FDA Warns Consumers Not to Use Stolen Albuterol Sulfate Inhalation Solution and Ipratropium Bromide Inhalation Solution

The U.S. Food and Drug Administration today advised consumers not to use certain respiratory medications purchased after Sept. 8, 2009 and manufactured by Dey L.P., a subsidiary of Mylan Inc., because the medications might have been part of a shipment being transported on a tractor-trailer stolen in Tampa, Fla., on Sept. 8, 2009.

The respiratory medications, Ipratropium Bromide Inhalation Solution, 0.02%, and Albuterol Sulfate Inhalation Solution, 0.083%, unit-dose vials, have not been recovered and may be dangerous to use because the drugs may not have been stored and handled properly.

Dey issued an advisory on Sept. 11, 2009 regarding the theft. Although the FDA is not aware of any reports of adverse events, the agency is advising patients who use these respiratory medications to check to see if products received or purchased after Sept. 8, 2009 are from one of the following lots:

Albuterol Sulfate Inhalation Solution (892,000 doses; all lots contain 3.0 ml vials and display the brand name “Dey”)

• Lot number 9G04, NDC # 49502-697-29
• Lot number 9FD8, NDC # 49502-697-61
• Lot number 9FD9, NDC # 49502-697-61
• Lot number 9FE1, NDC # 49502-697-61

Ipratropium Bromide Inhalation Solution (432,000 doses; all lots contain 2.5 ml vials and display the brand name “Dey”)

• Lot number F09089, NDC # 49502-685-31
• Lot number C09119, NDC # 49502-685-62
• Lot number C09120, NDC # 49502-685-62

Do not use Albuterol Sulfate Inhalation Solution or Ipratropium Bromide Inhalation Solution if it is from one of these lots and was purchased or received after Sept. 8, 2009. Replace it with the same product from another lot.

Notify your health care professional of any adverse effects you may have experienced as a result of taking these medications.

Bring products from these lots back to the pharmacy where you received the medicine to exchange for products from a different lot or call Dey customer service at 800-527-4278. Contact your health care professional if you must switch to another product for any reason for possible dose adjustments.

Dietary Supplements Linked to One Death; Pose Risk of Liver Injury.

The U.S. Food and Drug Administration is warning consumers to immediately stop using Hydroxycut products by Iovate Health Sciences Inc., of Oakville, Ontario and distributed by Iovate Health Sciences USA Inc. of Blasdell, N.Y. Some Hydroxycut products are associated with a number of serious liver injuries. Iovate has agreed to recall Hydroxycut products from the market.

The FDA has received 23 reports of serious health problems ranging from jaundice and elevated liver enzymes, an indicator of potential liver injury, to liver damage requiring liver transplant. One death due to liver failure has been reported to the FDA. Other health problems reported include seizures; cardiovascular disorders; and rhabdomyolysis, a type of muscle damage that can lead to other serious health problems such as kidney failure.

Liver injury, although rare, was reported by patients at the doses of Hydroxycut recommended on the bottle. Symptoms of liver injury include jaundice (yellowing of the skin or whites of the eyes) and brown urine. Other symptoms include nausea, vomiting, light-colored stools, excessive fatigue, weakness, stomach or abdominal pain, itching, and loss of appetite.

“The FDA urges consumers to discontinue use of Hydroxycut products in order to avoid any undue risk. Adverse events are rare, but exist. Consumers should consult a physician or other health care professional if they are experiencing symptoms possibly associated with these products,” said Linda Katz, M.D., interim chief medical officer of the FDA’s Center for Food Safety and Applied Nutrition.

Hydroxycut products are dietary supplements that are marketed for weight-loss, as fat burners, as energy-enhancers, as low carb diet aids, and for water loss under the Iovate and MuscleTech brand names. The list of products being recalled by Iovate currently includes:

• Hydroxycut Regular Rapid Release Caplets
• Hydroxycut Caffeine-Free Rapid Release Caplets
• Hydroxycut Hardcore Liquid Caplets
• Hydroxycut Max Liquid Caplets
• Hydroxycut Regular Drink Packets
• Hydroxycut Caffeine-Free Drink Packets
• Hydroxycut Hardcore Drink Packets (Ignition Stix)
• Hydroxycut Max Drink Packets
• Hydroxycut Liquid Shots
• Hydroxycut Hardcore RTDs (Ready-to-Drink)
• Hydroxycut Max Aqua Shed
• Hydroxycut 24
• Hydroxycut Carb Control
• Hydroxycut Natural

Although the FDA has not received reports of serious liver-related adverse reactions for all Hydroxycut products, Iovate has agreed to recall all the products listed above. Hydroxycut Cleanse and Hoodia products are not affected by the recall. Consumers who have any of the products involved in the recall are advised to stop using them and to return them to the place of purchase. The agency has not yet determined which ingredients, dosages, or other health-related factors may be associated with risks related to these Hydroxycut products. The products contain a variety of ingredients and herbal extracts.

