FDA Issued A Warning Letter To Valsartan API Manufacturer, Zhejiang Huahai Pharmaceutical Co. Ltd. (ZHP)

 Looks like not only iPhone and plastic toys are manufactured in China these days. Recently recalled Valsartan's active pharmaceutical ingredient too was manufactured in China by Zhejiang Huahai Pharmaceutical Co. Ltd. (ZHP). FDA is currently investigating probable cancer-causing impurities found in certain commonly prescribed heart medicines. FDA's letter to Zhejiang Huahai Pharmaceutical Co. Ltd. outlines several manufacturing violations at company’s Chuannan facility, including impurity control, change control and cross contamination from one manufacturing process line to another.

 

The U.S. Food and Drug Administration today released a warning letter issued to Zhejiang Huahai Pharmaceutical Co. Ltd. (ZHP), in Linhai, Taizhou Zhejiang China, the manufacturer of the active pharmaceutical ingredient (API) found in valsartan that is the subject of an ongoing FDA investigation into probable cancer-causing impurities in certain commonly prescribed heart medicines. The letter outlines several manufacturing violations at ZHP’s Chuannan facility, including impurity control, change control and cross contamination from one manufacturing process line to another. The warning letter is another step forward in the ongoing investigation. The agency is still looking into the root cause of the impurity.

“We’re continuing to investigate and take action to protect patient health and safety from products in this angiotensin II receptor blocker class that have been found to have dangerous impurities. As part of that investigation, we’ve uncovered serious manufacturing violations at ZHP, which is one of the manufacturing facilities that has been linked to these products. The issues cited in the warning letter are associated with the nitrosamine impurities found in these drugs, and these violations reveal a disturbing lack of oversight at this API manufacturer that puts patients at risk,” said FDA Commissioner Scott Gottlieb, M.D.

The ZHP facility manufactures API including valsartan, a drug in the angiotensin II receptor blocker (ARB) class used to treat high blood pressure and heart failure. On September 28, the FDA also put this facility on import alert, stopping all API made there and finished drug products made using its API from legally entering the U.S. The agency put ZHP on import alert based, in part, on high levels of impurities found in ZHP’s API.

The FDA announced recalls of valsartan beginning in July due to the presence of N-Nitrosodimethylamine (NDMA) in API supplied by ZHP. Subsequent international investigations expanded to include all manufacturers of API and finished drugs in the ARB class and have resulted in additional recalls of valsartan, irbesartan, and losartan-containing products found to contain NDMA and N-Nitrosodiethylamine (NDEA) – both known animal and suspected human carcinogens.  

There may be confusion regarding which products are affected by ARB recalls and which are not, especially concerning the most recent U.S. recalls of valsartan-containing products using API manufactured by Mylan that tested positive for unacceptable levels of NDEA. Certain ARB products have been recalled, and certain products that contain ARBs and one or more other active ingredients in a single dosage form have been recalled. It is important to note that the API in these products besides valsartan, irbesartan or losartan are not necessarily under a recall. As an example, valsartan/amlodipine/hydrochlorothiazide is one product that has been recalled. Neither amlodipine or hydrochlorothiazide are currently under recall. Similarly, losartan potassium and hydrochlorothiazide 100mg/25mg is a recalledproduct. The agency asks the public to pay careful attention to the agency’s website for the most accurate and up-to-date information. The agency’s website provides lists of valsartan products under recall, valsartan products not under recall and irbesartan products under recall for patients, health care providers and pharmacists to accurately confirm which products are affected.

The FDA continues to test all ARBs for the presence of impurities and has publicly posted two methods for manufacturers and regulatory agencies around the world to test their ARBs for the unexpected NDMA and NDEA impurities.

Patients taking any recalled ARB should continue taking their current medicine until their pharmacist provides a replacement or their doctor provides an alternative treatment option. It also is important to know that not all ARBs contain NDMA or NDEA, so pharmacists may be able to provide a refill of medication not affected by the recall, or doctors may prescribe a different medication that treats the same condition.

Patients, health care providers and pharmacists may contact the FDA’s Division of Drug Information for any questions regarding ARB recalls. Visit the FDA’s ARB recall webpage, call 855-543-3784 or email druginfo@fda.hhs.gov for more information. A question and answer webpage also provides information on these recalls.

American RED CROSS Fined 16Million For Failure To Meet Blood Safety Laws.

For Immediate Release: June 17, 2010
Media Inquiries: Shelly Burgess, 301-796-4651, shelly.burgess@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

FDA Fines American Red Cross $16 Million for Prior Failures to Meet Blood Safety Laws

The FDA announced today that the American Red Cross has been fined $16 million for prior failures to comply with Federal laws and regulations related to the collection and manufacture of blood products.
Despite the compliance failures, FDA found no evidence that the Red Cross violations endangered any patients and the blood supply is believed to be safe. Multiple layers of safeguards are in place to protect and enhance the safety of blood products. However, these types of violations decrease the assurance that blood products manufactured by American Red Cross will continue to be safe and have the potential to compromise the safety of the blood supply.

The FDA assessed fines totaling $16.18 million – $9.79 million for violations related to mismanagement of certain blood products and $6.39 million for Good Manufacturing Practice violations. Blood products include red cells, plasma and platelets.
FDA is encouraged by recent efforts made by the Red Cross leadership and will work closely with them to achieve full compliance. The FDA is hopeful these fines will encourage the Red Cross to act more quickly to take the actions necessary to address and correct the issues that have contributed to these violations.
In October 2009, the agency notified the American Red Cross that FDA inspections conducted during fiscal years 2008 and 2009 revealed violations that included failure to identify problems that occur during manufacturing and failure to adequately investigate identified problems.
The fines announced today were assessed under an amended 2003 consent decree that outlines requirements for the American Red Cross to ensure safety of the nation’s blood supply.
The original 1993 decree was amended in 2003 to allow the FDA to impose significant fines for failure to comply with agency regulations and provisions designed to ensure the safety of the nation’s blood supply.
Since 2003, the American Red Cross has made progress addressing some of its quality issues, including standardizing procedures, upgrading its National Testing Laboratories, and increasing oversight of the organization. However, to fully comply with federal regulations and consent decree provisions, the American Red Cross must make swift, additional progress on all of the issues the FDA has identified.
The agency has previously sent 12 similar letters to the American Red Cross and imposed a total of more than $21 million in fines under terms of the amended 2003 consent decree.
The American Red Cross is one of several organizations that is responsible for the nation’s blood supply.

