FDA Patient Safety News: Show #17, July 2003

New Drug-Eluting Coronary Stent

In a recent news release, FDA announced the approval of a new drug-eluting stent for angioplasty. The device is called the Cypher Sirolimus Eluting Coronary Stent, and it's manufactured by Cordis Corporation, with a license from Wyeth Pharmaceuticals for the use of the drug.

This stent differs from conventional ones in that it slowly releases a drug that helps prevent restenosis. The drug is sirolimus, an immunosuppressant that acts to help prevent restenosis, possibly by inhibiting the proliferation of smooth muscle and endothelial cells. About 800,000 angioplasty procedures are performed in the U.S. each year, and restenosis occurs in about 15 to 30 percent of them. This device could potentially have a significant impact in reducing restenoses.

In a U.S. study of about a thousand patients, the restenosis rate among those who received the drug-eluting stent was about 9 percent, compared to about 36 percent for those who received a conventional stent. The combined occurrence of repeat angioplasty, bypass surgery, myocardial infarctions and death was about 9 percent for patients with the drug-eluting stents and about 21 percent for the other patients.

This device wasn't studied under certain conditions. For example, the safety and effectiveness of this device weren't studied for blockages longer than 30 mm, or for arteries narrower than 15 mm. Also not studied were patients who had their occlusions in bypass grafts, those who had previous intravascular radiation therapy, and those in whom the stent might be used during an infarction.

FDA is requiring the manufacturer to conduct a 2000-patient post-approval study to assess the long-term safety and effectiveness of the device, and to look for rare adverse events that might result from using this product.

Additional Information:

FDA Public Health Web Notification - November 25, 2003.
http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/UCM064527


New Drug-Eluting Coronary Stent

In a recent news release, FDA announced the approval of a new drug-eluting stent for angioplasty. The device is called the Cypher Sirolimus Eluting Coronary Stent, and it's manufactured by Cordis Corporation, with a license from Wyeth Pharmaceuticals for the use of the drug.

This stent differs from conventional ones in that it slowly releases a drug that helps prevent restenosis. The drug is sirolimus, an immunosuppressant that acts to help prevent restenosis, possibly by inhibiting the proliferation of smooth muscle and endothelial cells. About 800,000 angioplasty procedures are performed in the U.S. each year, and restenosis occurs in about 15 to 30 percent of them. This device could potentially have a significant impact in reducing restenoses.

In a U.S. study of about a thousand patients, the restenosis rate among those who received the drug-eluting stent was about 9 percent, compared to about 36 percent for those who received a conventional stent. The combined occurrence of repeat angioplasty, bypass surgery, myocardial infarctions and death was about 9 percent for patients with the drug-eluting stents and about 21 percent for the other patients.

This device wasn't studied under certain conditions. For example, the safety and effectiveness of this device weren't studied for blockages longer than 30 mm, or for arteries narrower than 15 mm. Also not studied were patients who had their occlusions in bypass grafts, those who had previous intravascular radiation therapy, and those in whom the stent might be used during an infarction.

FDA is requiring the manufacturer to conduct a 2000-patient post-approval study to assess the long-term safety and effectiveness of the device, and to look for rare adverse events that might result from using this product.

Additional Information:

Summary Information for: CYPHER™ Sirolimus-eluting Coronary Stent on RAPTOR® Over-the-Wire Delivery System or RAPTORRAIL® Rapid Exchange Delivery System - P020026.
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTopic/pma/pma.cfm?num=P020026


New Products to Treat Rare Diseases

FDA has recently approved three new products used to treat rare conditions.

Fabrazyme, made by Genzyme Corporation, is used to treat Fabry disease, and Aldurazyme is used to treat several genetic disorders including Hurler syndrome. Both of these products are biotech drugs produced by Recombinant DNA technology. The third product is Somavert, made by Pharmacia Corporation. It's a growth hormone receptor antagonist used to treat acromegaly.

These approvals were granted under what's known as the Orphan Drug Act. This law provides for research grants and other incentives that encourage manufacturers to develop new drugs and biologics to treat rare conditions-those that affect fewer than 200,000 people in the U.S. One important incentive is that the company that makes the first product developed to treat a rare disease is allowed seven years of exclusive marketing for that product. Considering the small number of patients affected by these diseases, firms wouldn't be inclined to invest the time and money in product development and testing without these incentives.

