FDA Patient Safety News: Show #36, February 2005

IMPORTANT NEW INFORMATION -- First Monoclonal Antibody Treatment for MS

IMPORTANT NEW INFORMATION (June 5, 2006)

FDA notified healthcare professionals of the resumed marketing, with a special restricted distribution program of Tysabri (natalizumab), a monoclonal antibody for the treatment of patients with relapsing forms of multiple sclerosis. Tysabri was initially approved by the FDA in November 2004, but was withdrawn by the manufacturer in February 2005 after three patients in the drug’s clinical trials developed progressive multifocal leukoencephalopathy (PML), a serious viral infection of the brain. Tysabri will be available only through the Risk Management Plan, called the TOUCH Prescribing Program. In order to receive Tysabri, patients must talk to their doctor and understand the risks and benefits of Tysabri and agree to all of the instructions in the TOUCH Prescribing Program.

----------------- Original Story----------------------------

FDA recently approved the first monoclonal antibody treatment for patients with relapsing forms of multiple sclerosis. The product, called Tysabri (natalizumab), is intended to reduce the frequency of clinical exacerbations of the disease. Tysabri is marketed by Biogen Idec and Elan Pharmaceuticals.

The product is given intravenously every four weeks in a physician's office.
Tysabri appears to work by targeting part of the underlying inflammatory process in MS by inhibiting adhesion molecules on the surface of leukocytes. It's believed that this interaction prevents immune cells from migrating into the brain, where they can cause damage.

The drug's approval was based on positive results after the first year of treatment in two randomized, double-blind clinical trials. In one of the trials, in which Tysabri was compared to a placebo, it reduced the frequency of relapses by 66 percent. The manufacturer will continue these trials for another year.

Serious but uncommon side effects included infections, severe or life threatening allergic reactions, depression, and gallbladder problems. Common adverse reactions were generally mild and included non-serious infections, headache, and fatigue.

Additional Information:

Natalizumab (marketed as Tysabri) Information.
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm107198.htm


IMPORTANT NEW INFORMATION -- First Monoclonal Antibody Treatment for MS

IMPORTANT NEW INFORMATION (June 5, 2006)

FDA notified healthcare professionals of the resumed marketing, with a special restricted distribution program of Tysabri (natalizumab), a monoclonal antibody for the treatment of patients with relapsing forms of multiple sclerosis. Tysabri was initially approved by the FDA in November 2004, but was withdrawn by the manufacturer in February 2005 after three patients in the drug’s clinical trials developed progressive multifocal leukoencephalopathy (PML), a serious viral infection of the brain. Tysabri will be available only through the Risk Management Plan, called the TOUCH Prescribing Program. In order to receive Tysabri, patients must talk to their doctor and understand the risks and benefits of Tysabri and agree to all of the instructions in the TOUCH Prescribing Program.

----------------- Original Story----------------------------

FDA recently approved the first monoclonal antibody treatment for patients with relapsing forms of multiple sclerosis. The product, called Tysabri (natalizumab), is intended to reduce the frequency of clinical exacerbations of the disease. Tysabri is marketed by Biogen Idec and Elan Pharmaceuticals.

The product is given intravenously every four weeks in a physician's office.
Tysabri appears to work by targeting part of the underlying inflammatory process in MS by inhibiting adhesion molecules on the surface of leukocytes. It's believed that this interaction prevents immune cells from migrating into the brain, where they can cause damage.

The drug's approval was based on positive results after the first year of treatment in two randomized, double-blind clinical trials. In one of the trials, in which Tysabri was compared to a placebo, it reduced the frequency of relapses by 66 percent. The manufacturer will continue these trials for another year.

Serious but uncommon side effects included infections, severe or life threatening allergic reactions, depression, and gallbladder problems. Common adverse reactions were generally mild and included non-serious infections, headache, and fatigue.

