Serevent and Foradil asthma drugs may be risky

The risks of two widely used asthma drugs outweigh their benefits for both children and adults, a U.S. Food and Drug Administration advisory panel said Thursday.

The health panel targeted GlaxoSmithKline’s Serevent and Foradil, made jointly by Novartis AG and Schering-Plough, for restrictions, but it excludedAdvair, Glaxo’s biggest-selling drug in the class of medications known as long-acting beta-agonists. It also left alone a fourth such drug, AstraZeneca’s Symbicort.

The health experts did not say that the use of Serevent and Foradil should be abandoned altogether. Instead, they said the medications’ labeling should be reworded to urge doctors to use the drugs along with an inhaled corticosteroid — as guidelines already recommend.

That may help explain why Advair and Symbicort were spared. Serevent contains just one active ingredient, salmeterol, while Foradil contains only formoterol. Advair is a combination of both salmeterol and fluticasone (an inhaled cortocosteroid), while Symbicort contains formoterol and another steroid (budesonide). All of these drugs relax airway muscles, letting asthma patients breathe more easily.

The controversy over these drugs has been going on for several years, with two FDA officials recently calling for banning the use of these drugs for anyone under 17. The results of studies noting a rise in asthma-related deaths by people using the medications have already resulted in a black-box warning that use could “increase the risk of asthma-related death.”

The advisory panel voted 10 to 17 on whether the benefits of Serevent outweighed its risk as maintenance therapy for adults, and voted 6 to 21 on the same question for adolescents ages 12 to 17, Dow Jones reported. Foradil received similar votes on the same questions: 9 to 18 for adults and 6 to 21 for adults.

The panelists were unanimous in voting that the benefits of the two drugs did not outweigh risks when used for children ages 11 and younger.

The announcement followed a two-day meeting on the issue by the expert advisory panel. The FDA is not obligated to follow the advice of its advisory panels but usually does so.

Speaking before Thursday’s decision, one expert said the problem is not with the drugs, but with their misuse.

“This is an over-interpretation of the risk without adequate consideration of benefit,” said Dr. Miles Weinberger, a professor of pediatrics at the University of Iowa. “However, there has been irresponsible marketing of the products, salmeterol and formoterol, and irresponsible prescribing by many physicians.”

“Since most patients with chronic asthma can be controlled with inhaled steroids alone, using these more expensive combination formulations as first line is inappropriate but strongly encouraged by marketing practices” of drug makers, Weinberger said.

In the panel’s first day of hearings on Wednesday, FDA officials themselves were split over the risks of the drugs.

One official told the panel members that more than 14,000 people may have died since 1994 after taking the drugs, while another suggested that an even greater number might have died without them, according to The New York Times.

Last week, two FDA officials, who work in the agency’s safety division, posted an assessment on the agency Web site, saying asthma sufferers of all ages should not take the medicines. But a third FDA official concluded that Advair and Symbicort are safe for adults, but that all four drugs should no longer be used by children 17 and younger, the Times said.

The panel was reviewing an FDA study of 110 trials that included 60,954 people and found an increase in asthma-related hospitalization, asthma-related intubation, and asthma-related death in asthmatic patients with the use of these drugs. The risk varied, however, depending on the particular drug studied.

For example, there were 20 asthma-related deaths, 16 among people taking long-acting beta agonists compared with four patients not taking these drugs. All the deaths were in patients taking Serevent, the FDA notes.

The increased risk wasn’t seen when a long-acting beta agonist was used along with an inhaled corticosteroid, the agency found.

The greatest risk appears to be among children aged 4 to 11; women also appeared to be at greater risk than men.

Weinberger thinks that long-acting beta agonists should be used only in combination with inhaled steroids.

“All trials of the combination of long-acting beta agonists and an inhaled steroid demonstrate substantial additive effect for patients not fully controlled on the inhaled steroid alone,” Weinberger said. “The sensible approach is to use the combination products only after inadequate control is observed with an inhaled steroid alone.”

For their part, the drugs’ manufacturers said they believe there is adequate evidence that their products are safe and effective when used properly.

In a joint statement issued after the panel voted, Novartis and Schering-Plough said both companies “remain confident in the safety and efficacy of Foradil.” The statement added, “Novartis and Schering-Plough strongly disagree with the Joint Advisory Committees view that the benefits of Foradil do not outweigh its risks in patients using it according to current product labeling for the maintenance treatment of asthma. We believe this opinion is inconsistent with clinical evidence supporting the benefit/risk profile of Foradil in patients not adequately controlled on other asthma-controller treatments.”