The Orphan Drug Act was signed into law in 1983, and since then it's been used to approve more than 200 products used to treat rare conditions including Crohn's disease, Hansen's disease, sickle cell anemia, bleeding disorders like hemophilia A and B, rare cancers and leukemias, and the PCP pneumonia that affects HIV/AIDS patients.

Additional Information:

FDA Press Release - Somavert.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/Safety-RelatedDrugLabelingChanges/ucm123343.htm


New Products to Treat Rare Diseases

FDA has recently approved three new products used to treat rare conditions.

Fabrazyme, made by Genzyme Corporation, is used to treat Fabry disease, and Aldurazyme is used to treat several genetic disorders including Hurler syndrome. Both of these products are biotech drugs produced by Recombinant DNA technology. The third product is Somavert, made by Pharmacia Corporation. It's a growth hormone receptor antagonist used to treat acromegaly.

These approvals were granted under what's known as the Orphan Drug Act. This law provides for research grants and other incentives that encourage manufacturers to develop new drugs and biologics to treat rare conditions-those that affect fewer than 200,000 people in the U.S. One important incentive is that the company that makes the first product developed to treat a rare disease is allowed seven years of exclusive marketing for that product. Considering the small number of patients affected by these diseases, firms wouldn't be inclined to invest the time and money in product development and testing without these incentives.

The Orphan Drug Act was signed into law in 1983, and since then it's been used to approve more than 200 products used to treat rare conditions including Crohn's disease, Hansen's disease, sickle cell anemia, bleeding disorders like hemophilia A and B, rare cancers and leukemias, and the PCP pneumonia that affects HIV/AIDS patients.

Additional Information:

Somavert Labeling.

http://www.fda.gov/cder/foi/label/2003/21106_somavert_lbl.pdf


New Products to Treat Rare Diseases

FDA has recently approved three new products used to treat rare conditions.

Fabrazyme, made by Genzyme Corporation, is used to treat Fabry disease, and Aldurazyme is used to treat several genetic disorders including Hurler syndrome. Both of these products are biotech drugs produced by Recombinant DNA technology. The third product is Somavert, made by Pharmacia Corporation. It's a growth hormone receptor antagonist used to treat acromegaly.

These approvals were granted under what's known as the Orphan Drug Act. This law provides for research grants and other incentives that encourage manufacturers to develop new drugs and biologics to treat rare conditions-those that affect fewer than 200,000 people in the U.S. One important incentive is that the company that makes the first product developed to treat a rare disease is allowed seven years of exclusive marketing for that product. Considering the small number of patients affected by these diseases, firms wouldn't be inclined to invest the time and money in product development and testing without these incentives.

The Orphan Drug Act was signed into law in 1983, and since then it's been used to approve more than 200 products used to treat rare conditions including Crohn's disease, Hansen's disease, sickle cell anemia, bleeding disorders like hemophilia A and B, rare cancers and leukemias, and the PCP pneumonia that affects HIV/AIDS patients.

Additional Information:

Product Approval Information – Licensing Action – Fabrazyme.
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm128159.htm


Recall of Counterfeit Lipitor

FDA is alerting healthcare providers and patients about a recall of several lots of the cholesterol-lowering drug Lipitor. The product in these lots is counterfeit Lipitor and it represents a potentially significant risk to consumers.

The label on the counterfeit product says "Repackaged by: MED-PRO, INC., Lexington, NE 68850."

Healthcare providers and patients should check Lipitor packaging very carefully before using this product. Patients who have any product from these lots that are labeled as "Repackaged by Med-Pro, Inc." should be instructed not take it and instead return the product to their pharmacies.

FDA is continuing to investigate this counterfeiting incident, so check our web site frequently for updates.

Additional Information:

FDA Talk Paper: Update: FDA Investigation Into Counterfeit Lipitor Two Distributors Recalling All Lipitor Repacked by MED-PRO.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm153325.htm


Fatal Medication Errors with Temodar

FDA has received several reports of serious medication errors, some of them fatal, with the drug Temodar, manufactured by Schering. This drug is a chemo therapeutic agent used to treat adult patients with refractory anaplastic astrocytoma.

