ACCELERATED APPROVAL GRANTED TO TRAMEITNIB AND DABRAFENIB

FROM:  FOOD AND DRUG ADMINISTRATION

Trametinib and Dabrafenib

The U. S. Food and Drug Administration granted accelerated approval to trametinib (Mekinist tablets, GlaxoSmithKline, LLC) and dabrafenib (Tafinlar capsules, GlaxoSmithKline, LLC) for use in combination in the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation as detected by an FDA-approved test.

Trametinib was previously approved in 2013 as a single agent for treatment of BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma.   Dabrafenib was also approved in 2013 as a single agent for treatment of BRAF V600E mutation-positive unresectable or metastatic melanoma. Trametinib and dabrafenib target two different tyrosine kinases in the RAS/RAF/MEK/ERK pathway.

 

Approval of the combination therapy was based on the demonstration of durable objective responses in a multicenter, open-label, randomized (1:1:1), active-controlled, dose-ranging trial enrolling 162 patients with histologically confirmed Stage IIIC or IV melanoma determined to be BRAF V600E or V600K. No more than one prior chemotherapy regimen and/or interleukin-2 were permitted. Patients with prior exposure to BRAF inhibitors or MEK inhibitors were ineligible.

 

Patients were randomized to receive trametinib 2 mg orally once daily in combination with dabrafenib 150 mg orally twice daily (n=54), trametinib 1 mg orally once daily in combination with dabrafenib 150 mg orally twice daily (n=54), or single-agent dabrafenib 150 mg orally twice daily (n=54). Of the 162 patients enrolled, 57% were male, the median age was 53 years, all had baseline ECOG PS of 0 or 1, 67% had M1c disease, and 81% had not received prior anticancer therapy for unresectable or metastatic disease. All patients had tumor tissue with mutations in BRAF V600E (85%) or V600K (15%) on local or centralized testing.

 

The investigator-assessed objective response rates and response duration were 76% (95% CI: 62, 87) and 10.5 months (95% CI: 7, 15), respectively, in the trametinib 2 mg plus dabrafenib combination arm and 54% (95% CI: 40, 67) and 5.6 months (95% CI: 5, 7), respectively, in the single-agent dabrafenib arm. Objective response rates were similar in subgroups defined by BRAF V600 mutation subtype, V600E and V600K. Analyses of objective response rates based on blinded independent central review were consistent with the investigator results.

 

The incidence of cutaneous squamous cell carcinoma (including squamous cell carcinomas of the skin and keratoacanthomas), the trial’s primary safety endpoint, was 7% (95% CI: 2, 18) in the trametinib 2 mg plus dabrafenib combination arm compared to 19% (95% CI: 9, 32) in the single-agent dabrafenib arm.

 

The most frequent (greater than or equal to 20% incidence) adverse reactions from trametinib in combination with dabrafenib were pyrexia, chills, fatigue, rash, nausea, vomiting, diarrhea, abdominal pain, peripheral edema, cough, headache, arthralgia, night sweats, decreased appetite, constipation, and myalgia. The most frequent grades 3 and 4 adverse events (greater than or equal to 5% incidence) were acute renal failure, pyrexia, hemorrhage, and back pain.

 

Serious adverse drug reactions occurring in patients taking trametinib in combination with dabrafenib were hemorrhage, venous thromboembolism, new primary malignancy, serious febrile reactions, cardiomyopathy, serious skin toxicity, and eye disorders such as retinal pigmented epithelial detachments.

 

Granting of this accelerated approval is contingent upon the successful completion of the ongoing MEK115306 trial to verify the clinical benefit of trametinib for use in combination with dabrafenib. MEK115306 is an international, multicenter, randomized (1:1), double-blind, placebo-controlled trial comparing the combination of dabrafenib and trametinib to dabrafenib and placebo as first-line therapy in approximately 340 patients with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E or V600K mutation-positive cutaneous melanoma.  The primary endpoint is progression-free survival.  Overall survival is a key secondary endpoint.

 

The recommended dose and schedule for trametinib and dabrafenib when used in combination is trametinib 2 mg orally once daily with dabrafenib 150 mg orally twice daily continued until disease progression or unacceptable toxicity occurs. Trametinib and dabrafenib should be taken at least one hour before or two hours after a meal. The once daily dose of trametinib can be taken at the same time as either dose of dabrafenib.

