Drug maker urges limits on diet pill use
Wed, 13 Jun 2007 20:08:52 GMTBy ANDREW BRIDGES, Associated Press Writer
WASHINGTON - Sanofi-Aventis SA has failed to demonstrate the safety of its proposed weight-loss drug rimonabant, federal health advisers said Wednesday.
The unanimous decision by the expert panel's 14 voting members made it unlikely they would recommend the Food and Drug Administration approve the drug. They were to vote later Wednesday on whether the drug's benefits outweigh its risks, a finding generally required to merit approval.
This is a breaking news update. Check back soon for further information. AP's earlier story is below.
WASHINGTON — The maker of a weight-loss drug suggested Wednesday that prospective users be screened for depression, seeking to limit damage from a finding that the medication increases the risk of suicidal behavior.
In studies, patients given the once-daily tablet reported twice as many psychiatric side effects, including depression, anxiety and sleep problems, as those who received sham treatment, Dr. Amy Egan, a Food and Drug Administration medical officer, told federal health advisers.
"The numbers of events are small, but in aggregate they are worrisome," Egan said.
Officials from Sanofi-Aventis SA, the manufacturer of the drug, suggested patients be screened for depression before they are prescribed the drug, rimonabant. They also advised that patients visit their doctors five times during the first year of treatment to be reassessed.
"Who is the right patient to receive rimonabant? Not everybody," Sanofi-Aventis' Richard Gural told the panel of advisers. The drug is not appropriate for anyone with a history of depression or suicidal thoughts, or who has been diagnosed with depression or is taking antidepressant medication, he added.
The FDA is expected to decide by July 27 whether to allow the drug on the market. The company proposes selling it under the brand name Zimulti. Rimonabant already is sold in Europe as Acomplia.
The agency isn't required to follow the advice of its outside advisers, but it does so most of the time.
"My general feeling is I agree there is an underestimation of the psychiatric risk associated with this drug," said Dr. Domenic Ciraulo, a Boston Medical Center and Boston University psychiatrist, a member of the FDA advisory board considering the drug.
The findings make it highly likely the first-in-its-class drug would bear stern warnings if it is approved. Company officials embraced the idea of such warnings, which could exclude FDA-approved use in some patients.
Zimulti, when used in conjunction with a modest calorie diet and physical exercise, significantly decreases body weight and waist circumference in overweight or obese patients, according to Sanofi-Aventis. In yearlong studies, patients on the drug lost roughly 14 pounds. Those given dummy pills lost only about 4 pounds. Patients regained weight when treatment was stopped after a year, the company said.
FDA reviewers didn't question whether Zimulti works but remained worried the drug's effect on the body could lead to an array of psychiatric symptoms, including anxiety, phobias, post-traumatic stress disorders and depression.
The company believes those increased cases were associated with depression or other disorders and weren't directly caused by its drug. Egan, however, said they were.
"We strongly believe that it is causal," Egan said. She noted 88 percent of those reporting psychiatric problems while on the drug had no prior history of depression.
Furthermore, patients in the studies were carefully screened and monitored, suggesting the problems would be more common should the drug enter broad use, Egan added.
The screenings proposed by the company won't keep the depressed and obese from Zimulti, warned Lynn McAfee, head of medical advocacy for the Council on Size & Weight Discrimination, a fat acceptance group.
"If this gets out to be a real big deal in the public, you can figure out how to answer those questions to get the drug," McAfee said. "It's not going to stop anyone."
The potential market for the drug is huge, as obesity rates have exploded in the past two decades. Today, nearly one in three American adults age 20 or older is obese, according to government data.
Dr. Sidney Wolfe, of the advocacy group Public Citizen, said the obese are more likely to be depressed. Many of them likely would take Zimulti along with the antidepressants they already use — with unknown consequences, Wolfe told panelists.
Rimonabant blocks the same pleasure centers in the body activated when pot smokers get the munchies. Blocking the receptors leads to patients eating less and losing weight. Sanofi-Aventis also believes the drug decreases fat storage.
The FDA previously told the French company it would not approve the drug to help smokers quit.
Sanofi-Aventis seeks to sell 20-milligram Zimulti tablets to the obese and to those who are overweight and have type 2 diabetes, high blood pressure or other conditions that put them at risk of cardiovascular disease.