In its statement before the vote, AstraZeneca said the company “believes that Symbicort exhibits a favorable benefit-risk profile in patients 6 years of age and older. Symbicort offers an important therapeutic option for asthma patients who cannot be adequately controlled on other asthma controller medications [low- to medium-dose inhaled corticosteroids] or whose disease severity clearly warrants initiation of treatment with two maintenance therapies.”

Inhaled insulin Exubera may cause lung cancer

US drugmakers Pfizer Inc and Nektar Therapeutics on Wednesday warned of cases of lung cancer in clinical trials of their inhaled insulin Exubera.

The findings led Nektar to announce it was abandoning its search for a new marketing partner for the troubled drug, effectively signaling Exubera’s demise after entering the market in January 2006.

Pfizer, the world’s largest pharmaceutical company, announced last October it stopped marketing Exubera, saying it did not meet customer needs or the financial expectations of the company.

The rise in lung cancer apparently linked to Exubera led Pfizer to update the medication’s warning label to include information “about lung cancer cases observed in patients who used Exubera,” the company reported in a statement.

It said that over the course of the clinical trial, six out of 4,740 Exubera-treated patients developed lung cancer, versus one of the 4,292 patients not treated with Exubera.

An additional case of lung cancer in an Exubera-treated patient was discovered after the drug’s debut on the market following its approval by the US Food and Drug Administration.

The updated label states that all patients who developed lung cancer had a prior history of cigarette smoking, and that there were “too few cases to determine whether the development of lung cancer is related to the use of Exubera.”

“Some patients continue to take Exubera, including those enrolled in extended transition programs or clinical trials,” Pfizer chief medical officer Joe Feczko said in the statement.

“We are working closely with patients and their physicians to ensure the continued orderly transition from Exubera to alternative therapies,” he added.

Nektar announced it was stopping all spending on the drug, including research and marketing.

“The concern over this new data analysis from ongoing clinical trials has resulted in the termination of all negotiations with potential partners,” said Nektar president Howard Robin on the company’s website.

Diabetes affects 230 million people worldwide, including 21 million in the United States, according to Pfizer. Exubera is a short-acting insulin breathed in through an inhaler that helps control high blood sugar in people with diabetes.

Pfizer warns Exubera patients about risk

Pfizer Inc. said Wednesday it is warning patients using its inhaled insulin product Exubera about the risk of lung cancer, leading Nektar Therapeutics to terminate its inhaled insulin programs.

Nektar had been Pfizer’s partner on Exubera from 1995 until Pfizer discontinued the drug in October 2007 after lackluster sales. Some patients continue to take the drug, however, including some enrolled in extended transition programs or clinical trials.

On Wednesday, Pfizer said it updated the U.S. product labeling for Exubera Inhalation Powder to include a warning about lung cancer cases observed in patients who used the inhaled insulin treatment.

Over the course of Exubera’s clinical trial program, 6 of the 4,740 patients treated with Exubera developed lung cancer, compared with 1 of the 4,292 patients not treated with the drug.

There was also a post-marketing report of lung cancer in one Exubera-treated patient.

The label notes that all patients who developed lung cancer had a prior history of cigarette smoking, and that there were too few cases to determine whether the cancer is related to use of Exubera.

Pfizer said the data was reviewed by the company and the Food and Drug Administration.

Nektar said it will stop all spending associated with its inhaled insulin programs and will not incur any additional charges related to the action.

“The concern over this new data analysis from ongoing clinical trials has resulted in the termination of all negotiations with potential partners,” said Howard W. Robin, president and chief executive of Nektar, in a statement. “Fortunately, over the past year Nektar has significantly transformed its business, moving away from inhaled insulin.”

Exubera

Generic Name: insulin inhalation
Brand Names: Exubera

What is Exubera?

Insulin inhalation (Exubera) was withdrawn from the U.S. market in 2007 due to lack of consumer demand for the product. No drug safety concerns were cited in this withdrawal.

Exubera is a rapid-acting form of human insulin that is inhaled through the mouth. It works by lowering levels of glucose (sugar) in the blood.

Viagra’s 10th anniversary

Ten years ago this month the lives of millions of men and women were changed almost overnight by the advent of a little blue pill — the first oral treatment for impotence.