 

FDA GIVES APPROVAL FOR GENERIC VERSIONS OF CYMBALTA

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 
FDA NEWS RELEASE
 For Immediate Release: Dec. 11, 2013
FDA approves first generic versions of antidepressant drug Cymbalta

The U.S. Food and Drug Administration today approved the first generic versions of Cymbalta (duloxetine delayed-release capsules), a prescription medicine used to treat depression and other conditions.

Aurobindo Pharma Ltd., Dr. Reddy’s Laboratories Ltd., Lupin Ltd., Sun Pharma Global FZE, Teva Pharmaceuticals USA, and Torrent Pharmaceuticals Ltd. have received FDA approval to market duloxetine in various strengths.

“Health care professionals and consumers can be assured that these FDA-approved generic drugs have met our rigorous standards,” said Kathleen Uhl, M.D., acting director of the Office of Generic Drugs in the FDA’s Center for Drug Evaluation and Research. “Generic drugs offer greater access to health care for many people.”

Depression is characterized by symptoms that interfere with a person's ability to work, sleep, study, eat, and enjoy once-pleasurable activities. Episodes of depression often recur throughout a person's lifetime. Signs and symptoms of depression include: depressed mood, loss of interest in usual activities, significant change in weight or appetite, insomnia or excessive sleeping (hypersomnia), restlessness/pacing (psychomotor agitation), increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and suicide attempts or thoughts of suicide.

Duloxetine and other antidepressant drugs have a boxed warning describing the increased risk of suicidal thinking and behavior during initial treatment in children, adolescents, and young adults ages 18 to 24. The warning also says data do not show this increased risk in those older than 24 years and that patients ages 65 and older who take antidepressants have a decreased risk of suicidal thinking and behavior.

The warning says depression and other serious psychiatric disorders themselves are the most important causes of suicide and that close monitoring of patients starting these medications is necessary. Duloxetine must be dispensed with a patient medication guide that describes important information about the drug’s uses and risks.

Common adverse reactions reported by people taking Cymbalta include nausea, dry mouth, drowsiness, fatigue, decreased appetite, increased sweating, and dizziness.

Generic prescription drugs approved by the FDA have the same high quality and strength as brand-name drugs. Generic prescription drug manufacturing and packaging sites must pass the same quality standards as those of brand-name drugs.

Information about the availability of generic duloxetine can be obtained from the manufacturers.

FDA TOUTS ROLE IN PROTECTING THE HEALTH OF TRAVELERS

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 
FDA Protects Travelers' Health

The roots of the Interstate Travel Program at the Food and Drug Administration (FDA) can be traced back to long before the agency existed—to the presidency of John Adams.

Originally part of the Public Health Service, the program focused in the early days on the health of those traveling on Merchant Marine ships and was seen as instrumental in increasing the security of our young nation.

As the U.S. role in the world grew, so did the need for greater attention to the safety of travelers using both government-subsidized and privately owned transportation systems.

"During World War I and II there was nothing worse than sending 3,000 troops on a vessel and 400 of them show up well and the other 2,600 are sick," says Matt Albright, a consumer safety officer at FDA.

Throughout the 1800s the program expanded as trains traveling across the U.S. were struck by yellow fever and small pox outbreaks. In the early 1900s, buses joined the ranks of interstate transportation and the program went airborne in the 1920s.

For the past 45 years the program has been under the purview of FDA, which has been working diligently to keep travelers healthy.


Conception to Implementation
ITP is responsible for inspecting the food, water and waste-disposal systems in all commercial transport vehicles that travel from one state to another. However, its involvement begins long before the food and water are loaded aboard.
When the train, bus, ship or jet is being planned, ITP is involved from the beginning of the engineering process, including giving feedback on blueprints and designs.

With 20 years in the field conducting inspections and 10 more at FDA headquarters in College Park, Md., ITP manager Bruce Kummer knows that disease and infection can indeed be in the details.

"You don't want your sewage discharge in front of the intake for water," says Kummer, describing a basic design flaw. The team inspects for details that include making sure the fitting sizes are different for waste and water, so a worker couldn't accidentally hook up the waste hose to the potable water intake. Safeguards like this—when implemented during construction – decrease the likelihood of errors that could endanger passengers' health.

Another important aspect of the construction review process is limiting entrance and harborage areas for pests like rats, mice or cockroaches.

"You can't fix deficiencies and structural integrity of a conveyance once it is in operation if it was built poorly," says Albright. "You have to build it properly first."


Inspections Continue For Years
To ensure that the passenger conveyance is engineered and built in compliance with standards established by FDA, the ITP team inspects the prototype and addresses issues before mass production begins.
Kummer notes that FDA can withhold a Certificate of Sanitary Construction from a shipyard or other transport builder if there are major sanitary construction defects.