There currently are two FDA-approved prescription drugs for the long-term treatment of obesity: Meridia, an appetite suppressant, and Xenical, which limits the amount of fat the body can absorb. Sales of Alli, a lower dose version of Xenical that won't require a prescription, start this week.
Heart problems led to the withdrawal of the diet drug fenfluramine in 1997. It had made up with phentermine the popular yet unapproved fen-phen combination treatment.
Glaxo to donate flu vaccine for poor
Wed, 13 Jun 2007 14:45:12 GMTBy MARIA CHENG, AP Medical Writer
LONDON - Pharmaceutical company GlaxoSmithKline PLC has agreed to donate 50 million doses of H5N1 vaccine to the World Health Organization in an attempt to create a pandemic vaccine stockpile for poor countries, company officials announced Wednesday.
The vaccines will be delivered over a three-year period and should provide enough doses for 25 million people; two shots per person will be needed.
"This is excellent news," said Dr. John Oxford, a professor of virology at London's Queen Mary School of Medicine. "It's just what we need to reassure countries like Indonesia that they will get something in return from the viruses they provide, which will form the basis of these vaccines," Oxford said.
Until recently, Indonesia had refused to share its H5N1 virus samples with WHO, claiming that they would be used by pharmaceutical companies to make vaccines it and other poor countries could not afford.
"By having this vaccine stockpile, we will have a way to help reward countries like Indonesia and Vietnam who have provided virus samples in the past," Oxford said.
Still, if it is another flu subtype that causes the next pandemic — such as H7 or H9 — vaccines based on H5N1 will most likely be useless.
While the stockpile is a reassuring development in pandemic preparedness planning, many questions remain. WHO has not said how the vaccine stockpile might be distributed — a key concern since nearly every country worldwide will be clamouring for vaccine to save its population during a pandemic.
Nor has WHO addressed the question of how the vaccines might be delivered. In most countries that will need the vaccine, health infrastructures are weak and it is uncertain if people could get the vaccine, even if it were available.
And because no one knows how long flu vaccine remains effective, it is unknown how frequently the stockpile will need to be replenished. "It probably won't just wither away after a few years, but we really don't know," said Oxford.
Many of these questions, including the operational details of where the stockpile would be kept, will be addressed by WHO and partners in the coming months.
Other vaccine producers, including Sanofi-Aventis AS, Baxter Healthcare Corp., and Omnivest, a Hungarian pharmaceutical, have also told WHO they would be willing to contribute to a vaccine stockpile.
Novartis gets EU OK for new flu vaccine
Wed, 13 Jun 2007 12:43:45 GMTBASEL, Switzerland - Novartis AG has received European Union approval for flu vaccine Optaflu, the Swiss drugmaker said Wednesday.
Iceland and Norway also have approved Optaflu for use in vaccination against seasonal influenza, Novartis said, adding that its use of proprietary cell culture technology could help in the event of a flu pandemic.
"Optaflu marks the first major innovation in influenza vaccine manufacturing in over 50 years," said Dr. Joerg Reinhardt, chief executive of Novartis vaccines and diagnostics.
Reinhardt said the vaccine would provide a "more flexible and reliable production process," helping to meet demand for seasonal flu treatments and vaccines in case of a pandemic.
Health officials around the world have been preparing in case the bird flu virus that has killed at least 190 people since it began ravaging Asian poultry stocks in 2003 mutates into a form that spreads among humans. The World Health Organization has warned that a pandemic could kill hundreds of thousands around the globe.
Novartis said Optaflu is expected to be available in Germany and Austria for next winter's flu season. It will be available in the other 25 EU countries by the 2008-2009 season.
The company said it will likely seek U.S. regulatory approval next year.
Better labels urged for sports creams
Wed, 13 Jun 2007 03:16:32 GMTBy KAREN MATTHEWS, Associated Press Writer
NEW YORK - Arielle Newman was a high school track star who suffered from the typical aches and pains that result from a grueling training regimen. For relief, she covered her legs with large amounts of muscle cream.
The 17-year-old died from an accidental overdose of methyl salicylate, the wintergreen-scented ingredient found in liniments like BenGay, Icy Hot and Tiger Balm, the New York City medical examiner's office said last week. The death was the first of its kind in the city, authorities said.
Experts said the death of Newman, a cross-country runner for Notre Dame Academy on Staten Island, points to a need for clearer warnings about risks, especially because muscle creams have become a staple in locker rooms around the country.
