The U.S. Food and Drug Administration today released consumer and industry advisories regarding safe sources of puffer fish. Many puffer fish, also known as fugu, bok, blowfish, globefish, swellfish, balloonfish, or sea squab, contain deadly toxins that affect the central nervous system, if consumed.

Puffer fish can be safely consumed when special care is taken to ensure that the fish caught are free of toxins, or when they are processed to eliminate the toxins.

"Over the past year, several illnesses have been linked to puffer fish improperly processed and illegally imported into the United States," said Robert Brackett, Ph.D., director of the FDA's Center for Food Safety and Applied Nutrition. "If restaurateurs, retailers, and consumers follow the advice the FDA is providing, puffer fish can be safely enjoyed."

The only safe sources for imported puffer fish are fish that have been processed and prepared by specially trained and certified fish cutters in the city of Shimonoseki, Japan. Additionally, puffer fish caught in the mid-Atlantic coastal waters of the United States, typically between Virginia and New York, are safe to consume. Puffer fish from all other sources can either naturally contain deadly toxins or become toxic because of environmental factors and therefore are not considered safe.

Symptoms of ingesting the toxins found in puffer fish include tingling around the lips and in the extremities followed by problems speaking, loss of balance, muscle weakness and paralysis, vomiting, and diarrhea. In extreme cases, there may be respiratory paralysis that can lead to death.

Consumers should ask about the origin of the fish before ordering or buying. In cases where the source is uncertain or unknown, consumers should not eat the puffer fish.

Establishments that serve or sell puffer fish, including restaurants and fish markets, should obtain the product from a known safe source.

FDA officials are working with state and local health officials, along with food safety organizations, to raise awareness about the industry advisory to restaurants, fish markets, and food stores.

Consumer Advisory: Only Eat Puffer Fish from Known Safe Sources
www.cfsan.fda.gov/~dms/adpuffer.html

Industry Advisory on Puffer Fish
www.cfsan.fda.gov/~dms/ad2puff.html

The U.S. Food and Drug Administration has approved doripenem injection, 500 mg intravenous infusion, for the treatment of complicated urinary tract and intra-abdominal infections. Doripenem injection, sold under the trade name Doribax, has been shown to be active against several strains of bacteria.

“This is a significant new drug in the treatment of hospitalized patients with serious bacterial infections,” said Janet Woodcock, M.D., FDA’s deputy commissioner for scientific and medical programs, chief medical officer and acting director, Center for Drug Evaluation and Research.

In several multi-center, multinational studies, doripenem was shown to have a cure rate comparable to the currently prescribed medications levofloxacin, for complicated urinary tract infections, and meropenem, for complicated intra-abdominal infections.

The most common adverse reactions reported were headache, nausea, diarrhea, rash, and phlebitis. In addition, allergic reactions have occurred and some may require immediate treatment.

The safety and effectiveness of doripenem injection in pediatric patients have not been established. Doripenem has not been studied in pregnant women, and the drug should be used during pregnancy only if clearly needed.

Doripenem injection is manufactured by Johnson and Johnson Pharmaceutical Research and Development, LLC, Raritan, N.J.

The U.S. Food and Drug Administration today expanded the approved age range for Menactra, a bacterial meningitis vaccine, to include children ages 2 to 10 years.

Meningitis is a serious inflammation of the lining that surrounds the spinal cord and brain. It can result in death or permanent injury to the brain and nervous system. In the United States, about 2,600 people become ill from bacterial meningitis annually. About 10 percent die from the infection and another 15 percent or so suffer brain damage or limb amputation.

Menactra was first approved by FDA in January 2005 for people ages 11 to 55 years. Previously, Menomune was the only meningococcal vaccine available in the United States for use in children, ages 2 years and older. Both products are manufactured by sanofi pasteur Inc. of Swiftwater, Pa. Both vaccines offer protection against four groups of Neisseria meningitidis, the bacterium that can cause meningitis.