Additional Information:

FDA Public Health Advisory - Suspended Marketing of Tysabri (natalizumab).
http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm051761.htm


New Warning on Depo-Provera Contraceptive Injection

The FDA recently announced that a new black-box warning is being added to the labeling for Depo-Provera Contraceptive Injection. The warning alerts prescribers that prolonged use may result in loss of bone density. Pfizer, the drug's manufacturer, has also issued a Dear Doctor letter with the same information, and the new information also appears in the patient information sheet.

The loss of bone density increases the longer the woman is on the drug and so the black box warning says that Depo Provera shouldn't be used as a long-term birth control method (for example, longer than two years) unless other methods aren't adequate. This bone density loss may not be completely reversible after discontinuation of the drug. This bone density loss may not be completely reversible after discontinuing the drug.

The "warnings" section of the label says that women with osteoporosis risk factors (e.g., metabolic bone disease, chronic alcohol or tobacco use, anorexia nervosa, a strong family history of osteoporosis, or chronic use of drugs that can reduce bone mass, such as anticonvulsants or corticosteroids) should consider other birth control methods. Another high risk group is adolescent women. The label warns that it's not known whether Depo-Provera might reduce their peak bone mass and increase the risk of osteoporotic fractures later in life.

Additional Information:

FDA MedWatch 2004 Safety Alert - Depo-Provera (medroxyprogesterone acetate injectable suspension).
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm154784.htm


Warning on Lymphoma Risk with TNF Blockers

The manufacturers of the drugs Humira (adalibumab), Remicade (infliximab) and Enbrel (etanercept) have added new safety information to the labels for these products about malignancies. These three drugs are tumor necrosis factor (TNF) blocking agents, and they're used to treat rheumatoid arthritis and other autoimmune diseases.

In controlled studies of TNF blockers, more cases of lymphoma occurred among patients receiving the agents than among control patients. And in open-label, uncontrolled clinical studies, the rate of malignancies in patients treated with TNF blockers was several times higher than would be expected in the general population. These uncontrolled studies can't establish a causal relationship between the TNF blockers and the excess malignancies, because patients with highly active autoimmune disease may be at increased risk for lymphoma, independent of the drugs they're taking.

Additional Information:

FDA MedWatch Safety Alert 2004 - Remicade (infliximab).
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm155493.htm


Warning on Lymphoma Risk with TNF Blockers

The manufacturers of the drugs Humira (adalibumab), Remicade (infliximab) and Enbrel (etanercept) have added new safety information to the labels for these products about malignancies. These three drugs are tumor necrosis factor (TNF) blocking agents, and they're used to treat rheumatoid arthritis and other autoimmune diseases.

In controlled studies of TNF blockers, more cases of lymphoma occurred among patients receiving the agents than among control patients. And in open-label, uncontrolled clinical studies, the rate of malignancies in patients treated with TNF blockers was several times higher than would be expected in the general population. These uncontrolled studies can't establish a causal relationship between the TNF blockers and the excess malignancies, because patients with highly active autoimmune disease may be at increased risk for lymphoma, independent of the drugs they're taking.

Additional Information:

FDA Arthritis Advisory Committee - Briefing Information: Update on the TNF-a Blocking Agents. March 4, 2003.
http://www.fda.gov/ohrms/dockets/ac/03/briefing/3930B1_01_B-TNF.Briefing.htm


Warnings for Bextra Strengthened

In an earlier program, we talked about serious skin and hypersensitivity reactions associated with the drug Bextra (valdecoxib). Bextra is a Cox-2 selective inhibitor used to treat osteoarthritis, rheumatoid arthritis and dysmenorrhea. Now we want to tell you about strengthened warnings about these skin reactions, and also about cardiovascular risks associated with Bextra.

Despite earlier warnings, FDA is still receiving reports of rare but serious skin reactions with Bextra, including Steven-Johnson Syndrome and toxic epidermal necrolysis, both of which can be fatal. So now the manufacturer, Pfizer, has added a boxed warning about this risk.