For more information:
To access the adverse determination letters

Kanec USA Recalls Stud Capsule For Men Due To Undeclared Drug Ingredient

Audience: Consumers, Pharmacists
[Posted 04/06/2010] Kanec USA and FDA notified healthcare professionals of a nationwide recall of Stud Capsule For Men [Lot #060607-01/060108-01, Exp 6-2013], after being informed by FDA that laboratory analysis of a sample found the product to be adulterated with sildenafil, an FDA approved drug.
Use of this product may pose a threat to consumers because the analogue may interact with nitrates found in some prescription drugs (such as nitroglycerin) and may lower blood pressure to dangerous levels. Consumers with diabetes, high blood pressure, high cholesterol, or heart disease often take nitrates. ED is a common problem in men with these conditions, and consumers may seek these types of products to enhance sexual performance.
The products are sold as a blister pack containing one capsule per unit of use 24-packs in a Box. Lot number and expiration date appears on the seal. Consumers who have this recalled product in their possession should stop using them immediately.
[04/02/2010 - Press Release¹ - Kanec USA]

FDA has added a Boxed Warning to the label for propylthiouracil, to include information about reports of severe liver injury and acute liver failure, some of which have been fatal, in adult and pediatric patients using this medication.

Propylthiouracil

Audience: Endocrine healthcare professionals, Pharmacists, Pediatricians
[Updated 04/21/2010] FDA has added a Boxed Warning to the label for propylthiouracil, to include information about reports of severe liver injury and acute liver failure, some of which have been fatal, in adult and pediatric patients using this medication.
[Posted 06/04/2009] FDA notified healthcare professionals of the risk of serious liver injury, including liver failure and death, with the use of propylthiouracil in adult and pediatric patients. Reports to FDA’s Adverse Event Reporting System (AERS) suggest there is an increased risk of hepatotoxicity with proplythiouracil when compared to methimazole. FDA has identified 32 (AERS) cases (22 adult and 10 pediatric) of serious liver injury associated with propylthiouracil use. Although both proplythiouracil and methimazole are indicated for the treatment of hyperthyroidism due to Graves’ disease, healthcare professionals should carefully consider which drug to initiate in a patient recently diagnosed with Graves’ disease. Physicians should closely monitor patients on propylthiouracil therapy for symptoms and signs of liver injury, especially during the first six months after initiation of therapy. Propylthiouracil should not be used in pediatric patients unless the patient is allergic to or intolerant of methimazole, and there are no other treatment options available.
[04/21/2010 - Drug Safety Communication¹ - FDA]
[06/04/2009 - Healthcare Professional Sheet² - FDA]

   

FDA Takes Steps to Increase Safety of Foods During Transport

Agency poised to set new safety standards for the transportation of food in commerce; provides new guidance 
The U.S. Food and Drug Administration is asking commercial food transporters to follow new guidance the agency is issuing today to reduce the chances of physical, chemical, biological and other risks during transportation of foods while the agency reviews current food safety transportation regulations.
In an advance notice of proposed rulemaking (ANPRM) published in today's Federal Register, the FDA has requested input on writing the new rules from all interested parties, including the food and transportation industries and consumer interest organizations. The ANPRM is the first step in creating new regulations to govern sanitary practices by shippers, carriers by motor vehicle or rail vehicle, receivers, and others engaged in the transportation of food products for people and animals.
The new industry guidance covers safety measures that should be employed while the regulations are being written and finalized. They include ensuring that food in transit is maintained at appropriate temperatures; that such food is closely monitored for pests; that the vehicles used to transport foods are sanitary and in proper working condition; that pallets used are of good quality; and that sanitary measures are followed in the loading and unloading of foods.
"Our aim is to look at every component of the system to assess hazards, and to take science-based action where appropriate to maximize the safety of our food from farms all the way to consumers' tables," said FDA’s associate commissioner for food protection, Jeff Farrar. “Although contamination of food product during commercial transport is relatively infrequent, the potential harm can be widespread and serious.”
After evaluating comments received in response to the ANPRM, the FDA will propose specific regulations. The FDA will coordinate with the U.S. departments of Agriculture and Transportation in the rulemaking process.

For more information:

• ANPRM¹
• Sanitary Food Transportation Act²
• President’s Food Safety Working Group

FDA's Stance On IOM Sodium Report & Washington Post Story

FDA's Stance On IOM Sodium Report
FDA has issued an statement to clarify it's stance on the amount of sodium in foods and the regulation of it. A leading news paper Washington Post gives amistaken impression that the FDA has begun the process of regulating the amount of sodium in foods.
The FDA is not currently working on regulations nor have they made a decision to regulate sodium content in foods at this time.
Following is the statement issued by FDA in it's entirety.

For Immediate Release: April 20, 2010
Media Inquiries: Meghan Scott, 301-796-4675, Meghan.Scott@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA
FDA Issues Statement on IOM Sodium Report

Today’s average sodium intake is several times what the body requires and its long-term effect on our health is very serious. Hypertension, or high blood pressure, affects one in three U.S. adults – nearly 75 million people aged 20 or older. An additional 50 million adults suffer from pre-hypertension. High blood pressure can increase the risk for heart attacks, strokes, heart failure, and kidney failure. Too much sodium in the daily diet is a major contributor to high blood pressure.
A new report from the Institute of Medicine this week concludes that national action is imperative to reduce the sodium content of foods if we are to make significant progress toward reducing the risk of hypertension and major cardiovascular events for Americans.
A story in today’s Washington Post leaves a mistaken impression that the FDA has begun the process of regulating the amount of sodium in foods. The FDA is not currently working on regulations nor have they made a decision to regulate sodium content in foods at this time.
Over the coming weeks, the FDA will more thoroughly review the recommendations of the IOM report and build plans for how the FDA can continue to work with other federal agencies, public health and consumer groups, and the food industry to support the reduction of sodium levels in the food supply. The Department of Health and Human Services will be establishing an interagency working group on sodium at the Department that will review options and next steps
Success in reducing sodium intake will require coordinated national action, with participation of all. We are encouraged by the fact that some food manufacturers have already begun or announced their commitment to reduce sodium levels in their products.
As a consumer, you can start lowering your sodium intake today by purchasing foods low in sodium, asking your grocer to carry more low-sodium products, and asking for low-sodium options at restaurants.