“Approving Menactra for younger children offers another option for health care providers and parents. Now there are two vaccines available for children between 2 and 10 years of age who may be at increased risk of meningitis,” said Jesse L. Goodman, M.D., M.P.H., director of FDA's Center for Biologics Evaluation and Research.

The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) currently recommends meningococcal vaccination for children ages 2 to 10 years who are at increased risk of developing meningococcal disease, such as those who have had their spleen removed or whose spleen is not functioning; those with a medical condition called terminal complement component deficiency which makes it difficult to fight infection; and those who expect to travel to areas outside of the United States where the disease is common. Vaccination also is used to control outbreaks of bacterial meningitis.

Menactra’s effectiveness was measured in clinical trials that included people ages 2 to 55 years. The vaccine was shown to produce an immune response one month after vaccination. The safety of Menactra was evaluated in eight clinical studies that included a total of 10,057 participants who received Menactra and 5,266 participants who received Menomune. The most common adverse events reported in the studies were pain at the injection site and irritability. Diarrhea, drowsiness, and lack of appetite also were common.

While not observed in these clinical trials, Guillain-Barré syndrome (GBS), a neurological disorder that causes muscle weakness, was noted as a possible but unproven risk in some adolescents following immunization with Menactra, occurring in an estimated 1 in 1 million vaccine recipients. As a precaution, people who have previously been diagnosed with GBS should not receive Menactra.

FDA and CDC will continue to monitor the safety of Menactra through their jointly administered Vaccine Adverse Event Reporting System

Potential risk of sudden hearing loss with ED drugs to be displayed more prominently
The U.S. Food and Drug Administration has approved labeling changes for erectile dysfunction (ED) drugs in the class that includes Cialis, Levitra, and Viagra, to display more prominently the potential risk of sudden hearing loss, and to guide consumers on what to do if they experience sudden problems with their hearing.

In addition, the FDA plans to require the same changes in labeling for the drug Revatio, also a member of this drug class known as phosphodiesterase type 5 (PDE5) inhibitors. Revatio is used to treat pulmonary arterial hypertension (PAH). PAH is a serious medical condition in which continuous high blood pressure in arteries of the lungs weakens the heart muscle and often leads to right heart failure and death.

The FDA asked manufacturers of these drugs to revise product labeling after a very small number of patients taking the PDE5 inhibitors reported sudden hearing loss, sometimes accompanied by ringing in the ears and dizziness.

“Because some level of hearing loss is usually associated with the aging process, patients on these drugs may not think to talk to their doctor about it,” said Janet Woodcock, M.D., FDA’s deputy commissioner for scientific and medical programs, chief medical officer, and acting director of its Center for Drug Evaluation and Research.

Patients taking Cialis, Levitra, or Viagra who experience sudden hearing loss should immediately stop taking the drug and seek prompt medical attention. Those using Revatio should continue taking their medication but should contact their health care provider for further evaluation. Because Revatio is used to treat a potentially life-threatening condition, the FDA does not recommend patients abruptly stop taking this medication but should consult their physician if they experience sudden problems with their hearing.

A case report in the April 2007 issue of the Journal of Laryngology & Otology involving sudden hearing loss in a man taking Viagra prompted the FDA to search the FDA’s Adverse Events Reporting System for instances of hearing loss and PDE5 inhibitors. The FDA found a total of 29 postmarketing reports of sudden hearing loss, both with and without accompanying ringing in the ears, vertigo, or dizziness. In most of the cases, the hearing loss involved one ear. The hearing loss was either a partial or complete loss of usual hearing. In approximately one third of cases, the event was temporary. In the remainder, the hearing loss was ongoing at the time of the report or the final outcome was not described.

Although no causal relationship has been demonstrated, the strong relationship between the use of these drugs and sudden hearing loss in these cases warrants revisions to the product labeling for this drug class.

Product Web sites, marketing and educational materials, and advertisements for PDE5 inhibitors will reflect the revised product labeling. The label revisions can be viewed at: www.fda.gov/cder/drug/DrugSafety/DrugIndex.htm.