Health care professionals and consumers are encouraged to report serious adverse events (side effects) or product quality problems with the use of these products to the FDA’s MedWatch Adverse Event Reporting program online, by regular mail, fax or phone.

The FDA continues to investigate the potential relationship between Hydroxycut dietary supplements and liver injury or other potentially serious side effects.

Agency Warns Against Chronic Use of These Products to Treat Gastrointestinal Disorders.

The U.S. Food and Drug Administration announced today that manufacturers of metoclopramide, a drug used to treat gastrointestinal disorders, must add a boxed warning to their drug labels about the risk of its long-term or high-dose use. Chronic use of metoclopramide has been linked to tardive dyskinesia, which may include involuntary and repetitive movements of the body, even after the drugs are no longer taken.

Manufacturers will be required to implement a risk evaluation and mitigation strategy, or REMS, to ensure patients are provided with a medication guide that discusses this risk.

The FDA wants patients and health care professionals to know about this risk so they can make informed decisions about treatment, said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. The chronic use of metoclopramide therapy should be avoided in all but rare cases where the benefit is believed to outweigh the risk.

Current product labeling warns of the risk of tardive dyskinesia with chronic metoclopramide treatment. The development of this condition is directly related to the length of time a patient is taking metoclopramide and the number of doses taken. Those at greatest risk include the elderly, especially older women, and people who have been on the drug for a long time.

Tardive dyskinesia is characterized by involuntary, repetitive movements of the extremities, or lip smacking, grimacing, tongue protrusion, rapid eye movements or blinking, puckering and pursing of the lips, or impaired movement of the fingers. These symptoms are rarely reversible and there is no known treatment. However, in some patients, symptoms may lessen or resolve after metoclopramide treatment is stopped.

Metoclopramide works by speeding up the movement of the stomach muscles, thus increasing the rate at which the stomach empties into the intestines. It is used as a short-term treatment of gastroesophageal reflux disease in patients who have not responded to other therapies, and to treat diabetic gastroparesis (slowed emptying of the stomach’s contents into the intestines). It is recommended that treatment not exceed three months.

Metoclopramide is available in a variety of formulations including tablets, syrups and injections. Names of metoclopramide-containing products include Reglan Tablets, Reglan Oral Disintegrating Tablets, Metoclopramide Oral Solution, and Reglan Injection. More than two million Americans use these products.

Recently published analyses suggest that metoclopramide is the most common cause of drug-induced movement disorders. Another analysis of study data by the FDA showed that about 20 percent of patients in that study who used metoclopramide took it for longer than three months. The FDA has also become aware of continued spontaneous reports of tardive dyskinesia in patients who used metoclopramide, the majority of whom had taken the drug for more than three months.

The U.S. Food and Drug Administration (FDA) has asked manufacturers to include a new boxed warning on the product labeling of all gadolinium-based contrast agents which are used to enhance the quality of magnetic resonance imaging (MRI).

The requested warning would state that patients with severe kidney insufficiency who receive gadolinium-based agents are at risk for developing a debilitating, and a potentially fatal disease known as nephrogenic systemic fibrosis (NSF). In addition, it would state that patients just before or just after liver transplantation, or those with chronic liver disease, are also at risk for developing NSF if they are experiencing kidney insufficiency of any severity.

“FDA has been carefully monitoring potential safety signals related to these contrast agents after receiving reports about the risk of this potentially life-threatening disease,” said Steven Galson, M.D., M.P.H., director of FDA’s Center for Drug Evaluation and Research. “This latest action demonstrates FDA’s continuing vigilance about ensuring the safety of drug products once they enter the marketplace.”

Patients with NSF develop thickening of the skin and connective tissues that inhibits their ability to move and may result in broken bones. Other organs are at risk of thickening as well. The cause of NSF is not known and there is no consistently effective treatment of this condition.