Collaborating to Reduce Preventable Harm from Medications, FDA's Safe Use Initiative

Medicine safety
Today, tens of millions of people in the United States depend on prescription and over‐the‐counter (OTC) medications to sustain their health—as many as 3 billion prescriptions are written annually. Too many people, however, suffer unnecessary injuries, even death, as a result of preventable medication errors or misuse.
The approaches used today for managing medication risks in the United States were put in place over the last century, often in a piecemeal fashion and usually in response to various crises and specific needs. Although FDA and many other stakeholders have been working to improve how the healthcare system manages medication risks in the United States, it is widely recognized that more needs to be done to protect the public from preventable harm from medication use. All participants in the healthcare community at large—patients, consumers, caretakers, healthcare practitioners, pharmacists, healthcare systems, health insurers, drug manufacturers, FDA, and other Federal agencies—have a role to play in managing medication risks and reducing preventable harm from medication. We believe that much preventable harm from medications results from problems that can be addressed best in a more coordinated, systematic manner, with interventions across all sectors of the medication distribution and use system.Medicine safety
FDA’s Safe Use Initiative contained in the report (Click on the link at the end for a PDF version on the report). Through this initiative, FDA seeks to partner and collaborate with relevant stakeholders to measurably reduce preventable harm from medications, thereby improving patient health. FDA proposes to identify, using a transparent and collaborative process, specific candidate cases (e.g., drugs, drug classes, and/or therapeutic situations) that are associated with significant amounts of preventable harm. Cases will be carefully analyzed for their potential for coordinated FDA/stakeholder actions to better manage related risks and reduce harm. If the analysis suggests a potential benefit from an intervention, FDA and its interested partners will develop appropriate activities and evaluation metrics. In the months ahead, FDA intends to:

• Develop a general list of candidate cases for collaborative analysis and intervention. The list will be developed through extensive consultation with all interested public and private stakeholders and may include one or more of the existing opportunities listed in the Proposal section of this report.
• Collaborate with Federal partners to develop population‐based national estimates of  preventable harm from medications, categorized by drug, drug classes, and therapeutic situations.
• Open a public docket to receive suggestions and comments related to this report, risk management issues, and proposed candidate cases.
• Hold a series of meetings to gather broad public feedback as the candidate list is being developed.
• Based on the public contribution just outlined and the best available population‐based data, work with interested partners to select specific candidate cases for analysis, intervention proposals, and evaluation metrics.
• During the Initiative’s first 12 months, implement a small number of interventions. Each intervention will have an explicit plan for measuring impact. Interventions may involve FDA regulatory actions in concert with actions by other stakeholders.

Through a coordinated effort, involving all interested stakeholders, we can work to minimize the risks associated with using medications and reduce preventable harm.
FDA's (Food and Drug Administration)  Safe Use Initiative

Question And Answer Slim-Fast Recall By Unilever United States, Inc.

Question and answer series on recall of all Slim-Fast ready-to-drink products in cans  by Unilever due to the risk of contamination with Bacillus cereus
What is Bacillus cereus?
Bacillus cereus is a bacterium that can cause foodborne illness.
What are the symptoms of illness caused by Bacillus cereus?
Bacillus cereus can cause two types of foodborne illness -- a diarrheal illness and a vomiting illness.

• Symptoms of Bacillus cereus diarrheal illness include watery diarrhea, abdominal cramps, and pain beginning six to 15 hours after consumption of contaminated food. Nausea may accompany these symptoms, but vomiting rarely occurs. Symptoms for the diarrheal illness typically persist for 24 hours.
• Symptoms of Bacillus cereus vomiting type of illness include nausea and vomiting within 30 minutes to six hours after consumption of contaminated foods. Occasionally, abdominal cramps and/or diarrhea may also occur. Duration of the symptoms for the vomiting type of illness is generally less than 24 hours.
• More information on Bacillus cereus and the illness it causes is available at this link to FDA's Bad Bug Book¹.

How can I tell if the product I have is the same as the product under recall?
The recalled products are packaged in paperboard cartons and contain 4, 6 or 12 steel cans that are labeled as containing 11 FL OZ (325 mL) each. Individual cans are also sold in certain retail outlets. The recall involves all Slim-Fast ready-to-drink products in cans, regardless of flavor, Best-By date, lot code, or UPC number. A listing of all recalled Slim-Fast ready-to-drink products in cans and a photograph of a recalled product are attached to the firm's press release, which is available on the FDA's Safety Alerts Page².
Are all Slim-Fast products affected by this recall?
No. Only Slim-Fast ready-to-drink products in cans are affected by this recall.
I recently drank some of the recalled product and feel sick. What should I do?
If you are experiencing symptoms described above and have recently ingested some of the recalled product, FDA advises that you see a doctor.
I have some of the recalled product in my home. What should I do with it?
Consumers who have any of the recalled products on hand should throw them away immediately.
I drank some of the recalled product but did not get sick. Can I continue to drink the product I have on hand?
No. The product is under voluntary recall and consumers should not drink any of the recalled Slim-Fast products.
I feel sick but haven't drunk any of the recalled product for several days. Could it be the product that made me sick?
Highly unlikely. The onset of symptoms of Bacillus cereus illness normally occurs within a 1/2 hour to 15 hours after a contaminated food product has been consumed, but, if you are unsure, then you should see a doctor.
What is the FDA doing about this recall?
FDA is investigating at the processing plant where the recalled products were manufactured, and working directly with the company to ensure that all suspect products are removed from the marketplace and that the public and the media are informed about this product recall and the potential risk to consumers.
Can I get my money back for recalled product I have already purchased?
Unilever has advised customers to call 1-800-896-9479 for a full refund.

Xiadafil VIP Tablets Seized By Federal Authorities After SEI Pharmaceuticals Refuses to Recall The Product.

FOR IMMEDIATE RELEASE July 24, 2008

Media Inquiries: Rita Chappelle, 301-827-6242 Consumer Inquiries: 888-INFO-FDA

Federal Authorities Seize Xiadafil VIP Tablets After Company Refuses to Recall Product
Product contains undeclared ingredient that could harm consumers

At the request of the U.S. Food and Drug Administration, U.S. Marshals seized nearly $74,000 worth of Xiadafil VIP tablets, Lots 6K029 and 6K209-SEI, distributed by SEI Pharmaceuticals, Inc. of Miami, Fla. Although marketed as a dietary supplement to treat erectile dysfunction (ED) and for sexual enhancement, these lots represent an illegally marketed drug containing an undeclared ingredient.

Today's action follows a formal FDA request to SEI Pharmaceuticals (SEI) on May 27, 2008, to recall the lots of Xiadafil VIP tablets. The products were given away at trade shows and sold in eight tablet bottles (Lot # 6K029) and blister cards of two tablets (Lot # 6K029-SEI) bearing an expiration date of September 2009 (09/09). The company, however, refused to recall these products, making the seizure action necessary to prevent additional, illegal Xiadafil VIP products from entering the marketplace.