For more information:
http://www.fda.gov/cder/drug/infopage/ed_drugs/QA.htm

The U.S. Food and Drug Administration today approved a change in the storage conditions for Humate-P, a treatment for bleeding in certain patients with hemophilia A or von Willebrand Disease (vWD).

The treatment, a protein that helps blood form the clots necessary to stop bleeding, can now be safely stored for up to two years at 77 degrees Fahrenheit. Previously, Humate-P required colder, refrigerator-level temperatures for that storage length.

Approval of this change was based on stability data submitted by the company including laboratory tests of product potency conducted under different temperatures.

“The change in storage conditions will help patients, their families and treating physicians better manage the product, especially as part of medically supervised home treatment programs,” said Jesse L. Goodman, M.D., M.P.H., director of the FDA’s Center for Biologics Evaluation and Research.

Humate-P is approved for the treatment and prevention of bleeding in adult patients with hemophilia A, a rare clotting disorder. It is also approved for the treatment of spontaneous and trauma-induced bleeding and the prevention of excessive bleeding related to surgery in adult and pediatric patients with vWD, the most common inherited bleeding disorder in the United States.

Humate-P is manufactured from human plasma obtained from screened and tested U.S. donors.

Reported adverse reactions include allergic reactions such as hives, rash, chest tightness, swelling, and shock. Blood clots have been observed in patients under treatment for vWD.

Humate-P was first approved in 1986 for the treatment and prevention of bleeding in patients with hemophilia A. It was first approved for use in patients with vWD in 1999.

The product is manufactured by CSL Behring GmbH in Marburg, Germany

The U.S. Food and Drug Administration has approved Ixempra (ixabepilone), a new anti-cancer treatment, for use in patients with metastatic or locally advanced breast cancer who have not responded to certain other cancer drugs. The FDA evaluated Ixempra under priority review, completing its assessment of the drug's safety and effectiveness in six months.

"This approval is important because it provides certain patients with a new chemotherapy option in instances where other drugs have failed," said Douglas C. Throckmorton, M.D., deputy director of the FDA's Center for Drug Evaluation and Research. "FDA is working every day to support the development of safe and effective new therapies that benefit patients in need."

Ixempra was approved for use in combination with another cancer drug, capecitabine, in patients who no longer benefit from two other chemotherapy treatments. These prior treatments included an anthracycline (such as doxorubicin or epirubicin) and a taxane (such as paclitaxel or docetaxel).

Ixempra was also approved for use alone in patients who no longer benefit from an anthracycline, a taxane and capecitabine.

According to the American Cancer Society, about 180,000 new cases of breast cancer are diagnosed each year in the United States. Metastatic breast cancer is the most advanced stage of breast cancer and has the potential to spread to almost any region of the body.

Ixempra has been shown to bind to cancer cell microtubules, which are structures within cells that help to support and shape them. Microtubules also play a role in cell division.

The safety and efficacy of Ixempra in combination with capecitabine were evaluated in 752 patients in a randomized clinical trial comparing the combination to capecitabine alone. This combination therapy demonstrated improvements in delaying cancer progression or death compared to capecitabine alone.

The safety and efficacy of Ixempra administered alone were evaluated in a study of 126 patients. Clinically significant tumor shrinkage occurred in 12 percent of the patients.

Ixempra's significant side effects included peripheral neuropathy (numbness, tingling or burning in the hands or feet) and bone marrow suppression. Other commonly observed toxicities included constipation, nausea, vomiting, muscle paint, joint pain, fatigue and general weakness.

Women taking Ixempra should avoid taking drugs that are strong inhibitors of CYP3A4, one of the enzymes that metabolizes Ixempra.

Ixempra should not be taken by women who have had severe allergic reactions to drugs that contain Cremophor or its derivatives, or by women who have baseline bone marrow suppression determined by low white blood cell or platelet count.

The combination of Ixempra and capecitabine should not be given to patients with moderate or severe liver impairment due to the increased risk of toxicity and death.