Throughout the transport vehicle's construction and in the years that follow, FDA does spot checks and inspections as necessary. Larger companies, like Boeing, take advantage of a self-certification program in which FDA is provided with detailed reports on compliance with Agency regulations. FDA can – and has – entered facilities to perform audits to ensure that companies are complying with the construction guidelines.

Generally, FDA issues Warning Letters when deficiencies are discovered to give the company a short time to fix the problems while still operating its vehicle. If companies do not correct the problems, further regulatory steps may be taken and the transport vehicle can be taken out of service.

"Provisional" letters may be sent to operators of caterers, commissaries, watering points, and servicing areas if significant sanitary deficiencies are observed, giving the operators a limited amount of time to correct these items or risk losing their status as an FDA-approved facility. Transport companies are required under FDA regulations to use only approved facilities, which places more pressure on the servicing companies to clean up the deficiencies so they do not risk losing their approved status.

"I feel a lot of pride for my involvement in this work, in keeping travelers safe whether they're traveling by land, sea or air," Kummer says.

This article appears on FDA's Consumer Updates page, which features the latest on all FDA-regulated products.

Nov. 25, 2013

FDA RECOMMENDS SEEING PROFESSIONAL BEFORE ORDERING HEARING AIDS OR SOUND AMPLIFIERS

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 
Hearing Loss Signals Need for Diagnosis

Straining to hear? Do people say you’re talking loudly? Thinking about ordering a hearing aid or sound amplifier from a magazine or late-night TV advertiser?

Doing so could delay the diagnosis of a treatable or serious ear condition and lead to further hearing loss or other complications.

“The problem might be as simple as a wax impaction blocking the ear canal, which is easily treated, or at the other end of the spectrum, it could be something as serious as a tumor pressing on the hearing nerve,” says Eric Mann, M.D., Ph.D., clinical deputy director for the Division of Ophthalmic, and Ear, Nose, and Throat Devices at the Food and Drug Administration (FDA).

Many cases of hearing loss are related to aging and exposure to loud noises, and a hearing aid, or frequently one for each ear, might be the solution. But while a prescription is not required for most kinds of hearing aids, it’s important to see a health care professional not only to rule out other medical causes of hearing loss, but to ensure that hearing aids are properly fitted and come with follow-up care.

“Sometimes there are issues with comfort. Perhaps you can’t wear a particular hearing aid because it is scratching the ear canal,” said Mann. “There are sometimes problems with a whistling noise from the hearing aid known as ‘feedback’ because it’s not a proper fit in the ear canal. These are all issues a hearing health care professional will work through with you.”

Aids Versus Amplifiers
Mann adds that consumers should not confuse hearing aids with the personal sound amplification products (PSAPs.) Although some PSAP technology is similar to that of a hearing aid, only hearing aids are intended to make up for impaired hearing.

A PSAP, in contrast, is for people with normal hearing who have a desire or need to amplify sounds in certain situations. For example, a PSAP may be helpful for hunters or bird-watchers. They are often advertised as a way to listen to a television set to a low volume that won’t disturb someone sleeping nearby.

FDA regulates hearing aids as medical devices in order to assure their safety and effectiveness. PSAPs are not subject to medical device regulations, although they are subject to other safety regulations as an electronic product that emits sound vibrations. FDA recently issued a draft update to this guidance to clarify what claims are appropriate for each of these two distinct types of products.

Differences among hearing aids themselves are more complex, which is one of the reasons a professional should be involved. Because hearing loss affects people in different ways, you need a device appropriate for your condition, and tailored to your lifestyle. A librarian, for example, might need different features in a hearing aid than a concert manager or a salesperson who spends the workday on the phone.

Hearing aids of various sizes may be worn behind the ear, in the ear or completely in the ear canal. Some include directional microphones, which allows sound coming from a specific direction to be amplified to a greater degree than sound from another direction. Some have switches specifically for telephone conversations, or inputs to allow you to plug directly into an electrical device, such as a TV or computer.

Buyer Beware
FDA strongly encourages a medical evaluation before the purchase of a hearing aid. Hearing aid sellers are required to tell you about the importance of a medical evaluation before they sell the aid. If you decide to forego an evaluation, you must sign a waiver.

