B-12 is Brain Food

A study published in Neurology in 2010 evaluated the blood and levels of Vitamin B12 in 271 normal individuals between the ages of 65-79. The study ran for seven years and chose this age range because of the high risk in these age groups for memory loss and stroke. Vitamin B-12 helps maintain healthy nerve cells and red blood cells. A vitamin B-12 deficiency, most common in vegetarians and older adults, can cause various signs and symptoms, including difficulty in memorizing, remembering names and faces and cognitive functions.

 In this study, holotranscobalamin, the active ingredient in vitamin B12 (also known as cobalamin) is believed to lower the homocysteine blood levels associated in preventing brain shrinkage, reduce the risk of cognitive impairment, memory loss and dementia. Older people commonly have a low blood level of B12 (below 170-250 picomol per ml), and their risk for memory impairments are much greater. Results from the study showed the risk for Alzheimer’s Disease (AD) decreased by 16% for micromolar increase of B12 in their blood.

To put it into non-scientific terms: The higher your level of B12 in your blood, along with other risk factors, the better your risk of preventing Alzheimer’s or any other form of dementia. Although B12 is not the only consideration, this study shows there is good evidence to believe a lower level of B12 is a good indicator there could be memorizing and cognitive problems, and that more research will could prove or disprove this theory.

 Maintaining a healthy diet, which includes a diet rich in vitamins such as B12 and others, is optimal to good memory fitness. Researchers do want to stress, however, that a balanced diet is much better in the body’s absorption of vitamin B12 than dietary supplements are. It is not present in plant foods, generally, but is rich in animal foods such as meat, poultry, fish and eggs.

 Many breakfast cereals are also fortified with vitamin B-12 as well. If you’re concerned that you’re not getting enough B-12, consult your doctor — especially if you’re an older adult or a vegetarian who are more inclined to a vitamin B12 deficiency. 

 You may also need to know that the subjects in the trial studies over a 2-year period were given significantly more than the average minimum daily requirements on a vitamin bottle. That does not disprove the theory, but holds out new confidence that further study will come back with the message that vitamin B12 does help improve your memory, and is one of those valuable brain foods your body needs to help improve memorizing and cognitive functions.

Sources:

 Neurology: (2010; 75-1408-1414)

 Mayo Clinic: Can vitamin B-12 improve memory in Alzheimer’s disease?

 by Glenn Smith, PhD – http://www.mayoclinic.com/health/alzheimers/AN00478

New Test to help determine if breast cancer patients are candidates for Herceptin treatment

New genetic test that will help health care professionals determine if women with breast cancer are HER2-positive and, therefore, candidates for Herceptin (trastuzumab), a commonly used breast cancer treatment.

The test, called Inform Dual ISH, allows for measurement of the number of copies of the HER2 gene in tumor tissue. The HER2 gene is located on chromosome 17 in human cells. An excessive amount of the protein produced by the gene is found in some types of cancer cells, including breast cancer cells.

The Inform Dual ISH test allows lab personnel to count the number of copies of HER2 genes on chromosome 17 in a small sample of the breast tumor. The sample is stained with chemicals that cause copies of HER2 genes and chromosome 17 to change color. Copies of the HER2 gene appear black and copies of chromosome 17 appear red. These color changes can be seen under a standard microscope.

This feature allows lab personnel to see and count copies of chromosome 17 and HER2 genes on the same slide, similar to HER2 amplification measurements that have traditionally only been available using fluorescence microscopes. The Inform Dual ISH, however, allows lab staff to see the HER2 and chromosome 17 signals directly under a microscope, for longer periods of time.

"When used with other clinical information and laboratory tests, this test can provide health care professionals with additional insight on treatment decisions for patients with breast cancer," said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostic Device Evaluation and Safety in the FDA’s Center for Devices and Radiological Health.

The FDA based its approval of the Inform Dual ISH on a U.S. study involving tumor samples from 510 patients with breast cancer. This study showed that the test was effective in confirming that a patient’s tumor sample contained more than the normal number of copies of the HER2 gene in 96 percent of the HER2 positive tumor samples. Patients with more than the normal number of copies of the HER2 gene are considered candidates for Herceptin therapy.

The study also showed that the test was effective at excluding the possibility that more than the normal number of copies of the HER2 gene were present in 92.3 percent of the HER2 negative tumor samples. Patients who do not have more than the normal number of copies of the HER2 gene are typically not candidates for Herceptin therapy. The ability to identify patients who are HER2-positive is a useful tool for physicians who may be considering treatment with Herceptin for their breast cancer patients.

