles/20030821.asp


Drug Name Confusion Between Kuric and Carac

The Institute for Safe Medication Practices (ISMP) recently reported on the potential for mix-ups between two topical creams: Kuric (ketoconazole) and Carac (fluorouracil). Kuric is used to treat fungal infections and seborrheic dermatitis. Carac is used to treat multiple actinic or solar keratoses of the face and anterior scalp.

Sanofi-Aventis, the maker of Carac, recently sent a letter to pharmacists describing how one mix-up occurred. In this case, a verbal prescription for Kuric was mistakenly heard and transcribed as Carac, which was then dispensed. The patient developed severe rash with erythema, irritation, and peeling of the skin and secondary infection at the application site and surrounding areas.

The letter gave several ways to help avoid these kinds of errors. For example, clarify oral and written orders with the prescriber by verifying both the brand and generic name, as well as the spelling of the product; match the product's indication to the patient's condition; and create electronic alerts that appear when the pharmacist fills prescriptions for either medication.

Additional Information:

ISMP Medication Safety Alert! Carac-Kuric Mix-Ups. Volume 13, Issue 21. October 23, 2008.
http://www.ismp.org/newsletters/acutecare/articles/20081023-1.asp


Drug Name Confusion Between Kuric and Carac

The Institute for Safe Medication Practices (ISMP) recently reported on the potential for mix-ups between two topical creams: Kuric (ketoconazole) and Carac (fluorouracil). Kuric is used to treat fungal infections and seborrheic dermatitis. Carac is used to treat multiple actinic or solar keratoses of the face and anterior scalp.

Sanofi-Aventis, the maker of Carac, recently sent a letter to pharmacists describing how one mix-up occurred. In this case, a verbal prescription for Kuric was mistakenly heard and transcribed as Carac, which was then dispensed. The patient developed severe rash with erythema, irritation, and peeling of the skin and secondary infection at the application site and surrounding areas.

The letter gave several ways to help avoid these kinds of errors. For example, clarify oral and written orders with the prescriber by verifying both the brand and generic name, as well as the spelling of the product; match the product's indication to the patient's condition; and create electronic alerts that appear when the pharmacist fills prescriptions for either medication.

Additional Information:

Sanofi-Aventis “Dear Pharmacist” letter.
http://www.ismp.org/docs/CaracLetter20080110.pdf


New Labels for Non-prescription Cough and Cold Medications

Most makers of nonprescription cough and cold medicines are voluntarily changing the labels on these products to say "do not use" for children under 4 years of age. New child resistant packaging and measuring devices are also being introduced.

The changes were recently announced by the Consumer Healthcare Products Association (CHPA), which represents most of these manufacturers. FDA supports this action, which reflects a more restrictive use of these drugs in children.

FDA is working with other public health and scientific organizations to obtain, analyze and make available the most up-to-date information about the effects of these medicines on children, and FDA will take additional action as needed. In the meantime, here are some reminders for parents and caregivers:

• First, understand that these medicines do not cure a cold or cough or shorten its duration. They only treat a child's symptom(s) such as a runny nose, congestion, fever and aches.

• Do not give children medications labeled only for adults.

• Choose OTC cough and cold medicines with child-resistant safety caps, where possible. Be sure to close the cap tightly after use, and store the medication out of reach of children.

• Check the "Drug Facts" on the label, which tells how much medicine to give and how often to give it. Misusing or using too much of these products can cause serious and even life threatening side effects such as rapid heartbeat, drowsiness, suppression of the respiratory system and seizures.

• Be careful when giving a child more than one medicine. Using two medicines with the same or similar active ingredients could give a child too much of that drug.

• Only use measuring devices that come with the medicine, or those specially made for measuring drugs.

• Finally, if you have questions or are not sure how to use a product, check with the doctor or pharmacist.

Additional Information:

FDA MedWatch Safety Alert. Over The Counter Cough and Cold Medications. October 9, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094913.htm



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