Although other Cox-2 inhibitors and traditional NSAIDS also increase the risk of these skin reactions, the rate of these side effects appears to be greater for Bextra than for other COX-2 agents.

So the labeling advises practitioners to watch for these skin reactions. Although they're most likely to occur during the first 2 weeks of treatment, they can occur any time during therapy. The labeling says to discontinue Bextra at the first appearance of a skin rash, mucosal lesions, or any other sign of allergic reactions. Bextra is contraindicated in patients who are allergic to sulfonamides.

The new information on cardiovascular risks comes from a study that included over 1500 patients treated with Bextra for pain after coronary artery bypass surgery. The study showed that they were more likely to have cardiovascular adverse events such as MI, stroke, deep vein thrombosis and pulmonary embolism than placebo-treated patients. Bextra is contraindicated for treating pain immediately following CABG.

Additional Information:

FDA MedWatch Safety Alerts – Bextra (valdecoxib).
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm153099.htm


Drug Name Confusion: Reminyl and Amaryl

The Institute for Safe Medication Practices recently reported on three cases where the antidiabetic agent Amaryl (glimepiride) had been dispensed to geriatric patients instead of the Alzheimer's medication Reminyl (galantamine hydrobromide). We've also received other reports of prescribing and dispensing errors caused by confusion between these two drugs.

Mistakenly administering Amaryl to non-diabetic Alzheimer's patients has caused serious adverse events, including severe hypoglycemia and two deaths. According to the ISMP, accidentally giving Amaryl to an older patient can be especially dangerous, because they may be more sensitive to its hypoglycemic effects.

ISMP says that these mix-ups may have been linked to poor prescriber handwriting along with the sound-alike, look-alike names. Three other factors may contribute to possible confusion: both drugs come in tablets, both are available in a 4 mg dosage strength, and they have generic names that could lead to them being stored close together. ISMP also notes that since Amaryl may be prescribed more often than Reminyl, pharmacists and nurses may automatically assume that an illegible Reminyl prescription is for Amaryl.

The distributors of Reminyl and Amaryl have recently sent letters to prescribers and pharmacists, warning them about the potential for these mix-ups. These letters also contain recommendations on how to prevent such errors. For example, they remind prescribers to spell out the drug name when prescribing over the phone and to clearly print written prescriptions. And they suggest that pharmacists physically separate these two drugs on the shelf, confirm the brand name with prescribers, and counsel patients about the product.

ISMP has additional recommendations, for example, reminding prescribers to indicate the medication's purpose on prescriptions. And they advise pharmacists and nurses to confirm that the patient is diabetic before dispensing or administering any antidiabetic medication.

Additional Information:

FDA MedWatch Safety Alert 2004 - Reminyl (galantamine hydrobromide).
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm152595.htm


Drug Name Confusion: Reminyl and Amaryl

The Institute for Safe Medication Practices recently reported on three cases where the antidiabetic agent Amaryl (glimepiride) had been dispensed to geriatric patients instead of the Alzheimer's medication Reminyl (galantamine hydrobromide). We've also received other reports of prescribing and dispensing errors caused by confusion between these two drugs.

Mistakenly administering Amaryl to non-diabetic Alzheimer's patients has caused serious adverse events, including severe hypoglycemia and two deaths. According to the ISMP, accidentally giving Amaryl to an older patient can be especially dangerous, because they may be more sensitive to its hypoglycemic effects.

ISMP says that these mix-ups may have been linked to poor prescriber handwriting along with the sound-alike, look-alike names. Three other factors may contribute to possible confusion: both drugs come in tablets, both are available in a 4 mg dosage strength, and they have generic names that could lead to them being stored close together. ISMP also notes that since Amaryl may be prescribed more often than Reminyl, pharmacists and nurses may automatically assume that an illegible Reminyl prescription is for Amaryl.