Breast cancer is the second leading cause of cancer-related death among women. An estimated 207,090 new cases of breast cancer were diagnosed in the United States during 2010 and about 39,840 women died from the disease, according to the National Cancer Institute. About 20 percent of women diagnosed with breast cancer are HER2-positive.

Nulojix for kidney transplant patients

Nulojix (belatacept) is used to prevent acute rejection in adult patients who have had a kidney transplant. The drug is approved for use with other immunosuppressants (medications that suppress the immune system) -- specifically basiliximab, mycophenolate mofetil, and corticosteroids.

Nulojix is a type of drug called a selective T-cell costimulation blocker. The drug helps to prevent organ rejection after a kidney transplant. Without immunosuppression, the body can reject a transplanted organ because the immune system recognizes the new organ as foreign (transplant rejection). By preventing rejection, Nulojix, given through 30 minute intravenous infusions, works with other immunosuppressants to keep the new kidney working.

“Nulojix is a new option for kidney transplant patients,” said Edward Cox, M.D., M.P.H, director, Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. “This new medication used in combination with other immunosuppressants helps control the immune system and prevents organ rejection in patients receiving kidney transplants.”

Nulojix was evaluated in two open-label, randomized, multicenter, controlled Phase 3 studies that enrolled more than 1,200 patients and compared two dose regimens of Nulojix with another immunosuppressant, cyclosporine. These trials demonstrated that the recommended Nulojix regimen is safe and effective for the prevention of acute organ rejection.

Nulojix carries a Boxed Warning for an increased risk of developing post-transplant lymphoproliferative disorder (PTLD), a type of cancer where white blood cells grow out of control after an organ transplant. The risk of PTLD is higher for transplant patients who have never been exposed to Epstein-Barr virus (EBV), the cause of mononucleosis. Transplant patients who have not been exposed to EBV have more difficulty mounting an effective immune response to the virus if they get infected after transplant; typically they get exposed to the virus at time of transplant, as it is carried in around 80 percent of donated organs. Patients should be tested for EBV and should only receive Nulojix if the test shows they have already been exposed to EBV. Another Boxed Warning on the Nulojix label, as well as labels of other immunosuppressants, warns of an increased risk of serious infections and other cancers.

Common adverse reactions observed in transplant patients in the trials included low red blood count (anemia), constipation, kidney or bladder infection, and swollen legs, ankles, or feet. Any transplant patients, including those receiving Nulojix, should limit the amount of time spent in sunlight because of the risk of skin cancer and should not get live vaccines because of the risk of infection.

Sunscreen

Sunscreen products that meet modern standards for effectiveness may be labeled with new information to help consumers find products that, when used with other sun protection measures, reduce the risk of skin cancer and early skin aging, as well as help prevent sunburn.

These new requirements are part of an ongoing effort to ensure sunscreens meet modern-day standards for safety and efficacy and are based on the latest science available.  They will also reduce confusion about sunscreen. 

FDA Unveils New Cigarette Health Warnings

Consumers are getting a glimpse of warnings images that will be alternating on all cigarette packages and advertisements within 15 months—an effort by health officials to discourage smoking by bringing Americans face to face with tobacco-related disease.

The Food and Drug Administration unveiled the nine, color images—including some of  bodies ravaged by disease—at a news conference. The images, which are paired with text health warnings, are required under the 2009 Family Smoking Prevention and Tobacco Control Act. They must appear on every cigarette pack, carton, and advertisement by September 2012.

“President Obama is committed to protecting our nation’s children and the American people from the dangers of tobacco use. These labels are frank, honest and powerful depictions of the health risks of smoking and they will help encourage smokers to quit, and prevent children from smoking,” said Health and Human Services Secretary Kathleen Sebelius.

Nine Warnings

In November, FDA officials posted 36 images on the Internet and gave the public 90 days to comment. The agency received more than 1,700 comments from the public, retailers, health professionals, advocacy groups, the tobacco industry, state and local public health agencies, and others.