The FDA's chemical analysis of Xiadafil VIP tablets Lots # 6K029/6K029-SEI found that the product contains hydroxyhomosildenafil, which is chemically similar to sildenafil. Sildenafil is the active ingredient in Viagra, an FDA-approved prescription drug for ED. The FDA has not approved Xiadafil VIP for ED or any other drug use, and the safety and effectiveness of this product is unknown. Although offered for sale as dietary supplements, the seized articles are new drugs that may not be introduced into interstate commerce without an approved new drug application filed with FDA.

"Today's seizure action shows that FDA will take enforcement action to protect the public from dietary supplements that contain prescription drug ingredients that are potentially harmful to consumers," said Margaret O'K Glavin, associate commissioner of the FDA's Office of Regulatory Affairs. "FDA will not tolerate a company's failure to take voluntary action to protect the public health after being given the opportunity by FDA to do so," she added.

On April 22, 2008, the FDA initiated an inspection at SEI Pharmaceuticals following its analysis of the Xiadafil VIP tablets. The company was advised of the FDA's findings and informed of the potential adverse health risks the product posed to unsuspecting consumers. The FDA also warned the company of possible legal actions, including seizure and/or injunction if corrective and preventive actions were not implemented. Although the company committed to halting distribution of the product and deactivated its Internet site, it refused to recall the product already in the market.

On May 13, 2008, Florida state officials issued a "stop sale" action at SEI's distribution facility to keep the illegal product out of the marketplace. This action required SEI to hold, intact, violative Xiadafil VIP tablets found at the facility.

ED is a common problem in men who have diabetes, high blood pressure, high cholesterol, or heart disease. Because they may have been advised against taking ED drugs, men with these conditions may seek alternative products like Xiadafil VIP tablets because they are marketed as "all natural" or as not containing the active ingredients in approved, prescribed ED drugs. Furthermore, because the manufacturing source of the active ingredients in many of these alternative products is unknown, consumers should also be aware that the safety, efficacy, and purity of these ingredients have not been verified by the FDA.

Consumers should discontinue the use of Xiadafil VIP tablets immediately and consult their health care professional if they have experienced adverse events that they believe may be related to the use of this product.

Consumers and health care professionals can report adverse events to the FDA's MedWatch program at 800-FDA-1088, by mail at MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, Md 20852-9787, or online at www.fda.gov/medwatch/report.htm.

Tags: SEI Pharmaceuticals Recall, Xiadafil VIP Tablets Recall, FDA Action, FDA Seizure, erectile dysfunction

The Food and Drug Administration (FDA) Requests Stronger Warnings On Fluoroquinolones Drug's Label.

Stronger Warnings Requested for Fluoroquinolones

The Food and Drug Administration (FDA) has notified manufacturers of fluoroquinolone antimicrobial drugs that a boxed warning on the increased risk of tendinitis and tendon rupture is necessary. A boxed warning on a drug's label calls attention to serious or life-threatening risks.

The agency has also determined that manufacturers should provide patients with a Medication Guide about possible side effects. Medication Guides are paper handouts that come with certain prescription medications.

What are fluoroquinolones?

Fluoroquinolones are drugs approved for the treatment or prevention of certain bacterial infections. Like other antibacterial drugs, fluoroquinolones do not treat viral infections such as colds or flu.

Which drugs are involved in this action?

These warnings would apply to fluoroquinolones for systemic use (e.g., pills, tablets, capsules and injectable formulations). The warnings would not apply to fluoroquinolones for topical ophthalmic or otic use (e.g., eye and ear drops).

The medications involved in this action are: Cipro and generic ciprofloxacin, Cipro XR and Proquin XR (ciprofloxacin extended release), Factive (gemifloxacin), Levaquin (levofloxacin), Avelox (moxifloxacin), Noroxin (norfloxacin), and Floxin and generic ofloxacin.

What should patients know?

• The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is further increased in people older than 60, in people taking corticosteroid drugs, and in kidney, heart, and lung transplant recipients.
• Patients experiencing pain, swelling, inflammation of a tendon or tendon rupture should stop taking their fluoroquinolone medication and contact their health care professional promptly about changing their antimicrobial therapy.
• Patients should also avoid exercising and using the affected area at the first sign of tendon pain, swelling, or inflammation.

This article appears on FDA's Consumer Health Information Web page.

Meddesktop

Tags: FDA Action, Fluoroquinolones, tendinitis, tendon rupture, bacterial infections.antibacterial drugs, ophthalmic Use, otic use, Cipro, generic ciprofloxacin, Cipro XR, Proquin XR, Factive, Levaquin, Avelox, Noroxin, Floxin, generic ofloxacin

FDA Revises Communication Process For Drug Applications

FOR IMMEDIATE RELEASE July 9, 2008

Media Inquiries: Christopher DiFrancesco, 301-827-6242 Consumer Inquiries: 888-INFO-FDA

FDA Revises Process for Responding to Drug Applications

The U.S. Food and Drug Administration today announced that it is revising the way it communicates to drug companies when a marketing application cannot be approved as submitted.

Under new regulations that govern the drug approval process, FDA's Center for Drug Evaluation and Research (CDER) will no longer issue "approvable" or "not approvable" letters when a drug application is not approved. Instead, CDER will issue a "complete response" letter at the end of the review period to let a drug company know of the agency's decision on the application.

"These new regulations will help the FDA adopt a more consistent and neutral way of conveying information to a company when we cannot approve a drug application in its present form," said Janet Woodcock, M.D., director of the agency's Center for Drug Evaluation and Research (CDER). "Thorough and timely review of drug applications is a priority of the FDA, and these new processes will make our communications with sponsors of applications more consistent."

Taking the place of "approvable" and "not approvable" letters, a "complete response" letter will be issued to let a company know that the review period for a drug is complete and that the application is not yet ready for approval. The letter will describe specific deficiencies and, when possible, will outline recommended actions the applicant might take to get the application ready for approval.

Currently, when assessing new drug applications, the FDA can respond to a sponsor in one of three types of letters: an "approval" letter, meaning the drug has met agency standards for safety and efficacy and the drug can be marketed for sale in the United States; an "approvable" letter, which generally indicates that the drug can probably be approved at a later date provided that the applicant provides certain additional information or makes specified changes (such as to labeling); or a "not approvable" letter, meaning the application has deficiencies generally requiring the submission of substantial additional data before the application can be approved.

"Complete response" letters are already used to respond to companies that submit biologic license applications. The process for drugs and biologics will be consistent under the new regulations.

The revision should not affect the overall time it takes the FDA to review new or generic drug applications or biologic license applications. These changes, which will become effective on Aug. 11, 2008, are not expected to directly affect consumers.

In July 2004, the FDA issued a proposed rule on these topics. At that time the agency asked for comments on the proposal. Today's final rule addresses comments submitted to the agency.