The distributors of Reminyl and Amaryl have recently sent letters to prescribers and pharmacists, warning them about the potential for these mix-ups. These letters also contain recommendations on how to prevent such errors. For example, they remind prescribers to spell out the drug name when prescribing over the phone and to clearly print written prescriptions. And they suggest that pharmacists physically separate these two drugs on the shelf, confirm the brand name with prescribers, and counsel patients about the product.

ISMP has additional recommendations, for example, reminding prescribers to indicate the medication's purpose on prescriptions. And they advise pharmacists and nurses to confirm that the patient is diabetic before dispensing or administering any antidiabetic medication.

Additional Information:

ISMP Medication Safety Alert. September 9, 2004.
http://www.ismp.org/MSAarticles/20040909.htm


Warnings on Proper Use of Bicillin

In a previous program, we talked about the dangers of mistakenly injecting long-acting penicillin IV rather than IM. Now we want to update you on recent changes to the product labeling that emphasize this warning, and also tell you about other labeling changes that warn against using the wrong type of Bicillin product to treat sexually transmitted diseases.

If long-acting penicillin products, such as Bicillin C-R or Bicillin L-A, are administered IV, the insoluble matter in the injection can cause cardiorespiratory arrest and death due to pulmonary embolism. So these products should only be administered by deep intramuscular injection. King Pharmaceuticals, the maker of Bicillin, has now added a black box warning to the labeling of both of these products to remind practitioners about this risk. A new warning not to use these products IV also now appears on product cartons and syringe labels.

To reduce the risk of injecting these products IV, practitioners should also pay attention to safety features on pre-filled Bicillin syringes and Tubex cartridges. These improvements can help visualize aspirated blood if a blood vessel is entered.

With this design, blood that enters the needle can be quickly seen as a red or dark-colored spot on the barrel of the glass cartridge immediately proximal to the blue syringe hub. To find where to look for a blood spot, first locate the yellow rectangle at the base of the blue hub, and draw an imaginary straight line from that rectangle to the shoulder of the glass cartridge. When the needle cover is removed, look for a second yellow rectangle, which is also aligned with the spot. The old metal Tubex holder, which is no longer distributed, should NOT be used because the metal strut may obstruct the view of a blood spot if improperly aligned.

King Pharmaceuticals also reminded practitioners that Bicillin L-A is the only penicillin G benzathine product indicated for sexually transmitted infections, including syphilis. In a number of U.S. STD clinics, patients with syphilis have been inappropriately treated with Bicillin C-R, a combination of penicillin G benzathine and penicillin G procaine. This product should not be used to treat syphilis because the patient may receive inadequate treatment.

To help practitioners distinguish between the two types of Bicillin, the background colors on the Bicillin C-R cartons have been changed, and a reminder statement that syphilis should not be treated with Bicillin C-R now appears in several places on the carton and on syringe labels.

Additional Information:

FDA Press Release - FDA Strengthens Labels of Two Specific Types of Antibiotics to Ensure Proper Use.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm153100.htm


Warnings on Proper Use of Bicillin

In a previous program, we talked about the dangers of mistakenly injecting long-acting penicillin IV rather than IM. Now we want to update you on recent changes to the product labeling that emphasize this warning, and also tell you about other labeling changes that warn against using the wrong type of Bicillin product to treat sexually transmitted diseases.

If long-acting penicillin products, such as Bicillin C-R or Bicillin L-A, are administered IV, the insoluble matter in the injection can cause cardiorespiratory arrest and death due to pulmonary embolism. So these products should only be administered by deep intramuscular injection. King Pharmaceuticals, the maker of Bicillin, has now added a black box warning to the labeling of both of these products to remind practitioners about this risk. A new warning not to use these products IV also now appears on product cartons and syringe labels.

To reduce the risk of injecting these products IV, practitioners should also pay attention to safety features on pre-filled Bicillin syringes and Tubex cartridges. These improvements can help visualize aspirated blood if a blood vessel is entered.