Your primary care doctor may refer you to a specialist in ear, nose and throat conditions—an otolaryngologist (commonly known as an ENT specialist) -- for evaluation and diagnosis of hearing loss. Two types of hearing health professionals that are authorized to measure hearing loss and dispense hearing aids include:

Audiologists, who must have at least a master’s degree and specialized training in hearing loss.
Hearing aid dispensers, who are licensed by states under varied requirements.
The Federal Trade Commission advises consumers to avoid businesses that dismiss the need for a medical exam before selling you a hearing aid. Other advice includes:

Seek a licensed hearing aid professional who offers products from several manufacturers.
Ask whether there is a trial period—most states require 30-60 day trial periods. Find out what exactly is refundable if you return the hearing aid during the trial period.
Examine the details of the warranty, including whether you’ll get a free loaner if your device needs serving and repair.
Check whether the price quoted includes testing and follow-up services.
This article appears on FDA's Consumer Updates page, which features the latest on all FDA-regulated products.

FDA SAYS WILL COMPLETE PHASE-OUT OF INHALER PRODUCTS CONTAINING CHLOROFLUOROCARBONS

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 

The Division of Drug Information (DDI) is CDER's focal point for public inquiries. We serve the public by providing information on human drug products and drug product regulation by FDA.

The U.S. Food and Drug Administration will complete its phase-out of all inhaler medical products containing chlorofluorocarbons (CFCs) by Dec. 31, 2013. This effort is to comply with an international treaty to protect the ozone layer by phasing out the worldwide production of numerous substances, including CFCs, which contribute to ozone depletion.

While most inhaler products containing CFCs have already been phased out by the FDA, two products currently remain on the market: Combivent Inhalation Aerosol and Maxair Autohaler. However, these products will no longer be available after the end of this year. People with asthma or chronic obstructive pulmonary disease (COPD) who use these inhalers should talk to their health care professional about a prescription for an alternative treatment.

Inhalers are critical products for those persons suffering from asthma or COPD. In the United States, more than 25 million people suffer from asthma, a disease that affects the airways in the lungs and can cause coughing, trouble breathing, wheezing and tightness or pain in the chest. Additionally, 15 million people have been diagnosed with COPD, a serious lung disease that worsens over time. Symptoms can include chest tightness, chronic cough and excessive phlegm.

GOVERNMENT PROPOSING MEASURES TO PROTECT ANIMALS FROM CONTAMINATED FOODS

FROM:  FOOD AND DRUG ADMINISTRATION 
FDA Moves to Keep Foods Safe for Animals

For the first time, the Food and Drug Administration (FDA) is proposing preventive measures to protect all animal foods from disease-causing bacteria, chemicals and other contaminants.

This includes the food that pet owners give their dogs, cats and other companion animals, and the feed that farmers give their livestock.

Preventive Controls for Food for Animals is the fifth rule that FDA has proposed this year as part of the food-safety framework envisioned by the 2011 FDA Food Safety Modernization Act that focuses on preventing foodborne illnesses.

Daniel McChesney, Ph.D., director of the Office of Surveillance and Compliance at FDA’s Center for Veterinary Medicine (CVM), explains that this rule proposes establishing a whole new set of protections for animal foods. Currently, the agency primarily gets involved when there is evidence of contaminated animal food on the market.

“Unlike safeguards already in place to protect human foods, there are currently no regulations governing the safe production of most animal foods. There is no type of hazard analysis. This rule would change all that,” says McChesney.

McChesney notes that human and animal health are intertwined. People can get sick when pet food is contaminated by disease-causing bacteria like Salmonella. When such food is handled by pet owners and placed on kitchen surfaces, the bacteria can spread to foods consumed by their family.

And if an animal has eaten feed contaminated with a chemical like dioxin and then enters the food supply, consumers could likewise absorb the chemical, putting their health at risk.

By helping to prevent the contamination of animal foods, the proposed rule protects pets and people alike, he says.

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Requiring a Safety Plan
This proposed rule would create regulations that address the manufacturing, processing, packing and holding of animal food. Good manufacturing practices would be established for buildings, facilities and personnel, and would include cleaning and maintenance, pest control, and the personal hygiene of people who work there.

It would also require facilities to have a food safety plan, perform an analysis of potential hazards, and implement controls to minimize those risks. Those controls would have to be monitored and corrected as needed.

While this rule is similar in many ways to the Preventive Controls for Human Food rule that FDA proposed in January 2013, McChesney explains that it is different in a number of ways because animals face different hazards.

For example, he says, the proposed animal rule doesn’t address allergens—substances that could cause an allergic reaction. That’s because animals don’t get the kind of life-threatening allergic reactions that people do. They might get a skin reaction but not the kind of physical shock that a food allergen could trigger in a person.