"There has to be a heightened awareness that these products are something that needs to be used under medical supervision," said Dr. Gerard Varlotta, director of sports rehabilitation at the Rusk Institute of Rehabilitation Medicine at New York University Medical Center.
Newman put the muscle cream on her legs and used adhesive pads containing the anti-inflammatory, plus an unspecified third product, said Ellen Borakove, a spokeswoman for the medical examiner.
"There were multiple products, used to great excess, and that's how she ended up with high levels," Borakove said. The products were used and the chemical absorbed over time, rather than from a single instance of overuse, she said.
Although no clear documentation exists on deaths resulting from the application of muscle cream, experts said they have never heard of one other than Newman's.
Johnson & Johnson, the maker of BenGay, expressed sympathy to the Newman family and said in a statement that the product "is safe and effective when used as directed to provide relief from minor arthritis pain, sore, aching and strained muscles and backaches."
Chattem Inc., the maker of Icy Hot, did not return a call Tuesday seeking comment.
The labels on both products say to stop using them if "condition worsens or symptoms persist for more than 7 days."
The labels also say to keep the products out of the reach of children.
"It's on my one-swallow-to-kill list for kids," said Dr. Thomas Kearney, who directs a poison control center and is a professor of pharmacy at the University of California at San Francisco.
Topical application of methyl salicylate can be hazardous if it is smeared over 40 percent of the body, if someone has a skin condition or if another medication interacts negatively with the products, Kearney said.
The U.S. Food and Drug Administration should mandate the warning labels also include that the products contain aspirin, which can be harmful for some consumers, including those with asthma, Varlotta said.
"There are warnings, but I don't think they're strong enough. I don't think they're direct enough," he said. "There's nothing here that says 'contains an aspirin product.'"
Kimberley Rawlings, a spokeswoman for the FDA, said the agency is aware of Newman's death. "We are looking into it," she said. She would not say whether the labeling requirements for methyl salicylate products might be changed.
Methyl salicylate is not the only common pain reliever that can be dangerous if used improperly.
Accidental poisonings from acetaminophen, best known by the Tylenol brand, are the nation's leading cause of acute liver failure.
A big problem is that people don't read warning labels on over-the-counter drugs, said Rebecca Burkholder, vice president for health policy at the National Consumers League.
"People are thinking if it's on the shelf at their local drugstore that it's harmless," Burkholder said. "And they're going to take as much as they need to make the pain go away."
Obesity paradox seen in range of heart ills
Wed, 13 Jun 2007 17:36:36 GMTNEW YORK - Among men with symptoms of heart disease, those who are obese tend to live longer than their normal-weight counterparts, a new study suggests.
Researchers found that among nearly 6,900 male veterans assessed for symptoms of heart disease, those who were obese were less likely to die over the next 7.5 years compared with normal-weight men.
Past research has linked obesity to longer survival among people with heart failure, a chronic condition in which the heart muscle is too weak to pump enough blood to meet the body's needs. Some studies also suggest that obese patients fare better following heart bypass surgery.
Now the new findings, published in The American Journal of Medicine, suggest that this so-called &;obesity paradox&; extends to other heart disease patients as well.
The study does not, however, mean that obesity is a health boon, stress Dr. Paul McAuley and his colleagues at the VA Palo Alto Health Care System in California. Obesity is linked to a higher risk of developing type 2 diabetes, heart disease and other illnesses.
A lifetime of obesity might have different effects on longevity, they speculate.
It's also not clear that obesity, per se, confers a survival advantage in heart disease. One recent study found that the obesity paradox might be explained by doctors' tendency to treat obese heart disease patients more aggressively.
The current findings are based on a follow-up of 6,876 men who were referred for exercise stress testing due to possible heart disease symptoms. Over an average of 7.5 years, 23 percent of the men died.
After the researchers accounted for patients' fitness levels on the exercise test, as well as heart risk factors, such as high blood pressure and diabetes, they found that obese men were 35 percent less likely to die during the study period than were normal-weight men.
Because the study group consisted of older men with heart disease symptoms, the findings may not be broadly relevant, McAuley and his colleagues point out. It's not known, for example, whether in a group of initially healthy people, obese individuals would tend to live longer.
More studies, the researchers conclude, are needed to fully understand the reasons for the obesity paradox.
SOURCE: The American Journal of Medicine, June 2007.