Regulators used the comments, scientific literature, and the results of an 18,000-person study to narrow the images to nine. Each of the images—a mix of illustrations and photos depicting the negative health consequences of smoking—will be paired with one of these nine printed warnings:

• WARNING: Cigarettes are addictive—with an image of a man smoking through a hole in his throat 
• WARNING: Tobacco smoke can harm your children—with an image of a parent holding a baby as smoke drifts towards them
• WARNING: Cigarettes cause fatal lung disease—with an image of a disease-riddled lung and a healthy lung 
• WARNING: Cigarettes cause cancer—with an image of an open sore and stained teeth on the lips and mouth of a smoker with mouth cancer
• WARNING: Cigarettes cause strokes and heart disease—with an image of a man who needs an oxygen mask to breathe
• WARNING: Smoking during pregnancy can harm your baby—with an illustration of a crying newborn in an incubator and hooked-up to a monitor
• WARNING: Smoking can kill you—with the image of a dead man with a surgery-scarred chest  
• WARNING: Tobacco smoke causes fatal lung disease in nonsmokers—with an image of a grieving family member
• WARNING: Quitting smoking now greatly reduces serious risks to your health—with an image of a man wearing an “I Quit” T-shirt

Expected Impact

FDA Commissioner Margaret A. Hamburg, M.D., says she’s hopeful the graphic images will give smokers the incentive to quit and prevent potential smokers from ever starting. In fact, the phone number for the smoking cessation hotline—1-800-QUIT-NOW—will accompany each warning.

“The Tobacco Control Act requires FDA to provide current and potential smokers with clear and truthful information about the risks of smoking—these warnings do that,” she says. 

The bold health warnings will cover the top 50 percent of the front and rear panels of all cigarette packages and at least 20 percent of each advertisement. They are expected to decrease the number of smokers, which will save lives and increase life expectancy.

E Pharm: FDA unveils new global strategy to help ensure saf...

E Pharm: FDA unveils new global strategy to help ensure saf...: "The U.S. Food and Drug Administration today unveiled a new strategy to meet the challenges posed by rapidly rising imports of FDA-regulated..."

E Pharm: FDA Drug Safety Communication: Chantix (vareniclin...

E Pharm: FDA Drug Safety Communication: Chantix (vareniclin...: "Safety Announcement [6-16-2011] The U.S. Food and Drug Administration (FDA) is notifying the public that the smoking cessation aid Chantix..."

FDA unveils new global strategy to help ensure safety and quality of imported products

The U.S. Food and Drug Administration today unveiled a new strategy to meet the challenges posed by rapidly rising imports of FDA-regulated products and a complex global supply chain in a report called the "Pathway to Global Product Safety and Quality."

“Global production of FDA-regulated goods has exploded over the past ten years.  In addition to an increase in imported finished products, manufacturers increasingly use imported materials and ingredients in their U.S. production facilities, making the distinction between domestic and imported products obsolete,” said Commissioner of Food and Drugs Margaret A. Hamburg, M.D.  "There has been a perfect storm - more products, more manufacturers, more countries and more access.  A dramatic change in strategy must be implemented." 

The FDA report calls for the agency to transform the way it conducts business and to act globally in order to promote and protect the health of U.S. consumers. Highlights of the report include four key elements needed to make the change:

1. The FDA will partner with its counterparts worldwide to create global coalitions of regulators focused on ensuring and improving global product safety and quality.

2. The coalitions of regulators will develop international data information systems and networks and increase the regular and proactive sharing of data and regulatory resources across world markets.

3.  The FDA will build in additional information gathering and analysis capabilities with an increased focus on risk analytics and information technology.

4. The FDA increasingly will leverage the efforts of public and private third parties and industry and allocate FDA resources based on risk.

"FDA regulated imports have quadrupled since 2000,” Hamburg said. "The FDA and our global regulatory partners recognize this new reality and realize we must work proactively and collaboratively to address the challenges we face.  The FDA must further collaborate and leverage in order to close the gap between our import levels and our regulatory resources. This report is an important step in ensuring we are able to fulfill our critical public health mission."

The change in strategy will address trends expected to be seen worldwide in upcoming years:

• Western economies will increase their productivity to compete with emerging markets and economies, leading to more imports and increased pressure to reinvent manufacturing processes.
• Money, goods, data and people will increasingly and more quickly cross borders. Today, a typical U.S. manufacturing company relies on more than 35 different contract manufacturers around the world.
• Growing demand, constrained supply, and increased regulatory and social scrutiny will determine what resources are used, how they are used, and the cost. Manufacturers will adopt new manufacturing processes and emerging technologies in response.
• Governments worldwide will increasingly be called upon to mitigate the sometimes negative impacts of globalization on their citizens, making the operating environment for companies more complex.