FDA first notified health care professionals and the public about the gadolinium-related risks for NSF in June 2006 . Information on the risks was updated in December.

Gadolinium-based contrast agents are commonly used to improve the visibility of internal structures when patients undergo an MRI. Five gadolinium-based contrast agents have been approved for use in the United States: Magnevist (gadopentetate dimeglumine), Ominiscan (gadodiamide); OptiMARK (gadoversetamide); MultiHance;(gadobenate dimeglumine);and Prohance (gadoteridol).

Reports have identified the development of NSF following single and multiple administrations of the gadolinium-based contrast agents. The reports have not always identified a specific agent. Omniscan was the most commonly reported agent, when a specific agent was identified, followed by Magnevist and OptiMARK.

NSF also has developed after the sequential administration of Omniscan and MultiHance and Omniscan and ProHance. Because reports incompletely describe exposure to gadolinium-based contrast agents, it is not possible to know if the extent of risks for developing NSF is the same for all agents.

Patients should be screened for kidney problems prior to receiving one of these imaging agents. The recommended dose should not be exceeded and enough time should elapse to ensure that a dose has been eliminated from the body before the agent is used again.

There have been no reports of NSF among patients with normal kidney function or those with mild-to-moderate kidney insufficiency.

The U.S. Food and Drug Administration (FDA) today approved revised labeling for Trasylol (aprotinin injection) to strengthen its safety warnings and to limit its approved usage to specific situations. Trasylol is given to patients before heart surgery to reduce bleeding and the need for blood transfusions. Trasylol is marketed by Bayer Pharmaceuticals Corporation, Leverkusen, Germany.

“The purpose of the label change is to inform physicians and patients about the risks associated with Trasylol and to ensure they understand the new warnings and use the product as directed by the label,” said Steven Galson, M.D., MPH, Director of FDA’s Center for Drug Evaluation and Research.

The new labeling specifies that Trasylol should only be given to patients who are at an increased risk for blood loss and blood transfusion in the setting of coronary bypass graft surgery (a procedure used to improve blood flow to the heart) when patients undergo cardiopulmonary bypass (a procedure that allows a machine to take over the heart’s functions when it is stopped during surgery). The changes also include a warning that Trasylol increases the possible risk for kidney damage, and suggest ways to manage and reduce the patient’s risk for hypersensitivity (exaggerated immune) reactions.

The labeling changes follow an FDA-conducted review of safety information that FDA became aware of after the product was introduced to the market. FDA began this safety review of Trasylol in January 2006. The review was triggered by the results of two published research studies. One study reported an increase in the possibility of kidney failure, heart attack and stroke in patients treated with Trasylol compared to those treated with other drugs. The other study reported an increase in the possibility of kidney damage compared to other drugs, but did not show an increased risk of heart attack or stroke. On February 8, 2006, FDA issued a Public Health Advisory regarding these new findings with Trasylol. On September 21, 2006, FDA held a public meeting of the Cardiovascular and Renal Drugs Advisory Committee to discuss the safety and overall risk-benefit profile for Trasylol. At that meeting, the committee discussed the findings from the two published observational studies, a Bayer worldwide safety review, and the FDA review of its own post-marketing database, and made recommendations for labeling changes. The labeling changes for Trasylol are based upon the recommendations of that advisory committee.

FDA announced on September 29, 2006, that Bayer informed the agency of an additional safety study on September 27, 2006. The preliminary results from that study suggest that in addition to serous kidney damage, Trasylol may increase the chance for death, congestive heart failure (a weakening of the heart), and strokes. The FDA review of this additional Trasylol safety information is continuing and it may result in other actions, including additional changes to the labeling.

Trasylol FDA Advisory
The Food and Drug Administration (FDA) today issued a Public Health Advisory alerting doctors who perform heart bypass surgery, and their patients, that Trasylol (aprotinin injection), a drug used to prevent blood loss during surgery, has been linked in two scientific publications to higher risks of serious side effects including kidney problems, heart attacks and strokes in patients who undergo artery bypass graft surgery.

“FDA is conducting a thorough evaluation of the safety profile for this drug in light of the recent publications,” said Dr. Steven Galson, Director of FDA’s Center for Drug Evaluation and Research. “We’re working to evaluate the potential risks and determine whether there is a need for further action. In the meantime, we advise providers to carefully assess the benefits and risks of the drug for their patients.”