Indian gumshoe finds boom in busted marriages
Wed, 13 Jun 2007 05:25:51 GMTby Paul Peachey
MUMBAI - The successful Indian businessman had a wife, a lover who was an exotic bar dancer -- and an awful lot to lose, so he practised exceptionally safe sex.
His first precaution was to get on a plane and put nearly 2,000 kilometres between his wife at home in Dubai and the hotel in the western Indian city of Mumbai where his mistress waited for their regular weekend trysts.
In case anybody was watching, he left his car at one hotel and sneaked out the back exit of the car park before checking in at another hotel nearby.
It did him little good. When he answered his hotel doorbell early one Sunday morning it was not room service but his angry wife and his parents who had just arrived on a flight from Dubai to catch him out.
Rahul Rai was not there to see it. He had telephoned Dubai to tip off the wife after his team of &;street smart&; graduates and ex-detectives tracked him down after a 45-day surveillance operation.
With the job done they discreetly pulled out to leave the family to it.
For Rai, 30, an undemonstrative MBA graduate based in a suitably unobtrusive small first-floor office in a sprawling and dusty industrial estate in Mumbai, it was another successful outcome from an expanding caseload.
He runs one of India's many businesses benefiting from the growing wealth of the country's middle-class.
Most of the 50 people who contact him daily are put off by the 6,500 rupee a day investigation fee.
Yet he still runs up to 20 simultaneous investigations a day across India, up from one or two when he took over the family concern seven years ago.
Failing marriages provide the bulk of the work for the Globe Group's investigative wing. His operatives rely largely on surveillance, secret photography and fake phone calls from credit card companies to trace and track the targets of their investigations.
A team of four will trail the suspect across the city. If the target is a woman, a female sleuth will be part of the team in case she travels in one of the city's women-only train carriages that take millions of people to work every day.
Globe employs 450 investigators, some on the payroll and some freelance, and the little reliable data available suggests they are tapping into a growth industry with divorce on the up in urban India.
In the past many Indian women could be relied upon to suffer in silence in an abusive or adulterous relationship.
They are now heading to the divorce courts in growing numbers despite the potential for six of seven years of financially ruinous proceedings.
By Western standards, India's divorce rate is tiny. The 2001 census suggests that 3.3 million people are divorced or separated -- fewer than one percent of married people in a nation of more than one billion.
But the figures hide the story of growing changes in a nation where the vast majority of marriages are arranged.
After marriage, women traditionally move in with their husband's parents, an arrangement that has long been regarded as a model for family stability, but within which domestic violence has been a constant sore.
Thousands of women are killed every year over their family's failure to provide more money in dowry payments.
A new domestic violence act was introduced last year, designed to protect women from abuse in the home.
Lawyers and campaign groups say the new law is just one of a series of social changes, including a new generation of urban women going out to work, that has fuelled the popularity of divorce.
&;Women are getting a better position in the family,&; said Aafreen Siddiqui, from campaigning legal group Lawyer's Collective.
&;They are feeling a sense of empowerment and they have a better negotiating power in relationships.&;
Sudhir Shah, a leading lawyer in Mumbai with 40 years experience, says about 10 percent of couples in the major cities were divorcing.
&;Since they are now earning, society has accepted that a woman staying alone is acceptable and they are fighting for their rights,&; he says.
&;They don't tolerate any nonsense if their in-laws are repressing them.&;
One academic study that looked at 10 years of divorce court papers in Mumbai revealed that more women than men were instigating divorce. Cases lodged had risen by more than 50 percent in the decade to nearly 3,000 in 2001.
Rahul Rai normally sees the collapse of the marriage before it gets to court but is surprised that two-thirds of his wealthy clients had &;love marriages,&; still a relative rarity in India where an estimated 95 percent of marriages are arranged.
&;That's very shocking since they go into love marriages and later they find they are not fit for each other,&; he said. &;In the olden days they also used to be unhappy with each other but due to social pressures they carried on. Now they know they can go for divorce.&;
It is his job to reveal the evidence of his investigations to the suspicious, fearful and occasionally disbelieving.
He has comforted those who have broken down in his office. He even set up an investigation for a man in his 70s who -- wrongly, as it turned out -- believed his similarly elderly wife was having an affair.
But there are upsides to the emotional carnage. &;It is much more interesting than corporate investigations,&; he said.