Viagra, developed by accident by scientists at Pfizer Laboratories, was first approved for use by the US Food and Drug Administration on March 27, 1998.

“Originally, we were testing sildenafil, the active drug in Viagra, as a cardiovascular drug and for its ability to lower blood pressure,” said Dr Brian Klee, senior medical director at Pfizer.

“But one thing that was found during those trials is that people didn’t want to give the medication back because of the side effect of having erections that were harder, firmer and lasted longer.”

Since Viagra went on the market it has been used by 35 million men around the globe, and it took impotence off the taboo list, making it infinitely easier to treat.

Urologists’ waiting rooms became busier as news got round that the condition, which was rechristened with a new, scientific name — erectile dysfunction, or ED — could be treated with a triangular blue pill.

Previous treatments had involved surgically inserting a prosthesis into the penis, injecting a substance into the male sex organ or using urethral suppositories.

“Viagra brought a lot more people into the office because of the ease of treatment,” Dr Irwin Shuman, a urologist of 40 years’ experience in Washington, told AFP.

“In the old days, when we didn’t have much in the way of treatment, we would do a lot more evaluation, looking for answers as to why somebody had the problem,” he said.

In one test, men would be observed while sleeping to see if erections occurred.

Men who failed to get the usual five to six erections per night were deemed to have a physical problem, and those who did get nocturnal erections were said to have a psychological problem and were sent to see a sex counsellor.

So Viagra helped move impotence out of the psychological realm and into the world of physical illnesses. “What we have come to understand in the past 10 years is that ED is a vascular disease,” said Klee.

“What happens is veins and arteries that deliver and remove blood from the penis are not working the way they should, and Viagra allows those vessels to dilate and increase blood flow to the penis,” he said.

Dr Abraham Morgentaler, director of Men’s Health Boston, and associate clinical professor of urology at Harvard Medical School, hailed Viagra as a “benefit to medicine.”

But, he added, the drug has not delighted all those who took it.

“There are two truths to Viagra: for those who refill (get a new prescription), it’s wonderful and they’re happy,” Morgentaler told AFP.

“But a lot of people look to Viagra for personal happiness, thinking a hard penis can resolve relationship issues,” and they end up disappointed, added the doctor and author of the book “The Viagra Myth.”

Some patients say taking Viagra “does not correspond to the way they want to have sex,” Morgentaler said.

Viagra works best on an empty stomach or after eating a low-fat meal, the medication’s official website says. It kicks in about 30 minutes after being taken, works for four hours, and only with sexual arousal, the website says.

But it’s not the answer for everyone. Morgentaler said he had a 78-year-old patient in his office who “didn’t like the idea of programming sex. Guys, and often women, too, don’t necessarily want to compromise the ideal of sex as something magical, spontaneous, romantic.”

Morgentaler also spoke of the darker side of Viagra, which has evolved since it and two other ED treatments became easily available over the Internet.

“It’s the use of Viagra by healthy young men who don’t need it,” he said.

“These young men take a pill whenever they go out … Maybe because they are inexperienced or shy and Viagra makes them more confident, or maybe because they have inflated ideas about what sex is supposed to be like from seeing Internet porn, which they also have easy access to, and they want to heighten their feelings of masculinity,” he said.

“I am concerned — not that these young men will get addicted physically, but that they will become psychologically dependent on Viagra,” said Morgentaler.

“Sex is an entree into a relationship, and most often what we want from a relationship is to be loved for what we are.

“But some of these young men feel they have to take a pill to be acceptable, and I fear they are potentially missing the opportunity to have true emotional connections with a partner, based on reality, not mythology.”

Viagra celebrates its 10th birthday

The potency enhancing drug Viagra has been on the market for 10 years. In 1998, pharmaceutical company Pfizer introduced the erection drug that was to change millions of lives at a stroke. A solution to erectile dysfunction had been found, and the taboo surrounding impotence was largely a thing of the past.

The little blue pill that enabled millions of couples to reawaken their sex lives was discovered by accident, says sexologist Vera Steenhart of the Dutch Sexology Association. Pfizer was actually looking for a drug for the heart problem angina pectoris. The pills didn’t appear to be benefiting the test subjects, but they refused to give them back. Ms Steenhart:

“The manufacturers found this strange. On further investigation, they found the drug gave the male patients an erection. They were extremely happy about it.”