Temodar comes in four strengths: 5 mg, 20 mg, 100 mg and 250 mg. Each of those strengths is available in two package sizes: five or twenty capsules per bottle. Unfortunately, the milligram strength and the number of capsules per bottle appear alongside each other on the label, and that's been the source of some of the errors: the number of capsules can be misread as the strength in milligrams, and vice versa. One woman who was supposed to receive 20 mg capsules actually received 250 mg capsules because "20 capsules" on the label was misread as "20 mg". She died ten days later. The FDA is working with the manufacturer to change the labeling so that it's clearer.

Health professionals can take several steps to help reduce the likelihood of an error. First, the FDA recommends that you circle or highlight the mg strength on the label to distinguish it from the number of tablets.

As an alternative, you can dispense Temodar in unit-dose form rather than from a multiple-dose bottle.

Another source of error with Temodar involves the dosing schedule. In some cases, Temodar was used for far too long.

The dosing schedule for Temodar calls for five consecutive days of treatment in each 28-day dosing cycle, followed by 23 days off the drug. In some of the reported cases, it was used far longer than that. One patient died after taking the drug for 22 consecutive days, and another died after taking the drug five times a week for three consecutive weeks. It's not clear whether these errors were due to miscommunication by the pharmacist or noncompliance by the patient.

FDA is recommending two things to help prevent these problems. First, don't dispense more than a five day supply at one time. And second, be sure to clarify all orders or prescriptions that are vague or unclear about the dosage or dosing instructions.

Additional Information:

FDA Safety Page: Drug Topics, April 7, 2003: "Fatal Medication Errors Associated with Temodar".

http://www.fda.gov/cder/drug/MedErrors/temodar.pdf


Syringe Stoppers Linked to Amniocentesis Problem

FDA has recently received reports in which cell growth was inhibited in amniocentesis cell cultures. This seems to have happened when the amniotic fluid wasn't transferred quickly from the collection syringe to the transport tube. Initial testing suggests that this inhibition of cell growth may be caused by the syringe stopper, the black, rubber-like grommet on the end of the plunger rod.

The manufacturers of the affected syringes have sent letters to labs and clinicians suggesting two precautions to help avoid this inhibition of cell growth.

First, they said, minimize the time the amniotic fluid stays in the syringe. The fluid should be transferred to the transport tube as soon as possible and not stored in the syringe.

And second, keep the amniotic fluid from coming into contact with the stopper by keeping the syringe "tip down" until the fluid is transferred.

Although the recent reports have only concerned amniocentesis, syringe manufacturers note that these recommendations should be followed any time a syringe is used to collect amniotic fluid or other primary cell samples. They also emphasize that these syringes can still be used safely for routine clinical applications, like blood collection and intravenous or hypodermic injections.

We'll continue to work with syringe manufacturers on this issue, and will update you with any new information.

Additional Information:

Dear Dr. Letter: Important Product Safety Information About Amniocentesis - Cell Growth Inhibitor.

http://www.tycohealthcare.com/Amnio%20letter.pdf


Mix up Between TD and PPD

The Institute for Safe Medication Practices has reported on several cases where a mix-up between two products led to unnecessary treatment. The products are the vaccine tetanus diphtheria toxoid and tuberculin PPD, both manufactured by the same company, Aventis Pasteur.

In these situations, a series of patients who were supposed to get PPD skin tests inadvertently received intradermal injections of the Td vaccine instead. The reactions from the Td injections were read as positive PPDs and the patients were started on isoniazid. The errors were discovered after staff noticed a cluster of positive PPD skin tests. The patients were retested and the INH therapy was stopped after the retests were negative.

ISMP points out that the similar packaging of these two products may have contributed to the errors. They both come in stylized, colorful cartons, although the carton colors do differ. Both products are available in cartons of the same size, and both have a circle on the front panel with the number "5" in it.

Both products are stored in the refrigerator and may be located side by side. So if your facility uses these Aventis products, be particularly alert to this possible mix-up. ISMP also suggests removing Td and other vaccines from floor stock, if feasible, and have the pharmacy dispense the vaccine instead.