The new strategy also builds on changes already set in motion by the FDA. The FDA increased the number of foreign drug manufacturing inspections by 27 percent between 2007 and 2009 and has opened a series of international offices in key locations.  FDA has also collaborated with its counterparts in the European Union and Australia on drug inspections, worked to harmonize certain aspects of drug regulation via the International Conference on Harmonization, and joined the Pharmaceutical Inspection Cooperation/Scheme (PIC/S) which is an organization of the drug manufacturing inspectorates from 39 countries.  The FDA and other global leaders are also creating an expanded global regulators forum for medical devices. 

The FDA is also broadening its food safety efforts under the FDA Food Safety Modernization Act (FSMA). This new law creates a new foods safety system, in which FDA has a legislative mandate to require comprehensive preventive controls across the food supply chain and has new tools to hold players in the supply chain responsible.  There are also new inspection mandates, including a mandate leading to the inspection of more than 19,000 foreign food facilities in the year 2016.

The FSMA recognizes the importance of partnerships in the success of this new food safety system, particularly in the area of imports.  For example, importers now have an affirmative obligation to verify the safety of the food they bring into the United States.  In addition, the FDA will establish a program for qualified third parties to certify that foreign food facilities are in compliance with U.S. requirements and can require certification as a condition of entry into the United States.  And, FSMA explicitly encourages arrangements with foreign governments to leverage resources.

“In order to cope with the fundamental global shifts on the horizon, the FDA will have to substantially and fundamentally revise our approach to global product safety.  We can no longer rely on historical tools, activities and approaches,” said Acting Principal Deputy Commissioner of Food and Drugs John M. Taylor, J.D.  “Implementing this strategy is vital to the public health.”

For more information, visit:

• Pathway to Global Product Safety and Quality
• FDA Food Safety Modernization Act

FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

FDA Drug Safety Communication: Chantix (varenicline) may increase the risk of certain cardiovascular adverse events in patients with cardiovascular disease

Safety Announcement

[6-16-2011] The U.S. Food and Drug Administration (FDA) is notifying the public that the smoking cessation aid Chantix (varenicline) may be associated with a small, increased risk of certain cardiovascular adverse events in patients who have cardiovascular disease. This safety information will be added to the Warnings and Precautions section of the Chantix physician labeling. The patient Medication Guide will also be revised to inform patients about this possible risk.

FDA reviewed a randomized clinical trial of 700 smokers with cardiovascular disease who were treated with Chantix or placebo (see Data Summary below). In this trial, Chantix was effective in helping patients quit smoking and remain abstinent from smoking for as long as one year. Cardiovascular adverse events were infrequent overall, however, certain events, including heart attack, were reported more frequently in patients treated with Chantix than in patients treated with placebo.

Healthcare professionals should be aware that smoking is an independent and major risk factor for cardiovascular disease, and smoking cessation is of particular importance in this patient population. The known benefits of Chantix should be weighed against its potential risks when deciding to use the drug in smokers with cardiovascular disease.

Patients taking Chantix should contact their healthcare professional if they experience new or worsening symptoms of cardiovascular disease.

FDA is continuing to evaluate the cardiovascular safety of Chantix and is requiring the manufacturer to conduct a large, combined analysis (meta-analysis) of randomized, placebo-controlled trials. FDA will update the public when additional information is available.

Additional Information for Patients

• Smoking is a major risk factor for cardiovascular disease, and Chantix can help you quit smoking.
• If you have cardiovascular disease, taking Chantix may increase your risk of certain cardiovascular adverse events.
• Contact your healthcare professional if you experience new or worsening symptoms of cardiovascular disease while taking Chantix, for example:
  • Shortness of breath or trouble breathing
  • New or worsening chest pain
  • New or worse pain in legs when walking
• Read the Medication Guide you get along with your Chantix prescription. It explains the risks associated with the use of Chantix.
• Talk to your healthcare professional if you have questions or concerns about Chantix.
• Report side effects from the use of Chantix to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of the page.