For more information, see:

Link to the Complete Response Final Rule
http://www.fda.gov/cder/regulatory/complete_response_FR/default.htm

Link to the drug approval process page
http://www.fda.gov/fdac/special/testtubetopatient/default.htm

Tags: Center for Drug Evaluation and Research, CDER, FDA, FDA Action

FDA's Ongoing Drug Safety Reviews On CellCept, Singulair, And Spiriva Handihaler.

FDA has informed the health care community about ongoing safety reviews of several drugs. FDA is doing this as part of its commitment to inform health care professionals and the public about its ongoing drug safety reviews. Because this information is preliminary and there is scientific uncertainty, FDA is not taking regulatory action at this point, and is not advising health care professionals to stop using the drugs. FDA is continuing to evaluate the safety of these products, and will issue updates as more information becomes available.

• CellCept (mycophenolate mofetil) and Myfortic (mycophenolic acid)

One of the ongoing safety reviews concerns two drugs used to prevent organ rejection, CellCept (mycophenolate mofetil) and Myfortic (mycophenolic acid). CellCept is approved to prevent heart, liver and kidney transplant rejection. Myfortic is approved to prevent kidney transplant rejection.

This safety review focuses on a potential association between these drugs and a rare, life-threatening CNS disorder called or progressive multifocal leukoencephalopathy (PML). PML occurs when a latent polyoma virus called the JC virus is activated and attacks the myelin sheath surrounding nerve cells. Most adults carry the virus, which becomes activated mainly in immuno-compromised patients. Symptoms of PML include vision changes, apathy, memory loss or confusion, ataxia and muscular weakness.

FDA is reviewing data on the possible association between CellCept and PML. Roche, the manufacturer of CellCept, and Novartis, the manufacturer of Myfortic, have proposed changes in the labeling of these drugs to include information on PML.

Until FDA has more information, healthcare professionals should be alert to the localized neurologic signs and symptoms that could signal PML in patients taking CellCept and Myfortic. They should also consider reducing the amount of immuno-suppression if a patient develops PML.

• Singulair (montelukast)

In another communication, FDA is informing healthcare professionals about a possible association between the use of Singulair and behavior and mood changes, suicidality and suicide. Singulair (montelukast) is used to treat asthma and allergic rhinitis, and to prevent exercise-induced asthma.

Singulair's manufacturer, Merck & Co., has updated the adverse events information in the drug's labeling several times over the past year. Those adverse events include tremor, depression, suicidality and anxiety. Merck plans to highlight these changes to prescribers, and to provide patient information leaflets on the drug.

FDA is reviewing reports of behavior and mood changes, suicidality and suicide in patients on Singulair, and has asked Merck to review its own clinical trial data for more information about suicide and suicidality. FDA will let clinicians and patients know about the results of these evaluations as soon as they're complete. In the meantime, patients on Singulair should be monitored for suicidality and changes in mood or behavior, and they should be instructed not to discontinue the drug without medical advice.

FDA is also reviewing reports of mood and behavioral changes in other asthma drugs, including Accolate (zafirlukast) and Zyflo (zileuton), and will decide whether further investigation is needed.
FDA's Ongoing Drug Safety Issues On CellCept, Singulair, And Spiriva Handihaler.
• Spiriva Handihaler (tiotropium)

In another communication, FDA informed health professionals of a possible increase in the risk of stroke among patients using the Spiriva Handihaler. This product, which contains tiotropium bromide, is used to treat bronchospasm associated with chronic obstructive pulmonary disease.

The manufacturer, Boehringer Ingelheim, conducted a pooled analysis of 29 studies of two tiotropium products, including the Spiriva Handihaler. In this analysis, patients using Spiriva experienced a stroke risk of 8/1000 per year compared with 6/1000 per year for those using a placebo. Pooled analyses like this one have inherent limitations, and so these results must be confirmed by further investigation using other data sources.

FDA has asked for more information from Boehringer Ingelheim, and is also reviewing adverse event reports for this product. The company has conducted a large, four-year study of the Spiriva Handihaler which should provide more information on the potential risks of this product. Results are expected soon. At that point, FDA will analyze all of the data and report its results to health professionals and the public. In the meantime, patients should not stop using the Spiriva Handihaler without talking to their doctors.

Again, these communications are preliminary information, and they're in keeping with FDA's commitment to inform the public about its ongoing drug safety reviews. FDA urges healthcare professionals and patients to report adverse reactions from any of the products discussed here through FDA's Medwatch program at 1-800-FDA-1088 or at the link below.

FDA MedWatch Page. Voluntary Reporting by Health Professionals.
http://www.fda.gov/medwatch/report/hcp.htm

Tags: Spiriva Handihaler, CellCept, Myfortic, mycophenolate mofetil, Singulair, montelukast, mood changes, suicidality, Accolate, FDA Action, Drug Safety, zafirlukast, Zyflo, zileuton, Spiriva Handihaler, tiotropium

Animal Food Products Seized From PETCO Distribution Center.

FOR IMMEDIATE RELEASE June 19, 2008

Media Inquiries: Kimberly Rawlings, 301-827-6242 Consumer Inquiries: 888-INFO-FDA

FDA Requests Seizure of Animal Food Products at PETCO Distribution Center

Today, at the request of the U.S. Food and Drug Administration (FDA), U.S. Marshals seized various animal food products stored under unsanitary conditions at the PETCO Animal Supplies Distribution Center located in Joliet, Ill., pursuant to a warrant issued by the United States District Court in Chicago.

U.S. Marshals seized all FDA-regulated animal food susceptible to rodent and pest contamination. The seized products violate the Federal Food, Drug, and Cosmetic Act because it was alleged in a case filed by the United States Attorney that they were being held under unsanitary conditions. (The Act uses the term "insanitary" to describe such conditions).

During an FDA inspection of a PETCO distribution center in April, widespread and active rodent and bird infestation was found. The FDA inspected the facility again in May and found continuing and widespread infestation.

"We simply will not allow a company to store foods under filthy and unsanitary conditions that occur as a direct result of the company's failure to adequately control and prevent pests in its facility," said Margaret O'K. Glavin, associate commissioner for regulatory affairs. "Consumers expect that such safeguards will be in place not only for human food, but for pet food as well."

The distribution center in Joliet, Ill., provides pet food products and supplies to PETCO retail stores in 16 states including Alabama, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Michigan, Minnesota, Missouri, Nebraska, Ohio, Oklahoma, Tennessee, Texas, and Wisconsin.

FDA has no reports of pet illness or death associated with consumption of animal food distributed by PETCO, and does not have evidence that the food is unsafe for animals. However, the seized products were in permeable packages and held under conditions that could affect the food's integrity and quality.