On the other hand, contaminants that endanger animals are sometimes tolerated better by people and were not as great a concern in crafting protections for human food. For example, some animals are much more vulnerable to aflatoxin, a toxin caused by mold, and could die after consuming food containing the toxin.

The animal rule is also designed to prevent nutrient imbalances in animal foods. Unlike people, who get their foods from many sources, an animal’s food is meant to be a complete and balanced diet, explains McChesney. If a food doesn’t have enough of a particular nutrient, the animal has no way to make it up. For example, cats need thiamine (also known as Vitamin B1) but their bodies don’t produce it. If they don’t get enough in their food, they can suffer severe neurological problems.

The proposed rule has been published in the Federal Register, with a 120-day public-comment period. The rule is filed in FDA's official docket at www.regulations.gov and can also be accessed at www.fda.gov/fsma.

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Import Rules Add Safeguards
The proposed animal rule would work in concert with two rules proposed in July 2013 to help ensure that foods exported to the United States are held to the same FDA food safety standards applied to foods produced in the United States. Together, the three rules would help ensure the same level of safety for domestic and imported foods for animals.

In one of the most infamous examples of pet food contamination, dogs and cats across the country were sickened and killed in 2007 when melamine, a chemical used to make plastic, was added to pet food ingredients imported from China. McChesney noted that FDA received about 18,000 calls from anxious pet owners at the time.

The requirements proposed in both the animal and import rules are designed to help prevent that from happening again, he says.

Overall, McChesney says that the animal food supply is very safe. However, with the marketplace becoming more global and more diverse, more protections are needed. When you buy food for your animals, those ingredients could come from anywhere in the world, so animal food producers and their suppliers, no matter where they are based, have to be held to the same high standards, he says.

“Whether in the home or on the farm, people take the safety of their animals very seriously, and so do we,” says McChesney.

This article appears on FDA's Consumer Updates page, which features the latest on all FDA-regulated products.

Oct. 25, 2013

DRUG APPROVED TO HELP ALLEVIATE DRUG SHORTAGE FOR INTRAVENOUS FEEDING

FROM:  FEDERAL DRUG ADMINISTRATION 
FDA approves Clinolipid for intravenous nutrition
Action addresses shortages of drugs needed by patients unable to eat or drink

The U.S. Food and Drug Administration today approved Clinolipid (lipid injectable emulsion, USP) for intravenous feeding (parenteral nutrition) in adult patients, providing a source of calories and essential fatty acids for adult patients who are unable to eat or drink. Clinolipid was granted a priority review to help alleviate a drug shortage.

“Preventing and mitigating drug shortages is a top priority for the FDA,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “Approving submissions from manufacturers who can start new production or increase existing production of a product in short supply is one of the many effective mitigation tools that the FDA employs to address a shortage problem.”

Clinolipid is a lipid emulsion that contains a mixture of refined olive oil and refined soybean oil. The fatty acids contained in Clinolipid serve as an important source of energy in patients receiving parenteral nutrition. The omega-3: omega-6 fatty acid ratio in Clinolipid has not been shown to improve clinical outcomes compared to other lipid emulsion products.

“The FDA has been very concerned about the short supply of injectable lipid emulsion products,” said Donna Griebel, M.D., director of the Division of Gastroenterology and Inborn Errors Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval of Clinolipid will help in the effort to resolve this shortage so that patients have access to these parenteral nutrition products.”
                                         
Clinolipid is intended for adults, and like other intravenous lipid emulsions, should be used with caution in patients with preexisting liver disease or liver insufficiency. Clinolipid should not be used in patients with a known hypersensitivity to egg or soybean proteins, or in those with severe disorders of lipid metabolism (hyperlipidemia).
 
The safety and effectiveness of Clinolipid were evaluated in clinical efficacy and safety studies comparing Clinolipid with a soybean oil-based lipid emulsion. Clinolipid is an effective source of energy in adults. The most common side effects in patients treated with Clinolipid during clinical trials included infectious complications, nausea and vomiting, excess fat (lipids) in the blood, high blood sugar, low levels of protein in the blood and abnormal liver function tests.

Clinolipid is not indicated for use in preterm infants. The product carries a warning in its label about the risk of death in preterm infants after infusion of intravenous lipid emulsions such as Clinolipid.

Clinolipid is also not indicated for use in other pediatric patients because it is not known whether the amount of essential fatty acids found in Clinolipid is enough to meet the nutritional needs of children.

Clinolipid is marketed by Deerfield, Ill.-based Baxter Healthcare Corporation.