Additional Information for Healthcare Professionals

• Smoking is an independent and major risk factor for cardiovascular disease, and Chantix is effective in helping patients quit smoking.
• Be aware that a small, increased risk of certain cardiovascular adverse events was reported in a study of patients with cardiovascular disease receiving Chantix. The events included angina pectoris, nonfatal myocardial infarction, need for coronary revascularization, and new diagnosis of peripheral vascular disease or admission for a procedure for the treatment of peripheral vascular disease.
• Weigh the known benefits of Chantix against the potential risks of its use in smokers with cardiovascular disease.
• Counsel patients to seek medical attention if they experience new or worsening symptoms of cardiovascular disease while taking Chantix.
• Encourage patients to read the Medication Guide they receive along with their Chantix prescription.
• Report adverse events involving Chantix to the FDA MedWatch program using the information in the "Contact Us" box at the bottom of this page.

Data Summary

FDA reviewed a randomized, double-blind, placebo-controlled clinical trial designed to assess the efficacy and safety of Chantix for smoking cessation in 700 patients aged 35 to 75 years with stable, documented cardiovascular disease (other than, or in addition to, hypertension) that had been diagnosed at least two months prior to the screening visit. Patients were randomized to treatment with Chantix 1 mg twice daily (n=350) or placebo (n=350). The study consisted of a 12-week treatment period that was followed by a 40-week non-treatment period. Patients also received smoking cessation counseling throughout the study. The 4-week Continuous Quit Rate (CQR) for Weeks 9 through 12 was obtained through weekly reports of cigarette or other nicotine use since the last study visit, and confirmed by measurement of end-expiratory exhaled carbon monoxide ≤10 ppm.

The results showed a statistically significantly higher 4-week CQR in the Chantix arm compared with the placebo arm (47% versus 14%, respectively; p<0.0001). The continuous abstinence rate from Week 9 through Week 52 of the study was also significantly higher in the Chantix group compared with the placebo group (19% versus 7%, respectively; p<0.0001).

Certain cardiovascular adverse events were reported in more patients treated with Chantix than patients treated with placebo. These included angina pectoris, nonfatal myocardial infarction, need for coronary revascularization, and new diagnosis of peripheral vascular disease or admission for a procedure for the treatment of peripheral vascular disease, as is shown in the table below. These events were reviewed by an independent cardiovascular endpoint committee. Some of the patients requiring coronary revascularization underwent the procedure as part of management of nonfatal myocardial infarction and hospitalization for angina pectoris. The trial was not designed to have statistical power to detect differences between the arms on the safety endpoints.

Adjudicated Cardiovascular Events During the 52-Week Study Period (≥1% in any group)

	Varenicline N=353* n (%)	Placebo N=350 n (%)
Nonfatal myocardial infarction	7 (2.0)	3 (0.9)
Need for coronary revascularization†	8 (2.3)	3 (0.9)
Hospitalization for angina pectoris	8 (2.3)	8 (2.3)
New diagnosis of peripheral vascular disease (PVD) or admission for a procedure for the treatment of PVD	5 (1.4)	3 (0.9)

*Three patients in the varenicline arm did not meet the protocol-specified definition of stable cardiovascular disease but were included in the safety analysis population.

^†Patients with need for coronary revascularization in the varenicline arm include 5 patients who are also counted under nonfatal myocardial infarction and/or hospitalization for angina pectoris events. Patients with need for coronary revascularization in the placebo arm include 2 patients who are also counted under nonfatal myocardial infarction and/or hospitalization for angina pectoris.

FDA Notification to Industry Regarding Potential Adulteration of Pharmaceutical Ingredients used as Emulsifying Agents and Flavorings

FDA's Center for Drug Evaluation and Research (CDER) recently learned that there have been recent instances when clouding and flavoring agents, which have been used outside the U.S. in certain food manufacturing processes, contain undeclared phthalate plasticizers, specifically diethylhexyl-phthalate (DEHP) and diisononyl-phthalate (DINP).

CDER is not aware at this time of any intentional phthalate substitution, in part or whole, in finished pharmaceuticals or pharmaceutical ingredients used in the U.S. market. Nonetheless, significant overlap of global food and pharmaceutical ingredient supply chains raises the potential for adulterated food ingredients to enter the U.S. pharmaceutical supply chain.

CDER advises manufacturers of drug products and suppliers of pharmaceutical ingredients, both in the U.S. and abroad, to be aware of the potential substitution of phthalate plasticizers for vegetable oils in clouding and flavoring agents. Manufacturers using emulsions containing vegetable oils should exercise caution to prevent the use of ingredients that might be intentionally adulterated with phthalates