As a precaution, consumers who have handled products originating from the PETCO distribution center should thoroughly wash their hands with hot water and soap. Any surfaces that came in contact with the packages should be washed as well. Consumers are further advised as a precaution to thoroughly wash products sold in cans and glass containers from PETCO in the 16 affected states.

If a pet has become ill after eating these food products, pet owners should contact their veterinarian and report illnesses to FDA state consumer complaint coordinators.

Tags: FDA Action, Animal Food, Pet Food, PETCO, rodent and pest contamination

Changes In Albuterol Delivery System, Albuterol Inhaler With HFA.

Click On The Image Above To Download A PDF Version Of This Report

Albuterol is a quick-relief medication that's used to open up the airways so that it's easier to breathe. The medication is used by people with certain airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), a group of lung diseases that includes chronic bronchitis and emphysema.

One method of delivering albuterol is the metered dose inhaler, a hand-held device that delivers a specific amount of medication directly into the lungs. Traditionally, inhalers have contained chlorofluorocarbons (CFCs), a type of propellant that helps the albuterol reach the lungs. But inhalers with CFCs are being phased out because they are harmful to the environment.

Here are facts you should know about switching from your CFC-propelled albuterol inhaler to inhalers that contain propellants called hydrofluoroalkanes (HFAs).

CFCs deplete the ozone layer.

CFCs deplete ozone high up in the stratosphere--the part of the earth's atmosphere that protects us from the sun's harmful ultraviolet radiation. In the stratosphere, the ozone layer serves as a shield that absorbs ultraviolet radiation and keeps it from reaching the earth's surface. CFCs are among the substances that damage the ozone layer. This leads to higher levels of ultraviolet B radiation, which has negative effects, including increases in skin cancers and cataracts. Under an international agreement, the United States, along with almost all countries of the world, agreed to phase out CFCs and other ozone-depleting substances.

CFC-propelled albuterol inhalers will no longer be available after Dec. 31, 2008.

In accordance with an FDA Final Rule and under the authority of the Clean Air Act of the U.S. Environmental Protection Agency, no CFC-propelled albuterol inhalers can be produced, marketed, or sold in the United States after Dec. 31, 2008. Manufacturers have been increasing production of HFA-propelled albuterol inhalers so that sufficient supplies exist to replace the CFC-containing inhalers. If you haven't done so already, you should talk with your health care professional about switching to an HFA-propelled albuterol inhaler.

Albuterol inhalers containing HFAs deliver the same medicine, but there are some differences.

The HFA-propelled albuterol inhalers are still convenient and have been shown to be safe and effective in studies with patients. But you may find that the spray from an HFA inhaler tastes and feels different than the spray from the CFC-propelled albuterol inhalers. The spray from an HFA inhaler may feel less forceful, but this does not mean that the medication is not working.

Cleaning and priming your HFA inhaler are especially important.

Cleaning and priming helps prevent medication build-up and blockages, and ensures that the inhaler works properly. Priming an inhaler involves shaking it well and then releasing test sprays into the air. Be sure to hold the inhaler away from your face so that you don't get medication in your eyes. Each inhaler has specific instructions for cleaning and priming that you should follow. Refer to the patient information that accompanies the product.

Four alternative HFA-propelled inhalers are approved by FDA.

There are four products available that can be used to replace your CFC-propelled albuterol inhaler:

• Proair HFA Inhalation Aerosol (Ivax Corp.)
• Proventil HFA Inhalation Aerosol (Schering-Plough)
• Ventolin HFA Inhalation Aerosol (GlaxoSmithKline)
• Xopenex HFA Inhalation Aerosol (Sepracor)

While they have all been shown to be effective, there are some differences between the products. You may need to talk with your health care professional and try different inhalers to find the product that is right for you.

For More Information

Metered Dose Inhalers (MDIs)
www.fda.gov/cder/mdi/default.htm

FDA Safety Update: Asthma Medications
www.fda.gov/consumer/updates/asthmameds051308.html

FDA's Web Page on Eliminating Ozone-depleting Substances from Metered-Dose Inhalers
www.fda.gov/cder/mdi/albuterol.htm

Tags: FDA Guidance, FDA Action, Asthma Medication, COPD Medication, Albuterol, Proair HFA Inhalation Aerosol, Proventil HFA Inhalation Aerosol, Ventolin HFA Inhalation Aerosol, Xopenex HFA Inhalation Aerosol

Pregnancy and Lactation Labeling

The U.S. Food and Drug Administration today proposed major revisions to the physician labeling for prescription drugs (including biological products) to provide better information about the effects of medicines used during pregnancy and breast-feeding.

The proposed changes to prescription drug labeling would give health care professionals more comprehensive information for making prescribing decisions and for counseling women who are pregnant, breast-feeding, or of child-bearing age about using prescription medications.

Although physician labeling is directed to health care professionals, it is sometimes adapted for use in consumer-directed labeling such as patient package inserts or medication guides when such labeling is approved for a prescription drug.

"With this proposal, FDA's goal is to help women, their physicians and their pharmacists have better information about the effects of prescription medicines so that pregnant women, nursing mothers, and breast-feeding infants will benefit," said Rear Admiral Sandra Kweder, M.D., Center for Drug Evaluation and Research, FDA. "This proposal would help make drug labeling a better communication tool, and would potentially have a huge impact on public health and well being for women."

There are about six million pregnancies in the United States every year, and pregnant women take an average of three to five prescription drugs during pregnancy. Additionally, women with pre-existing medical conditions, such as asthma or high blood pressure, may need to continue to use prescription drugs to treat those conditions during pregnancy.

The proposed rule outlines what important information about the use of medicines during pregnancy and breast-feeding would be required to be added to product labeling for newly approved drugs. Under the proposal, drug labeling would explain, based on available information, the potential benefits and risks for the mother and the fetus, and how these risks may change during the course of pregnancy.

In the 1990s, the FDA recognized the shortcomings of pregnancy and breastfeeding information in prescription drug labeling and began reviewing ways to improve the information. The agency held public meetings and focus groups to obtain comment on the current labeling from health care professionals and scientific experts. Current labeling uses a letter category system to describe the risks of drug use during pregnancy. Stakeholders have said the letter category system leads to an inaccurate and overly simplified view of these risks, and does not facilitate updating of labeling as new information becomes available.