With this design, blood that enters the needle can be quickly seen as a red or dark-colored spot on the barrel of the glass cartridge immediately proximal to the blue syringe hub. To find where to look for a blood spot, first locate the yellow rectangle at the base of the blue hub, and draw an imaginary straight line from that rectangle to the shoulder of the glass cartridge. When the needle cover is removed, look for a second yellow rectangle, which is also aligned with the spot. The old metal Tubex holder, which is no longer distributed, should NOT be used because the metal strut may obstruct the view of a blood spot if improperly aligned.

King Pharmaceuticals also reminded practitioners that Bicillin L-A is the only penicillin G benzathine product indicated for sexually transmitted infections, including syphilis. In a number of U.S. STD clinics, patients with syphilis have been inappropriately treated with Bicillin C-R, a combination of penicillin G benzathine and penicillin G procaine. This product should not be used to treat syphilis because the patient may receive inadequate treatment.

To help practitioners distinguish between the two types of Bicillin, the background colors on the Bicillin C-R cartons have been changed, and a reminder statement that syphilis should not be treated with Bicillin C-R now appears in several places on the carton and on syringe labels.

Additional Information:

FDA MedWatch Safety Alert - Bicillin C-R (penicillin G benzathine and penicillin G procaine injectable suspension)/Bicillin L-A (penicillin G benzathine injectable suspension).
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm153100.htm


New FDA Website on Cochlear Implants

Patients with cochlear implants and their caregivers need an up-to-date source of information on these devices. FDA is now providing that service in a new web site.

The site explains what cochlear implants are and how they work, and what the surgery entails. It presents the benefits and risks involved, provides news about cochlear implant recalls and safety issues, and tells how to report problems. And it gives information that educators of implant patients need to know.

Additional Information:

FDA/CDRH Cochlear Implant Website.
http://www.fda.gov/cdrh/cochlear/


IMPORTANT NEW INFORMATION -- First Monoclonal Antibody Treatment for MS

IMPORTANT NEW INFORMATION (June 5, 2006)

FDA notified healthcare professionals of the resumed marketing, with a special restricted distribution program of Tysabri (natalizumab), a monoclonal antibody for the treatment of patients with relapsing forms of multiple sclerosis. Tysabri was initially approved by the FDA in November 2004, but was withdrawn by the manufacturer in February 2005 after three patients in the drug’s clinical trials developed progressive multifocal leukoencephalopathy (PML), a serious viral infection of the brain. Tysabri will be available only through the Risk Management Plan, called the TOUCH Prescribing Program. In order to receive Tysabri, patients must talk to their doctor and understand the risks and benefits of Tysabri and agree to all of the instructions in the TOUCH Prescribing Program.

----------------- Original Story----------------------------

FDA recently approved the first monoclonal antibody treatment for patients with relapsing forms of multiple sclerosis. The product, called Tysabri (natalizumab), is intended to reduce the frequency of clinical exacerbations of the disease. Tysabri is marketed by Biogen Idec and Elan Pharmaceuticals.

The product is given intravenously every four weeks in a physician's office.
Tysabri appears to work by targeting part of the underlying inflammatory process in MS by inhibiting adhesion molecules on the surface of leukocytes. It's believed that this interaction prevents immune cells from migrating into the brain, where they can cause damage.

The drug's approval was based on positive results after the first year of treatment in two randomized, double-blind clinical trials. In one of the trials, in which Tysabri was compared to a placebo, it reduced the frequency of relapses by 66 percent. The manufacturer will continue these trials for another year.

Serious but uncommon side effects included infections, severe or life threatening allergic reactions, depression, and gallbladder problems. Common adverse reactions were generally mild and included non-serious infections, headache, and fatigue.

Additional Information:

Drug Information Page - Tysabri (natalizumab).

http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089809.pdf



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