Additional Information:

ISMP Medication Safety Alert – May 1, 2003: Hazard Alert! Confusion between tetanusdiphtheria toxoid (Td) and tuberculin purified protein derivative (PPD) led to unnecessary treatment.
http://www.ismp.org/hazardalerts/confusion.asp


Updated FDA Websites

Before we go, we wanted to draw your attention to several recently updated FDA web sites. First, there's FDA's SARS page. Here you can find out what FDA's doing to help develop SARS treatments, vaccines and diagnostic tools. You'll also find FDA's guidance for blood establishments on safeguarding the blood supply, including recommendations on deferring potential blood donors who have had SARS or may have been exposed to SARS.

On a different site, there's revised guidance for blood establishments on assessing donors for West Nile infection. In particular, there's a new recommendation that donors be asked a specific question about whether they've experienced a fever with headache within the week prior to donation.

And finally, some people have been asking whether they can use flu vaccine left over from last year for this coming season's immunizations, since the composition of this year's vaccine will be the same as last year's. FDA does not recommend this, because last year's vaccine will be past its expiration date, and the potency of the vaccine may have declined.

Additional Information:

FDA and SARS.
http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/BloodSafety/ucm095546.htm


Updated FDA Websites

Before we go, we wanted to draw your attention to several recently updated FDA web sites. First, there's FDA's SARS page. Here you can find out what FDA's doing to help develop SARS treatments, vaccines and diagnostic tools. You'll also find FDA's guidance for blood establishments on safeguarding the blood supply, including recommendations on deferring potential blood donors who have had SARS or may have been exposed to SARS.

On a different site, there's revised guidance for blood establishments on assessing donors for West Nile infection. In particular, there's a new recommendation that donors be asked a specific question about whether they've experienced a fever with headache within the week prior to donation.

And finally, some people have been asking whether they can use flu vaccine left over from last year for this coming season's immunizations, since the composition of this year's vaccine will be the same as last year's. FDA does not recommend this, because last year's vaccine will be past its expiration date, and the potency of the vaccine may have declined.

Additional Information:

FDA West Nile Virus Information.
http://www.fda.gov/ForConsumers/ByAudience/ForWomen/ucm118577.htm


Updated FDA Websites

Before we go, we wanted to draw your attention to several recently updated FDA web sites. First, there's FDA's SARS page. Here you can find out what FDA's doing to help develop SARS treatments, vaccines and diagnostic tools. You'll also find FDA's guidance for blood establishments on safeguarding the blood supply, including recommendations on deferring potential blood donors who have had SARS or may have been exposed to SARS.

On a different site, there's revised guidance for blood establishments on assessing donors for West Nile infection. In particular, there's a new recommendation that donors be asked a specific question about whether they've experienced a fever with headache within the week prior to donation.

And finally, some people have been asking whether they can use flu vaccine left over from last year for this coming season's immunizations, since the composition of this year's vaccine will be the same as last year's. FDA does not recommend this, because last year's vaccine will be past its expiration date, and the potency of the vaccine may have declined.

Additional Information:

FLU (Influenza) Vaccine.
http://www.fda.gov/cber/flu/flu.htm


New Products to Treat Rare Diseases

FDA has recently approved three new products used to treat rare conditions.

Fabrazyme, made by Genzyme Corporation, is used to treat Fabry disease, and Aldurazyme is used to treat several genetic disorders including Hurler syndrome. Both of these products are biotech drugs produced by Recombinant DNA technology. The third product is Somavert, made by Pharmacia Corporation. It's a growth hormone receptor antagonist used to treat acromegaly.

These approvals were granted under what's known as the Orphan Drug Act. This law provides for research grants and other incentives that encourage manufacturers to develop new drugs and biologics to treat rare conditions-those that affect fewer than 200,000 people in the U.S. One important incentive is that the company that makes the first product developed to treat a rare disease is allowed seven years of exclusive marketing for that product. Considering the small number of patients affected by these diseases, firms wouldn't be inclined to invest the time and money in product development and testing without these incentives.

The Orphan Drug Act was signed into law in 1983, and since then it's been used to approve more than 200 products used to treat rare conditions including Crohn's disease, Hansen's disease, sickle cell anemia, bleeding disorders like hemophilia A and B, rare cancers and leukemias, and the PCP pneumonia that affects HIV/AIDS patients.

Additional Information:

Product Approval Information – Licensing Action – Aldurazyme.
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm080438.htm



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