The proposed rule would remove the letter categories from the pregnancy section of prescription drug labeling. The newly designed format, for the pregnancy section of the labeling would have three sections:

• The first section, called the "Fetal Risk Summary," would describe what is known about the effects of the drug on the fetus, and if there is a risk, whether this risk is based on information from animals or humans. The proposal calls for a risk conclusion based on the available data and provides a number of examples depending on the quality and quantity of that data. For example, one risk conclusion might be: "Human data indicate that (name of drug) increases the risk of cardiac abnormalities." This would be followed by a summary of the most important data on the drug’s effects.
• Another section, called "Clinical Considerations," would include information about the effects of the use of the drug if it is taken before a woman knows she is pregnant. This section also would feature discussions about the risks of the disease to the mother and the baby, dosing information, and tell how to address complications.
• The third section, under the heading "Data," would describe in more detail the available data regarding use of the drug in humans and from animal studies that were used to develop the Fetal Risk Summary.

The pregnancy section would also include information about whether there is a pregnancy exposure registry for the drug. Pregnancy exposure registries collect and maintain data on the effects of approved drugs that are prescribed to and used by pregnant women.

The lactation (breastfeeding) section of prescription drug labeling would use the same format as the pregnancy section. The lactation section would provide information about using the drug while breastfeeding, such as the amount of drug in breast milk and potential effects on the breastfed infant.

Certain newly approved drugs would use the new pregnancy and lactation labeling format, while labeling for previously approved drugs will be phased in gradually under FDA’s recent Physician Labeling Rulemaking.

Electronic comments can be submitted within 90 days via the Federal Documents Management System/eRulemaking portal at www.regulations.gov. The FDA will carefully consider the comments in preparing a final rule.

For more information, visit: http://www.fda.gov/cder/regulatory/pregnancy_labeling/default.htm

Tags: Pregnancy, Lactation, prescription drugs Labeling, biological products Labeling

Request for Comments: Potential for a Registry of Breast Cancer Treatment Using Thermal Ablation Devices.

SUMMARY: The Food and Drug Administration (FDA) is requesting comments on whether a registry could facilitate standardization of feasibility trials studying local treatment of small breast cancers with different thermal ablation devices and therapies (i.e. cryoablation, focused ultrasound, interstitial laser, microwave, radiofrequency ablation). FDA is specifically interested in understanding how breast cancer ablation feasibility trials can be constructed so that there exists standardized evaluation of tissue biopsy pathology, selection of tumors amenable to ablation, image guidance for ablation, post-ablation imaging and assessment, and tissue pathology of ablated specimens. The agency seeks to facilitate its understanding of local treatment for breast cancer using thermal ablation devices.

DATES: Submit written or electronic comments by November 24, 2008.

ADDRESSES: Submit written comments concerning this document to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments to http://www.regulations.gov.
To ensure timelier processing of comments, FDA is no longer accepting comments submitted to the agency by e-mail.

FOR FURTHER INFORMATION CONTACT: Binita Ashar or Long Chen, Center for Devices and Radiological Health (HFZ-500), Food and Drug Administration, 1350 Piccard Dr., Rockville, MD 20850, 240-276-3600, e-mail: binita.ashar@fda.hhs.gov or long.chen@fda.hhs.gov.
The complete documents could be viewed either at FDA or ar Regulations.gov.

Tags: breast cancer, FDA Action, RFC, cryoablation, focused ultrasound, interstitial laser, microwave, radiofrequency ablation

New Chantix (Varennicline) Medication Guide and Label Approved By FDA

FDA approves new Medication Guide and Label for Varenicline (marketed as Chantix)
FDA ALERT [2/1/2008]: FDA is issuing this Alert to highlight important revisions to the WARNINGS and PRECAUTIONS sections of the full prescribing information for Chantix regarding serious neuropsychiatric symptoms. Serious neuropsychiatric symptoms have occurred in patients taking Chantix. These symptoms include changes in behavior, agitation, depressed mood, suicidal ideation, and attempted and completed suicide. While some patients may have experienced these types of symptoms and events as a result of nicotine withdrawal, some patients taking Chantix who experienced serious neuropsychiatric symptoms and events had not yet discontinued smoking. In most cases, neuropsychiatric symptoms developed during Chantix treatment, but in others, symptoms developed following withdrawal of Chantix therapy.

FDA first informed the public about the possibility of serious neuropsychiatric symptoms in the November 20, 2007 FDA Early Communication About an Ongoing Safety Review. At that time, information about serious neuropsychiatric symptoms in patients taking Chantix was added to the POST-MARKETING EXPERIENCE section of the prescribing information. As FDA’s review of the issue has progressed, it appears increasingly likely that there is an association between Chantix and serious neuropsychiatric symptoms. As a result, FDA requested that Pfizer, the manufacturer of Chantix, elevate the prominence of this safety information to the WARNINGS and PRECAUTIONS sections of the Chantix prescribing information. In addition, FDA is working with Pfizer to finalize a Medication Guide for patients.

[5/16/2008]: The issues described in this communication have been addressed in the product labeling and FDA has approved the Medication Guide. If either you, your family or caregiver notice agitation, depressed mood, or changes in behavior that are not typical for you, or if you have suicidal thoughts or actions, stop taking Chantix and call your doctor right away.

Tags: FDA Alert, FDA Action, Chantix label change, Varenicline

Federal Agents Seize Nearly $1.3 Million Worth of Illegal Dietary Supplements from LG Sciences, LLC

Federal Agents Seize Nearly $1.3 Million of Illegal Dietary Supplements.
Products alleged to be adulterated under the Federal Food, Drug, and Cosmetic Act

At the request of the U.S. Food and Drug Administration, on Wednesday U.S. Marshals seized more than $1,301,712 of dietary supplements from LG Sciences, LLC, of Brighton, Mich., because the products contain unapproved food additives and/or new dietary ingredients that cause the products to violate the law. Labeled as dietary supplements, the products are marketed for use by body builders.

The dietary supplements seized were marketed and distributed on-line and in retail stores under the names "Methyl 1-D," "Methyl 1-D XL," and "Formadrol Extreme XL."

The seized products previously were tested and found to contain one or more unapproved food additives and/or new dietary ingredients for which there is inadequate information to provide reasonable assurance that the ingredients do not present a significant or unreasonable risk of illness or injury.

"The FDA takes seriously its responsibility to protect Americans from unsafe dietary supplements," said Margaret Glavin, FDA's Associate Commissioner of the Office of Regulatory Affairs. "Wednesday's action shows FDA's commitment to protecting consumers from potentially harmful products."

"Working with the FDA, we are taking prompt civil action to protect the public health by seizing these illegal products and forestalling their shipment into the stream of commerce in any manner that could create harm to the public," said U.S. Attorney Stephen J. Murphy. "I commend the professionalism and swift action of the FDA investigators who discovered and investigated this serious problem, and I am glad our lawyers could provide the legal muscle needed to support the seizure."