Ixempra is administered by intravenous infusion. It is distributed by Bristol-Meyers Squibb Company, Princeton, New Jersey

Background: The U.S. Food and Drug Administration (FDA) issued an Early Communication about an Ongoing Safety Review of Aprotinin Injection (marketed as Trasylol), a drug used to control bleeding during heart surgery.

Last week, FDA was notified that a Canadian research group stopped a study on Trasylol because the drug appeared to increase the risk for death compared to the other antifibrinolytic drugs used in the study. Antifibrinolytic drugs help slow the breakdown of blood clots and subsequent excessive bleeding. The data also suggested that fewer patients receiving the drug experienced serious bleeding events.

This most recent data support the results from other comparison studies of Trasylol. The comparison studies were discussed at a September 2007 joint meeting of FDA's Cardiovascular and Renal Drugs and Drug Safety and Risk Management Advisory Committees, which represent one part of FDA's oversight and review of drugs throughout their life cycles.

FDA anticipates further review of the risk and benefits of Trasylol, which may result in additional labeling or other regulatory action. FDA will work with the sponsor of the recently terminated study to evaluate the data fully.

In the meantime, FDA recommends that health care providers review the risks and benefits of Trasylol outlined in the label and in the Early Communication about an Ongoing Safety Review, and discuss the information with their patients.

In 2006, FDA revised the labeling for Trasylol to strengthen its safety warning and limit its approved usage to patients at an increased risk for blood loss and blood transfusion during coronary bypass graft surgery.

Trasylol is marketed by Bayer Pharmaceuticals Corp., Leverkusen, Germany.

This early communication is in keeping with FDA's commitment to inform the public about its ongoing safety reviews. Full text of the Early Communication about an Ongoing Safety Review can be found at http://www.fda.gov/cder/drug/early_comm/aprotinin.htm.

The U.S. Food and Drug Administration (FDA) has approved Tasigna (nilotinib) capsules for treatment of Philadelphia chromosome positive chronic myeloid leukemia (CML) in adult patients whose disease has progressed on or who cannot tolerate other therapies that included imatinib. Imatinib (Gleevec) is approved for the treatment of new diagnosed patients with Philadelphia chromosome positive CML.

FDA's approval of Tasigna includes a black box warning for possible life-threatening heart problems that may lead to an irregular heartbeat and possible sudden death.

CML accounts for 15 percent of all leukemias in adults. Approximately 4,500 new cases of CML will be diagnosed in 2007. An abnormal chromosome, called the Philadelphia chromosome, is located in the leukemic cells and is present in the majority of CML patients.

"This represents another treatment option for CML patients who are resistant to or can no longer tolerate imatinib," said Janet Woodcock, M.D., FDA's deputy commissioner for scientific and medical programs, chief medical officer and acting director, Center for Drug Evaluation and Research. "Patients should consult with their physicians, however, because of possible life-threatening heart problems associated with this drug."

The effectiveness of Tasigna is based on response rates observed in an ongoing clinical trial. Responses are associated with normalization of blood counts and bone marrow examinations. Further follow-up of patients is needed to determine how long these responses will last.

Patients may lower their chances for the heart problems by taking Tasigna without food, and by avoiding grapefruit products. Patients should also consult with their physician or other health care professional about avoiding other medications that can cause heart problems when taking Tasigna.

Patients with low blood potassium or magnesium should not use Tasigna.

The most common side effects include low blood counts, rash, headache, nausea and itching. Other possible serious side effects include liver damage, fluid accumulation and pancreas inflammation.

Women are advised to avoid becoming pregnant while taking Tasigna. Women who become pregnant are advised that Tasigna can harm their unborn child. Nursing mothers are advised not to breastfeed their child while taking the drug.

Tasigna is manufactured by Novartis Pharmaceuticals Corporation, East Hanover, N.J.