Effect
The forerunner to Viagra was developed to make blood vessels relax. The test subjects were given the drug to improve blood circulation to the heart to reduce the chance of heart failure. Viagra has the same effect on the penis. When the man is sexually stimulated, the blood supply is improved and it becomes easier for him to maintain an erection.

It’s a myth that the pill can produce an unwanted erection. The user does actually have to be in the mood, so Viagra has little or no effect if he is unwilling to have sex or feels anxious about it. In that case it would be more appropriate for him to have a good talk with his partner or pay a visit to a psychologist or sexologist.

Free drug samples make you spend more!

Patients who receive free drug samples from their doctors end up having significantly higher out-of-pocket costs for their prescription drugs than people who don’t receive free samples, a new study finds.

In fact, patients who received free samples spent about $166 in out-of-pocket costs on prescription drugs in the six months before receiving the samples, $244 for the six months in which they received samples, and $212 for the six months following receipt of the free drugs, the study found.

But patients who didn’t get free samples spent about $178 on prescription drugs over six months.

“This is a curious finding because one would think, intuitively, that if you receive a free sample, one’s out-of-pocket prescription cost would be lower, not higher,” said lead researcher Dr. G. Caleb Alexander, an assistant professor of medicine at the University of Chicago Medical Center.

There are several possible explanations for the finding, Alexander said. One is that patients who receive free samples may be sicker than patients who don’t get samples.

“The second possibility is that patients who receive free samples may go on to receive and fill prescriptions for the very same medicine that were initially begun as free samples,” Alexander said. “We know that drugs that are available as free samples are those that are being widely marketed and promoted and these drugs are more expensive than their older, less promoted counterparts.”

The study findings are published in the March 24 issue of the journal Medical Care.

For the study, Alexander’s team collected data on 5,709 patients who had participated in the Medical Expenditure Panel Survey. The survey was done by the U.S. Agency for Healthcare Research and Quality and the patients were followed for up to two years.

Seventy-six percent of the patients had private health insurance. During the study period, 14 percent of them were given at least one drug sample. A total of 2,343 samples were distributed during the period, the researchers found.

Patients who received free samples were more likely to be younger and have private insurance, while patients with Medicaid were less likely to receive samples, the researchers noted.

The findings follow earlier research, reported in the February issue of the American Journal of Public Health, in which Harvard University researchers showed that more than 80 percent of free drug samples were given to wealthy and insured patients, not to uninsured and poorer patients.

Alexander said there are many ways doctors and patients can work together to reduce drug costs, but giving away free samples may not be the best one.

“Doctors and patients both should be encouraged to consider alternative ways to reduce patients’ out-of-pocket costs,” he said. “There are many other strategies doctors can use, such as prescribing a three-month rather than a one-month supply, such as using greater numbers of generic medicines, and discontinuing non-essential medicines.”

Dr. David Katz, director of the Yale University School of Medicine’s Prevention Research Center, said free samples aren’t designed to help lower drug costs, but rather to sell newer and more expensive drugs.

“Almost every clinician’s office is stocked with drug samples,” he said. “For patients and providers alike, these free drugs can take on the aura of Halloween goodies. Passing them out feels like giving a gift.”

But, Katz added, “free samples are by no means a long-term solution to high prescription drug costs. Rather, they are at least, in part, a marketing device, a chance to sample the wares.”

The pharmaceutical industry had this to say: “Free pharmaceutical samples are beneficial to patients of all income levels. Patients are able to try out a new therapy - gaining valuable first-hand experience of its benefits and side effects - without making a co-payment,” said Pharmaceutical Research and Manufacturers of America (PhRMA) senior vice president Ken Johnson.

“What’s more, contrary to statements made by critics, America’s physicians prescribe medicines based on a wide range of factors, not simply receipt of free prescription drug samples,” Johnson added in a prepared statement.

Free Drug Samples? Bad Idea, Some Say

Everyone loves freebies, and patients are no exception. So drug company sales representatives try to keep sample cabinets in medical offices well stocked with the latest medications, for doctors to dispense as the need arises.

Patients like going home with free samples because it saves them a trip to the drugstore and a co-pay, and doctors are happy to oblige, because samples help patients get started on treatment right away.

But now some leading academic medical centers are restricting the use of samples, and a smattering of physician practices are shutting down the sample cabinet. These critics say doctors should be choosing the most appropriate medication for a patient based on the best scientific evidence available — not just grabbing something from the office stash that happens to fit the bill.