FDA has not received scientific information on the safety of the seized products and cannot determine, at this time, whether they represent a hazard to consumers. Therefore, consumers who still have the products should strongly consider discussing the use of these products with their health care professionals. FDA also recommends that consumers consult their health care professionals if they have experienced any adverse events that they suspect are related to the products' use. Consumers and health care professionals can report adverse events to the FDA's MedWatch program at 800-FDA-1088 or online at www.FDA.gov/medwatch/report.htm.

On March 2006, the FDA warned Legal Gear (the predecessor of LG Sciences) to cease distribution of a different product that was marketed as a dietary supplement but was actually an unapproved new drug containing synthetic steroids.

FDA Seeks $2.2 Million Penalties From Advanced Bionics, LLC and its president and co-CEO, Jeffrey H. Greiner.

FDA Seeks Civil Penalties from Calif. Device Maker

The U.S. Food and Drug Administration (FDA) today announced it is seeking a $2.2 million penalty against a California hearing aid manufacturer for violations of federal law, including manufacturing standards violations and the failure to notify the FDA of a change in an outside supplier or vendor, which may have exposed recipients of the devices to unnecessary health risks.

The hearing aids pose a public health risk due to excessive moisture, exposing patients to the risk of device failure, possible surgery, and the potential for additional hearing loss.

The agency's complaint, originally filed this past November and amended on March 17, seeks penalties against California medical device manufacturer Advanced Bionics, LLC and its president and co-CEO, Jeffrey H. Greiner.

The complaint alleges that Advanced Bionics shipped hearing aids to customers in the United States prior to filing appropriate supplemental information with the Agency, including a notice of changes made to the devices that affected their safety and effectiveness.

On July 7, 2003, Advanced Bionics received FDA approval to market the HiRes90k Implantable Cochlear Stimulator, a cochlear implant hearing aid surgically implanted under the skin behind the ear to treat profound hearing loss in adults and children. The hearing aid is considered a Class III device by the FDA—the most stringent regulatory category for devices.

The complaint alleges that the company failed to comply with the FDA's current Good Manufacturing Practice (GMP) requirements for devices. GMP requires that companies manufacturing medical devices for sale in the United States establish and follow quality systems procedures to assure the safety and quality of their products.

Advanced Bionic's alleged GMP violations include the failure to sufficiently evaluate and select a new vendor as the supplier of a critical device component and the failure to adequately validate the continued safety and effectiveness of the hearing aid by testing lots under actual or simulated use when the unapproved vendor's component was used.

The complaint also states that Advanced Bionics shipped hearing aids in violation of the law between January 2005 and July 2006. Two hearing aids shipped and implanted after a March 2006 recall contained the component from the unapproved vendor.

FDA's complaint states that the company's failure to file the required supplement occurred after a 2001 inspection. At that time, the company was cited for similar failures and made commitments to correct the problems.

Advanced Bionics, LLC, is located in Sylmar, Calif.

tag: FDA Action, Advanced Bionics, FDA Penalties, HiRes90k Implantable Cochlear Stimulator, hearing aid manufacturing standards violations, Good Manufacturing Practice,

FDA Early Communication About Montelukast (Singulair)

Early Communication About an Ongoing Safety Review of Montelukast (Singulair)

This information reflects FDA’s current analysis of available data concerning these drugs. Posting this information does not mean that FDA has concluded there is a causal relationship between the drug product and the emerging safety issue. Nor does it mean that FDA is advising health care professionals to discontinue prescribing this product. FDA is considering, but has not reached a conclusion about whether this information warrants any regulatory action. FDA intends to update this document when additional information or analyses become available.

FDA is investigating a possible association between the use of Singulair and behavior/mood changes, suicidality (suicidal thinking and behavior) and suicide. Singulair is a medicine in the drug class known as leukotriene receptor antagonists. Singulair is used to treat asthma and the symptoms of allergic rhinitis (sneezing, stuffy nose, runny nose, itching of the nose) and to prevent exercise-induced asthma.

Over the past year, the maker of Singulair, Merck & Co, Inc., has updated the prescribing information and patient information for Singulair to include the following post-marketing adverse events: tremor (March 2007), depression (April 2007), suicidality (suicidal thinking and behavior) (October 2007), and anxiousness (February 2008).

In February 2008, FDA and Merck discussed how best to communicate these labeling changes to prescribers and patients. Merck plans to highlight the recent changes in the prescribing information in face-to-face interactions with prescribers and provide prescribers with patient information leaflets about Singulair. The Singulair website includes the most current prescribing information and patient information for Singulair (www.singulair.com).

FDA is working with Merck to further evaluate a possible link between the use of Singulair and behavior/mood changes, suicidality and suicide in response to inquiries received by FDA. FDA has requested that Merck evaluate Singulair study data for more information about suicidality and suicide. FDA is reviewing the postmarketing reports it has received of behavior/mood changes, suicidality and suicide in patients who took Singulair.

Due to the complexity of the analyses, FDA anticipates that it may take up to 9 months to complete the ongoing evaluations. As soon as this review is complete, FDA will communicate the conclusions and recommendations to the public.

Singulair is an effective medicine that is indicated for the treatment of asthma and symptoms of allergic rhinitis. Patients should not stop taking Singulair before talking to their doctor if they have questions about this new information. Until further information is available, healthcare professionals and caregivers should monitor patients taking Singulair for suicidality (suicidal thinking and behavior) and changes in behavior and mood.

Other leukotriene modifying medications include zafirlukast (Accolate), which is also a leukotriene receptor antagonist and zileuton (Zyflo and Zyflo CR), which is a leukotriene synthesis inhibitor. FDA is reviewing postmarketing reports it has received of behavior/mood changes, suicidality and suicide in patients who took Accolate, Zyflo, and Zyflo CR and will assess whether further investigation is warranted.

This early communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs.

The FDA urges both healthcare professionals and patients to report side effects from the use of Singulair, Accolate, Zyflo, and Zyflo CR to the FDA's MedWatch Adverse Event Reporting program

• on-line at [www.fda.gov/medwatch/report.htm];
• by returning the postage-paid FDA form 3500 [available in PDF format at [www.fda.gov/medwatch/getforms.htm] to 5600 Fishers Lane, Rockville, MD 20852-9787;
• faxing the form to 1-800-FDA-0178; or
• by phone at 1-800-332-1088

tag: FDA Action, Singulair, suicidality, Montelukast, Merck & Co, tremor, depression, anxiousness, leukotriene, zafirlukast, Accolate, zileuton, Accolate, Zyflo, Zyflo CR