DOD POLICY ON ANTIMALARIAL DRUG MEFLOQUINE

FROM:  U.S. DEPARTMENT OF DEFENSE 
DOD Mefloquine Policy Mirrors FDA Update on Malaria Drug
By Cheryl Pellerin
American Forces Press Service

WASHINGTON, Sept. 26, 2013 - The Defense Department's policy on the antimalarial drug mefloquine, which has been in use for decades, is consistent with a stronger, updated warning about the drug from the Food and Drug Administration, senior DOD officials said.

On July 29, the FDA posted on its website a public advisory about neurologic and psychiatric side effects associated with mefloquine hydrochloride, a drug used to prevent and treat the deadly mosquito-borne disease.

The regulatory agency added a boxed warning -- the most serious kind -- to modify the drug's label and revise the patient medication guide and wallet-information card given with each prescription to include the possibility that the neurologic side effects could persist or become permanent if the drug is used.

The FDA uses a boxed warning when an adverse reaction is so serious in proportion to the drug's potential benefit that prescribers should consider this when evaluating the drug's risks and benefits. The warning also is used to alert prescribers that they can prevent or reduce a serious adverse reaction in patients by using the drug appropriately.

Neurologic side effects can include dizziness, loss of balance or ringing in the ears. Psychiatric side effects can include anxiety, mistrust, depression, or hallucinations.

At the Defense Department, mefloquine was designated as the antimalarial drug of last resort in April, according to a DOD policy letter issued that month by Dr. Jonathan Woodson, assistant secretary of defense for health affairs.

"According to the April 15, 2013, Health Affairs guidance, mefloquine should be the last drug that's used. There are other drugs we use first, which would be chloroquine, doxycycline or Malarone, and we save mefloquine for last," Air Force Col. (Dr.) Scott Stanek, a preventive medicine physician in the Office of Force Health Protection and Readiness, told American Forces Press Service.

Malaria is rare in the United States, Stanek said, adding that about 1,700 cases were reported here in 2010 and all were acquired outside the country, leading to six deaths.

"But we send our service members to areas where there is malaria," he said. "It's a serious disease that kills many people around the world, so that's one of the reasons we go through these steps to make sure our service members are protected, and part of the protection package is to use antimalarial medications."

Stanek said that when service members find out they are deploying to an area, they come to the clinic to find out if there is malaria in that location, its type and sensitivity to medications, or whether any resistance to certain antimalarial medications may be present in that location as identified by the Centers for Disease Control and Prevention or the National Center for Medical Intelligence.

Air Force Col. (Dr.) Jose Rodriguez-Vazquez, a family practice and aerospace physician and director of medical readiness in the Office of Force Health Protection and Readiness, said no antimalarial drug is 100 percent protective. Every drug should be used along with personal protective measures such as insect repellent, long sleeves, long pants, sleeping in a mosquito-free setting or using an insecticide-treated bed net, he said.

Stanek added that protection is a multipronged approach.

"We try to minimize the amount of activity we do at times when there are high levels of mosquitoes out there. We provide [service members] with permethrin-treated uniforms; DEET, a very effective insect repellent for the exposed areas of their skin; mosquito netting if needed; and then the last one is antimalarial medicine. It's kind of a package deal," he said.

In areas of the world where service members need protection from malaria parasites, it's only 30 or 40 species of the female Anopheles mosquito infected with the parasites whose bite can transmit the Plasmodium falciparum parasites to humans.

The female mosquito bites mainly between 9 p.m. and 5 a.m., which is why sleeping under a mosquito net is so important.

If a mosquito is infected with Plasmodium parasites and bites someone, the parasites enter the body and travel through the blood stream to the liver, where they multiply about 10,000 times, producing no symptoms at first. About two weeks later, the parasites burst into the blood stream and start infecting red blood cells.

This is where the parasites start producing symptoms of the disease, including chills, fever, headache, sweats and nausea. But it's also where mefloquine works, killing the parasites and keeping them from multiplying.

Mefloquine is effective in preventing malaria, with a demonstrated success rate of 91 percent, according to studies of travelers to East Africa, military health officials said.

"This medication has been around for quite a few years," Stanek said. "It has been used by tens of thousands of individuals, and it works well. It is well known that there is a risk of side effects in some individuals, and although the number of those people is relatively small, we need to make sure that patients are screened so they're not inappropriately given the medication."

On Aug. 12, Woodson notified all military health care providers of the FDA mefloquine boxed warning and labeling change due to potential neurologic and psychiatric side effects associated with the drug.

"This FDA notice focuses on warnings in the prescribing information," he said, "but does not change the indications for the medication."