“The doctor will say, ‘Here, start on this, and let’s see how it works,’ ” said David J. Rothman, president of the Institute on Medicine as a Profession, a research group at Columbia. “The question to the doctor is: If you didn’t have it in your drawer, would that have been your drug of choice?”

The crackdown on free samples comes amid growing concern about the close ties between physicians and drug companies. Critics like Dr. Rothman say physicians don’t realize the extent to which their medical judgment is influenced by their acceptance of the samples. They point to studies like a 2002 paper in the journal Annals of Family Medicine finding that the number of doctors who treated high blood pressure with the “first line” drugs recommended by national guidelines was low, but increased sharply when free samples were removed.

So far, the University of Michigan Health System has banned free samples altogether, and the University of Pennsylvania and Stanford University medical schools have prohibited staff members from accepting them (though samples can be given to Stanford’s pharmacy for use in free clinics).

Some medical groups and solo practitioners have also changed their policies. Dr. Jonathan Mohrer, an internist in Forest Hills, Queens, said he closed his sample cabinet in part because his office was overrun with sales representatives. “It was totally spinning out of control,” Dr. Mohrer said. “They were meeting each other and schmoozing in the waiting room — it was like a party.”

His office staff had to spend time arranging the cabinet, throwing out expired medications and rummaging around for the right drug. Patients were kept waiting while sales representatives were whisked in.

But there’s an upside to the samples. Using samples, a doctor can see if a patient can tolerate a new medication before the patient goes out and buys a 30-day supply. Physicians who treat poor people like to have samples on hand for them, and for uninsured patients.

Samples also provide patients with the convenience of one-stop shopping, said Dr. Hema A. Sundaram, a dermatologist in suburban Washington. “Usually a patient has waited some time to see a doctor and rearranged their whole working schedule, and then it may be another four or five days before they can fill a prescription,” she said. “They’re often busy, working people, with family responsibilities. I feel there shouldn’t be any further delay.” (Dr. Sundaram acknowledges that she is paid for speaking on behalf of drug companies.)

And many physicians say they like using samples because the sales representatives are an important source of medical education, helping to keep the doctors up to date on the latest therapies.

“Doctors who are shutting the door to sales reps are cutting themselves off from a lot of valuable information,” said Scott Lassman, senior assistant general counsel for the Pharmaceutical Research and Manufacturers of America, a trade association. “Sales reps can explain when it’s right to use a drug, when it’s not right to use the drug, which patients might benefit and which patients it might not work for.”

Some doctors are skeptical. “The sales reps are nice people, and they try to do a really good job,” said Dr. Judith Chamberlain, medical director of the Bowdoin Medical Group, a practice near Portland, Me., that banned samples this year. “But their job is to get you to use their product.”

A 1995 study in The Journal of the American Medical Association found that 11 percent of the statements drug company representatives made during presentations were inaccurate, and all of the inaccuracies were skewed in favor of their products.

The drugs promoted through free samples tend to be the newer medications that doctors are less familiar with, experts say. Some critics of samples say they prefer using older drugs anyway, because their side effects are better known. Critics also point out that helping poor and uninsured patients is not the intent of the sample distribution, and they add that developments like Medicare’s prescription-drug coverage, the proliferation of generic drugs and improvements in drug company patient-assistance programs have eased access to medication.

As for the bottom line, it’s not at all clear that samples save patients money. Critics say they may actually drive up the cost of health care in the long run, because the drugs being promoted are the most expensive brand-name medications. Since many conditions require lifelong treatment, the patient would have to buy the medicine sooner or later.

“You’re going to be paying more, because you’re taking the new, advanced drug,” Dr. Rothman said. “And you may have done just fine on the old-fashioned generic.”

Do free drug samples influence residents’ prescribing decisions?

When a pharmaceutical company puts drug samples into the hands of residents as a form of marketing, how does it influence their prescribing behavior? To what extent are treatment decisions based on which samples are available and further, what are the implications for patient care as well as resident education? While this is a frequently debated issue, there has been little objective data describing how drug samples affect resident physicians. In a study published in the August issue of The American Journal of Medicine, researchers from the University of Minnesota and Abbott Northwestern Hospital conducted a randomized study of 29 internal medicine residents over a 6-month period in an inner-city primary care clinic. Highly advertised drugs were matched with drugs commonly used for the same indication that were less expensive, available over-the-counter, or available in generic formulation. By random selection, half of the residents agreed not to use available free drug samples. The authors observed 390 decisions to initiate drug therapy in five drug class pairs.