Self-medication a concern; FDA-approved generics may be cheaper alternative
A yearlong U.S. Food and Drug Administration (FDA) investigation into drugs mailed to the United States from foreign countries suggests that consumers may be buying drugs online to avoid the need for a prescription from their physician. The FDA sampling of imported drugs also indicates that consumers continue to spend money unnecessarily on potentially risky drug products bought over the Internet.

The investigation found 88 percent of the 2,069 drug packages examined appeared to be prescription medicines available in the United States. Of the remaining products, some were dietary supplements, some were foreign products with labeling that was illegible or incomprehensible, and some were medications not available in the United States. More than half (53 percent) of the products sampled have FDA-approved generic versions, likely sold at lower costs, according to earlier studies that have shown generics in the United States to be generally cheaper than a comparable drug in Canada or Western Europe. In fact, approved generic versions of approximately half (47 percent) of the sampled products can be bought for $4 at several national chain pharmacies, a price often lower than the shipping costs for the same drugs purchased online.

"The data lead us to believe that many people are buying drugs online not to save money but to bypass the need for a prescription from their doctor since these Web sites typically do not require the purchaser to have a prescription," said Randall Lutter, Ph.D., FDA's deputy commissioner for policy. "In essence, they seem to be getting and using prescription drugs without a prescription, an intrinsically risky practice."

These data are based on surveys conducted from September 2006 to August 2007 in international mail facilities and courier facilities across the country. At each city surveyed, a selection of parcels suspected by U.S. Customs and Border Protection of containing pharmaceuticals were stopped. FDA then recorded data on the contents of these parcels, before handling them in accordance with its usual procedures.

In general, a Web site can appear legitimate, but in fact be a front for an illegal operation. FDA urges consumers to beware of unregulated Internet drug sellers, because many of their products might not contain the correct ingredients and could contain toxic substances. Several drugs found in this survey require special monitoring by physicians or other health care professionals for potential adverse events and to ensure their effectiveness. These include antibiotics, antidepressants, the blood thinner warfarin, and levothyroxine (a thyroid replacement hormone).

For more information:
FDA Finds Consumers Continue to Buy Potentially Risky Drugs Over the Internet
http://www.fda.gov/bbs/topics/NEWS/2007/NEW01663.html

Buying Medicines and Medical Products Online
http://www.fda.gov/buyonline/

Some lacked FDA approval, maintained under unsanitary conditions
At the request of the U.S. Food and Drug Administration, on Wednesday, U.S. Marshals seized more than $300,000 worth of product, including NC Solution, an antifungal product, and other drugs for human or animal use, dietary supplements, and ingredients to make those products because some lacked FDA approval and all were maintained under grossly unsanitary conditions by General Therapeutics Corp., of St. Louis, Mo.

The FDA considers NC Solution to be a drug because it is intended for the use in the diagnosis, cure, or treatment of disease in people or animals. NC Solution is also a new drug because it is not generally recognized as safe and effective for its intended uses.

Before a new drug product may be legally marketed, it must be shown to be safe and effective, and approved by the FDA. The company does not have approval for NC Solution.

“The action taken Wednesday is the culmination of the concerted efforts by the FDA to get the firm to follow the law when it comes to manufacturing safe products for consumers,” said Margaret O'K. Glavin, FDA Associate Commissioner for Regulatory Affairs.

In August and September, FDA inspectors found that the company was still manufacturing drugs and dietary supplements under unsanitary conditions, including insects and rodent filth on and around manufacturing equipment, despite a warning by FDA of serious violations in 1999. Following the 1999 inspection, a company official told the FDA in January, 2000, it would stop manufacturing drugs.

The FDA recommends that consumers who have any products manufactured by General Therapeutics, including NC Solution, consult their health care provider about discontinuing use and if they have experienced any adverse events that they suspect are related to the product's use.

Catherine L. Hanaway, U.S. Attorney for the Eastern District of Missouri, filed the complaint requesting the seizure, and her office will continue to coordinate with the FDA to ensure proper disposal of the seized items.

The FDA's action against the company is consistent with the agency's initiative on unapproved drugs which pose potentially harmful risks to consumers.