Woodson said the April 2013 DOD guidance reiterated that mefloquine should be reserved for those who can't take first-line medications and reinforces the need to evaluate each patient for contraindications before starting mefloquine.

Such contraindications include a history of traumatic brain injury and posttraumatic stress disorder, and in those with psychiatric diagnoses, specifically depression, schizophrenia and anxiety disorders, he said.

"As a result of DOD guidance limiting its use," Woodson added, "the number of active-duty service members who received prescriptions for mefloquine decreased from 17,361 in 2008 to 889 through July 2013. Use in other DOD beneficiaries has also decreased dramatically."

Mefloquine use at all points of service for all TRICARE beneficiaries during calendar year 2012 was 5,370 prescriptions given to 4,770 individuals, defense officials said. Of these beneficiaries, 2,030 were active-duty personnel.

"Based on the FDA guidance," Stanek said, "there needs to be a pretty strong reason why somebody uses mefloquine. They either can't take one of the other medicines because of contraindications, or they can't take them because they don't work for that particular [geographical] area."

ARSENIC AND APPLE JUICE

FROM:  FOOD AND DRUG ADMINISTRATION 
Why FDA Proposes an ‘Action Level’ for Arsenic in Apple Juice
Posted on July 12, 2013 by FDA Voice
By: Michael R. Taylor, J.D. 

FDA has always been—and will always be—committed to making sure that the food you eat is safe for you and your family. It’s a challenging job in today’s complex, global marketplace.
One of those challenges can be summed up in one word: arsenic. This chemical element is found in the Earth’s crust. It’s everywhere in the environment and can be found in water, air and soil, in both organic and inorganic forms. Human activities also can introduce arsenic into the environment. That means that it can also be found in some foods and beverages.

Today, FDA is acting to help ensure that consumers do not come in contact with apple juice that has levels of inorganic arsenic that exceed 10 parts per billion. That’s the same level that the Environmental Protection Agency (EPA) has set for drinking water, which is consumed in much greater quantities.

FDA tests hundreds of foods and beverages for all kinds of potentially harmful substances, and we have been monitoring the levels of arsenic in foods for decades. Of the two forms of arsenic, we worry about the inorganic kind because long-term exposure can be harmful.
The agency has always found that the amount of arsenic in apple juice is generally low—much lower, in fact, than the levels allowed in drinking water. Consumer Reports did an important story highlighting its own testing. And in 2011, we substantially increased testing and analysis of apple juice to continue and enhance our monitoring efforts.

We found that our original belief was correct, that the levels of inorganic arsenic in apple juice are too low to cause immediate or short-term health damage. Working with colleagues in EPA, the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC), we then looked at potential risk from long-term exposure.

That risk assessment helped lead us to the “action level” of 10 parts per billion. We believe that this action level will keep any apple juice that may have more inorganic arsenic than that out of the marketplace.

We will continue to remain vigilant, work with the food industry, and take regulatory action when appropriate to minimize as much as we can the presence of arsenic and other unwanted contaminants in our food supply.

Michael R. Taylor, J.D., is Deputy Commissioner for Foods and Veterinary Medicine

FDA APPROVES NEW TREATMENT FOR LATE-STAGE LUNG CANCER

 FROM:  U.S. FOOD AND DRUG ADMINISTRATION 

The Division of Drug Information (DDI) is CDER's focal point for public inquiries. We serve the public by providing information on human drug products and drug product regulation by FDA.

The U.S. Food and Drug Administration today approved Gilotrif (afatinib) for patients with late stage (metastatic) non-small cell lung cancer (NSCLC) whose tumors express specific types of epidermal growth factor receptor (EGFR) gene mutations, as detected by an FDA-approved test.

Lung cancer is the leading cause of cancer-related death among men and women. According to the National Cancer Institute, an estimated 228,190 Americans will be diagnosed with lung cancer, and 159,480 will die from the disease this year. About 85 percent of lung cancers are NSCLC, making it the most common type of lung cancer. EGFR gene mutations are present in about 10 percent of NSCLC, with the majority of these gene mutations expressing EGFR exon 19 deletions or exon 21 L858R substitution.

Gilotrif is a tyrosine kinase inhibitor that blocks proteins that promote the development of cancerous cells. It is intended for patients whose tumors express the EGFR exon 19 deletions or exon 21 L858R substitution gene mutations. Gilotrif is being approved concurrently with the therascreen EGFR RGQ PCR Kit, a companion diagnostic that helps determine if a patient’s lung cancer cells express the EGFR mutations.

FDA ISSUES RECALL OF CERTAIN INFANT BREATHING CIRCUITS

CareFusion Airlife Infant Breathing Circuit: Class I Recall - Potential for Leak in Closed Ventilation System

AUDIENCE: Anesthesiology, Risk Manager

ISSUE: FDA notified healthcare professionals of the Class 1 recall of the Airlife infant breathing circuit due to the risk that the Y-adapter within the breathing circuit may spontaneously crack, causing a leak in the closed ventilation system. This leak could lead to a decrease in the tidal volume delivered to the ventilated patient. These products may cause serious adverse health consequences, including death. The recalled products were distributed from July 1, 2010 through May 7, 2012.

See the Recall Notice for a listing of affected lot numbers.

BACKGROUND: Respiratory breathing circuits are used with a ventilator when mechanical ventilation is administered to a patient.

RECOMMENDATION: On May 29, 2012, the firm sent an Urgent Recall Notice to customers and distributors. The distributors were requested to immediately destroy any affected product in-stock at their facilities and to cease distributing these products. They were also requested to forward the recall notice to any customers to whom these products were sold, notifying them of the potential risk. CareFusion is requesting that customers destroy all affected product or return any unused product to the distributor.

Read the MedWatch safety alert, including a link to the FDA Recall Notice, at:

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm310871.htm

FDA WEBSITE DISCUSSES HAND HELD X-RAY UNITS

FROM:  U.S. FOOD AND DRUG ADMINISTRATION
Hand-held Dental X-Ray Units: FDA Safety Communication - Unreviewed Products May Not Be Safe or Effective
[Posted 02/10/2012]
AUDIENCE: Dentistry

ISSUE: FDA notified healthcare professionals, including dentists, dental care professionals and veterinarians, about the illegal sale of hand-held dental X-ray units that have not been reviewed by the FDA. The FDA is aware of hand-held dental X-ray units being sold online by manufacturers outside the U.S. and directly shipped to customers in the U.S. These devices may not be safe or effective and could potentially expose the user and the patient to unnecessary and potentially harmful X-rays.

BACKGROUND: All hand-held dental X-ray units that have been certified by the manufacturer to meet the FDA’s radiation safety standards bear a certification label/tag, a warning label, and an identification (ID) label/tag on the unit's housing. All labels/tags should be in the English language and permanently affixed or inscribed on each product so that they are legible and readily accessible when the X-ray unit is fully assembled for use.

RECOMMENDATION: Healthcare professionals should:
Verify that your device bears certification, warning and ID labels as described in the FDA Safety Communication.
Ask your vendor whether the device has been reviewed and cleared by the FDA.
Access the FDA Medical Device Approvals and Clearances searchable database to verify that the X-ray unit you are using has been reviewed by the FDA.
If you become aware of a device that you think is hazardous or does not meet FDA’s radiation safety or premarket clearance requirements, contact your state regulatory agency, which will then notify the FDA. The Conference of Radiation Control Program Directors (CRCPD)   website has a list of contacts for each state

LIXIPRO, BONIVA, PLAVIX, AVAPRO DRUGS WILL SOON BE IN GENERIC FORM

The following excerpt is from an FDA e-mail: 

Generic versions of several popular brand-name drugs are muscling their way onto the prescription shelves. Generic equivalents of Lexipro (escitalopram)used to treat depression and generalized anxiety disorder; Boniva (ibandronate) to prevent and treat osteoporosis; Plavix (clopidogrel) used to prevent strokes and heart attacks; and Avapro (irbesartan) used alone or in combination with other medications to treat high blood pressure, are appearing soon with others to follow.

FDA WARNS OF RISKS IN GASTRIC BANDING SURGERY

The following excerpt is from the FDA website:

"Beware of ads that glamorize this surgery without giving the risks. FDA has warned eight surgical centers  in California about misleading advertising of the Lap-Band - a device implanted in a surgery called gastric banding to help adults eat less and lose weight. FDA has approved two gastric bands: Lap-Band, by Allergan Inc., and Realize Adjustable Gastric Band, by Ethicon Endo-Surgery Inc. These devices are implanted around the upper part of the stomach to create a “pouch.” The small pouch limits the amount of food that can be eaten at one time, making you feel full faster and potentially lose weight. Both bands are approved for use in adults age 18 and older who have not lost weight with non-surgical methods, such as diet, exercise or behavior modification. Health care providers who choose to promote the gastric banding procedure are required to educate patients about the risks involved, which must also be included in any advertising and promotional materials. Patients considering the surgery should read the patient information provided by their doctor and should ask any questions they have about gastric banding before having surgery."